Yellow Fever

Yellow fever in short

• a viral disease transmitted by mosquitoes
• occurs in Africa and parts of South America
• illness ranges in severity from mild, self-limiting fever to severe hepatitis and hemorrhagic fever
• a safe and effective vaccine is available and applicable to theoretically prevent devastating outbreaks
• in most countries, the vaccination rate is too low to effectively prevent outbreaks
• yellow fever is highly underreported, but the WHO estimates 200,000 cases of yellow fever annually and 30,000 deaths

Yellow fever in detail

Pathogenic agent
The yellow fever virus belongs to the genus Flavivirus within the family of Flaviviridae. It is a single-stranded RNA virus (ssRNA) with a size of approximately 40 to 50 nm. The RNA genome is associated with a C-protein to form a nucleocapsid. Two proteins named "M" and "E" are embedded in the membrane.

In Africa two genetic types exist, one associated with West Africa, the other with East Africa. South America has two different types as well, but since the 1970s only one has caused disease outbreaks.

Transmission/pathogenesis
Mosquitoes are the reservoir of the yellow fever virus. They can infect humans and monkeys by biting and also pass the virus vertically to their offspring (via the eggs). As the eggs can endure the dry season, the virus is transmitted from one rainy season to the next. In Africa different species of Aedes mosquitoes transmit the disease, and in South America mosquitoes of the Haemogogus genus carry the virus.

On the African continent, the affected regions lie within a band from 15º N to 10º S of the equator. The World Health Organization (WHO) has defined 33 African countries with a combined population of about 508 million people as "at risk". In South America, 9 countries within the "yellow fever belt" between 20º N and 40º S are affected. Several Caribbean islands are also at risk.

Infection of humans can occur via three different transmission cycles. Sylvatic (or jungle) yellow fever occurs in dense tropical rainforest where the virus is passed from one monkey to the other by mosquitoes. Humans sporadically entering the forest (e.g. loggers, forest workers) may be bitten by a mosquito and infected. Cases of sylvatic yellow fever are usually isolated, seldom spreading beyond the infected individual. Small-scale epidemics may occur among populations living in areas (e.g. close to forests) where mosquitoes, humans and monkeys live close together; according to the WHO, this intermediate yellow fever is the most common form of outbreak seen in Africa in recent decades. Urban yellow fever occurs in areas with high human density. Large epidemics may occur when the virus is introduced into the population and transmitted from one infected individual to others via domestic mosquitoes.

Symptoms
After infection, an incubation period of 3 to 6 days follows. Some individuals don’t show symptoms at all, while others develop unspecific symptoms such as fever, muscle pain, headache, nausea or vomiting during the acute phase. Within 24 hours approximately 15% of symptomatic individuals enter the toxic phase, with symptoms including high fever, abdominal pain, bleeding (from nose, mouth, eyes or stomach), vomiting (also with blood) and finally a deterioration of kidney and liver function. The latter leads to a typical jaundice, although this is less pronounced than could be anticipated by the name "yellow" fever. Approximately 50% of patients in the toxic phase die within 10–14 days. Altogether, yellow fever lethality lies between 10 and 20%.

Treatment
There is no specific treatment for the viral infection, only the symptoms can be treated. Dehydration, for example, can be counteracted by oral rehydration. Bacterial superinfection should be treated with antibiotics.

Prevention
Vaccination has proven to be the most effective means to prevent yellow fever epidemics. Control of mosquitoes (by insecticide killing, individual mosquito protection with nets, appropriate clothing, etc.) can be used to prevent transmission at the beginning of an epidemic or until vaccination has taken effect. Travellers to high-risk areas should get vaccinated.

Vaccination
Since the 1950s a safe and highly effective vaccine consisting of a live, attenuated virus has been used. Immunity develops in 95% of vaccinated individuals within 1 week and lasts for at least 10 years, perhaps even for a lifetime. Serious side effects are extremely rare. Adverse reactions may occur in the elderly. The vaccine is not recommended for infants, pregnant woman or immunosuppressed individuals.

The WHO prefers routine childhood vaccination in affected regions over emergency vaccination campaigns. Mass vaccination can be incorporated into other vaccination programs; for example, the vaccine can be administered to children as young as 9 months of age together with the measles vaccine.

Incidence and mortality
According to the WHO, approximately 200,000 cases of yellow fever resulting in 30,000 deaths occur annually. However, the number of officially reported cases is much lower due to insufficient yellow fever surveillance. In 2005, for example, only 588 cases of yellow fever were reported worldwide. Few countries in high-risk areas have a sufficient vaccination rates to effectively prevent disease outbreaks. Global vaccination coverage was 43% in 2005, only 37% in the African region and 70% in the Americas; the WHO reports that 80% immunity is the threshold for effective prevention of an epidemic.

To know or not to know...
During the building of the Panama Canal, more than 100,000 people died of yellow fever infection. The canal could only be finished after the mosquitoes had been eradicated.

More information
- WHO: www.who.int/topics/yellow_fever/en/
- Centers for Disease Control and Prevention: www.cdc.gov/ncidod/dvbid/yellowfever/

Literature
- WHO fact sheet on yellow fever: www.who.int/mediacentre/factsheets/fs100/en/
- Centers for Disease Control and Prevention: www.cdc.gov/ncidod/dvbid/yellowfever/
- Robert Koch Institute (in German only): http://www.rki.de/cln_091/nn_467542/DE/Content/Infekt/EpidBull/Merkblaetter/Rat__Gelbfieber.html
- Molekulare Virologie, Susanne Modrow, Dietrich Falke, Spektrum Akademischer Verlag GmbH Heidelberg, 1997