Tuberculosis in leprosy patients detected between 1902 and 1991 in French Polynesia.

From 1902 onward, notification and follow up of leprosy patients has been systematic in French Polynesia. Since 1960, a tuberculosis control program and a register has also been implemented. From 1902 to 1959, 673 cases of leprosy were detected [346 multibacillary (MB), 138 paucibacillary (PB), and 179 unclassified due to the loss of medical files by the time of classification which was done during the 1980s]. Of these 673 cases, 89 (13.2%) died from tuberculosis, giving a mean annual death rate of tuberculosis in leprosy patients of 232 per 100,000. Mortality from tuberculosis in leprosy patients detected between 1901 and 1930 was 20.7%, and decreased to 8.04% in patients detected from 1931 to 1959. In total, it was estimated that 26.4% of the leprosy cases had developed tuberculosis. From 1960 to 1991, 350 new cases of leprosy were detected (141 MB, 209 PB). Of them, 12 (3.4%) developed tuberculosis (7 before detection of leprosy, 5 after detection of leprosy). The dramatic decrease of the proportion of leprosy patients who developed tuberculosis between the periods 1902-1959 (26.4%) and 1960-1991 (3.4%) might be related to the important decline of the tuberculosis situation since 1960. From 1902 to 1959, mortality from tuberculosis occurred significantly more frequently in MB patients (13%) than in PB patients [4%, relative risk (RR) = 3.21, p = 0.003]. From 1960 to 1991, the incidence of tuberculosis seemed more frequent in MB patients (RR = 2.96, p = 0.07) whatever the sequence of detection of the two diseases. Our study suggests that lepromatous patients could share factors of susceptibility to mycobacterial diseases with patients developing tuberculosis.

Chemoprophylaxis of leprosy with a single dose of 25 mg per kg rifampin in the southern Marquesas; results after four years.

In January-February 1988, a program of chemoprophylaxis for leprosy, using a single 25 mg/kg dose of rifampin, was conducted among 2786 (98.7%) inhabitants of the Southern Marquesas and 3144 South Marquesan "emigrants" and their families. Among the treated population, during the 4 years which followed the implementation of the program, two leprosy patients were detected, one of whom can be considered as a failure of chemoprophylaxis because she was not known by the leprosy control unit. During the same period (1988-1991), a decrease in detection rates for leprosy in the entire French Polynesian population has been observed, an event which makes the interpretation of these findings very difficult. Nevertheless, according to presently available data, the effectiveness of chemoprophylaxis with a single dose of 25 mg/kg rifampin is estimated to be about 40% to 50%. When considering not only the results of the present study but also the financial and logistic constraints raised by such a program, one is led to the conclusion that chemoprophylaxis, even with a single dose of rifampin, is not likely to become an effective component of leprosy control programs.

Leprosy in French Polynesia. The possible impact of multidrug therapy on epidemiological trends.

In 1982, following the recommendations of a WHO study group, multidrug therapy (MDT) was introduced into French Polynesia to treat all patients suffering from active leprosy, and--only on request--those still on dapsone monotherapy. After 5 years, a clear-cut decrease of prevalence and mean annual detection rates for leprosy (except for detection rates among children aged less than 15 years, many of such cases being detected early by increased household contact training) has been observed. There was also a decrease in the proportion of newly detected cases with disabilities. During the 21-year period preceding the introduction of MDT into the control programme, mean annual detection rates for leprosy had remained stable, and this led to the consideration that such a decrease was due neither to the natural decline of the disease nor to the economic improvement of the country. Our results, together with the fact that, to date, the relapse rate was nil in the Polynesian patients put on MDT, strongly suggest that the implementation of MDT has resulted in a decrease of detection rates for leprosy which may be a consequence of a decrease in the transmission of the disease.

[Dapsone inhibition of the bactericidal action of rifampicin on Mycobacterium leprae in mice]. / Inhibition par la dapsone de l'action de type bactéricide de la rifampicine sur Mycobacterium leprae chez la souris.

In the experimental infection of mice by Mycobacterium leprae, the bactericidal effect of 4 weekly doses of rifampicin (RMP) is completely suppressed if this administration is preceded by a daily treatment of dapsone (DDS) during one month then continued in conjunction with rifampicin. The application of this methodology: the delayed adding of rifampicin clearly shows the bacillary persistence induced by dapsone (DDS). The rifampicin appears to be less effective on Mycobacterium leprae when its metabolism is inhibited either by the action of a drug such as dapsone (DDS), or spontaneously. The highlighting of this late-appearing antagonism between rifampicin and dapsone in mice, should not at present lead to the questioning of the therapeutic procedures recommended by the WHO, because of the limits of this experimental model, namely the small size of bacillary populations studied over relatively short periods of time.

Antagonism between dapsone and rifampicin in experimental Mycobacterium leprae infections in mice.

In experimental infections of normal mice with Mycobacterium leprae, the bactericidal activity of four consecutive weekly doses of rifampicin (RMP) was suppressed when this treatment was preceded, for one month, by daily administration of dapsone (DDS), and then the latter. Up until now, it has been impossible to detect this antagonism between the action of RMP and DDS, since all studies involved the simultaneous administration of these two drugs, and such a phenomenon would therefore have been masked by the rapid and potent action of RMP. Previous clinical observations suggest that such a delayed antagonistic effect may also occur in humans. The demonstration of this antagonism between RMP and DDS raises the problem of the long-term efficacy of therapeutic regimens currently used in leprosy and that of the role of DDS in induction of bacillary persistence. It is suggested that this particular methodology, the delayed combination of RMP with a less active drug, should be applied to the study of other drug combinations recommended in the treatment of leprosy.