Different mechanisms for heterogeneity in leprosy susceptibility can explain disease clustering within households.

Egil Fischer,Dik Habbema,Abraham Meima,Jan Richardus,Sake De Vlas

doi:10.1371/journal.pone.0014061

Abstract

The epidemiology of leprosy is characterized by heterogeneity in susceptibility and clustering of disease within households. We aim to assess the extent to which different mechanisms for heterogeneity in leprosy susceptibility can explain household clustering as observed in a large study among contacts of leprosy patients.We used a microsimulation model, parameterizing it with data from over 20,000 contacts of leprosy patients in Bangladesh. We simulated six mechanisms producing heterogeneity in susceptibility: (1) susceptibility was allocated at random to persons (i.e. no additional mechanism), (2) a household factor, (3, 4) a genetic factor (dominant or recessive), or (5, 6) half a household factor and half genetic. We further assumed that a fraction of 5%, 10%, and 20% of the population was susceptible, leading to a total of 18 scenarios to be fitted to the data. We obtained an acceptable fit for each of the six mechanisms, thereby excluding none of the possible underlying mechanisms for heterogeneity of susceptibility to leprosy. However, the distribution of leprosy among contacts did differ between mechanisms, and predicted trends in the declining leprosy case detection were dependent on the assumed mechanism, with genetic-based susceptibility showing the slowest decline. Clustering of leprosy within households is partially caused by an increased transmission within households independent of the leprosy susceptibility mechanism. Even a large and detailed data set on contacts of leprosy patients could not unequivocally reveal the mechanism most likely responsible for heterogeneity in leprosy susceptibility.

Highlights

Leprosy, caused by infection with Mycobacterium leprae, was detected in a quarter of a million people in 2008, and many more people are living with impairments caused by this disease.[1]
Our model, called SIMCOLEP, simulates the spread of M. leprae in a population divided into households, and the development of leprosy by infected individuals
Different mechanisms for heterogeneity of leprosy susceptibility can explain the observed clustering in household contacts of leprosy patients

Summary

Introduction

Leprosy, caused by infection with Mycobacterium leprae, was detected in a quarter of a million people in 2008, and many more people are living with impairments caused by this disease.[1]. Clustering of leprosy patients within households, families, and neighborhoods has been reported many times.[3,4,5,6,7,8] This clustering is partly due to a higher contact intensity, an elevated possibility of transmission between contacts. Only a few people that are exposed to the infection, within or outside households, develop the disease.[9,10,11] Introduction of leprosy on an island shows the heterogeneity in susceptibility most clearly, as the number of cases is limited to a proportion of the total population, smaller than expected given the initial rapid increase of cases.[12] The fraction of susceptible members of the population of the Indian subcontinent is thought to be approximately 10%.[9,10,13] We hypothesize that the clustering of leprosy in households is due to a combination of the increased exposure to infection and specific mechanisms that cluster susceptibility within households

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Conclusion