Transmissibility of Mycobacterium africanum compared with the Cameroon strain of M tuberculosis

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Mycobacterium africanum causes up to half of TB in West Africa. It is closely related to regular M. tuberculosis, but we have identified some important differences. One of these is that a new diagnostic test does not perform well in people infected with M. africanum. This test is based on the protein ESAT-6, which is also used in a new generation TB vaccine. Another difference is that HIV infected people are even more susceptible to infection with M. africanum than with M. tuberculosis. Thirdly, people who were exposed to M. africanum are less likely to develop TB than those exposed to M. tuberculosis. Based on findings elsewhere, we suspect that the Cameroon strain, which has replaced M. africanum as the most important cause of TB in Cameroon, will be transmitted to other people more readily than M. africanum.||We continue the tests which identify the different bacteria which cause TB, including M. africanum and M. tuberculosis. We try to identify bacteria that spread more readily to contacts exposed to someone with TB. Ultimately we hope our findings may assist in optimization of diagnostic tests and in the control of the spread of tuberculosis.

Technical Summary

Within the Tuberculosis Case contact (TBCC) study at MRC in the Gambia, we identified Mycobacterium africanum as an important cause of TB with 38% prevalence among smear positive TB patients. We identified several differences between M. africanum and M. tuberculosis sensu stricto, including an association with HIV infection, and a lower IFNg response among cases and contacts infected with M. africanum. ||The present study aims at clarifying further differences, by continued mycobacterial genotyping within the next Case Contact study, the Isoniazid Reversion Study (IRS). These include the hypothesis that the Cameroon strain, a subspecies of M. tuberculosis sensu stricto which in Cameroon appears to have replaced M. africanum over the last 30 years, is more readily transmissible than M. africanum. The Cameroon strain was found at low prevalence (3%) in the TBCC study, and continued genotyping of Case Contact isolates allows us to study this and other strains in more detail.||For genotyping, we use spoligotyping as well as PCR for strain defining Large Sequence Polymorphisms.||So far, 376 isolates of TB patients have been genotyped (both TBCC and IRS Case Contact studies), and these patients have in total 2495 household contacts. IRS isolates continue to include 38% M. africanum. We identified one group of isolates within M. tuberculosis sensu stricto which has only sporadically been identified elsewhere and may be named the Gambian family. When comparing tuberculin skin test positivity rates, as a measure of transmission, by strain for those strains with information on ? 100 contacts, we did not identify a significant difference between strains. However, the rate of primary progression within the 2 year follow-up differed between contacts of different strains, and was higher for contacts of Beijing family isolates and of strain RD174, and lower for contacts exposed to M. africanum. This fits with other findings on the Beijing and RD174 strains, which identified respectively a stronger immunosuppressive effect and a deletion in the DosR latency regulon.||In summary, this ongoing genotyping work has defined the molecular epidemiology of TB in the Gambia and highlighted the high prevalence of M. africanum in the region. Important phenotypic differences between M. africanum and M. tuberculosis, from the current and prior Case Contact Study, include an association with HIV infection and attenuated ESAT-6 immunogenicity. In addition, M. africanum infection appears to progress to disease at lower rates than M. tuberculosis. Genomic studies that aim to explain these differences may aid in our understanding of immunity to TB.

Publications

10 25 50
publication icon
Adetifa IM (2007) Rising ELISPOT count prior to the onset of symptoms of full-blown tuberculosis disease. in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

publication icon
De Jong BC (2007) Clinical presentation and outcome of tuberculosis patients infected by M. africanum versus M. tuberculosis. in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

 
Description NIH K01 award
Amount £237,457 (GBP)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 10/2007 
End 08/2010
 
Title spoligotype automated interpretation 
Description The software automatically grids and classifies spoligotype results 
Type Of Material Data analysis technique 
Year Produced 2009 
Provided To Others? Yes  
Impact publication PMID: 19674444 
URL http://europepmc.org/abstract/MED/19674444
 
Description WANETAM 
Organisation University of Dakar
Department Centre Hospitalier Universitaire
Country Senegal 
Sector Academic/University 
PI Contribution Together with Dr Martin Antonio we provide the TB trainings for 7 partner institutions as part of the West African Node of Excellence for TB, AIDS, malaria, funded in 2009 by EDCTP.
Collaborator Contribution Through the network we will genotype isolates from the region for drug resistance and phylogeny.
Impact Capacity building visits to partner institutions and trainings at the MRC Gambia unit
Start Year 2009