Impaired responses to Mycobacterium leprae antigens in rhesus monkeys experimentally inoculated with simian immunodeficiency virus and M. leprae.

Seven of eight rhesus monkeys (RM) coinfected with simian immunodeficiency virus (SIV) and Mycobacterium leprae harboured acid-fast bacilli (AFB) at sites of dermal inoculation and/or at disseminated sites at times of humane sacrifice (up to 270 days post-M. leprae inoculation) due to SIV-induced debilitation or, in one long term survivor's case, to date over 3 years post-M. leprae inoculation.

Guidelines for the prevention of simian immunodeficiency virus infection in laboratory workers and animal handlers.

The authors are members of a working group that formulated guidelines to minimize transmission of simian immunodeficiency virus (SIV) infection to man. Biosafety level (BSL) 2 standards are recommended for handling of clinical specimens and housing of SIV inoculated animals. Manipulation of SIV preparations may be performed in a BSL 2 facility with additional BSL 3 practices and equipment; for large volume or concentrated preparations of SIV BSL 3 containment is necessary.

A second sooty mangabey monkey with naturally acquired leprosy: first reported possible monkey-to-monkey transmission.

The existence of naturally acquired leprosy in a second sooty mangabey monkey has been documented. The disease has the clinical and histopathological characteristics of subpolar lepromatous leprosy (LLs), and microbiological studies thus far confirm the etiologic agent as Mycobacterium leprae. This mangabey had been housed in direct contact with the first mangabey in which naturally acquired leprosy was diagnosed in 1979.

Leprosy as a zoonosis: an update.

Naturally-acquired leprosy has been reported in nine-banded armadillos captured in the southern United States, a chimpanzee from Sierra Leone, and in two "sooty" mangabey monkeys from Nigeria. A significant prevalence of leprosy in wild armadillos establishes this animal as a reservoir of M. leprae, and exposure to armadillos has been implicated as a source of leprosy in humans.

Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine and recombinant human beta interferon alone and in combination on simian varicella virus infection in monkeys.

Treatment of viral infections with combinations of antiviral agents may permit administration of reduced doses of either or both drugs. Lowered doses may reduce associated toxicity. Intravenous administration of substantial doses of either human recombinant beta interferon (rHuIFN-beta) or 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) prevents development of simian varicella virus infection in African green monkeys.

Activity of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil against simian varicella virus infections in African green monkeys.

The fluorinated pyrimidines 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU) are highly effective inhibitors of herpesvirus infections in vitro and in vivo. This report is concerned with an evaluation of their activities in African green monkeys (Cercopithecus aethiops) infected with simian varicella virus, a herpesvirus closely related to human varicella-zoster virus. Oral or intravenous administration of FIAU at 50 mg/kg per day as divided doses beginning 48 h after virus inoculation prevented the development of evidences of clinical infection.

Leprosy in a mangabey monkey--naturally acquired infection.

Naturally acquired leprosy was detected in an otherwise normal "sooty" mangabey monkey (Cercocebus atys). This animal was imported from West Africa in 1975 and developed clinical symptoms of leprosy in 1979. Histopathologic findings were those of subpolar-lepromatous to borderline-lepromatous leprosy in the Ridley-Jopling classification.

Depression of lymphocyte responses to mitogens in mangabeys with disseminated experimental leprosy.

Mononuclear cells from mangabey monkeys with disseminated experimental leprosy had increasingly severe depression of blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen as the disease progressed. Blastogenic responses were not depressed in cells from mangabeys with more localized disease. Blastogenic responses of cells from normal mangabeys appeared to vary with a circannual rhythm.

Investigation of antiviral activity of 1-beta-D-arabinofuranosylthymine (ara-T) and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-ara-U) in monkeys infected with simian varicella virus.

1-beta-D-Arabinofuranosylthymine (ara-T) and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-ara-U) were shown to have antiviral activity in vitro and in vivo against simian varicella virus. Both compounds successfully prevented clinical disease caused by inoculation of African green monkeys with simian varicella virus, eliminating the development of rash and substantially suppressing viremia. Ara-T treatment was effective by either intraperitoneal or oral routes of administration and BV-ara-U was active by both oral and intramuscular routes.

Electron microscopic study of leprosy in a mangabey monkey (natural infection).

Ultrastructural features of the leproma of a) a naturally infected mangabey monkey, and lepromas and liver of b) a passage mangabey monkey, c) a rhesus monkey, d) an African green monkey, and e) a nine-banded armadillo inoculated with leprosy bacilli isolated from the leproma of a naturally infected mangabey monkey were studied by the freeze-etching technique. The size, shape, and ultrastructural features of leprosy bacilli in the phagolysosomes of macrophages in all of these samples were essentially the same as those in humans, nude mice, and armadillos inoculated with human Mycobacterium leprae. Distinct accumulations of small spherical droplets were observed around leprosy bacilli inside lepra cells of all the samples but were scarce in the specimen from the green monkey.

In vivo antiviral activity of recombinant type alpha interferon A in monkeys with infections due to simian varicella virus.

Recombinant type alpha interferon A (rIFN-alpha-A) administered to African green monkeys (Cercopithecus aethiops) intramuscularly in a dose of 3 X 10(6) units/kg of body weight resulted in substantial blood levels of interferon. Peak levels of greater than 1,000 units/ml of serum appeared at 1 and 2 hr after inoculation and interferon was detectable for as long as 12 hr after inoculation. Injection of rIFN-alpha-A at a dose of 10(6) units/kg twice daily for eight days effectively inhibited simian varicella virus infection of the African green monkey.

Acyclovir in the treatment of simian varicella virus infection of the African green monkey.

Acyclovir (9-(2-hydroxyethoxymethyl)guanine) administered as an intramuscular formulation twice daily at a dosage of 100 mg/kg per day prevented the development of disease in African green monkeys inoculated with simian varicella virus. Viremia, appearance of a vesicular rash, and elevations of serum transaminases, each indicative of infection, were suppressed by acyclovir treatment. Plasma concentrations of acyclovir were measured and showed rising levels after repeated intramuscular injection with a prolonged period of absorption of acyclovir into the plasma circulation.

Acyclovir treatment of experimental simian varicella infection of monkeys.

Replication of simian varicella virus (SVV) in Vero cell cultures was inhibited by acyclovir, 9-(2-hydroxyethoxymethyl)guanine (ACV), at a concentration of 10 micrograms/ml in culture medium. Intravenous administration of ACV at 10 mg/kg twice a day for 10 days or 15 mg/kg three times a day for 5 days to patas monkeys (Erythrocebus patas) beginning 48 h after SVV inoculation blocked the appearance of rash and other clinical symptoms but did not affect viremia. ACV treatment of African green monkeys (Cercopithecus aethiops) at 10 mg/kg twice a day by intravenous injection beginning 24 or 72 h after SVV inoculation and continuing for 10 days had no effect on clinical symptoms, including the development of rash, or on the appearance of viremia.

Ineffectiveness of adenine arabinoside and adenine arabinoside 5'-monophosphate in simian varicella infection.

Adenine arabinoside and adenine arabinoside 5'-monophosphate (ara-AMP) have been evaluated for antiviral activity against simian varicella virus infection in monkeys. In a preliminary study for toxicity, intramuscular injection of ara-AMP at 15 mg/kg per day as a single injection for 5 days to two normal patas monkeys caused no detectable local reaction, no weight loss or changes in serum transaminase levels, and no hematological abnormalities. When this dose was given in the treatment of four simian varicella virus-infected patas monkeys, no effect was observed on the clinical course of infection, as compared with four infected monkeys which received phosphate-buffered saline.

Phosphonoacetic acid in the treatment of simian varicella.

Phosphonoacetic acid inhibited replication of simian varicella virus (Delta herpesvirus) in tissue culture. The drug was tested in patas monkeys 40 h after infection with Delta herpesvirus. A total of 200 mg/kg per day was given intramuscularly, divided into two doses every day for a total of 10 days.

Effect of interferon respiratory infections of animals.

Several animal models are available for the evaluation of interferon in respiratory virus infections. Considerable variability exists among the respiratory viruses with respect to sensitivity to exogenous interferon or induced endogenous interferon. Due to this apparent variability, combinations of interferon with immune serum and chemotherapeutic agents may provide a means of more efficient control of respiratory infections.

Aerosol inoculator for exposure of human volunteers.

The performance of an aerosol inoculator for human volunteers is described in tests that used the PR8 strain of type A influenza virus and sodium fluorescein as a physical tracer. Virus recovery from the aerosols was approximately 1% and was unaffected by such variables as prolonged aerosolization, total airflow, relative humidity, or method of sampling. The recovery of sodium fluorescein from the aerosol was approximately 12% and was influenced by total airflow rates and relative humidity.

Inhibition of respiratory virus infections of mice with aerosols of synthetic double-stranded ribonucleic Acid.

Aerosols of double-stranded complexes of polyinosinic and polycytidylic acids (poly I:C) were useful in protecting mice infected with aerosols of influenza (A(2)/Taiwan/64) and parainfluenza type 1 (Sendai) viruses. Administration of poly I:C as an aerosol offers an advantage, particularly in therapy, by eliminating the risk of pulmonary dissemination of viral infections due to intranasally instilled fluids. Treatment of mice with aerosols of poly I:C reduced the infection rate with influenza virus but did not inhibit virus multiplication in the lungs of most of those animals where infection became established.

Growth of Rio Bravo virus in cell cultures.

The growth of Rio Bravo virus (RBV) in eight cell culture systems was studied. Highest yields of virus were produced in BHK-21 (C13), L, and Vero cell lines, but L cells were resistant to low doses of virus. LLC-MK(2), HeLa, and human embryo skin cells produced moderate amounts of virus, but FL amnion and primary chick embryo fibroblasts supported little virus growth.