Progression to active tuberculosis, but not transmission, varies by Mycobacterium tuberculosis lineage in The Gambia.
BACKGROUND
There is considerable variability in the outcome of Mycobacterium tuberculosis infection. We hypothesized that Mycobacterium africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease.


METHODS
In a cohort study of patients with tuberculosis and their household contacts in The Gambia, we categorized 1808 HIV-negative tuberculosis contacts according to exposure to M. tuberculosis or M. africanum. Positive skin test results indicated transmission, and development of tuberculosis during 2 years of follow-up indicated progression to disease.


RESULTS
Transmission rates were similar, but rates of progression to disease were significantly lower in contacts exposed to M. africanum than in those exposed to M. tuberculosis (1.0% vs. 2.9%; hazard ratio [HR], 3.1 [95% confidence interval {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 relative to M. africanum, 6.7 [95% CI, 2.0-22]).


CONCLUSIONS
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 tuberculosis variability matters in clinical settings and should be accounted for in studies evaluating tuberculosis vaccines and treatment regimens for latent tuberculosis infection.
de Jong
Bouke C
BC
Medical Research Council Laboratories, Banjul, The Gambia. bdejong@mrc.gm
Hill
Philip C
PC
Aiken
Alex
A
Awine
Timothy
T
Antonio
Martin
M
Adetifa
Ifedayo M
IM
Jackson-Sillah
Dolly J
DJ
Fox
Annette
A
Deriemer
Kathryn
K
Gagneux
Sebastien
S
Borgdorff
Martien W
MW
McAdam
Keith P W J
KP
Corrah
Tumani
T
Small
Peter M
PM
Adegbola
Richard A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D013045:Species Specificity; D014376:Tuberculosis / Q000382:microbiology / Q000635:transmission*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis