Table of Contents:

• Taxonomy Information
• Lifecycle Information
• Genome Information
• Biosafety Information
• Culturing Information
• Epidemiology Information
• Diagnostic Tests Information
• Infected Hosts Information
• Phinet: Pathogen-Host Interaction Network
• Lab Animal Pathobiology & Management
• References
• Data Provenance and Curators

1. Species:
   1. Yellow fever virus (Website 1):
      1. GenBank Taxonomy No.: 11089
      2. Description: Despite the availability of a safe and efficacious vaccine, yellow fever (YF) remains a disease of significant public health importance, with an estimated 200,000 cases and 30,000 deaths annually. The disease is endemic in tropical regions of Africa and South America; nearly 90% of YF cases and deaths occur in Africa. It is a significant hazard to unvaccinated travelers to these endemic areas. Virus transmission occurs between humans, mosquitoes, and monkeys. The mosquito, the true reservoir of YF, is infected throughout its life, and can transmit the virus transovarially through infected eggs. Man and monkeys, on the other hand, play the role of temporary amplifiers of the virus available for mosquito infection. Recent increases in the density and distribution of the urban mosquito vector, Aedes aegypti, as well as the rise in air travel increase the risk of introduction and spread of yellow fever to North and Central America, the Caribbean, the Middle East, Asia, Australia, and Oceania(Tomori, 2004). YF virus, the first arthropod-borne human virus to be isolated, is the prototype member of the Flavivirus genus of the Flaviviridae family(Tomori, 2004).
      3. Variant(s):
         • Yellow fever virus (STRAIN 17D) (Website 2):
           • GenBank Taxonomy No.: 11090
           • Parents: Yellow fever virus
           • Description: In 1927, Mahaffy and Bauer of the West Africa Rockefeller Yellow Fever Commission (RYFC) isolated YF virus by inoculation the blood of a Ghanaian patient into rhesus monkeys. This strain, the Asibi strain, was attenuated by passage in chick embryo tissue and the modified (17D) virus later became the source of human YF vaccine(Tomori, 2004).
         • Yellow fever virus (strain 1899/81) (Website 3):
           • GenBank Taxonomy No.: 31641
           • Parents: Yellow fever virus
           • Description: Strain 1899/81 (human isolate from Peru)(Miller and Mitchell, 1986).
         • Yellow fever virus (STRAIN PASTEUR 17D-204) (Website 4):
           • GenBank Taxonomy No.: 11091
           • Parents: Yellow fever virus
           • Description: The 17D yellow fever vaccine virus family is the foundation for both the 17D-204 lineage and the 17DD lineage. Vaccine type 17D-204 is used in both the United States and Australia, whereas vaccine type 17DD is used in Brazil(Cetron et al., 2002).

1. Yellow Fever Virus Lifecycle
   1. Description: YF is a zoonotic infection, maintained in nature by wild non-human primates and diurnally active mosquitoes. Three different epidemiological patterns, leading to the same clinical picture, are recognized for YF virus transmission. These are the sylvatic or forest cycle, the Aedes aegypti-mediated urban cycle and an intermediate cycle bridging the sylvatic and urban cycles. Virus transmission in the sylvatic cycle is between monkeys and mosquitoes that breed in tree holes in the forest canopy (Haemagogus spp in the Americas and Aedes spp in Africa). Humans are sporadically exposed to infected mosquitoes when they encroach on this cycle during occupational or recreational activities. The intermediate cycle occurs in the moist savanna regions of Africa (the so-called 'zone of emergence'), where tree-hole breeding Aedes species mosquitoes reach very high densities and are implicated in endemic and epidemic transmission, transferring virus from monkey to people and between people. In the urban cycle, YF is transmitted between human beings by Ae. aegypti, a domestic mosquito that breeds in manmade containers. Virus transmission occurs between humans, mosquitoes and monkeys. The mosquito vector, which may belong to one of several species, becomes infected by feeding on a viremic host (man or monkey) and then transmits the virus to another susceptible human or monkey(Tomori, 2004).

1. Genome of Yellow fever virus
   1. YF_chromosome(Website 5, Website 7, Website 8, Website 9, Website 10, Website 11, Website 12, Website 13, Website 14, Website 15, Website 16)
      1. GenBank Accession Number: NC_002031 AY640589 AY603338 X03700 AY572535 U54798 AF094612 U17067 U17066 U21055 U21056
      2. Size: 10862 bp ss-RNA(Website 5).
      3. Gene Count: The genomic RNA is about 11,000 nt long and contains a single long open reading frame (ORF)(Pugachev et al., 2004).
      4. Description: The genome consists of 10,862 nucleotides and a relative mass of 3.75 x 10 (6). This is arranged into a single open-reading frame of 10,233 nucleotides, which encodes three structural and seven non-structural proteins, flanked by a short non-coding region of 511 nucleotides. The three structural genes are the capsid (C), premembrane/membrane (prM/M), and envelope (E) genes, while the non structural (NS) genes are NS1, NS2A, NS2B, NS3, NS4A, 2K, NS4B, and NS5, respectively(Tomori, 2004).
      5. Picture(s):
         • Yellow fever virus, complete genome (Website 6)
           
           
           
           
         • Yellow fever virus, complete genome (Website 6)
           
           
           
           

1. Biosafety information for Yellow fever virus
   1. Level: Biosafety Level 3(Website 45).
   2. Precautions: Biosafety Level 3 practices, safety equipment, and facilities are recommended for activities using potentially infectious clinical materials and infected tissue cultures, animals, or arthropods.A licensed attenuated live virus is available for immunization against yellow fever. It is recommended for all personnel who work with this agent or with infected animals, and those qualified to enter rooms where the agents or infected animals are present. Indeed, but for this vaccine, the aerosol infectivity and high case fatality of yellow fever virus would make its classification BSL-4(Website 45).
   3. 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 52). Only needle-locking syringes or disposable syringe-needle units (i.e., needle is integral to the syringe) are used for injection or aspiration of infectious materials. Used disposable needles must not be bent, sheared, broken, recapped, removed from disposable syringes, or otherwise manipulated by hand before disposal; rather, they must be carefully placed in conveniently located puncture-resistant containers used for sharps disposal. Non-disposable sharps must be placed in a hard-walled container for transport to a processing area for decontamination, preferably by autoclaving(Website 52). Broken glassware must not be handled directly by hand, but must be removed by mechanical means such as a brush and dustpan, tongs, or forceps. Containers of contaminated needles, sharp equipment, and broken glass are decontaminated before disposal, according to any local, state, or federal regulations(Website 52). Cultures, tissues, specimens of body fluids, or potentially infectious wastes are placed in a container with a cover that prevents leakage during collection, handling, processing, storage, transport, or shipping(Website 52).

1. Culture Summary :
   1. Description: The virus is most readily isolated from acute stage serum obtained during the first four days of illness, but may be recovered from serum up to the 14th day and, as earlier indicated, from the liver tissue at death. Several methods are available for the isolation of YF virus from clinical specimens. These include, intracerebral inoculation of suckling mice, the intrathoracic inoculation of mosquitoes, the inoculation of mosquito cell cultures (especially Ae. pseudoscutellaris (AP61) cells), or the inoculation of mammalian cell cultures (e.g. Vero, SW 13, BHK-21)(Tomori, 2004). Yellow fever virus can be propagated in a wide variety of primary and continuous cell cultures. Vaccine strains (17D and French neurotropic viruses) grow to higher titer and produce more evident CPE and plaques than do wild stains in various continuous monkey kidney (MA-104, Vero, LLC-MK2), rabbit kidney (MA-11), baby hamster kidney (BHK), and PS cell lines, as well as in primary chick and ducky embryo fibroblast monolayers. Wild yellow fever virus strains can also be propagated in these cell cultures, but plaque formation is inconsistent and variable from strain to strain(Burke and Monath, 2001). Mosquito cell cultures are useful for primary isolation and are more sensitive than Vero cells or infant mice. A. pseudoscutellaris (AP-61), cloned A. aegypti, and A. albopictus cells are susceptible; infection is generally assessed by IF or subpassaged to mice or Vero cells(Burke and Monath, 2001).
2. Viral isolation in Vero Cell Culture :
   1. Description: Aliquots of each of the serum samples were injected intracerebrally into litters of eight newborn (2448 hours after birth) Swiss albino mice. The mice were observed daily for signs of illness. Sick mice were euthanized, and a preparation was made of 10% of the harvested mouse brain suspension made in Eagles Maintenance Media with 2% serum albumin, 2% glutamine, and 1% antibiotics (penicillin, streptomycin, and amphotericin B) and centrifuged at 3,000 rpm for 10 min. The clarified supernatant fluid was filtered with a 0.45-m syringe filter and injected intracerebrally into a litter of suckling mice to confirm the isolation.All the sera were diluted 1:10 in sterile phosphate-buffered saline pH 7.4 (without magnesium and calcium), and viral isolation attempts in Vero cell cultures were made by injecting 100 L of the diluted sample onto confluent monolayer of Vero cells in 25 ml culture flasks. Flasks were incubated at 37 C and observed daily for evidence of cytopathogenic effect (CPE). After CPE was evident, the supernatant fluid was clarified by centrifugation at 3,000 rpm for 10 min. Viral RNA was extracted from both the 10% brain suspension from sick mice and from the clarified cell culture media and screened for flavivirus and YFV viral nucleic acid RNA by RT-PCR(Onyango et al., 2004).
   2. Medium: Sterile phosphate-buffered saline (without magnesuim and calcium)(Onyango et al., 2004).
   3. Optimal Temperature: 37 C(Onyango et al., 2004).
   4. Optimal pH: pH 7.4(Onyango et al., 2004).

1. Outbreak Locations:
   1. During the first week of May 2003, the Early Warning and Response Network, established in 1999 in southern Sudan, reported an outbreak of fatal hemorrhagic fever of unknown etiology in the Imatong region of Torit County, which is near the Ugandan border, in a mountainous area covered with tropical rain forest. During the civil unrest in early 2002, many residents were relocated to an internally displaced persons camp in Ikotos County, but in 2003, a number of the residents moved back to the Imatong region. During April and May 2003 suspected cases of hemorrhagic illness were reported, and blood samples collected from Sarianga, Itohom, Lenyleny, Tarafafa, Lofi, and Locomo villages were tested at the Kenya Medical Research Institute (KEMRI), in Nairobi, where yellow fever virus was identified as the causative agent of the outbreak(Onyango et al., 2004).
   2. In the summer of 2001, during the occurrence of a sylvatic YF outbreak in the State of Minas Gerais, Southeast Region of Brazil, a mass vaccination campaign was carried out in order to control the outbreak, which involved 81 suspected cases, 32 confirmed cases with 17 deaths, a case fatality rate of 53%(Filippis et al., 2004).
   3. Up to 5000 cases in Africa and 300 in South America are reported annually, but the true incidence is believed to be 1050 fold higher than the official reports. Between 1990 and 1999, 11 297 cases and 2648 deaths were reported in Africa. The largest number of cases was in Nigeria, which suffered a series of epidemics between 1986 and 1994. Epidemics have also occurred in Cameroon (1990), Ghana (19931994, 1996), Liberia (1995, 1998), Gabon (1994), Senegal (1995, 1996), Benin (1996), and Kenya (1992). An epidemic is currently occurring along the border of Liberia and Guinea, an area torn by war with disruption of vaccination and medical services. During epidemics in Africa, the incidence of infection may be as high as 20% and the incidence of disease 3%. In South America, yellow fever occurs principally in the Amazon region and contiguous grasslands. Between 1990 and 1999, 1939 cases and 941 deaths were reported. Peru and Bolivia had the highest incidence, reflecting low vaccination coverage(Monath, 2001).
2. Transmission Information:
   1. From: Mosquitoes, Mosquito Nonhuman_Primate , To: Nonhuman Vertebrates, Mosquito Nonhuman_Primate , With Destination:Nonhuman Vertebrates, Mosquito Nonhuman_Primate
      Mechanism: Suggestions that yellow fever was transmitted by mosquito bite were advanced by Nott in 1848, by Beauperthuy in 1854, and by Carlos J. Finlay in 1881. Finlay's theory later spurred Major Walter Reed to undertake his landmark studies in Cuba on mosquito transmission of yellow fever. In 1900 Reed and colleagues demonstrated transmission of yellow fever to volunteers by mosquitoes (Aedes aegypti) which had previously fed on clinically ill patients(Monath, 1989).
   2. From: Nonhuman Vertebrates, Mosquito Nonhuman_Primate , To: Mosquitoes, Mosquito Nonhuman_Primate , With Destination:Mosquitoes, Mosquito Nonhuman_Primate
      Mechanism: Yellow fever is a zoonotic disease. The primary transmission cycle involves wild nonhuman primates and various sylvatic (tree-hole-breeding) aedine mosquitoes. Humans may be tangentially exposed when they encroach on this cycle (so-called jungle yellow fever), and epidemic spread from human to human can subsequently be continued by sylvatic vectors. Alternatively, the domestic mosquito, Aedes aegypti, which lives in close relationship with humans, may transmit the virus, with humans being the sole viremic hosts in the cycle (A. aegypti-borne yellow fever or urban yellow fever)(Burke and Monath, 2001).
   3. From: Mosquitoes, Mosquito Nonhuman_Primate , To: Mosquitoes, Mosquito Nonhuman_Primate , With Destination:Mosquitoes, Mosquito Nonhuman_Primate
      Mechanism: The current theory for YF is that transmission occurs in cyclic waves of 7 to 10 years that result in epidemics. Our results, especially in Altamira, do not confirm that observation. Based on our results, we speculate that the occurrence of epidemics in the same limited geographic region of two neighboring municipalities was only possible because mosquitoes were born infected by vertical transmission. Infections in monkeys in 1998 should have made a large number of them immune, and the short interval between the outbreaks was not enough to renew the monkey population. We hypothesize that the persistence of YF virus in a region occurs by passing through several generations of mosquitoes and that this is the main mechanism responsible for maintenance of the virus and not the epidemic wave as has been suggested(Vasconcelos et al., 2001).
3. Environmental Reservoir:
   1. Mosquito Nonhuman_Primate:
      1. Description: Although monkeys and humans have been considered as the reservoirs of YF, the true reservoir is the susceptible mosquito species that not only remains infected throughout life, but can also transmit the virus transovarially to a proportion of the descendants through infected egg. Ova containing the virus survive in dry tree-holes and hatch infected progeny mosquitoes when the rains resume(Tomori, 2004). The most widely accepted hypothesis of YFV ecology in South America is that the virus is maintained by wandering epizootics of nonhuman primate species that move continuously throughout the Amazon region or along gallery forests of the river courses. Virtually all New World primate species are highly susceptible to YFV infection, and many neotropical species die of the infection. The acute viremic phase in monkeys is followed by solid immunity, and although persistent infection has been documented for some primate species in the laboratory, such infections are probably not accompanied by viremia levels sufficient to infect vectors. In Panama, Trinidad, and Brazil, finding dead monkeys (particularly Alouatta sp.) near forested regions has signaled the onset of epizootics. Many researchers have suggested that epizootics are cyclical events recurring at fairly regular intervals; the length of interepidemic intervals has been interpreted as the time required for reconstitution of susceptible monkey populations(Bryant et al., 2003). Viremia in monkeys is of relatively short duration, usually lasting for several days at titers in excess of those needed to infect vectors. The maximum duration of viremia is 9 days. The acute viremic phase is followed by solid immunity. Whereas these animals play an essential role in the amplification of virus transmission, there is no evidence that latent infections contribute to recrudescent virus activity in nature, and monkeys, therefore, do not constitute a true virus reservoir(Monath, 1989).
      2. Survival: Deleterious effects of yellow fever virus on vector mosquitoes have not been extensively studied. The longevity of infected and uninfected Aedes aegypti was found to be similar. However, transovarially infected progeny of Aedes aegypti took longer to pupate than uninfected siblings(Monath, 1989). Virtually all New World primate species are highly susceptible to YFV infection, and many neotropical species die of the infection(Tomori, 2004).
4. Intentional Releases:
   1. Currently no intentional releases information is available.

1. Organism Detection Test:
   1. Plaque Assay :
      1. Time to Perform: unknown
      2. Description: For quantifying the load of infectious particles either in cell culture or serum samples, the plaque assay is still a method commonly used(Bae et al., 2003). The plaque assay was carried out as a modified version of the assay described by De Madrid and Porterfield. Briefly, 6 x 10(5) porcine kidney cells in 200 ul RPMI 1640 were seeded in each well of a 24-well plate. Serial dilutions (1:20,000, 1:40,000 and 1:80,000) of the different viral suspensions were added to the wells (200 ul each). After an incubation period of 4 h, overlay medium (1.6% carboxymethyl-cellulose, 3% fetal calf serum in RPMI) was added, and the plates were incubated for 5 days at 37 C. After a 15 min fixation step with 4% formalin in PBS, the cells were stained with Naphtalin Black for 20 min. The plaques caused by lysis of infected cells were counted and the calculation of plaque forming units (pfu) was carried out according to Reed and Munch(Bae et al., 2003).
   2. Micro-culture Plaque Assay :
      1. Time to Perform: 2-to-7-days
      2. Description: Thirty-nine group B arboviruses have been titrated by a simple micro-culture method. The technique uses a stable line of pig kidney cells (PK cells) in which plaques develop when cells are first infected in suspension in the wells of hemagglutination trays and are incubated for 3 to 10 days under an overlay containing carboxymethyl-cellulose. This method can be adapted to measure neutralizing antibodies, and the principle underlying the test is applicalbe to other cells and tother viruses(de Madrid and Porterfield, 1969). The median time for optimal staining of plaques was 6 days, with a scatter down to 3 days and up to 10 days(de Madrid and Porterfield, 1969).
   3. Indirect Immunofluorescence Assay :
      1. Time to Perform: unknown
      2. Description: Viral antigens were detected by indirect immunofluoresence assay (IFA) using anti-yellow fever hyperimmunized mouse ascitic fluid (HMAF) and fluorescein-conjugated anti-mouse IgG(Deubel et al., 1997).
   4. Immunofluorescence assay of mosquitoes :
      1. Time to Perform: unknown
      2. Description: At day 15 after infection, mosquitoes were allowed to feed on 8-day-old mice. (Mice were used in preference to adult hamsters because they are more susceptible to fatal infection.) After feeding, mosquitoes were assayed for YFV infection and dissemination by whole-body titration and immunofluorescence assay (IFA) of head-squash material, respectively. For IFA, a broadly reactive antiflavivirus monoclonal antibody (813) with biotin-streptavidin amplification was used(Mutebi et al., 2002).
2. Immunoassay Test:
   1. Haemagglutination Inhibition Test :
      1. Time to Perform: unknown
      2. Description: The haemagglutination inhibition test (HIT) was performed according to standard procedures. Briefly, YF 17D was propagated in suckling mice. Virus was recovered from mouse brain with acetone-sucrose extraction. Virus antigen titres were determined by haemagglutination of goose erythrocytes. The sera were free from inhibitors as assessed by repeated acetone treatment and tested in serial dilutions from 1:10 to 1:80 against 8 units of haemagglutination antigen(Niedrig et al., 1999).
   2. Neutralization Assay :
      1. Time to Perform: unknown
      2. Description: A plaque reduction assay first described by De Madrid and Porterfield was used as neutralization test (NT). It was slightly modified and performed as described by Reinhardt et al. Briefly, PS-cells at a concentration of 3-4 x 10(5)/ml were seeded into 24-well plates (Nunc, Denmark) at a volume of 0.5 ml/well. Cells were cultured in Leibovitz medium (L-15, Gibco BRL, Germany) overnight at 37 C and washed once with L-15 medium supplemented with 5% FCS before adding 0.3 ml of a 1:5 dilution of the test sera. All sera were assayed four in parallel in two-fold dilutions ranging from 1:10 to 1:320 for the final dilutions. The sera were mixed with approximately 100 tissue culture infectivity doses of the reference 17D virus preparation used in our laboratory (lot number: 354/1). After 1 h of incubation at 37 C, 0.2 ml of this mixture was added to an equal volume of PS-cells at a density of 6 x 10(5) cells/ml. A 1.6% methylcellulose/L-15 solution (BDH Chemicals Ltd, UK) supplemented with 3% FCS was overlaid after 4 h of incubation. Cultures were incubated for 5 days at 37 C. Thereafter cells were washed with PBS and fixed with 10% formaldehyde solution for 10 min. Naphthalene black was used for staining cell layers, plaques were counted and the 90% neutralization titres calculated. NT titres less than 1:10 were considered negative. Titres of 1:10 were interpreted as borderline(Niedrig et al., 1999). The NT seems to give the most reliable results in assessing virus neutralizing antibodies(Niedrig et al., 1999).
   3. Enzyme Immunoassay and Immunofluorescence assay :
      1. Time to Perform: unknown
      2. Description: Flavivirus infections are a significant public health problem, since several members of the Flaviviridae family are highly pathogenic to humans. Accurate diagnosis and differentiation of the infecting virus is important, especially in areas where many flaviviruses are circulating. In this study we evaluated a newly developed commercially available immunofluorescence assay (IFA) (INDX, Baltimore, MD, USA) for the detection of IgM and IgG antibodies against dengue virus, yellow fever virus, Japanese encephalitis virus and West Nile virus. IFA was compared with standard diagnostic enzyme immunoassays (EIAs) specific for the detection of IgM and IgG antibodies against these viruses. Forty-seven serum samples from patients with a defined flavivirus infection were tested. As controls, serum samples from individuals with antibodies against tick-borne encephalitis virus and hepatitis C virus as well as healthy individuals were included. The results obtained from this study indicate that IFA showed a significantly better discrimination for flavivirus specific IgM antibodies than did the standard IgM specific EIAs (the overall cross-reactivity varied between 4 and 10% by IFA and 30-44% by EIA for the respective viruses). In contrast, the detection of flavivirus specific IgG antibodies showed high cross-reactions in both IFA and EIAs (overall cross-reactivity 16-71 and 62-84%, respectively). This study clearly stated the complexity of flavivirus diagnosis, showing that one cannot rely on one assay or search for one virus only. The flavivirus IFA is a useful tool for the identification of flavivirus infections during the acute stage of disease. In particular, IFA can be an important diagnostic tool for testing samples from travelers who have been accidentally exposed to these viruses(Koraka et al., 2002). In general, IFA for the detection of IgM serum antibodies was more type specific than the in-house and commercial EIAs used for the respective viruses(Koraka et al., 2002). For the detection of flavivirus antibodies, both IFA and EIAs showed very poor specificity, with IFA being slightly better than EIA(Koraka et al., 2002).
      3. False Negative: Six of the 10 serum samples obtained from patients with YFV infection were positive in IFA and all 10 samples were positive in the YFV specific EIA(Koraka et al., 2002). All 10 samples obtained from patients with a YFV infection were positive by IFA, whereas nine were positive in the YFV specific IgG EIA(Koraka et al., 2002).
      4. Antigen:
         • • Antigen Source: Yellow fever virus
      5. Antibody:
         • • Antibody Source: Yellow fever virus
   4. MAC-ELISA and ELISA :
      1. Time to Perform: unknown
      2. Description: The IgM antibody capture ELISA (MAC-ELISA) and ELISA inhibition methods for the detection of antibodies against dengue virus were modified to detect antibodies against yellow fever virus. Tests were carried out in 21 persons vaccinated with 17D and compared with the Plaque reduction neutralizing test. Of 17 naive subjects vaccinated, 16 (94%) seroconverted using the MAC-ELISA test and 14 (82%) seroconverted (or >/=fourfold titer increase) in the ELISA inhibition method. Cross-reactivity was evaluated by both tests and resulted in a high specificity to IgM antibodies against yellow fever, when all the samples from vaccinated individuals were negative by MAC-ELISA using dengue antigen. However, 10.7% of the positive dengue sera from the Santiago de Cuba epidemic cross-reacted by MAC-ELISA using yellow fever antigen. ELISA inhibition method showed high cross-reactivity when the 21 sera pairs were worked with yellow fever and dengue antigens. The MAC-ELISA and ELISA inhibition methods have become indispensable tools in our laboratory in order to maintain a surveillance system for dengue and dengue hemorrhagic fever. They are relatively rapid, simple, and they do not require sophisticated equipment. Both MAC-ELISA and ELISA inhibition methods for yellow fever could be useful for diagnosis, surveillance and yellow fever vaccine evaluation(Vasquez et al., 2003). The presence of IgM antibodies in a single serum taken in the late acute or early convalescent phase provides a presumptive diagnosis, and demonstration of a rising titre in paired sera is confirmatory(Monath, 2001).
      3. False Negative: In our study, only 1 out of 17 paired sera from yellow fever 17D vaccinees were found to be negative by MAC-ELISA/yellow fever, a 94% seroconversion rate. Nogueira et al. found 100% positives in a study on yellow fever vaccinated individuals by MAC-ELISA. From 17 sera pairs just two cases were negative by ELISA inhibition method/yellow fever and a third one did not show any increase in antibody titer; however they were positive by MAC-ELISA/yellow fever(Vasquez et al., 2003).
      4. Antigen:
         • Yellow fever antigen
           • Antigen Source: Yellow fever virus
3. Nucleic Acid Detection Test:

1. Humans
   1. Taxonomy Information:
      1. Species:
         1. Homo sapiens (Website 26):
            • Common Name: Homo sapiens
            • GenBank Taxonomy No.: 9606
            • Description: Yellow fever is the original viral haemorrhagic fever (VHF), a pansystemic viral sepsis with viraemia, fever, prostration, hepatic, renal, and myocardial injury, haemorrhage, shock, and high lethality. In recent years, popular attention has been drawn to another VHFEbolaas the most frightening emerging infection of humankind. However, patients with yellow fever suffer as terrifying and untreatable a clinical disease, and yellow fever is responsible for 1000-fold more illness and death than Ebola. Yellow fever stands apart from Ebola and other VHFs in its severity of hepatic injury and the universal appearance of jaundice.Yellow fever virus is the prototype of the genus Flavivirus (family Flaviviridae) which comprises approximately 70 viruses, most of which are arthropod-borne. The earliest description of yellow fever is found in a Mayan manuscript in 1648, but by genome sequence analysis it appears that yellow fever virus evolved from other mosquito-borne viruses about 3000 years ago, probably in Africa from where it was imported to the New World during the slave trade. Yellow fever was a major scourge in the 18th and 19th centuries in colonial settlements in the Americas and west Africa. The discoveries (in 1900) that mosquitoes were responsible for transmission and that the disease was preventable by vector control, as well as the development of vaccines (in the 1930s), have reduced both the fear associated with the disease and its medical impact. However, yellow fever remains an endemic and epidemic disease problem affecting thousands of people in tropical Africa and South America, and is a continued threat to people who travel to these regions without vaccination(Monath, 2001).
   2. Infection Process:
      1. Infectious Dose: The extreme lethality of yellow fever virus is evident when one considers that the 50% lethal dose for monkeys is less than 1 plaque forming unit(Monath, 2001),
   3. Disease Information:
      1. Yellow Fever :
         1. Incubation: Severe or 'classical' YF, usually recognized during epidemics, begins abruptly, following an incubation of 3-6 days or longer, after the bite of an infected mosquito(Tomori, 2004),
         2. Prognosis:
            Jones and Wilson in their study of 103 YF patients in Nigeria, found that the average stay in hospital for surviving patients was 14 days (range 5-42 days) and the average duration of acute illness was 17.8 days. Patients surviving the acute illness may have superimposed bacterial sepsis or pneumonia, or may require dialysis to manage renal tubular necrosis. The case fatality rate of severe YF is 50% or higher. Death usually occurs between the seventh and tenth day after onset. Convalescence, with profound weakness and fatigue, may last several weeks. Deaths occurring weeks after recovery have been described, possibly caused by cardiac arrhythmia, but this complication is not well documented. The duration of jaundice in survivors is unknown, but abnormal liver function tests have been found many months after the onset of recovery. Healing of the liver and kidneys is complete without post-necrotic scarring(Tomori, 2004),
         3. Diagnosis Summary: While clinical diagnosis of the severe disease in an unvaccinated patient with a history of exposure in the YF endemic zone presents little difficulty, it is clinically difficult to distinguish YF disease from many other tropical conditions, and often impossible when the condition is mild or atypical. The clinical symptoms associated with the early stages of YF infection are indistinguishable from those of malaria, and where the two diseases co-exist, YF should not be ruled out even in the absence of jaundice or the finding of malaria parasites in a blood smear. Other diseases resembling YF are leptospirosis and louse-borne relapsing fever (Borrelia recurrentis), which are also characterized by jaundice, hemorrhage, disseminated intravascular coagulation, and a high case-fatality rate. Anicteric YF must be differentiated from the following conditions: typhoid fever, rickettsial infections, other arboviral fevers, and influenza. YF must also be differentiated from other diseases with hepatorenal dysfunction and/or hemorrhagic manifestations, such as viral hepatits (especially severe hepatitis E in pregnancy and delta hepatits), and severe malaria (blackwater fever). Other VHFs (Lassa fever, Marburg and Ebola virus diseases, Crimean-Congo hemorrhagic fever, Rift Valley fever) and leptospirosis are not usually associated with jaundice, but dengue and Congo-Crimean hemorrhagic fever may occasionally present with features resembling YF(Tomori, 2004),
         4. Symptom Information :
            • Syndrome -- Very Mild Yellow Fever :
              • Description: In very mild yellow fever the only symptoms are fever and headache lasting from a few hours to a day or two. The disease is clinically undiagnosable, even in the presence of an epidemic of yellow fever. But a positive diagnosis can be made by means of special laboratory procedures. It is possible for completely unapparent infections to occur, especially in endemic areas where, as a result of long contact with the virus, the population is genetically selected in respect to yellow fever. Such infections may occur in babies who are losing the passive immunity bestowed upon them by immune mothers and who are infected with exactly the amount of virus which 'vaccinates' them without symptoms(Kerr, 1951).
              • Symptom -- Fever :
                • Description: In very mild yellow fever the only symptoms are fever and headache lasting from a few hours to a day or two(Kerr, 1951).
              • Symptom -- Headache :
                • Description: In very mild yellow fever the only symptoms are fever and headache lasting from a few hours to a day or two(Kerr, 1951).
            • Syndrome -- Mild Yellow Fever :
              • Description: In mild infections the fever and headache, which usually begin suddenly, are more pronounced. Additional symptoms appear: nausea, epistaxis, Faget's sign (relatively slow pulse in relation to constant or rising temperature), slight albuminuria, and subicterus. The illness lasts only 2 or 3 days and is clinically undiagnosable except during an epidemic, more especially where there are other cases in the same household. Without studying the patient by laboratory methods, the clinician can diagnose such cases only as 'suspect yellow fever'(Kerr, 1951).
              • Symptom -- Albuminuria :
                • Description: The mild and very mild cases are characterized by the relative absence of marked albuminuria. There may be a trace of albumin in the urine, but no more than would be expected in a ny patient with a slight degree of fever(Kerr, 1951).
              • Symptom -- Bradycardia (Faget's sign) :
                • Description: A slow pulse in relation to the fever (Faget's sign) is also typical at this stage(Tomori, 2004).
              • Symptom -- Epistaxis :
                • Description: Epistaxis is common at or soon after the onset of fever because of the congestion of the nasopharynegeal mucous membranes(Kerr, 1951).
              • Symptom -- Fever :
                • Description: On physical examination the patient is febrile and appears acutely ill, with congestion of the conjunctivae and face(Tomori, 2004). Fever (39-40 C)(Tomori, 2004). The average fever is 39 C and lasts 3.3 days(Monath, 2001).
              • Symptom -- Headache :
                • Description: Fever and headache, which usually begin suddenly, are more pronounced(Kerr, 1951).
              • Symptom -- Nausea :
                • Description: Additional symptoms appear: nausea, epistaxis, Faget's sign (relatively slow pulse in relation to constant or rising temperature), slight albuminuria, and subicterus(Kerr, 1951).
            • Syndrome -- Moderately Severe Yellow Fever :
              • Description: Moderately severe yellow fever is clinically diagnosable because one of the more classic symptoms is present. The fever is higher, and Faget's sign is more definite. Headache and backache may be severe. Nausea and vomiting are more troublesome. Definite jaundice and marked albuminuria are present. There may even be black vomit or uterine hemorrhages. The duration of the fever is from 5 to 7 days. Abortive infections are severe at onset, but the patient recovers rapidly, usually in 3 or 4 days. These infections are an exception to the rule that moderately severe yellow fever has an appreciably longer course than mild yellow fever(Kerr, 1951).
              • Symptom -- Albuminuria :
                • Description: Definite jaundice and marked albuminuria are present(Kerr, 1951).
              • Symptom -- Back pain :
                • Description: Headache and backache may be severe(Kerr, 1951).
              • Symptom -- Black vomit :
                • Description: Epistaxis is common at or soon after the onset of fever because of the congestion of the nasopharynegeal mucous membranes. If such blood is swallowed, flecks of black vomit may appear very early in the disease, before there is any bleeding from the stomach(Kerr, 1951).
              • Symptom -- Bradycardia (Faget's sign) :
                • Description: A slow pulse in relation to the fever (Faget's sign) is also typical at this stage(Tomori, 2004).
              • Symptom -- Epistaxis :
                • Description: Epistaxis is common at or soon after the onset of fever because of the congestion of the nasopharynegeal mucous membranes(Kerr, 1951).
              • Symptom -- Fever :
                • Description: Fever (39-40 C)(Tomori, 2004). The duration of the fever is from 5 to 7 days(Kerr, 1951).
              • Symptom -- Headache :
                • Description: Headache and backache may be severe(Kerr, 1951).
              • Symptom -- Uterine hemorrhage :
                • Description: There may even be black vomit or uterine hemorrhages(Kerr, 1951).
              • Symptom -- Jaundice :
                • Description: Definite jaundice and marked albuminuria are present(Kerr, 1951).
              • Symptom -- Nausea :
                • Description: Nausea and vomiting are more troublesome(Kerr, 1951).
              • Symptom -- Vomiting :
                • Description: Nausea and vomiting are more troublesome(Kerr, 1951).
            • Syndrome -- Malignant Yellow Fever :
              • Description: Moderately severe and malignant attacks of yellow fever are characterized by three distinct clinical periods: the period of infection, the period of remission, and period of intoxication.During the period of infection, which lasts about three days, the virus is present in the circulating blood, often in large amounts, but this, presumably, represents merely an overflow from the tissues in which multiplication of the virus takes place. The hyperemia of the skin is an index of the generalized hyperemia which occurs. The patient may be extremely uncomfortable because of severe headache and generalized aches and pains in muscles and joints. He is usually unable to sleep, over alert and irritable. The fever continues high at 39 to 40 C, or even higher. The nausea and vomiting are sometimes severe.Then follows the period of remission indicated by the fall of the temperature to or toward normal. The patient rather suddenly feels much better, although it is during this period that the prognosis must be most guarded. His headache and other aches are much less severe, or even disappear. He is less nauseated and may sleep quietly. This stage lasts from a few hours to a couple of days. The variability of clinical yellow fever being what it is, the period of remission may not be present at all, or it may merge into frank convalescence.The third stage is the period of intoxication. In this stage free virus usually is not present in the circulating blood(Kerr, 1951). While the virus is gone from the blood, the toxemia it produced remains. The classic symptoms of yellow fever, which are manifestations of this toxemia, become fully developed. The fever rises again, but the pulse remains slow; moderate jaundice becomes evident; vomiting is more troublesome and the vomitus usually contains blood that has been blackened by the action of the gastric juices, that is, black vomit. Albuminuria is always present and may be very intense; oliguria frequently occurs. When it is realized that the toxemia affects the liver, the heart, the kidneys and the blood vessels generally, not to mention the small vessels of the vital centers of the brain, it is to be expected that sometimes the natural defenses of the body will be unable to overcome the deleterious effects of the intoxication, and the patient will die.The period of intoxication is the most variable of the three periods. At its maximum, it is much the longest. In mild infections it is not recognizable at all. When recognizable, its usual length is 3 or 4 days, but it may be extended to as much as 2 weeks - in rather exceptional instances in which an uncomplicated attack of yellow fever is followed either by a long period of asthenia with recovery, or by a late death, probably due to cardiac failure(Kerr, 1951).
              • Symptom -- Albuminuria :
                • Description: Moderate to very intense albuminuria is always found in severe infections, but it rarely appears before the 3rd day of illness. In the classic picture heavy albuminuria develops suddenly; within a period of 12 hours, the amount of albumin may increase from insignificant traces to quantities such that the urine coagulates in the tube when tested for the presence of albumin. Albuminuria may last a few days and then disappear almost as rapidly as it appeared(Kerr, 1951). There is a rough positive correlation between the severity of the attack and the amount of albumin in the urine. If, as has been done in some epidemics, albuminuria is considered requisite for the clinical diagnosis of yellow fever, many mild cases may be missed. As with jaundice and hemorrhage, albuminuria may or may not be present, and if it is present, may be either slight in degree or exceedingly intense(Kerr, 1951).
              • Symptom -- Back pain :
                • Description: Fever (3940 C), chills, intense headache, lower back pain and generalized muscular pains, nausea and vomiting and conjuctival injection are the signs and symptoms associated with the first phase or period of infection(Tomori, 2004).
              • Symptom -- Black vomit :
                • Description: Epistaxis is common at or soon after the onset of fever because of the congestion of the nasopharynegeal mucous membranes. If such blood is swallowed, flecks of black vomit may appear very early in the disease, before there is any bleeding from the stomach(Kerr, 1951). The bleeding into the stomach occurs from ecchymoses of the mucosa, usually in the region of the pylorus. The amount of blood in the stomach is sometimes small, and the vomitus resembles coffee grounds. However large the amount of blood, it is almost always much darkened. Indeed, in the early days, before it came to be generally recognized that the black material was really altered blood , there was much controversy as to the nature of the vomitus(Kerr, 1951).
              • Symptom -- Bradycardia (Faget's sign) :
                • Description: A slow pulse in relation to the fever (Faget's sign) is also typical at this stage(Tomori, 2004). Faget's sign, which makes its appearance by the 2nd day, if not sooner, is one of the most constant findings in yellow fever if the attack is at all severe(Kerr, 1951). Still later, in the period of intoxication, the pulse continues slow in relation to temperature, except that there may be a terminal tachycardia. Often there is a true bradycardia, which occurs independently of the jaundice present. The pulse is usually weak; extrasystoles frequently occur. The heart sounds are muffled and a variety of anomalous heart sounds may develop. When the patient goes into collapse, the blood pressure falls, but otherwise it is variable(Kerr, 1951).
              • Symptom -- Chills (Monath, 2001):
                • Description: Fever (3940 C), chills, intense headache, lower back pain and generalized muscular pains, nausea and vomiting and conjuctival injection are the signs and symptoms associated with the first phase or period of infection(Tomori, 2004).
              • Symptom -- Coma (Monath, 2001):
                • Description: In malignant infections coma frequently sets in, sometimes 2 or 3 days before death. However, some patients do recover after being in coma for a day or two. Sometimes coma develops in patients whose kidneys are still functioning adequately; then it is clearly hepatic in origin. But in most cases the marked disturbance in kidney function makes it impossible to ascertain whether the coma is of hepatic or uremic origin(Kerr, 1951).
              • Symptom -- Conjunctiva injected :
                • Description: Examination of the patient reveals a flushed face, neck, and upper chest. The conjunctivae are injected(Kerr, 1951).
              • Symptom -- Convulsions (Monath, 2001):
                • Description: Small children may experience an initial convulsion(Kerr, 1951).
              • Symptom -- Epigastric pain (Monath, 2001):
                • Description: In approximately 1525% of cases, the remission phase is followed by the intoxication period or hepatorenal phase, which is marked by a rise in temperature, the reappearance of generalized symptoms, more frequent vomiting, epigastric pain, and prostration(Monath, 2001).
              • Symptom -- Dizziness (Monath, 2001):
                • Description: Headache and dizziness develop rapidly while the individual is in the midst of usual tasks, or he may awaken from sleep with these symptoms(Kerr, 1951).
              • Symptom -- Epistaxis :
                • Description: Epistaxis is common at or soon after the onset of fever because of the congestion of the nasopharynegeal mucous membranes(Kerr, 1951).
              • Symptom -- Fever :
                • Description: On physical examination the patient is febrile and appears acutely ill, with congestion of the conjunctivae and face(Tomori, 2004). Fever (39-40 C)(Tomori, 2004). The average fever is 39 C and lasts 3.3 days(Monath, 2001).
              • Symptom -- Furred tongue :
                • Description: The tongue gradually acquires a rather characteristic appearance, with bright red margins and tip and a furred center. The gums become congested and ooze blood under slight pressure(Kerr, 1951).
              • Symptom -- Headache :
                • Description: Minor hemorrhages may occur early in the period of infection(Kerr, 1951). Headache and dizziness develop rapidly while the individual is in the midst of usual tasks, or he may awaken from sleep with these symptoms. The temperature rises rapidly to 39 or 40 C, and the headache becomes more severe(Kerr, 1951).
              • Symptom -- Hemorrhage :
                • Description: On the 3rd day or early 4th day, anuria, copious hemorrhages from the gastrointestinal tract, or wildly agitated delirium - or a combination of all three - supervene, and the patient dies(Kerr, 1951).
              • Symptom -- Hiccup :
                • Description: Hiccough, often intractable, is a most distressing symptom. It may even continue after a patient has lapsed into coma, or commence while he is in coma(Kerr, 1951).
              • Symptom -- Hypotension (Monath, 2001):
                • Description: Pre-terminal events include hypotensionan increasingly difficult symptom to manage with fluids and vasopressors(Tomori, 2004).
              • Symptom -- Hypothermia (Monath, 2001):
                • Description: Patients also experience agitated delirium, stupor, coma, Cheyene-Stokes respirations, metabolic acidosis, hyperkalaemia, hypoglycaemia, and hypothermia(Monath, 2001).
              • Symptom -- Jaundice :
                • Description: Jaundice first becomes detectable about the 3rd day as a subicterus of sclerae. It seldom appears before the 2nd day of fever. The earlier jaundice appears, the more likely it is to be severe. In spite of the name yellow fever, jaundice is often not a prominent symptom of the disease, even in fatal cases. It always develops more or less gradually and may not be severe enough to be noticed by the family of the sick person until he has died or has recovered from his illness. Jaundice of the skin is sometimes very pronounced when death is somewhat delayed, or during convalescence. When of clinical degree, jaundice varies from a subicterus of the sclerae though a moderate generalized icterus to, rarely, an intense icterus(Kerr, 1951).
                • Observed:
                  In approximately 1525% of people affected, the illness reappears in a more severe form (the so-called period of intoxication) with fever, vomiting, epigastric pain, jaundice, renal failure, and a haemorrhagic diathesis(Monath, 2001),
              • Symptom -- Malaise (Monath, 2001):
                • Description: Disease onset is typically abrupt, with fever, chills, malaise, headache, lower back pain, generalized myalgia, nausea, and dizziness(Monath, 2001).
              • Symptom -- Myalgia (Monath, 2001):
                • Description: Muscular aches and pains become generalized(Kerr, 1951).
              • Symptom -- Nausea :
                • Description: Often there is nausea, with vomiting of food or mucus(Kerr, 1951).
              • Symptom -- Oliguria (Monath, 2001):
                • Description: Complete anuria is very rare, but severe oliguria is often accompanied by paresis of the bladder(Kerr, 1951). Oliguria is a phenomenon of the period of intoxication, except in fulminant infections where the periods of infection and intoxication are merged(Kerr, 1951).
              • Symptom -- Prostration (Monath, 2001):
                • Description: In approximately 1525% of cases, the remission phase is followed by the intoxication period or hepatorenal phase, which is marked by a rise in temperature, the reappearance of generalized symptoms, more frequent vomiting, epigastric pain, and prostration(Monath, 2001).
              • Symptom -- Shock (Monath, 2001):
                • Description: Progressive tachycardia, shock, and intractable hiccups are considered ominous and terminal signs(Tomori, 2004).
              • Symptom -- Stupor (Monath, 2001):
                • Description: Patients also experience agitated delirium, stupor, coma, Cheyene-Stokes respirations, metabolic acidosis, hyperkalaemia, hypoglycaemia, and hypothermia(Monath, 2001).
              • Symptom -- Tender liver (Monath, 2001):
              • Symptom -- Vomiting :
                • Description: Often there is nausea, with vomiting of food or mucus(Kerr, 1951).
            • Symptom -- Yellow Fever - Case Definition :
              • Description: A case definition was established as follows: an illness in a patient of any age with high fever, severe headache, neck and back pain, possibly accompanied by vomiting, abdominal pain, diarrhea, hematemesis, bloody diarrhea, jaundice, and epistaxis(Onyango et al., 2004).
         5. Treatment Information:
            • Supportive care : In absence of specific therapy, treatment of YF is chiefly supportive(Tomori, 2004). Intensive supportive care may not rescue the patient with YF from the inevitable course of fatal infection. An expert panel recommended the following steps for the management of YF case: maintenance of nutrition and prevention of hypoglycemia; nasogastric suction to prevent gastric distension and aspiration; intravenous cimetidine to prevent gastric bleeding; treatment of hypotension by fluid replacement and vasoactive drugs (dopamine); administration of oxygen; correction of metabolic acidosis; treatment of bleeding with fresh-frozen plasma; dialysis if indicated by renal failure; and treatment of secondary infections with antibiotics. Since most YF cases occur in areas lacking basic hospital facilities and drugs, they do not benefit from the recommendations(Tomori, 2004). Most patients with yellow fever have not benefited from the availability of modern intensive care, and it is unknown to what extent fluid management and correction of hypotension and electrolyte and acid-base disturbances would reverse the apparently inexorable course of severe yellow fever(Burke and Monath, 2001).
   4. Prevention:
      1. Vector Control
         • Description: Epidemics of Ae. aegypti-born yellow fever may be prevented by reduction and maintenance of domestic breeding at a level sufficiently low to make virus transmission unlikely (generally below a Breteau index of 5.0). This objective has only been occasionally accomplished. Methods for achieving a marked reduction in Ae. aegypti populations include environmental sanitation to remove sources of larval development, perifocal spraying of breeding sites with residual formulations which kill both larvae and emerging adults, and addition of temephos (often in slow-release formulations) to sites containing potable water. Long-term use of larvicides, however, is associated with a high risk that resistance will develop. Source reduction is most successful when it involves participation of the community rather than vertically organized programs. More novel methods for reducing Ae. aegypti populations include the use of 'autocidal' ovitraps, mass-rearing and release of predatory Toxorynchites mosquitoes, and placement of predatory fish in potable water (jars and cisterns).In the event of an established epidemic of Ae. aegypti-borne yellow fever, adulticidal space sprays must be used to kill infected adult female mosquitoes, since even the most effective application of larvicides will result only in a gradual reduction in the adult vector population over 10 to 14 days. Thermal fogs or nonthermal, ultralow-volume (ground or aerial) applications of a suitable insecticide may be used. Organophophate formulations are generally effective, but careful assessment should be made of the effect of spraying on the wild mosquito population and on caged mosquitoes exposed in spray zones(Monath, 1989), Because of the inaccessibility of breeding sites of wild vectors, prevention of sylvatic yellow fever by vector control is not feasible. Several studies have shown that ultralow volume (or thermal fog) applications of malathion can be quite effective in reducing populations of Ae. simpsoni group mosquitoes, Ae. africans, and Haemagogus spp. despite the presence of dense vegetation, but this approach has not been utilized in a setting where effectiveness in interrupting yellow fever transmission has been demonstrated(Monath, 1989),
         • Efficacy:
           • Rate: Since the insecticides used in emergency control have minimal residual effect, the adult population will recover rapidly, and generally two treatments spaced 3 to 4 days apart will be required to break the virus transmission chain(Monath, 1989). Ground and aerial applications of malathion rapidly suppressed populations of A. africanus in forest habitats of West Africa for a period of time believed sufficient to interrupt virus transmission. Aerial ULV was also used for the control of Haemagogus species vectors in forested areas in eastern Panama in 1974(Burke and Monath, 2001).
           • Duration:
      1. 17D Vaccine
         • Description: Yellow fever 17D vaccine developed by passage in chick embryo is in wide-scale use and has been proven to be highly effective and extremely safe(Monath, 1989), There is only a single U.S. manufacturer of YF 17D vaccine, and supplies may be insufficient in an emergency. A randomized, double-blind outpatient study was conducted in 1,440 healthy individuals, half of whom received the U.S. vaccine (YF-VAX) and half the vaccine manufactured in the United Kingdom (ARILVAX). A randomly selected subset of approximately 310 individuals in each treatment group was tested for YF neutralizing antibodies 30 days after vaccination. The primary efficacy endpoint was the proportion of individuals who developed a log neutralization index (LNI) of 0.7 or higher. Seroconversion occurred in 98.6% of individuals in the ARILVAX group and 99.3% of those in the YF-VAX group. Statistically, ARILVAX was equivalent to YF-VAX (P = .001). Both vaccines elicited mean antibody responses well above the minimal level (LNI 0.7) protective against wild-type YF virus. The mean LNI in the YF-VAX group was higher (2.21) than in the ARILVAX group (2.06; P = .010) possibly because of the higher dose contained in YF-VAX. Male gender, Caucasian race, and smoking were associated with higher antibody responses. Both vaccines were well tolerated. Overall, the treatment groups were comparable with respect to safety except that individuals in the ARILVAX group experienced significantly less edema, inflammation, and pain at the injection site than those in the YF-VAX group. No serious adverse events were attributable to either vaccine. YF-VAX participants (71.9%) experienced one or more nonserious adverse events than ARILVAX individuals (65.3%; P = .008). The difference was due to a higher rate of injection site reactions in the YF-VAX group(Monath et al., 2002),
         • Efficacy:
           • Rate: Yellow fever 17D vaccine confers long-lasting immunity in nearly 99% of vaccinated persons(Monath, 1989).
           • Duration: Although for the purposes of the international certificate vaccination is valid for only 10 years, several studies have shown that neutralizing (N) antibodies persist for at least 30 to 35 years(Monath, 1989). After subcutaneous inoculation of YF vaccine, neutralizing antibodies appear by Day 10 after inoculation, and immunity is probably lifelong, although revaccination is recommended every 10 years(Monath et al., 2002).
         • Contraindicator: Increased susceptibility of the very young has led to the restricted use of vaccine in endemic areas to children 9 months or older (6 months or older in the case of a high risk acquisition of natural infection and 4 months or older in an active epidemic focus). Other contraindications include those for other live vaccines, including severe chronic illness, immunodeficiency or immunosuppressive therapy, and pregnancy. The latter is a theoretical risk only, and no untoward effects on the fetus of women vaccinated during pregnancy have been reported. Since the vaccine is made in chick embryos, persons with a history of egg allergy should be skin tested according to the directions in the vaccine package insert. Yellow fever vaccine has been reported on rare occasions to induce sensitization to other egg-based vaccines, but this has not been a major practical problem(Monath, 1989),
         • Complication: Mild systemic symptoms (fever, headache) occur in up to 5% of vaccinees on the 5th or 6th day after inoculation, but are very rarely incapacitating. Despite the fact that tens of millions of doses of 17D vaccine have been administered, only 17 cases of central nervous postvaccinal encephalitis have been reported, of which 16 were in infants 7 months of age or less (14 cases in infants 4 months of age or less)(Monath, 1989), Mild systemic reactions (headache, myalgia, malaise, asthenia) occurred in roughly 10% to 30% of participants during the first few days after vaccination, with no significant difference across treatment groups(Monath et al., 2002),
   5. Model System:
      1. Guinea pigs
         1. Model Host: Vertebrate.
            Cavia porcellus(Monath, 1989),
         2. Model Pathogens: Yellow fever virus(Monath, 1989).
         3. Description: Hamsters and guinea pigs develop viremia following parenteral infection, but do not show signs of illness unless inoculated by the i.c. route, in which case encephalitis develops(Monath, 1989),
      1. Hamsters
         1. Model Host: Vertebrate.
            Mesocricetus auratus(Monath, 1989),
         2. Model Pathogens: Yellow fever virus(Monath, 1989).
         3. Description: Hamsters and guinea pigs develop viremia following parenteral infection, but do not show signs of illness unless inoculated by the i.c. route, in which case encephalitis develops(Monath, 1989),
      1. Mice
         1. Model Host: Vertebrate.
            Mus musculus(Monath, 1989),
         2. Model Pathogens: Yellow fever virus(Monath, 1989).
         3. Description: Mice of all ages succumb to lethal encephalitis following intracerebral (i.c.) inoculation. Newborns die following i.p. infection as do weanling mice inoculated with some virus strains(Monath, 1989), Neurotropic yellow fever infection of mice has been used as a model system for studies on the pathogenesis of flavivirus encephalitis(Burke and Monath, 2001),
      1. Primate
         1. Model Host: Vertebrate.
            Primates(Burke and Monath, 2001),
         2. Model Pathogens: Yellow fever virus(Burke and Monath, 2001).
         3. Description: Rhesus and cynomolgus macaques, as well as certain neotropical monkeys, are highly susceptible. Monkey intracerebrally inoculated with wild-type virus develop encephalitis but die of viscerotropic yellow fever(Burke and Monath, 2001), A large number of species of nonhuman primates have been experimentally inoculated with yellow fever virus. In many cases only a few animals have been studied, making generalizations about response to infection difficult. In addition, different strains of yellow fever virus have been employed. Nevertheless, several conclusions are possible. With a very few exceptions, primates are highly susceptible to infection, developing viremia and a strong antibody response. Many South American species become severely or fatally ill, whereas most African species have mild or inapparent infections. This difference has been interpreted as indicating a longer period of coevolution of yellow fever virus with African than neotropical host species. However, Laemmert found marked differences in the responses of Callithrix jacchus to yellow fever strains of neotropical and African origin, the South American virus strain being more highly virulent(Monath, 1989), Monkeys from Asia, where yellow fever does not occur, are highly susceptible to lethal infection(Monath, 1989),
      1. Rabbits
         1. Model Host: Vertebrate.
            Oryctolagus cuniculus(Monath, 1989),
         2. Model Pathogens: Yellow fever virus(Monath, 1989).
         3. Description: Rabbits inoculated i.c or i.p. become immune without demonstrable viremia or illness(Monath, 1989),
      1. Sudanese Hedgehog
         1. Model Host: Vertebrate.
            Erinaceus pruneri(Monath, 1989),
         2. Model Pathogens: Yellow fever virus(Monath, 1989).
         3. Description: The Sudanese hedgehog (Erinaceus pruneri) develops high viremia and hepatits following yellow fever inoculation(Monath, 1989),
2. Mosquitoes
   1. Taxonomy Information:
      1. Species:
         1. Aedes aegypti :
            • Common Name: Aedes aegypti
            • GenBank Taxonomy No.: 7159
            • Description: The mosquito, Aedes aegypti is the primary, worldwide arthropod vector for the yellow fever and dengue viruses. It has a cosmotropical distribution between 30N and 20S, and exhibits a distinct preference for human habitats, including artificial oviposition sites, e.g., tires, flower vases, water storage containers(Severson et al., 2004). In the urban cycle, YF is transmitted between human beings by Ae. aegypti, a domestic mosquito that breeds in manmade containers(Tomori, 2004).
         2. Aedes africanus (Website 24):
            • Common Name: Aedes africanus
            • GenBank Taxonomy No.: 7158
            • Description: The principal jungle vector throughout tropical Africa is Ae. africanus. Ae. africanus is well adapted to the role of transmitting YF virus between susceptible monkeys(Mutebi et al., 2002).
         3. Aedes bromeliae (Website 24):
            • Common Name: Aedes bromeliae
            • GenBank Taxonomy No.: 7158
            • Description: The first isolation of virus from a sylvatic vector was from Ae. bromeliae during a human yellow fever outbreak in Bwamba County, Uganda in 1941. The virus was again isolated from this species in 1942 after completion of an extensive vaccination campaign, suggesting that it had become infected from a nonhuman source. Extensive studies in western Uganda confirmed an important role for Ae. bromeliae as the link between the enzootic cycle (involving monkeys and Ae. africanus) and humans. This mosquito, which is abundant in plantations and around villages near the forest, becomes infected from viremic monkeys which enter the forest edge or raid banana plantations and, subsequently, transmits the virus to humans. This role was fulfilled to its most spectacular degree during the 1960 to 1962 epidemic in the Omo River Valley of Ethiopia, where nearly 100,000 cases occurred. Twelve isolations of yellow fever virus were recovered from Ae. bromeliae during the epidemic(Monath, 1989).
         4. Aedes dentatus (Website 24):
            • Common Name: Aedes dentatus
            • GenBank Taxonomy No.: 7158
            • Description: Little is known of the bionomics of Ae dentatus. Interest in it as a vector was first raised in 1963 when yellow fever virus was isolated in follow-up studies in the Omo River area of Ethiopia. Subsequently, Ae. dentatus was considered to be a candidate vector in Marsabit, northern Kenya, an endemic focus defined by serological survey. In Marsabit and Ngong and Langata forests of Kenya, as well as in the Jos Plateau of Nigeria, Ae. dentatus was found to be abundant on the basis of human-biting collections(Monath, 1989).
         5. Aedes furcifer (Website 18):
            • Common Name: Aedes furcifer
            • GenBank Taxonomy No.: 299627
            • Description: Ae. furcifer, Ae. taylori and Ae luteocephalus are the main vectors in the moist and dry savannahs (the emergence zone) of West Africa. Ae. furcifer and Ae. taylori are morphologically indistinguishable and usually referred to as the Ae. furcifer-taylori group. The Ae. furcifer-taylori group seems to be highly anthropophilic throughout its distribution range and has been implicated in several outbreaks, including in Gambia in 1978-1979. Ae. furcifer and Ae. taylori are abundant in West Africa, but virtually absent in Central and East Africa, and do not play a significant role in YF transmission in East and Central Africa(Mutebi et al., 2002).
         6. Aedes luteocephalus (Website 19):
            • Common Name: Aedes luteocephalus
            • GenBank Taxonomy No.: 299629
            • Description: Ae. furcifer, Ae. taylori and Ae luteocephalus are the main vectors in the moist and dry savannahs (the emergence zone) of West Africa(Mutebi et al., 2002). Ae. luteocephalus is widely distributed, but it is only important as a YF vector in regions where Ae. africanus is absent. However, it was implicated as the principal vector in the outbreak in Nigeria in 1969(Mutebi et al., 2002).
         7. Aedes metallicus (Website 24):
            • Common Name: Aedes metallicus
            • GenBank Taxonomy No.: 7158
            • Description: Ae metallicus, an experimentally proven vector, was among the more frequent species collected in human bait in the Nuba mountains of Sudan, but probably played a minor role in the 1940 human epidemic. It is a drought-resistant species found principally in the dry Sudan and Sahel savannah zones. It was not a common species in the yellow fever focus in eastern Senegal and, in general, probably has a patchy distribution with localized areas of abundance. The sole virus isolate from this species in nature was made during the 1983 outbreak in Burkina Faso(Monath, 1989).
         8. Aedes opok (Website 24):
            • Common Name: Aedes opok
            • GenBank Taxonomy No.: 7158
            • Description: Ae. opok, described in 1962 from Uganda and in 1975 from the Guinea and Sudanese savannah zones (but not in forests) of West and Central Africa, is closely related morphologically to Ae. africanus. It was first implicated by virus isolation at Bozo, Central African Republic, and was believed on the basis of its bionomics to play a role in enzootic transmission. Virus isolates also have been obtained from Ae. opok in Ivory Coast(Monath, 1989).
         9. Aedes simpsoni (Website 30):
            • Common Name: Aedes simpsoni
            • GenBank Taxonomy No.: 7161
            • Description: The Ae. simpsoni group is comprised of at least three sibling species - Ae. simpsoni, Ae bromeliae, and Ae lilii. Ae. simpsoni (sensu strictu) occurs only in South Africa and Zimbabwe and is not involved in the ecology of yellow fever. The anthropophilic species, Ae. bromeliae, occurs in Central and East Africa and represents the principal yellow fever vector described originally as Ae. simpsoni by Haddow(Monath, 1989).
         10. Aedes taylori (Website 20):
             • Common Name: Aedes taylori
             • GenBank Taxonomy No.: 299628
             • Description: Ae. furcifer, Ae. taylori and Ae luteocephalus are the main vectors in the moist and dry savannahs (the emergence zone) of West Africa. Ae. furcifer and Ae. taylori are morphologically indistinguishable and usually referred to as the Ae. furcifer-taylori group. The Ae. furcifer-taylori group seems to be highly anthropophilic throughout its distribution range and has been implicated in several outbreaks, including in Gambia in 1978-1979. Ae. furcifer and Ae. taylori are abundant in West Africa, but virtually absent in Central and East Africa, and do not play a significant role in YF transmission in East and Central Africa(Mutebi et al., 2002).
         11. Aedes vittatus (Website 24):
             • Common Name: Aedes vittatus
             • GenBank Taxonomy No.: 7158
             • Description: Ae. vittatus, a drought-resistant species, is most abundant in open, dry savannah areas with rocky outcroppings and breeds preferentially in rock pools. Ae. vittatus was probably an important vector during the 1940 epidemic in the Nuba Mountains of Sudan and was assumed also to have been involved in the 1959 outbreak in the Upper Nile Province. In West Africa, Ae vittatus has a widespread by patchy distribution. It was represented in biting collections on the Jos Plateau, Nigeria and may have played a minor role in yellow fever transmission during the outbreaks in the 1950's and in 1969(Monath, 1989). Yellow fever virus was isolated for the first time from Ae vittatus in eastern Senegal (Kedougou) in 1977; however the minimum infection rate in female mosquitoes was significantly lower than that for Ae. furcifer-taylori and Ae. luteocephalus. Because of it breeding sites and biting habits, Ae. vittatus probably has less opportunity for contact with monkeys than the other species(Monath, 1989).
         12. Coquillettidia fuscopennata :
             • Common Name: Coquillettidia fuscopennata
             • Description: In 1972 an isolate of yellow fever virus was made from Coquillettidia fuscopennata during an epizootic in Zika forest, Uganda. This species is among the most common of those collected on human bait in Uganda. On the basis of studies of the age composition of this species, Germain et al. concluded that it was unlikely to play a major role in yellow fever cycles. No experimental studies have been conducted with this species(Monath, 1989).
         13. Haemagogus capricornii (Website 25):
             • Common Name: Haemagogus capricornii
             • GenBank Taxonomy No.: 7180
             • Description: The first sylvatic vector found naturally infected was identified as Hg. capricornii(Monath, 1989). Hg. capricornii has a relatively restricted range in southeasten Brazil and parts of Argentina. Because of the taxonomic confusion with Hg. janthinomys, the field evidence for a role of the former species in virus transmission is problematic, and yellow fever outbreaks have not occurred in areas where Hg. capricornii was the only potential vector(Monath, 1989).
         14. Haemagogus equinus (Website 21):
             • Common Name: Haemagogus equinus
             • GenBank Taxonomy No.: 53526
             • Description: In deciduous forest, with prolonged dry season along the Pacific slope, Hg. equinus was significantly more abundant than Hg. janthinomys. This species was found to have a wide distribution in Central America and Mexico, extending as far north as Brownsville, Texas. It was considered to be the principal vector on the Pacific side of Nicaragua and was the only Haemagogus species present in an area of Honduras affected by the yellow fever epizootic. Yellow fever virus was isolated from Hg. equinus in Guatemala(Monath, 1989).
         15. Haemagogus iridicolor (Website 25):
             • Common Name: Haemagogus iridicolor
             • GenBank Taxonomy No.: 7180
             • Description: In Costa Rica, Hg. lucifer is replaced by the closely related species, Hg. iridicolor. In some areas of Costa Rica affected by yellow fever, Hg. iridicolor was more abundant than Hg. equinus, and in Nicaragua Hg. iridicolor was believed to be the principal vector on the Atlantic slope(Monath, 1989).
         16. Haemagogus janthinomys (Haemagogus spegazzinii falco) (Website 25):
             • Common Name: Haemagogus janthinomys (Haemagogus spegazzinii falco)
             • GenBank Taxonomy No.: 7180
             • Description: Hg. janthinomys is now generally considered to be the principal vector in South America. Yellow fever virus has been repeatedly isolated from Hg. janthinomys (formerly named Hg. spegazzinii flaco), and it has been shown to be a highly efficient vector in the laboratory. Hg. janthinomys was implicated as the principal vector in focus of yellow fever activity in Rincon del Tigre, easter Bolivia, and in Belterra, Brazil, but in some other outbreaks in South America it has been absent(Monath, 1989).
         17. Haemagogus leucocelanenus (Website 25):
             • Common Name: Haemagogus leucocelanenus
             • GenBank Taxonomy No.: 7180
             • Description: An epidemic in Santa Cruz, Bolivia was apparently due to transmission by Hg leucocelaenus and Sa. chloropterus. Entomological investigation of the 1966 outbreak in Missiones, Province, Argentina revealed the presence of Hg capricornii, Hg leucocelaenus, and Sa chloropterus(Monath, 1989).
         18. Haemagogus lucifer (Website 25):
             • Common Name: Haemagogus lucifer
             • GenBank Taxonomy No.: 7180
             • Description: Hg. lucifer is an abundant species in Colombia and Panama. Yellow fever virus has been isolated from a mixed pool of Hg. equinus, Hg. janthinomys, and Hg. lucifer, and two isolations were made from pure pools of Hg. lucifer in Panama in 1956(Monath, 1989).
         19. Haemagogus mesodentatus (Website 22):
             • Common Name: Haemagogus mesodentatus
             • GenBank Taxonomy No.: 7181
             • Description: Hg. mesodentatus (a species complex) is found from western Panama to Sinaloa. In Guatemala, El Salvador and southern Mexico it is an abundant species, and field studies resulted in recovery of multiple strains of yellow fever virus. Hg. mesodentatus was shown to be the principal vector in Guatemala in 1956, with Hg. equinus and Sa. chloropterus as secondary vectors(Monath, 1989).
         20. Sabethes chloropterus (Website 23):
             • Common Name: Sabethes chloropterus
             • GenBank Taxonomy No.: 53551
             • Description: Sa. chloropterus played a role in yellow fever transmission in Central America. Virus was recovered from this species in Guatemala. In areas subject to a prolonged dry season during which Haemagogus activity subsides, the long-lived, drought-resistant Sa. chloropterus was considered to play an important role in maintenance of the virus(Monath, 1989).
3. Nonhuman Vertebrates
   1. Taxonomy Information:
      1. Species:
         1. Alouatta belzebul (Website 29):
            • Common Name: Alouatta belzebul
            • GenBank Taxonomy No.: 30590
            • Description: Three howler monkeys (Alouatta belzebul) were euthanized. The specimens from the monkeys produced three YF virus isolates, two from the blood and liver of the same monkey and another from the liver of a second monkey. These monkeys were found within 200 m to 500 m of human dwellings. They had been showing abnormal behavior, i.e., moving slowly and not trying to escape from people(Vasconcelos et al., 2001).
         2. Alouatta caraya (Website 28):
            • Common Name: Alouatta caraya
            • GenBank Taxonomy No.: 9502
            • Description: Following howling monkey (Alouatta caraya) deaths and yellow fever (YF) antigen detection by immunohistochemistry in the liver sample of a dead monkey in April and May 2001 in the municipalities of Garruchos and Santo Antonio das Missoes, Rio Grande do Sul State, Brazil, epidemiological field investigations were initiated(Vasconcelos et al., 2003).
         3. Alouatta fusca (Website 27):
            • Common Name: Alouatta fusca
            • GenBank Taxonomy No.: 9500
            • Description: Many brown howlers (Alouatta fusca) have died in a 3-month period in a subtropical forest in Southern Brazil. One was examined after a systemic illness. According to clinical signs, and necropsy and histopathology findings, yellow fever virus (YFV) infection was suspected. Tissue sections from liver, kidney, and lymphoid organs were screened by immunohistochemistry for YFV antigens. Cells within those tissues stained positively with a polyclonal antibody against YFV antigens (1:1,600 dilution), and yellow fever was diagnosed for the first time in the brown howler in the area(Sallis et al., 2003).
         4. Alouatta palliata (Website 47):
            • Common Name: Alouatta palliata
            • GenBank Taxonomy No.: 30589
            • Description: No direct experimentation with A. palliata has been reported, but the work of Courtney indicated that the species very probably plays a role in jungle yellow fever in Panama. Courtney has set forth the results of the studies of Clark, who found that a large percentage of the black howlers from the neighborhood of the Panama Canal had positive protection tests. While critical experimentation has not been done with any of the howler monkeys, it is reasonable to presume that their immunologic reactions may be interpreted on the same basis as those of other primates, and, therefore, that the positive protection tests are valid evidence that these monkeys have participated in the forest cycle of yellow fever(Bugher, 1951).
         5. Alouatta seniculus (Website 32):
            • Common Name: Alouatta seniculus
            • GenBank Taxonomy No.: 9503
            • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 18 of 98 Alouatta seniculus(da Thoisy et al., 2004). Howler monkeys were more exposed to YFV, with a seroneutralizing antibody prevalence of 18%(da Thoisy et al., 2004).
         6. Ateles paniscus (Website 28A):
            • Common Name: Ateles paniscus
            • GenBank Taxonomy No.: 9510
            • Description: Eight free-ranging black spider monkeys (Ateles paniscus chamek) were immobilized with Telazol in Bolivia for the purpose of radio-collaring. During this procedure, the animals received complete medical examinations, and samples were collected for health analyses. Biochemical test results varied with the degree of condition of the animals, and a variety of physical abnormalities were found. Evidence of previous infections with Leptospira sp., encephalitis virus, and yellow fever virus was found(Karesh et al., 1998).
         7. Bradypus tridactylus (Website 40):
            • Common Name: Bradypus tridactylus
            • GenBank Taxonomy No.: 9354
            • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 1 of 29 Bradypus tridactylus(da Thoisy et al., 2004).
         8. Callithrix penicillata, Callithrix jacchus penicillata (Website 46):
            • Common Name: Callithrix penicillata, Callithrix jacchus penicillata
            • GenBank Taxonomy No.: 57378
            • Description: The importance of the marmosets in the epidemiology of jungle yellow fever in a particular region was shown by the very extended studies of Laemmert, de Castro Ferreira, and Taylor of an outbreak in the Ilheus region of Brazil. Yellow fever virus was isolated from C. penicillata on four separate occasions over a period of 9 weeks from June to August 1944(Bugher, 1951).
         9. Caluromys (Website 43):
            • Common Name: Caluromys
            • GenBank Taxonomy No.: 42712
            • Description: Haemagglutination inhibition (HI) and neutralization antibodies were found in 1 out of 1 Caluromys spp. tested(Pinheiro et al., 1981).
         10. Cebus (Website 42):
             • Common Name: Cebus
             • GenBank Taxonomy No.: 9513
             • Description: Only one strain of YF virus was isolated. It came from the viscera of one of 15 Cebus monkeys examined(Pinheiro et al., 1981).
         11. Choloepus didactylus (Website 41):
             • Common Name: Choloepus didactylus
             • GenBank Taxonomy No.: 27675
             • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 1 of 26 Choloepus didactylus(da Thoisy et al., 2004).
         12. Coendou (Website 37):
             • Common Name: Coendou
             • GenBank Taxonomy No.: 43319
             • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 2 of 42 Coendou spp(da Thoisy et al., 2004).
         13. Dasyprocta leporina, Dasyprocta aguti, Dasyprocta agouti (Website 38):
             • Common Name: Dasyprocta leporina, Dasyprocta aguti, Dasyprocta agouti
             • GenBank Taxonomy No.: 42152
             • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 6 of 29 Dasyprocta leporina(da Thoisy et al., 2004).
         14. Didelphis marsupialis (Website 48):
             • Common Name: Didelphis marsupialis
             • GenBank Taxonomy No.: 9268
             • Description: Wild-caught animals from an area of recent yellow fever showed as high as 33 per cent positives(Bugher, 1951).
         15. Eira barbara, Mustela barbara (Website 36):
             • Common Name: Eira barbara, Mustela barbara
             • GenBank Taxonomy No.: 204263
             • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 1 of 3 Eira barbara(da Thoisy et al., 2004).
         16. Pan troglodytes troglodytes (Website 49):
             • Common Name: Pan troglodytes troglodytes
             • GenBank Taxonomy No.: 37011
             • Description: Findlay, Stefanopoulo et al. concluded that the chimpanzee may be infected under natural conditions. They found one of six animals from French West Africa near Sierra Leone gave a positive reaction in the intraperitoneal mouse protection test. This was considered specific indication that the animal had been infected before capture(Bugher, 1951).
         17. Pecari tajacu, Tayassu tajacu, Tayassu angulatus (Website 35):
             • Common Name: Pecari tajacu, Tayassu tajacu, Tayassu angulatus
             • GenBank Taxonomy No.: 9829
             • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 1 of 3 Tayassu tajacu(da Thoisy et al., 2004).
         18. Perodicticus potto (Website 50):
             • Common Name: Perodicticus potto
             • GenBank Taxonomy No.: 9472
             • Description: A few positive protection tests in captured animals have been encountered and may be taken as reliable indication that pottos are occasionally infected in nature(Bugher, 1951).
         19. Pithecia pithecia (Website 33):
             • Common Name: Pithecia pithecia
             • GenBank Taxonomy No.: 43777
             • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 2 of 5 Pithecia pithecia(da Thoisy et al., 2004).
         20. Saguinus midas (Website 34):
             • Common Name: Saguinus midas
             • GenBank Taxonomy No.: 30586
             • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 5 of 42 Saguinus midas(da Thoisy et al., 2004).
         21. Otolemur crassicaudatus, Galago crassicaudatus (Website 51):
             • Common Name: Otolemur crassicaudatus, Galago crassicaudatus
             • GenBank Taxonomy No.: 9463
             • Description: That this species does play an active role in the epidemiology of yellow fever was shown by the protection tests of 66 galagos captured in the Gede and Kilifi forests of the Kenya coastal area. Nine of the 66 gave positive results, indicating that yellow fever had recently been active among primates of the Kenya coast(Bugher, 1951).
         22. Tamandua tetradactyla (Website 39):
             • Common Name: Tamandua tetradactyla
             • GenBank Taxonomy No.: 48850
             • Description: Yellow fever seroneutralizing antibodies (titers greater than 10) were found in 2 of 26 Tamandua tetradactyla(da Thoisy et al., 2004).
4. Ticks
   1. Taxonomy Information:
      1. Species:
         1. Amblyomma variegatum (Website 31):
            • Common Name: Amblyomma variegatum
            • GenBank Taxonomy No.: 34610
            • Description: The yellow fever virus is isolated in nature from eggs of a Tick Amblyomma variegatum. It is then isolated from larvae issued from the same egg-cluster and also from blood of a monkey bitten by larvae of the same origin. It is reported that the same virus has been previously obtained from adults of the same species of Tick. An acarine appears for the first time as a sylvatic vector and reservoir (at least temporary) of yellow fever(Germain et al., 1979).

Not available for this pathogen.

NA

Bae et al., 2003: Bae HG, Nitsche A, Teichmann A, Biel SS, Niedrig M. Detection of yellow fever virus: a comparison of quantitative real-time PCR and plaque assay. J Virol Methods. 2003; 110(2); 185-191. [PubMed: 12798247].

Bryant et al., 2003: Bryant J, Wang H, Cabezas C, Ramirez G, Watts D, Russell K, Barrett A. Enzootic transmission of yellow fever virus in Peru. Emerg Infect Dis. 2003; 9(8); 926-933. [PubMed: 12967489].

Bugher, 1951: Bugher JC. The mammalian host in yellow fever. 301-384. In: . Yellow Fever. 1951. McGraw-Hill, New York.

Burke and Monath, 2001: Burke DS, Monath TP. Flaviviurses. 1043-1125. In: . Fields Virology. 2001. Lippincott Williams and Wilkins, Philadelphia Pa.

Burke and Monath, 2001: Burke DS, Monath TP. Flaviviurses. 1043-1125. In: . Fields Virology. 2001. Lippincott Williams and Wilkins, Philadelphia Pa.

Deubel et al., 1997: Deubel V, Huerre M, Cathomas G, Drouet MT, Wuscher N, Le Guenno B, Widmer AF. Molecular detection and characterization of yellow fever virus in blood and liver specimens of a non-vaccinated fatal human case. Journal of Medical Virology. 1997; 53(3); 212-217. [PubMed: 9365884].

Filippis et al., 2004: Filippis AM, Nogueira RM, Jabor AV, Schatzmayr HG, Oliveira JC, Dinis SC, Galler R. Isolation and characterization of wild type yellow fever virus in cases temporally associated with 17DD vaccination during an outbreak of yellow fever in Brazil. Vaccine. 2004; 22(9-10); 1073-1078. [PubMed: 15003633].

Germain et al., 1979: Germain M, Saluzzo JF, Cornet JP, Herve JP, Sureau P, Camicas JL, Robin Y, Salaun JJ, Heme G. [Isolation of the yellow fever virus from an egg-cluster and the larvae of the tick Amblyomma variegatum]. C R Seances Acad Sci D. 1979; 289(8); 635-637. [PubMed: 117946].

Karesh et al., 1998: Karesh WB, Wallace RP, Painter RL, Rumiz D, Braselton WE, Dierenfeld ES, Puche H. Immobilization and health assessment of free-ranging black spider monkeys (Ateles paniscus chamek). Am J Primatol. 1998; 44(2); 107-123. [PubMed: 9503123].

Kerr, 1951: Kerr JA. The clinical aspects and diagnosis of yellow fever. 387-425. In: . Yellow Fever. 1951. McGraw-Hill, New York.

Koraka et al., 2002: Koraka P, Zeller H, Niedrig M, Osterhaus AD, Groen J. Reactivity of serum samples from patients with a flavivirus infection measured by immunofluorescence assay and ELISA. Microbes Infect. 2002; 4(12); 1209-1215. [PubMed: 12467761].

Monath et al., 2002: Monath TP, Nichols R, Archambault WT, Moore L, Marchesani R, Tian J, Shope RE, Thomas N, Schrader R, Furby D, Bedford P. Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX and YF-VAX) in a phase III multicenter, double-blind clinical trial. Am J Trop Med Hyg. 2002; 66(5); 533-541. [PubMed: 12201587].

Monath, 1989: Monath TP. Yellow Fever. 139-232. In: . The Arboviruses: Epidemiology and Ecology. Volume V. 1989. CRC Press, Boca Raton, Florida.

Monath, 2001: Monath TP. Yellow fever: an update. Lancet Infect Dis. 2001; 1(1); 11-20. [PubMed: 11871403].

Mutebi et al., 2002: Mutebi JP, Barrett ADT. The epidemiology of yellow fever in Africa. Microbes Infect. 2002; 4(14); 1459-1468. [PubMed: 12475636].

Niedrig et al., 1999: Niedrig M, Lademann M, Emmerich P, Lafrenz M. Assessment of IgG antibodies against yellow fever virus after vaccination with 17D by different assays: neutralization test, haemagglutination inhibition test, immunofluorescence assay and ELISA. Trop Med Int Health. 1999; 4(12); 867-871. [PubMed: 10632996].

Onyango et al., 2004: Onyango CO, Ofula VO, Sang RC, Konongoi SL, Sow A, De Cock KM, Tukei PM, Okoth FA, Swanepoel R, Burt FJ, Waters NC, Coldren RL. Yellow fever outbreak, Imatong, southern Sudan. Emerg Infect Dis. 2004; 10(6); 1063-1068. [PubMed: 15207058].

Onyango et al., 2004: Onyango CO, Grobbelaar AA, Gibson GV, Sang RC, Sow A, Swaneopel R, Burt FJ. Yellow fever outbreak, southern Sudan, 2003. Emerg Infect Dis. 2004; 10(9); 1668-1670. [PubMed: 15498174].

Pinheiro et al., 1981: Pinheiro FP, Travassos da Rosa PA, Moraes MAP. An epidemic of yellow fever in Central Brazil, 1972-1973. II. Ecological studies. Am J Trop Med Hyg. 1981; 30(1); 204-211. [PubMed: 6111231].

Pugachev et al., 2004: Pugachev KV, Guirakhoo F, Ocran SW, Mitchell F, Parsons M, Penal C, Girakhoo S, Pougatcheva SO, Arroyo J, Trent DW, Monath TP. High fidelity of yellow fever virus RNA polymerase. J Virol. 2004; 78(2); 1032-1038. [PubMed: 14694136].

Sallis et al., 2003: Sallis ES, de Barros VL, Garmatz SL, Fighera RA, Graca DL. A case of yellow fever in a brown howler (Alouatta fusca) in Southern Brazil. J Vet Diagn Invest. 2003; 15(6); 574-576. [PubMed: 14667022].

Severson et al., 2004: Severson DW, Knudson DL, Soares MB, Loftus BJ. Aedes aegypti genomics. Insect Biochem Mol Biol. 2004; 34(7); 715-721. [PubMed: 15242713].

Tomori, 2004: Tomori O. Yellow fever: the recurring plague. Crit Rev Clin Lab Sci. 2004; 14(4); 391-427. [PubMed: 15487593].

Vasconcelos et al., 2001: Vasconcelos PFC, Rosa APAT, Rodrigues SG, Rosa ES, Monteiro HA, Cruz AC, Barros VL, Souza MR, Rosa JF. Yellow fever in Para State, Amazon region of Brazil, 1998-1999: entomologic and epidemiologic findings. Emerg Infect Dis. 2001; 7(3 Supple); 565-569. [PubMed: 11485676].

Vasconcelos et al., 2003: Vasconcelos PF, Sperb AF, Monteiro HA, Torres MA, Sousa MR, Vasconcelos HB, Mardini LB, Rodrigues SG. Isolations of yellow fever virus from Haemagogus leucocelaenus in Rio Grande do Sul State, Brazil. Trans R Soc Trop Med Hyg. 2003; 97(1); 60-62. [PubMed: 12892055].

Vasquez et al., 2003: Vasquez S, Valdes O, Pupo M, Delgado I, Alvarez M, Pelegrino JL, Guzman MG. MAC-ELISA and ELISA inhibition methods for detection of antibodies after yellow fever vaccination. J Virol Methods. 2003; 110(2); 179-184. [PubMed: 12798246].

Website 10: Yellow fever virus strain Gambia 2001, complete genome

Website 11: Yellow fever virus strain 85-82H Ivory Coast, complete genome

Website 12: Yellow fever virus strain Trinidad 79A isolate 788379, complete genome

Website 13: Yellow fever virus vaccine strain 17D-213, complete genome

Website 14: Yellow fever virus vaccine strain 17DD, complete genome

Website 15: Yellow fever virus French neurotropic strain, complete genome

Website 16: Yellow fever virus French viscerotropic strain, complete genome

Website 18: Aedes furcifer

Website 19: Aedes luteocephalus

Website 20: Aedes taylori

Website 21: Haemagogus equinus

Website 22: Haemagogus mesodentatus

Website 23: Sabethes

Website 24: Aedes

Website 25: Haemagogus

Website 26: Homo sapiens

Website 27: Alouatta fusca

Website 28: Alouatta caraya

Website 28A: Ateles paniscus

Website 29: Alouatta belzebul

Website 30: Aedes simpsoni

Website 31: Amblyomma variegatum

Website 32: Alouatta seniculus

Website 33: Pithecia pithecia

Website 34: Saguinus midas

Website 35: Pecari tajacu

Website 36: Eira barbara

Website 37: Coendou

Website 38: Dasyprocta leporina

Website 39: Tamandua tetradactyla

Website 40: Bradypus tridactylus

Website 41: Choloepus didactylus

Website 42: Cebus

Website 43: Caluromys

Website 45: BMBL Section VII. Arboviruses and Arenaviruses Assigned to Biosafety Level 3

Website 46: Callithrix penicillata

Website 47: Alouatta palliata

Website 48: Didelphis marsupialis

Website 49: Pan troglodytes troglodytes

Website 5: Yellow fever virus, complete genome

Website 50: Perodicticus potto

Website 51: Otolemur crassicaudatus

Website 52: BMBL Section III. Laboratory Biosafety Level Criteria

Website 6: Yellow fever virus, complete genome

Website 7: Yellow fever virus strain ASIBI, complete genome

Website 8: Yellow fever virus strain Ivory Coast 1999, complete genome

Website 9: Yellow fever virus complete genome, 17D vaccine strain

da Thoisy et al., 2004: da Thoisy B, Dussart P, Kazanji M. Wild terrestrial rainforest mammals as potential reservoirs for flaviviruses (yellow fever, dengue 2 and St Louis encephalitis viruses) in French Guiana. Trans R Soc Trop Med Hyg. 2004; 98(7); 401-412. [PubMed: 15138077].

de Madrid and Porterfield, 1969: de Madrid AT, Porterfield JS. A simple micro-culture method for the study of group B arboviruses. Bull World Health Organ. 1969; 40(1); 113-121. [PubMed: 4183812].

 

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