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: