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Yellow Fever

INFORMATION ABOUT THE DISEASE

Yellow fever is an acute tropical disease prevalent mainly in tropical areas of Africa, Central and South America.

It is caused by an Arbovirus of the Flaviviridae family. First identified in the 17th century as Yellow Fever, it had a major impact in Livorno in 1804, giving rise to "La Cigna" cemetery. Because of the significant risks associated with the disease, Yellow Fever vaccination is mandatory in many countries for travelers from endemic areas. Today, Yellow Fever still poses a serious threat, especially in at-risk areas.

The disease is caused by a positive single-stranded RNA virus that contains the virus genome; it belongs to the Flaviviridae family, genus Flavivirus, to which the Dengue , Zika and Japanese Encephalitis viruses also belong.

Under an electron microscope, the virus appears as a spherical virion about 40 nm (nanometer) in diameter, with an icosahedral pericapsid (the outer wall of the virus), characteristic of Flaviviruses. A lipid envelope derived from the host cell is present, containing two proteins E and M, which are critical for virus access into host cells.

The name ofyellow fever comes from theyellow coloring of the eyes and skin as a result of liver damage caused by the virus. Itis transmitted through the bites of infected mosquitoes, of the genus Aedes (which transmit other diseases such as Zika , Chikungunya and Dengue ) or Haemagogus, during their blood meal in humans. Unlike the anopheles mosquito, the vector of malaria , which is active during nighttime hours, the Aedes mosquito bites during daylight hours.

Mosquitoes live and breed in tropical rainforests, humid and semi-humid environments, as well as around bodies of standing water near human dwellings in the urban setting. Increased contact between humans and infected mosquitoes, particularly in urban areas where people have not been vaccinated for yellow fever, can create major epidemics.

The main vector is Aedes aegypti, whichis found in Africa and South America, but mosquitoes of the genus Haemagogus are also present in the forests of South America. The ability of Aedes aegypti to move to more temperate areas, such as Europe, is currently limited due to its inability to survive temperate winters. This trend may reverse as a result of climate change.

Aedes albopictus is a species of mosquito found throughout most of the world, including Italy where it is commonly called the tiger mosquito. Although less effective than the other Aedes,the tiger mosquito alsocan transmit at least 22 arboviruses, includingYellow Fever, Rift Valley Fever, Dengue , Japanese Encephalitis , West Nile virus, Chikungunya , and Zika.

The virus enters the host cell by a mechanism called endocytosis, which is the process in which the cell engulfs the virus in its cytoplasm, where it can replicate. At that point it can infect other mosquitoes that perform their blood meal in the 2 days prior to symptoms and up to 5 days later (it is not transmissible to other people, however).

The spread of the disease, epidemiologically speaking, can have two cycles:

  • urban cycle: in this cycle the reservoir of the virus is humans; mosquitoes become infected by biting humans during the viremic phase, that is, in the first 3 days of infection. The Aedes aegypti mosquito thus remains infected for life by transmitting the virus during its meal to humans and eggs.
  • sylvatic cycle: in this case, mosquitoes contract the infection from infected monkeys or other primates, which act as reservoirs of the virus. Later, mosquitoes sting humans by infecting them.

Deforestation, climate change, more incursions into forests and jungles for mining and oil extraction, construction, and farmland reclamation are phenomena that increase contacts between humans and mosquitoes responsible for yellow fever virus transmission.

All these factorsamplifying the risk of contracting yellow fever-urbanization, extensive population movements, climate change, and increasing exposure of workers to infected mosquitoes in jungles and forests-are driving thechange in the epidemiology of the virosis.

Want to learn more about it? Read our article Countries at Risk of Yellow Fever.

Yellow fever is endemic in rural and humid areas such as tropical forests. Most cases occurin sub-Saharan Africa and Central and South America, while in Asia the disease has never been detected.

Globally, 42 countries-29 in Africa and 13 in Central and South America-are endemic or have endemic regions for yellow fever. About 50 percent of infected people do not complain of symptoms, which is precisely why the World Health Organization (the WHO) estimates that84,000 to 170,000 people become infected each year and about 29,000 to 60,000 die ( because it is an infection that occurs in rural areas, confirmed figures are always underestimated).

One of the major issues related to yellow fever concerns its transfer outside endemic regions. Occasionally, travelers visiting yellow fever endemic countries may bring the disease to free countries. In order to prevent such importation of the disease, many countries require certification of yellow fever vaccination before issuing a visa, particularly if travelers are from or have visited areas endemic for the disease.

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Symptoms of yellow fever generally appear 3-6 days after the mosquito bite. The infection can be totally asymptomatic, or have mild to very severe courses, becoming fatal in some cases.

The symptoms of the disease can be distinguished into several stages:

  • Onset picture: in the initial phase, symptoms start abruptly with very high fever up to 39-40°C, headache, chills, rachialgia (pain in the spine), nausea and vomiting.
  • The red phase: a few hours after the onset of the first symptoms, the red phase takes over. In this phase, the patient assumes a bright red color to the face, with epistaxis, oliguria (decreased urine output) and persistent fever. It coincides with viremia (the presence of viral particles in the blood) and resolves in 3 days.
  • Apparent remission: which lasts about 24 hours.
  • Yellowphase: the yellow phase appears around the fourth or fifth day of the disease, characterized by the appearance of jaundice (the yellowish discoloration of the skin), hemorrhagic phenomena in various areas of the body and persistent fever, around 40°C .
  • Exitus: the stage in which liver failure occurs, due to cytopathic damage and necrosis of hepatocytes, to which renal failure may also be added. In the intestines, on the other hand, extensive bleeding, melena (presence of stool blood) and vomiting also called "black vomiting" occur.
  • Healing: In some cases, patients make a full recovery after about 12 to 14 days of illness, without significant damage and gaining permanent immunity against the disease.

Especially in the early stages, yellow fever can be confused with other diseases, for example, malaria , dengue , and fulminant viral hepatitis. For this reason, its diagnosis is not always obvious.

For confirmation of the diagnosis it uses to the technique of PCR (Reverse transcriptase-polymerase Chain Reaction), by which one can amplify the viral genome to trace the RNA of the virus. This technique is effective if it is used in the early days of the disease. Serological investigation is done by ELISA testing to detect the presence of IgM-class antibodies, typical of a recent infection, which appear in the first 10 to 14 days of the disease. Further laboratory analysis can eventually show through altered levels of several components.

To date, there is no specific treatment for yellow fever as there is for most infections caused by Flavivirus. Only supportive therapy is given for symptoms such as dehydration, respiratory failure and fever. In cases of bacterial overinfection, antibiotics may be administered.

In endemic areas, it is necessary to isolate the patient so as to avoid mosquito bites, thus blocking the chain of transmission.

Preventive vaccination against yellow fever infectionis the safest and most effective weapon against transmission of the virus.

The vaccine is administered from the age of 9 months, subcutaneously, as it is a live attenuated vaccine. WHO recommends a single dose of the vaccine, as it has been shown to be protective in conferring lifelong immunity.

Side effects are rare, although the risk is greater in individuals over 60 years of age, children under 9 months of age, pregnant women, and immunocompromised individuals. In each case, risks and benefits are evaluated, comparing the risk of contracting the disease compared with the possibility of post-vaccination adverse events.

The yellow fever vaccine has been used for many decades and is safe and affordable. It provides effective immunity against yellow fever within 10 days of vaccination for more than 90 percent of vaccinated persons and within 30 days of vaccination for 99 percent of vaccinated persons.

Travelers to yellow fever endemic areas, in addition to vaccination, should adopt appropriate behaviors to prevent mosquito bites by using repellents with an approved efficacy and pyrethrum-based insecticides on clothing, suitcases, and corners of accommodation to make sure they do not import vectors upon return.

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The information presented is general in nature, is published for general audiences and is not a substitute for the relationship between patient and physician.