Mycobacterium africanum Subtype II Is Associated with Two Distinct Genotypes and Is a Major Cause of Human Tuberculosis in Kampala, Uganda

Abstract

Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex, which also comprises the closely related species M. tuberculosis, M. bovis, M. microti, and M. canetti (21, 24). Since its first description in 1968 (3), M. africanum has been found in several regions of Africa, where it represents up to 60% of clinical strains obtained from patients with pulmonary tuberculosis (7,18,19,23).Recent surveys show highly variable prevalences of M. africanum in different African regions. For example, M. africanum was found in approximately 5% of patients with tuberculosis in the Ivory Coast and in at least 60% of patients in GuineaBissau (2, 10). Most of the studies presented so far have analyzed small numbers of strains from different regions, and systematic studies of prevalence and geographic distribution of M. africanum are still infrequent.In contrast to M. tuberculosis and M. bovis, M. africanum strains show a higher variability of phenotypic attributes, comprising characteristics common to both M. tuberculosis and M.bovis. This phenotypic heterogeneity of M. africanum complicates its unequivocal identification and may lead to misclassification of clinical strains. According to their biochemical characteristics, two major subgroups of M. africanum have been described, corresponding to their geographic origin in western (subtype I) or eastern (subtype II) Africa. Numerical analyses of biochemical characteristics revealed that M. africanum subtype I is more closely related to M. bovis, whereas subtype II more closely resembles M. tuberculosis (5).In our recent work, we determined diagnostic criteria, including phenotypic and biochemical characteristics as well as results of the molecular spoligotyping technique, that permit the accurate differentiation of M. africanum subtypes I and II (15). Spoligotyping is a rapid molecular test based on the detection of various nonrepetitive spacer sequences located between small repetitive units (direct repeats) in the direct repeat locus of M. tuberculosis complex strains. However, spoligotyping does not allow differentiation of M. africanum subtypes from M. tuberculosis without additional routine laboratory procedures. This drawback led us to evaluate the usefulness of gyrB DNA sequence polymorphisms as a further molecular marker for differentiation of the species of the M. tuberculosis complex (16).

Pulmonary Tuberculosis andMycobacterium bovis,Uganda

“…However, the prevalence of M. bovis was <4.2% and confi rmed the lowlevel involvement of M. bovis in human TB in Mbarara district. These fi ndings are consistent with previous work in Uganda's capital, Kampala, and in other African or Asian countries (2,8,9). The estimation of extrapulmonary cases among all TB cases (95% confi dence interval 2%-15.2%) did not differ from the offi cial estimate.…”

Mycobacterium boviswith different genotypes and from different hosts induce dissimilar immunopathological lesions in a mouse model of tuberculosis

“…More recently, three new members of the complex have been described: M. canetti [4], a smooth variant that was isolated first from a Somali patient; M. bovis subsp. caprae, related closely to 'classical' M. bovis, infecting primarily goats in Spain and humans and cattle in Central Europe [5,6], causing one-third of all human M. bovis cases of tuberculosis in Germany; and finally, M. pinnipedii, which causes tuberculosis in marine mammals [7][8][9]. Despite the high overall genetic relationship, the species of the MTBC show variability in their phenotypes, host range and importance for human TB.…”

The Species Mycobacterium africanum in the Light of New Molecular Markers

“…According to their biochemical characteristics, two major M. africanum subgroups have been described, and these subgroups correspond to their geographic origins in West Africa (subtype I, cluster G) or East Africa (subtype II, cluster F) (4, 16). Numerical analyses of biochemical characteristics revealed that M. africanum subtype I is more closely related to M. bovis, whereas subtype II more closely resembles M. tuberculosis (4).More recently, the application of molecular methods has permitted new insights into the molecular characteristics and phylogeny of MTBC species to be obtained (2,7,8,13,14,16,26). In those studies M. africanum strains from West African countries (subtype I) were characterized by the presence of low or medium numbers of IS6110 bands and a specific spoligotype pattern with characteristics of M. bovis and M. tuberculosis.…”

“…However, despite this high degree of similarity at the DNA level, the members of MTBC differ in their host ranges, geographical prevalences, and pathogenicities (27). Hence, the accurate species differentiation of clinical isolates remains necessary for epidemiological and public health purposes.Since its first description in 1968 (3), M. africanum has been found in several regions of Africa, where it represents up to 60% of clinical strains from patients with pulmonary tuberculosis (TB) (16,17,20,26). Recent surveys showed highly variable prevalences of M. africanum in different regions of Africa; e.g., approximately 5% of patients with TB from the Ivory Coast, approximately 10% of patients with TB from Cameroon (17), and at least 60% of patients with TB from Guinea-Bissau (1, 8) were found to be infected with M. africanum.…”