Effect of administration of diethylcarbamazine on murine leukemia virus (Cas-Br-M) infected mice.

Previous studies indicate that decreased serum viral infectivity and viral antigen levels follow oral administration of diethylcarbamazine (DEC) in feline leukemia virus infected cats, even though DEC has not been shown to exhibit in vitro antiviral activity. In this investigation, DEC was given by oral administration or (single dose) IP injection to murine leukemia virus (Cas-Br-M) inoculated mice to permit evaluation of its effect on viral-induced central nervous system disease. The survival of Cas-Br-M inoculated mice receiving DEC in water was significantly prolonged relative to similarly inoculated mice receiving distilled water. Among the Cas-Br-M inoculated mice euthanatized after the study, higher body weights and trend toward less severe brain and splenic lesions were noted in those receiving DEC in drinking water. Given these results, the possible utility of DEC in treatment of retroviral and other infections warrants further study.

New tissue schizontocidal antimalarial drugs.

Over 700 causal prophylactic and radical curative antimalarial drugs have been discovered during the screening of approximately 4000 chemical compounds in rodent and simian malaria models. Causal prophylactic activity in the Plasmodium berghei-rodent model was demonstrated by 10 distinct groups of chemicals: 1) tetrahydrofolate dehydrogenase inhibitors, 2) naphthoquinones, 3) dihydroacridinediones, 4) tetrahydrofurans, 5) guanylhydrazones, 6) analogues of clopidol, 7) quinoline esters, 8) dibenzyltetrahydro-pyrimidines, 9) 6-aminoquinolines, 10) 8-aminoquinolines.Of the causal prophylactic compounds, only the 6- and 8-aminoquinolines were capable of curing persistent exoerythrocytic infections of P. cynomolgi in rhesus monkeys. The 6-aminoquinolines were substantially less active than primaquine.This report describes a series of 4-methyl-5-phenoxy-6-methoxy-8-aminoquinolines, which are potent blood schizontocides and radical curative drugs. The most active member of this series, 4-methyl-5-(3-trifluoromethylphenoxy)-6-methoxy-8-[(4-amino-1-methylbutyl)| amino]quinoline succinate (WR 225448), was 5 times more active than primaquine in curing persistent exoerythrocytic infections of P. cynomolgi in rhesus monkeys.As a blood schizontocide, WR 225448 was effective in animal models against P. berghei, P. cynomolgi, P. vivax, and both drug-sensitive and drug-resistant strains of P. falciparum. WR 225448 was also more toxic than primaquine in rats on subacute (28-day) administration.

Unilateral hypoplasia of the palate and associated structures in a white-handed gibbon (Hylobates lar).

A hole in the palate was detected in a ten-day-old white-handed gibbon (Hylobates lar). The clinical observations demonstrated a unilateral hypoplasia of the palate, of the maxilla, of a tooth, and of the adjacent facial musculature and skin.

Dengue-2 vaccine: viremia and immune responses in rhesus monkeys.

Studies were undertaken in Indian rhesus monkeys (Macaca mulatta) to determine the safety, potency, immunogenicity, and mosquito infectivity of a small-plaque, temperature-sensitive variant of dengue type 2 (DEN-2) virus, a vaccine candidate. Fifteen monkeys were inoculated subcutaneously with the vaccine virus, ten receiving 10(3.1) plaque-forming units (PFU) and five receiving 10(4.5) PFU. After primary immunization, viremia was detected in only one monkey, a recipient of the higher dose of vaccine. The recovered virus had the same growth characteristics as the vaccine strain. Aedes aegypti mosquitoes did not become infected when they were allowed to feed on monkeys that received the lower dose of vaccine. As expected, the immunization produced no evidence of illness in any of the animals. A dose response to vaccine was detected; all five of the high-dose recipients developed neutralizing antibodies, whereas only five of ten low-dose recipients did so. In both groups, neutralizing antibody was often transient. Its presence at 30 days did not always correlate with protection from viremia in those animals challenged 4 to 6 months after vaccination with wild-type DEN-2 virus. However, immunized animals developed anamnestic antibody responses after challenge, and none demonstrated adverse effects to infection. Reimmunization of monkeys 4 months after primary immunization led to the production of low-titered but persistent neutralizing antibody which protected the animals from a wild-type virus challenge.

Cerebral tuberculosis in a rhesus monkey.

Tuberculosis of the cerebrum was diagnosed in a young adult male rhesus monkey (Macaca mulatta). Tuberculous granulomas were also found in the lungs, bronchial lymph nodes, liver, and spleen. The affected monkey was the probable index case for 7 other Macaca mulatta with tuberculosis.