New biological tools for leprosy surveillance

International Journal of Leprosy and Other Mycobacterial Diseases, Dec 1999 by Cho, Sang-Nae, Brennan, Patrick J

New biological tools are required for leprosy surveillance, both for detection of Mycobacterium leprae infection and for early diagnosis of the disease, particularly in the final phases of the elimination strategy. Now that the prevalence of leprosy has declined dramatically in most leprosy-endemic countries over the last decade, incidence of the disease will become a more important measurement of true disease than prevalence for leprosy surveillance. The incidence of leprosy, however, varies markedly even within the same broad geographical region, depending on the level of effort being devoted to finding new cases, i.e., the extent of active or passive case finding. It will be difficult to adopt incidence data for leprosy surveillance throughout the leprosy-endemic world unless a uniform method of determining true incidence is employed. Therefore and alternatively, determination of the infection rate with M. leprae within a population could become an important determinant of the extent of leprosy control. In addition, much earlier diagnosis of leprosy would be of great value in preventing more severe disease, perhaps leading to disabilities, by simply initiating chemotherapy at an early stage, thereby removing the source of M. leprae transmission. New biological tools for detection of M. leprae infection and for early diagnosis of leprosy are of paramount importance in surveillance of control programs and for the ultimate eradication of the disease.

M. leprae and the biological stages of leprosy: theoretical and practical considerations. In order to develop the biological tools for detection of M. leprae infection and for early diagnosis of leprosy, more information is required with respect to both the organism and the biological stages of the disease. For example, are there important extra-human reservoirs of M. leprae, such as soil or water or nonhuman animal sources? Are strain variations important in terms of virulence, transmission rate, or the expression of major antigens in humans? For instance, the presence of M. leprae to a significant extent in extra-human reservoirs, if proven, will prove to be a major obstacle for disease eradication and will pose problems in understanding the degree of exposure to the organism related to "true" infection or transient infection and subsequent immune response in the host. It has long been claimed that the genomic DNA of M. leprae is highly conserved. However, there is now recent evidence of polymorphism. It will be important to determine whether this polymorphism is reflected in variations in virulence and transmission efficiency. Also, variations in the expression level of major antigens of M. leprae in humans, if such exist, will be reflected in the host's immune responses and will have a bearing on the extent/duration of disease and the creation of new biological tools to detect it. It remains to be explained whether variation in antibody level and T-cell responses to certain M. leprae antigens among leprosy patients is due to the difference in host response to the same antigens or due to differences in antigen expression levels between M. leprae strains, or possibly due to both. All such information related to the biology of M. leprae will help in the development of a generation of more specific and sensitive biological tools for leprosy surveillance.

Among the biological stages of leprosy, one needs more information on the infection route, degree of exposure leading to disease, incubation period, host response and clinical sequelae, and how chemotherapy can lead not only to cure, but also to relapse, lepra reactions, and re-infection. The route of M. leprae infection is an important factor affecting the host's immune responses, resulting in variations in antibody classes and levels and T-cell responses to M. leprae antigens. The degree of exposure to M. leprae has been considered as a major factor in the development of leprosy among household contacts. However, although being a household contact is a major risk factor, the majority of leprosy cases arise from situations in which there was no contact with patients. The principle of the nonsymptomatic carrier in leprosy is now becoming accepted, and more information is needed, such as the infectivity of the temporary or continuous carrier. We need to know more about the meaning of the presence of M. leprae in nasal mucosa, which, thanks to the art of polymerase chain reaction (PCR) amplification, is now regarded as the most likely source of M. leprae transmission. The incubation period for leprosy varies from three to forty years, although five to ten years have been most widely cited. No information is yet available on whether or not M. leprae transmission occurs during this incubation period.

The host's immune responses to M. leprae infection and early clinical symptoms will be the most important factors in developing new biological tools for detection of infection and for early diagnosis. There is a considerable body of evidence on variations in antibody levels, subclasses, and T-cell responses to each of the known M. leprae antigens among leprosy patients with different clinical types of disease. However, more information is required for understanding the basis of such variations and the factors influencing the clinical course of the disease. Without such information, any biological tools for detection of infection and disease at the early stage will have serious limitations in terms of sensitivity and specificity.