Protective effect of the combination BCG vaccination and rifampicin prophylaxis in leprosy prevention.

BCG vaccination and rifampicin chemoprophylaxis are both strategies for leprosy prevention. While the combined effect is unknown, the combination may give the desired push to halt leprosy transmission. Secondary analysis was done on results from a single centre, double blind, cluster randomized, and placebo-controlled trial. Individually, BCG (given at infancy) and rifampicin showed to protect against leprosy (57% [95% CI: 24-75%] and 58% [95% CI: 30-74%], respectively). The combined strategies showed a protective effect of 80% (95% CI: 50-92%). This is the first time that the additive effect of BCG and rifampicin are shown; the combined strategies can possibly lower leprosy incidence.

Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy.

BACKGROUND: The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer TIRAP has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers. METHODS: We assessed the TIRAP S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh. RESULTS: In Ghana, the TIRAP S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous TIRAP 180L tend to increase the risk of sepsis in the German study (P = 0.04). CONCLUSION: A broad protective effect of TIRAP S180L against infectious diseases per se is not discernible.

Polymorphism N248S in the human Toll-like receptor 1 gene is related to leprosy and leprosy reactions.

We investigated the association between a polymorphism of a key innate immunity receptor, Toll-like receptor 1 (TLR1) N248S, and susceptibility to leprosy and its clinical presentation. TLR1 N248S has been shown elsewhere to diminish TLR1 signaling and subsequent leprosy disease. The homozygous genotype SS was more frequent (P=.012) and the heterozygous SN genotype was less frequent (P=.015) in patients with leprosy than in control subjects. Additional observed differences in allelic frequency in patients who experienced reversal reactions and/or erythema nodosum leprosum reactions indicates that altered TLR1 function, or at least a TLR1 N248S-linked trait, may affect the progression from infection to disease as well as the disease course and the risk of debilitating reactional episodes in this population.

Preventing nerve function impairment in leprosy: validation and updating of a prediction rule.

BACKGROUND: To validate and update a prediction rule for estimating the risk of leprosy-related nerve function impairment (NFI). METHODOLOGY/PRINCIPAL FINDINGS: Prospective cohort using routinely collected data, in which we determined the discriminative ability of a previously published rule and an updated rule with a concordance statistic (c). Additional risk factors were analyzed with a Cox proportional hazards regression model. The population consisted of 1,037 leprosy patients newly diagnosed between 2002 and 2003 in the health care facilities of the Rural Health Program in Nilphamari and Rangpur districts in northwest Bangladesh. The primary outcome was the time until the start of treatment. An NFI event was defined as the decision to treat NFI with corticosteroids after diagnosis. NFI occurred in 115 patients (13%; 95% confidence interval 11%-16%). The original prediction rule had adequate discriminative ability (c = 0.79), but could be improved by substituting one predicting variable: 'long-standing nerve function impairment at diagnosis' by 'anti-PGL-I antibodies'. The adjusted prediction rule was slightly better (c = 0.81) and identified more patients with NFI (80%) than the original prediction rule (72%). CONCLUSIONS/SIGNIFICANCE: NFI can well be predicted by using the risk variables 'leprosy classification' and 'anti-PGL-I antibodies'. The use of these two variables that do not include NFI offer the possibility of predicting NFI, even before it occurs for the first time. Surveillance beyond the treatment period can be targeted to those most likely to benefit from preventing permanent disabilities.

The prevalence of previously undiagnosed leprosy in the general population of northwest bangladesh.

BACKGROUND: The prevalence of previously undiagnosed leprosy (PPUL) in the general population was determined to estimate the background level of leprosy in the population and to compare this with registered prevalence and the known PPUL in different levels of contacts of leprosy patients. METHODOLOGY AND PRINCIPAL FINDINGS: Multistage cluster sampling including 20 clusters of 1,000 persons each in two districts with over 4 million population. Physical examination was performed on all individuals. The number of newly found leprosy cases among 17,862 people above 5 years of age from the cluster sample was 27 (19 SLPB, 8 PB2-5), giving a PPUL rate of 15.1 per 10,000. CONCLUSIONS AND SIGNIFICANCE: PPUL in the general population is six times higher than the registered prevalence, but three times lower than that in the most distant subgroup of contacts (neighbour of neighbour and social contacts) of leprosy patients in the same area. Full village or neighbourhood surveys may be preferable to contact surveys where leprosy is highly endemic.

Asociación entre niveles ANTI-PGL-I IgM y parámetros clínicos y demográficos en la lepra / No disponible

Objetivo: Determinar los factores de riesgo y significado clínico de la seropositividad anti-PGL-I. Diseño: Se llevó a cabo un gran estudio sero-epidemiológico (COLEP) en el noroeste de Bangladesh. Se obtuvo sangre en papel de filtro de 1025 nuevos pacientes antes del tratamiento y se analizaron mediante un ELISA anti-PGL_I; la relación entre los factores determinantes del paciente y la seropositividad se calculó mediante regresión logística. Resultados: La edad media era de 30 años y la proporción varón-hembra era 1.9. En total, 342 pacientes (33-4%) eran seropositivos. Las siguientes variables revelaron una correlación significativa con la seropositividad (P<0,05) en un análisis multivariable: sexo, edad, grado de discapacidad, índice bacteriológica y clasificación de acuerdo con el sistema de la Organización Mundial de la Salud. La cantidad y extensión de los signos clínico se correlacionaron con la seropositividad, excepto la presencia de lesiones satélite. Las personas con o sin cicatriz de vacunación BCG presentaron riesgos similares en cuanto a seropositividad. Conclusión: La serología es un marcador de una carga bacteriana sistémica y puede identificar fuentes de infección con los pacientes con pocos síntomas clínicos. El tamaño de la lesión se correlaciona positivamente con la seropositividad. No hallamos distintos niveles de seropositividad en pacientes con o sin lesiones satélite (AU)

Objetive: To determinate the risk factors and clinical significance of anti-PGL-I seropositivity. Design A large-scale sero-epidemiological study (COLEP) was carried out in northwest Bangladesh. Blood on filter paper from 1025 newly diagnosed patients was collected before treatment was started and tested with an anti-PGL-I-ELISA, the relation between patient determinants and seropositivity was calculated using logistic regression. Results. The median age was 30 years and the male: female ratio 1.9. Overall 342 patients (33.4%) were seropositive. The following determinants showed a significant correlation with seropositivity (P<0,05) in multivariate analysis: sex, age, disability grade, bacterial index and classification according to the World Health Organization (WHO) system. The number and extent of clinical signs correlated with seropositivity, except for the presence of satellite lesions. People with or without a BCG vaccination scar had a similar to be seropositive. Conclusion Serology is a marker for a higher systemic bacterial load and may identify potential infectious sources among patients with few clinical signs. The size of skin lesions was positively correlated with seropositive. We did not find different level of seropositivity among patients with one or two skin lesions, neither did we find different levels among patients with or without satellite lesions (AU)

Physical distance, genetic relationship, age, and leprosy classification are independent risk factors for leprosy in contacts of patients with leprosy.

BACKGROUND: Close contacts of patients with leprosy have a higher risk of developing leprosy. Several risk factors have been identified, including genetic relationship and physical distance. Their independent contributions to the risk of developing leprosy, however, have never been sufficiently quantified. METHODS: Logistic-regression analysis was performed on intake data from a prospective cohort study of 1037 patients newly diagnosed as having leprosy and their 21,870 contacts. RESULTS: Higher age showed an increased risk, with a bimodal distribution. Contacts of patients with paucibacillary (PB) leprosy with 2-5 lesions (PB2-5) and those with multibacillary (MB) leprosy had a higher risk than did contacts of patients with single-lesion PB leprosy. The core household group had a higher risk than other contacts living under the same roof and next-door neighbors, who again had a higher risk than neighbors of neighbors. A close genetic relationship indicated an increased risk when blood-related children, parents, and siblings were pooled together. CONCLUSIONS: Age of the contact, the disease classification of the index patient, and physical and genetic distance were independently associated with the risk of a contact acquiring leprosy. Contact surveys in leprosy should be not only focused on household contacts but also extended to neighbors and consanguineous relatives, especially when the patient has PB2-5 or MB leprosy.

Association between anti-pGL-I IgM and clinical and demographic parameters in leprosy.

OBJECTIVE: To determine the risk factors and clinical significance of anti-PGL-I seropositivity. DESIGN: A large-scale sero-epidemiological study (COLEP) was carried out in northwest Bangladesh. Blood on filter paper from 1025 newly diagnosed patients was collected before treatment was started and tested with an anti-PGL-I ELISA; the relation between patient determinants and seropositivity was calculated using logistic regression. RESULTS: The median age was 30 years and the male:female ratio 1.9. Overall, 342 patients (33.4%) were seropositive. The following determinants showed a significant correlation with seropositivity (P < 0-05) in multivariate analysis: sex, age, disability grade, bacterial index and classification according to the World Health Organization (WHO) system. The number and extent of clinical signs correlated with seropositivity, except for the presence of satellite lesions. People with or without a BCG vaccination scar had a similar risk to be seropositive. CONCLUSION: Serology is a marker for a higher systemic bacterial load and may identify potential infectious sources among patients with few clinical signs. The size of skin lesions was positively correlated with seropositivity. We did not find different levels of seropositivity among patients with one or two skin lesions, neither did we find different levels among patients with or without satellite