The combined effect of chemoprophylaxis with single dose rifampicin and immunoprophylaxis with BCG to prevent leprosy in contacts of newly diagnosed leprosy cases: a cluster randomized controlled trial (MALTALEP study).

BACKGROUND: Despite almost 30 years of effective chemotherapy with MDT, the global new case detection rate of leprosy has remained quite constant over the past years. New tools and methodologies are necessary to interrupt the transmission of M. leprae. Single-dose rifampicin (SDR) has been shown to prevent 57% of incident cases of leprosy in the first two years, when given to contacts of newly diagnosed cases. Immunization of contacts with BCG has been less well documented, but appears to have a preventive effect lasting up to 9 years. However, one major disadvantage is the occurrence of excess cases within the first year after immunization. The objective of this study is to examine the effect of chemoprophylaxis with SDR and immunoprophylaxis with BCG on the clinical outcome as well as on host immune responses and gene expression profiles in contacts of newly diagnosed leprosy patients. We hypothesize that the effects of both interventions may be complementary, causing the combined preventive outcome to be significant and long-lasting. METHODS/DESIGN: Through a cluster randomized controlled trial we compare immunization with BCG alone with BCG plus SDR in contacts of new leprosy cases. Contact groups of around 15 persons will be established for each of the 1300 leprosy patients included in the trial, resulting in approximately 20,000 contacts in total. BCG will be administered to the intervention group followed by SDR, 2 months later. The control group will receive BCG only. In total 10,000 contacts will be included in both intervention arms over a 2-year period. Follow-up will take place one year as well as two years after intake. The primary outcome is the occurrence of clinical leprosy within two years. Simultaneously with vaccination and SDR, blood samples for in vitro analyses will be obtained from 300 contacts participating in the trial to determine the effect of these chemo- and immunoprophylactic interventions on immune and genetic host parameters. DISCUSSION: Combined chemoprophylaxis and immunoprophylaxis is potentially a very powerful and innovative tool aimed at contacts of leprosy patients that could reduce the transmission of M. leprae markedly. The trial intends to substantiate this potential preventive effect. Evaluation of immune and genetic biomarker profiles will allow identification of pathogenic versus (BCG-induced) protective host biomarkers and could lead to effective prophylactic interventions for leprosy using optimized tools for identification of individuals who are most at risk of developing disease. TRIAL REGISTRATION: Netherlands Trial Register: NTR3087.

A qualitative exploration of social contact patterns relevant to airborne infectious diseases in northwest Bangladesh.

In South Asia, the burden of infectious diseases is high. Socioeconomically and culturally-defined social interaction patterns are considered to be an important determinant in the spread of diseases that are transmitted through person-to-person contact. Understanding of the contact patterns in this region can be helpful to develop more effective control measures. Focus group discussions were used in exploring social contact patterns in northwest Bangladesh. The patterns were assessed for perceived relevance to the spread of airborne infectious diseases, with special focus on diseases, like leprosy and tuberculosis, in which the role of social determinants is well-recognized. Highly-relevant social contact patterns inside the home and the neighbourhood, across age and sex groups, were reported in all group discussions. Outside the home, women and girls reported relevant contacts limited to the close neighbourhood while men mentioned high relevant contacts beyond. This implies that, in theory, infectious diseases can easily be transmitted across age and sex groups in and around the home. Adult men might play a role in the transmission of airborne infectious diseases from outside this confined area since only this group reported highly-relevant social contacts beyond the home. This concept needs further exploration but control programmes in the South Asian region could benefit from considering differences in social contact patterns by gender for risk assessments and planning of preventive interventions.

Patient-related factors predicting the effectiveness of rifampicin chemoprophylaxis in contacts: 6 year follow up of the COLEP cohort in Bangladesh.

OBJECTIVES: The COLEP trial in Bangladesh showed a 57% reduction in leprosy incidence among contacts of newly diagnosed patients in the first 2 years after chemoprophylaxis with single dose rifampicin (SDR). We assessed the impact of this intervention after 6 years and identified characteristics of the leprosy index patients predicting the effectiveness of this intervention. DESIGN: The cohort of 1037 patients and their 28 092 contacts that participated in the randomised placebo controlled field trial with single dose rifampicin was followed for 6 years. The leprosy status of contacts was established at 2, 4 and 6 years after the intervention. We assessed the association between characteristics of the index leprosy patients and the development of clinical leprosy among their contacts using logistic regression. RESULTS: The protective effect of SDR was seen only in the first 2 years, with no additional effect after 4 and 6 years. However, the total impact of the intervention was still statistically significant (P = 0.025) after 6 years and no excess cases were observed in the SDR arm at a later stage. The intervention prevented leprosy in contacts that actually received SDR, but did not offer protection to members of the same contact group who did not take chemoprophylaxis. The intervention was most effective in contact groups of female index patients, an enhanced effect was also observed in contact groups of patients belonging to a cluster of two or more leprosy patients at intake as well. CONCLUSION: These easy to recognise patient characteristics indicate a possible enhanced risk of transmission of Mycobacterium leprae to contacts in the vicinity of patients and are useful for deciding about preventive measures, such as early detection or chemoprophylaxis.

Aceptación de quimioprofilaxis por los convivientes de pacientes de lepra en Bangladesh: estudio cualitativo / No disponible

Objetivos: La quimioprofilaxis con dosis única de rifampicina constituye una intervención prometedora para prevenir la lepra en los contactos de los pacientes. Sin embargo, su implementación en los programas de control requiere frecuentemente hacer público el diagnóstico de lepra, que en muchos países sigue siendo una infección estigmatizante. Promocionar el control y el tratamiento de la afecciones estigmatizantes sin contribuir a reducir el estigma de los individuos afectados puede resultar deficiente. El objetivo de este estudio era evaluar la aceptación social al revelar el diagnóstico y predisposición hacia la toma de medicamentos profilácticos en un área endémica de lepra de Bangladesh. Metodología: Estudio cualitativo a través de grupos de discusión con 136 hombres y mujeres sanos, de diferentes edades y religiones, procedente de dos aldeas rurales y un área urbana del noroeste de Bangladesh, y 14 trabajadores sanitarios con experiencia en tratar a paciente de lepra. Resultados: Los participantes no se opondrían a revelar el diagnóstico de lepra a los convivientes y parientes más cercanos si fueron diagnosticados de lepra. Sin embargo, muchos participantes no quisieron compartir esta información con sus vecinos y contactos sociales por el estigma de esta enfermedad. Todos los participantes estaban dispuestos a tomar quimioprofilaxis si cualquier contacto cercano a ellos resultara diagnosticado de lepra, incluso después de explicarles que no estaba garantizada la protección total contra la lepra. Conclusión: Se puede afirmar que la quimioprofilaxis para los convivientes de los pacientes de lepra es una condición efectiva y socialmente aceptable para los programas de control actuales. La quimioprofilaxis para otro tipo de contacto que podría beneficiarse sólo sería factible sin revelar la información sobre los pacientes, si se administra en forma de campañas para toda la población del área (AU)

No disponible

Acceptability of chemoprophylaxis for household contacts of leprosy patients in Bangladesh: a qualitative study.

OBJECTIVES: Chemoprophylaxis with single dose rifampicin is a promising intervention to prevent leprosy in close contacts of patients. However, application in control programmes often requires disclosure of the leprosy diagnosis, which is still a stigmatised disease in many countries. Promoting control and treatment of stigmatised diseases without contributing towards stigma of the individuals involved can be very difficult. The objective of this study was to assess the social acceptability of disclosure of the diagnosis and the attitude towards taking prophylactic medicines in a leprosy endemic area in Bangladesh. DESIGN: Qualitative study through focus group discussions with 136 healthy men and women from different age groups and religions, coming from two rural villages and an urban area in northwest Bangladesh, and 14 health workers with extensive experience with leprosy patients. RESULTS: The participants would not object to disclosure of the diagnosis to household members and nearby family if they were diagnosed with leprosy. However, many participants were not willing to share this information with their neighbours and other social contacts due to stigma of the disease. All healthy participants were willing to take chemoprophylaxis if any of their close contacts were diagnosed with leprosy, even after explaining that full protection against leprosy was not guaranteed. CONCLUSION: It can be concluded that chemoprophylaxis for household contacts of leprosy patients is an effective and socially acceptable addition to the current leprosy control programme. Chemoprophylaxis for other categories of contacts likely to benefit would only be feasible, without disclosure of patient information, if given in the form of mass campaigns for the whole population in the area.

Recent food shortage is associated with leprosy disease in Bangladesh: a case-control study.

BACKGROUND: Leprosy is remaining prevalent in the poorest areas of the world. Intensive control programmes with multidrug therapy (MDT) reduced the number of registered cases in these areas, but transmission of Mycobacterium leprae continues in most endemic countries. Socio-economic circumstances are considered to be a major determinant, but uncertainty exists regarding the association between leprosy and poverty. We assessed the association between different socio-economic factors and the risk of acquiring clinical signs of leprosy. METHODS AND FINDINGS: We performed a case-control study in two leprosy endemic districts in northwest Bangladesh. Using interviews with structured questionnaires we compared the socio-economic circumstances of recently diagnosed leprosy patients with a control population from a random cluster sample in the same area. Logistic regression was used to compare cases and controls for their wealth score as calculated with an asset index and other socio-economic factors. The study included 90 patients and 199 controls. A recent period of food shortage and not poverty per se was identified as the only socio-economic factor significantly associated with clinical manifestation of leprosy disease (OR 1.79 (1.06-3.02); p = 0.030). A decreasing trend in leprosy prevalence with an increasing socio-economic status as measured with an asset index is apparent, but not statistically significant (test for a trend: OR 0.85 (0.71-1.02); p = 0.083). CONCLUSIONS: Recent food shortage is an important poverty related predictor for the clinical manifestation of leprosy disease. Food shortage is seasonal and poverty related in northwest Bangladesh. Targeted nutritional support for high risk groups should be included in leprosy control programmes in endemic areas to reduce risk of disease.