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Table of Contents:
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Taxonomy Information
- Species:
- Plasmodium falciparum (Website 1):
- Common Name: Malaria parasite P. falciparum
- GenBank Taxonomy No.: 5833
- Description: Malaria is the most serious tropical disease of humankind and the cause of much debilitation and morbidity in areas where it is endemic. Globally, the annual disease burden in over 90 endemic countries is estimated at 250 to 500 million clinical cases with the greatest impact in sub-Saharan Africa, where it claims the lives of 1.5 to 2 million children every year. The disease is caused by a protozoan parasite from the genus Plasmodium, transmitted through the bite of the female Anopheles mosquito. Four species of Plasmodium are known to cause disease in humans, P. vivax, P. ovale, P. malariae and P. falciparum, the latter being the most virulent and the major cause of mortality(de Souze and Riley, 2002).
- Variant(s):
- Plasmodium falciparum (isolate 311) (Website 2):
- Plasmodium falciparum (isolate 7G8) (Website 3):
- GenBank Taxonomy No.: 57266
- Parents: Plasmodium falciparum
- Description: The parental stock of falciparum parasites to be cloned was isolated from 12 year-old male near Manaus, Brazil on 12 March 1980 and cryopreserved. The isolate IMTM22 was later put into a static culture system(Burkot et al., 1984). After more than 19 weeks in culture, a sample of IMTM 22 was cloned by the limiting dilution method (Burkot et al., 1984). The clones, of which 7G8 is one, were subcultured at weekly intervals until three flasks of each clone were established(Burkot et al., 1984).
- Plasmodium falciparum (isolate CAMP / Malaysia) (Website 4):
- Plasmodium falciparum (isolate CDC / Honduras) (Website 5):
- GenBank Taxonomy No.: 5836
- Parents: Plasmodium falciparum
- Description: The Honduras I/CDC strain (isolated 25 Jan 1980, and cultured from frozen material in May and in June 1980) was placed in culture from frozen material on Sept 1981, and maintained by the continuous flow technique(Bhasin and Trager, 1984).
- Plasmodium falciparum (isolate DD2) (Website 6):
- Plasmodium falciparum (isolate FC27 / Papua New Guinea ) (Website 7):
- GenBank Taxonomy No.: 5837
- Parents: Plasmodium falciparum
- Description: FCQ-27/PNG was collected originally from a 4 year old donor(Chen et al., 1980). Venous blood was collected asceptically into bottles containing heparin from 37 patients with clinical malaria in Madang Hospital, Madang Province, Papua New Guinea. The cells were washed twice in culture medium lacking serum and resuspended to 10% v/v in medium for transportation on wet ice by air to Brisbane or Melbourne where they were cultured after 1 to 4 days in transit (Chen et al., 1980).
- Plasmodium falciparum (isolate FcB1 / Columbia) (Website 8):
- Plasmodium falciparum (isolate FCBR / Columbia) (Website 9):
- GenBank Taxonomy No.: 33631
- Parents: Plasmodium falciparum
- Description: Two chloroquine-resistant strains were used to infect owl monkeys or squirrel monkeys: the culture-adapted FCBR (FCB) strain, originally isolated from a patient in Bogota, Colombia, and the Palo Alto strain, originally isolated from a patient in Uganda and then adapted to owl monkeys(Raether et al., 1989).
- Plasmodium falciparum (isolate FCH-5) (Website 10):
- Plasmodium falciparum (isolate FCM17 / Senegal) (Website 11):
- GenBank Taxonomy No.: 5845
- Parents: Plasmodium falciparum
- Description: Malaria parasites from three different strains (FCM-17 from Senegal, FCM-22 from Madagascar, and FCM-29 from Cameroon) were cultured in vitro(Lenstra et al., 1987).
- Plasmodium falciparum (isolate FCR-3 / Gambia) (Website 12):
- GenBank Taxonomy No.: 5838
- Parents: Plasmodium falciparum
- Description: This strain originated from the Gambia, West Africa. A culture line was established in 1976 at the Rockefeller Institute directly from an infected patient(Fandeur et al., 1991).
- Plasmodium falciparum (isolate fid3 / India) (Website 13):
- GenBank Taxonomy No.: 70152
- Parents: Plasmodium falciparum
- Description: Blood samples were collected from three malaria patients in different geographic areas of India. These locations (New Delhi, Shahjahanpur and Jabalpur) are separated by a few hundred kilometers from each other. These isolates, FID3, FIS1 and FIJ4, were maintained in continuous in vitro culture using the standard candle-jar method of Trager and Jensen(Bhattacharya et al., 1995).
- Plasmodium falciparum (isolate hb3) (Website 13a):
- GenBank Taxonomy No.: 137071
- Parents: Plasmodium falciparum
- Description: Three clones have been prepared from the Honduras I/CDC strain of Plasmodium falciparum by a method of microscopic selection. One of these (HB-2) does not form gametocytes whereas the others (HB-1 and HB-3) do. All three are as resistant to pyrimethamine as the original line, and all three form knobs on the erythrocyte surface(Bhasin and Trager, 1984).
- Plasmodium falciparum (isolate IMR143) (Website 14):
- GenBank Taxonomy No.: 57268
- Parents: Plasmodium falciparum
- Description: Isolates FCQ27/PNG (FC27), IMR143/PNG (IMR143), IMR144/PNG (IMR144), IMR147/PNG (IMR147) and MAD71/PNG (Mad71) were all obtained from Papua New Guineans living in the Madang Province of Papua New Guinea(Saint et al., 1987).
- Plasmodium falciparum (isolate K1 / Thailand) (Website 15):
- Plasmodium falciparum (isolate KF1916) (Website 16):
- Plasmodium falciparum (isolate LE5) (Website 17):
- GenBank Taxonomy No.: 5840
- Parents: Plasmodium falciparum
- Description: This strain was isolated from a native Liberian by Dr. M. Swartz and sent to us on 21 October, 1980. It was cryopreserved on the day of arrival. A vial was subsequently thawed and the strain was grown for 16 days before cloning(Graves et al., 1984). Parasites in rapid growth phase were cloned by limiting dilution in 96-well plates or tissue-culture flasks(Graves et al., 1984). Strain LE5 was one of these clones(Graves et al., 1984).
- Plasmodium falciparum (isolate mad20 / Papua New Guinea) (Website 18):
- Plasmodium falciparum (isolate mad71 / Papua New Guinea) (Website 19):
- GenBank Taxonomy No.: 70154
- Parents: Plasmodium falciparum
- Description: Isolates FCQ27/PNG (FC27), IMR143/PNG (IMR143), IMR144/PNG (IMR144), IMR147/PNG (IMR147) and MAD71/PNG (Mad71) were all obtained from Papua New Guineans living in the Madang Province of Papua New Guinea(Saint et al., 1987).
- Plasmodium falciparum (isolate NF54) (Website 20):
- Plasmodium falciparum (isolate NF7 / Ghana) (Website 21):
- Plasmodium falciparum (isolate nig32 / Nigeria) (Website 22):
- Plasmodium falciparum (isolate PALO ALTO / UGANDA) (Website 23):
- GenBank Taxonomy No.: 57270
- Parents: Plasmodium falciparum
- Description: The Uganda-Palo Alto (FUP) strain of Plasmodium falciparum was originally isolated from a patient who had contracted the infection in Uganda and was hospitalized at Stanford Medical Center, Palo Alto, California, in 1966. In 1967, blood-induced infections with this isolate were established in Aotus trivirgatus monkeys at Stanford. The FUP strain was maintained by serial passage in Aotus monkeys by Dr. Schmidt of the Southern Research Institute, Birmingham, Alabama. In 1970, the FUP monkey-passaged strain was obtained from Dr. Schmidt and maintained in this laboratory at the University of Hawaii by serial passage in Aotus monkeys. In 1977, continuous cultures of the FUP strain in human erythrocytes were established at the University of Hawaii and have been maintained in this laboratory since that time(Chang et al., 1988).
- Plasmodium falciparum (isolate RO-33 / Ghana) (Website 24):
- Plasmodium falciparum (isolate T4 / Thailand) (Website 25):
- Plasmodium falciparum (isolate TAK 9) (Website 26):
- GenBank Taxonomy No.: 57276
- Parents: Plasmodium falciparum
- Description: The isolate used (T9) was obtained from a patient at Tak, Thailand, and was established in continuous culture by Sodsri Thaithong at Chulalongkorn University, Bangkok, by the petri-dish method(Rosario, 1981).
- Plasmodium falciparum (isolate thtn / thailand) (Website 27):
- Plasmodium falciparum (isolate V1) (Website 28):
- GenBank Taxonomy No.: 5847
- Parents: Plasmodium falciparum
- Description: Various isolates of Plasmodium falciparum originally obtained from patients attending outpatient clinics in hospitals either in the respective countries of origin of the isolate or in the United States were cryopreserved and later thawed and cultured continuously(Udeinya et al., 1983). V1 was obtained from a Vietnamese refugee in Canada who traveled through Cambodia on his way to Canada. The origin of the isolate is either Vietnam or Cambodia. The date of isolation is 3 December 1980(Udeinya et al., 1983).
- Plasmodium falciparum (isolate WELLCOME) (Website 29):
- Plasmodium falciparum 3D7 (Website 30):
- GenBank Taxonomy No.: 36329
- Parents: Plasmodium falciparum
- Description: 3D7 is a clone from NF54 which was isolated from a patient who lived near the airport in Amsterdam. The origin of the infection is unknown(Miller et al., 1993).
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Lifecycle Information
- Exo-erythrocytic cycle
- Stage Information:
- Sporozoite:
- Size: 11 um in length and 1.0 um in diameter.
- Shape: Elongate
- Description: The sporozoites are more elongated than either erythrocytic or exoerythrocytic merozoites. They measure about 11 um in length and 1.0 um in diameter. The organelles found in the sporozoites are essentially the same as those of the merozoites(Aikawa and Seed, 1980).
- Trophozoite:
- Shape: Irregular
- Picture(s):
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Trophozoite Progression (Website 125)
Description: Fig 1: Normal red cells. Figs. 2-10: Increasingly mature ring stage parasties. Illustartion from Coatneyu GR, Collins WE, Warren M, Contacos PG. The Primate Malarias. U.S. Department of Health, Education and Welfare, Bethesda, 1971. Copyright CDC(Website 125).
- Description: The trophozoite is the stage in which ingestion of host cell cytoplasm and growth of the parasite occur(Aikawa and Seed, 1980). The trophozoite is surrounded by only a single plasma membrane in addition to the parasitophorous vacuole membrane which originated from the host cell. Apical end organelles such as polar rings, rhoptries, micronemes, and spherical bodies also break down. The trophozoite becomes irregular in shape(Aikawa and Seed, 1980).
- Schizont:
- Shape: Round
- Picture(s):
- Description: The schizont is defined as a parasite possessing more than one nucleus. The schizont is larger than either the merozoite or uninucleate trophozoite. During schizogony, nuclear division and differentiation of the cytoplasmic organelles occur(Aikawa and Seed, 1980). With the progression of merozoite budding, various organelles, including a nucleus, mitochondria, spherical bodies together with endoplasmic reticulum, and ribosomes migrate into the developing merozoites from the schizont. As the merozoites develop and grow, the size of the original schizont decreases until finally only a residual body with malarial pigment particles remains(Aikawa and Seed, 1980).
- Merozoite:
- Size: The exoerythrocytic merozoite is more elongate than the erythrocytic merozoite and is 3 to 4 um in length and 1 to 2 um in width.
- Shape: The merozoite is oval in shape
- Description: The exoerythrocytic merozoite is more elongate than the erythrocytic merozoite and is 3 to 4 um in length and 1 to 2 um in width. There are more micronemes in the exoerythrocytic stages, and the rhoptries appear to be more elongated(Aikawa and Seed, 1980). Merozoites can be seen by light microscopy to round up upon entry into a new red blood cell. This phenomenon has been observed in detail by electron microscopy. The round-up process appears to be caused by the rapid degradation of the inner membrane and microtubules of the pellicular complex(Aikawa and Seed, 1980). The free merozoite is very small, approximately 1.2 um long, but it contains all things necessary to invade and establish itself in a new RBC. At the apex of the egg-shaped merozoite are three sets of secretory vesicles: (1) the twin pear-shaped rhoptries; (2) the more numerous but smaller micronemes; and (3) small rounded vesicles called dense granules. The nucleus lies at the other end, and a plastid and a mitochondrion lie along one side of the merozoite, near a band of two or three microtubules. Apically, three dense cytoskeletal rings (polar rings) brace the apical prominence. A flat sac of membrane underlies most of the merozoite surface membrane, forming with it the merozoite's pellicle, which lines the whole cell except most apically. The merozoite also contains numerous free ribosomes. Over the whole surface of the merozoite, there is a thick, bristly adhesive coat(Bannister and Mitchell, 2003).
- Progression Information:
- Sporozoite-Trophozoite:
- From Stage: Sporozoite
- To Stage: Trophozoite
- Description: In their search for capillaries, mosquitoes probe the skin of the host and, in the process, deposit sporozoites. Sporozoites remain in the skin for more than 5 mins and it is not clear how they enter the bloodstream(Kappe et al., 2003). When injected directly into the bloodstream, sporozoites invade hepatocytes within a few minutes. Most circulating sporozoites are sequestered in the liver after a single passage, suggesting that a specific receptor is present on the cells lining the sinusoids(Kappe et al., 2003). Once within a hepatic cell, the parasite metamorphoses into a feeding trophozoite(Schmidt and Roberts, 1985).
- Trophozoite-Schizont:
- From Stage: Trophozoite
- To Stage: Schizont
- Description: After about a week the trophozoite is mature and begins schizogony. Numerous daughter nuclei are first formed, transforming the parasite into a schizont, also known as a cryptozoite(Schmidt and Roberts, 1985).
- Schizont-Merozoite:
- From Stage: Schizont
- To Stage: Merozoite
- Picture(s):
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Rupturing Schizont (Website 128)
Description: Ruptured schizont in a thin blood smear. Copyright CDC(Website 128).
- Description: During the nuclear divisions the nuclear membranes persist, and the microtubular spindle fibers are formed within the nucleus. The mitochondrion becomes larger during the growth of the trophozoite, forms buds, and then breaks up into many mitochondria. Elements of the apical complex form subjacent to the outer membrane, and schizogony proceeds. The merozoites thus formed after cytokinesis are referred to as metacryptozoites(Schmidt and Roberts, 1985). Eventually, merozoites leave liver cells to penetrate erythrocytes in the blood, initiating the erythrocytic cycle(Schmidt and Roberts, 1985).
- Picture(s):
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Malaria Life Cycle (Website 124)
Description: The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host (1). Soporozoites infect liver cells and mature into schizonts (2), which rupture and release merozoites (3). Of note, in P. vivax and P. ovale a dormant stage, hynozoites, can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later (4). After this initial replication in the liver, called(exo-erythrocytic schizogony (A), the parasites undergo asexual multiplication in the erythrocytes, called erythrocytic schizogony (B). Merozoites infect red blood cells (5). The ring stage trophozoites mature into schizonts, which rupture releasing merozoites (6). Some parasites differentiate into sexual erythrocytic stages (gametocytes) (7). Blood stage parasites are responsible for the clinical manifestations of the disease.The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal (8). The parasites' multiplication in the mosquito is known as the sporogonic cycle (C). While in the mosquito's stomach, the microgametes penetrate the macrogametes generation zygotes (9). The zygotes in turn become motile and elongated ookinetes (10) which invade the midgut wall of the mosquito where they develop into oocysts (11). The oocysts grow, rupture, and release sporozoites (12), which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle (1). Copyright CDC(Website 124).
- Description: After being injected into the bloodstream, the sporozoites quickly disappear (within an hour) from the circulating blood. Their immediate fate was a great mystery until the mid-1940's, when it was shown that within 1 or 2 days they enter the parenchyma of the liver or other internal organ, depending on the species of Plasmodium. Where they are the first 24 hours still is unknown. Entry into the liver initiates a series of asexual reproductions known as the preerythrocytic cycle or primary exoerythrocytic schizogony, often abbreviated as the PE or EE stage. Once within a hepatic cell, the parasite metamorphoses into a feeding trophozoite(Schmidt and Roberts, 1985). The preerythrocytic stages of mammalian malaria parasites apparently undergo within hepatic cells only a single developmental cycle that forms many merozoites that invade erythrocytes(Trager, 1986).
- Erythrocytic Cycle
- Stage Information:
- Trophozoite:
- Size: The young ring forms of P. falciparum, as usually seen in the peripheral blood, are very small, measuring about one-sixth of the diameter of a red blood cell.. Later in the attack, the ring forms of P. falciparum may be considerably larger, measuring one-quarter and sometimes nearly one-half the diameter of a red cell, and may sometimes be mistaken for parasites of P. malariae.
- Shape: Irregular
- Picture(s):
- Description: The trophozoite is surrounded by only a single plasma membrane in addition to the parasitophorous vacuole membrane which originated from the host cell. Apical end organelles such as polar rings, rhoptries, micronemes, and spherical bodies also break down. The trophozoite becomes irregular in shape(Aikawa and Seed, 1980). This is the period of most active feeding, growth and RBC modification. New molecules are exported into the RBC, some assembling into flat membranous sacs of various forms, including those visible in stained smears as Maurer's clefts. Others interact with the RBC membrane and cytoskeleton to form small knobs on its surface, and some penetrate it, for example, P. falciparum erythrocyte membrane protein (PfEMP)1 to stick the infected RBC to the endothelium of blood vessels, thus reducing parasite removal from the blood stream by the defenses of the body via the spleen. If the infected RBC adheres to brain-blood vessel walls, cerebral malaria can result, while in the placenta, fetal growth can be affected by similar cytoadherence. Other exported molecules increase RBC permeability to nutrients. The parasite continues feeding on haemoglobin, and the haeme products of haemoglobin digestion crystallize into particles of dark pigment, haemozoin, scattered within the food (pigment) vacuole(Bannister and Mitchell, 2003).
- Schizont:
- Size: Smaller than normal red cells.. When the schizont is fully grown it occupies about two-thirds of the red cell.
- Picture(s):
- Description: The schizont is defined as a parasite possessing more than one nucleus. The schizont is larger than either the merozoite or uninucleate trophozoite. During schizogony, nuclear division and differentiation of the cytoplasmic organelles occur(Aikawa and Seed, 1980). With the progression of merozoite budding, various organelles, including a nucleus, mitochondria, spherical bodies together with endoplasmic reticulum, and ribosomes migrate into the developing merozoites from the schizont. As the merozoites develop and grow, the size of the original schizont decreases until finally only a residual body with malarial pigment particle remains(Aikawa and Seed, 1980).
- Merozoite:
- Size: 1.5 um in length, and 1 um in diameter.
- Shape: The merozoite is oval in shape.
- Description: With the progression of merozoite budding, various organelles, including a nucleus, mitochondria, spherical bodies together with endoplasmic reticulum, and ribosomes migrate into the developing merozoites from the schizont. As the merozoites develop and grow, the size of the original schizont decreases until finally only a residual body with malarial pigment particles remains(Aikawa and Seed, 1980). The merozoite is oval in shape, 1.5 um in length, and 1 um in diameter, posses a nucleus and various cytoplasmic organelles, and is bounded by a pellicular complex(Aikawa and Seed, 1980).
- Microgametocyte:
- Shape: The gametocytes of Plasmodium falciparum are sausage-shaped, though they are generally referred to as crescents. They are totally unlike the sexual stages of any other human Plasmodium. The male cell is shorter and more blunt at the ends than is the female, and has more dispersed chromatin and pigment.
- Description: When development of the merozoites is complete, the host cell ruptures(Schmidt and Roberts, 1985). After an indeterminate number of asexual generations, some merozoites enter erythrocytes to become macrogamonts (macrogametocytes) and microgamonts (microgametocytes). The size and shape of these cells are characteristic for each species. Unless they are ingested by a mosquito, gametocytes soon die and are phagocytized by the reticuloendothelial system(Schmidt and Roberts, 1985).
- Macrogametocyte:
- Shape: The gametocytes of Plasmodium falciparum are sausage-shaped, though they are generally referred to as crescents. They are totally unlike the sexual stages of any other human Plasmodium.
- Description: When development of the merozoites is complete, the host cell ruptures(Schmidt and Roberts, 1985). After an indeterminate number of asexual generations, some merozoites enter erythrocytes to become macrogamonts (macrogametocytes) and microgamonts (microgametocytes). The size and shape of these cells are characteristic for each species. Unless they are ingested by a mosquito, gametocytes soon die and are phagocytized by the reticuloendothelial system(Schmidt and Roberts, 1985).
- Progression Information:
- Merozoite-Trophozoite:
- From Stage: Merozoite
- To Stage: Trophozoite
- Description: The 48-h P. falciparum intraerythrocytic developmental cycle (IDC) initiates with merozoite invasion of red blood cells (RBCs) and is followed by the formation of the parasitophorous vacuole (PV) during the ring stage. The parasite then enters a highly metabolic maturation phase, the trophozoite stage, prior to parasite replication(Bozdech et al., 2003). The IDC represents all of the stages in the development of P. falciparum responsible for the symptoms of malaria and is also the target for the vast majority of antimalarial drugs and vaccine strategies(Bozdech et al., 2003). On entry into an erythrocyte, the merozoite again transforms into a trophozoite. The host cytoplasm ingested by the trophozoite forms a large food vacuole, giving the young plasmodium the appearance of a ring of cytoplasm with the nucleus conspicuously displayed at one edge(Schmidt and Roberts, 1985).
- Trophozoite-Schizont:
- From Stage: Trophozoite
- To Stage: Schizont
- Description: The parasite rapidly develops into a schizont. The stage in the erythrocytic schizogony at which the cytoplasm is coalescing around the individual nuclei, before cytokinesis, is called the segmenter(Schmidt and Roberts, 1985).
- Schizont-Merozoite:
- From Stage: Schizont
- To Stage: Merozoite
- Description: Within the human bloodstream, the malaria organism Plasmodium falciparum is an intracellular parasite, cyclically invading, feeding and multiplying in red blood cells (RBCs). In its multiplicative phase (the schizont), the parasite generates in the region of 16 invasive forms (merozoites) that bud off from its perimeter and are eventually released from their surrounding membranes to invade fresh RBCs. During this phase the nucleus undergoes four or more mitotic divisions, whereas, in the cytoplasm, there ensues the coordinated synthesis, targeting and assembly of invasion-specific organelles. These include three types of secretory vesicle: rhoptries, micronemes and dense granules, which have different shapes, sizes, contents and roles in invasion(Bannister et al., 2003). When development of the merozoites is completed, the host cell ruptures, releasing parasite metabolic wastes and residual body, including hemozoin. The metabolic wastes thus released are one factor responsible for the characteristic symptoms of malaria, although hemozoin itself is nontoxic(Schmidt and Roberts, 1985).
- Merozoite-Microgametocyte_Macrogametocyte:
- From Stage: Merozoite
- To Stage: Microgametocyte, Macrogametocyte
- Description: Concomitantly, a small proportion of the parasites terminally differentiate from merozoites into gametocytes. Little is known about the genes that control the developmental switch to the gametocyte stage. This is a subject of key importance, because inhibition of gametocyte differentiation could be powerful means for the control of malaria transmission(Ghosh et al., 2000). After an indeterminate number of asexual generations, some merozoites enter erythrocytes and become macrogamonts (macrogametocytes) and microgamonts (microgametocytes). The size and shape of these cells are characteristic for each species; they also contain hemozoin. Unless they are ingested by a mosquito, gametocytes soon die and are phagocytized by the reticuloendothelial system(Schmidt and Roberts, 1985).
- Picture(s):
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Malaria Life Cycle (Website 124)
Description: The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host (1). Soporozoites infect liver cells and mature into schizonts (2), which rupture and release merozoites (3). Of note, in P. vivax and P. ovale a dormant stage, hynozoites, can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later (4). After this initial replication in the liver, called(exo-erythrocytic schizogony (A), the parasites undergo asexual multiplication in the erythrocytes, called erythrocytic schizogony (B). Merozoites infect red blood cells (5). The ring stage trophozoites mature into schizonts, which rupture releasing merozoites (6). Some parasites differentiate into sexual erythrocytic stages (gametocytes) (7). Blood stage parasites are responsible for the clinical manifestations of the disease.The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal (8). The parasites' multiplication in the mosquito is known as the sporogonic cycle (C). While in the mosquito's stomach, the microgametes penetrate the macrogametes generation zygotes (9). The zygotes in turn become motile and elongated ookinetes (10) which invade the midgut wall of the mosquito where they develop into oocysts (11). The oocysts grow, rupture, and release sporozoites (12), which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle (1). Copyright CDC(Website 124).
- Description: Malarial parasites have a life cycle even more complicated than that of trypanosomes and not yet fully reproduced in culture. In their vertebrate hosts (lizards, birds, or mammals), the principal propagative cycle, and the one responsible for the human disease malaria, occurs intracellularly within the red blood cells. This is a cycle of asexual reproduction in which a small invasive form, a merozoite, enters an erythrocyte, grows rapidly within it, and then undergoes schizogony to produce 8 to 24 daughter merozoites (depending upon the species), each potentially able to invade another erythrocyte and reproduce the cycle. Each cycle takes 24, 48, or 72 hr, again depending on the species. This portion of the life cycle clearly is capable of indefinite propagation as long as the parasites are supplied with appropriate red cells and other environmental conditions(Trager, 1986).
- Sporogonic Cycle
- Stage Information:
- Microgametocyte:
- Shape: The gametocytes of Plasmodium falciparum are sausage-shaped, though they are generally referred to as crescents. They are totally unlike the sexual stages of any other human Plasmodium. The male cell is shorter and more blunt at the ends than is the female, and has more dispersed chromatin and pigment.
- Description: After an indeterminate number of asexual generations, some merozoites enter erythrocytes to become macrogamonts (macrogametocytes) and microgamonts (microgametocytes). The size and shape of these cells are characteristic for each species. Unless they are ingested by a mosquito, gametocytes soon die and are phagocytized by the reticuloendothelial system(Schmidt and Roberts, 1985).
- Macrogametocyte:
- Shape: The gametocytes of Plasmodium falciparum are sausage-shaped, though they are generally referred to as crescents. They are totally unlike the sexual stages of any other human Plasmodium.
- Picture(s):
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Mature Macrogametocytes (Website 131)
Description: Figs. 27, 28: Mature macrogametocytes (female); Figs. 29, 30: Mature microgametocytes (male)Illustration from: Coatney GR, Collins WE, Warren M, Contacos PG. The Primate Malarias. U.S. Department of Health, Education and Welfare, Bethesda, 1971. Copyright CDC(Website 131).
- Description: After an indeterminate number of asexual generations, some merozoites enter erythrocytes to become macrogamonts (macrogametocytes) and microgamonts (microgametocytes). The size and shape of these cells are characteristic for each species. Unless they are ingested by a mosquito, gametocytes soon die and are phagocytized by the reticuloendothelial system(Schmidt and Roberts, 1985).
- Microgamete:
- Size: 16-25 um in length
- Picture(s):
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Gametocytes in Thick Blood Smear (Website 131)
Description: Two gametocytes captured from a thick blood smear. Copyright CDC(Website 131).
- Description: Four to six microgametes are produced during exflagellation, each measuring 16-25 um in length(Aikawa and Seed, 1980).
- Macrogamete:
- Shape: The crescent-shaped macrogamete rounds up as it sheds the host red cell.
- Description: As the microgametocyte becomes extracellular, within 10 to 12 minutes its nucleus divides repeatedly to form six to eight daughter nuclei, each of which is associated with elements of a developing axoneme. The doubled outer membrane of the microgametocyte becomes interrupted; the flagellar buds with their associated nuclei move peripherally between the interruptions and then continue outward covered by the outer membrane of the gametocyte. These break free and are the microgametes(Schmidt and Roberts, 1985).
- Zygote:
- Shape: When cultured for 10 h after exflagellation, most zygotes showed an oval or budding shape, indicating they had just started transformation into the invasive form.
- Description: The microgamete swims about until it finds a macrogamete, which it penetrates and fertilizes. The resultant diploid zygote quickly elongates to become a motile ookinete(Schmidt and Roberts, 1985).
- Ookinete:
- Size: 11-13 um in length.
- Shape: The ookinete of P. falciparum is generally more slender than that of P. vivax and measures 11-13 um in length.
- Description: The ookinete of P. falciparum is generally more slender than that of P. vivax and measures 11-13 um in length. In typical fashion, one end of the ookinete is truncated and the other rounded and more bulbous. The two poles appear light yellow and pink, respectively, in Giemsa-stained preparations. The nucleus is irregular in shape and slightly acentric. The cytoplasm is uneven, appearing pigmented and at times striated because of the presence of the anterior organelles(Aikawa and Seed, 1980).
- Oocyst:
- Size: 8 to 60 um
- Description: Oocyst development requires approximately 10 days. This varies, however, depending on the species of anopheline mosquito infected and on an assortment of environmental conditions. At maturity, oocyst diameters range from 8 to 60 um. The distribution of coarse, black pigment granules (10 to 20), in semicircular rows or chains, is somewhat characteristic of the species. The processes of nuclear division and cytoplasmic segmentation into sporoblastic islands are morphologically similar to those of other species(Aikawa and Seed, 1980).
- Sporozoite:
- Size: 11 um in length and 1.0 um in diameter.
- Shape: Elongate
- Description: The sporozoites are more elongated than either erythrocytic or exoerythrocytic merozoites. They measure about 11 um in length and 1.0 um in diameter. The organelles found in the sporozoites are essentially the same as those of the merozoites(Aikawa and Seed, 1980).
- Progression Information:
- Microgametocyte-Microgamete:
- From Stage: Microgametocyte
- To Stage: Microgamete
- Description: Once the parasites have entered the mosquito gut, they differentiate from gametocytes into gametes. Each male gametocyte generates eight haploid motile gametes within minutes of a bloodmeal by a process known as exflagellation. Exflagellation can be induced in vitro by dropping the temperature of cultured gametes from 37 C to 28 C, thus stimulating the change from host to vector temperatures, and by either increasing the pH of cultured gametes from 7.5 to 8.2 or by the addition of a gametocyte-activating factor (GAF). GAF has been isolated from the mosquito gut and has been shown to stimulate exflagellation in vitro. GAF has recently been identified as zanthurenic acid, and intermediate product of tryptophan metabolism. It is not clear what role, if any zanthurenic acid or pH play in triggering exflagellation in vivo, and neither is their mechanism of action known(Ghosh et al., 2000). The microgametocyte displays a rather astonishing transformation, exflagellation. As the microgametocyte becomes extracellular, within 10 to 12 minutes its nucleus divides repeatedly to form six to eight daughter nuclei, each of which is associated with the elements of a developing axoneme. The doubled outer membrane of the microgametocyte becomes interrupted; the flagellar buds with their associated nuclei move peripherally between the interruptions and then continue outward covered by the outer membrane of the gametocyte. These break free and are the microgametes. The stimulus for exflagellation is an increase in pH caused by escape of dissolved carbon dioxide from the blood. The life span of the microgametes is short, since they contain little more than the nuclear chromatin and the flagellum covered by a membrane(Schmidt and Roberts, 1985).
- Macrogametocyte-Macrogamete:
- From Stage: Macrogametocyte
- To Stage: Macrogamete
- Description: After release from its enclosing erythrocyte, maturation of the macrogametocyte to the macrogamete involves little obvious change other than a shift of the nucleus toward the periphery(Schmidt and Roberts, 1985).
- Macrogamete_Microgamete-Zygote:
- Zygote-Ookinete:
- From Stage: Zygote
- To Stage: Ookinete
- Description: The diploid zygote quickly elongates to become a motile ookinete(Schmidt and Roberts, 1985). After fertilization, the resulting zygotes transform into motile ookinetes. Little is known about the factors that govern this dramatic morphological transition. Comparison of the number of gametocytes ingested by the mosquito with the number of resulting ookinetes indicates that only a small proportion of the parasites complete the differentiation from gametocyte to ookinete(Ghosh et al., 2000). Within approximately 24 hours of differentiation into an ookinete, the parasite has to cross two barriers, the peritrophic membrane and the midgut epithelium. How the ookinetes find their way from the interior of the blood mass out towards the epithelium (random or directed movement?) is an interesting question for which no information is available(Ghosh et al., 2000).
- Ookinete-Oocyst:
- From Stage: Ookinete
- To Stage: Oocyst
- Description: The ookinete penetrates the peritrophic membrane in the mosquito's gut, migrates to the hemocoel side of the gut, and begins its transformation into an oocyst(Schmidt and Roberts, 1985). After traversing the midgut epithelium, the ookinete reaches the extracellular space between the midgut epithelium and the overlaying basal lamina where it develops into an oocyst(Ghosh et al., 2000).
- Oocyst-Sporozoite:
- From Stage: Oocyst
- To Stage: Sporozoite
- Description: The oocyst progresses through a complex developmental process that, after 10 to 24 days (depending on species), culminates with the release of thousands of sporozoites into the hemocoel(Ghosh et al., 2000). As the oocyst differentiates, nuclei divide extensively in a common cytoplasm to yield several thousand sporozoites. One gene that is expressed selectively during this process encodes the circumsporozoite (CS) protein, a major sporozoite surface protein(Ghosh et al., 2000). Once in the hemocoel, sporozoites have access to a large number of organs and cell types. However, they invade only cells of the salivary gland epithelium(Ghosh et al., 2000). After salivary gland cell invasion, the parasites remain in the cytoplasm only transiently. They soon exit though the opposite (basal) side of the cell into the secretory cavity. Here, large numbers of sporozoites become organized in bundles and remain viable for the life of the mosquito. At each feeding cycle, a small number of sporozoites penetrate the secretory duct, from where they are expelled into the vertebrate host at the time of bloodfeeding(Ghosh et al., 2000).
- Picture(s):
-
Malaria Life Cycle (Website 124)
Description: The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host (1). Soporozoites infect liver cells and mature into schizonts (2), which rupture and release merozoites (3). Of note, in P. vivax and P. ovale a dormant stage, hynozoites, can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later (4). After this initial replication in the liver, called(exo-erythrocytic schizogony (A), the parasites undergo asexual multiplication in the erythrocytes, called erythrocytic schizogony (B). Merozoites infect red blood cells (5). The ring stage trophozoites mature into schizonts, which rupture releasing merozoites (6). Some parasites differentiate into sexual erythrocytic stages (gametocytes) (7). Blood stage parasites are responsible for the clinical manifestations of the disease.The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal (8). The parasites' multiplication in the mosquito is known as the sporogonic cycle (C). While in the mosquito's stomach, the microgametes penetrate the macrogametes generation zygotes (9). The zygotes in turn become motile and elongated ookinetes (10) which invade the midgut wall of the mosquito where they develop into oocysts (11). The oocysts grow, rupture, and release sporozoites (12), which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle (1). Copyright CDC(Website 124).
- Description: The cycle of malaria in the vector mosquito is a self-limited one that begins with zygote formation by male and female gametes and ends with the formation of sporozoites(Trager, 1986).
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Genome Summary
- Genome of Plasmodium falciparum
- Description: The P. falciparum 3D7 nuclear genome is composed of 22.8 megabases (Mb) distributed among 14 chromosomes ranging in size from approximately 0.643 to 3.29 Mb. Thus the P. falciparum genome is almost twice the size of the genome of the fission yeast Schizosaccharomyces pombe. The overall (A + T) composition is 80.6%, and rises to 90% in introns and intergenic regions. The structures of protein-encoding genes were predicted using several gene-finding programs and manually curated. Approximately 5,300 protein-encoding genes were identified, about the same as in S. pombe. This suggests an average gene density in P. falciparum of 1 gene per 4,338 base pairs (bp), slightly higher than was found previously with chromosomes 2 and 3 (1 per 4,500 bp and 1 per 4,800 bp, respectively). The higher gene density reported here is probably the result of improved gene finding software and larger training sets that enabled the detection of genes overlooked previously. Introns were predicted in 54% of P. falciparum genes, a proportion roughly similar to that in S. pombe and Dictyostelium discoideum, but much higher than observed in Saccharomyces cerevisiae where only 5% of genes contain introns. Excluding introns, the mean length of P. falciparum genes was 2.3 kb, substantially larger than in the other organisms in which the average gene lengths range from 1.3 to 1.6 kb. Plasmodium falciparum genes showed a markedly greater proportion of genes (15.5%) longer than 4 kb compared to S. pombe and S. cerevisiae (3.0% and 3.6%, respectively). The explanation for the increased gene length in P. falciparum is not clear. Many of these large genes encode uncharacterized proteins that may be cytosolic proteins, as they do not possess recognizable signal peptides. No transposable elements or retrotransposons were identified(Gardner et al., 2002B). Contiguous DNA sequences (contigs) have been obtained for chromosomes 1, 3, 4, 5 and 9, whereas chromosomes 6, 7, 8 and 13 contain a few gaps; most contigs have been ordered and oriented(Hall et al., 2002). As we were unable to produce unbroken sequence from telomere to telomere for all nine chromosomes, contiguous 'pseudo-chromosomes' were constructed by artificially joining all contigs that could be mapped to an individual chromosome. In most cases, the order and orientation of the contigs could be inferred using mapping data or read-pair information. Small contigs (of less than 5 kilobases, kb) that could not be mapped onto a chromosome have not been included in the analysis, and thus a small number of genes on the unmapped contigs will be missing from the genome sequence. The construction of pseudo-chromosomes does, however, have the advantage of allowing a global analysis of chromosome structure, and also removes redundancy from the analysis that would otherwise occur owing to contamination between chromosomes during purification and aberrant contigs formed during assembly(Hall et al., 2002). P. falciparum chromosomes were resolved on preparative pulsed field gels, and used to prepare shotgun libraries of 1 to 2 kilobase (kb) DNA fragments in plasmid vectors. Sequences of randomly selected clones were assembled, and gaps were closed using primer walking on plasmid templates or polymerase chain reaction (PCR) products. The cross-contamination of the chromosomal libraries with sequences from other chromosomes (up to 25%) and the high (A + T) content (80.6%) of P. falciparum DNA caused extreme difficulties in the gap closure process. Intergenic regions and introns frequently contained long runs of up to 50 consecutive A or T residues that were difficult to clone and sequence. The high (A plus T) content of the chromosomes also prevented the construction of large insert libraries that could be used to construct scaffolds of ordered and oriented contiguous DNA sequences (contigs) during assembly. Similar but more severe problems were reported in the sequencing of the (A plus T)-rich chromosome 2 of the slime mould Dictyostelium discoideum, illustrating the need to develop better methods for the cloning and sequencing of very (A plus T)-rich genomes. The reported sequences contain three or four short gaps (less than 2 kb) in each chromosome. Contigs comprising these chromosomes were joined end-to-end before annotation. Efforts to close the remaining gaps will continue.Examination of the sequences of chromosomes 2, 10, 11 and 14 revealed that the structure of these chromosomes was similar to that of the other chromosomes. All contained the 97 to 99% (A plus T) putative centromeric sequences reported previously. Conserved subtelomeric sequences were observed in chromosomes 2, 10 and 11, but most of these elements had been deleted from both ends of chromosome 14(Gardner et al., 2002). P. falciparum chromosome 12 is composed of 2,271,477 base pairs (bp). The sequence is completely contiguous; there are no gaps. This sequence is supported by a total of 91,191 reads (14.9-fold chromosome 12 coverage). Overall, the guanine-plus-cytosine (G plus C) content of chromosome 12 is 19.3%. As expected from this very low (G plus C) content, the P. falciparum chromosome 12 sequence contains many long runs of consecutive adenine and thymine residues. Runs of, at least, 20 such bases cover 18% of the chromosome 12 sequence. Bowman et al. were able to identify a region of extremely low (G plus C) content as the best candidate location for the centromere of P. falciparum chromosome 3. Our chromosome 12 sequence contains an analogous region between base positions 1,282,701 and 1,284,791 (2,090 bp; 0.092% of chromosome 12). That region has a (G plus C) content of 1.9%, is composed of the short tandem repeats characteristic of centromeres, and is, therefore, the putatative centromere of P. falciparum chromosome 12. To predict the genes encoded by P. falciparum chromosome 12, we used 'gene-calling' software in parallel with our colleagues at the WTSI2. Plasmodium falciparum chromosome 12 is predicted to encode 529 genes, including 23 genes from known Plasmodium-specific protein-encoding gene families (eight vars, twelve rifs, and three stevors) and three transfer RNA genes. The segmental (G plus C) content affects the speed and accuracy of sequencing. The predicted exons are, on average, 23.8% (G plus C), which is significantly higher than the overall average (19.3%). The predicted introns are, on average, 13.4% (G plus C), which is significantly lower than the overall average(Hall et al., 2002).
- Mitochondrion(Website 32)
- GenBank Accession Number: NC_002375
- Size: 5967 bp(Website 32).
- Gene Count: 3 genes(Website 32).
- Description: The complete 6 kb mitochondrial genome was sequenced from the single known isolate of P. reichenowi and from four different cultured isolates of P. falciparum, and aligned with the two previously derived P. falciparum sequences. The extremely low synonymous nucleotide polymorphism in P. falciparum (small pi, Greek equals 0.0004) contrasts with the divergence at such sites between the two species (K equals 0.1201), and supports a hypothesis that P. falciparum has recently emerged from a single ancestral population(Conway et al., 2000).
- Picture(s):
-
Plasmodium falciparum mitochondrion, complete genome (Website 32)
-
Plasmodium falciparum mitochondrion, complete genome (Website 32)
- Plastid(Website 61, Website 62)
- GenBank Accession Number: X95275 X95276
- Size: 15421 bp and 14001 bp(Website 61, Website 62). 34682 bp(Wilson et al., 1996).
- Gene Count: 67 genes(Williamson et al., 2002).
- Description: Malaria parasites and other members of the phylum apicomplexa harbour a relict plastid, homologous to the chloroplasts of plants and algae. The 'apicoplast' is essential for parasite survival, but its exact role is unclear. The apicoplast is known to function in the anabolic synthesis of fatty acids, isoprenoids and haeme, suggesting that one or more of these compounds could be exported from the apicoplast, as is known to occur in plant plastids. The apicoplast arose through a process of secondary endosymbiosis, in which the ancestor of all apicomplexan parasites engulfed a eukaryotic alga, and retained the algal plastid, itself the product of a prior endosymbiotic event. The 35-kb apicoplast genome encodes only 30 proteins, but as in mitochondria and chloroplasts, the apicoplast proteome is supplemented by proteins encoded in the nuclear genome and post-translationally targeted into the organelle by the use of a bipartite targeting signal, consisting of an amino-terminal secretory signal sequence, followed by a plastid transit peptide(Gardner et al., 2002).
- Plasmodium falciparum 3D7 chromosome 1(Website 3, Website 34)
- GenBank Accession Number: NC_004325
- Size: 643292(Website 34).
- Gene Count: 140(Website 3).
- Plasmodium falciparum 3D7 chromosome 2(Website 35, Website 36)
- GenBank Accession Number: NC_000910
- Size: 947102 bp(Website 36).
- Gene Count: 223(Website 35).
- Plasmodium falciparum 3D7 chromosome 3(Website 37, Website 38)
- GenBank Accession Number: NC_000521
- Size: 1060087 bp(Website 38).
- Gene Count: 237(Website 37).
- Plasmodium falciparum 3D7 chromosome 4(Website 39, Website 40)
- GenBank Accession Number: NC_004318
- Size: 1204112 bp(Website 40).
- Gene Count: 231(Website 39).
- Plasmodium falciparum 3D7 chromosome 5(Website 41, Website 42)
- GenBank Accession Number: NC_004326
- Size: 1343552 bp(Website 42).
- Gene Count: 312(Website 41).
- Plasmodium falciparum 3D7 chromosome 6(Website 43, Website 44)
- GenBank Accession Number: NC_004327
- Size: 1378756 bp(Website 44).
- Gene Count: 307(Website 43).
- Plasmodium falciparum 3D7 chromosome 7(Website 45, Website 46)
- GenBank Accession Number: NC_004328
- Size: 1351552 bp(Website 46).
- Gene Count: 262(Website 45).
- Plasmodium falciparum 3D7 chromosome 8(Website 47, Website 48)
- GenBank Accession Number: NC_004329
- Size: 1325595 bp(Website 48).
- Gene Count: 289(Website 47).
- Plasmodium falciparum 3D7 chromosome 9(Website 49, Website 50)
- GenBank Accession Number: NC_004330
- Size: 1541723 bp(Website 50).
- Gene Count: 355(Website 49).
- Plasmodium falciparum 3D7 chromosome 10(Website 51, Website 52)
- GenBank Accession Number: NC_004314
- Size: 1694445 bp(Website 52).
- Gene Count: 403(Website 51).
- Plasmodium falciparum 3D7 chromosome 11(Website 53, Website 54)
- GenBank Accession Number: NC_004315
- Size: 2035250 bp(Website 54).
- Gene Count: 486(Website 53).
- Plasmodium falciparum 3D7 chromosome 12(Website 55, Website 56)
- GenBank Accession Number: NC_004316
- Size: 2271477 bp(Website 56).
- Gene Count: 526(Website 55).
- Plasmodium falciparum 3D7 chromosome 13(Website 57, Website 58)
- GenBank Accession Number: NC_004331
- Size: 2732359 bp(Website 58).
- Gene Count: 669(Website 57).
- Plasmodium falciparum 3D7 chromosome 14(Website 59, Website 60)
- GenBank Accession Number: NC_004317
- Size: 3291006 bp(Website 60).
- Gene Count: 769(Website 59).
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Biosafety Information
-
Biosafety information for Plasmodium falciparum
- Level: Biosafety level 2(Website 118).
- Applicable: Laboratory-associated infections with Plasmodium spp. (including P. cynomologi); Trypanosoma spp.; and Leishmania spp. have been reported. Although no laboratory infections with Babesia spp. have been reported, they could result from accidental needlestick or from the bite of an infected tick.Although laboratory animal-associated infections are not common, mosquito-transmitted malaria infections do occur(Website 118).
- Precautions: Biosafety Level 2 practices and facilities are recommended for activities with infective stages. Infected arthropods should be maintained in facilities which reasonably preclude the exposure of personnel or their escape to the outside. Primary containment (e.g., biological safety cabinet) or personal protection (e.g., face shield) may be indicated when working with cultures of Leishmania spp., T. cruzi, or with tissue homogenates or blood containing hemoflagellates. Gloves are recommended for activities where there is the likelihood of direct skin contact with infective stages of the parasites listed(Website 118).
- Disposal: All cultures, stocks, and other regulated wastes are decontaminated before disposal by an approved decontamination method such as autoclaving. Materials to be decontaminated outside of the immediate laboratory are to be placed in a durable, leakproof container and closed for transport from the laboratory. Materials to be decontaminated outside of the immediate laboratory are packaged in accordance with applicable local, state, and federal regulations before removal from the facility(Website 119).
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Culturing Information
- P. falciparum liver stage in human hepatoma cell line :
- Description: Liver parasites completed their development within a Thai human hepatoma cell line (HHS-102), and the presence of ring-form parasites in erythrocytes overlying the liver cell culture confirmed that an entire liver cycle was completed, culminating in the production of viable blood-stage parasites. The HHS-102 cell line allows investigation of the undefined liver stage of falciparum malaria previously unavailable in the laboratory(Karnasuta et al., 1995).
- Medium: The human hepatoma cell line (HHS-102) cells were seeded into a sex-well tissure culture palte at a concentration of 2.0 x 10(5) cells/well and were maintained in 3 ml/well of a complete culture medium (a 1:1 mixture of RPMI 1640 meduim with L-glutamine[Sigma, St. Louis, MO] and minimum essential medium with L-glutamine [Gibco, Grand Island, NY] supplemented with 2.2 mg/ml of sodium bicarbonate, 150 U/ml penicillin, 150 mg/ml of streptomycin, and 10% fetal bovine serum)(Karnasuta et al., 1995).
- Continuous culture :
- Description: Continuous culture of any species of malarial parasite was first obtained in 1976 with Plasmodium falciparum, most important of the four species causing human malaria. The methods then reported have been widely used and have undergone relatively little modification. They depend on the maintenance of human erythrocytes under conditions that support intracellular development of the parasites(Trager, 1994).
- Medium: The culture medium is RPMI-1640, originally developed for human white blood cells supplemented with HEPES buffer and with hypoxanthine(Trager, 1994).
- Optimal Temperature: Dishes or plates must be incubated at 37-38 C(Trager, 1994).
- Note: Serum is an essential and important part of the medium(Trager, 1994). The ABO type should of course be compatible with the cells being used. Type O cells can be used with any type of serum, and AB serum with any type of cells. AB serum is also useful if cultures are being initiated with infected Aotus monkey erythrocytes(Trager, 1994).
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Epidemiology Information:
- Outbreak Locations:
- New data are presented from the Democratic Republic of the Congo, Tanzania, Ethiopia, and Zimbabwe on the increasing urban malaria problem and on epidemic malaria. Between 6% and 28% of the malaria burden may occur in cities, which comprise less than 2% of the African surface. Macroeconomic projections show that the costs are far greater than the costs of individual cases, with a substantial deleterious impact of malaria on schooling of patients, external investments into endemic countries, and tourism. Poor populations are at greatest risk; 58% of the cases occur in the poorest 20% of the world's population and these patients receive the worst care and have catastrophic economic consequences from their illness. The social vulnerability requires better understanding for improving deployment, access, quality, and use of effective interventions. Studies from Ghana and elsewhere indicate that for every patient with febrile illness assumed to be malaria seen in health facilities, 4 to 5 episodes occur in the community. Effective actions for malaria control mandate rational public policies; market forces, which often drive sales and use of drugs and other interventions, are unilkely to guarantee their use. Artemisinin-based combination therapy (ACT) for malaria is rapidly gaining acceptance as an effective approach for countering the spread and intensity of Plasmodium falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs. Although costly, ACT ($1.20 to 2.50 per adult treatment) becomes more cost-effective as resistance to alternative drugs increases; early use of ACT may delay development of resistance to these drugs and prevent the medical toll associated with use of ineffective drugs(Breman et al., 2004).
- Malaria is a major public health problem in sub-Saharan Africa. The high-elevation areas in East Africa had infrequent epidemic malaria between the 1920s and the 1950s. Malaria epidemics were not reported between the 1960s and the early 1980s after a malaria eradication campaign. Although the lack of documented epidemics in the highlands between the 1960s and the early 1980s could have been due to the methods for health data recording at the health clinics, it is well recognized that a series of malaria epidemics have occurred in the East African highlands, including the highlands in western Kenya, Uganda, Ethiopia, Tanzania, Rwanda, and Madagascar. As a consequence of low immunity in the human population of the highlands, malaria epidemics have caused significant human mortality in both children and adults. Compared to the malaria situation between the 1920s and 1950s, the current pattern of malaria in the highlands is characterized by increased frequencies, expanded geographic areas, and increased case-fatality rates(Zhou et al., 2004).
- We report an epidemic of Plasmodium falciparum malaria in the remote valley of Bamian (altitude 2250 m-2400 m) in the central highlands of Afghanistan. A team of malaria experts from the World Health Organization and HealthNet International carried out the investigation. A total of 215 peripheral blood smears were obtained and 63 cases of malaria (90.5% P. falciparum, the remainder P. vivax) were confirmed. The study revealed that areas vulnerable to malaria in Afghanistan are more widespread than previously recognized. The area had been malaria-free until recently, when the disease appears to have been introduced as a consequence of protracted conflict and resultant population movement, and transmitted locally during the short summer months. The outbreak led to severe morbidity and high mortality in a province having only a few poorly-provisioned health care facilities(Abdur et al., 2003).
- In August 2000, a charter flight brought 224 refugees from Tanzanian refugee camps to Mirabel airport just north of Montreal, Quebec, Canada. These refugees were immediately dispersed to smaller communities throughout the province to hasten their integration into Quebec society. Within 3 to 4 weeks of their resettlement, the McGill University Centre for Tropical Diseases (TDC), which acts as a reference center for the province, noted a striking increase in requests for confirmatory testing and assistance in treatment. There appeared to be an outbreak of malaria across the province. Malaria parasites were identified in 15 blood smears (11 with Plasmodium falciparum, 2 with Plasmodium ovale, and 2 with mixed infection) from African refugees submitted to the TDC during first 6 weeks after their arrival. Parasitemias ranged from 0.3 to 7%. Six children had parasitemias of greater than 3%, and one pregnancy was complicated by a diagnosis of P. falciparum(Ndao et al., 2004).
- Based on the reports of 18 fever related deaths in Bhojpur Primary Health Centre (PHC) of Moradabad District (UP), a study was undertaken during September and October, 2000 to explore the possibility of outbreak of malaria in the area and the reasons of the outbreak. The slide positivity rate (SPR) and slide falciparum rate (SFR) in active fever surveys were found to be 84.7% and 82.2% respectively. Among children the average enlarged spleen and spleen rate were 1.9 and 27.4 per cent respectively. The mortality rate of Anopheles culicifacies in DDT, Malathion and Deltamethrin was 42.5, 86.7 and cent per cent respectively. The results of the study revealed that the outbreak was of malaria with predominance of Plasmodium falciparum causing several deaths in the affected villages(Shukla et al., 2002).
- Parasitologic and entomologic cross-sectional surveys were carried out during an outbreak of malaria between December 1998 and August 2000 in forest villages near the Mohkhed Primary Health Center in the Chhindwara District of Madhya Pradesh in central India. In December 1998, surveys showed that more than 70% of the fever cases had malaria, with 87% of the malaria caused by Plasmodium falciparum. The rate of enlarged spleens in children was 74.5%. In November 1999, 58% of the inhabitants were infected with malaria, with 80% of these cases caused by P. falciparum. Chloroquine resistance was seen in 23% of the cases. Anopheles culicifacies was the dominant mosquito species in all surveys (70-85%) and was resistant to DDT. The results indicate that the incidence of malaria in Chhindwara has increased gradually from 0.31 per 1,000 in 1990 to 6.75 per 1,000 in 2000(Singh et al., 2003).
- Haiti is the only Caribbean island where malaria, practically always due to Plasmodium falciparum, persists in an epidemic-endemic state(Raccurt, 2002).
- Malaria epidemics in highland areas of East Africa have resulted in significant morbidity and mortality in the past decade. Highland areas of East Africa have been characterized as having unstable transmission, with similar rates of infection and disease in children and adults(John et al., 2004).
- Transmission Information:
- From:
Anopheles, Humans (at lifecycle stage: Sporozoite)
, To:
Homo sapiens, Humans (at lifecycle stage: Sporozoite)
--(at lifecycle progression level: Sporozoite-Trophozoite)
Mechanism: Malaria infection in humans is initiated with the bite of an infectious female mosquito, which inject sporozoites of Plasmodium species into the circulation. These sporozoites rapidly bind and invade liver cells and undergo rapid multiplication, leading to the release of thousands of infective merozoites(Raether et al., 1989).
- From:
Homo sapiens, Humans (at lifecycle stage: Microgametocyte, Macrogametocyte)
, To:
Anopheles, Humans (at lifecycle stage: Microgametocyte, Macrogametocyte)
--(at lifecycle progression level: Merozoite-Microgametocyte_Macrogametocyte)
Mechanism: The journey of Plasmodium within the mosquito begins as the mosquito ingests gametocytes with the blood of an infected host(Ghosh et al., 2003).
- From:
Homo sapiens, Humans , To:
Homo sapiens, Humans
Mechanism: Plasmodium sometimes is transmitted by means other than the bite of a mosquito. The blood cycle may be initiated by blood transfusion, by malaria therapy of certain paralytic disease, by syringe-passed infection among drug addicts, or, rarely, by congenital infection(Schmidt and Roberts, 1985). Transmission of malaria via blood transfusion is relatively uncommon in the U.S. Over the past 30 years the incidence has decreased and is now estimated at less than one case/million units. In most cases, the implicated donor had visited an endemic area or had emigrated from such an area. There were 1,402 cases of malaria reported in the U.S. in 2000. Two of those cases were congenital and two were blood related(Smith and Wright-Kanuth, 2003). In 1917, Wagner-Jauregg induced malaria for the first time to treat paresis. A soldier with tertian malaria (P. vivax) was admitted to the psychiatric clinic at the University Hospital for Nervous and Mental Disease in Vienna, Austria, in June 1917. Blood was passsaged to 3 patients with 'dementia paralytica', marking the beginning of malaria therapy. As a result of studies on the development of malaria therapy, Wagner-Jauregg was awarded the Nobel Prize for Medicine in 1927. The first detailed report of laboratory-based malarial studies associated with the treatment of neurosyphilitic patients in England was that of Colonel S. P. James (a member of the Malaria Committee of the League of Nations), and P.G. Shute in 1926. Because of objections to induction of malarial attacks by the direct inoculation of blood from patient to patient, they conducted extensive studies at the Horton Mental Hospital in Epsom on the use of bites of plasmodial-infected mosquitoes to induce malaria. The clinical, chemotherapeutic, and immunologic aspects of infections with P. vivax, P. falciparum, P. malariae, and P. ovale in some 2,500 patients observed in the Horton Hospital were reported(Collins and Jeffery, 1999). Eleven narcotic injectors from a prison in Saigon were hospitalized with falciparum malaria. Coma and intense parasitemia were common and eight patients died soon after admission. Two of three autopsied cases also had purulent pulmonary infections. No non-addicted prisoners were hospitalized for malaria. Nine more unsuspected falciparum infections were found among 29 other addicts in the prison. The clustering of malaria infections among narcotic injectors who had not been in malarious areas indicates that the malaria was transmitted by the common use of needles and syringes. Cerebral malaria in an addict may be misdiagnosed as drug intoxication. Malaria surveillance is recommended for the increasing addict population in the cities of Southeast Asia(Brown and Khoa, 1975). Congenital infection certainly occurs, but with very varying frequency in different parts of the world, and apparently in a way related to the absence or presence of immunity. In those places where malaria is endemic and relatively stable in character transmission to the child is very rare, and the many documented cases come mainly from places where the disease is less regular in occurrence, or less stable, or refer to mothers whose experience of the disease has been relatively recent(Russell et al., 1963).
- Environmental Reservoir:
- Humans:
- Description: The human reservoir of infection (during the non-transmission season) will depend on the rate of recovery from infection, which in turn depends on the extent of previous exposure and the immune reaction to infection. Both these factors will alter with age for a given intensity of transmission. Therefore, in the absence of novel infections, the human reservoir of infection will have an age-specific distribution(Paul et al., 2004).
- Survival: The prognosis in well-treated malaria is excellent, even under military conditions. For instance, the case mortality rate in American troops in the Second World War averaged less than 0.1 percent, on death per thousand hospital admissions for malaria. Untreated or poorly treated falciparum malaria in some areas may be fatal in up to 25 percent of cases(Russell et al., 1963). The prognosis of severe falciparum is poor, with a case fatality rate of 15-20% in African children. Mortality is higher when multiple syndromes of severe disease are present(Weatherall et al., 2002).
- Intentional Releases:
- Currently no intentional releases information is available.
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Diagnostic Tests Information
- Organism Detection Test:
- Conventional light microscopy :
- Description: Conventional light microscopy is the established method for the laboratory confirmation of malaria. The careful examination by an expert microscopist of a well prepared and well stained blood film remains currently the 'gold standard' for detecting and identifying malaria parasites. In most settings, the procedure consists of: collecting a finger-prick blood sample; preparing a thick blood smear (in some settings a thin smear is also prepared); staining the smear (most frequently with Giemsa); and examining the smear though a micrroscope (preferably with a 100X oil-immersion objective) for the presence of malaria parasite(Website 120). The detection limit of microscopy is approximately 5-20 parasites per ul(Hanscheid and Grobusch, 2002). Thick smears are 20 to 40 times more sensitive than thin smears for screening of Plasmodium parasites, with a detection limit of 10 to 50 trophozoites/ul. Thin smears allow one to identify malaria species (including the diagnosis of mixed infections), quantify parasitemia, and assess for the presence of schizonts, gametocytes, and malarial pigment in neutrophils and monocytes(Trampuz et al., 2003). The establishment and maintenance of a reliable and efficient diagnostic facility for malaria at the primary health care level is dependent on many (or a combination of) factors, which can seriously degrade the utility and relevance of the malaria laboratory. These can be broadly summarized as follows: A. DEFICIENCIES IN PERSONNEL: inadequate training; poor supervision; bad management including the improper utilization of the available expertise and work time. B. SUBSTANDARD OR INAPPROPRIATE EQUIPMENT: incorrect or poorly coordinated specifications, particularly of microscopes; irregular maintenance and replacement of worn-out parts; poor quality control of stains and reagents; inappropriate supply schedules which either cause delays in the supply of material or accumulate stocks which exceed the shelf-life of the material. C. INAPPROPRIATE TECHNOLOGY: improper use of techniques (e.g. think films for routine malaria diagnosis) or the introduction of new technology which in use is less efficient at the peripheral level than well-established methods; continuation of programs and routines which were once relevant but do not meet the current needs of primary health care. D. ORGANIZATIONAL DEFICIENCIES: the maintenance of an efficient and relevant organizational structure calls for frequent review and analysis of the current aims and objectives of the malaria diagnostic facility as well as the necessary changes in staffing and methods to meet these requirements with the resources available. From time to time this may involve radically changing how personnel and other resources are utilized and overcoming the inertia to change at both local and higher levels(Payne, 1988).
- Immunoassay Test:
- Rapid Diagnostic Tests :
- Description: Various test kits are available to detect antigens derived from malaria parasites. Such immunologic ("immunochromatographic") tests most often use a dipstick or cassette format, and provide results in 2-10 minutes. These "Rapid Diagnostic Tests" (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in some clinical settings and programs. However, before malaria RDTs can be widely adopted, several issues remain to be addressed, including improving their accuracy; lowering their cost; and ensuring their adequate performance under adverse field conditions. Malaria RDTs are currently not approved by the U. S. Food and Drug Administration (FDA) for use in the United States(Website 122). Dipstick antigen-capture assays are cost-effective for the management of P. falciparum malaria in specific conditions: in epidemics and emergencies; in mobile clinics; where laboratory services are inadequate; where first-line treatment is much more expensive than the dipstick assay; and in previously treated severe cases for whom blood films may have become negative. Unit cost will determine the future choice in many geographical areas(Guerin et al., 2002). A study was conducted to measure the overall performance of several rapid diagnostic tests for Plasmodium falciparum infection, in order to select the most appropriate test to be used in the field. A total of 742 patients attending the out-patient department of Mbarara Hospital with a clinical suspicion of malaria were included in the study. For each patient, a thick/thin film and 5 rapid tests based on the detection of histidine-rich protein II (HRP-II) (Paracheck Pf dipstick and device, ParaHIT f, Malaria Rapid and BIO P.F.) were performed. Outcomes were validity, inter-reader reliability and 'ease of use in the field', measured by both the general characteristics of the test and by the opinion of the readers. About half (57%) of the patients were positive for P. falciparum. The Paracheck Pf (dipstick and device) was considered as the most appropriate for the use in the field, being sensitive (97%), moderately specific (88%), reliable (kappa coefficient = 0.97), easy to use and cheap (about US $0.5/test). The ParaHIT f represented a good alternative(Guthmann et al., 2002).
- Indirect Fluorescent Antibody Test :
- Description: Malaria antibody detection is performed using the indirect fluorescent antibody (IFA) test. The IFA procedure can be used to determine if a patient has been infected with Plasmodium. Because of the time required for development of antibody and also the persistence of antibodies, serologic testing is not practical for routine diagnosis of acute malaria. However, antibody detection may be useful for: 1. Screening blood donors involved in cases of transfusion-induced malaria when the donor's parasitemia may be below the detectable level of blood film examination; 2. Testing a patient with a febrile illness who is suspected of having malaria and from whom repeated blood smears are negative; 3. Testing a patient who has been recently treated for malaria but in whom the diagnosis is questioned(Website 121).
- Nucleic Acid Detection Test:
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Infected Hosts Information
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- Homo sapiens
- Taxonomy Information:
- Species:
- Homo sapiens (Website 63):
- Common Name: Homo sapiens
- GenBank Taxonomy No.: 9606
- Description: Malaria in humans is caused by the transmission of sporozoites from infected anopheline mosquitoes during blood feeding. The complex life cycle results in the multiplication of parasites in the bloodstream following a 48-h (for Plasmodium falciparum) cycle of invasion, replication and release. The characteristic spikes of fever are seen after the rupture of the infected red blood cells(Craig et al., 2003). Mortality from P. falciparum malaria has been estimated at between one and two million deaths per year (mainly in children under five in sub-Saharan Africa), making it one of the big three infectious diseases in developing countries, the other two being tuberculosis and HIV/AIDS. In addition, although difficult to estimate, the economic burden on the poorest countries is also substantial. Despite an overall reduction in childhood mortality in Africa over the past few decades, the proportion of deaths attributable to malaria might have actually risen due to increasing drug resistance and lack of effective vector control programs(Craig et al., 2003).
- Disease Information:
- Falciparum Malaria :
- Incubation: Minimal prepatent periods are 5 days in falciparum, 8 in ovale and vivax, and 14 in malariae infections. Commonly, these periods may be longer, extending up to 15 days in falciparum, 17 in ovale and vivax, and 30 or more in malariae malaria. Average incubation periods are 12 days in falciparum, 14 in ovale and vivax, and 30 days in quartan infections(Russell et al., 1963),
- Prognosis:
Severe malaria usually occurs with parasitemia of 5% or more, and even with optimal management, the mortality rate exceeds 20%. At highest risk of complications from malaria are nonimmune people and children and pregnant women who live in endemic regions. Complications generally involve the central nervous, pulmonary, renal and hematopoietic systems. Hypoglycemia occurs because of parasite consumption of glucose and treatment with quinine; acidosis is another common metabolic derangement. Severe anemia, acute renal failure, respiratory failure, intravascular hemolysis and coagulopathies, and shock may develop. Bacterial infection may occur as a complication of malaria itself (e.g., aspiration pneumonia) or may be iatrogenic. One of the most serious complications is cerebral malaria, manifested by altered level of consciousness, focal neurologic findings and seizures. Mortality is high (15% to 25%), and survivors may have residual neurologic deficits. Although semi-immune people and those living in endemic regions tend not to experience severe malaria, they may still experience complications from recurrent infections. In children, severe anemia is the most common complication of chronic malaria, with hematocrits not infrequently approaching 15%. Massive splenomegaly causing abdominal pain may be associated with both bone marrow and immune dysfunction (hyperactive malarial splenomegaly). Nephrotic syndrome has also been attributed to falciparum malaria in endemic areas, as has splenic lymphoma(Suh et al., 2004),
- Diagnosis Summary: A high degree of suspicion and rapid diagnosis are essential to optimize outcome. Thick and thin peripheral blood smears, stained with Giemsa stain (or, alternatively, Wright's or Field's stains), remain the "gold standard" for routine clinical diagnosis. Malaria smears permit both species identification and quantification (expressed as a percentage of erythrocytes infected or as parasites per microlitre) of parasites. Malaria should not be excluded until at least 3 negative blood smears have been obtained within 48 hours. However, processing and interpretation of malaria smears require appropriate equipment as well as considerable training and expertise, factors that limit their use in endemic regions. Furthermore, accurate interpretation of malaria smears remains problematic in many established clinical laboratories, especially those outside major referral centres. Rapid malaria tests, which require minimal skill to perform and interpret, have been developed to overcome the problems of malaria smears. The most practical of these are the rapid antigen detection tests (RDTs), which detect parasite proteins in finger-prick blood samples. RDTs currently available can identify only P. falciparum and P. vivax, however. Malaria rapid test, manufactured by Makro Medical (Pty) Ltd., is the only test currently licensed for use in Canada. Important shortcomings of RDTs include their inability to quantitate parasitemia and suboptimal test performance with low-level parasitemia. Furthermore, because antigenemia may persist for prolonged periods even after treatment, some RDTs are unreliable as tests of cure. Nonetheless, their simplicity may make them attractive and useful alternatives to blood smears, particularly in laboratories where expertise in reading blood films is lacking or in centres where malaria is infrequently encountered. Based on clinical studies involving both travelers to and residents of endemic areas, the overall sensitivity and specificity of RDTs for the detection of falciparum malaria are over 90%. However, sensitivity falls dramatically with low-level parasitemia, and at present RDTs cannot be used alone to exclude malaria.Polymerase chain reaction (PCR) is a sensitive (more than 90%) and highly specific (almost 100%) test. It can detect extremely low numbers of parasites (and thus may be particularly useful in smear-negative cases) and is species-specific. However, most PCR assays do not have sufficiently rapid turnaround times to be clinically useful; therefore, PCR remains largely an investigational tool. Recent advances in real-time detection and automated DNA extraction may soon become available for routine laboratory diagnosis. Acridine orange staining (fluorescence microscopy) is technically difficult, requires special equipment and training, and is not widely used. Other diagnostic methods include automated detection of malaria pigment and flow cytometry. Serologic tests have no role in the diagnosis of acute malaria(Suh et al., 2004),
- Symptom Information :
- Syndrome -- Uncomplicated P. falciparum malaria :
- Description: The classical malaria attack or paroxysm has a sudden onset, followed by four well-marked stages - cold, hot, sweating, and apyrexial(Russell et al., 1963). A frank chill may not occur in falciparum infections by only slight chilliness followed by a more prolonged hot stage and much less sweating. The paroxysm is likely to be more exhausting than that of either vivax or malariae. Irregularity in the course of the paroxysm, which may last from 20 to 36 hours, is typical of falciparum infections. There is more prostration, headache is more severe, vomiting more frequent, mental confusion and torpor more common(Russell et al., 1963). The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of: a cold stage (sensation of cold, shivering); a hot stage (fever, headaches, vomiting; seizures in young children); and finally a sweating stage (sweats, return to normal temperature, tiredness)(Website 117).
- Symptom -- Anorexia :
- Description: The presenting symptoms were fever 100%, headache 97-100%, anorexia 78-90%, and nausea 28-40%(Wattanakoon et al., 2003).
- Observed:
- Symptom -- Chills :
- Description: A frank chill may not occur in falciparum infections by only slight chilliness followed by a more prolonged hot stage and much less sweating(Russell et al., 1963). The patient first experiences a chill or rigor during which he feels very cold although his temperature is rapidly rising. Shivering may rattle the bed. Teeth chatter, small hairs of the body stand erect in typical goose-flesh appearance, skin is dry, features pinched and blue, extremities somewhat cyanotic. The patient curls up in bed, covering himself with all available blankets, sweaters, and overcoats, but still feels cold(Russell et al., 1963). This stage lasts from 15 minutes to an hour or two(Russell et al., 1963).
- Observed:
- Symptom -- Fever :
- Description: The fever curve may be either subcontinuous or remittent, rather than sharply intermittent. In other words, there may not be a well-marked apyrexial period. Temperatures may rise more gradually and fall by lysis rather than by crisis. A temperature of 104 F or more should be considered a serious sign in falciparum malaria(Russell et al., 1963). A typical attack of benign tertian or quartan malaria begins with a feeling of intense cold as the hypothalamus, the body's thermostat, is activated, and the temperature then rises rapidly to 104 to 106 F. The teeth chatter, and the bed may rattle from the victim's shivering(Schmidt and Roberts, 1985).
- Observed:
- Symptom -- Headache :
- Description: The hot stage begins after 1/2 to 1 hour, with intense headache and feeling of intense heat(Schmidt and Roberts, 1985). There may be headache, nausea, and vomiting. This stage lasts from 15 minutes to an hour or two(Russell et al., 1963). As shivering ceases, the patient begins to feel hot so that he discards his covers. His face is now flushed, eyes are suffused, skin remains dry but hot, and instead of appearing blue it may have a slight icteric tinge. His pulse is full and bounding, respiration rapid. He suffers from increased headache, parched throat, coated tongue, great thirst, nausea, and sometimes vomiting(Russell et al., 1963).
- Observed:
- Symptom -- Hepatomegaly :
- Description: In P. falciparum malaria, additional findings may include enlargement of the liver(Website 117).
- Symptom -- Jaundice :
- Description: In P. falciparum malaria, additional findings may include mild jaundice(Website 117).
- Symptom -- Myalgia :
- Description: Patients with P. falciparum malaria present with high fever that may be accompanied by chills, rigors, sweats, and headache. Other common findings include generalized weakness, backache, myalgias, vomiting, and pallor(Stauffer and Fischer, 2003).
- Symptom -- Nausea :
- Description: There may be headache, nausea, and vomiting. This stage lasts from 15 minutes to an hour or two(Russell et al., 1963). As shivering ceases, the patient begins to feel hot so that he discards his covers. His face is now flushed, eyes are suffused, skin remains dry but hot, and instead of appearing blue it may have a slight icteric tinge. His pulse is full and bounding, respiration rapid. He suffers from increased headache, parched throat, coated tongue, great thirst, nausea, and sometimes vomiting(Russell et al., 1963).
- Observed:
- Symptom -- Sweats :
- Description: Rather suddenly, the patient begins to perspire profusely, first on face and hands, then from every pore, drenching garments and sheets. He feels a great sense of relief, his headache and vomiting cease, his pulse becomes more normal, he feels tired and drowsy and usually falls asleep, with temperature normal or perhaps a little subnormal. The sweating stage lasts 1 to 5 hours(Russell et al., 1963).
- Symptom -- Tachycardia :
- Description: As shivering ceases, the patient begins to feel hot so that he discards his covers. His face is now flushed, eyes are suffused, skin remains dry but hot, and instead of appearing blue it may have a slight icteric tinge. His pulse is full and bounding, respiration rapid(Russell et al., 1963).
- Symptom -- Tachypnea :
- Description: In P. falciparum malaria, additional findings may include increased respiratory rate(Website 117). As shivering ceases, the patient begins to feel hot so that he discards his covers. His face is now flushed, eyes are suffused, skin remains dry but hot, and instead of appearing blue it may have a slight icteric tinge. His pulse is full and bounding, respiration rapid(Russell et al., 1963).
- Symptom -- Vomiting :
- Description: There may be headache, nausea, and vomiting. This stage lasts from 15 minutes to an hour or two(Russell et al., 1963). As shivering ceases, the patient begins to feel hot so that he discards his covers. His face is now flushed, eyes are suffused, skin remains dry but hot, and instead of appearing blue it may have a slight icteric tinge. His pulse is full and bounding, respiration rapid. He suffers from increased headache, parched throat, coated tongue, great thirst, nausea, and sometimes vomiting(Russell et al., 1963).
- Syndrome -- Complicated P. falciparum malaria :
- Description: Severe malaria, as defined by the World Health Organization, refers to a parasitemic person with 1 or more of the following: prostration (inability to sit up without help), impaired consciousness, respiratory distress or pulmonary edema, seizures, circulatory collapse, abnormal bleeding, jaundice, hemoglobinuria or severe anemia (hemoglobin less than 50 g/L or hematocrit less than 15%). Prostration and altered consciousness occur frequently in both children and adults with severe disease; respiratory distress, seizures and severe anemia are more common in children, whereas renal failure and jaundice occur more frequently in adults. Acute respiratory distress syndrome, an immune-mediated complication, often occurs during the second to fourth day of treatment, even when parasitemia is decreasing. Severe malaria usually occurs with parasitemia of 5% or more, and even with optimal management, the mortality rate exceeds 20%. At highest risk of complications from malaria are nonimmune people and children and pregnant women who live in endemic regions. Complications generally involve the central nervous, pulmonary, renal and hematopoietic systems. Hypoglycemia occurs because of parasite consumption of glucose and treatment with quinine; acidosis is another common metabolic derangement. Severe anemia, acute renal failure, respiratory failure, intravascular hemo-lysis and coagulopathies, and shock may develop. Bacterial infection may occur as a complication of malaria itself (e.g., aspiration pneumonia) or may be iatrogenic. One of the most serious complications is cerebral malaria, manifested by altered level of consciousness, focal neurologic findings and seizures. Mortality is high (15% to 25%), and survivors may have residual neurologic deficits(WHO, 2000). Severe malaria occurs when P. falciparum infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism(Website 117). In all areas, severe malaria is a medical emergency and should be treated urgently and aggressively(Website 117).
- Symptom -- Abnormal bleeding :
- Description: This is rare in children with severe malaria. A check should be made for bleeding from gums, nose, gastrointestinal tract or venopuncture sites. When possible clinical evidence of bleeding should lead to appropriate laboratory investigations(WHO, 2000).
- Symptom -- Anemia :
- Description: Anemia is one of the commonest complications of malaria in children and pregnant women living in endemic areas, where the specific effect of the infection may be combined with iron or folate deficiency and with inborn hemoglobin disorders or enzymopathies. The degree of normocytic, hemolytic anemia following the plasmodial infection is usually greater than can be explained by simple destruction of the parasitized erythrocytes(Bruce-Chwatt, 1985).
- Observed:
Severe anemia (Hb less than 50 g/L) occurred in 42 (17.1%) and moderate anemia (Hb 50-89 g/L) was present in 104 patients (42.2%)(Banzal et al., 1999),
- Symptom -- Chills/rigor :
- Description: The symptoms and signs of severe falciparum malaria are non-specific. The illness usually starts with aching of the head, back and limbs, dizziness, malaise, anorexia, vague abdominal pain, vomiting, or mild diarrhea with fevers and chills(WHO, 2000). A typical attack of benign tertian or quartan malaria begins with a feeling of intense cold as the hypothalamus, the body's thermostat, is activated, and the temperature then rises rapidly to 104 to 106 F. The teeth chatter, and the bed may rattle from the victim's shivering(Schmidt and Roberts, 1985). The clinical symptoms of malaria are primarily due to schizont rupture and destruction of erythrocytes. Malaria can have a gradual or a fulminant course with nonspecific symptoms. The presentation of malaria often resembles those of common viral infections; this may lead to a delay in diagnosis. The majority of patients experience fever (>92% of cases), chills (79%), headaches (70%), and diaphoresis (64%)(Trampuz et al., 2003).
- Observed:
- Symptom -- Dark urine :
- Description: The urine may be at first like light red wine, deepening in color to tat of port wine and then becoming dark brown. During the period of recovery the urine turns to light brown and finally yellow. Some abnormal color may persist for a week or longer. The urine is colored by oxyhaemoglobin, methaemoglobin, and urobilin. The reaction is markedly acid and there is much albumin. Bile may be present. One finds microscopic brown debris and haemoglobin casts by few red cells(Russell et al., 1963).
- Observed:
- Symptom -- Diarrhea :
- Description: The symptoms and signs of severe falciparum malaria are non-specific. The illness usually starts with aching of the head, back and limbs, dizziness, malaise, anorexia, vague abdominal pain, vomiting, or mild diarrhea with fevers and chills(WHO, 2000). The clinical symptoms of malaria are primarily due to schizont rupture and destruction of erythrocytes. Malaria can have a gradual or a fulminant course with nonspecific symptoms. The presentation of malaria often resembles those of common viral infections; this may lead to a delay in diagnosis. The majority of patients experience fever (>92% of cases), chills (79%), headaches (70%), and diaphoresis (64%). Other common symptoms include dizziness, malaise, myalgia, abdominal pain, nausea, vomiting, mild diarrhea, and dry cough(Trampuz et al., 2003).
- Observed:
- Symptom -- Drowsiness :
- Description: Rather suddenly, the patient begins to perspire profusely, first on face and hands, then from every pore, drenching garments and sheets. He feels a great sense of relief, his headache and vomiting cease, his pulse becomes more normal, he feels tired and drowsy and usually falls asleep, with temperature normal or perhaps a little subnormal. The sweating stage lasts 1 to 5 hours(Russell et al., 1963).
- Observed:
- Symptom -- Fever :
- Description: The symptoms and signs of severe falciparum malaria are non-specific. The illness usually starts with aching of the head, back and limbs, dizziness, malaise, anorexia, vague abdominal pain, vomiting, or mild diarrhea with fevers and chills(WHO, 2000). A typical attack of benign tertian or quartan malaria begins with a feeling of intense cold as the hypothalamus, the body's thermostat, is activated, and the temperature then rises rapidly to 104 to 106 F. The teeth chatter, and the bed may rattle from the the victim's shivering(Schmidt and Roberts, 1985).
- Observed:
- Symptom -- Headache :
- Description: The symptoms and signs of severe falciparum malaria are non-specific. The illness usually starts with aching of the head, back and limbs, dizziness, malaise, anorexia, vague abdominal pain, vomiting, or mild diarrhea with fevers and chills(WHO, 2000). The hot stage begins after 1/2 to 1 hour, with intense headache and feeling of intense heat(Schmidt and Roberts, 1985). The clinical symptoms of malaria are primarily due to schizont rupture and destruction of erythrocytes. Malaria can have a gradual or a fulminant course with nonspecific symptoms. The presentation of malaria often resembles those of common viral infections; this may lead to a delay in diagnosis. The majority of patients experience fever (>92% of cases), chills (79%), headaches (70%), and diaphoresis (64%)(Trampuz et al., 2003).
- Observed:
- Symptom -- Hepatosplenomegaly :
- Description: Children who are partially immune (e.g., newly arrived immigrants or refugees from areas where malaria is highly endemic) frequently present with signs such as hepatosplenomegaly, anemia, and jaundice(Stauffer and Fischer, 2003).
- Observed:
Of children with positive test results, one-third were asymptomatic, and splenomegaly was the only manifestation of disease in one-third(Stauffer and Fischer, 2003),
- Symptom -- Jaundice :
- Description: This is detected clinically by examining the sclera and/or mucosal surfaces of the mouth(WHO, 2000). Renal failure and jaundice occur more frequently in adults(WHO, 2000).
- Observed:
- Symptom -- Malaise :
- Description: Other common symptoms include dizziness, malaise, myalgia, abdominal pain, nausea, vomiting, mild diarrhea, and dry cough(Trampuz et al., 2003).
- Symptom -- Myalgia :
- Description: The symptoms and signs of severe falciparum malaria are non-specific. The illness usually starts with aching of the head, back and limbs, dizziness, malaise, anorexia, vague abdominal pain, vomiting, or mild diarrhea with fevers and chills(WHO, 2000). Other common symptoms include dizziness, malaise, myalgia, abdominal pain, nausea, vomiting, mild diarrhea, and dry cough(Trampuz et al., 2003).
- Symptom -- Pallor :
- Description: Other common findings include generalized weakness, backache, myalgias, vomiting, and pallor(Stauffer and Fischer, 2003).
- Observed:
- Symptom -- Prostration :
- Description: This is the inability to sit unassisted in a child who is normally able to do so. In children not old enough to sit up it is defined as the inability to feed. Prostration must always be recorded directly and not based on history. Many children who are pyrexial and feel unwell prefer to lie or be carried but are capable of sitting if gently encouraged to do so(WHO, 2000). In adults prostration is usually manifested as extreme weakness(WHO, 2000).
- Symptom -- Pulmonary edema :
- Description: Pulmonary oedema appears to be a rare manifestation of malaria in children, but diagnosis is often difficult and really requires a chest X-ray(WHO, 2000).
- Symptom -- Respiratory distress :
- Description: Deep breathing (acidotic breathing, Kussmaul breathing) is the most important respiratory sign of severe malaria as it has good sensitivity and specificity for the detection of metabolic acidosis by trained observers. The important component is increased inspiratory and expiratory excursion of the chest(WHO, 2000).
- Observed:
- Symptom -- Renal failure :
- Description: Renal failure and jaundice occur more frequently in adults(WHO, 2000). Acute renal failure did not occur as an isolated complication without the presence of one or more of the other major complications(Banzal et al., 1999).
- Observed:
- Symptom -- Seizures :
- Description: Many children with malaria have convulsions. In the absence of severe malaria, generalized seizures were associated with a 9-fold increase in risk of fatal outcome in children. The length, nature and number of convulsions should be recorded. Many convulsions associated with malaria are focal and care should be taken to detect minor manifestations such as twitching of a digit, repetitive jerky eye movements with deviation, increased salivation or abnormal respiratory patterns(WHO, 2000).
- Observed:
- Symptom -- Severe anemia :
- Description: Respiratory distress, seizures, and severe anemia are more frequent in children(WHO, 2000). Severe anemia was the commonest feature of severe malaria present in 395 (67.8%,) of the children(Dzeing-Ella et al., 2005).
- Observed:
- Symptom -- Sweats :
- Description: Rather suddenly, the patient begins to perspire profusely, first on face and hands, then from every pore, drenching garments and sheets. He feels a great sense of relief, his headache and vomiting cease, his pulse becomes more normal, he feels tired and drowsy and usually falls asleep, with temperature normal or perhaps a little subnormal. The sweating stage lasts 1 to 5 hours(Russell et al., 1963).
- Symptom -- Vomiting :
- Description: The symptoms and signs of severe falciparum malaria are non-specific. The illness usually starts with aching of the head, back and limbs, dizziness, malaise, anorexia, vague abdominal pain, vomiting, or mild diarrhea with fevers and chills(WHO, 2000). The clinical symptoms of malaria are primarily due to schizont rupture and destruction of erythrocytes. Malaria can have a gradual or a fulminant course with nonspecific symptoms. The presentation of malaria often resembles those of common viral infections; this may lead to a delay in diagnosis. The majority of patients experience fever (>92% of cases), chills (79%), headaches (70%), and diaphoresis (64%). Other common symptoms include dizziness, malaise, myalgia, abdominal pain, nausea, vomiting, mild diarrhea, and dry cough(Trampuz et al., 2003).
- Observed:
- Syndrome -- Cerebral Malaria/Severe Malaria :
- Description: The onset of cerebral malaria varies greatly and may be gradual or sudden. For instance, a man may be seen in the outpatient clinic in the morning, afebrile and complaining only of headache, but he may be brought in with comatose malaria in the afternoon. Patients may be found in a malaria coma an hour or two after ward rounds, when they had seemed normally responsive. The potentialities of cerebral malaria have given rise to the common saying that falciparum malaria is a medical emergency to be treated promptly and to be observed with great care through the acute phases. Signs of meningeal irritation in pernicious malaria have been observed by most clinicians in the tropics, where they are common in children. Headache, vomiting, sighing respiration, full rapid pulse, transitory amblyopia, diplopia, stiff neck, and positive Kernig's sign have been noted. Other indications of cerebral malaria are excitement, disorientation, delirium, negativism, convulsions (especially in children), somnolence, and coma. The comatose condition in malaria may resemble that of encephalitis lethargica. The patient may be stimulated to answer a question, but sinks back into deep stupor. Occasionally ataxia, aphasia, amnesia, or collapse will mark the early stages of cerebral malaria. Sometimes hiccup or loss of sphincteric control will be the first sign(Russell et al., 1963).
- Observed:
In many parts of the world cerebral malaria is the most common clinical presentation and cause of death in adults with severe malaria. In Thailand and Viet Nam about half the cases of severe malaria had cerebral malaria. Among Melanesian adults with severe falciparum malaria in Central Province, Papua, New Guinea, only 17% presented with cerebral malaria(WHO, 2000),
- Symptom -- Abnormal behaviour :
- Description: Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities(Website 117).
- Symptom -- Amnesia (Russell et al., 1963):
- Symptom -- Aphasia (Russell et al., 1963):
- Symptom -- Ataxia (Russell et al., 1963):
- Symptom -- Collapse (Russell et al., 1963):
- Symptom -- Coma :
- Description: Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities(Website 117). The depth of coma may be assessed by observing the response to standard painful or vocal stimuli(WHO, 2000).
- Symptom -- Convulsions :
- Description: Convulsions are common before or after the onset of coma(WHO, 2000). Convulsions may be generalized or focal, single or recurrent and, unlike febrile convulsions, may occur in children of any age and at any level of body temperature(WHO, 2000).
- Observed:
Over 50% of children with cerebral malaria have convulsion(WHO, 2000), The incidence of convulsions in adult Thai and Vietnamese patients has fallen from 50% to less than 20% over the past 10 years without obvious explanation(WHO, 2000),
- Symptom -- Coughing :
- Description: Vomiting and coughing were reported in the majority(WHO, 2000).
- Symptom -- Delirium :
- Description: In the past patients with headache, neck stiffness, drowsiness, delirium, febrile convulsions, focal neurological signs or even behavioral disturbances who were not comatose were often described as having cerebral malaria(WHO, 2000).
- Symptom -- Diplopia (Russell et al., 1963):
- Symptom -- Disorientation :
- Description: Sudden onset may be marked by mania and psychotic symptoms or convulsions, especially in children(Schmidt and Roberts, 1985).
- Symptom -- Excitement (Russell et al., 1963):
- Symptom -- Fever :
- Description: In children with cerebral malaria who are admitted to hospital, the duration of febrile symptoms is usually short. In a series of 131 patients studied in Malawi, the mean length of reported history was 47 h (range 2 h to 7 d); in 195 Zambian children with cerebral malaria, the median duration of preceding fever had been 49.3 h (range 0 to 13 d). The earliest sign is fever(WHO, 2000). An uncontrollable rise in temperature to above 108 F may occur(Schmidt and Roberts, 1985).
- Symptom -- Headache :
- Description: In the past patients with headache, neck stiffness, drowsiness, delirium, febrile convulsions, focal neurological signs or even behavioral disturbances who were not comatose were often described as having cerebral malaria(WHO, 2000). A progressive headache may be followed by coma(Schmidt and Roberts, 1985).
- Symptom -- Hiccup :
- Description: Sometimes hiccup or loss of sphincteric control will be the first sign(Russell et al., 1963).
- Symptom -- Impairment of consciousness :
- Description: Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities(Website 117).
- Symptom -- Jaundice :
- Description: Jaundice is reported to be less common in children than in adults with cerebral malaria(WHO, 2000).
- Symptom -- Kernig's sign (Russell et al., 1963):
- Symptom -- Negativism (Russell et al., 1963):
- Symptom -- Seizures :
- Description: Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities(Website 117).
- Symptom -- Sighing respiration :
- Description: Breathing may be rapid or labored; deep breathing suggests acidosis(WHO, 2000).
- Symptom -- Somnolence (Russell et al., 1963):
- Symptom -- Stiff neck (Russell et al., 1963):
- Symptom -- Transitory amblyopia (Russell et al., 1963):
- Symptom -- Vomiting :
- Description: Vomiting and coughing were reported in the majority(WHO, 2000).
- Syndrome -- Blackwater Fever :
- Description: Hemoglobinuric fever, malarial hemoglobinuria, or as it is commonly called, blackwater fever, is a serious condition occurring in highly malarious areas and characterized by sudden onset, chills, fever, and intravascular hemolysis with the discarge of urine containing hemoglobin. Most observers believe that blackwater fever is malaria complicated with hemoglobinuria(Russell et al., 1963). Blackwater fever (BWF) is a severe clinical syndrome, characterized by intravascular hemolysis, hemoglobinuria, and acute renal failure that is classically seen in European expatriates chronically exposed to Plasmodium falciparum and irregularly taking quinine(Bruneel et al., 2001). In recent years, with much less use of quinine therapy and with greatly intensified malaria control, blackwater fever has disappeared from numerous areas where it was once common. World-wide incidence of blackwater fever is now at a low level(Russell et al., 1963). Although prodomal jaundice or mild fever may occur, the onset of blackwater fever is generally abrupt and an attack usually consists of a single severe hemoclastic explosion which does its damage in a few hours(Russell et al., 1963).
- Observed:
BWF virtually disappeared after 1950, when chloroquine superseded quinine(Bruneel et al., 2001), During our study period, the incidence of BWF per 100 cases of malaria was about 2.6%. However, this figure may be an overestimation, since it has been suggested that approximately 50% of malaria cases go unreported(Bruneel et al., 2001),
- Treatment Information:
- Antibiotics : Various antibiotics that are known to be antibacterial agents also exhibit antimalarial activity(Wiesner et al., 2003). In practice, doxycycline is the most frequently used antibiotic in antimalarial therapy, either on its own as a prophylactic, or in combination (commonly used with quinine or artesunate) for treatment in cases of multiresistance(Wiesner et al., 2003). Tetracycline is an antibiotic that probably acts by inhibiting the binding of aminoacyl tRNA to the ribosome. It acts fairly slowly (over days rather than hours), is well absorbed orally, and has an elimination half-time of 8 h, which is similar to that of quinine. Tetracycline maintains activity against multidrug resistant parasites(Kremsner and Krishna, 2004).
- Contraindicator: Doxycycline and other tetracycline's are contraindicated in individuals with hepatic dysfunction(Petersen, 2004). Doxycycline is contra-indicated in children and pregnant women and is potentially responsible for photosensitizing reactions(Wiesner et al., 2003). Tetracycline is contraindicated in children and pregnant women(Kremsner and Krishna, 2004).
- Complication: Reported side effects vary between different studies but about 15% report some kind of adverse events and 3% some kind of rash but the incidence of photo-allergic reactions in sun-loving tourists still needs to be established. A common side effect is heartburn, which can be avoided by taking doxycycline with food and abundant fluid. Vaginal candidasis is well known in women but the risk is unknown(Petersen, 2004).
- Success Rate: Because of their slow effect, antibiotics are only applied as prophylactics or in combination with other antimalarial drugs(Wiesner et al., 2003).
- Drug Resistance: There is no known resistance against doxycycline in Plasmodium falciparum(Petersen, 2004).
- Amodiaquine : Amodiaquine is structurally similar and cross-resistant to chloroquine. It is effective against low-level chloroquine-resistant P. falciparum but not against highly chloroquine-resistant parasites. Amodiaquine had fallen out of favour because of its serious toxicity when used as prophylaxis. However, it is becoming increasingly recognized that amodiaquine is a useful drug for treating falciparum malaria in Africa. It is inexpensive, has good tolerability and lacks a bitter taste, an advantage for paediatric use. The WHO recommended dosage is 10 mg/kg base once daily for 3 days(Taylor and White, 2004).
- Contraindicator: Amodiaquine must not be used as prophylaxis. Know allergy contraindicates the use of amodiaquine(Taylor and White, 2004).
- Complication: When used for malaria prophylaxis, in multiple doses over prolonged periods, agranulocytosis and hepatitis claimed a small number of deaths (mainly in Europe) in the mid-1980s; this caused its withdrawal as a chemoprophylactic agent. There is little or no evidence that amodiaquine is similarly toxic when used for treatment in a 25 mg/kg dose over 3 d; certainly, despite extensive use in Papua New Guinea the drug has a good safety reputation(Winstanley et al., 2002).
- Success Rate: In a study of Nigerian children, amodiaquine appears more effective than chloroquine, effective against chloroquine-resistant infections, and well tolerated by children with acute, uncomplicated, P. falciparum malaria. It may therefore be useful as an alternative to chloroquine in areas of chloroquine resistance(Sowunmi et al., 2001).
- Drug Resistance: The in vivo response of Plasmodium falciparum parasites to amodiaquine or chloroquine was assessed in children with symptomatic malaria attending different health facilities in the Madang area. Among the 27 subjects who were completely followed up, 4 (15%) were infected with parasites fully susceptible and 23 (85%) with parasites exhibiting some degree of resistance. The level of in vivo resistance was similar for amodiaquine and chloroquine. 86% of the isolates tested in vitro showed resistance to amodiaquine, 86% to chloroquine and 7% to quinine. In ten years the prevalence of resistant isolates in vivo has increased from 47% to 85%(al-Yaman et al., 1996).
- Artemisinin and derivatives (eg, artemether, artesunate, and dihydroartemisinin) : Artemisinin is a potent antimalarial compound extracted from plant material. Artemether, artesunate, and dihdroartemisinin are semisynthetic derivatives of artemisinin that are in common clinical use. Members of the artemisinin group are used in the management of severe malaria and also, usually in combination with other drugs, in the treatment of uncomplicated falciparum malaria. The artemisinin group is potent and well tolerated, and resistance has not been encountered in the field. It would not be an exaggeration to say that many public health strategies worldwide are now dependent on this drug class; its major disadvantage is its relatively high cost, but this is falling at present. It is thought that breakdown of a labile peroxide bridge within the sesquiterpene lactone molecule generates free radicals that rapidly alkylate parasite membranes. Hemazoin probably catalyzes the decomposition of these drugs, which may explain the large therapeutic index of the drug group. One strain of P. berghei (an animal malaria parasite) that lacks hemozoin is resistant to the artemisinins, but resistant P. falciparum strains have not yet been encountered in the field. In contrast to other antimalarial drug groups, the artemisinins have marked effects on the circulating forms of the parasite, whose viability declines soon after the start of treatment. The artemisinins have gametocytocidal effects on P. falciparum, and this may help reduce transmission(Winstanley et al., 2004).
- Contraindicator: Contraindications are few; namely, documented drug allergy. Because animal studies have shown embryonic death, artemisinin derivative use in the first trimester of pregnancy should be restricted to women with severe malaria or uncomplicated, multidrug-resistant P. falciparum for whom there is no safer alternative. The artemisinin derivatives may be used in the second and third trimesters of pregnancy in areas of drug resistance or where other drugs are less effective(Taylor and White, 2004).
- Complication: Artemisinins form a safe and well-tolerated drug group. The main current concern centers on reproductive safety. The Chinese literature contains reference to the embryotoxic effects of this drug class. Recent drug development work provides further evidence of morphological abnormalities in mammalian species; most concern focuses on long-bone shortening. These effects are seen at doses and concentrations similar to those used in clinical practice. It is reassuring that the artemisinins have been extensively used without apparent problems for many years in China and Southeast Asia, and huge numbers of patients have been treated. Pharmacovigilance systems are not well established in China and Southeast Asia, but, despite this, it is important to note that no spontaneous reports of congenital abnormalities have been published. Furthermore, published data on nearly 1,000 pregnancies (nearly 100 from the first trimester) have shown no evidence of treatment-related adverse pregnancy outcomes. While these results are encouraging, the numbers are too small to establish the safety of these compounds when used to treat malaria in pregnant women, and pharmacovigilance systems are now being established to increase the database. The WHO has concluded that (i) the artemisinins cannot be recommended for treatment of malaria in the first trimester (but should not be withheld if they are lifesaving for the mother) and (ii) they should be used in later pregnancy only when other treatments are considered unsuitable. It is salutary to remember that many women exposed to artemisinins may not know that they are pregnant and, given the inadequacy of diagnostic facilities, that these women may not have malaria(Winstanley et al., 2004).
- Success Rate: Several hundred thousands of patients have been treated with artemisinin derivatives, particularly in China, Vietnam, and Thailand, and so far, no major side effects have been reported. No significant differences were found in efficacy and/or toxicity profiles among the different compounds. They were effective against all human malaria Plasmodia. The drugs showed rapid clinical improvement, good tolerability, and clearance of parasites from the blood within 2 days. Artemisinin and its derivatives should be administered preferably in combination with another effective antimalarial drug (with a blood schizonticide) in order to reduce recrudescences and to prevent or slow the development of resistance(Balint, 2001).
- Drug Resistance: Resistance has not been encountered in the field(Winstanley et al., 2004).
- Artesunate/amodiaquine combination : WHO developed artesunate+amodiaquine for treatment of malaria in African children through a private-public partnership. In a multicentre phase III trial in Gabon, Kenya, and Senegal, this new drug combination showed a better overall efficacy than amodiaquine alone. However, 6% of patients in both groups developed neutropenia, a finding that warrants further investigations, especially since this adverse event is often associated with amodiaquine. Moreover, as is the case for artesunate and mefloquine and artesunate and sulfadoxine-pyrimethamine, this combination shows a high degree of pharmacokinetic mismatch. In most African regions where malaria is hyperendemic, widespread use of this regimen will necessarily lead to a prolonged exposure of parasites to low doses of amodiaquine and its active metabolite. Despite the rather disappointing findings of a multicentre trial, WHO recommends this regimen for treatment of uncomplicated falciparum malaria in African children. Indeed, in some African countries artesunate and amodiaquine is considered as first-line treatment for children with uncomplicated malaria(Kremsner and Krishna, 2004).
- Artesunate/lumefantrine combination : Artemether and lumefantrine is the only fixed-dose artemisinin-containing formulation registered after internationally recognized guidelines. It seemed safe and well tolerated in children as well as in adults; however, a study showed irreversible hearing impairment. Like atovaquone, lumefantrine absorption is enhanced with food, causing problems in children with malaria. It is also expensive. Lumefantrine is structurally related to halofantrine and has a half-life of several days but, unlike halofantrine, does not cause cardiotoxicity. Like artesunate and mefloquine, there is considerable mismatch in elimination half-lives of artemether and lumefantrine. In early studies, a four-dose regimen was not particularly effective. These findings led to the recommendation of a more complex 3-day regimen, which should be given at 0, 8, 24, 36, 48, and 60 h. Efficacy of the six-dose regimen is adequate, but inferior to the combination of artesunate and mefloquine in Thailand(Kremsner and Krishna, 2004).
- Artesunate/mefloquine combination : A 3-day regimen of artesunate and mefloquine has been the preferred treatment for malaria in Thailand for almost a decade. It is safe, well tolerated, and highly effective, and has also been investigated in South America and Africa. In Thailand, malaria incidence and in-vitro mefloquine resistance of parasites has decreased since this combination has come into use. Disadvantages of this regimen include its price and the pharmacokinetic mismatch of each drug. In a hyperendemic area, widespread treatment with this combination would lead to long-term exposure of parasites to low doses of mefloquine(Kremsner and Krishna, 2004).
- Success Rate: In Thailand, when other treatments were failing, an artesunate and mefloquine combination as first-line treatment was successful and remains so many years later(Kremsner and Krishna, 2004).
- Artesunate/sulfadoxine-pyrimethamine combination : Artesunate/sulfadoxine-pyrimethamine has also been assessed in African children. It gave promising results in The Gambia, where it was as well tolerated and as efficacious as sulfadoxine-pyrimethamine alone. However, in further WHO-led trials in African children, the combination was disappointing(Kremsner and Krishna, 2004).
- Atovaquone-Proguanil (aka Malarone) : Proguanil and chlorproguanil are metabolized by human CYP2C19 and CYP3A4 to the active metabolites cycloguanil and chlorcycloguanil, which inhibit parasite dihydrofolate reductase(Winstanley, 2001).
- Complication: Adverse effects during treatment were mild, and were likely to be due to the malaria itself(Thybo et al., 2004). Gastrointestinal intolerance and mouth ulceration are common adverse effects, but serious toxicity is very unusual(Winstanley, 2001).
- Success Rate: All patients treated with Malarone were cured without complications. The mean fever clearance times differed among the groups and according to various degrees of prior exposure to malaria and ranged from 1.3 to 2.2 days(Thybo et al., 2004). A randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of Malarone for the chemoprophylaxis of Plasmodium falciparum malaria in Zambia. The prophylaxis success rates in the Malarone and placebo groups were 98% and 63%, respectively. Malarone appears to have an excellent safety and efficacy profile for the chemoprophylaxis of P. falciparum infection(Sukwa et al., 1999).
- Drug Resistance: Malarone (atovaquone-proguanil) is an effective drug for the treatment and prophylaxis of multidrug-resistant falciparum malaria. However, first cases of resistance have been reported, which are associated with mutations at codon 268 of the parasite's cytochrome b gene. We report the first case of Malarone treatment failure from Central Africa. Drug concentration was well within curative range. Pre- and post-treatment Plasmodium falciparum isolates revealed codon 268 wild-type alleles, and no other mutations of the putative atovaquone-binding domain. These findings illustrate the spread of atovaquone-proguanil-resistance in Africa and question the usefulness of codon 268 as the only target for the surveillance of its emergence(Wichmann et al., 2004).
- Chlorproguanil-dapsone combination : Dapsone is a sulfa drug, with an elimination half-life of about 30 h, which has been combined with chlorproguanil (which has an elimination half-life of about 20 h). Chlorproguanil-dapsone was developed by a private-public partnership as an affordable combination treatment for African children. A phase III multicentre study compared the efficacy and safety of chlorproguanil-dapsone with sulfadoxine-pyrimethamine in children in Gabon, Kenya, Malawi, Nigeria, and Tanzania. Results indicate that the combination is well tolerated and efficacious. However, there was a higher frequency of serious haematological adverse events after chlorproguanil-dapsone treatment than after treatment with sulfadoxine-pyrimethamine. The safety of this combination is, therefore, a major concern, particularly since dapsone can cause methaemoglobinaemia and haemolysis in individuals with glucose-6-phosphate dehydrogenase deficiency. To test for glucose-6-phosphate dehydrogenase routinely in malaria-endemic areas before giving antimalarials is impracticable. There are also concerns about the potential for rapid emergence of cross-resistance to this combination in areas where resistance to sulfadoxine-pyrimethamine is established or becoming so. In Thailand, for example, efficacy of this combination has been severely limited for some time(Kremsner and Krishna, 2004).
- Chloroquine : The quinoline antimalarial drugs, chloroquine, quinine and mefloquine, are thought to act by interfering with the digestion of haemoglobin in the blood stages of the malaria life-cycle. These quinoline antimalarials traverse down the pH gradient to accumulate to millimolar concentrations in the acidic vacuole of the parasite. It has been suggested that this high intravacuolar concentration prevents haem sequestration, causing a build up of the toxic haem moiety and the death of the parasite by its own toxic waste(Raynes, 1999). Despite the extent of chloroquine-resistant P. falciparum, chloroquine remains the most widely used antimalarial drug worldwide. Chloroquine works by joining with ferriprotoporphyrin IX in the parasite, thereby antagonizing the polymerization of this toxic metabolic product into inert crystals of haemozoin(Winstanley, 2001).
- Contraindicator: In practice, the few contraindications to using chloroquine as treatment are known allergy, and unacceptable toxicity from previous use. As prophylaxis, chloroquine is contraindicated in patients with epilepsy, severe renal disease, and severe hepatic disease. The WHO also includes a history of psoriasis(Taylor and White, 2004).
- Complication: If used intravenously, it is important that chloroquine is diluted in crystalloid and infused slowly. Chloroquine is generally well-tolerated but pruritus is common in dark-skinned races, and when plasma concentrations are high (particularly when chloroquine is given intravenously) dizziness, headache, diplopia, disturbed accommodation, dysphagia, nausea, and malaise can develop: these are usually minor and reversible. Serious adverse effects such as hypotension and electrocardiograph abnormalities can take place at high chloroquine concentration. Rare adverse effects include photosensitivity, aggravation of psoriasis, skin pigmentation, leucopenia, bleaching of the hair, and aplastic anaemia. It can exacerbate epilepsy(Winstanley, 2001). Chloroquine is usually well tolerated when used for treatment or prophylaxis. Commonly reported symptoms include headache, malaise, dizziness, blurred vision, difficulty focusing, mild gastrointestinal upset, and itching. Itching is a particular problem in dark-skinned patients and affects compliance(Taylor and White, 2004). Severe toxicity may occur with long-term chloroquine usage (e.g. neuromyopathy, retinopathy) or as an idiosyncratic reaction (e.g. erythema multiforme, bone-marrow toxicity). These reactions are rare(Taylor and White, 2004).
- Drug Resistance: Chloroquine resistance has been reported from wherever falciparum malaria is endemic, except Central America and the Caribbean. In the late 1950's, resistance to chloroquine was noted on the Thai-Cambodian border and in Colombia. All endemic areas in South America were affected by 1980 and almost all in Asia and Oceania by 1989. In Africa, chloroquine resistance was first documented in the east in 1978. Resistance spread to the central and southern parts of the continent before arriving in west Africa in 1983. By 1989, chloroquine resistance was widespread in sub-Saharan Africa. Extensive reviews of the spread of chloroquine resistance have been published by Wernsdorfer and Payne and Peters. In general, resistance is currently less severe in west and central Africa than in east Africa, but even in west Africa, its intensity varies from an advanced stage with severe effects on mortality and morbidity in focal areas of Senegal, to a moderate degree in Ghana and Cameroon, and a low level in Mali. Owing to high-intensity chloroquine resistance, more than ten countries in Africa have already switched their first-line treatment to sulfadoxine-pyrimethamine or a combination of chloroquine and sulfadoxine-pyrimethamine(Wongsrichanalai et al., 2001). In vitro tests of resistance to chloroquine, mefloquine, quinine, halofantrine, tetracycline, and sulfadoxine/pyrimethamine were performed on Plasmodium falciparum isolates obtained from 52 German travelers returning from malarious areas in sub-Saharan Africa. Of these 32 isolates, 11 were multiresistant. Resistance to chloroquine was most frequently observed (55.8%), followed by sulfadoxine/pyrimethamine (11.5%), mefloquine (9.6%), quinine (3.8%), and halofantrine (1.9%)(Jelinek et al., 2001).
- Halofantrine : Halofantrine is an antimalarial drug which is widely prescribed for the treatment of infections with chloroquine-resistant strains of Plasmodium falciparum. Chemically, it is a phenanthrene methanol, belonging to the aryl-amino-alcohol family(Touze et al., 1997).
- Contraindicator: Halofantrine is potentially lethal and should not be given to patients with prolonged QTc interval. Contraindications are: (i) halofantrine allergy; (ii) pre-existing cardiac disease (e.g. ischaemic heart disease, beriberi); (iii) congenital prolongation of the QTc interval (e.g. Romano-Ward syndrome); (iv) a family history of sudden unexpected death; (v) concomitant use of drugs that prolong the QTc interval (e.g. tricyclic antidepressants, phenothiazines, antihistamines, erythromycin); (vi) mefloquine treatment within the previous 3 weeks; (vii) pregnant and breast-feeding women; and (viii) children under 1 year (because of lack of data)(Taylor and White, 2004).
- Complication: Although usually well tolerated, halofantrine lengthens the QT interval, has caused ventricular arrhythmias, and is associated with some cases of sudden death; this effect could be exacerbated by mefloquine(Winstanley, 2001). In Thailand, a higher-dose regimen (72 mg/kg over 3 days) increased efficacy, and was better tolerated than mefloquine, but was associated with significant cardiac arrhythmogenic potential(Winstanley, 2001).
- Success Rate: Halofantrine has been shown to be effective against multidrug resistant Plasmodium falciparum. One hundred and twenty falciparum malaria cases were randomly assigned to one of three different halofantrine regimes. No significant difference in the cure rate was observed among the three regimes, with cure rates of 89%, 73%, and 97% respectively(Krudsood et al., 2001).
- Drug Resistance: In vitro tests of resistance to chloroquine, mefloquine, quinine, halofantrine, tetracycline, and sulfadoxine/pyrimethamine were performed on Plasmodium falciparum isolates obtained from 52 German travelers returning from malarious areas in sub-Saharan Africa. Of these 32 isolates, 11 were multiresistant. Resistance to chloroquine was most frequently observed (55.8%), followed by sulfadoxine/pyrimethamine (11.5%), mefloquine (9.6%), quinine (3.8%), and halofantrine (1.9%)(Jelinek et al., 2001).
- Mefloquine : The quinoline antimalarial drugs, chloroquine, quinine and mefloquine, are thought to act by interfering with the digestion of haemoglobin in the blood stages of the malaria life-cycle. These quinoline antimalarials traverse down the pH gradient to accumulate to millimolar concentrations in the acidic vacuole of the parasite. It has been suggested that this high intravacuolar concentration prevents haem sequestration, causing a build up of the toxic haem moiety and the death of the parasite by its own toxic waste(Raynes, 1999).
- Contraindicator: Mefloquine should not be given to patients with known allergy to mefloquine or quinine or previous mefloquine-related toxicity(Taylor and White, 2004). Treatment contraindications are: (i) epilepsy or psychiatric disease; (ii) mefloquine treatment within the past 2 months; (iii) after severe malaria; (iv) pregnant women in the first trimester (unless no other choice is available); and (v) concurrent halofantrine treatment. Mefloquine should be used with caution in individuals with cardiac conduction disorders(Taylor and White, 2004).
- Complication: Mefloquine is generally well tolerated by malaria patients. However, in some treatment trials, mefloquine recipients reported a higher rate of certain adverse effects compared with chloroquine (dizziness), halofantrine (nausea, vomiting, fatigue, and dizziness) and artemether/lumefantrine (nausea, vomiting, dizziness, insomnia)(Taylor and White, 2004). Much attention has focused on the neuropsychiatric effects of mefloquine. Several reviews have summarized the data. A neuropsychiatric event includes and DNS or psychiatric symptom (e.g. headache, dizziness, insomnia, nightmares, anxiety) or illness and a serious neuropsychiatric event encompasses the following principal diagnoses: convulsions, disturbance of consciousness, acute confusion, inability to walk unaided because of vertigo or ataxia, psychosis, disorder of affect, and acute neurosis. Dizziness and anxiety are the most frequently reported neuropsychiatric adverse effects(Taylor and White, 2004).
- Success Rate: In a study of the treatment of uncomplicated falciparum malaria in the union of Myamar, mefloquine was found to be five times more likely to be effective than chloroquine and sulfadoxine pyrimethamine(Ejov et al., 1999).
- Drug Resistance: Mefloquine resistance was first observed near the Thai-Cambodian border in the late 1980s. The advent of mefloquine resistance in Thailand may have been influenced by the heavy use of the chemically related drug quinine just before the introduction of mefloquine. Mefloquine alone is no longer effective on the Thai-Myanmar and Thai-Cambodian borders, although it is still operationally useful in most other endemic areas in and around Thailand with field efficacy of more than 75%. By in-vitro assays, resistant strains are common in the neighboring countries. Migrant gem-miners returning from Cambodia may have been the means of the spread of mefloquine resistance to Bangladesh and India. There are also case-reports of mefloquine resistance from the Amazon Basin, but the degree and scope of resistance in South America are still far below those of southeast Asia. In-vitro studies suggest the presence of P. falciparum strains with low mefloquine sensitivity in Africa, but clinical mefloquine resistance is rare in Africa(Wongsrichanalai et al., 2001).
- Quinine : Quinine is an alkaloid isolated from the bark of cinchona trees and numerous legends exist on South American Indians' use of the bark prior to Francisco Pizzaro's conquista. In 1633, quinine's benefits were recognized in Peru by Antonio de Calancha, an Augustinian monk. The bark was given to the feverish Countess Anna de Chinch?n, the Peruvian Viceroy's shivering and delirious wife and now, although erroneously misspelled by Carolus Linnaeus, bears her reputable name. Cinchona proved invaluable in treating malaria and the remedy was widely used in Europe in the 17th and 18th centuries for its alleviating properties in various aguish and other conditions(Meyer et al., 2004). Quinine is one of the oldest malaria remedies known, although its use has never been as widespread as that of more contemporary drugs. Quinine occurs naturally in the bark of cinchona trees in South America. Cinchona bark was introduced into Europe as a treatment for "the ague" in the early 17th century. In 1820, the alkaloid quinine was isolated from cinchona bark(Wongsrichanalai et al., 2001). As monotherapy, quinine has to be given for 7 days to achieve cure but because of its unpleasant adverse effects, patient adherence is often poor. In the treatment of severe malaria, a loading dose of 20 mg of the dihydrochloride salt/kg of quinine is required to achieve rapidly parasiticidal drug concentrations; this can be administered by intramuscular injection (split dose; anterior thigh) or by intravenous infusion(Taylor and White, 2004). Quinidine is the parenteral antimalarial of choice in the United States, and quinine and the artemisinin compounds are available outside the United States(Stauffer and Fischer, 2003).
- Contraindicator: Quinine should not be given to patients know to be allergic to quinine or other cinchona alkaloids. This also includes quinine hypersensitivity to quinine-containing foods and drinks. Relative contraindications include: (i) myasthenia gravis (quinine-induced exacerbation); (ii) optic neuritis; (iii) tinnitus; and (iv) acute hemolysis. Quinine should be used with caution in hepatic disease and in cardiac disease, e.g. atrial fibrillation, conduction defects, heart block. Patients with severe malaria and prolonged QTc intervals on admission should be monitored closely(Taylor and White, 2004).
- Complication: When the correct regimen is used quinine is a relatively safe drug, but overdoses can be serious and can cause visual impairment, arrhythmias, hypotension, and seizures. Activated charcoal has been shown to increase the clearance of quinine, but stellate-ganglion block confers no benefit. Hypersensitivity reactions are rare but include rashes, thrombocytopenia, leucopenia, disseminated intravascular coagulopathy, haemolytic-uraemic syndrome, bronchospasm, and pancytopenia. By contrast, symptomatic toxicity is usual in conscious patients (tinnitus, deafness, headache, nausea, and visual disturbance cinchonism) and does not require dose reduction(Winstanley, 2001).
- Success Rate: Quinine needs to be administered on 7 consecutive days when given as a monotherapy, which is not always achievable because of cinchonism (dysphoria, tinnitus, nausea) and the very bitter flavor of most salts. However, apart from artemisinins, quinine is the only drug used to treat severe malaria and, despite widespread use, it (with a combination partner such as clindamycin or tetracycline in Thailand) retains excellent efficacy(Kremsner and Krishna, 2004).
- Drug Resistance: Although recrudescence strongly suggestive of quinine resistance was noted in Brazil nearly 100 years ago, successive observations of clinical resistance to quinine only began to accumulate during the mid-1960's, especially from the Thai-Cambodian border. Currently, clinical resistance to quinine monotherapy occurs sporadically in southeast Asia and western Oceania. Data from in-vitro assays indicate that resistance is less frequent in South America and Africa. Widespread use of quinine in Thailand in the early 1980s as an interim therapy in the face of declining sulfadoxine-pyrimethamine efficacy resulted in significant reduction of its sensitivity. Therefore, for the past two decades, quinine has been consistently used in combination with a partner antibiotic such as tetracycline or doxycycline to increase the effectiveness of treatment. Quinine is presently reserved as a second-line or third-line drug and is used in cases of severe malaria(Wongsrichanalai et al., 2001).
- Quinine/tetracycline combination : In Thailand, a 7-day course of quinine/tetracycline, in which the drugs need to be taken three-to-four times a day, has been used to treat falciparum malaria successfully for decades. A major limiting factor in compliance has been symptoms of cinchonism, leading to replacement of this combination by artemisinin-based regimens. Because the use of tetracycline is contraindicated in children and pregnant women, use of this combination has always been restricted. Emergence of parasite resistance over the past 10 years in areas where the combination has been extensively used has further hampered its use(Kremsner and Krishna, 2004).
- Quinine/clindamycin combination : Quinine/clindamycin has never been widely used, although numerous studies show both good efficacy and sound safety profiles in adults, children, and pregnant women. Results of studies in South America, Africa, southeast Asia, and in non-immune travelers who acquired malaria in different endemic areas, support the efficacy of this combination. Both drugs have fairly short plasma half lives (clindamycin about 2-4 h), perhaps reducing the risk of selecting for resistant parasites. A clear disadvantage is cinchonism(Kremsner and Krishna, 2004).
- Sulfadoxine/pyrimethamine combination : Some consider sulfadoxine-pyrimethamine a single drug rather than a combination in which each component acts independently, since, although pyrimethamine inhibits dihydrofolate reductase (DHFR) and sulfadoxine inhibits dihydropteroate synthase (DHPS), inhibition of both enzymes prevents synthesis of folic acid in parasites. Pyrimethamine is also structurally related to proguanil, and to cycloguanil and chlorproguanil, other drugs that inhibit DHFR. Discovered during World War II, pyrimethamine has good oral bioavailability, is absorbed in a few hours in children with malaria, and has an elimination half-life of about 80 h. Its use as a prophylactic agent for malaria began half a century ago(Kremsner and Krishna, 2004).
- Contraindicator: Sulfadoxine/pyrimethamine is contraindicated in patients with known allergy to sulphonamides or related compounds (e.g. thiazides), acute haemolysis following pervious sulphonamide use, patients with confirmed folate deficiency, severe renal disease, and severe hepatic disease. As a class, sulphonamides should not be administered to neonates aged less than 6 weeks because of the possible risk of causing haemolysis (as a result of their relative G6PD deficiency) and kernicterus (via displacement of conjugated bilirubin)(Taylor and White, 2004).
- Complication: The following list is presented to allow an awareness of the range of possible sulphonamide-related adverse effects: gastrointestinal toxicity; skin reactions; CNS; haemotological; renal effects; drug fever; pulmonary eosinophilia(Taylor and White, 2004). As efficacy falters, the risk-benefit ratio for use of sulfadoxine-pyrimethamine is also falling, as a result of reports of rare occurrences of severe and fatal adverse events, mainly Stevens-Johnson and Lyell syndromes, as well as even rarer instances of hepatotoxicity and agranulocytosis almost exclusively described after use in chemoprophylaxis in expatriates or travelers to the tropics. The risk of administering this combination is further raised by the frequency of serious adverse events, mainly skin reactions, noted in patients infected with HIV-1. However, sulfadoxine-pyrimethamine continues to be used in many countries in Africa, predominantly because it is a single-dose treatment and cheaper than the alternatives(Kremsner and Krishna, 2004).
- Success Rate: The lessons over the past 20 years with the introduction of amodiaquine, pyrimethamine/dapsone (Maloprim, GlaxoSmithKline) and pyrimethamine/sulfadoxine (Fansidar, Roche), which were all withdrawn for prophylaxis after a few years, show how sensitive drugs for chemoprophylaxis are to side effects(Petersen, 2004).
- Drug Resistance: Fever resolution is slower with chloroquine or amodiaquine, and resistance has eroded its efficacy. It is not largely ineffective in many parts of Latin America, and South East Asia, where P. vivax is also highly resistant. In Thailand it had a useful life span of only 5 years before falling to resistance(Taylor and White, 2004). Resistant parasites emerged within weeks, and half the population carried resistant parasites within 2 years. Single point mutations in the DNA of the target enzyme are responsible for resistance, explaining its rapid emergence. Higher grade resistance to pyrimethamine is associated with accumulation of various mutations at the target site(Kremsner and Krishna, 2004).
- Sulfadoxine-pyrimethamine plus amodiaquine combination : This ad-hoc triple combination regimen is used sporadically in some endemic areas, despite the fact that it combines the potential of rare but fatal adverse events associated with amodiaquine and with sulfadoxine-pyrimethamine, as observed when the drugs were used as chemoprophylactic agents in travelers to malaria-endemic areas. These observations have led to the withdrawal of both amodiaquine and sulfadoxine-pyrimethamine in almost all European countries. However, when used to treat malaria, similar serious (and perhaps allergic) adverse events have not been observed so often, perhaps because such events only arise after repeated exposure, particularly during chemoprophylaxis. If repeated exposure is indeed a prerequisite for adverse events, then newer intermittent prophylactic regimens in infants and pregnant women might carry similar risks. Nevertheless, renewed interest in this combination for treating African children has been generated by favorable results from Tanzania and elsewhere(Kremsner and Krishna, 2004).
- Sulfadoxine-pyrimethamine plus chloroquine combination : Chloroquine is an aminoquinoline, which interferes with the parasite's haem degradative pathway and thereby prevents detoxification of harmful products of metabolism. It was used as the antimalarial treatment of choice for decades in all malaria-endemic areas and is still used as first-line treatment in central America and parts of Africa for P. falciparum malaria. Today, P. falciparum is resistant to chloroquine in all endemic areas except central America. The combination of chloroquine with sulfadoxine-pyrimethamine has been sporadically tried in the past. The results of a review, which summarized the findings from five trials of sulfadoxine-pyrimethamine+4-aminoquinolines, showed a quicker resolution of symptoms with the combination than with sulfadoxine-pyrimethamine alone. However, other data do not encourage the use of this combination on grounds of poor effectiveness(Kremsner and Krishna, 2004).
- Sulfadoxine-pyrimethamine-mefloquine combination : This single dose, fixed, triple combination formulation has never been extensively used in most countries, and was introduced onto the market when the efficacy of sulfadoxine-pyrimethamine against parasites was already impaired. It is not an additively or synergistically acting combination, and each drug has a different pharmacokinetic profile. Mefloquine has a long (about 3 weeks) half-life. Other disadvantages are its high price and moderate safety profile(Kremsner and Krishna, 2004).
- Sulfadoxine-pyrimethamine plus quinine combination : Quinine+sulfadoxine-pyrimethamine has been used in several trials to improve efficacy, but with unconvincing results in Brazil and Bangladesh, where parasite resistance to sulfadoxine-pyrimethamine was already established. In an area where most parasites are still sensitive to sulfadoxine-pyrimethamine, this drug combined with a 3-day regimen of quinine might be more effective than either drug alone, as suggested by the results of a study from South Africa. Preliminary results from a study in progress at our unit (Albert Schweitzer Hospital, Lambar?n?, Gabon) are also promising. Comparative trials are, however, needed(Kremsner and Krishna, 2004).
- Prevention:
- Insecticide Impregnated Bednets
- Description: One of the most encouraging recent developments in malaria control has been the finding that impregnation of bed nets and curtains with insecticides can significantly reduce morbidity and mortality(Phillips, 2001), Beneficial features of bed nets are that they are readily accepted by the population and that they have the high usage rate of 86%, even in the absence of expensive promotional programs. There is an argument that governments willing to invest money in residual insecticide spraying might be willing to redirect some of this expenditure into bed nets(Phillips, 2001), House spraying, mosquito net impregnation, and larval control all rely on the effects of insecticides (DDT, permethrin, and temephos, respectively)(Over et al., 2004), A recent review suggested that pyrethroid-treated nets were as effective for malaria control as house spraying with DDT, malathion, or a pyrethroid, while a comparison in South Africa estimated that impregnated nets were more effective but much less cost-effective than house spraying. The evidence from the current study suggests that impregnated bed nets cannot easily replace DDT spraying without substantial increases in malaria incidence(Over et al., 2004),
- Efficacy:
- Rate: When impregnated nets were compared with plain nets or no nets, the summary relative risk was 0. 83. This translates to an estimate of protective efficacy of 17%. For treated nets compared with untreated nets, the relative risk of child mortality was 0.77. About six lives can be saved each year for every 1000 children protected with insecticide-treated nets. Insecticide-treated nets also reduced the incidence of mild malarial episodes by 48% (controls=no nets) and 34% (controls=untreated nets)(Lengeler, 2000).
- Duration: For permethrin, bioassay studies in Solomon Islands found 100% mortality in An. punctulatus exposed to a net up to 50 weeks after impregnation(Over et al., 2004).
- Complication: Proper maintenance of bednets and periodic reimpregnation with insecticide are essential for full efficacy. In areas where bednets and insecticide are not free, the costs associated with their upkeep may be beyond the means of the population. In the Gambia, when a charge of $0.50 for insecticide was introduced, usage declined from more than 70 to less than 20%. In some communities, the concept of paying for a health delivery system may be new and not readily accepted, and therefore a sustained and monitored bed net program will require some level of subsidy 30. If the nets and/or insecticide is not manufactured locally, purchase uses valuable foreign exchange(Phillips, 2001), Also, the reduced level of exposure through bed net intervention is likely to have an adverse effect on the acquisition of immunity, and any beneficial outcome is likely to be transitory in areas of high transmission(Phillips, 2001),
- Indoor residual spraying
- Description: Chemicals for mosquito control broadly fall into five groups. Petroleum oils and derivatives sprayed onto water, forming a film, prevent larvae and pupae from breathing through the surface of the water. Paris green (copper acetoarsenite) is another larvicide. Pyrethrins and pyrethroids form another group. Organochlorines, which include dichlorodiphenyltrichloroethane (DDT) and dieldrin; the organophosphates, such as malathion and temephos; and carbamates, such as propoxur, constitute the three remaining groups(Phillips, 2001), House spraying, mosquito net impregnation, and larval control all rely on the effects of insecticides (DDT, permethrin, and temephos, respectively)(Over et al., 2004),
- Efficacy:
- Rate: Vector control in Thailand has been the primary means of malaria control, mainly by the use of routine residual insecticide spray inside houses. The use of DDT in vector control has resulted in measurable successes to interrupt malaria transmission in many parts of the country(Chareonviriyaphap et al., 2000). The results show that DDT spraying, permethrin impregnation of mosquito nets, and educational activities were all independently associated with reduction in malaria cases, while larval control using temephos was not. The associations held even after adjusting for variables such as rainfall and proximity to water(Over et al., 2004).
- Duration: Estimating the effect of insecticides required some assumptions about their persistence. Although the recommended interval between DDT house spraying cycles is usually six months, Metselaar found that the mortality rate of An. punctulatus caught in huts sprayed with two grams of DDT /m2 decreased from 89% to 67% after six months. Slooff also demonstrated very little decrease in the mortality rates of either An. koliensis or An. farauti caught in sprayed huts over a nine-month period(Over et al., 2004).
- Complication: Organophosphates and carbamates are relatively dangerous in handling, requiring specialist equipment for their use (Phillips, 2001). Also, the problems of resistance are well documented and have increased with time and use, from 2 species of mosquito being resistant to DDT in 1946 to 55 or more species being resistant to one or more insecticides 50 years later(Phillips, 2001), Exposure to insecticides may also result in modifications in mosquito behavior whereby mosquitoes and insecticide have fleeting, if any, contact(Phillips, 2001),
- Acquired immunity through natural exposure
- Description: Semi-immunity against Plasmodium falciparum occurs after many infections. In areas of high malaria transmission, the prevalence of asymptomatic parasite carriers increases with age(Kun et al., 2002), Most residents living in areas of endemicity and exposed to P. falciparum malaria on a regular basis do develop an acquired immunity to malaria, and with few exceptions, the process of acquisition of immunity starts in babies and infants and is sustained into later life. Most of these young people survive infection with P. falciparum, but in about 1 to 2% of infections, severe malaria develops and can be fatal(Phillips, 2001),
- Efficacy:
- Rate:
- Duration: Natural immunity helps to prevent severe malaria and malaria-related deaths but does not give complete protection. People who move out of an area of endemicity for an extended period appear to lose their immunity, suggesting that repeated exposure is necessary to maintain resistance(Phillips, 2001).
- Complication: In areas of endemicity, the pattern is for babies and infants up to the age of about 5 years to be at risk of dying from the disease, but parasite prevalence, parasite density, and the number of clinical episodes do decline progressively with increasing age. Even in adulthood immunity is never complete, and during the transmission season, it is not unusual for the occasional clinical episode to occur and for parasites to be detectable in the blood even when the patient is clinically well(Phillips, 2001),
- Chemoprophylaxis
- Description: Malaria chemoprophylaxis concerns prescribing healthy individuals medication for an infection they have an unknown chance of getting. Sensible use of malaria chemoprophylaxis is a balance between the risk of infection and death, and the risk of side effects. The risk of infection can be broken down into the risk of being bitten by a malaria-infected mosquito and the risk of the malaria parasites being resistant to the drug used for prophylaxis. Our knowledge of these parameters is patchy. The risk of infection is not uniform at a given location and the standard of living will greatly influence risk. It is suggested that chemoprophylaxis should not be recommended in areas with less than ten reported cases of P. falciparum malaria per 1000 inhabitants per year. The resistance pattern is known to a certain extent but, for instance, diverging opinion of how much resistance to chloroquine there is in West Africa illustrates the lack of data. There is much debate on rare adverse events, which usually escape Phase III studies prior to registration and are only picked up by passive, postmarketing surveillance. The lessons over the past 20 years with the introduction of amodiaquine, pyrimethamine/dapsone (Maloprim, GlaxoSmithKline) and pyrimethamine/sulfadoxine (Fansidar, Roche), which were all withdrawn for prophylaxis after a few years, show how sensitive drugs for chemoprophylaxis are to side effects. Three levels of chemoprophylaxis are used: chloroquine in areas with sensitive P. falciparum, chloroquine plus proguanil in areas with low level chloroquine resistance, and atovaquone/proguanil (Malarone, GlaxoSmithKline), doxycycline or mefloquine (Lariam, Roche) in areas with extensive resistance against chloroquine and proguanil. Primaquine and the primaquone analog tafenoquine may be future alternatives but otherwise there are few new drugs for chemoprophylaxis on the horizon(Petersen, 2004),
- Efficacy:
- Rate: Targeted chemoprophylaxis of those at highest risk of severe malaria (children and pregnant women, particularly primigravidae) has been successfully implemented in some regions, although drug cost and delivery may still be problematic. Anemia (which also contributes to childhood mortality) and malaria-related morbidity and mortality can be reduced in children less than 5 years of age who receive either intermittent or continuous chemoprophylaxis(Suh et al., 2004).
- Duration:
- Vector control through environmental management to reduce or eliminate mosquito breeding sites
- Description: Includes filling in ditches, covering water containers, flushing irrigation channels, and clearing ponds of weed growth to allow introduction of fish predatory to mosquito eggs and larvae(Phillips, 2001),
- Model System:
- Aotus
- Model Host: Primate.
Aotus nancymaae(Nino-Vasquez et al., 2000),
- Model Pathogens:
Plasmodium falciparum(Nino-Vasquez et al., 2000).
- Description: The New World primate Aotus nancymaae is susceptible to infection with the human malaria parasite Plasmodium falciparum and Plasmodium vivax and has therefore been recommended by the World Health Organization as a model for evaluation of malaria vaccine candidates(Nino-Vasquez et al., 2000),
- Pan
- Model Host: Primate.
Pan troglodytes(Nino-Vasquez et al., 2000),
- Model Pathogens:
Plasmodium falciparum(Hickman et al., 1966).
- Description: The splenectomized chimpanzee was demonstrated to be susceptible to blood induced Malayan (Camp.) strain P. falciparum infection(Hickman et al., 1966),
- Primates
- Taxonomy Information:
- Anopheline mosquitoes
- Taxonomy Information:
- Species:
- Anopheles (Website 64):
- Common Name: Anopheles
- GenBank Taxonomy No.: 7164
- Description: Unlike other major infectious diseases such as AIDS and tuberculosis that are transmitted directly from person to person, malaria is transmitted only via anopheline mosquitoes. In principle, reducing or eliminating mosquito populations should stop disease transmission. In practice, this approach is difficult to implement, especially in sub-Saharan Africa, where mosquitoes can easily grow in environments such as small pools of water, which are extremely difficult to manage or target with insecticides. Insecticide campaigns might reduce mosquito populations temporarily, but leave a largely intact biological niche, where mosquitoes can continue to thrive(Ghosh et al., 2003).
- Anopheles aconitus (Website 65):
- Common Name: Anopheles aconitus
- GenBank Taxonomy No.: 93947
- Description: Malaria transmission was studied in a newly irrigated area of the Mahaweli project in the dry zone of Sri Lanka. Observations were performed for a three-month period following the northeast monsoon. Parasitemia in the population varied from 20.2% in February to 7% in May, and infection was due to both Plasmodium falciparum and P. vivax. Night catches of mosquitoes collected with human bait included a high proportion of Anopheles annularis. Mosquitoes containing sporozoites in the salivary glands were identified by an enzyme-linked immunosorbent assay. Anopheles culicifacies, An. annularis, and An. aconitus were all implicated as vectors in the area(Ramasamy et al., 1992).
- Anopheles albimanus (Website 66):
- Common Name: Anopheles albimanus
- GenBank Taxonomy No.: 7167
- Description: We have verified for specimens of Anopheles albimanus that an enzyme-linked immunosorbent assay (ELISA) used to assess Plasmodium vivax and P. falciparum sporozoite antigen rates gives results comparable to the salivary gland dissection method for estimating sporozoite rates. For 14,150 adults of An. albimanus, captured at five locations in Guatemala, we report sporozoite antigen rates of 0.03-0.57%, which correlate with the malaria prevalences at the study sites(Beach et al., 1992).
- Anopheles albitarsis (Website 67):
- Common Name: Anopheles albitarsis
- GenBank Taxonomy No.: 58236
- Description: Because An. albitarsis s.l. was caught with human bait, presented the highest density over localities, was positive by ELISA for the four tested species of Plasmodium and positive by salivary glands dissection for malaria sporozoites, it probably plays an important role in the epidemiology of malaria in these localities(Povoa et al., 2001).
- Anopheles annularis (Website 68):
- Common Name: Anopheles annularis
- GenBank Taxonomy No.: 59163
- Description: A study on malaria conducted in tribal villages of Darrang district, Assam during April 1994 to March 1995 revealed that the malaria incidence due to Plasmodium falciparum was considerably high. Slide positivity rate (SPR) ranged between 2.3 to 45.67 per cent with transmission from May to October. P. falciparum was the dominant species (91.7 per cent) followed by P. vivax (7.25 per cent) and mixed infection (Pv + Pf = 1.05 per cent). Malaria cases were recorded throughout the year in all the age groups including infants, however, age groups between 0-1 and 21-30 years were more affected. Among 17 anophelines collected, Anopheles vagus, An. jamesii, An. crawfordi and An. minimus were the most abundant species. Known vectors of malaria like An. annularis, An. culicifacies, An. minimus, An. philippinensis and An. varuna were detected. Perennial transmission of malaria was attributed to low socio-economic conditions, poor surveillance and inadequate intervention measures(Kamal and Das, 2001).
- Anopheles anthropophagus (Website 69):
- Common Name: Anopheles anthropophagus
- GenBank Taxonomy No.: 74872
- Description: The results revealed that the susceptibility of An. anthropophagus to Plasmodium falciparum was significantly higher than that of An. sinensis. The oocyst rate and sporozoite rate of the former were 27.9% and 10.9%, while those of the latter being 11.3% and 3.0%. Significant difference in natural infection rate of the two species was also observed. The mean sporozoite rate of An. anthropophagus was 0.58% (105/17984), and that of An. sinensis was 0.02% (4/17718). Taking several essential parameters (man-biting rate, human blood index, vectorial capacity and entomological inoculation rate) into consideration, the role of An. anthropophagus in malaria transmission was 20 times more vigorous than that of An. sinensis. The malaria incidence and parasite rate of the inhabitants in site were closely related to the proportion of An. anthropophagus in human dwellings. According to the survey pursued in 1983; An. anthropophagus was the major vector playing an important role in the outbreak of vivax malaria in Shenzhen(Liu, 1990).
- Anopheles aquasalis (Website 70):
- Common Name: Anopheles aquasalis
- GenBank Taxonomy No.: 42839
- Description: A. (N.) darlingi is in French Guyana the almost sole vector, except for Upper-Oyapok where A. (K.) neivai is responsible for a malaria caused by Bromeliaceae. In exceptional conditions and localized foci A. (N.) braziliensis and less often A. (N.) aquasalis may be effective vectors(Juminer et al., 1981).
- Anopheles arabiensis (Website 71):
- Common Name: Anopheles arabiensis
- GenBank Taxonomy No.: 7173
- Description: An entomological study was conducted in a village of Sudano-Guinean savanna in Senegal, during the rainy season from July to November 2001, to investigate the biology and the involvement of each anopheline species in malaria transmission. Mosquitoes were captured when landing on human volunteers and by pyrethrum spray catches. Twelve anopheline species were captured. Four species amounted to 97% of human-bait sampling: Anopheles gambiae molecular form S, An. arabiensis, An. funestus, and An. nili s.s. All An. gambiae and An. nili females were fed on human, whereas the anthropophilic rate was 94.5% for An. funestus and 88.9% for An. arabiensis. Plasmodium falciparum was the only malaria parasite found, and infecting only An. gambiae, An. arabiensis, An. funestus, and An. nili. The circumsporozoite rate was 4.5% for An. gambiae, 1.6% for An. arabiensis, 3.9% for An. funestus, and 2.1% for An. nili. During the period of study, the entomological inoculation rate was estimated to 264 infected bites. An. gambiae, An. arabiensis, An. funestus, and An. nili were responsible respectively of 56, 3, 20, and 21% of malaria transmission(Dia et al., 2003).
- Anopheles balabacensis (Website 72):
- Common Name: Anopheles balabacensis
- GenBank Taxonomy No.: 59124
- Description: Using both the immunoradiometric assay (IRMA) and the dissection technique, more sporozoite-positive infections were detected in An. balabacensis and An. flavirostris in November than in March. IRMA confirmed the presence of Plasmodium falciparum sporozoites. An average of 76.2% of the An. balabacensis population lived long enough to have reached a point where infectivity with P. falciparum was possible in November. Although fewer than five adult females bit humans per night at any time, a resident could theoretically have received more than 160 infective bites in one year. A high frequency of feeding on humans, coupled with increased anopheline life expectancy, contributed to high estimates of falciparum malaria vectorial capacity (number of infections distributed per case per day); for An. balabacensis (1.44-7.44 in March and 9.97-19.7 in November) and for An. flavirostris (0.19-5.14 in March and 6.27-15.8 in November). These high values may explain the increased malaria parasite rates obtained from at least two forest communities(Hii et al., 1988).
- Anopheles benarrochi (Website 73):
- Common Name: Anopheles benarrochi
- GenBank Taxonomy No.: 43061
- Description: Anopheles benarrochi is the dominant malaria vector in western Loreto (in the Peruvian Amazon region)(Aramburu Guarda et al., 1999).
- Anopheles braziliensis (Website 74):
- Common Name: Anopheles braziliensis
- GenBank Taxonomy No.: 58242
- Description: A. (N.) darlingi is in French Guyana the almost sole vector, except for Upper-Oyapok where A. (K.) neivai is responsible for a malaria caused by Bromeliaceae. In exceptional conditions and localized foci A. (N.) braziliensis and less often A. (N.) aquasalis may be effective vectors(Juminer et al., 1981).
- Anopheles culicifacies (Website 75):
- Common Name: Anopheles culicifacies
- GenBank Taxonomy No.: 139723
- Description: A study on malaria conducted in tribal villages of Darrang district, Assam during April 1994 to March 1995 revealed that the malaria incidence due to Plasmodium falciparum was considerably high. Slide positivity rate (SPR) ranged between 2.3 to 45.67 per cent with transmission from May to October. P. falciparum was the dominant species (91.7 per cent) followed by P. vivax (7.25 per cent) and mixed infection (Pv + Pf = 1.05 per cent). Malaria cases were recorded throughout the year in all the age groups including infants, however, age groups between 0-1 and 21-30 years were more affected. Among 17 anophelines collected, Anopheles vagus, An. jamesii, An. crawfordi and An. minimus were the most abundant species. Known vectors of malaria like An. annularis, An. culicifacies, An. minimus, An. philippinensis and An. varuna were detected. Perennial transmission of malaria was attributed to low socio-economic conditions, poor surveillance and inadequate intervention measures(Kamal and Das, 2001).
- Anopheles darlingi (Website 76):
- Common Name: Anopheles darlingi
- GenBank Taxonomy No.: 43151
- Description: Paralleling the malaria epidemic has been an increase in the highly competent and anthropophpilic malaria vector, Anopheles darlingi, the principal P. falciparum vector in the Brazilian Amazon(Aramburu Guarda et al., 1999). Five anopheline species, Anopheles deaneorum, An. albitarsis, An. triannulatus, An. oswaldoi, and An. mediopunctatus were compared to An. darlingi for susceptibility to infection by P. falciparum in Costa Marques, Rondonia, Brazil(Klein et al., 1991). Mosquitoes were dissected and examined for oocysts on day 9, and for sporozoites on days 16-20 after feeding. Anopheles mediopunctatus had higher mean numbers of oocysts and oocyst positive rates than An. darlingi. The oocyst positive rate and the mean number of oocysts in An. deaneorum and An. darlingi were similar. Anopheles triannulatus and An. oswaldoi had fewer oocysts than An. darlingi. The salivary gland sporozoite infection rate was similar for An. mediopunctatus and An. deaneorum and much lower for An. triannulatus and An. oswaldoi when compared to An. darlingi (Klein et al., 1991). In relative levels of susceptibility to P. falciparum, An. darlingi was equal to An. mediopunctatus which was greater than An. deaneorum, which was greater than An. triannulatus, which was greater than An. oswaldoi(Klein et al., 1991).
- Anopheles deaneorum (Website 77):
- Common Name: Anopheles deaneorum
- GenBank Taxonomy No.: 58243
- Description: Five anopheline species, Anopheles deaneorum, An. albitarsis, An. triannulatus, An. oswaldoi, and An. mediopunctatus were compared to An. darlingi for susceptibility to infection by P. falciparum in Costa Marques, Rondonia, Brazil(Klein et al., 1991). Mosquitoes were dissected and examined for oocysts on day 9, and for sporozoites on days 16-20 after feeding. Anopheles mediopunctatus had higher mean numbers of oocysts and oocyst positive rates than An. darlingi. The oocyst positive rate and the mean number of oocysts in An. deaneorum and An. darlingi were similar. Anopheles triannulatus and An. oswaldoi had fewer oocysts than An. darlingi. The salivary gland sporozoite infection rate was similar for An. mediopunctatus and An. deaneorum and much lower for An. triannulatus and An. oswaldoi when compared to An. darlingi (Klein et al., 1991). In relative levels of susceptibility to P. falciparum, An. darlingi was equal to An. mediopunctatus which was greater than An. deaneorum, which was greater than An. triannulatus, which was greater than An. oswaldoi(Klein et al., 1991). Of the 3056 specimens collected, 2610 were Anopheles oswaldoi, 362 A. deaneorum, 60 A. triannulatus and 24 were A. darlingi. The infection rates of A. oswaldoi were 3.41% for P. falciparum, 2.26% for P. vivax, 1.22 for P. vivax VK247, and 0.42% for P. malariae. For A. deaneorum, the infection rates were 2.76% for P. falciparum, 0.55% for P. vivax, and 0.82% for P. vivax VK247(Branquinho et al., 1993).
- Anopheles dirus (Website 78):
- Common Name: Anopheles dirus
- GenBank Taxonomy No.: 7168
- Description: Anopheline mosquitoes and their relation to malaria transmission were studied 3 times: in July and August, 1999; in December, 1999; and in August and September, 2000. The studies took place in the malaria endemic villages of Khammouane Province, southeast of Lao PDR. A total of 28 species were collected using human and animal bait. Human bait attracted predominantly Anopheles dirus and An. minimus, which were identified as vectors by the detection of sporozoites by dissection, PCR, and enzyme-linked immunosorbent assays for Plasmodium falciparum and P. vivax. The vectorial capacity of An. dirus was 0.009-0.428, while that of An. minimus was 0.048-0.186. The inoculation rate of An. dirus was 0.052-0.137(Toma et al., 2002). Vectorial capacity of An. dirus was highest, 0.779 for Plasmodium vivax (Pv) and 0.649 for Plasmodium falciparum (Pf), during the hot-monsoon season (June-September) and decreased to 0.08 (Pv) and 0.07(Pf) in the temperate postmonsoon season (October-November) before attaining zero values in the cool-dry season (December-February)(Prakash et al., 2001).
- Anopheles farauti (Website 79):
- Common Name: Anopheles farauti
- GenBank Taxonomy No.: 69004
- Description: Of 1,156 An. farauti s.s. specimens examined by enzyme-linked immunosorbent assay for malaria sporozoites, 20 were found to be positive; 12 were positive for Plasmodium falciparum and 8 were positive for P. vivax (247 variant = 5; 210 variant = 3). Anopheles farauti s.s. seems to be the major malaria vector on these islands, whereas An. punctulatus may play a minor role on Buka Island(Cooper and Frances, 2002).
- Anopheles flavirostris (Website 80):
- Common Name: Anopheles flavirostris
- GenBank Taxonomy No.: 59147
- Description: Using both the immunoradiometric assay (IRMA) and the dissection technique, more sporozoite-positive infections were detected in An. balabacensis and An. flavirostris in November than in March. IRMA confirmed the presence of Plasmodium falciparum sporozoites. An average of 76.2% of the An. balabacensis population lived long enough to have reached a point where infectivity with P. falciparum was possible in November. Although fewer than five adult females bit humans per night at any time, a resident could theoretically have received more than 160 infective bites in one year. A high frequency of feeding on humans, coupled with increased anopheline life expectancy, contributed to high estimates of falciparum malaria vectorial capacity (number of infections distributed per case per day); for An. balabacensis (1.44-7.44 in March and 9.97-19.7 in November) and for An. flavirostris (0.19-5.14 in March and 6.27-15.8 in November). These high values may explain the increased malaria parasite rates obtained from at least two forest communities(Hii et al., 1988).
- Anopheles fluviatilis (Website 81):
- Common Name: Anopheles fluviatilis
- GenBank Taxonomy No.: 111615
- Description: During this study An. fluviatilis was noted to be mostly endophilic whereas earlier workers noted this mosquito to be exophilic in a large number of districts. The majority of the tribal districts seem to be under the influence of two malaria vectors, An. culicifacies and An. fluviatilis and these tribal districts are maintaining a high malaria endemicity with predominance of Plasmodium falciparum infection(Joshi et al., 1998). Malaria has declined around Chilika Lake (85 degrees 20'E, 19 degrees 40'N) in Orissa State, India, from hyperendemicity in the 1930s to hypoendemicity during recent decades. Six decades ago, 21 spp. of Anopheles mosquitoes (Diptera: Culicidae) were recorded from this area, including the well known Indian malaria vectors An. culicifacies Giles, An. fluviatilis James, An. maculatus Theobald, An. stephensi Liston and An. sundaicus (Rodenwaldt), the last formerly regarded as the main vector locally(Dash et al., 2000).
- Anopheles freeborni (Website 82):
- Common Name: Anopheles freeborni
- GenBank Taxonomy No.: 7170
- Description: Anopheles freeborni Aitken, An. gambiae Giles, and An. albimanus Weidemann exhibit excellent, good, and poor susceptibility to Plasmodium falciparum Welch, respectively(Chege and Beier, 1998). A micro-membrane feeding technique was used to evaluate sporozoite transmission for Anopheles freeborni and An. gambiae experimentally infected with Plasmodium falciparum. From cohorts of infected mosquitoes with equivalent sporozoite loads, 75.9% of 29 An. freeborni transmitted a geometric mean (GM) of 4.9 sporozoites and 80% of 30 An. gambiae transmitted a GM of 11.3 sporozoites. Ingested sporozoites, in the blood meal immediately after feeding, were detected in 86.2% of 29 An. freeborni (GM = 9.0) and in 70% of 30 An. gambiae (GM = 44.1). Overall, sporozoites were transmitted and/or ingested by 90% of both species. Most infective mosquitoes transmitted less than 1% of the total sporozoites in the salivary glands, and only up to 30% of the variation in transmission, ingestion, or total sporozoite output was related to sporozoite loads. The demonstration that An. gambiae transmitted more than twice as many sporozoites as An. freeborni is the first indication that vector species of anopheline mosquitoes differ in their innate potential for sporozoite transmission(Beier et al., 1992).
- Anopheles funestus (Website 83):
- Common Name: Anopheles funestus
- GenBank Taxonomy No.: 62324
- Description: An entomological study was conducted in a village of Sudano-Guinean savanna in Senegal, during the rainy season from July to November 2001, to investigate the biology and the involvement of each anopheline species in malaria transmission. Mosquitoes were captured when landing on human volunteers and by pyrethrum spray catches. Twelve anopheline species were captured. Four species amounted to 97% of human-bait sampling: Anopheles gambiae molecular form S, An. arabiensis, An. funestus, and An. nili s.s. All An. gambiae and An. nili females were fed on human, whereas the anthropophilic rate was 94.5% for An. funestus and 88.9% for An. arabiensis. Plasmodium falciparum was the only malaria parasite found, and infecting only An. gambiae, An. arabiensis, An. funestus, and An. nili. The circumsporozoite rate was 4.5% for An. gambiae, 1.6% for An. arabiensis, 3.9% for An. funestus, and 2.1% for An. nili. During the period of study, the entomological inoculation rate was estimated to 264 infected bites. An. gambiae, An. arabiensis, An. funestus, and An. nili were responsible respectively of 56, 3, 20, and 21% of malaria transmission(Dia et al., 2003).
- Anopheles gambiae (Website 84):
- Common Name: Anopheles gambiae
- GenBank Taxonomy No.: 7165
- Description: Anopheles gambiae is the principal mosquito vector of malaria, a disease that afflicts more than 500 million people and causes more than 2-3 million deaths each year(Land, 2003).
- Anopheles hancocki (Wanji et al., 2003):
- Common Name: Anopheles hancocki
- Description: There is a lack of data on the Anopheles fauna, its biology and the roles played by different vector species in the transmission of malaria in the mount Cameroon region. The biting habits, feeding behaviour and entomological inoculation rates of different Anopheles species during the dry and rainy season were investigated. A total of 2165 Anopheles was collected, 805 in the rainy season and 1360 in the dry season. Five Anopheles species were identified: Anopheles gambiae s.l., An. funestus, An. hancocki, An. moucheti and An. nili. An. gambiae, An. funestus and An. hancocki, recorded during both seasons, were the main vectors of malaria in the region. An. gambiae s.s. was the only member of the An. gambiae (Giles) complex. These three species had their peak activity between 1 and 2 am. A human blood index (HBI) of 98.29% was recorded for fed Anopheles. The sporozoite rate, for all vectors together, was significantly higher in the rainy season (9.4%) than in the dry season (4.2%) with all the species infected by Plasmodium falciparum(Wanji et al., 2003).
- Anopheles karwari (Website 85):
- Common Name: Anopheles karwari
- GenBank Taxonomy No.: 59148
- Description: Circumsporozoite positivity rates for both Plasmodium falciparum Welch and P. vivax (Grassi and Feletti) in A. punctulatus and A. farauti s.l. were significantly higher in light trap collections than in either indoor or outdoor landing catches, suggesting that light traps may selectively sample older mosquitoes of these species(Hii et al., 1988).
- Anopheles koliensis (Website 86):
- Common Name: Anopheles koliensis
- GenBank Taxonomy No.: 30065
- Description: Vector studies revealed that Anopheles punctulatus and An. koliensis were the potential vectors as was confirmed by ELISA positive test with a sporozoite rate of 1.43% and 0.33% respectively. The vectors were indoor and outdoor resting(Pribadi et al., 1998).
- Anopheles labranchiae (Website 87):
- Common Name: Anopheles labranchiae
- GenBank Taxonomy No.: 41428
- Description: Climatic changes must have greatly affected the distribution of malaria in prehistoric times. Paleobotanical evidence, snowline depression studies and information obtained from deep sea sediment cores, indicate that southern Europe must have suffered a drop of summer temperatures of approximately 9 degrees C during the last glacial maximum, 18,000 years ago. Such a drop would have been decisive as regards the distribution of malaria and its vectors. If present at all, the disease would have been confined to the southernmost parts of the continent but P. falciparum and today's most effective vectors--A. labranchiae and A. sacharovi--would have been excluded from Europe(de Zulueta et al., 1987).
- Anopheles leucosphyrus (Harbach et al., 1987):
- Common Name: Anopheles leucosphyrus
- Description: Human bait collections of biting anopheline mosquitoes were made on five consecutive nights during September 1986 in a remote village located in a heavily forested area of South Kalimantan, Indonesia. Anopheles leucosphyrus and An. balabacensis comprised 97.7% of the total number of specimens collected outside houses in the village. Anopheles balabacensis were slightly fewer in total numbers than leucosphyrus. Mosquitoes were collected simultaneously in the village and the forest on two nights. The numbers of leucosphyrus and balabacensis biting in the forest were small in comparison with the populations encountered in the village. Approximately 75% of the specimens were checked individually for sporozoite infections using ELISA for P. falciparum and P. vivax. Sporozoites of P. falciparum were detected in one specimen of leucosphyrus and one of balabacensis. The sporozoite infection rate was 1.0% for leucosphyrus and 1.3% for balabacensis(Harbach et al., 1987).
- Anopheles maculatus (Website 88):
- Common Name: Anopheles maculatus
- GenBank Taxonomy No.: 74869
- Description: Malaria has declined around Chilika Lake (85 degrees 20'E, 19 degrees 40'N) in Orissa State, India, from hyperendemicity in the 1930s to hypoendemicity during recent decades. Six decades ago, 21 spp. of Anopheles mosquitoes (Diptera: Culicidae) were recorded from this area, including the well known Indian malaria vectors An. culicifacies Giles, An. fluviatilis James, An. maculatus Theobald, An. stephensi Liston and An. sundaicus (Rodenwaldt), the last formerly regarded as the main vector locally(Dash et al., 2000). Circumsporozoite proteins, in most cases of Plasmodium falciparum, were detected in Anopheles minimus species A, An. dirus s.l., An. maculatus s.s. and An. sawadwongporni in residential villages and/or farm huts, suggesting transmission could occur there(Somboon et al., 1998).
- Anopheles mangyanus (Website 113):
- Common Name: Anopheles mangyanus
- GenBank Taxonomy No.: 59156
- Description: The principal vector of malaria in the Philippines is An. minimus flavirostris which breeds in clear, fresh-water streams in foothills and mountain slopes. An. mangyanus and An. maculatus appear to play a secondary role. The vectorial capacity of the former appears to be confined only where conditions are primitive, while the latter is associated with malaria transmission in high altitudes(Cabrera et al., 1977).
- Anopheles mediopunctatus (Website 89):
- Common Name: Anopheles mediopunctatus
- GenBank Taxonomy No.: 184758
- Description: Five anopheline species, Anopheles deaneorum, An. albitarsis, An. triannulatus, An. oswaldoi, and An. mediopunctatus were compared to An. darlingi for susceptibility to infection by P. falciparum in Costa Marques, Rondonia, Brazil(Klein et al., 1991). Mosquitoes were dissected and examined for oocysts on day 9, and for sporozoites on days 16-20 after feeding. Anopheles mediopunctatus had higher mean numbers of oocysts and oocyst positive rates than An. darlingi. The oocyst positive rate and the mean number of oocysts in An. deaneorum and An. darlingi were similar. Anopheles triannulatus and An. oswaldoi had fewer oocysts than An. darlingi. The salivary gland sporozoite infection rate was similar for An. mediopunctatus and An. deaneorum and much lower for An. triannulatus and An. oswaldoi when compared to An. darlingi(Klein et al., 1991). In relative levels of susceptibility to P. falciparum, An. darlingi was equal to An. mediopunctatus which was greater than An. deaneorum, which was greater than An. triannulatus, which was greater than An. oswaldoi(Klein et al., 1991).
- Anopheles melas (Website 90):
- Common Name: Anopheles melas
- GenBank Taxonomy No.: 34690
- Description: The results of ELISA-based analyses of bloodmeals indicated that An. gambiae s.s., An. melas and An. moucheti were predominantly anthropophagic whereas An. arabiensis was largely zoophagic. Among all of the females investigated, 3.6% of the An. gambiae s.s., 1.9% of the An. melas, 1.8% of the An. moucheti and 0% of the An. arabiensis were found to be infected with P. falciparum (i.e. carrying the parasite's circumsporozoite antigen). The corresponding proportions for the females collected during the dry season were 1.3%, 2.3%, 2.7% and 0%. The entomological inoculation rates for An. melas and An. moucheti were significantly higher during the dry season than at other times of the year. Taken together, these results indicate that An. melas and An. moucheti maintain transmission of P. falciparum during the dry season, while the biting population of An. gambiae s.s. is relatively small(Awolola et al., 2002).
- Anopheles minimus (Website 91):
- Common Name: Anopheles minimus
- GenBank Taxonomy No.: 112268
- Description: A study on malaria conducted in tribal villages of Darrang district, Assam during April 1994 to March 1995 revealed that the malaria incidence due to Plasmodium falciparum was considerably high. Slide positivity rate (SPR) ranged between 2.3 to 45.67 per cent with transmission from May to October. P. falciparum was the dominant species (91.7 per cent) followed by P. vivax (7.25 per cent) and mixed infection (Pv + Pf = 1.05 per cent). Malaria cases were recorded throughout the year in all the age groups including infants, however, age groups between 0-1 and 21-30 years were more affected. Among 17 anophelines collected, Anopheles vagus, An. jamesii, An. crawfordi and An. minimus were the most abundant species. Known vectors of malaria like An. annularis, An. culicifacies, An. minimus, An. philippinensis and An. varuna were detected(Kamal and Das, 2001).
- Anopheles moucheti (Website 92):
- Common Name: Anopheles moucheti
- GenBank Taxonomy No.: 186751
- Description: The results of ELISA-based analyses of bloodmeals indicated that An. gambiae s.s., An. melas and An. moucheti were predominantly anthropophagic whereas An. arabiensis was largely zoophagic. Among all of the females investigated, 3.6% of the An. gambiae s.s., 1.9% of the An. melas, 1.8% of the An. moucheti and 0% of the An. arabiensis were found to be infected with P. falciparum (i.e. carrying the parasite's circumsporozoite antigen). The corresponding proportions for the females collected during the dry season were 1.3%, 2.3%, 2.7% and 0%. The entomological inoculation rates for An. melas and An. moucheti were significantly higher during the dry season than at other times of the year. Taken together, these results indicate that An. melas and An. moucheti maintain transmission of P. falciparum during the dry season, while the biting population of An. gambiae s.s. is relatively small(Awolola et al., 2002).
- Anopheles multicolor (Website 114):
- Common Name: Anopheles multicolor
- GenBank Taxonomy No.: 273151
- Description: Plasmodium infection rates determined by enzyme-linked immunosorbent assay (ELISA) were compared for Anopheles sergentii (Theobald) and An. multicolor Cambouliu in Siwa Oasis, Egypt, an area with low-level Plasmodium vivax transmission, and in Bahariya and Farafra, two other Egyptian oases which appear to be free of malaria. Initial testing indicated that 4.4% (23 of 518) and 0.8% (4 of 518) of the An. sergentii were positive for P. vivax and P. falciparum, respectively, and that 1.4% (1 of 71) of the An. multicolor were positive for P. falciparum(Kenawy et al., 1990).
- Anopheles neivai (Website 93):
- Common Name: Anopheles neivai
- GenBank Taxonomy No.: 139046
- Description: Malaria in the people of Zacarias, a community on the Pacific Coast of Colombia where malaria transmission is low and unstable, was the subject of the present study. Within a 9-year period, a negative correlation between rainfall and documented malaria cases was recorded for this area. Thick smears of blood samples of 319 individuals revealed that 8.5% had malarial infections. As most (67%) of the smear-positive cases were asymptomatic, it seems that, despite the low prevalence of malaria in this area, the establishment of clinical symptoms is attenuated, probably because of the acquisition of permunition. Within this region, the most commonly found Anopheles species (representing 61.1% of the mosquitoes caught) and that giving the highest monthly biting rate (4.0 bites/man) was An. neivai. Most (90%) of the human sera tested possessed antibodies to blood-stage forms of Plasmodium falciparum, and 18% had antibodies to sporozoites(Gonzalez et al., 1997).
- Anopheles nili (Website 94):
- Common Name: Anopheles nili
- GenBank Taxonomy No.: 185578
- Description: An entomological study was conducted in a village of Sudano-Guinean savanna in Senegal, during the rainy season from July to November 2001, to investigate the biology and the involvement of each anopheline species in malaria transmission. Mosquitoes were captured when landing on human volunteers and by pyrethrum spray catches. Twelve anopheline species were captured. Four species amounted to 97% of human-bait sampling: Anopheles gambiae molecular form S, An. arabiensis, An. funestus, and An. nili s.s. All An. gambiae and An. nili females were fed on human, whereas the anthropophilic rate was 94.5% for An. funestus and 88.9% for An. arabiensis. Plasmodium falciparum was the only malaria parasite found, and infecting only An. gambiae, An. arabiensis, An. funestus, and An. nili. The circumsporozoite rate was 4.5% for An. gambiae, 1.6% for An. arabiensis, 3.9% for An. funestus, and 2.1% for An. nili. During the period of study, the entomological inoculation rate was estimated to 264 infected bites. An. gambiae, An. arabiensis, An. funestus, and An. nili were responsible respectively of 56, 3, 20, and 21% of malaria transmission. This study shows for the first time the implication of An. nili in malaria transmission in this area and the complexity of the malaria vectorial system that should be taken into account for any malaria control strategy(Dia et al., 2003).
- Anopheles nivipes (Website 95):
- Common Name: Anopheles nivipes
- GenBank Taxonomy No.: 74871
- Description: Recently, circumsporozoite antigens of P. falciparum and/or P. vivax have been detected by ELISA in An. nivipes in several areas of Thailand, suggesting a potential role in malaria transmission (Kobayashi et al., 2000). An. nivipes accounted for more than 65% of all mosquitoes collected and was the most common species collected from human baits. The results of this study show that endemic areas of malaria in Lao PDR are not necessarily related to forest. Rather, An. nivipes is suspected to be the most important vector(Kobayashi et al., 2000).
- Anopheles nuneztovari (Website 96):
- Common Name: Anopheles nuneztovari
- GenBank Taxonomy No.: 30067
- Description: Other Anopheles species in Loreto (in the Peruvian Amazon region) known to be malaria vectors are An. oswaldoi, An. nuneztovari, and An. rangeli(Aramburu Guarda et al., 1999).
- Anopheles oswaldoi (Website 97):
- Common Name: Anopheles oswaldoi
- GenBank Taxonomy No.: 43181
- Description: Five anopheline species, Anopheles deaneorum, An. albitarsis, An. triannulatus, An. oswaldoi, and An. mediopunctatus were compared to An. darlingi for susceptibility to infection by P. falciparum in Costa Marques, Rondonia, Brazil(Klein et al., 1991). Mosquitoes were dissected and examined for oocysts on day 9, and for sporozoites on days 16-20 after feeding. Anopheles mediopunctatus had higher mean numbers of oocysts and oocyst positive rates than An. darlingi. The oocyst positive rate and the mean number of oocysts in An. deaneorum and An. darlingi were similar. Anopheles triannulatus and An. oswaldoi had fewer oocysts than An. darlingi. The salivary gland sporozoite infection rate was similar for An. mediopunctatus and An. deaneorum and much lower for An. triannulatus and An. oswaldoi when compared to An. darling(Klein et al., 1991). Other Anopheles species in Loreto (in the Peruvian Amazon region) known to be malaria vectors are An. oswaldoi, An. nuneztovari, and An. rangeli (Aramburu Guarda et al., 1999).
- Anopheles pharoensis (Website 98):
- Common Name: Anopheles pharoensis
- GenBank Taxonomy No.: 221566
- Description: Plasmodium vivax and P. falciparum epidemiology were studied for parasitological and entomological samples collected during the period 1989 and 1990, respectively, from Gambella, South West Ethiopia. Of the total population examined (n = 1091), 147 (13.5%) were found to be positive for malaria parasites. Prevalence rates among males and females were 13.8% and 13.1%, respectively. Differences in the prevalence rates of malaria in the eleven villages were observed, the highest (33.3%) being in Ukuna 2 and the lowest (3.9%) in Ukuna 22. The dominant species of malaria found were both P. falciparum and P. vivax. 88.9% and 11.1% of the malaria cases of the general population were due to these parasites, respectively. It was also recognized that P. falciparum and P. vivax were prevalent in 81.6% and 18.4% of the Anuak population, respectively. The mosquito species responsible for malaria transmission were the indoor-resting A. gambiae s. l. and A. pharoensis. The parasite infection rates of these species were 0.76% and 0.46% and they were found to be the exclusive vectors of P. falciparum and P. vivax, respectively(Nigatu et al., 1992).
- Anopheles philippinensis (Prakash et al., 2004):
- Common Name: Anopheles philippinensis
- Description: In north-eastern India, Anopheles minimus, An. dirus and An. fluviatilis are considered the three major vectors of the parasites causing human malaria. The role in transmission of the other Anopheles species present in this region is not, however, very clear. To examine the vectorial role of the more common anopheline mosquitoes, the heads and thoraces of 4126 female Anopheles belonging to 16 species (collected using miniature light traps set in human dwellings in a foothill village in the Jorhat district of Assam state) were tested, in ELISA, for the circumsporozoite proteins (CSP) of Plasmodium falciparum or the VK-210 and VK-247 polymorphs of P. vivax. Sixty-five pools of head-thorax homogenates, representing 10 different species of Anopheles, were found reactive, giving an overall minimum prevalence of infection (MPI) of 1.58%, with a 95% confidence interval (CI) of 1.21%-2.0%. Among the CSP-reactive pools of mosquitoes, 31% were positive only for P. falciparum, 45% only for P. vivax VK 247, 6% only for P. vivax VK 210, and 18% for both P. falciparum and P. vivax VK 247. The results indicate that not only the proven vector, An. minimus s.l. (MPI = 0.71%), but also several species of Anopheles previously considered unimportant in the epidemiology of malaria, especially An. aconitus (MPI = 3.95%), An. annularis (MPI = 5.8%), the An. hyrcanus group (MPI = 0.48%), An. kochi (MPI = 1.28%), the An. philippinensis-nivipes complex (MPI = 0.94%), and An. vagus (MPI = 3.87%), are important vectors in the foothills of Assam(Prakash et al., 2004).
- Anopheles plumbeus (Website 99):
- Common Name: Anopheles plumbeus
- GenBank Taxonomy No.: 227531
- Description: Autochthonous Plasmodium falciparum malaria (PFM) in Central Europe has been reported repeatedly, transmission of the parasite being attributed to blood transfusion or imported P. falciparum-infected vectors. We report two cases of PFM in German children without travel history to malaria-endemic areas. Both infections occurred during a stay in a hospital where a child from Angola with chronic P. falciparum infection was hospitalized at the time. Known routes of transmission, such as imported mosquitoes or blood transfusion, were very unlikely or could be excluded, whereas evidence was obtained for transmission by the indigenous mosquito species Anopheles plumbeus(Kruger et al., 2001).
- Anopheles pulcherrimus (Website 100):
- Common Name: Anopheles pulcherrimus
- GenBank Taxonomy No.: 159154
- Description: Anopheline vectors and malaria transmission were studied in 2 river-irrigated, rice-growing districts of eastern Afghanistan from May 1995 to December 1996. Clinical malaria was monitored in 12 rural villages (population 14,538) by passive case detection at local clinics. Adult mosquitoes were collected by space-spraying of living quarters and stables and by cattle bait catches. Mosquito head-thoraces (17,255 specimens) were tested for Plasmodium falciparum and P. vivax circumsporozoite protein (CSP) using enzyme-linked immunosorbent assay. The recorded incidence of P. vivax and P. falciparum was 199 and 41 episodes per 1000 person years, respectively. Twelve species of anopheline were recorded; Anopheles stephensi comprised 82% and A. culicifacies 5%. Eight species tested positive for CSP: A. stephensi, A. culicifacies, A. fluviatilus, A. annularis, A. pulcherrimus, A. maculatus, A. splendidus and A. superpictus. Among infected mosquitoes 46% were positive for P. falciparum, 45% for P. vivax VK-247, and 9% for P. vivax PV-210. Estimates of the feeding rates of infective vectors on humans indicated that A. stephensi would contribute 76% of infective bites, A. fluviatilis and A. pulcherrimus 7% each, and A. culicifacies and A. superpictus 3% each(Rowland et al., 2002).
- Anopheles pseudopunctipennis (Website 115):
- Common Name: Anopheles pseudopunctipennis
- GenBank Taxonomy No.: 46955
- Description: Haiti is the only Caribbean island where malaria, practically always due to Plasmodium falciparum, persists in an epidemic-endemic state. In 1995 Haitian strains of P. falciparum were still sensitive to chloroquine. The principal vector is Anopheles albimanus, but the recent introduction in the south of Haiti of An. pseudopunctipennis, which is an effective vector of P. falciparum in Central America, requires appropriate entomological surveillance. Essentially rural and seasonal, malaria is increasingly observed in the suburban areas around Port-au-Prince. The epidemiologic indicators have regressed since the 1980s and 1990s. The plasmodic index in 1995 was low: 3.9%(Raccurt, 2002).
- Anopheles punctulatus (Website 101):
- Common Name: Anopheles punctulatus
- GenBank Taxonomy No.: 30068
- Description: Of 1,156 An. farauti s.s. specimens examined by enzyme-linked immunosorbent assay for malaria sporozoites, 20 were found to be positive; 12 were positive for Plasmodium falciparum and 8 were positive for P. vivax (247 variant = 5; 210 variant = 3). Anopheles farauti s.s. seems to be the major malaria vector on these islands, whereas An. punctulatus may play a minor role on Buka Island(Cooper and Frances, 2002).
- Anopheles rangeli (Website 102):
- Common Name: Anopheles rangeli
- GenBank Taxonomy No.: 42840
- Description: Other Anopheles species in Loreto (in the Peruvian Amazon region) known to be malaria vectors are An. oswaldoi, An. nuneztovari, and An. rangeli(Aramburu Guarda et al., 1999).
- Anopheles sacharovi (Website 103):
- Common Name: Anopheles sacharovi
- GenBank Taxonomy No.: 72408
- Description: Climatic changes must have greatly affected the distribution of malaria in prehistoric times. Paleobotanical evidence, snowline depression studies and information obtained from deep sea sediment cores, indicate that southern Europe must have suffered a drop of summer temperatures of approximately 9 degrees C during the last glacial maximum, 18,000 years ago. Such a drop would have been decisive as regards the distribution of malaria and its vectors. If present at all, the disease would have been confined to the southernmost parts of the continent but P. falciparum and today's most effective vectors--A. labranchiae and A. sacharovi--would have been excluded from Europe(de Zulueta et al., 1987).
- Anopheles sawadwongporni (Website 104):
- Common Name: Anopheles sawadwongporni
- GenBank Taxonomy No.: 142886
- Description: Transmission of forest-related malaria was observed entomologically and epidemiologically for 2 transmission seasons in 1990 and 1991 in 5 villages of Mae Sariang district, Mae Hong Son Province, north-west Thailand. The entomological study included collections of mosquitoes and determination of infection rate by using enzyme-linked immunosorbent assay in the residential villages and the farm huts. The epidemiological study included fortnightly visits to 30% of the households to interview and record movement activities and illness of villagers. Circumsporozoite proteins, in most cases of Plasmodium falciparum, were detected in Anopheles minimus species A, An. dirus s.l., An. maculatus s.s. and An. sawadwongporni in residential villages and/or farm huts, suggesting transmission could occur there(Somboon et al., 1998).
- Anopheles sergenti (Shehata et al., 1989):
- Common Name: Anopheles sergenti
- Description: Two immunoassays for malaria sporozoite detection and identification, the immunoradiometric assay (IRMA) and the enzyme-linked immunosorbent assay (ELISA) using the species-specific monoclonal antibodies are routinely performed in our laboratory. We analyzed (573) anopheline mosquitoes of A. sergenti (463), A. pharoensis (81) and A. multicolor (29) collected from Siwa-oases and Faiyum Governorate (two known active malaria foci in Egypt), for detection of P. falciparum and P. vivax sporozoites. P. falciparum sporozoites were detected by both IRMA and ELISA tests in two A. sergenti mosquitoes (one from Siwa 1/389 = (0.26%) and one from Faiyum Governorate 1/74 = (1.35%)). No P. vivax sporozoites were detected. This finding is important in explaining the malaria transmission and provide first incrimination of An. sergenti as the responsible vector of malaria in Siwa-oasis, Egypt(Shehata et al., 1989).
- Anopheles sinensis (Website 105):
- Common Name: Anopheles sinensis
- GenBank Taxonomy No.: 74873
- Description: In Hainan, circa 80% of malaria cases were infected via transmission by An. dirus away from villages, hence difficulties existed in malaria control; in areas affected by An. anthropophagus where a population of more than 100 million resided, relatively high incidence of malaria was noted, the prevalence was unstable, sometimes focal outbreaks occurred, and incidence of 20% was reported in a few villages and townships; in area where the only vector was An. sinensis, the prevalence was rather stable, the incidence of malaria was decreased to less than 0.1 per 1000 in most places(Anonymous, 2000).
- Anopheles stephensi (Website 106):
- Common Name: Anopheles stephensi
- GenBank Taxonomy No.: 30069
- Description: A focal outbreak of malaria occurred in the villages situated close to the main Indira Gandhi canal near Ramgarh in Jaisalmer district, western Rajasthan. Stagnation of water over a month's period in the main canal as well as long standing rain water in the form of expansive lakes near these villages formed vast breeding grounds for the vectors like Anopheles culicifacies, along with A. stephensi already breeding in the 'tanka' and 'beri' in the epidemichit villages. Rapid mass blood surveys along with other entomological and parasitological investigations were conducted in four of the ten affected villages, viz., Seuva, Raghwa, Raimala and Sadhna. A total of 992 specimens belonging to four vector species were sampled, namely, A. stephensi (47.4%), A. culicifacies (41.0%), A. subpictus (11.2%) and A. annularis (0.4%). Epidemiologically, about one-fourth of the examined persons were positive (SPR 25.5%), although Plasmodium falciparum dominated the parasitaemia (49.5%). Available data are indicative of changed malariological scenario in the Indira Gandhi Nahar Pariyojna command area, where epidemics are regular features every year(Tyagi et al., 2001).
- Anopheles subpictus (Website 107):
- Common Name: Anopheles subpictus
- GenBank Taxonomy No.: 59160
- Description: Anopheles culicifacies Giles is regarded as the principal vector of malaria in Sri Lanka with Anopheles subpictus Grassi as a secondary vector. From ELISA tests for circumsporozoite proteins of P. vivax and P. falciparum, these two mosquito species, as well as Anopheles varuna, were incriminated as vectors in the Elahera gem-mining area(Yapabandara et al., 2001).
- Anopheles superpictus (Website 116):
- Common Name: Anopheles superpictus
- GenBank Taxonomy No.: 262673
- Description: Anopheline vectors and malaria transmission were studied in 2 river-irrigated, rice-growing districts of eastern Afghanistan from May 1995 to December 1996. Clinical malaria was monitored in 12 rural villages (population 14,538) by passive case detection at local clinics. Adult mosquitoes were collected by space-spraying of living quarters and stables and by cattle bait catches. Mosquito head-thoraces (17,255 specimens) were tested for Plasmodium falciparum and P. vivax circumsporozoite protein (CSP) using enzyme-linked immunosorbent assay. The recorded incidence of P. vivax and P. falciparum was 199 and 41 episodes per 1000 person years, respectively. Twelve species of anopheline were recorded; Anopheles stephensi comprised 82% and A. culicifacies 5%. Eight species tested positive for CSP: A. stephensi, A. culicifacies, A. fluviatilus, A. annularis, A. pulcherrimus, A. maculatus, A. splendidus and A. superpictus. Among infected mosquitoes 46% were positive for P. falciparum, 45% for P. vivax VK-247, and 9% for P. vivax PV-210. Estimates of the feeding rates of infective vectors on humans indicated that A. stephensi would contribute 76% of infective bites, A. fluviatilis and A. pulcherrimus 7% each, and A. culicifacies and A. superpictus 3% each(Rowland et al., 2002).
- Anopheles sundaicus (Website 108):
- Common Name: Anopheles sundaicus
- GenBank Taxonomy No.: 34692
- Description: Malaria has declined around Chilika Lake (85 degrees 20'E, 19 degrees 40'N) in Orissa State, India, from hyperendemicity in the 1930s to hypoendemicity during recent decades. Six decades ago, 21 spp. of Anopheles mosquitoes (Diptera: Culicidae) were recorded from this area, including the well known Indian malaria vectors An. culicifacies Giles, An. fluviatilis James, An. maculatus Theobald, An. stephensi Liston and An. sundaicus (Rodenwaldt), the last formerly regarded as the main vector locally(Dash et al., 2000).
- Anopheles tessellatus (Website 109):
- Common Name: Anopheles tessellatus
- GenBank Taxonomy No.: 59161
- Description: In An. tessellatus the movement of the ookinete from the lumen to the midgut epithelium is linked to the release of trypsin in the midgut and the peritrophic matrix is not a firm barrier to this movement. The passage of the P. vivax ookinete through the peritrophic matrix may take place before the latter is fully formed. The late ookinete development in P. falciparum requires chitinase to facilitate penetration of the peritrophic matrix(Ramasamy et al., 1997).
- Anopheles triannulatus (Website 110):
- Common Name: Anopheles triannulatus
- GenBank Taxonomy No.: 58253
- Description: Five anopheline species, Anopheles deaneorum, An. albitarsis, An. triannulatus, An. oswaldoi, and An. mediopunctatus were compared to An. darlingi for susceptibility to infection by P. falciparum in Costa Marques, Rondonia, Brazil(Klein et al., 1991). Mosquitoes were dissected and examined for oocysts on day 9, and for sporozoites on days 16-20 after feeding. Anopheles mediopunctatus had higher mean numbers of oocysts and oocyst positive rates than An. darlingi. The oocyst positive rate and the mean number of oocysts in An. deaneorum and An. darlingi were similar. Anopheles triannulatus and An. oswaldoi had fewer oocysts than An. darlingi. The salivary gland sporozoite infection rate was similar for An. mediopunctatus and An. deaneorum and much lower for An. triannulatus and An. oswaldoi when compared to An. darlingi(Klein et al., 1991). In relative levels of susceptibility to P. falciparum, An. darlingi was equal to An. mediopunctatus which was greater than An. deaneorum, which was greater than An. triannulatus, which was greater than An. oswaldoi(Klein et al., 1991). Anopheles triannulatus is the dominant vector in eastern Loreto (in the Peruvian Amazon region)(Aramburu Guarda et al., 1999).
- Anopheles vagus (Website 111):
- Common Name: Anopheles vagus
- GenBank Taxonomy No.: 142887
- Description: Wild caught zoophilic Anopheles and suspected malaria vector species collected in northwest Thailand were experimentally infected with local human malaria parasites using a membrane feeding. One week post-feeding a number of mosquitoes were dissected for oocyst examination. The remainder were kept for another one week or more, and then the salivary glands were examined for the presence of sporozoites. The results revealed that An. vagus, An. kochi and An. annularis were susceptible to both Plasmodium falciparum and P. vivax(Somboon et al., 1994).
- Anopheles varuna (Website 112):
- Common Name: Anopheles varuna
- GenBank Taxonomy No.: 93948
- Description: A study on malaria conducted in tribal villages of Darrang district, Assam during April 1994 to March 1995 revealed that the malaria incidence due to Plasmodium falciparum was considerably high. Slide positivity rate (SPR) ranged between 2.3 to 45.67 per cent with transmission from May to October. P. falciparum was the dominant species (91.7 per cent) followed by P. vivax (7.25 per cent) and mixed infection (Pv + Pf = 1.05 per cent). Malaria cases were recorded throughout the year in all the age groups including infants, however, age groups between 0-1 and 21-30 years were more affected. Among 17 anophelines collected, Anopheles vagus, An. jamesii, An. crawfordi and An. minimus were the most abundant species. Known vectors of malaria like An. annularis, An. culicifacies, An. minimus, An. philippinensis and An. varuna were detected. Perennial transmission of malaria was attributed to low socio-economic conditions, poor surveillance and inadequate intervention measures(Kamal and Das, 2001).
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Phinet: Pathogen-Host Interaction Network
Not available for this pathogen.
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Lab Animal Pathobiology & Management
NA
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References:
Abdur et al., 2003: Abdur RM, Freeman TW, Rahim S, Durrani N, Simon-Taha A, Rowland M. High altitude epidemic malaria in Bamian province, central Afghanistan. East Mediterr Health. 2003; 9(3); 232-239. [PubMed: 15751914].
Aikawa and Seed, 1980: Aikawa M, Seed TM. Morphology of Plasmodia. 285-344. In: . Malaria Vol. 1.. 1980. Academic Press, New York, New York.
Anonymous, 2000: . Malaria situation in the People's Republic of China in 1999. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2000; 18(3); 129-131. [PubMed: 12567683].
Aramburu Guarda et al., 1999: Aramburu Guarda J, Ramal Asayag C, Witzig R. Malaria reemergence in the Peruvian Amazon region. Emerg Infect Dis. 1999; 5(2); 209-215. [PubMed: 10221872].
Awolola et al., 2002: Awolola TS, Okwa , Hunt RH, Ogunrinade AF, Coetzee M. Dynamics of the malaria-vector populations in coastal Lagos, south-western Nigeria. Ann Trop Med Parasitol. 2002; 96(1); 75-82. [PubMed: 11989536].
Balint, 2001: Balint GA. Artemisinin and its derivatives: an important new class of antimalarial agents. Pharmacol Ther. 2001; 90(2-3); 261-265. [PubMed: 11578659].
Bannister and Mitchell, 2003: Bannister L, Mitchell G. The ins, outs and roundabouts of malaria. Trends Parasitol. 2003; 19(5); 209-213. [PubMed: 12763426].
Bannister et al., 2003: Bannister LH, Hopkins JM, Dluzewski AR, Margos G, Williams IT, Blackman MJ, Kocken CH, Thomas AW, Mitchell GH. Plasmodium falciparum apical membrane antigen 1 (PfAMA-1) is translocated within micronemes along subpellicular microtubules during merozoite development. J Cell Sci. 2003; 116(Pt 18); 3825-3834. [PubMed: 12902400].
Banzal et al., 1999: Banzal S, Ayoola EA, El Sammani EE, Rahim SI, Subramaniam P, Gadour MOE, Jain AK. The Clinical Pattern and Complications of Severe Malaria in the Gizan Region of Saudi Arabia. Annals of Saudi Medicine. 1999; 19(4); 378-380.
Beach et al., 1992: Beach RF, Cordon-Rosales C, Molina E, Wirtz RA. Field evaluation of an enzyme-linked immunosorbent assay for estimating the sporozoite rate in Anopheles albimanus. Am J Trop Med Hyg. 1992; 47(4); 478-483. [PubMed: 1443346].
Beier et al., 1992: Beier JC, Beier MS, Vaughan JA, Pumpuni CB, Davis JR, Noden BH. Sporozoite transmission by Anopheles freeborni and Anopheles gambiae experimentally infected with Plasmodium falciparum. J Am Mosq Control Assoc. 1992; 8(4); 404-408. [PubMed: 1474388].
Bozdech et al., 2003: Bozdech Z, Llinas M, Pulliam BL, Wong ED, Zhu J, DeRisi JL. The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum. PLoS Biol. 2003; 1(1); E pub ahead of print-. [PubMed: 12929205].
Branquinho et al., 1993: Branquinho MS, Lagos CB, Rocha RM, Natal D, Barata JM, Cochrane AH, Nardin E, Nussenzweig RS, Kloetzel JK. Anophelines in the state of Acre, Brazil, infected with Plasmodium falciparum, P. vivax, the variant P. vivax VK247 and P. malariae. Trans R Soc Trop Med Hyg. 1993; 87(4); 391-394. [PubMed: 8249059].
Breman et al., 2004: Breman JG, Alilio MS, Mills A. Conquering the intolerable burden of malaria: what's new, what's needed: a summary. Am J Trop Med Hyg. 2004; 71(2 Suppl); 1-15. [PubMed: 15331814].
Brown and Khoa, 1975: Brown JD, Khoa NQ. Fatal falciparum malaria among narcotic injectors. Am J Trop Med Hyg. 1975; 24(5); 729-733. [PubMed: 1103639].
Bruce-Chwatt, 1985: Bruce-Chwatt LJ. The Malaria Parasites. 12-50. In: . Essential Malariology. 1985. William Heinemann Medical Books Ltd, 23 Bedford Square, London.
Bruneel et al., 2001: Bruneel F, Gachot B, Wolff M, Regnier B, Danis M, Vachon F. Resurgence of blackwater fever in long-term European expatriates in Africa: report of 21 cases and review. Clin Infect Dis. 2001; 32(8); 1133-1140. [PubMed: 11283802].
Cabrera et al., 1977: Cabrera A, Arambulo PV. Malaria in the Republic of the Philippines. A review. Acta Trop. 1977; 34(3); 265-279. [PubMed: 21558].
Chareonviriyaphap et al., 2000: Chareonviriyaphap T, Bangs MJ, Ratanatham S. Status of malaria in Thailand. Southeast Asian J Trop Med Public Health. 2000; 31(2); 225-237. [PubMed: 11127318].
Chege and Beier, 1998: Chege GM, Beier JC. Blood acquisition and processing by three Anopheles (Diptera: Culicidae) species with different innate susceptibilities to Plasmodium falciparum. J Med Entomol. 1988; 35(3); 319-323. [PubMed: 9615552].
Collins and Jeffery, 1999: Collins WE, Jeffery GM. A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity during primary infection. Am J Trop Med Hyg. 1999; 61((1 Suppl)); 4-19. [PubMed: 10432041].
Conway et al., 2000: Conway DJ, Fanello C, Lloyd JM, Al-Joubori BM, Baloch AH, Somanath SD, Roper C, Oduola AM, Mulder B, Povoa MM, Singh B, Thomas AW. Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA. Mol Biochem Parasitol. 2000; 111(1); 163-171. [PubMed: 11087926].
Cooper and Frances, 2002: Cooper RD, Frances SP. Malaria vectors on Buka and Bougainville Islands, Papua New Guinea. J Am Mosq Control Assoc. 2002; 18(2); 100-106. [PubMed: 12083350].
Craig et al., 2003: Craig A, Kyes S, Ranson H, Hemingway, J. Malaria parasite and vector genomes: partners in crime. Trends in Parasitology. 2003; 19(8); 356-362. [PubMed: 12901937].
Dash et al., 2000: Dash AP, Hazra RK, Mahapatra N, Tripathy HK. Disappearance of malaria vector Anopheles sundaicus from Chilika Lake area of Orissa State in India. Med Vet Entomol. 2000; 14(4); 445-449. [PubMed: 11129711].
Dia et al., 2003: Dia I, Diop T, Rakotoarivony I, Kengne P, Fontenille D. Bionomics of Anopheles gambiae Giles, An. arabiensis Patton, An. funestus Giles and An. nili (Theobald) (Diptera: Culicidae) and transmission of Plasmodium falciparum in a Sudano-Guinean zone (Ngari, Senegal). J Med Entomol. 2003; 40(3); 279-283. [PubMed: 12943105].
Dzeing-Ella et al., 2005: Dzeing-Ella A, Nze Obiang PC, Tchoua R, Planche T, Mboza B, Mbounja M, Muller-Roemer U, Jarvis J, Kendjo E, Ngou-Milama E, Kremsner PG, Krishna S, Kombila M. Severe falciparum malaria in Gabonese children: clinical and laboratory features. Malar J. 2005; 4(1); 1-. [PubMed: 15638948].
Ejov et al., 1999: Ejov MN, Tun T, Aung S, Sein K. Response of falciparum malaria to different antimalarials in Myanmar. Bulletin of the World Health Organization. 1999; 77(3); 244-249. [PubMed: 10212515].
Gardner et al., 2002: Gardner MJ, Shallon S, Carlton JM, Salzberg SL, Nene V, Shoaibi A, Ciecko A, Lynn J, Rizzo M, Weaver B, Jarrahi B, Brenner M, Parvizi B, Tallon L, Moazzez A, Granger D, Fujii C, Hansen C, Pederson J, Feldblyum T, Peterson J, Suh B, Angiuoli S, Pertea M, Allen J, Selengut J, White O, Cummings LM, Smith HO, Adams MD, Venter JC, Carucci DJ, Hoffman SL, Fraser CM. Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14. Nature. 2002; 419(6906); 531-534. [PubMed: 12368868].
Gardner et al., 2002B: Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002; 419(6906); 498-511. [PubMed: 12368864].
Ghosh et al., 2000: Ghosh A, Edwards MJ, Jacobs-Lorena M. The journey of the malaria parasite in the mosquito: hopes for the new century. Parasitol Today. 2000; 16(5); 196-201. [PubMed: 10782078].
Ghosh et al., 2003: Ghosh A, Srinivasan P, Abraham EG, Fujioka H, Jacobs-Lorena M. Molecular strategies to study Plasmodium-mosquito interactions. Trends Parasitol. 2003; 19(2); 94-101. [PubMed: 12586478].
Gonzalez et al., 1997: Gonzalez JM, Olano V, Vergara J, Arevalo-Herrera M, Carrasquilla G, Herrera S, Lopez JA. Unstable, low-level transmission of malaria on the Colombian Pacific Coast. Ann Trop Med Parasitol. 1997; 91(4); 349-358. [PubMed: 9290841].
Guerin et al., 2002: Guerin PJ, Olliaro P, Nosten F, Druilhe P, Laxminarayan R, Binka F, Kilama WL, Ford N, White NJ. Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development. The Lancet Infectious Diseases. 2002; 2(9); 564-573. [PubMed: 12206972].
Guthmann et al., 2002: Guthmann JP, Ruiz A, Priotto G, Kiguli J, Bonte L, Legros D. Validity, reliability and ease of use in the field of five rapid tests for the diagnosis of Plasmodium falciparum malaria in Uganda. Trans R Soc Trop Med Hyg. 2002; 96(3); 254-257. [PubMed: 12174772].
Hall et al., 2002: Hall N, Pain A, Berriman M, Churcher C, Harris B, Harris D, Mungall K, Bowman S, Atkin R, Baker S, Barron A, Brooks K, Buckee CO, Burrows C, Cherevach I, Chillingworth C, Chillingworth T, Christodoulou Z, Clark L, Clark R, Corton C, Cronin A, Davies R, Davis P, Dear P, Dearden F, Doggett J, Feltwell T, Goble A, Goodhead I, Gwilliam R, Hamlin N, Hance Z, Harper D, Hauser H, Hornsby T, Holroyd S, Horrocks P, Humphray S, Jagels K, James KD, Johnson D, Kerhornou A, Knights A, Konfortov B, Kyes S, Larke N, Lawson D, Lennard N, Line A, Maddison M, McLean J, Mooney P, Moule S, Murphy L, Oliver K, Ormond D, Price C, Quail MA, Rabbinowitsch E, Rajandream MA, Rutter S, Rutherford KM, Sanders M, Simmonds M, Seeger K, Sharp S, Smith R, Squares R, Squares S, Stevens K, Taylor K, Tivey A, Unwin L, Whitehead S, Woodward J, Sulston JE, Craig A, Newbold C, Barrell BG. Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Nature. 2002; 419(6906); 527-531. [PubMed: 12368867].
Hanscheid and Grobusch, 2002: H?nscheid T, Grobusch MP. How useful is PCR in the diagnosis of malaria?. Trends in Parasitology. 2002; 18(9); 395-398. [PubMed: 12377256].
Harbach et al., 1987: Harbach RE, Baimai V, Sukowati S. Some observations on sympatric populations of the malaria vectors Anopheles leucosphyrus and Anopheles balabacensis in a village-forest setting in South Kalimantan. Southeast Asian J Trop Med Public Health. 1987; 18(2); 241-247. [PubMed: 3313741].
Hickman et al., 1966: Hickman RL, Gochenour WSJ, Marshall JDJ, Guilloud NB. Drug resistant Plasmodium falciparum in the chimpanzee. Mil Med. 1966; 131(9); 935-943. [PubMed: 4957842].
Hii et al., 1988: Hii JL, Kan S, Vun YS, Chin KF, Tambakau S, Chan MK, Lye MS, Mak JW, Cochrane AH. Transmission dynamics and estimates of malaria vectorial capacity for Anopheles balabacensis and An. flavirostris (Diptera: Culicidae) on Banggi island, Sabah, Malaysia. Ann Trop Med Parasitol. 1988; 82(1); 91-101. [PubMed: 3041932].
Jelinek et al., 2001: Jelinek T, Grobusch MP, Loscher T. Patterns of Plasmodium falciparum drug resistance in nonimmune travelers to Africa. Eur J Clin Microbiol Infect Dis. 2001; 20(4); 284-286. [PubMed: 11399022].
John et al., 2004: John CC, Koech DK, Sumba PO, Ouma JH. Risk of Plasmodium falciparum infection during a malaria epidemic in highland Kenya, 1997. Acta Trop. 2004; 92(1); 55-61. [PubMed: 15301975].
Joshi et al., 1998: Joshi RD, Sharma SN, Dhingra N, Thapar BR, Yadava RL, Lal S. Some aspects of changing behaviour of malaria vectors in tribal areas of India. J Commun Dis. 1998; 30(4); 267-278. [PubMed: 10810568].
Juminer et al., 1981: Juminer R, Robin Y, Pajot FX, Eutrope R. Malaria pattern in French Guyana. Med Trop (Mars). 1981; 41(2); 135-146. [PubMed: 7017337].
Kamal and Das, 2001: Kamal S, Das SC. Epidemiological observations on malaria in some parts of Darrang District, Assam. Indian J Malariol. 2001; 38(1-2); 25-31. [PubMed: 11963817].
Kappe et al., 2003: Kappe SHI, Kaiser K, Matuschewski K. The Plasmodium sporozoite journey: a rite of passage. Trends Parasitol. 2003; 19(3); 135-143. [PubMed: 12643997].
Karnasuta et al., 1995: Karnasuta C, Pavanand K, Chantakulkij S, Luttiwongsakorn N, Rassamesoraj M, Laohathai K, Webster HK, Watt G. Complete development of the liver stage of Plasmodium falciparum in a human hepatoma cell line. Am J Trop Med Hyg. 1995; 53(6); 607-611. [PubMed: 8561262].
Kenawy et al., 1990: Kenawy MA, Beier BC, Asiago CM, el Said SE, Roberts CR. Interpretation of low-level Plasmodium infection rates determined by ELISA for anophelines (Diptera: Culicidae) from Egyptian oases. J Med Entomol. 1990; 27(4); 681-685. [PubMed: 2201771].
Klein et al., 1991: Klein TA, Lima JB, Tada MS. Comparative susceptibility of anopheline mosquitoes to Plasmodium falciparum in Rondonia, Brazil. Am J Trop Med Hyg. 1991; 44(6); 598-603. [PubMed: 1858963].
Kobayashi et al., 2000: Kobayashi J, Somboon P, Keomanila H, Inthavongsa S, Nambanya S, Inthakone S, Sato Y, Miyagi I. Malaria prevalence and a brief entomological survey in a village surrounded by rice fields in Khammouan province, Lao PDR. Trop Med Int Health. 2000; 5(1); 17-21. [PubMed: 10672201].
Kremsner and Krishna, 2004: Kremsner PF, Kirshna S. Antimalarial combinations. Lancet. 2004; 364(9430); 285-294. [PubMed: 15262108].
Krudsood et al., 2001: Krudsood S, Singhasivanon P, Silachamroon U, Treeprasertsuk S, Kaivipakbanyai W, Chalermrut K, Phophak N, Horton J, Kyle D, Looareesuwan S. Clinical trial of halofantrine with modified doses for treatment of malaria in the hospital for tropical diseases. Southeast Asian J Trop Med Public Health. 2001; 32(2); 255-261. [PubMed: 11556573].
Kruger et al., 2001: Kruger A, Rech A, Su XZ, Tannich E. Two cases of autochthonous Plasmodium falciparum malaria in Germany with evidence for local transmission by indigenous Anopheles plumbeus. Trop Med Int Health. 2001; 6(12); 983-985. [PubMed: 11737834].
Kun et al., 2002: Kun JF, Missinou MA, Lell B, Sovric M, Knoop H, Bojowald B, Dangelmaier O, Kremsner PG. New emerging Plasmodium falciparum genotypes in children during the transition phase from asymptomatic parasitemia to malaria. American Journal of Tropical Medicine and Hygiene. 2002; 66(6); 653-658. [PubMed: 12224569].
Land, 2003: Land KM. The mosquito genome: perspectives and possibilities. Trends Parasitol. 2003; 19(3); 103-105. [PubMed: 12643988].
Lengeler, 2000: Lengeler C. Insecticide-treated bednets and curtains for preventing malaria. Cochrane Database Syst Rev. 2000; 2; CD000363-. [PubMed: 10796535].
Liu, 1990: Liu C. Comparative studies on the role of Anopheles anthropophagus and Anopheles sinensis in malaria transmission in China. Zhonghua Liu Xing Bing Xue Za Zhi. 1990; 11(6); 360-363. [PubMed: 2276188].
Meyer et al., 2004: Meyer CG, Marks F, May J. Editorial: Gin tonic revisited. Trop Med Int Health. 2004; 9(2); 1239-1240. [PubMed: 15598254].
Ndao et al., 2004: Ndao M, Bandyayera E, Kokoskin E, Gyorkos TW, MacLean JD, Ward BJ. Comparison of blood smear, antigen detection, and nested-PCR methods for screening refugees from regions where malaria is endemic after a malaria outbreak in Quebec, Canada. J Clin Microbiol. 2004; 42(6); 2694-2700. [PubMed: 15184454].
Nigatu et al., 1992: Nigatu W, Abebe M, Dejene A. Plasmodium vivax and P. falciparum epidemiology in Gambella, south-west Ethiopia. Trop Med Parasitol. 1992; 43(3); 181-185. [PubMed: 1470839].
Nino-Vasquez et al., 2000: Nino-Vasquez JJ, Vogel D, Rodriguez R, Moreno A, Patarroyo ME, Pluschke G, Daubenberger CA. Sequence and diversity of DRB genes of Aotus nancymaae, a primate model for human malaria parasites. Immunogenetics. 2000; 51(3); 219-230. [PubMed: 10752632].
Over et al., 2004: Over M, Bakote'e B, Velayudhan R, Wilikai P, Graves PM. Impregnated nets or ddt residual spraying? Field effectiveness of malaria prevention techniques in solomon islands, 1993-1999. Am J Trop Med Hyg. 2004; 71(2 Suppl); 214-223. [PubMed: 15331840].
Paul et al., 2004: Paul RE, Diallo M, Brey PT. Mosquitoes and transmission of malaria parasites - not just vectors. Malar J. 2004; 3(1); 1-13. [PubMed: 15533243].
Payne, 1988: Payne D. Use and limitations of light microscopy for diagnosing malaria at the primary health care level. Bull World Health Organ. 1988; 66(5); 621-626. [PubMed: 2463112].
Petersen, 2004: Petersen E. Malaria chemoprophylaxis: when should we use it and what are the options?. Expert Rev Anti Infect Ther. 2004; 2(1); 119-132. [PubMed: 15482177].
Phillips, 2001: Phillips RS. Current status of malaria and potential for control. Clinical Microbiology Reviews. 2001; 14(1); 208-226. [PubMed: 11148010].
Povoa et al., 2001: Povoa MM, Wirth RA, Lacerda RNL, Miles M, Warhurst D. Malaria vectors in the municipality of Serra do Navio, State of Amapa, Amazon Region, Brazil. Mem Inst Oswaldo Cruz. 2001; 96(2); 179-184. [PubMed: 11285494].
Prakash et al., 2001: Prakash A, Bhattacharyya DR, Mohapatra PK, Mahanta J. Estimation of vectorial capacity of Anopheles dirus (Diptera: Culicidae) in a forest-fringed village of Assam (India). Vector Borne Zoonotic Dis. 2001; 1(3); 231-237. [PubMed: 12653151].
Prakash et al., 2004: Prakash A, Bhattacharyya DR, Mohapatra PK, Mahanta J. Role of the prevalent Anopheles species in the transmission of Plasmodium falciparum and P. vivax in Assam state, north-eastern India. Ann Trop Med Parasitol. 2004; 98(6); 559-568. [PubMed: 15324463].
Pribadi et al., 1998: Pribadi W, Sutanto I, Atmosoedjono S, Rasidi R, Surya LK, Susanto L. Malaria situation in several villages around Timika, south central Irian Jaya, Indonesia. Southeast Asian J Trop Med Public Health. 1998; 29(2); 228-235. [PubMed: 9886103].
Raccurt, 2002: Raccurt C. Malaria in Haiti today. Sante. 2004; 14(4); 201-204. [PubMed: 15745868].
Raether et al., 1989: Raether W, Enders B, Hoffman J, Schwannecke U, Seidenath H, Hanel H, Uphoff M. Antimalarial activity of new floxacrine-related acridinedione derivatives: studies on blood schizontocidal action of potential candidates against P. berghei in mice and P. falciparum in vivo and in vitro. Parasitol Res. 1989; 75(8); 619-626. [PubMed: 2671988].
Ramasamy et al., 1992: Ramasamy R, De Alwis R, Wijesundere A, Ramasamy MS. Malaria transmission at a new irrigation project in Sri Lanka: the emergence of Anopheles annularis as a major vector. Am J Trop Med Hyg. 1992; 47(5); 547-553. [PubMed: 1449195].
Ramasamy et al., 1997: Ramasamy MS, Kulasekera R, Wanniarachchi IC, Srikrishnaraj KA, Ramasamy R. Interactions of human malaria parasites, Plasmodium vivax and P.falciparum, with the midgut of Anopheles mosquitoes. Med Vet Entomol. 1997; 11(3); 290-296. [PubMed: 9330262].
Raynes, 1999: Raynes K. Bisquinoline antimalarials: their role in malaria chemotherapy. International Journal of Parasitology. 1999; 29(3); 367-379. [PubMed: 10333319].
Rowland et al., 2002: Rowland M, Mohammed N, Rehman H, Hewitt S, Mendis C, Ahmad M, Kamal M, Wirtz R. Anopheline vectors and malaria transmission in eastern Afghanistan. Trans R Soc Trop Med Hyg. 2002; 96(6); 620-626. [PubMed: 12625136].
Russell et al., 1963: Russell PF, West LS, Manwell RD, Macdonaldl G. The Human Plasmodia. 47-75. In: . Practical Malariology Second Edition. 1963. Oxford University Press, Great Britain.
Schmidt and Roberts, 1985: Schmidt GD, Roberts LS. Phylum Apicomplexa: Malaria and piroplasms. 149-178. In: . Foundations of Parasitology.. 1985. Times Mirror/Mosby College Publishing, St. Louis, Missouri.
Shehata et al., 1989: Shehata MG, Kenawy MA, el Said SM, Beier JC, Gwadz R, Shaaban M. Anopheles sergenti (Theobald) a potential malaria vector in Egypt. Ann Parasitol Hum Comp. 1989; 64(1); 72-76. [PubMed: 2648934].
Shukla et al., 2002: Shukla RP, Sharma SN, Bhat K. Malaria outbreak in Bhojpur PHC of district Moradabad, Uttar Pradesh, India. Commun Dis. 2002; 34(2); 118-123. [PubMed: 14768829].
Singh et al., 2003: Singh N, Mishra AK, Shukla MM, Chand SK. Forest malaria in Chhindwara, Madhya Pradesh, central India: a case study in a tribal community. Am J Trop Med Hyg. 2003; 68(5); 602-607. [PubMed: 12812354].
Smith and Wright-Kanuth, 2003: Smith LA, Wright-Kanuth MS. Transfusion-transmitted parasites. Clin Lab Sci. 2003; 16(4); 239-245. [PubMed: 14626442].
Somboon et al., 1994: Somboon P, Suwonkerd W, Lines JD. Susceptibility of Thai zoophilic Anophelines and suspected malaria vectors to local strains of human malaria parasites. Southeast Asian J Trop Med Public Health. 1994; 25(4); 766-770. [PubMed: 7667729].
Somboon et al., 1998: Somboon P, Aramrattana A, Lines J, Webber R. Entomological and epidemiological investigations of malaria transmission in relation to population movements in forest areas of north-west Thailand. Southeast Asian J Trop Med Public Health. 1998; 29(1); 3-9. [PubMed: 9740259].
Sowunmi et al., 2001: Sowunmi A, Ayede AI, Falade AG, Ndikum VN, Sowunmi CO, Adedeji AA, Falade CO, Happi TC, Oduola AM. Randomized comparison of chloroquine and amodiaquine in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children. Annals of Tropical Medicine and Parasitology. 2001; 95(6); 549-558. [PubMed: 11672461].
Stauffer and Fischer, 2003: Stauffer W, Fischer RO. Diagnosis and treatment of malaria in children. Clin Infect Dis. 2003; 37(10); 1340-1348. [PubMed: 14583868].
Suh et al., 2004: Suh KN, Kain KC, Keystone JS. Malaria. CMAJ. 2004; 170(11); 1693-1702. [PubMed: 15159369].
Sukwa et al., 1999: Sukwa TY, Mulenga M, Chisdaka N, Roskell NS, Scott TR. A randomized, double-blind, placebo-controlled field trial to determine the efficacy and safety of Malarone (atovaquone/proguanil) for the prophylaxis of malaria in Zambia. American Journal of Tropical Medicine and Hygiene. 1999; 60(4); 521-525. [PubMed: 10348223].
Taylor and White, 2004: Taylor WRJ, White NJ. Antimalarial drug toxicity: a review. Drug Saf. 2004; 27(1); 25-61. [PubMed: 14720085].
Thybo et al., 2004: Thybo S, Gjorup I, Ronn AM, Meyrowitsch D, Bygberg IC. Atovaquone-proguanil (malarone): an effective treatment for uncomplicated Plasmodium falciparum malaria in travelers from Denmark. J Travel Med. 2004; 11(4); 220-223. [PubMed: 15541224].
Toma et al., 2002: Toma T, Miyagi I, Okazawa T, Kobayashi J, Saita S, Tuzuki A, Keomanila H, Nambanya S, Phompida S, Uza M, Takakura M. Entomological surveys of malaria in Khammouane Province, Lao PDR, in 1999 and 2000. Southeast Asian J Trop Med Public Health. 2002; 33(3); 532-546. [PubMed: 12693588].
Touze et al., 1997: Touze JE, Fourcade L, Peyron F, Heno P, Deharo JC. Is halofantrine still advisable in malaria attacks?. Annals of Tropical Medicine and Parasitology. 1997; 91(7); 867-873. [PubMed: 9625944].
Trager, 1986: Trager W. Differentiation in the life cycle. 121-146. In: . Living Together. The Biology of Animal Parasitism. 1986. Plenum Press, New York, New York.
Trager, 1994: Trager W. Cultivation of Malaria Parasites. Methods Cell Biol. 1994; 45; 7-26. [PubMed: 7707996].
Trampuz et al., 2003: Trampuz A, Jereb M, Muzlovic I, Prabhu RM. Clinical review: Severe malaria. Crit Care. 2003; 7(4); 315-323. [PubMed: 12930555].
Tyagi et al., 2001: Tyagi BK, Yadav SP, Sachdev R, Dam PK. Malaria outbreak in the Indira Gandhi Nahar Pariyojna command area in Jaisalmer district, Thar Desert, India. J Commun Dis. 2001; 33(2); 88-95. [PubMed: 12170943].
WHO, 2000: . Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000; 94(Suppl 1); S1-S90. [PubMed: 11103309].
Wanji et al., 2003: Wanji S, Tanke T, Atanga SN, Ajonina C, Nicholas T, Fontenille D. Anopheles species of the mount Cameroon region: biting habits, feeding behaviour and entomological inoculation rates. Trop Med Int Health. 2003; 8(7); 643-649. [PubMed: 12828548].
Wattanakoon et al., 2003: Wattanakoon Y, Chittamas S, Pornkulprasit V, Kanda T, Thimasarn K, Rojanawatsirivej C, Looareesuwan S, Bunnag D. Six-years monitoring the efficacy of the combination of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria. Southeast Asian J Trop Med Public Health. 2003; 34(3); 542-545. [PubMed: 15115124].
Weatherall et al., 2002: Weatherall DJ, Miller LH, Baruch DI, Marsh K, Doumbo OK, Casals-Pascual C, Roberts DJ. Malaria and the red cell. Hematology (Am Soc Hematol Educ Program). 2002; ; 35-57. [PubMed: 12446418].
Website 100: Anopheles pulcherrimus
Website 101: Anopheles punctulatus
Website 102: Anopheles rangeli
Website 103: Anopheles sacharovi
Website 104: Anopheles sawadwongporni
Website 105: Anopheles sinensis
Website 106: Anopheles stephensi
Website 107: Anopheles subpictus
Website 108: Anopheles sundaicus
Website 109: Anopheles tessellatus
Website 110: Anopheles triannulatus
Website 111: Anopheles vagus
Website 112: Anopheles varuna
Website 113: Anopheles mangyanus
Website 114: Anopheles multicolor
Website 115: Anopheles pseudopunctipennis
Website 116: Anopheles superpictus
Website 117: Malaria
Website 118: BMBL Section VII. Agent Summary Statements. Section VII-C: Parasitic Agents
Website 119: BMBL Section III. Laboratory Biosafety Level Criteria
Website 120: New Perspectives - Malaria Diagnosis
Website 121: Malaria. Serology. Indirect Fluorescent Antibody Test
Website 122: Malaria. Diagnosis
Website 124: Malaria
Website 125: Plasmodium falciparum: Ring Stage Parasites
Website 126: Plasmodium falciparum: Schizonts
Website 127: Plasmodium falciparum: Schizonts
Website 128: Plasmodium falciparum: Schizonts
Website 129: Plasmodium falciparum: Trophozoites
Website 131: Plasmodium falciparum: Gametocytes
Website 3: Plasmodium falciparum chromosome 1
Website 32: Plasmodium falciparum mitochondrion, complete genome
Website 34: Plasmodium falciparum 3D7 chromosome 1, complete sequence
Website 35: Plasmodium falciparum chromosome 2
Website 36: Plasmodium falciparum 3D7 chromosome 2, complete sequence
Website 37: Plasmodium falciparum chromosome 3
Website 38: Plasmodium falciparum 3D7 chromosome 3, complete sequence
Website 39: Plasmodium falciparum chromosome 4
Website 40: Plasmodium falciparum 3D7 chromosome 4, complete sequence
Website 41: Plasmodium falciparum chromosome 5
Website 42: Plasmodium falciparum 3D7 chromosome 5, complete sequence
Website 43: Plasmodium falciparum chromosome 6
Website 44: Plasmodium falciparum 3D7 chromosome 6, complete sequence
Website 45: Plasmodium falciparum chromosome 7
Website 46: Plasmodium falciparum 3D7 chromosome 7, *** SEQUENCING IN PROGRESS
Website 47: Plasmodium falciparum chromosome 8
Website 48: Plasmodium falciparum 3D7 chromosome 8, *** SEQUENCING IN PROGRESS
Website 49: Plasmodium falciparum chromosome 9
Website 50: Plasmodium falciparum 3D7 chromosome 9, complete sequence
Website 51: Plasmodium falciparum chromosome 10
Website 52: Plasmodium falciparum 3D7 chromosome 10, complete sequence
Website 53: Plasmodium falciparum chromosome 11
Website 54: Plasmodium falciparum 3D7 chromosome 11, complete sequence
Website 55: Plasmodium falciparum chromosome 12
Website 56: Plasmodium falciparum 3D7 chromosome 12, complete sequence
Website 57: Plasmodium falciparum chromosome 13
Website 58: Plasmodium falciparum 3D7 chromosome 13, *** SEQUENCING IN PROGRESS
Website 59: Plasmodium falciparum chromosome 14
Website 60: Plasmodium falciparum 3D7 chromosome 14, complete sequence
Website 61: P.falciparum complete gene map of plastid-like DNA (IR-A)
Website 62: P.falciparum complete gene map of plastid-like DNA (IR-B
Website 63: Homo sapiens
Website 64: Anopheles
Website 65: Anopheles aconitus
Website 66: Anopheles albimanus
Website 67: Anopheles albitarsis
Website 68: Anopheles annularis
Website 69: Anopheles anthropophagus
Website 70: Anopheles aquasalis
Website 71: Anopheles arabiensis
Website 72: Anopheles balabacensis
Website 73: Anopheles benarrochi
Website 74: Anopheles braziliensis
Website 75: Anopheles culicifacies
Website 76: Anopheles darlingi
Website 77: Anopheles deaneorum
Website 78: Anopheles dirus
Website 79: Anopheles farauti
Website 80: Anopheles flavirostris
Website 81: Anopheles fluviatilis
Website 82: Anopheles freeborni
Website 83: Anopheles funestus
Website 84: Anopheles gambiae
Website 85: Anopheles karwari
Website 86: Anopheles koliensis
Website 87: Anopheles labranchiae
Website 88: Anopheles maculatus
Website 89: Anopheles mediopunctatus
Website 90: Anopheles melas
Website 91: Anopheles minimus
Website 92: Anopheles moucheti
Website 93: Anopheles neivai
Website 94: Anopheles nili
Website 95: Anopheles nivipes
Website 96: Anopheles nuneztovari
Website 97: Anopheles oswaldoi
Website 98: Anopheles pharoensis
Website 99: Anopheles plumbeus
Wichmann et al., 2004: Wichmann O, Muehlen M, Gruss H, Mockenhaupt FP, Suttorp N, Jelinek T. Malarone treatment failure not associated with previously described mutations in the cytochrome b gene. Malar J. 2004; 3(1); 14-. [PubMed: 15186499].
Wiesner et al., 2003: Wiesner J, Ortmann R, Jomaa H, Schlitzer M. New antimalarial drugs. Angew Chem Int Ed Engl. 2003; 42(43); 5274-5293. [PubMed: 14613157].
Williamson et al., 2002: Williamson DH, Preiser PR, Moore PW, McCready S, Strath M, Wilson RJ. The plastid DNA of the malaria parasite Plasmodium falciparum is replicated by two mechanims. Molecular Microbiology. 2002; 45(2); 533-542. [PubMed: 12123462].
Wilson et al., 1996: Wilson RJM, Denny PW, Preiser PR, Rangachari K, Roberts K, Roy A, Whyte A, Strath M, Moore DJ, Moore PW, Williamson DH. Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum. Journal of Molecular Biology. 1996; 261; 155-172. [PubMed: 8757284].
Winstanley et al., 2002: Winstanley PA, Ward SA, Snow RW. Clinical status and implications of antimalarial drug resistance. Microbes and Infection. 2002; 4(2); 157-164. [PubMed: 11880047].
Winstanley et al., 2004: Winstanley P, Ward S, Snow R, Breckenridge A. Therapy of falciparum malaria in sub-saharan Africa: from molecule to policy. Clin Microbiol Rev. 2004; 17(3); 612-637. [PubMed: 15258096].
Winstanley, 2001: Winstanley P. Modern chemotherapeutic options for malaria. The Lancet Infectious Diseases. 2001; 1(4); 242-250. [PubMed: 11871511].
Wongsrichanalai et al., 2001: Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR. Epidemiology of drug-resistant malaria. The Lancet Infectious Diseases. 2001; 2(4); 209-218. [PubMed: 11937421].
Yapabandara et al., 2001: Yapabandara AM, Curtis CF, Wickramasinghe MP, Fernando WP. Control of malaria vectors with the insect growth regulator pyriproxyfen in a gem-mining area in Sri Lanka. Acta Trop. 2001; 80(3); 265-276. [PubMed: 11700185].
Zhou et al., 2004: Zhou G, Minakawa N, Githeko AK, Yan G. Association between climate variability and malaria epidemics in the East African highlands. Proc Natl Acad Sci U S A. 2004; 101(8); 2375-2380. [PubMed: 14983017].
al-Yaman et al., 1996: al-Yaman F, Genton B, Mokela D, Narara A, Raiko A, Alpers MP. Resistance of Plasmodium falciparum malaria to amodiaquine, chloroquine and quinine in the Madang Province of Papua New Guinea, 1990-1993. P N G Med J. 1996; 39(1); 16-22. [PubMed: 9522846].
de Zulueta et al., 1987: de Zulueta J. Changes in the geographical distribution of malaria throughout history. Parassitologia. 1987; 29(2-3); 193-205. [PubMed: 3334082].
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