A prospective, randomized, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin (loading dose of 33 mg/kg, 16 mg/kg every 6 h for 4 days, and 8 mg/kg every 8 h for 3 days) was conducted in 242 patients with serologically confirmed hemorrhagic fever with renal syndrome (HFRS) in the People's Republic of China. Mortality was significantly reduced (sevenfold decrease in risk) among ribavirin-treated patients, when comparisons were adjusted for baseline risk estimators of mortality (P = .01; two-tailed). HFRS typically consists of five consecutive but frequently overlapping clinical phases. Only occurrence of oliguric phase and hemorrhage was associated with severity of clinical disease in the placebo group. Ribavirin therapy also resulted in a significant reduction in the risk of entering the oliguric phase and experiencing hemorrhage. The only ribavirin-related side effect was a well-recognized, fully reversible anemia after completion of therapy.

No abstract

From October to December 1977, an extensive epizootic occurred in Egypt resulting in abortions and increased mortality in domestic animals, and severe clinical disease with fatalities in man. Rift Valley Fever (RVF) virus was isolated and identified as the causative agent. In humans, acute febrile, encephalitic, ocular and fatal haemorrhagic diseases were documented as resulting from RVF virus infection. A retrospective serological survey indicated RVF was recently introduced into the area. The 1977 epizootic extensively involved five Governorates. In the summer and autumn of 1978, epizootic RVF reappeared in Egypt and spread to previously uninfected areas. Virological, serological and epidemiological studies, and factors related to the spread of RVF are discussed.

Epidemiological factors related to the introduction, spread and maintenance of Rift Valley fever (RVF) virus were studied during the 1977-78 epizootic in Egypt, Culex pipiens is the most ubiquitous and prevalent mosquito species in the Nile Valley and Delta. Isolation of RVF virus from unengorged C. pipiens, and demonstration of laboratory transmission of the virus by this species, strongly implicate it as the chief vector in Egypt. Virus transmission to man also occurs by contamination when handling infected meat and by inhaling natural virus aerosols. Wild rodents apparently do not serve as RVF virus reservoirs. Domestic sheep, cattle, buffaloes, camels, goats, donkeys and dogs act as amplifying hosts. Over 30% of the camels sampled at the southern border of Egypt were serologically positive for antibodies to RVF virus and it appears likely that the virus was introduced into Egypt, either by these animals or by other vehicles from the south.

SUMMARY Ocular manifestations resulting from Rift Valley fever (RVF) virus infection were studied during an extensive RVF epidemic in Egypt during 1977. Colour photography and fluorescein angiography of 7 serologically diagnosed patients showed the commonest manifestations to be macular, paramacular, and/or extramacular retinal lesions, often occurring bilaterally. Haemorrhage and oedema were frequently associated with the lesions, and vasculitis, retinitis, and vascular occlusion were also observed. Patients were monitored during a 6-month convalescence, and, though resorption of the lesions occurred, approximately half the patients experienced permanent loss of visual acuity. Ocular disease was one form of the clinical spectrum of RVF; acute febrile, encephalitic, and fatal haemorrhagic RVF illnesses were also observed during the epidemic.

No abstract

The antigenic relationship of the 31 currently recognized phlebotomus fever group viruses was examined by plaque reduction neutralization test. Although some low-level 0cross-neutralization was observed, each of the viruses was easily differentiated by this method. Rift Valley fever virus was shown to be antigenically related to Candiru, Frijoles, Karimabad and Punta Toro viruses. Naples, Tehran and Toscana viruses were also shown to be closely related. Preliminary results of indirect fluorescent antibody tests indicate that this technique is broadly reacting and less specific than either the complement-fixation or neutralization test for identifying phlebotomus fever group viruses. A discussion follows on some of the difficulties encountered in attempting to classify phleboviruses. Recently published reports" that Rift Valley infection has been demonstrated with seven other fever (RFV) virus is antigenically and biochemi-PF group viruses (Arumowot, Bujaru, Gabek cally related to several viruses in the phlebotomus Forest, Gordil, Karimabad, Saint Floris and Tosfever group (family Bunyaviridae, genus Phle-cana). 8 .9 bovirus) have renewed interest in this little studied In 1975, Tesh et al. 3 described the antigenic group of arthropod-borne viruses. The phlebotorelationship of 22 PF serotypes known at that mus fever (PF) group currently consists of 31 dis-time. By hemagglutination-inhibition (HI) test, trict virus serotypes (Table 1). These agents occur the viruses showed considerable cross-reactivity. 3 in both the Old and New Worlds, and each se-Results of complement-fixation (CF) and plaque rotype appears to have a different geographic disreduction neutralization (PRN) tests were more tribution. 3 In general their natural history is poorspecific, however, allowing clear separation of the ly understood. The majority have been associated various serotypes. 3 Since publication of the aforewith phlebotomine sandflies, 3. 4 but at least three mentioned data, nine additional virus serotypes of the serotypes (Arumowot, Itaporanga and Rift have been included in the PF group. In order to. Valley fever) appear to be mosquito-borne. 3 ' 5 Sevupdate these earlier serologic studies and to de-J en PF group viruses (Alenquer, Candiru, Chagres, termine the antigenic relationship of RVF virus, Naples, Punta Toro, Rift Valley fever and Sicil-cross-neutralization tests were performed on the ian) have been isolated from sick persons.6 31 currently recognized Phlebovirus serotypes. SThree of these agents (Naples, Sicilian and Rift The present paper summarizes this work and also Valley fever) are of proven public health impordescribes preliminary studies on the use of imtance. In addition, serologic evidence of human munofluorescence to identify PF group viruses and antibodies.

An enzyme-linked immunosorbent assay was compared with an indirect fluorescent antibody test for its ability to detect antibodies to the Lyme disease spirochete in sera of naturally infected humans, dogs, and whitefooted mice and experimentally infected Swiss mice. Ninety-five percent of the total 123 sera analyzed reacted similarly in both tests. For 36 human sera, the correlation coefficient (r = 0.47) for logarithmic transformations of indirect fluorescent antibody and enzyme-linked immunosorbent assay titers was significant at P < 0.01. Within each mammalian species, mean titers for indirect fluorescent antibody and enzyme-linked immunosorbent assay antibodies were within threefold. Comparisons of different naturally infected mammals revealed relatively higher average titration endpoints in both tests for patients with Lyme disease. Human sera also had the widest range of titers. Both methods proved satisfactory for serological confirmation of prior spirochetal infections.