Granulomatous reaction to intradermal injection of lepromin (Mitsuda reaction) is linked to the human NRAMP1 gene in Vietnamese leprosy sibships.

The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.

Granulomatous reaction to intradermal injection of lepromin (Mitsuda reaction) is linked to the human NRAMP1 gene in Vietnamese leprosy

The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.

Susceptibility to leprosy is linked to the human NRAMP1 gene.

Leprosy is a debilitating infectious disease of human skin and nerves. Genetic factors of the host play an important role in the manifestation of disease susceptibility. The human NRAMP1 gene is a leprosy susceptibility candidate locus since its murine homologue Nramp1 (formerly Lsh/Ity/Bcg) controls innate resistance to Mycobacterium lepraemurium. In this study, 168 members of 20 multiplex leprosy families were genotyped for NRAMP1 alleles and 4 closely linked polymorphic markers. Highly informative haplotypes overlapping the NRAMP1 gene were constructed, and the haplotype segregation into leprosy-affected offspring was analyzed. It was observed that the segregation of NRAMP1 haplotypes into affected siblings was significantly nonrandom. This finding is consistent with the hypothesis that NRAMP1 itself is a leprosy susceptibility locus.

Rising HIV infection rates in Ho Chi Minh City herald emerging AIDS epidemic in Vietnam.

OBJECTIVE: To describe the epidemiology of HIV in Ho Chi Minh City in the context of current surveillance data from Vietnam. METHODS: Since the late 1980s, HIV surveillance data have been collected in Ho Chi Minh City from centers for the treatment of venereal disease and tuberculosis, centers for the rehabilitation of injecting drug users and sex workers, prenatal clinics, blood banks and other sites. RESULTS: The first case of HIV infection in Vietnam was identified in 1990 in Ho Chi Minh City. The cumulative number of reported HIV infections in this city at the end of 1996 was 2774, about half of the number of cases in the country; 86% of infections were among men, 86% among injecting drug users, 2.5% among patients with sexually transmitted diseases and 2.5% among sex workers. The first HIV infection among antenatal women was detected in 1994. The prevalence of HIV among injecting drug users rose dramatically from 1% in 1992 to 39% in 1996, compared with 1.2% among sex workers, 0.3% among blood donors and 1.3% among tuberculosis patients in 1996. The populations of injecting drug users and sex workers in Ho Chi Minh City are estimated to be 30000 and 80000, respectively, and rates of sexually transmitted diseases are 2-3 per 1000 persons per year. By the end of December 1996, 42 out of 53 provinces had reported HIV infections, and border areas near China and Cambodia began identifying large numbers of HIV-seropositive people. CONCLUSIONS: Ho Chi Minh City is at the forefront of a new HIV epidemic in Vietnam. This epidemic shows similarities to that in Thailand nearly a decade ago, with rapidly rising HIV rates among injecting drug users and infection already established among sex workers. Prevention efforts should include the targeting of injecting drug users and sex workers outside rehabilitation centers, the availability of sterile needles and condoms, the establishment of anonymous testing sites, the control of sexually transmitted diseases and the coordination of programs within southeast Asia.

PIP: An analysis of annual sentinel surveillance data from Viet Nam indicates that Ho Chi Minh City is at the forefront of a new HIV epidemic. Since 1990, data on HIV cases have been collected from prenatal clinics, blood banks, centers for the treatment of sexually transmitted diseases (STDs) and tuberculosis, and rehabilitation centers for injecting drug users and commercial sex workers. The first HIV case in Viet Nam was reported in 1990 in Ho Chi Minh City. By the end of 1996, a cumulative total of 4961 HIV cases had been documented in Viet Nam, 2774 of which were in Ho Chi Minh City. In Ho Chi Minh City, 86.5% of cumulative HIV infections involved men. The distribution of total HIV cases by group has been: injecting drug users, 86.0%; tuberculosis patients, 3.3%; sex workers, 2.5%; STD patients, 2.5%; and pregnant women, 0.6%. By 1996, 42 of Viet Nam's 53 provinces had reported HIV cases and infection rates are rising dramatically in border areas near China and Cambodia. The pattern documented in this analysis resembles that observed in Thailand a decade ago: rapidly rising HIV rates among injecting drug users and infection already established among sex workers, without dissemination to the general population. The necessary infrastructure and resources for control of the epidemic are far more limited in Viet Nam than Thailand, however. Recommended, to prevent the further spread of HIV in Viet Nam, are educational activities targeted at injecting drug users and sex workers outside of rehabilitation centers, the availability of condoms and sterile needles, establishment of anonymous testing sites, control of STDs, and the coordination of programs within southeast Asia.

Protective effect of BCG against leprosy and its subtypes: a case-control study in southern Vietnam.

A case-control study was conducted to assess the protective effect of intradermal BCG against leprosy and its subtypes in southern Vietnam. A total of 177 cases were selected with a distribution by subtypes as follows: 38 TT, 23 BT, 51 BB, 36 BL, 22 LL, and 7 indeterminate. Two controls were matched with a case for age, sex, ethnic group, socioeconomic status, and district area. The odds ratio assessing the protective effect of BCG varied from 0.44 (0.19-1.03) in the BB subtype to 3.00 (0.24-37.5) in indeterminate leprosy; whereas its overall value was 0.71 (0.45-1.10) for leprosy per se. When all borderline leprosy types were pooled, the protective effect of BCG was found significant with an odds ratio of 0.48 (0.27-0.84). In the polar forms of leprosy, TT and LL, the odds ratio was > 1 with large confidence intervals. It is possible that BCG induces a shift in the immune response to a higher level of cell-mediated immunity. When BCG vaccination is given after primary infection with Mycobacterium leprae, this shift could be the cause of an increase in the risk of the occurrence of milder and transient forms of the disease. In TT forms BCG might reinforce the preexisting subclinical immunopathological reactions, and in stable LL forms BCG might be unable to induce any protective form of immunity. These results confirm the important variability in the protection offered by BCG with respect to the different types of leprosy, and may have important implications for the design and the interpretation of vaccine trials that should take into account the respective proportions of leprosy forms observed in the study region.