HIV Infection Disrupts the Sympatric Host–Pathogen Relationship in Human Tuberculosis

Abstract

The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of HIV–infected and HIV–negative patients with tuberculosis (TB) between 2000 and 2008 in Switzerland. We analyzed 518 TB patients of whom 112 (21.6%) were HIV–infected and 233 (45.0%) were born in Europe. We found that among European-born TB patients, recent transmission was more likely to occur in sympatric compared to allopatric host–pathogen combinations (adjusted odds ratio [OR] 7.5, 95% confidence interval [95% CI] 1.21–infinity, p = 0.03). HIV infection was significantly associated with TB caused by an allopatric (as opposed to sympatric) M. tuberculosis lineage (OR 7.0, 95% CI 2.5–19.1, p<0.0001). This association remained when adjusting for frequent travelling, contact with foreigners, age, sex, and country of birth (adjusted OR 5.6, 95% CI 1.5–20.8, p = 0.01). Moreover, it became stronger with greater immunosuppression as defined by CD4 T-cell depletion and was not the result of increased social mixing in HIV–infected patients. Our observation was replicated in a second independent panel of 440 M. tuberculosis strains collected during a population-based study in the Canton of Bern between 1991 and 2011. In summary, these findings support a model for TB in which the stable relationship between the human host and its locally adapted M. tuberculosis is disrupted by HIV infection.

Genetic Diversity and Dynamic Distribution of Mycobacterium tuberculosis Isolates Causing Pulmonary and Extrapulmonary Tuberculosis in Thailand

“…There is some evidence of disruption of sympatric host-pathogen coevolution by HIV infection (30). The dynamic distribution of M. tuberculosis genotypes among different age groups of the HIV-negative PTB patients indicated the presence of clonal selection among patient age groups (Fig.…”

Diversity and Evolution of Mycobacterium tuberculosis: Moving to Whole-Genome-Based Approaches

“…The role of social factors is suggested (e.g., a contrario by the observation of a weaker association between lineages and host populations in situations or places favoring everyday contacts between human population groups [Varghese et al 2013]). The hypothesis of biological adaptation is likewise supported by the observation that the association between a pathogen's lineages and host population groups appears disrupted in immunodeficient patients (Gagneux et al 2006a;Fenner et al 2013).…”

Standard Genotyping Overestimates Transmission of Mycobacterium tuberculosis among Immigrants in a Low-Incidence Country

“…In 2012, we conducted a nationwide study of the molecular epidemiology of TB in Switzerland as a collaborative project involving the Swiss HIV Cohort Study (SHCS), the National Center for Mycobacteria, diagnostic microbiology laboratories, departments of respiratory medicine and public health, and the Federal Office of Public Health (www.tb-network.ch) (9,(25)(26)(27)(28). The study setting was previously described in detail (9).…”

“…The study population consisted of 520 TB patients from the nationwide study in Switzerland (9,(25)(26)(27)(28). The patient characteristics are described in Table 1.…”