Venezuelan Hemorrhagic Fever Often Mistaken for Dengue

ABSTRACT & COMMENTARY

Synopsis: Venezuelan hemorrhagic fever, caused by Guanarito virus (an arenavirus) and transmitted by rodents, is readily mistaken for dengue fever.

Source: de Manzione N, et al. Venezuelan hemorrhagic fever: Clinical and epidemiological studies of 168 cases. Clin Infect Dis 1998;26:308-313.

De manzione and colleagues in venezuela and the United States evaluated 165 cases of Venezuelan hemorrhagic fever (VHF) identified since the initial discovery of this disease and its etiologic agent, Guanarito virus, in 1989. Sixty-six (40%) of the cases were confirmed by viral isolation and/or seroconversion. The remaining cases, classified as probable VHF, had a compatible clinical picture and epidemiological history.

All the cases occurred in persons living in or having other epidemiological association with an approximately 9000 square kilometer area in portions of Portuguesa State and adjacent regions of Barinas State in Venezuela, a tropical region with heavy seasonal rainfall. The endemic area is reported to correlate closely with areas in which Guanarito virus can be isolated from wild rodents.

Cases of VHF occurred throughout the year, but 53% were identified during November through January. There also appeared to be an approximately 36-month cycle of VHF activity.

Forty-seven (71%) patients were male. The mean age of confirmed cases was 27.6 years (range, 5-79 years). All patients were thrombocytopenic (mean platelet count, 632,000/mm3; range, 10,000-140,000/mm3), 92.7% were febrile, and 85.7% were leukopenic (mean WBC, 2500/mm3; range, 800-6600/mm3). The illness was usually gradual in onset, with progressive increase in severity. The correct diagnosis was initially considered in only six (10.7%) of the 56 patients who were hospitalized. Dengue or dengue hemorrhagic fever was the admitting diagnosis in 15 (27%) of those hospitalized. The fatality rate in both confirmed and probable cases was 33.3%.

COMMENT BY STAN DERESINSKI, MD, FACP

The clinical presentation and laboratory findings in patients with VHF are similar to those observed in patients with other hemorrhagic fevers caused by the other four arenaviruses. (See Table.) A sixth arenavirus, lymphocytic choriomeningitis virus, is not a cause of hemorrhagic fever. All the arenaviruses infect rodents.

Table

Arenaviruses Causing Hemorrhagic Fever in Humans*

    Virus Disease

    Lassa Lassa fever

    JuniArgentine hemorrhagic fever

    Machupo Bolivian hemorrhagic fever

    Guanarito Venezuelan hemorrhagic fever

    Saba Sao Paulo hemorrhagic fever

    *Lymphocytic choriomeningitis is caused by an arenavirus not associated with hemorrhagic fever.

Key features of VHF include gradual onset of a febrile illness with sore throat, headache, myalgia, and other non-specific symptoms. Conjunctivitis, lymphadenopathy, and facial edema may occur. Leukopenia and thrombocytopenia are almost universally present, and proteinuria is common. VHF cannot be clinically distinguished initially from dengue fever, except in those dengue patients who eventually develop a maculopapular skin eruption-a finding not described in any of these patients with VHF. Patients with VHF are often febrile for as long as 8-12 days-a finding not usually seen in dengue fever.

Thrombocytopenia was universal in the cases described here, with platelet counts as low as 10,000/mm3 at the time of hospitalization. There was no relationship between initial platelet count and outcome. In contrast, recent seizures or observed seizures at the time of admission were associated with a very poor outcome-16 (72.7%) of 22 died.

Despite the fact that most patients were not placed in isolation, no secondary cases involving health care workers were identified in this series. The wife of a patient died of a VHF-like illness 19 days after her husband was hospitalized, but no diagnostic studies were performed. Secondary cases of patients or staff of Lassa and Bolivian hemorrhagic fevers have been reported. No proven effective antiviral therapy is available.

Let us all hope that this virus remains confined to this relatively small area of the central plains of Venezuela-or, better, that it permanently disappears.