Publications

OBJECTIVES

Targeting high Tuberculosis (TB) transmission sites may offer a novel approach to TB prevention in sub-Saharan Africa. We sought to characterise TB transmission sites in a rural Ugandan township.

METHODS

We recruited adults starting TB treatment in Tororo, Uganda, over 1 year. Fifty four TB cases provided names of frequent contacts, sites of residence, health care, work and social activities, and two sputum samples. Mycobacterium tuberculosis (MTB) culture-positive specimens underwent spoligotyping to identify strains with shared genotypes. We visualised TB case social networks, and obtained, mapped and geo-coded global positioning system measures for every location that cases reported frequenting 1 month before treatment. Locations of spatial overlap among genotype-clustered cases were considered potential transmission sites.

RESULTS

Six distinct genotypic clusters were identified involving 21 of 33 (64%) MTB culture-positive, genotyped cases; none shared a home. Although 18 of 54 (33%) TB cases shared social network ties, none of the genotype-clustered cases shared social ties. Using spatial analysis, we identified potential sites of within-cluster TB transmission for five of six genotypic clusters. All sites but one were healthcare and social venues, including sites of drinking, worship and marketplaces. Cases reported spending the largest proportion of pre-treatment person-time (22.4%) at drinking venues.

CONCLUSIONS

Using molecular epidemiology, geospatial and social network data from adult TB cases identified at clinics, we quantified person-time spent at high-risk locations across a rural Ugandan community and determined the most likely sites of recent TB transmission to be healthcare and social venues. These sites may not have been identified using contact investigation alone.

Despite recent advances in delineating the pathogenic mechanisms of autoimmune disease, the puzzle that reveals the true picture of these diverse immunological disorders is yet to be solved. We know that the human leukocyte antigen (HLA) loci as well as many different genetic susceptibility loci with relatively small effect sizes predispose to various autoimmune diseases and that environmental factors are involved in triggering disease. Models for mechanisms of disease become increasingly complex as relationships between components of both the adaptive and innate immune systems are untangled at the molecular level. In this article, we pose some of the important questions about autoimmunity where the answers will advance our understanding of disease pathogenesis and improve the rational design of novel therapies. How is autoimmunity triggered, and what components of the immune response drive the clinical manifestations of disease? What determines whether a genetically predisposed individual will develop an autoimmune disease? Is restoring immune tolerance the secret to finding cures for autoimmune disease? Current research efforts seek answers to these big questions.