Yellow Fever virus

I. Organism Information

A. Taxonomy Information
  1. Species:
    1. Yellow fever virus (Website 1):
      1. Ontology: UMLS:C0043396
      2. GenBank Taxonomy No.: 11089
      3. 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).
      4. Variant(s):
        • Yellow fever virus (STRAIN 17D) (Website 2):
          • GenBank Taxonomy No.: 11090
          • Parent: 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 PASTEUR 17D-204) (Website 4):
          • GenBank Taxonomy No.: 11091
          • Parent: 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).
B. Lifecycle Information :

  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).
C. Genome Summary:
  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):
        1. Yellow fever virus, complete genome (Website 6):


II. Epidemiology Information

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 (Tomori, 2004). Yellow fever occurs in tropical areas of South America and Africa, but not in Asia. Aedes aegypti-infested areas of Central America, the Caribbean, North America, and Europe were subject to introduction and spread of the disease up to the early part of this century and must still be considered receptive zones (Monath, 1989). The disease occurs primarily in tropical regions of Africa and South America, and the WHO estimated that, annually, there are 200,000 cases, including 30,000 deaths, worldwide, with over 90% of the cases in Africa. Because of inconsistent and gross under-reporting of YF cases to the WHO by the African countries, Monath and Nasidi et al. concluded that the actual annual number of cases in Africa may be 10 to 500 times higher than reported (Tomori, 2004).

A. 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).
B. Transmission Information:
  1. Ontology: UMLS:C0417744 From: Mosquitoes To: Nonhuman Vertebrates , With Destination: 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. Ontology: UMLS:C0417744 From: Nonhuman Vertebrates To: Mosquitoes , With Destination: 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. Ontology: UMLS:C0242648 From: Mosquitoes To: Mosquitoes , With Destination: 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)

C. Environmental Reservoir:
  1. Mosquito Nonhuman_Primate :
    1. Ontology: UMLS:C0026584 C0237798, SNOMED:A3567757
    2. 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).
    3. Survival Information: 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).
D. Intentional Release:

No release information is currently available here.

III. Infected Hosts

  1. Humans:
    1. Taxonomy Information:
      1. Species:
        1. Human (Website 26):
          • Ontology: UMLS: C0086418
          • GenBank Taxonomy No.: 9606
          • Scientific Name: Homo sapiens (Website 26)
          • 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).
      2. Description:

    3. Disease Information:
      1. Yellow Fever :
        1. Pathogenesis Mechanism: Fixed macrophages (Kupffer cells) in the liver are infected 24 hours after inoculation. Infection of the kidney, bone marrow, spleen and lymph nodes follow. Infection and degeneration of hepatocytes is a relatively late event, occurring in the last 2448 h before death in the monkey and in the last phase of infection in people. A unique feature of yellow fever hepatic injury is its mid-zonal distribution, with sparing of cells around the central vein and portal tracts. This distribution of hepatic lesions in yellow fever might simply reflect low-flow hypoxia due to terminal shock. However, yellow fever virus antigen and RNA have been observed principally in hepatocytes in the midzone, indicating that these cells are most susceptible to virus replication. The infected hepatocyte undergoes eosinophilic degeneration with condensed nuclear chromatin (Councilman bodies) typical of apototic cell death and distinct from the ballooning and rarefaction necrosis seen in viral hepatitis. Apoptosis has been documented as a late event in human hepatoma cells infected with yellow fever virus. Hepatic injury from apoptosis rather than necrosis explains the virtual absence of inflammatory cells in yellow fever, preservation of the reticulin framework, and healing without fibrosis. The renal pathology is characterised by eosinophilic degeneration and fatty change of tubular epithelium, once again without inflammation. Yellow fever antigen is found in renal tubular cells of fatal human cases, suggesting that direct viral injury has a role. However, in the monkey model, renal tubular function was maintained during the course of the illness. Oliguria was shown to be caused by pre-renal failure associated with hypotension, and acute tubular necrosis was a terminal event. The marked albuminuria in yellow fever may be due to alteration of glomerular function, since histological changes are observed in basement membrane and cells lining Bowman's capsule and yellow fever antigen is present in glomerulae 23 days after infection of monkeys. Necrosis of germinal centers of spleen, lymph nodes, tonsils, and Peyer's patches has been noted in monkeys and human beings, but it is uncertain whether this is due to viral injury or depletion by corticoid induced stress. Hypotension and shock in the late stage of illness are probably mediated by cytokine dysregulation, as in other VHFs and bacterial sepsis. Tumour necrosis factor (TNF) and other cytokines produced by infected/activated Kupffer cells and splenic macrophages in response to direct virus injury and cytotoxic T cells involved in viral clearance might be responsible for cell injury, oxygen free radical formation, endothelial damage and microthrombosis, disseminated intravascular coagulation, tissue anoxia, oliguria, and shock. It is noteworthy that the dramatic pathophysiological events are initiated at the stage when immune clearance of yellow fever virus infected cellsie, at the inception of the period of intoxication. Future studies of patients or experimentally infected monkeys are required to define the cytokine mediators of the shock syndrome. Direct viral injury to myocardial fibres, which contain viral antigen and show changes consistent with apoptosis, may contribute to shock (Monath, 2001).


        2. Incubation Period: 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).


        3. 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).


        4. Diagnosis Overview: 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).


        5. 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).


              • Symptoms Shown in the Syndrome:

            • Fever:
              • Ontology: UMLS:C0015967
              • 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).
            • Headache:
              • Ontology: UMLS:C0018681
              • 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)


              • Symptoms Shown in the Syndrome:

            • Albuminuria:
              • Ontology: UMLS:C0001925
              • 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).
            • Bradycardia (Faget's sign):
              • Ontology: UMLS:C0428977
              • Description: A slow pulse in relation to the fever (Faget's sign) is also typical at this stage (Tomori, 2004).
            • Epistaxis:
              • Ontology: UMLS:C0014591
              • Description: Epistaxis is common at or soon after the onset of fever because of the congestion of the nasopharynegeal mucous membranes (Kerr, 1951).
            • Fever:
              • Ontology: UMLS:C0015967
              • 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).
            • Headache:
              • Ontology: UMLS:C0018681
              • Description: Fever and headache, which usually begin suddenly, are more pronounced (Kerr, 1951).
            • Nausea:
              • Ontology: UMLS:C0027497
              • 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).


              • Symptoms Shown in the Syndrome:

            • Albuminuria:
              • Ontology: UMLS:C0001925
              • Description: Definite jaundice and marked albuminuria are present (Kerr, 1951).
            • Back pain:
              • Ontology: UMLS:C0004604
              • Description: Headache and backache may be severe (Kerr, 1951).
            • Black vomit:
              • Ontology: UMLS:C0554631
              • 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).
            • Bradycardia (Faget's sign):
              • Ontology: UMLS:C0428977
              • Description: A slow pulse in relation to the fever (Faget's sign) is also typical at this stage (Tomori, 2004).
            • Epistaxis:
              • Ontology: UMLS:C0014591
              • Description: Epistaxis is common at or soon after the onset of fever because of the congestion of the nasopharynegeal mucous membranes (Kerr, 1951).
            • Fever:
              • Ontology: UMLS:C0015967
            • Headache:
              • Ontology: UMLS:C0018681
              • Description: Headache and backache may be severe (Kerr, 1951).
            • Uterine hemorrhage:
              • Ontology: UMLS:C0042134
              • Description: There may even be black vomit or uterine hemorrhages (Kerr, 1951).
            • Jaundice:
              • Ontology: UMLS:C0022346
              • Description: Definite jaundice and marked albuminuria are present (Kerr, 1951).
            • Nausea:
              • Ontology: UMLS:C0027497
              • Description: Nausea and vomiting are more troublesome (Kerr, 1951).
            • Vomiting:
              • Ontology: UMLS:C0042963
              • 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).


              • Symptoms Shown in the Syndrome:

            • Albuminuria:
              • Ontology: UMLS:C0001925
              • 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).
            • Back pain:
              • Ontology: UMLS:C0004604
              • 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).
            • Black vomit:
              • Ontology: UMLS:C0554631
              • 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).
            • Bradycardia (Faget's sign):
              • Ontology: UMLS:C0428977
              • 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).
            • Chills (Monath, 2001):
              • Ontology: UMLS:C0085593
              • 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).
            • Coma (Monath, 2001):
              • Ontology: UMLS:C0009421
              • 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).
            • Conjunctiva injected:
              • Description: Examination of the patient reveals a flushed face, neck, and upper chest. The conjunctivae are injected (Kerr, 1951).
            • Convulsions (Monath, 2001):
              • Ontology: UMLS: C0009951
              • Description: Small children may experience an initial convulsion (Kerr, 1951).
            • Epigastric pain (Monath, 2001):
              • Ontology: UMLS:C0232493
              • 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).
            • Dizziness (Monath, 2001):
              • Ontology: UMLS:C0012833
              • 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).
            • Epistaxis:
              • Ontology: UMLS:C0014591
              • Description: Epistaxis is common at or soon after the onset of fever because of the congestion of the nasopharynegeal mucous membranes (Kerr, 1951).
            • Fever:
              • Ontology: UMLS:C0015967
              • 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).
            • Furred tongue:
              • Ontology: UMLS:C0009144
              • 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).
            • Headache:
              • Ontology: UMLS:C0018681
              • 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).
            • Hemorrhage:
              • Ontology: UMLS:C0019080
              • 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).
            • Hiccup:
              • Ontology: UMLS:C0019521
              • 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).
            • Hypotension (Monath, 2001):
              • Ontology: UMLS:C0020649
              • Description: Pre-terminal events include hypotensionan increasingly difficult symptom to manage with fluids and vasopressors (Tomori, 2004).
            • Hypothermia (Monath, 2001):
              • Ontology: UMLS:C0020672
              • Description: Patients also experience agitated delirium, stupor, coma, Cheyene-Stokes respirations, metabolic acidosis, hyperkalaemia, hypoglycaemia, and hypothermia (Monath, 2001).
            • Jaundice:
              • Ontology: UMLS:C0022346
              • 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).
            • Malaise (Monath, 2001):
              • Ontology: UMLS:C0231218
              • Description: Disease onset is typically abrupt, with fever, chills, malaise, headache, lower back pain, generalized myalgia, nausea, and dizziness (Monath, 2001).
            • Myalgia (Monath, 2001):
              • Ontology: UMLS:C0231528
              • Description: Muscular aches and pains become generalized (Kerr, 1951).
            • Nausea:
              • Ontology: UMLS:C0027497
              • Description: Often there is nausea, with vomiting of food or mucus (Kerr, 1951).
            • Oliguria (Monath, 2001):
              • Ontology: UMLS:C0028961
              • 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).
            • Prostration (Monath, 2001):
              • Ontology: UMLS:C0277794
              • 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).
            • Shock (Monath, 2001):
              • Ontology: UMLS:C0036974
              • Description: Progressive tachycardia, shock, and intractable hiccups are considered ominous and terminal signs (Tomori, 2004).
            • Stupor (Monath, 2001):
              • Ontology: UMLS:C0085628
              • Description: Patients also experience agitated delirium, stupor, coma, Cheyene-Stokes respirations, metabolic acidosis, hyperkalaemia, hypoglycaemia, and hypothermia (Monath, 2001).
            • Tender liver (Monath, 2001):
              • Ontology: UMLS:C0151767
            • Vomiting:
              • Ontology: UMLS:C0042963
              • Description: Often there is nausea, with vomiting of food or mucus (Kerr, 1951).
          • 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).

        6. 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).
            • Applicable:

    4. Prevention:
      1. Vector Control:
        • Ontology: UMLS:C0031249
        • 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).
      2. 17D Vaccine:
        • Ontology: UMLS:C0301508
        • 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. Ontology: UMLS:C0999699
        2. Model Host: Nonhuman Vertebrates. Cavia porcellus (Monath, 1989)
        3. Model Pathogens:
        4. 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).
      2. Hamsters:
        1. Ontology: UMLS:C0018561
        2. Model Host: Nonhuman Vertebrates. Mesocricetus auratus (Monath, 1989)
        3. Model Pathogens:
        4. 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).
      3. Mice:
        1. Ontology: UMLS: C0025914
        2. Model Host: Nonhuman Vertebrates. Mus musculus (Monath, 1989)
        3. Model Pathogens:
        4. 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).
      4. Primate:
        1. Ontology: UMLS:
        2. Model Host: Nonhuman Vertebrates. Primates (Burke and Monath, 2001)
        3. Model Pathogens:
        4. 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).
      5. Rabbits:
        1. Ontology: UMLS:C0034493
        2. Model Host: Nonhuman Vertebrates. Oryctolagus cuniculus (Monath, 1989)
        3. Model Pathogens:
        4. Description: Rabbits inoculated i.c or i.p. become immune without demonstrable viremia or illness (Monath, 1989).
      6. Sudanese Hedgehog:
        1. Ontology: UMLS:
        2. Model Host: Nonhuman Vertebrates. Erinaceus pruneri (Monath, 1989)
        3. Model Pathogens:
        4. 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. Yellow fever mosquito :
          • Ontology: UMLS:C0322859
          • GenBank Taxonomy No.: 7159
          • Scientific Name: Aedes aegypti (Website 17)
          • 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):
          • Ontology: UMLS:C0322873
          • GenBank Taxonomy No.: 7158
          • Scientific Name: Aedes africanus (Website 24)
          • 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):
          • GenBank Taxonomy No.: 7158
          • Scientific Name: Aedes bromeliae (Website 24)
          • 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):
          • GenBank Taxonomy No.: 7158
          • Scientific Name: Aedes dentatus (Website 24)
          • 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):
          • GenBank Taxonomy No.: 299627
          • Scientific Name: Aedes furcifer (Website 18)
          • 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):
          • Ontology: UMLS:C0322839
          • GenBank Taxonomy No.: 299629
          • Scientific Name: Aedes luteocephalus (Website 19)
          • 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):
          • Ontology: UMLS:C0322875
          • GenBank Taxonomy No.: 7158
          • Scientific Name: Aedes metallicus (Website 24)
          • 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):
          • GenBank Taxonomy No.: 7158
          • Scientific Name: Aedes opok (Website 24)
          • 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):
          • Ontology: UMLS: C0322840
          • GenBank Taxonomy No.: 7161
          • Scientific Name: Aedes simpsoni (Website 30)
          • 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):
          • Ontology: UMLS:C0322866
          • GenBank Taxonomy No.: 299628
          • Scientific Name: Aedes taylori (Website 20)
          • 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):
          • Ontology: UMLS:C0322874
          • GenBank Taxonomy No.: 7158
          • Scientific Name: Aedes vittatus (Website 24)
          • 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 :
          • Scientific Name: Coquillettidia fuscopennata (Monath, 1989)
          • 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):
          • GenBank Taxonomy No.: 7180
          • Scientific Name: Haemagogus capricornii (Website 25)
          • 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):
          • Ontology: UMLS:C0322904
          • GenBank Taxonomy No.: 53526
          • Scientific Name: Haemagogus equinus (Website 21)
          • 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):
          • GenBank Taxonomy No.: 7180
          • Scientific Name: Haemagogus iridicolor (Website 25)
          • 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):
          • GenBank Taxonomy No.: 7180
          • Scientific Name: Haemagogus janthinomys (Haemagogus spegazzinii falco) (Website 25)
          • 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):
          • GenBank Taxonomy No.: 7180
          • Scientific Name: Haemagogus leucocelanenus (Website 25)
          • 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):
          • GenBank Taxonomy No.: 7180
          • Scientific Name: Haemagogus lucifer (Website 25)
          • Description: Hg. lucifer is an abundant species in Colomb