Yellow Fever Medication
- Author: Mary T Busowski, MD; Chief Editor: Mark R Wallace, MD, FACP, FIDSA more...
Prior to the development of a vaccine, passive immunization was utilized in the prevention and management of yellow fever. This posed many challenges because of difficulty in obtaining sufficient amounts of human serum and subsequent serum sickness; its use was discontinued in 1936.
Present day supplies of intravenous immunoglobulin (IVIG) have been found to contain high titers of yellow fever antibodies. In 2000, an unpublished case of a patient being treated with IVIG to prevent illness prior to a trip to the Amazon was reported. Vaccination was contraindicated in this individual, who had chronic lymphatic leukemia. Despite this event, no published reports exist of off-label use of IVIG in the treatment of yellow fever.
Currently, no approved antiviral drug against yellow fever is available. To date, nonclinical testing of antiviral agents has yielded modest results. Ribavirin, given at high doses to hamsters challenged with yellow fever, has been shown to reduce mortality when administered as late as 120 hours after infection. Interferon-α has also been found to reduce mortality when administered to monkeys with yellow fever; however, it was only effective when given within 24 hours of infection. These findings suggest that antiviral therapies may only be effective early in the course of disease, when clinical symptoms are nonspecific and indistinguishable from other viral infections.
Trials by Julander et al involving an active carboxamide drug [AT-1106 (2,4-dihydro-3-oxo-4-β-D-ribofuranosyl-2-pyrazinecarboxamide)] have been effective in hamsters when treatment started on day 4, after the development of liver infection.[12, 26] Ongoing research and advances show promise for the future.
Adjunctive measures include nonhepatotoxic antipyretics to reduce fever and pain and an H2-receptor antagonist to prevent gastric bleeding. Use of heparin for documented cases of DIC is controversial. Additionally, the use of stress-dose corticosteroids is currently under investigation. Avoid drugs that act centrally, including phenothiazines, barbiturates, and benzodiazepines, because they may precipitate or aggravate encephalopathy. Avoid drugs dependent on hepatic metabolism; in cases of reduced renal function, medications should be renally dosed.
The yellow fever vaccine has been regarded as one of the safest and most effective vaccines in use. Nonetheless, the live-attenuated 17D vaccine has been shown to cause wild-type disease in a subset of patients. Between 1952 and 1959, 15 cases of postvaccination encephalitis were reported after administration of vaccine ; since 1945 a total of 28 cases have been reported. Sixteen of these cases occurred in infants younger than 6 months. This resulted in the restriction of vaccine use in children younger than age 6 months and in limited use in patients aged 6-9 months.
The syndrome of YEL-AND is characterized by fever, headache, and focal or generalized neurologic dysfunction. Symptomatic onset ranges from 4-23 days after vaccination. In addition to encephalitis, cases of disseminated encephalomyelitis and Guillain-Barré syndrome have been reported. Case- fatality rates are less than 5%; most individuals recover from YEL-AND without sequelae.[3, 22]
YEL-AVD is characterized by fever, jaundice, and multiorgan system failure similar to the wild-type strain. Symptoms begin 2-5 days after immunization; they are usually mild but can be fatal. As of August 2006, more than 30 cases of YEL-AVD had been described worldwide; it has occurred only in nonimmune, first-time vaccinees. Unlike YEL-AND, YEL-AVD has been reported primarily in individuals of advanced age.
The proposed cause of vaccine-associated disease is an unsuited host response to the live-attenuated 17D vaccine. Individuals younger than age 6 months and those older than age 60 years, persons with a history of thymic disease (eg, DiGeorge syndrome, thymomas, and post-thymectomy), and those with a cell-mediated immunodeficiency status (eg, cancer, transplant, human immunodeficiency virus [HIV]) are all considered to be at a greater risk of developing YEL-AND and YEL-AVD with its subsequent sequelae. A careful medical history to exclude the above should be obtained before the vaccine is administered.
The live attenuated virus (17D) vaccine was created by serial passages of yellow fever virus through chick and mouse embryo cells. Dr. Max Theiler of the Rockefeller Institute developed this vaccine in 1937. Since 1945, more than 200,000,000 doses have been administered.
The WHO, United Nations Children's Fund (UNICEF), and the World Bank have recommended that yellow fever vaccine be added to the routine Expanded Program on Immunization in developing nations. However, poor financing remains a problem and a major reason for low vaccination rates among residents of endemic areas. In the United States, the yellow fever vaccine is available at designated state health departments and selected travel clinics.
Up-to-date information on yellow fever vaccination and travel requirements may be obtained by contacting Health Information for Travelers, Centers for Disease Control and Prevention, Atlanta, GA 30333, fax (404) 332-4265, document number 220022#, phone (404) 332-4559.
This vaccine should be administered to residents of and travelers to endemic areas. The seroconversion rate for adults and children receiving the vaccine is 99%. Protective antibodies form within 7-10 days, and protection lasts for at least 10 years. The vaccine is safe and effective in asymptomatic adult patients with HIV and CD4 counts of greater than 200/μL. The vaccine appeared ineffective when administered to 1-year-old infants who were HIV positive (CD4 count >200/μL).
Histamine H2 antagonists
These agents are useful as an adjunctive therapy to prevent gastric bleeding. H2-receptor antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents. These are potent inhibitors of all phases of gastric acid secretion. They inhibit secretions caused by histamine, muscarinic agonists, and gastrin.
Famotidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations.
Nizatidine competitively inhibits histamine at the H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations.
Ranitidine competitively inhibits histamine at the H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations.
Treatment of yellow fever is symptomatic and supportive. Bed rest and mild analgesic-antipyretic therapy often help to relieve associated lethargy, malaise, and fever.
Acetaminophen inhibits the action of endogenous pyrogens on heat-regulating centers. It reduces fever by direct action on the hypothalamic heat-regulating centers, which, in turn, increase dissipation of body heat via sweating and vasodilation.
Aspirin lowers elevated body temperature by vasodilating peripheral vessels, thereby enhancing dissipation of excess heat. It also acts on the heat-regulating center of the hypothalamus to reduce fever.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic activities. Although its exact mode of action not known, ibuprofen appears to inhibit cyclooxygenase activity and prostaglandin synthesis. It may inhibit lipoxygenase, leukotriene synthesis, lysosomal enzyme release, neutrophil aggregation, and various cell-membrane functions.
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