Rift Valley Fever

 

a. Clinical Syndrome.

(1) Characteristics. Rift Valley Fever (RVF) is a viral disease caused by RVF virus. The virus circulates in sub-Saharan Africa as a mosquito-borne agent. Epizootics occur when susceptible domestic animals are infected, and because of the large amount of virus in their serum, amplify infection to biting arthropods. Deaths and abortions among susceptible species such as cattle and sheep constitute a major economic consequence of these epizootics, as well as providing a diagnostic clue and a method of surveillance. Humans become infected by the bite of mosquitoes or by exposure to virus-laden aerosols or droplets. Although disease may occur during an unexceptional rainy season, outbreaks are typically associated with very high densities of arthropod vector populations that may occur during heavy and prolonged rains or in association with irrigation projects. During epidemics the virus may be transmitted by many species of mosquitoes; its potential for introduction into areas with susceptible livestock and dense mosquito populations is believed to be high, as exemplified by a major epidemic in the Nile valley in 1977-79. The human disease appears to be similar whether acquired by aerosol or by mosquito bite. A biological warfare attack, most likely delivered by aerosol, would be expected to elicit the rather specific spectrum of human clinical manifestations and to cause disease in sheep and cattle in the exposed area. If disease occurred in the absence of heavy vector populations or without domestic animals as amplifiers of mosquito infection, a BW attack would also be a likely cause. Domestic animals are probably susceptible to aerosol infection or could be covertly infected to initiate an epidemic which might propagate itself by the usual means.

(2) Clinical Features. The incubation is two to five days and is usually followed by an incapacitating febrile illness of similar duration. The typical physical findings are fever, conjunctival injection, and sometimes abdominal tenderness. A few petechiae or epistaxis may occur. A small proportion of cases (approximately one percent) will progress to a viral hemorrhagic fever syndrome, often with associated hepatitis. These cases may manifest petechiae, mucosal bleeding, icterus, anuria, and shock; mortality in this group is roughly 50 percent. A similar proportion will develop clinically significant ocular changes; macular lesions associated with retinal vasculitis, hemorrhage, edema, and infarction. Ocular manifestations begin after the patient enters convalescence from acute illness and about half of the patients will have permanent visual defects. A small number of infections will lead to a late encephalitis. After apparent recovery from a typical febrile illness, the patient develops fever, meningeal signs, obtundation, and focal defects. These patients may die or often have serious sequelae.

b. Diagnosis.

(1) Differential Diagnosis. The clinical syndrome in an individual is not pathognomonic, but the occurrence of an epidemic with febrile disease, hemorrhagic fever, eye lesions, and encephalitis in different patients would be characteristic of RVF.

(2) Routine Laboratory Findings. In acute uncomplicated disease, there is often a transient leucopenia, but liver and clotting function tests are normal. In hemorrhagic fever, abnormalities of hepatic and coagulation tests are proportional to severity of disease. Disseminated intravascular coagulation may be present. Patients with encephalitis have up to several hundred cells/mm in CSF, predominantly lymphocytes.

(3) Specific Laboratory Diagnosis. Demonstration of viral antigen in blood by ELISA is rapid and successful in a high proportion of acute cases of uncomplicated disease or hemorrhagic fever. IgM antibodies appear with cessation of viremia and are present when ocular or central nervous system (CNS) manifestations are noted. False positive reactions may occasionally be noted in patients with multiple sandfly fever infections. Encephalitis patients have IgM and IgG antibodies in CSF. A proportion of cases should be studied by classical means such as determination of neutralizing antibodies and virus isolation. Wide-scale surveillance is readily accomplished by simultaneous determination of IgG (infection or vaccination at an indeterminate time) and IgM (recent exposure) antibodies in human or domestic animal blood.

c. Therapy. In hemorrhagic fever, supportive therapy may be indicated for hepatic and renal failure, as well as replacement of coagulation factors. The virus is sensitive to ribavirin in vitro and in rodent models. No studies have been performed in human or the more realistic monkey model to ascertain whether administration to an acutely ill patient would be of benefit. It would be reasonable to treat patients with early signs of hemorrhagic fever with intravenous ribavirin (30 mg/kg followed by 15 mg/kg q 6 hr for 4 days and 7.5 mg/kg q 8 hr for 6 days). This regimen is safe and effective in hemorrhagic fevers caused by some viruses, although a reversible anemia may appear. Therapy may be stopped 2-3 days after improvement begins or antibody appears. Penetration of ribavirin into the CNS is slow and perhaps limited, but in the absence of any other specific therapy, the drug might be used in ocular and encephalitic cases.

d. Prophylaxis. Avoidance of mosquitoes and contact with fresh blood from dead domestic animals and respiratory protection from small particle aerosols are the mainstays of prevention. An effective inactivated vaccine is available in limited quantities. The dose is one ml given sc on days 0, 7, and 28; exact timing is not critical. Protective antibodies begin to appear within 10-14 days and last for a year, at which time a one ml booster should be given. A single injection probably is not protective, but two inoculations may provide marginal short-term protection. Ribavirin prophylaxis (400 mg q 8 hr) of a related sandfly fever virus was successful, but the dose used might be expected to produce anemia and other effects in some recipients. The utility of lower doses has not been determined. Interferon alpha in doses not expected to be reactogenic in humans (5 x 103 – 5 x 104 U/kg daily) is preventive in monkeys and might be considered for post-exposure prophylaxis in humans.

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