Yellow fever is a classic viral hemorrhagic fever and is an example of diseases of antiquity. It was first described in 1667 in Barbados. The name of the disease is derived from the appearance of those infected (usually a yellow tinted skin). It was earlier called as Yellow Jack because jaundice is a prominent sign in severe cases. Devastating epidemics of yellow fever were prevalent in the Americas, Europe and Africa from the seventeenth to the twentieth century. The mortality rate for yellow fever is about 20% (Narins 2003).
Yellow fever virus belongs to the genus Flavivirus (Family: Flaviviridae) and is the most studied member of the family. The virus was discovered in 1927 when it was demonstrated to transmit from a human patient to a rhesus monkey. Manfred Bayer first visualized the yellow fever virus in cultured cells. Yellow fever virus is a spherical particle of 40 nm diameter. It has an inner core surrounded by an adherent lipid envelop.
Mosquitoes are the vectors for the yellow fever virus. Once inside the person, the virus spreads to local lymph nodes and multiplies. It further moves to liver, spleen, kidneys and heart (Narins 2003).
In the year 1848, Nott proposed that yellow fever was transmitted by the bite of mosquito. This proposal was taken further and in 1900, Walter Reed demonstrated the transmission of yellow fever by mosquitoes using human volunteers. In 1901, Walter Reed demonstrated that this disease was due to a filterable agent. Hence, yellow fever was the first human disease revealed to be caused by a filterable agent.
The transmission cycles of yellow fever virus and the ecological inter-relationships of its vectors and reservoirs are complex. Humans are infected when the virus is transmitted to humans from monkeys by mosquitoes. This type of transmission is called as horizontal transmission). Transovarial pattern of transmission is followed in the mosquito vector (Mosquitoes can pass the virus to their next generation, also called as vertical transmission). Three cycles of transmission have been recognized viz. enzootic forest cycle, jungle yellow fever cycle and urban yellow fever cycle (Narins 2003).
- Enzootic forest cycle: Haemagogus mosquitoes are the major amplification hosts for the virus and monkeys are transient vertebrate hosts. Monkeys experience a short lived viremia whereas the mosquitoes remain infected for life and may transmit the virus to humans (when people venture into the forests).
- Jungle yellow fever cycle (or sylvatic cycle): This cycle is seen in tropical rainforests where the infected monkeys pass the virus to mosquitoes biting them. Human infections occur when infected forest mosquitoes invade nearby areas. A single infected human may transmit the disease to many others and epidemic out breaks may result. The mosquitoes responsible for transmission are Haemagogus, Aedes simpsoni, Aedes aegypti, Aedes furcifer and Aedes africanus.
- Urban yellow fever cycle: This cycle is exclusively maintained by Aedes aegypti. It was the dominant form of yellow fever in urban areas before the extensive mosquito control programs (Zuckerman 2009).
Immunity to the yellow fever may be active or passive. Active immunity results from the actual natural infection or vaccination. Passive immunity is the result of transfer of antibodies from a mother to her offspring. Passive immunity may also result from the inoculation of a susceptible person with the antibodies derived from an immune person.
The attack from the yellow fever virus leads to the formation of complement-fixing antibody. This antibody disappears from the serum of the infected person after about six months of the infection. This antibody is not produced after the immunization with 17D vaccine. Hence, if the antibody is found in the serum of a person, it can be concluded that s/he may have been infected by the virulent form of yellow fever in recent past (Smithburn 1954).
A number of host-related factors may affect the clinical symptoms and severity of the illness. Young adult of age 20 to 25 years were found to be more susceptible to infection in South America. Gender is also noted to play a role in some epidemics. In the 1972-73 epidemic of Brazil, men were ten times more affected that women. However, in 1986 Nigerian epidemic, only a slight male predominance was noted (Zuckerman 2009).
Yellow fever virus has an incubation period of three to six days followed by the clinical presentation of acute biphasic illness. The first phase is characterized by viraemia in which the patient is infectious to mosquitoes. Major symptoms are headache, malaise, nausea, lassitude and muscle pain. More specific symptoms conclusive of yellow fever are flushing of head and neck, conjunctival injection, strawberry tongue and bradycardia.
In cases of severe yellow fever, the early acute illness is followed by a period of remission. This period is followed by the second phase of illness. This phase is presented by fever, vomiting, abdominal pain, dehydration and prostration. ‘Black vomit’ characterizes the onset of hemorrhagic diathesis accompanied by jaundice, albuminuria and oligouria. Deepening jaundice, increased haematemesis, progressive renal failure, hypotension and shock leads to coma or death by a week or ten days (Zuckerman 2009).
Diagnosis and Treatment
Classical tests used for yellow fever are HAI, CF and NT tests but these cannot be used for a definitive diagnosis. The IgM antibody ELISA is a rapid diagnostic serological test for yellow fever virus. Another test is based on immuno-fluorescence wherein infected cells are spotted onto microscopic slides and IgG and IgM antibodies are detected.
There is no specific treatment for yellow fever. Only supportive care to treat dehydration, respiratory failure and fever is provided. Antibiotics are occasionally given to treat associated bacterial infections.
Asibi strain of the yellow fever virus was the first discovered strain and was used in the preparation of 17D vaccine (developed by Max Theiler at Rockefeller Foundation, New York in 1937). It was developed by serial passage of the virus through mouse embryo culture followed by chick embryo culture and then through minced chick embryo. The obtained virus was immunogenic but attenuated. It was proved to be safe as well as effective and was known to produce lifelong immunity after one injection only. The vaccine should be given to pregnant women only if there is substantial risk of exposure.
The French neurotropic vaccine is a live attenuated product is prepared by growing the virus on chick embryos. This vaccine is out-of-use because of the danger of encephalitic complications. Side effects to the immunization are reported rarely and include mild fever, muscle pain and headache. The vaccine should never be given to children less than nine months of age (Zuckerman 2009).
Prevention and Control
A concerted campaign to kill the breeding populations of mosquitoes and protecting people from vector mosquitoes is required for yellow fever. Worldwide control of yellow fever has been achieved by immunization and vector control programs. Urban yellow fever has been eradicated in the Americas by the control of A. aegpti. However, the jungle yellow fever is endemic in many parts of America.
Several strategies have been devised at international levels for the effective control of yellow fever. One of these strategies is the inclusion of yellow fever vaccine national childhood immunization programmes. Vaccine is administered at nine months of age along with the first dose of measles vaccines. This strategy has been combined with the mass preventive vaccination campaigns. During the yellow fever epidemics, outbreak response vaccination campaigns are established to limit the spread of the disease. For meeting the increased demand for the vaccine during the outbreaks, Global Alliance for Vaccine and Immunization (GAVI) financed a global stockpile for adequate supplies.
Yellow fever vaccination is carried out for three reasons: 1) to protect populations of endemic and epidemic areas, 2) to protect travelers visiting these areas and 3) to prevent the international spread by importation of the virus by infected travelers (World Health Organization 2014).
Vector control strategies include aerial sprays, domiciliary sprays and enforcement of public health regulation to decrease stagnant water and mosquito breeding sites. These strategies have been successful in eliminating the urban yellow fever; however, these are impractical for the control of jungle yellow fever. Mosquito nets are used over the beds in susceptible regions. Antimicrobial and antiviral drugs may be used to either defeat an infection or prevent the spread of the infection (Zuckerman 2009).
Zuckerman, A.J., Banatvala, J.E., Schoub, B.D., Griffiths, P.D. and Motimer, P. (eds.) 2009, Principles and practice of clinical virology, 6th ed., Wiley-Blackwell, Chichester, UK.
Narins, B. (ed.) 2003, World of microbiology and immunology, Thomson Gale, Farmington Hills, MI.
Smithburn, K.C. 1956, Immunology of yellow fever, World Health Organization, Geneva, viewed 20 May 2014, <whqlibdoc.who.int/monograph/WHO_MONO_30_(part1).pdf>
World Health Organization 2014, Yellow fever, Geneva, viewed 20 May 2014, <http://www.who.int/topics/yellow_fever/en/>