Previously, 8 rhesus monkeys (RM) were inoculated on the same day with SIV + M. leprae (ML); another 4 control RM received only ML. As previously noted, clinical results of these studies were consistent with our prior observations, i.e., SIV coinfection renders RM more susceptible to leprosy. Last year, we continued to clinically and immunologically monitor the surviving animals in this experiment, and longitudinally-acquired continuing immunologic data were collected, calculated and plotted. To date, 7 of 8 of the coinfected group have died as a result of simian AIDS (SAIDS) (with one exception--a RM that was euthanized for an unrelated clinical problem and was SAIDS-negative, but leprosy-positive at inoculation sites). Six of the 7 SAIDS-positive RM had leprosy at inoculation sites and 1 had positive dissemination to distant sites. The surviving RM has disseminated leprosy, but no clinical signs of SAIDS. In summary, 2 of 8 coinfected RM developed disseminated leprosy and 5 had leprosy at dermal sites of ML inoculation within 9 months postinoculation with ML. Biopsies of dermal ML inoculation sites at 1 and 2 months PI failed to show significant numbers of ML in 3 of the 4 control RM inoculated with ML only. Longitudinal immunologic studies showed that all 4 ML-only inoculated and the one surviving SAIDS-negative/leprosy-positive RM made antibodies to ML-specific phenolic glycolipid-I (PGL-I) antigen, but the remaining 7 coinfected RM failed to make anti-PGL-I responses. All 8 coinfected RM made significant anti-Gp 120 antibody responses prior to and after ML inoculation until just prior to death or, in the case of the remaining surviving coinfected RM, to date many months after ML coinoculation. Similarly blastogenic responses to Concanavalin A were normal before ML inoculation and progressively diminished in the coinfected RM post-ML inoculation. There was also a progressive decrease in blastogenic responses to lepromin with time after ML coinfection, but not in the ML-only infected RM. The data show that SIV causes a significant specific reduction in both the humoral and cellular immune compartments towards ML, adding further support to our clinical observations suggesting that coinfection with SIV and ML enhances the susceptibility towards leprosy, i.e., leprosy can be an opportunistic infection in SIV-positive animals. Last year, these studies were enlarged by beginning a study in which 18 RM were divided into 3 groups of 6. One group was inoculated with SIV and, after 2 weeks, with ML. Another group was inoculated with SIV + ML at the same time and the third group was given ML alone. These animals remain under study and should provide information regarding the possible influence of the relative timing of the two infections on clinical outcome.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-36
Application #
6247262
Study Section
Project Start
1997-05-09
Project End
1998-09-29
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
36
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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