Trials of preventive therapy

International Journal of Leprosy and Other Mycobacterial Diseases, Dec 1999 by Blanc, Leopold J

In five countries in the Western Pacific Region of the World Health Organizationthe Federated States of Micronesia (FSM), the Republic of the Marshall Islands (RMI), Kiribati, Papua New Guinea and Guam, the prevalence of leprosy is still greater than I per 10,000 population. The continuing high prevalence of leprosy in these countries has kindled renewed interest in chemoprophylaxis.

A number of formal studies of chemoprophylaxis have been carried out in the past, and I wish briefly to review three of them. Dr. S. K. Noordeen carried out a trial in Chingleput, India, in 1965, in which dapsone (DDS) was administered orally to child contacts of patients with leprosy. Subsequently, based on the results of this trial, a trial was carried out by the U.S. Public Health Service and the University of Hawaii on the island of Pingelap and in the Pingelapese community on the island of Pohnpei, as has been mentioned by Dr. Pretrick, employing injectable diacetyldapsone (DADDS), which was administered to the entire population. The third trial about which I wish to speak was carried out by Dr. Jean-Louis Cartel in French Polynesia, in the South Marquesas Islands, employing a single dose of rifampin, which also was administered to the entire population.

As shown in Table 1, all three of the trials were prospective studies. Only in Chingleput was a control group included; the results of this trial were sufficiently convincing to render the later inclusion of a control group unethical. In the Chingleput trial, only the children who were contacts of patients with multibacillary (MB) leprosy were treated, whereas the trials in both Pingelap and the Marquesas targeted entire populations. In Chingleput, 700 contacts were treated, whereas larger numbers were treated in both the Pingelap and South Marquesas trials. In both the Chingleput and Pingelap trials, the prophylaxis was administered for at least three years, a very long time, whereas the prophylaxis was administered in only a single dose in the South Marquesas trial. The prevalence of leprosy before beginning the trial was very high among household child contacts in Chingleput, and also high in the total population in Pingelap, whereas it was considerably lower, although still well above the target of I per 10,000 population in the South Marquesas Islands. It must be remembered, of course, that the Chingleput and Pingelap trials were conducted well before the introduction of multidrug therapy (MDT) whereas that in French Polynesia was conducted against a background of a declining rate of detection of new cases after MDT had been introduced. In Chingleput, the efficacy of the prophylaxis was estimated to be 50 percent, comparing the incidence among treated and control subjects. In Pohnpei, no new cases appeared during the first two years after the course of prophylaxis, but new cases were observed later. During the four years following the trial in the South Marquesas Islands, the new-case detection rate was reduced by 80 percent, in comparison with that recorded before the trial; however, because the prophylaxis was administered against a background of declining incidence, the result of MDT, the efficacy of the treatment was calculated to be of the order of 50 percent.

With respect to the trial in French Polynesia, the population of the South Marquesas Islands was 2786, 98.7 percent of whom received prophylaxis. As shown in Table 2, however, in addition to those residing on the Island, the members of the population who were living off the Island, numbering more than those residing on the Island, were also treated in an attempt to "sterilize" the reservoir of Mycobacterium leprae. During the four years following administration of the prophylaxis, one patient with a single lesion, who had been administered the prophylaxis, was encountered among those living on the Island, obviously a case of failure of the treatment. Among those residing off the Island, two patients with MB leprosy were detected, neither of whom had been administered chemoprophylaxis.

In addition to these formal trials, chemoprophylaxis has recently been introduced in three countries-the FSM, Kiribati and the RMI-as a component of their leprosy-control programs, in reaction to the failure of new-case detection rates to fall (The Figure). In these three countries, entire populations rather than the population of a single island have been screened, and chemoprophylaxis has been administered either to the entire population or to household contacts. The second round of screening has not been completed in Kiribati, and even the first round has not yet been completed in the RMI, whereas the program in the FSM was completed only one year ago so that only preliminary data are available for presentation at this time. These programs will be described in detail in the following papers.

Discussion

Dr. Noordeen: Can you tell us whether case detection rates in the Western Pacific Region have changed over the last number of years?