Crimean-Congo Hemorrhagic Fever.

a. Clinical Syndrome.

(1) Characteristics. Crimean-Congo hemorrhagic fever (CCHF) is a viral disease caused by CCHF virus. The virus is transmitted by ticks, principally of the genus Hyalomma, with intermediate vertebrate hosts varying with the tick species. The disease was first recognized in the Crimea, but occurs over most of Africa, the Middle East, the Balkans, the former USSR, and eastern China. Little is known about variations in the virus properties over the huge geographic area involved. Humans become infected through tick bites, crushing an infected tick, or at the slaughter of viremic livestock. (Domestic animals become infected but do not have significant disease.) The spread of disease within hospitals has been documented with this virus and poses a potentially significant problem. Even in epidemics, cases do not show narrow clustering and person-to-person spread is rare. CCHF would probably be delivered by aerosol if used as a BW agent.

(2) Clinical Features.

(a) Typical cases present with sudden onset of fever and chills 3-12 days after tick exposure. Flushing, conjunctival injection, and mild hypotension may be present. After 2-3 days, perhaps with a temporary remission of fever, the patient develops bleeding manifestations such as petechiae, ecchymoses, oozing from puncture sites, melena, hematuria, and gastrointestinal (GI) hemorrhage. Crimean-Congo hemorrhagic fever may cause quite severe ecchymoses and extensive GI bleeding. There is severe headache, lumbar pain, nausea and vomiting, delirium, and prostration. Fatal cases are associated with extensive hemorrhage, coma, and shock. Other common physical findings are epigastric tenderness, modest hepatomegaly, and less frequently icterus.

(b) Mortality among cases recognized as hemorrhagic fever is 15-30%. Convalescence in survivors is prolonged with asthenia, dizziness, and often hair loss. Milder clinical disease occurs in an unknown proportion of infections. There may be geographic variations, possibly related to viral strain differences.

b. Diagnosis.

(1) Differential Diagnosis. Thrombocytopenia and elevated aspartate aminotransferase (AST) may provide a clue to suggest CCHF in the febrile patient seen early in the course of infection. Other viral hemorrhagic fevers, meningococcemia, rickettsial diseases, and similar conditions may resemble full-blown CCHF. Particular care should be taken in the case of massive GI bleeding not to confuse CCHF with surgical conditions.

(2) Routine Laboratory Findings. Leukopenia, thrombocytopenia, and elevated AST are all seen early. Abnormal coagulation tests are common and usually indicate disseminated intravascular coagulation (DIC). Platelets <20,000/ml, APT >260 sec, or AST >200U/ml carry a poor prognosis.

(3) Specific Laboratory Diagnosis. Most fatal cases and half the others will have detectable antigen by rapid enzyme-linked immunosorbant assay (ELISA) testing of acute serum samples. IgM ELISA antibodies occur early in recovery. IgG ELISA and fluorescent antibodies also show rising titers. Virus isolation in suckling mice is usually successful from acute sera.

c. Therapy.

(1) Supportive therapy with replacement of clotting factors is indicated. Crimean-Congo hemorrhagic fever virus is sensitive to ribavirin in vitro and clinicians have been favorably impressed in uncontrolled trials. Patients should be treated with intravenous ribavirin (30 mg/kg followed by 15 mg/kg q 6 h for 4 days and 7.5 mg/kg q 8 h for 6 days). Mild reversible anemia may occur. Immune globulin has also been recommended but is available only in Bulgaria.

(2) Because of several well-defined outbreaks within hospitals, protective measures for medical personnel are an issue. The weight of evidence points to large droplets or fomites as the mediators of transmission and so strict barrier nursing is indicated and probably sufficient for the care of naturally acquired disease. The virus is aerosol-infectious and additional precautions (for example, respirators) might be considered in a biological warfare setting.

d. Prophylaxis.

(1) Although there is little field experience and no definitive data on efficacy, the sensitivity of the virus to ribavirin and the severity of disease suggests that prophylaxis of high-risk exposures is indicated. Persons with percutaneous exposure to contaminated needles or instruments and those exposed directly to fresh blood from CCHF patients should receive 400 mg ribavirin po tid (three times daily) for one day and then continue with 400 mg po tid for 7 days after the last exposure. If more than 48 hours have elapsed after the first such exposure, 30 mg/kg should be given intravenous (IV) followed by three IV doses of 15 mg/kg at 8 hourly intervals; then continue with 400 mg po q 8 hours. If there is GI intolerance, the 400 mg oral dose can be substituted with 180 mg IV. Monitoring for anemia is suggested.

(2) In the case of a suspected biological attack, ribavirin could be considered for prophylaxis, but there is insufficient information to make a firm recommendation for dosing. Use of 400 mg tid may result in mild to modest anemia in some recipients, GI intolerance in a small proportion, and the drug is embryopathic in rodents; there are unresolved issues of reversible testicular damage in rodents. An inactivated mouse-brain vaccine is used in Bulgaria, but there is no general experience with this product.

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