Abstract
Molecular genotyping has shown Mycobacterium tuberculosis lineages to be geographically restricted and associated with distinct ethnic populations. Whether tuberculosis (TB) caused by some M. tuberculosis lineages can present with a differential clinical spectrum is controversial because of very limited clinical data. We recently reported on the discovery of RD(Rio) M. tuberculosis, a Latin American-Mediterranean sublineage that is the predominant cause of TB in Rio de Janeiro, Brazil. To investigate the clinical attributes of TB caused by RD(Rio) strains, we studied a cohort of TB cases from Belo Horizonte, Brazil, in which clinical information recorded on a standardized questionnaire was collected at the time of microbiological testing. These patients were referred for culture and drug susceptibility testing because of the clinical suspicion of "complicated" TB, as demonstrated by high rates of multidrug resistance (12%) and cavitary TB (80%). We performed spoligotyping and RD(Rio) genotyping on the M. tuberculosis strains and analyzed the clinical data from these patients. RD(Rio) M. tuberculosis accounted for 37% of the total TB burden. Multivariate analysis found a significant association between TB caused by RD(Rio) strains and pulmonary cavitation and residence in Belo Horizonte. Since cavitary TB is associated with higher sputum bacillary load, our findings support the hypothesis that RD(Rio) M. tuberculosis is associated with a more "severe" disease as a strategy to increase transmission. Future studies are needed to confirm these observations and to better define the contribution of RD(Rio) M. tuberculosis to the global TB epidemic.
Highlights
Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), is estimated to have infected one-third of the world’s population and annually causes ϳ8 million new TB cases and Ͼ2 million deaths [16, 58]
The presence of infection with more than one strain of M. tuberculosis in the same episode is well described in the literature [19, 46, 60], and our previous report confirmed RDRio and wild-type” non-RDRio (WT) strains in the same specimen [33]
The importance of the Latin American-Mediterranean (LAM) family is reinforced by reports that it has been associated with outbreaks and multiple drug resistance (MDR) [9, 30, 49], including the recent description that a strain from the LAM4 subfamily is the leading cause of XDR-TB in South Africa [43]
Summary
Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), is estimated to have infected one-third of the world’s population and annually causes ϳ8 million new TB cases and Ͼ2 million deaths [16, 58]. Genome-wide single nucleotide polymorphism (SNP) and deletion analyses have been used to organize the global M. tuberculosis population structure into overlapping phylogenies with major lineages that show distinct geographic distribution and that may be associated with specific host adaptation [1, 21, 23, 24, 27, 28, 50]. For example, is the predominant family in major SNP cluster II, accounts for ϳ10% of strains causing TB globally, and is localized mainly to Asia but has spread internationally. The Latin American-Mediterranean (LAM) family, a member of SNP cluster VI, appears to be the single most prevalent M. tuberculosis lineage globally [8], accounting for ϳ15% of the global TB burden. Records showed trends in the data suggesting that RDRio strains may cause a form of TB with a distinct clinical presentation even though an association with MDR or specific risk factors for TB was lacking
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