Yellow fever

Yellow fever is an acute viral haemorrhagic disease transmitted by infected mosquitoes, and can present in one or two phases. After a 3-6 day incubation period infection typically presents as an acute illness (the ‘acute phase’) characterised by fever with rigors, myalgia, prominent backache, headache, loss of appetite, and nausea or vomiting. Fifteen percent of patients then develop a second, severe phase of illness (the ‘toxic phase’) within 24 hours of apparent remission, marked by recurrence of high fever and evidence of multi-organ involvement including: jaundice, abdominal pain with vomiting, renal failure and/ or haemorrhage.

This second phase carries a case fatality rate of 20% to 50%.The virus is endemic in tropical areas of Africa and Latin America. Vaccination is the single most important preventive measure.Under the International Health Regulations, South Africans travelling to endemic countries must receive yellow fever vaccine at least 10 days prior to departure.Yellow fever vaccination certificates are valid for 10 years.

Vaccine is contraindicated in pregnant women, infants <9 months, individuals with egg allergies, and certain immunosuppressed individuals (including HIV-infected persons with CD4<200/ mm3). These individuals still require a health certificate indicating the reason for non-receipt of vaccine.Vaccinated travellers should still take precautionary measures to avoid being bitten by mosquitoes due to the many other communicable disease risks transmitted by these vectors (e.g. malaria, dengue).All curable forms of the disease confer lifelong immunity to the patients.No specific antiviral treatment is available against yellow fever.

Epidemiology and vaccination against Yellow fever

WHO estimates that a total of 200,000 cases of Yellow fever occur each year, with about 30,000 deaths.Yellow fever is a threat for over three million travelers visiting endemic regions each year.Although the usefulness of vaccination campaigns have been demonstrated to be beneficial over the past 60 years, yellow fever still remains a major concern in tropical regions in both Africa and South America. In countries at risk for yellow fever, vaccination is recommended in order to prevent and fight epidemics. It is also recommended for travelers visiting endemic regions.


Signs and symptoms of Yellow Fever:

Yellow fever begins after an incubation period of three to six days. Most cases only cause a mild infection with fever, headache, chills, back pain, loss of appetite, nausea, and vomiting. In these cases the infection lasts only three to four days.(Thus resembles non-specific flu-like symptoms).

In fifteen percent of cases, however, sufferers enter a second, toxic phase of the disease with recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain. Bleeding in the mouth, the eyes, and the gastrointestinal tract will cause vomiting containing blood (hence the Spanish name for yellow fever, vomito negro (black vomit)). The toxic phase is fatal in approximately 20% of cases, making the overall fatality rate for the disease 3% (15% -20%). In severe epidemics, the mortality may exceed 50%.

Surviving the infection provides lifelong immunity and normally there is no permanent organ damage.

Transmission of Yellow Fever:

The yellow fever virus is mainly transmitted through the bite of the yellow fever mosquito Aedes aegypti, but other mosquitoes such as the "tiger mosquito" (Aedes albopictus) can also serve as a vector for the virus. Like other Arboviruses which are transmitted via mosquitoes, the yellow fever virus is taken up by a female mosquito which sucks the blood of an infected person or primate. Viruses reach the stomach of the mosquito, and if the virus concentration is high enough, the virions can infect epithelial cells and replicate there. From there they reach the haemocoel (the blood system of mosquitoes) and from there the salivary glands. When the mosquito next sucks blood, it injects its saliva into the wound, and thus the virus reaches the blood of the bitten person

Epidemiological cycles of Yellow Fever:

There are three epidemiologically different infectious cycles in which the virus is transmitted from mosquitoes to humans or other primates. In the "urban cycle," only the yellow fever mosquito Aedes aegypti is involved. It is well adapted to urban centres and can also transmit other diseases, including Dengue and Chikungunya. The urban cycle is responsible for the major outbreaks of yellow fever that occur in Africa. Except in an outbreak in 1999 in Bolivia, this urban cycle no longer exists in South America.

Besides the urban cycle there is, both in Africa and South America, a sylvatic cycle (forest cycle or jungle cycle), where Aedes africanus (in Africa) or mosquitoes of the genus Haemagogus and Sabethes (in South America) serve as a vector. In the jungle, the mosquitoes infect mainly non-human primates; the disease is mostly asymptomatic in African primates. In South America, the sylvatic cycle is currently the only way humans can infect each other, which explains the low incidence of yellow fever cases on this continent. People who become infected in the jungle can carry the virus to urban centres, where Aedes aegypti acts as a vector. It is because of this sylvatic cycle that yellow fever cannot be eradicated.

In Africa there is a third infectious cycle, also known as "savannah cycle" or intermediate cycle, which occurs between the jungle and urban cycle. Different mosquitoes of the genus Aedes are involved. In recent years, this has been the most common form of transmission of yellow fever in Africa.

Diagnosis of Yellow Fever:

Yellow fever is a clinical diagnosis, which often relies on the whereabouts of the diseased person during the incubation time. The medical practitioner needs to have a high index of suspicion when asking about the travel history of the presenting patient.  Mild courses of the disease can only be confirmed virologically. Since mild courses of Yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea and vomiting six to ten days after leaving the affected area) has to be treated seriously.

If Yellow fever is suspected, the virus cannot be confirmed until six to ten days after the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction where the genome of the virus is amplified. Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take one to four weeks.

Serologically, an enzyme linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG-titer (compared to an earlier sample) can confirm yellow fever. Together with clinical symptoms, the detection of IgM or a fourfold increase in IgG-titer is considered sufficient indication for yellow fever. Since these tests can cross-react with other flaviviruses, like Dengue virus, these indirect methods can never prove yellow fever infection.

In a differential diagnosis, infections with yellow fever have to be distinguished from other feverish illnesses like malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, have to be excluded as cause.

Yellow fever vaccination:

For journeys into affected areas, vaccination is highly recommended, since mostly non-native people suffer severe cases of yellow fever. The protective effect is established 10 days after vaccination in 95 percent of the vaccinated people and lasts for at least 10 years (even 30 years later, 81% of patients retained immunity). The attenuated live vaccine (stem 17D) was developed in 1937 by Max Theiler from a diseased patient in Ghana and is produced in chicken eggs. The WHO recommends routine vaccinations for people living in endemic areas between the 9th and 12th month after birth.

In about 20% of all cases, mild, flu-like symptoms may develop.

In rare cases (less than one in 200,000 to 300,000), the vaccination can cause YEL-AVD (yellow fever vaccine-associated viscerotropic disease), which is fatal in 60% of all cases. It is probably due to a genetic defect in the immune system. But in some vaccination campaigns, a 20-fold higher incidence rate has been reported. Age is an important risk factor; in children, the complication rate is less than one case per 10 million vaccinations.

Another possible side effect is an infection of the nervous system that occurs in one in 200,000 to 300,000 of all cases, causing YEL-AND (yellow fever vaccine-associated neurotropic disease), which can cause meningoencephalitis and is fatal in less than 5% of all cases.

In 2009, the largest mass vaccination against yellow fever began in West Africa, specifically Benin, Liberia, and Sierra Leone. When it is completed in 2015, more than 12 million people will have been vaccinated against the disease. According to the World Health Organization (WHO), the mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected. The WHO plans to continue the vaccination campaign in another five African countries — Central African Republic, Ghana, Guinea, Côte d'Ivoire, and Nigeria — and stated that approximately 160 million people in the continent could be at risk unless the organization acquires additional funding to support widespread vaccinations.

Treatment:

Like most viral haemorrhagic viruses treatment is symptomatic. There is no specific treatment for yellow fever.

For yellow fever there is, like for all diseases caused by Flaviviruses, no causative cure. Hospitalization is advisable and intensive care may be necessary because of rapid deterioration in some cases. Different methods for acute treatment of the disease have been shown to not be very successful; passive immunisation after emergence of symptoms is probably without effect. Ribavirin and other antiviral drugs as well as treatment with interferons do not have a positive effect in patients. A symptomatic treatment includes rehydration and pain relief with drugs like paracetamol (known as acetaminophen in the United States). Acetylsalicylic acid (aspirin) should not be given because of its anticoagulant effect, which can be devastating in the case of inner bleeding that can occur with yellow fever.

History of Yellow fever ( an interesting read):

The evolutionary origins of yellow fever most likely lie in Africa, with transmission of the disease from primates to humans. It is thought that the virus originated in East or Central Africa and spread from there to West Africa. As it was endemic in Africa, the natives had developed some immunity to it. When an outbreak of yellow fever would occur in an African village where colonists resided, most Europeans died, while the native population usually suffered nonlethal symptoms resembling influenza. This phenomenon, in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood, is known as acquired immunity. The virus, as well as the vector A. aegypti, were probably transferred to North and South America with the importation of slaves from Africa.

The first definitive outbreak of yellow fever was in 1647 on the island of Barbados. An outbreak was recorded by Spanish colonists in 1648 in Yucatan, Mexico, where the indigenous Mayan people called the illness xekik (black vomit).In 1685 Brazil experienced its first epidemic, in Recife.

Although yellow fever is most prevalent in so-called “tropical” climates, the Northern United States was not exempted from the fever. The first outbreak in English-speaking North America occurred in New York in 1668 and a serious outbreak afflicted Philadelphia in 1793. English colonists in Philadelphia and the French in the Mississippi River Valley recorded major outbreaks in 1669, as well as those occurring later in the eighteenth and nineteenth centuries. The southern city of New Orleans was plagued with major epidemics during the nineteenth century, most notably in 1833 and 1853. At least 25 major outbreaks took place in the Americas throughout the eighteenth and nineteenth centuries, including particularly serious ones in Cartagena in 1741, Cuba in 1762 and 1900, Santo Domingo in 1803, and Memphis in 1878. Major outbreaks have also occurred in southern Europe. Barcelona suffered the loss of several thousand citizens during an outbreak in 1821. Urban epidemics continued in the United States until 1905, with the last outbreak affecting New Orleans.

Due to yellow fever, in colonial times and during the Napoleonic wars, the West Indies were known as a particularly dangerous posting for soldiers. Both English and French forces posted there were decimated by the "Yellow Jack". Wanting to regain control of the lucrative sugar trade in Saint-Domingue, and with an eye on regaining France's New World empire, Napoleon sent an army under the command of his brother-in-law to Saint-Domingue to seize control after a slave revolt. The historian J. R. McNeill asserts that yellow fever accounted for approximately 35,000 to 45,000 casualties during the fighting. Only one-third of the French troops survived for withdrawal and return to France, and in 1804 Haiti proclaimed its independence as the second republic in the western hemisphere.

The yellow fever epidemic of 1793 in Philadelphia, which was then the capital of the United States, resulted in the deaths of several thousand people, more than nine percent of the population. The national government fled the city, including president George Washington. Additional yellow fever epidemics in North America struck Philadelphia, as well as Baltimore and New York in the eighteenth and nineteenth centuries, and traveled along steamboat routes of interior rivers from New Orleans. They have caused some 100,000–150,000 deaths in total.

In 1858 St. Matthew's German Evangelical Lutheran Church in Charleston, South Carolina suffered 308 yellow fever deaths, reducing the congregation by half. In 1873, Shreveport,Louisiana lost almost a quarter of its population to yellow fever. In 1878, about 20,000 people died in a widespread epidemic in the Mississippi River Valley. That year, Memphis had an unusually large amount of rain, which led to an increase in the mosquito population. The result was a huge epidemic of yellow fever. The steamship John D. Porter took people fleeing Memphis northward in hopes of escaping the disease, but passengers were not allowed to disembark due to concerns of spreading yellow fever. The ship roamed the Mississippi River for the next two months before unloading her passengers. The last major U.S. outbreak was in 1905 in New Orleans.

Ezekiel Stone Wiggins, known as the Ottawa Prophet, proposed that the cause of a Yellow fever epidemic in Jacksonville, Florida in 1888 was astronomical.

"The planets were in the same line as the sun and earth and this produced, besides Cyclones, Earthquakes, etc., a denser atmosphere holding more carbon and creating microbes. Mars had an uncommonly dense atmosphere, but its inhabitants were probably protected from the fever by their newly discovered canals, which were perhaps made to absorb carbon and prevent the disease."

Carlos Finlay, a Cuban doctor and scientist, first proposed in 1881 that yellow fever might be transmitted by mosquitoes rather than direct human contact. Since the losses from yellow fever in the Spanish–American War in the 1890s were extremely high, Army doctors began research experiments with a team led by Walter Reed, composed of doctors James Carroll, Aristides Agramonte, and Jesse William Lazear. They successfully proved Finlay's ″Mosquito Hypothesis″. Yellow fever was the first virus shown to be transmitted by mosquitoes. The physician William Gorgas applied these insights and eradicated yellow fever from Havana. He also campaigned against yellow fever during the construction of the Panama Canal, after a previous construction effort on the part of the French failed (in part due to the high incidence of yellow fever and malaria, which decimated the workers).

Although Dr. Reed has received much of the credit in American history books for "beating" yellow fever, Reed had fully credited Dr. Finlay with the discovery of the yellow fever vector, and how it might be controlled. Dr. Reed often cited Finlay's papers in his own articles and also gave him credit for the discovery in his personal correspondence. The acceptance of Finlay's work was one of the most important and far-reaching effects of the Walter Reed Commission of 1900. Applying methods first suggested by Finlay, the United States government and Army eradicated yellow fever in Cuba and later in Panama, allowing completion of the Panama Canal. While Dr. Reed built off of the research of Carlos Finlay, historian François Delaporte notes that yellow fever research was a contentious issue, and scientists, including Finlay and Reed, became successful by building off of the work of less prominent scientists, without giving them the credit they were due. Regardless, Dr. Reed's research was essential in the fight against yellow fever and he should receive full credit for his use of the first type of medical consent form during his experiments in Cuba. The Rockefeller Foundation’s International Health Board (IHB) undertook an expensive and successful yellow fever eradication campaign in Mexico during 1920-1923. The IHB gained the respect of Mexico’s federal government because of the success. The eradication of yellow fever strengthened the relationship between the US and Mexico, which had not been very good in the past. The eradication of yellow fever was a major step toward better global health.

In 1927, scientists isolated the yellow fever virus in West Africa, which led to the development of two vaccines in the 1930s. The vaccine 17D was developed by the South African microbiologist Max Theiler at the Rockefeller Institute. This vaccine was widely used by the U.S. Army during World War II. Following the work of Ernest Goodpasture, he used chicken eggs to culture the virus and won a Nobel Prize in 1951 for this achievement. A French team developed the vaccine FNV (French neurotropic vaccine), which was extracted from mouse brain tissue but, since it was associated with a higher incidence of encephalitis, after 1961 FNV was not recommended. 17D is still in use and more than 400 million doses have been distributed. Little research has been done to develop new vaccines. Some researchers worry that the 60-year-old technology for vaccine production may be too slow to stop a major new yellow fever epidemic. Newer vaccines, based on vero cells, are in development and should replace 17D at some point.

Using vector control and strict vaccination programs, the urban cycle of yellow fever was nearly eradicated from South America. Since 1943 only a single urban outbreak in Santa Cruz de la Sierra, Bolivia has occurred. But, since the 1980s, the numbers of yellow fever cases have been increasing again and A. aegypti has returned to the urban centers of South America. This is partly due to limitations on available insecticides, as well as habitat dislocations caused by climate change, and partly because the vector control program was abandoned. Although no new urban cycle has yet been established, scientists fear that this could happen again at any point. An outbreak in Paraguay in 2008 was feared to be urban in nature, but this ultimately proved not to be the case.

In Africa, virus eradication programs have mostly relied upon vaccination. These programs have largely been unsuccessful, since they were unable to break the sylvatic cycle involving wild primates. With few countries establishing regular vaccination programs, measures to fight yellow fever have been neglected, making the virus a dangerous threat to spread again.


Yellow Fever Countries:

Africa

Angola

Benin

Burkina Faso

Burundi

Cameroon

Central African Republic

Chad

Congo, Republic of the

Côte d’Ivoire

Democratic Republic of

the Congo (DRC)

Equatorial Guinea

Ethiopia

Gabon

The Gambia

Ghana

Guinea

Guinea-Bissau

Kenya

Liberia

Mali

Mauritania

Niger

Nigeria

Rwanda

Sierra Leone

São Tomé and Principe

Senegal

Somalia

Sudan

Tanzania

Togo

Uganda

Zambia

Central and South America

Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Panama, Paraguay, Peru,Suriname,TrinidadandTobago,Venezuela.