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Biomedical subjects

M J Frigerio

Publications and source records attributed to M J Frigerio.

At least 19 recordsLinked to original sources
PubMed1985

Attenuated Junin virus infection in Callithrix jacchus.

Twenty marmosets, male Callithrix jacchus, were used during this study. Fifteen of the marmosets were inoculated with 5,000 TCID50 of the attenuated XJC13 strain of Junin virus by intramuscular route and five were left as uninoculated controls. Animals were observed for a 420-day period. In order to carry out virologic, hematologic, serologic, and histologic studies the animals were bled and/or killed at different days post infection(pi). Results obtained showed that the attenuated strain produced an infection with no mortality or signs of illness. There was only a slight loss of weight at 18-40 days pi, which was soon recovered. Viremia was present from day 6 to 22, titers peaking at 4.0 log. Viral spread was limited to the lungs, spleen, lymph nodes, and bone marrow in the animal killed on day 14. No virus was found in the organs of the animal killed on day 23, and neither hematologic alterations nor pathologic lesions were seen in these monkeys except for ganglionar hypertrophy with immunoblast proliferation. Antigen was detected by immunofluorescence (IF) in lymph nodes, spleen, adrenals, lungs and brain. Neutralizing antibodies were detected from the third week onward. Protection conferred by the XJC13 strain proved effective when XJC13-inoculated monkeys were challenged with 1,000 TCID50 of the pathogenic XJ strain at days 60 or 380 pi, while normal controls died. When viral persistence was searched for on days 370, 390, and 420 pi, no infectious virus was detected, but viral antigen was seen in certain organs, which, however, lacked tissue damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Nasal and intrathalamic inoculations of primates with Tacaribe virus: protection against Argentine hemorrhagic fever and absence of neurovirulence.

Callithrix jacchus marmosets were inoculated by different routes with two stocks of Tacaribe virus, one from suckling mouse brain and another from human diploid MRC5 cells. All 12 primates inoculated by nasal route developed neutralizing serum antibodies without any clinical signs. All 6 primates receiving the mouse brain-Tacaribe virus were protected against lethal challenge with pathogenic XJ strain of Junin virus, while protection was also conferred in 4 out of 6 primates receiving the diploid cell-Tacaribe virus stock. Intramuscular (i.m.) inoculation also elicited antibodies and conferred protection to 4 primates receiving the diploid cell-virus stock. Intrathalamic (i.t.) inoculation of mouse brain-virus stock caused no clinical signs or histopathologic changes in groups of 3 primates each examined on days 33 and 90 post-infection (p.i.). All primates developed antibody response, but no virus could be detected in their brain. Thus, Tacaribe virus proved harmless and immunogenic in Callithrix jacchus and protected most marmosets against challenge with the lethal XJ strain of Junin virus.

Administration, Intranasal↗
PubMed1983

Alteration of blood coagulation and complement system in neotropical primates infected with Junin virus.

The neotropical primate Callithrix jacchus infected with Junin virus presented an acute disease with hematological and neurological manifestations and died 17 to 24 days after infection. This picture is similar to that of human Argentine hemorrhagic fever (AHF). Blood coagulation and complement studies were performed in ten C jacchus animals inoculated with 10(3) TCID50 of Junin virus, the prototype pathogenic XJ strain. Four monkeys were used as normal controls. Infected monkeys and normal controls were bled to death on days 7, 14, 17, and 21. A progressive decrease in the number of platelets was found after day 7 of infection. On day 21, the last monkey had a value of 24,000/microliters. The levels of blood clotting factors did not change until day 17, when a shortened partial thromboplastin time activated with Kaolin (PTTK) (36 sec) and increased factors VIII (192.2%) and VII-X (266.6%) were found. On day 21, the PTTK was prolonged (50.7 sec) and factors II, V, and VIII, were decreased. Thrombin time was found prolonged from day 14 onward. Fibrinogen and fibrin degradation products (FDPs) were increased on days 17 (754 mg/dl and 9.2 microliters/ml) and 21 (457 mg/dl and 29.4 micrograms/ml). No changes in the levels of alpha 2 macroglobulin were observed. Complement hemolytic levels were found to be low on day 7 (58.3 UCH50, increased on day 14 (165.1), and within normal range at the end of infection (107.2). C3 levels showed a similar pattern. The bone marrow was active and hypercellular, and the number and morphology of megakaryocytes were normal in all but one of infected animals. The results of blood clotting suggest a limited activation. The complement system presented a profile of activation followed by a rebound phenomenon. The activation of complement appeared ten days before the alteration of the clotting system was evident.

Animals↗
PubMed1983

Junin virus infection of Callithrix jacchus: pathologic features.

Infection of Callithrix jacchus, a New World primate, with the prototype strain of Junin virus produced a severe disease. The animals developed multifocal hemorrhages and characteristic microscopic lesions such as meningoencephalitis, interstitial pneumonia, lymphocytic depletion of lymphatic tissue, hepatocytic necrosis, and a variable decrease in bone marrow cellularity. High virus concentrations correlated with lesions, and with the presence of viral antigenic determinants as revealed by immunofluorescent methods. With the exception of central nervous system damage, the morphological features and immunohistochemical and viral findings were similar to those recorded in human Argentine hemorrhagic fever.

Animals↗
PubMed1983

[Detection of laboratory infections caused by Junín virus using the neutralization and immunofluorescence technics comparatively].

To study Junin virus infection among laboratory workers and to compare immunofluorescence and neutralization tests, blood samples were taken from 48 individuals, of which 42 were considered high risk personnel. None of the 16 low risk workers exhibited antibodies. Neutralizing antibodies were detected in 15 high risk laboratory workers. Nine of the latter were already known to carry antibodies from a previous survey in 1978. Titers detected were either at previous levels or slightly higher. Of the remaining 6 out of the 15 positive cases, 3 showed mild clinical and subclinical infection, equivalent to a 12% incidence rate over the 1978-1980 period. An adequate correlation was observed between neutralization and immunofluorescence test: 66.6% for both positive tests and 97.1% for both negative tests. Although the immunofluorescence test ies easier to perform the neutralization test appears to be more reliable clinically. The overall prevalence rate of neutralizing antibodies among non-vaccinated personnel was almost 19%, which warns against the health hazard involved in Junin virus handling.

Antibodies, Viral↗
PubMed1983

[Infection of New World primates with Junín virus. IV. Aotus trivirgatus].

Owl monkeys (Aotus trivirgatus) were inoculated with XJ, a pathogenic strain of Junin virus, seeking new animal models for Argentine Hemorrhagic Fever. Nine monkeys were inoculated intramuscularly with 30 or 300,000 TCID50 of junin virus. Hematological and virological studies showed no alteration in blood elements such as red cell, reticular cell and platelets, up to 28 days after inoculation. Hemoglobin and hematocrit determinations also remained constant. However, significant neutropenia was seen at day 11 and minimal viremia was detected in some animals during the second and third week post-inoculation. No clinical or behavioral modifications were observed during the eighty-days observation period. Non-specific necropsy findings included pyelonephritis, pneumonitis, liver abscess and eosinophilic spleen infiltrate. All of these findings seem to be unrelated to Junin virus inoculation. No virus was present in organs of animals killed 29, 57 or 85 days post-inoculation. All nine owl monkeys developed serum neutralizing antibodies by day 22. It is concluded that the owl monkey suffers a subclinical infection when inoculated with Junin virus, similar to that seen in other primate species (Saimiri sciureus and Alouatta caraya).

Animals↗
PubMed1982

Cross-protection in nonhuman primates against Argentine hemorrhagic fever.

The susceptibility of the marmoset Callithrix jacchus to Tacaribe virus infection was investigated to perform cross-protection studies between Junin and Tacaribe viruses. Five marmosets inoculated with Tacaribe virus failed to show any signs of disease, any alterations in erythrocyte, leukocyte, reticulocyte, and platelet counts or any changes in hematocrit or hemoglobin values. No Tacaribe virus could be recovered from blood at any time postinfection. Anti-Tacaribe neutralizing antibodies appeared 3 weeks postinfection. The five Tacaribe-infected marmosets and four noninfected controls were challenged with the pathogenic strain of Junin virus on day 60 post-Tacaribe infection. The former group showed no signs of disease, no viremia, and no challenge virus replication, whereas the control group exhibited the typical symptoms of Argentine hemorrhagic fever, high viremia, and viral titers in organs. Soon after challenge, the Tacaribe-protected marmosets synthesized neutralizing antibodies against Junin virus. These results indicate that the marmoset C. jacchus can be considered an experimental model for protection studies with arenaviruses and that the Tacaribe virus could be considered as a potential vaccine against Junin virus.

Animals↗
PubMed1982

Junin virus infection of Calithrix jacchus: haematological findings.

Haematological changes produced by experimental Junin virus infection of a platyrrhine monkey, Callithrix jacchus were studied. Normocytic and normochromic anaemia appeared after 7 days post infection (p. i.), and increased steadily until day 21 p. i. Reticulocytes and circulating erythroblasts were elevated during the anaemia, reached a peak on day 7 p. i., and disappeared later. Platelets and leukocytes showed a significant decrease from days 14 and 18 p. i., respectively. These alterations could be attributed to the damage of bone marrow and lymphatic tissue.

Animals↗
PubMed1981

Cell-mediated immunity and lymphocyte populations in experimental Argentine hemorrhagic fever (Junín Virus).

Guinea pigs infected with the XJ prototype strain of Junín virus reproduce the main features of Argentine hemorrhagic fever, showing hemorrhages, leukothrombocytopenia, and focal lymphoid tissue necrosis. Viral lymphotropism is shown by the presence of viral antigens, severe cytopathic effect, and high virus titers in lymphoid organs. A pronounced depression of humoral immune response to sheep erythrocytes as well as to the virus is described. This study was carried out to determine whether cellular immune response was also modified and which cell populations were affected. Delayed hypersensitivity skin reaction to purified protein derivative was found to be markedly depressed after infection. A noticeable decrease in both percentages and absolute T lymphocyte numbers, detected by E rosettes, in spleen and lymph nodes, together with a low absolute T cell number in peripheral blood, were observed. Total cell counts in spleen, lymph nodes, and peripheral blood were also reduced. On the contrary, no modification in percentages of B lymphocytes, as measured by EAC rosettes, was found. These results indicate that cell-mediated immunity is markedly impaired in guinea pigs infected with the XJ strain of Junín virus. Its relationship with the pathogenesis of the disease is discussed.

Animals↗
PubMed1980

Serological survey to detect subclinical Junín virus infection in laboratory personnel.

Serological survey for detecting subclinical infections with Junín virus, the etiological agent of Argentine hemorrhage fever, was carried out in a group of 107 individuals working in laboratories where this virus was handled. The group was divided into high risk and low risk personnel according to the degree of exposure to the virus. Neutralizing tests were performed in Vero cell cultures to detect circulating antibodies. Results were evaluated comparatively with those obtained in a previous survey. This study shows that among high risk personnel three out of 52 developed neutralizing antibodies (NA) against Junín virus; one of them had a mild clinical illness, and the other two showed no overt disease during this period. No one among the low risk group developed NA against Junín virus.

Antibodies, Viral↗
PubMed1979

Argentine hemorrhagic fever: a primate model.

Experimental Junin virus infection of a New World primate, Callithrix jacchus, was evaluated. The virus produced anorexia, loss of weight, thrombocytopenia, leukopenia, and hemorrhagic and neurological symptoms and terminated in death. Virus was recovered from urine, blood samples and all tissues taken at autopsy. These preliminary observations show that several aspects of the experimental disease in C. jacchus are quite similar to severe natural Argentine hemorrhagic fever of man.

Animals↗
PubMed1977

Junín virus infection of guinea pigs: electron microscopic studies of peripheral blood and bone marrow.

Thin sections of peripheral white blood cells and samples of bone marrow from guinea pigs infected with Junín virus were examined by electron microscopy. In peripheral blood cells, 40% of the granulocytes showed cytoplasmic lysis seven days after viral infection. After day 11 up to 80% of these cells showed morphological alterations. However, no intra- or extracellular viral particles were detected in these samples. Microscopy of bone marrow preparations revealed that 10% of the cells were altered five days after infection, and approximately 50% were affected after nine days. At this stage the megakaryocyte channels were seen to contain pleomorphic particles with a mean diameter of 80-100 nm. These particles had a unit membrane envelope and internal dense granules similar to those observed during other arenavirus infections. Therefore, it is suggested that the effect of Junín virus upon megakaryocytes may be a factor responsible for the acute thrombocytopenia observed in Argentine hemorrhagic fever.

Animals↗