The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis |
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Authors: | Caws Maxine Thwaites Guy Dunstan Sarah Hawn Thomas R Lan Nguyen Thi Ngoc Thuong Nguyen Thuy Thuong Stepniewska Kasia Huyen Mai Nguyet Thu Bang Nguyen Duc Loc Tran Huu Gagneux Sebastien van Soolingen Dick Kremer Kristin van der Sande Marianne Small Peter Anh Phan Thi Hoang Chinh Nguyen Tran Quy Hoang Thi Duyen Nguyen Thi Hong Tho Dau Quang Hieu Nguyen T Torok Estee Hien Tran Tinh Dung Nguyen Huy Nhu Nguyen Thi Quynh Duy Phan Minh van Vinh Chau Nguyen Farrar Jeremy |
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Affiliation: | Oxford University Clinical Research Unit, Hospital for Tropical Diseases, District 5, Ho Chi Minh City, Vietnam. mcaws@hotmail.com |
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Abstract: | The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193-0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15-2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis. |
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