Chemoprophylaxis against leprosy: expectations and methodology of a trial

Abstract

Because of the great efficacy of multidrug therapy (MDT), it had been hoped that the widespread use of MDT would bring about a rapid decrease of the incidence of leprosy. To the present, a decrease of incidence has not been observed, possibly because of the long incubation period of the disease, and because general implementation of MDT is still recent. Other reasons, such as environmental sources of infection or the role of healthy carriers in transmitting Mycobacterium lepr ae, cannot be excluded. Therefore, one must seek alternative or supplementary strategies, such as chemoprophylaxis. Household contacts of leprosy patients are at greater risk of developing leprosy than is the general population. Therefore, a randomized, controlled trial of chemoprophylaxis, using a single 10 mglkg dose of rifampicin, or a placebo, is planned in nine proj ects in India, among the household contacts of newly detected leprosy patients. Based upon assumptions of a protective efficacy of the chemoprophylaxis of 50%, an annual incidence of 2 per 1000 contacts, a desired power of the study of 90%, and a level of significance of 95%, 15,000 household contacts will be allocated randomly by household to each arm of the study, and followed for 5 years. Considered as household contacts will be all persons living in the same household as an index case and sharing the same kitchen. Pregnant women and infants will be excluded. To be certain that transmission of the organisms from the index case cannot occur once the prophylaxis is administered, rifampicin will be administered 2 months after diagnosis of the index case. Diagnosis of leprosy will be clinical, and confirmed independently. Although household contacts usually consti tute only a small proportion of the new patients detected in a control programme, their high-risk status makes them particularly appropriate for a study of the potential effect of chemoprophylaxis. Following the trial, one could evaluate the usefulness and feasibility of using the same strategy in other popUlation-groups, based on the number of persons necessary to treat to prevent one case.

Leprosy reactions: the effect of gender and household contacts

“…All people living in the same household as an index case and sharing the same kitchen will be considered as household contacts. To be certain that transmission of the organisms from the index case cannot occur once the prophylaxis has been administered, rifampicin will be given two months after diagnosis of the index case (Vijayakumaran et al 2000).…”

Endemias e epidemias brasileiras, desafios e perspectivas de investigação científica: hanseníase

“…Os resultados dessas experiências operacionais não possibilitam avaliar a eficácia dessa intervenção e são difíceis de serem extrapolados para outros contextos 67,68 . Um ensaio preventivo, aleatório, placebo controlado, para avaliar a efetividade de dose única de rifampicina em contatos domiciliares de pacientes com hanseníase vem sendo planejado para ser conduzido em múltiplas regiões da Índia 69 . Chama a atenção o tamanho da amostra requerido de 15.000, calculado considerando-se a eficácia da quimioprofilaxia de 50%, em incidência anual de 2 casos por 1.000 contatos (poder estatístico de 90% e alfa de 95%), e seguimento de 5 anos.…”

The potential for vaccination in leprosy elimination: new tools for targeted interventions

“…Various chemoprophylaxis trials have been conducted to determine whether pre-emptive "treatment" can interrupt leprosy transmission and reduce disease prevalence. These studies have demonstrated a significant benefit to treating non-diseased individuals, although each has reported a different magnitude and length of protection (Daulako 1999, Tin 1999, Diletto et al 2000, Nguyen et al 2000, Vijayakumaran et al 2000, Moet et al 2004, Bakker et al 2005, Smith 2008). The findings of the heralded COLEP trial, which was conducted on approximately 20,000 contacts of new cases in north-west Bangladesh, showed a protective effect associated with single-dose rifampicin (RIF) treatment of 57% in household and other contacts (Moet et al 2008a).…”