Preventive treatment of leprosy: Needs, opportunities, and feasibility

International Journal of Leprosy and Other Mycobacterial Diseases, Dec 1999 by Smith, W C S, Smith, C M

That the rates at which new cases of leprosy are detected have failed to decrease suggests that we should review the current approaches to leprosy control, and consider in particular whether there are justifiable arguments to explore preventive approaches. There are complex reasons for the continuing high levels of global new-case detection rates. What is not clear is whether the trends in case detection reflect underlying secular trends in transmission. This is the first issue to be addressed in this review.

Having considered the case for preventive strategies, the second issue to be addressed is what potential approaches are available. The evidence of effectiveness of the available approaches should be systematically reviewed. These may be single approaches or combinations of methods, which together could confer protection. It is also possible that other interventions would be effective but have not yet been tested in the field. These should be reviewed and recommendations made regarding the value of such research.

The final stage in this analysis is to consider the feasibility of implementing these preventive strategies. Practical and ethical issues must considered, the groups to be treated must be identified, and the magnitude of the effect if such preventive approaches were implemented should be estimated.

Need for preventive strategies

The global number of new cases of leprosy detected each year for the last ten years has remained relatively static; indeed, there has been an increase over the last few years (The Figure). However, this global trend masks a diverse picture at the national level; some countries (34) show increasing numbers of new cases, others show decreases, and some show considerable variation. It is clear that case detection does not directly reflect the true incidence of disease or current transmission of Mycobacterium leprae (7,15,30). One of the expectations of the elimination strategy was that extensive use of multidrug therapy (MDT) would reduce the quantum of infection in the community, leading in time to a reduction of transmission. However, although administration of MDT is thought to block transmission almost immediately, it is more than likely that transmission occurs prior to detection and treatment. Recent developments using polymerase chain reaction (PCR) technology have suggested the possibilities that there may be asymptomatic carriage (1) and environmental reservoirs of M. leprae. However, pre-treatment transmission and the long incubation period are probably sufficient to explain the lack of an immediate effect of MDT on new-case detection rates. Moreover, it is well accepted that leprosy cases do not occur randomly in the community, but rather in clusters.

Operational factors profoundly affect case detection (11), and are likely to be responsible for the sustained high levels of case detection and the recent increases of the rates at which new cases are detected in some countries. The intensity of case detection activities influences case-detection rates, as does the "earliness" of case detection in the disease process (1). Geographical coverage has increased as the leprosy elimination program has been implemented. Initiatives such as the leprosy elimination campaigns have increased new-case detection in several countries (35), partly through finding patients who have had the disease for a long time (so-called back-log cases), and also by re-registering patients who had defaulted from treatment in the past. The quality of leprosy information systems has also improved; this would lead to an apparent increase of case numbers.

The occurrence of disease is the result of a balance among the agent, the environment and the host. Most attention in the leprosy elimination program has been paid to attacking the organism by means of MDT; however, important changes have also occurred in the environment and in the host. Socioeconomic improvements such as better nutrition, better sanitation, improved housing, and less overcrowding are likely to contribute to changes of the epidemiologic pattern. The widespread use of BCG (12) is likely to have been responsible for increased host immunity to M. leprae.

Disease modeling is a scientific approach that has been used to understand the epidemiology of leprosy and predict future trends. This approach is useful because, among other things, it identifies the gaps in our understanding with respect to transmission of the organism. These models demonstrate that chemotherapy has an effect, but because MDT was implemented immediately after dapsone monotherapy, it is impossible to detect a difference. On the other hand, they predict that if chemotherapy were withdrawn, the incidence would increase. Although the output of these models must be interpreted with caution, they suggest that trends in leprosy incidence are likely to be gradual, and it is not realistic to expect large changes of disease incidence in the course of a few years. These observations are not surprising, in view of the long incubation period of leprosy and the slowness of change of the disease process.