Progression to Active Tuberculosis, but Not Transmission, Varies byMycobacterium tuberculosisLineage in The Gambia

Abstract

Considerable variability exists in the outcome of M. tuberculosis infection. We hypothesized that M. africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease. In a cohort study of tuberculosis patients and their household contacts in the Gambia, we categorized 1,808 HIV negative tuberculosis contacts according to exposure to M. tuberculosis or to M. africanum. A positive skin test indicated transmission and development of tuberculosis during 2 years of follow-up indicated progression to disease. Transmission was similar, but progression to disease was significantly lower in contacts exposed to M. africanum than to M. tuberculosis (1.0% vs 2.9%; Hazard Ratio (HR) 3.1, 95% CI 1.1–8.7). Within M. tuberculosis sensu stricto, contacts exposed to a Beijing family strain were most likely to progress to disease (5.6%; HR 6.7 (2.0–22) relative to M. africanum). M. africanum and M. tuberculosis transmit equally well to household contacts, but contacts exposed to M. africanum are less likely to progress to tuberculosis disease than those exposed to M. tuberculosis. The variable rate of progression by lineage suggests that TB variability matters in clinical settings and should be taken into account in studies evaluating tuberculosis vaccines and treatment regimens for latent tuberculosis infection.

Innate and Adaptive Immune Responses during Acute M. tuberculosis Infection in Adult Household Contacts in Kampala, Uganda

“…Finally, the natural history of MTB infection and TB disease is also influenced by a number of factors related to clinical characteristics of infectious TB cases that come into contact with an individual genetic variation in MTB, and genetic susceptibility of the human host; this study did not account for these factors, but these shall be the focus of future research. 9,[32][33][34] In summary, this study shows that adaptive immune responses can differentiate adult contacts of TB patients who will convert their TST from those already infected and those who remain TST-. Furthermore, for those who convert the TST by 3 months, immune responses to MTB antigens are dynamic and reach those of TST+ contacts anywhere from 3 to 12 months depending on the complexity of the MTB antigen.…”

Association between spoligotype-VNTR types and virulence ofMycobacterium bovisin cattle

“…24 On the other hand, other non-Beijing strains were more virulent than Beijing lineage in human macrophages. 25 Other authors have also investigated the differential virulence of M. tuberculosis complex isolates [26][27][28][29][30] and we previously demonstrated this differential virulence with M. bovis isolates. 31 An essential aspect of this kind of study is that the scoring system has to be a reliable correlate of the pathogenesis.…”

Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

“…It could also be a sign of accelerated recovery from disease by the Mtb-infected patients following treatment or may suggest that Maf is the less virulent of the two pathogens and the group with a more competent immune profile will respond vigorously to the weaker pathogen [3,4].…”

“…The heterogeneity in chest x-rays, bacillary load in sputum and clinical symptoms, likely reflects the variation in host immune response to the invading pathogen, and/or the differences between the lineages within the MTBC. For instance, Maf has slower growth in culture medium compared with Mtb [6,7], which may influence progression to active disease [4].The recently published genome of Maf reveals a high content of pseudogenes and the presence of a unique sequence -the region of difference 900 "RD900" that has been deleted evolutionarily from Mtb and M. bovis strains [8]. Many studies have concentrated on the pathogen strain differences in various geographical locations, with only a few analyzing host-related factors (reviewed in [9]).…”