Julio I. Maiztegui

Antiviral treatment of argentine hemorrhagic fever

Argentine hemorrhagic fever is a systemic viral disease caused by Junin virus, with a mortality of 15-30% in untreated individuals. Current specific therapy is highly effective in reducing mortality, and consists of the early administration of immune plasma in defined doses of specific neutralizing antibodies per kg of body weight. However, several reasons suggest the need to investigate alternative therapies. Ribavirin, a broad spectrum antiviral agent, is effective in the treatment of other viral hemorrhagic fevers, and the studies done with Junin virus infections to date indicate that this drug may also have a beneficial effect in Argentine hemorrhagic fever.

Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response.

Abstract We investigated immunologic mechanisms and the role of complement in the pathogenesis of Argentine hemorrhagic fever, a disease caused by the Junin virus, a member of the arenavirus group. Total serum complement activity was reduced to 68 per cent of control values in patients with severe or moderate disease (P<0.001). C2, C3 and C5 values were also low (12 to 60 per cent) during the early acute period of the disease. However, serum C4 content was increased to 160 per cent of the control values in the same patients. Total complement activity returned to normal with clinical and laboratory recovery, at the time of detection of antibodies against Junin virus. C1q reactive material was found in four of 19 cases and no relation to the evolution of the disease could be established. These results suggest that immune complexes are not important in the pathogenesis of Argentine hemorrhagic fever, but that activation of the complement system has a role. (N Engl J Med 299:216–221, 1978)

Junin Virus Isolation from Lympho-Mononuclear Cells of Patients with Argentine Hemorrhagic Fever

Detection of viremia was attempted by three different methods in 30 cases of Argentine hemorrhagic fever (AHF). Cocultivation of peripheral blood mononuclear cells (PBMC) with Vero cell monolayers was the most sensitive, detecting Junin virus (JV) in 96% of the cases. Inoculation of whole blood into suckling mice and on Vero cells rendered 53 and 46% of positive isolations, respectively. The results presented suggest that PBMC are infected with JV during the acute period of AHF. JV was isolated with decreasing frequency up to 3 days after treatment with immune plasma, but no virus was recovered from PBMC during early convalescence.

Plasminogen abnormalities in patients with argentine hemorrhagic fever

Plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin and fibrinogen degradation products (FDP) were studied in 45 patients with Argentine hemorrhagic fever. Patients were grouped into: 17 mild, 14 moderate and 14 severe cases. Plasminogen antigen level and functional activity were found to be reduced in the moderate and severe groups, when compared to the results obtained at recovery. The functional activity of alpha 2-antiplasmin was within the normal range, except for a slight decrease on days 10-11, alpha 2-macroglobulin remained normal during the course of illness. alpha 1-antitrypsin also remained normal except on days 10-11, when an increase in the antigen level was noted. FDP titre was normal (less than 10 micrograms/ml) in all patients during the course of disease. Plasminogen decrease was not attributable to liver insufficiency neither to a primary nor secondary fibrinolysis. The decreased antigen and reduced functionality of plasminogen in these patients we believe is related to proteolytic degradation by leukocyte enzymes.

Presence of viral particles in the salivary gland of Calomys musculinus infected with Junin virus by a natural route.

Calomys musculinus, a wild cricetid rodent, is one of the main reservoirs of Junin virus. Six of these animals were infected by being placed in close contact with animals that had been experimentally infected with the virus. They were sacrificed at 10, 15 and 20 months after contact, and their salivary glands were studied by ultrastructural, immunohistochemical and virological methods. Two animals developed chronic viremia and low titers of complement-fixing antibodies. These animals were the only ones that had high viral titers in salivary glands and blood and viral antigen and particles in salivary glands. Although some of the other animals had viremia at the beginning of the experiment, it was absent 5 months later. Complement-fixing antibodies developed in all animals. On the basis of these findings, we assumed that the salivary gland is an important site of viral synthesis and excretion. This type of chronic infection, with persistent viremia and virus shedding, is possibly important for virus perpetuation in nature and transmission to man.