Yellow fever overview

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Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Yellow Fever from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Other Diagnostic Studies

Treatment

Medical Therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Yellow fever is an acute viral disease.[1] It is an important cause of hemorrhagic illness in many African and South American countries despite existence of an effective vaccine. The yellow refers to the jaundice symptoms that affect some patients.[2] Yellow fever has been a source of several devastating epidemics. French soldiers were attacked by yellow fever during the 1802 Haitian Revolution; more than half of the army perished due to the disease.[3] Outbreaks followed by thousands of deaths occurred periodically in other Western Hemisphere locations until research, which included human volunteers (some of whom died), led to an understanding of the method of transmission to humans (primarily by mosquitos) and development of a vaccine and other preventative efforts in the early 20th century. Despite the costly and sacrificial breakthrough research by Cuban physician Carlos Finlay, American physician Walter Reed, and many others over 100 years ago, unvaccinated populations in many developing nations in Africa and Central and South America continue to be at risk.[4] As of 2001, the World Health Organization (WHO) estimates that yellow fever causes 200,000 illnesses and 30,000 deaths every year in unvaccinated populations.[5]

Historical Perspective

Yellow fever has had an important role in the history of Africa, the Americas, Europe, and the Caribbean. Scientists believe that yellow fever evolved in Africa around 3,000 years ago. [6] In 1937 Max Theiler working at the Rockefeller Foundation developed a vaccine for yellow fever that gives a ten-year or more immunity from the disease and effectively protects people traveling to affected areas, while at the same time being a means to control the disease.

Pathophysiology

Yellow fever is caused by a single-stranded RNA virus that belongs to the genus Flavivirus. Vectorborne transmission occurs via the bite of an infected mosquito, primarily Aedes or Haemagogusspp. Nonhuman and human primates are the main reservoirs of the virus, with anthroponotic (human-to-vector-to-human) transmission occurring. Humans infected with YFV experience the highest levels of viremia and can transmit the virus to mosquitoes shortly before onset of fever and for the first 3–5 days of illness. Given the high level of viremia, bloodborne transmission theoretically can occur via transfusion or needlesticks.

Causes

Yellow fever virus is caused by an arthropodborne virus of the Flaviviridae family in the genus Flavivirus. Flaviviruses are single stranded ribonucleic acid (RNA) viruses that replicate in the cytoplasm of infected cells. Seven genotypes of yellow fever virus have been identified, two in South America and five in Africa.

Differentiating Yellow Fever from other Diseases

Yellow fever must be differentiated from other diseases that cause fever, diarrhea, dehydration and tachycardia, such as ebola, typhoid fever, malaria, Zika virus, and lassa fever.

Epidemiology and Demographics

Yellow fever occurs in sub-Saharan Africa and tropical South America, where it is endemic and intermittently epidemic. Urban yellow fever occurs periodically in Africa and sporadically in the Americas. In Africa, natural immunity accumulates with age, and thus, infants and children are at highest risk for disease. In South America, yellow fever occurs most frequently in unimmunized young men who are exposed to mosquito vectors through their work in forested areas.

Risk Factors

A traveler’s risk of acquiring yellow fever is determined by various factors, including immunization status, location of travel, season, duration of exposure, occupational and recreational activities while traveling, and the local rate of virus transmission at the time of travel.

Natural History, Complications and Prognosis

Initial symptoms of yellow fever start 3-6 days after the mosquito bite, these include sudden onset of fever, chills, severe headache, back pain, general body aches, nausea and vomiting, fatigue, and weakness. Most people improve after these initial symptoms. However, roughly 15% of people will have a brief period of hours to a day without symptoms and will then develop a more , severe form of yellow fever disease. Possible complications include coma, disseminated intravascular coagulation (DIC), kidney failure, liver failure and shock. The prognosis is good in the majority of patients, infected persons will be asymptomatic or have mild disease with complete recovery.

Diagnosis

History and Symptoms

Patients infected may have no symptoms; if they develop the disease, they can develop symptoms such as fever, muscle pain (with prominent backache), headache, shivers, loss of appetite, and nausea or vomiting. After three or four days most patients improve and their symptoms disappear. Fifteen percent of patients, however, enter a toxic phase within 24 hours. Fever reappears, the patient rapidly develops jaundice and abdominal pain with vomiting. Bleeding occurs and kidney function deteriorates.

Physical Examination

Physical findings include fever, scleral and dermal icterus, hemorrhages (e.g., hematemesis, melena, petechiae, ecchymoses), and epigastric tenderness with or without hepatomegaly.[7]

Laboratory Findings

Multiple laboratory abnormalities can be observed in patients with yellow fever, including leukopenia or leukocytosis, bleeding dyscrasias, thrombocytopenia, increased bilirubin and transaminases. Laboratory diagnosis of yellow fever is generally accomplished by testing of serum to detect virus-specific IgM and neutralizing antibodies. Sometimes the virus can be found in blood samples taken early in the disease.

Other Diagnostic Studies

Treatment

Medical Therapy

There is no antivirals approved for the treatment of for yellow fever, therefore vaccination is important. Treatment is symptomatic and supportive only. Fluid replacement, managing hypotension and transfusion of blood derivates is generally needed only in severe cases. In cases that result in acute renal failure, dialysis may be necessary.

Primary Prevention

The two methods to prevent yellow fever are vaccination and vector control. Yellow fever vaccine is recommended for persons aged ≥9 months who are traveling to or living in areas at risk for yellow fever virus transmission in South America and Africa. Yellow fever vaccine may be required for entry into certain countries. The best way to prevent mosquitoborne diseases, including yellow fever, is to avoid mosquito bites.

References

  1. Schmaljohn AL, McClain D. (1996). Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae). In: Baron's Medical Microbiology (Baron S et al, eds.) (4th ed. ed.). Univ of Texas Medical Branch. ISBN 0-9631172-1-1.
  2. Anker M, Schaaf D; et al. (2000-01-07). "WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases" (PDF). WHO. p. 11. Retrieved 2007-06-11.
  3. Bollet, AJ (2004). Plagues and Poxes: The Impact of Human History on Epidemic Disease. Demos Medical Publishing. pp. pp. 48&ndash, 9. ISBN 188879979X.
  4. Tomori O (2002). "Yellow fever in Africa: public health impact and prospects for control in the 21st century". Biomedica. 22 (2): 178–210. PMID 12152484.
  5. "Yellow fever fact sheet". WHO—Yellow fever. Retrieved 2006-04-18.
  6. "Centers for Disease Control and Prevention (CDC). Yellow Fever: History, Epidemiology and Vaccination Information. (Internet). Atlanta, GA: US Department of Health and Human Services, CDC; 2010".
  7. "CDC Yellow Fever Clinical and Laboratory Evaluation".


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