RD^Rio Mycobacterium tuberculosis Infection Is Associated With A Higher Frequency of Cavitary Pulmonary Disease

Division of International Medicine and Infectious Diseases, Department of Medicine. Weill Medical College of Cornell University, New York, USA; Tuberculosis Research Unit, Medical School of Federal University of Rio de Janeiro. Brazil; Departamento de Clinica Medica/Pneumologia da Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Division of Biostatistics and Epidemiology, Department of Public Health, Weill Medical College of Cornell University, New York, USA; Faculdade de Farmacia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Fundação Ezequiel Dias (FUNED), Minas Gerais, Belo Horizonte, Brazil; Clinical Microbiology Service and the Department of Pathology, Columbia University Medical Center, New York-Presbyterian Hospital, New York, NY

^* To whom correspondence should be addressed. Email: jlho{at}med.cornell.edu.

	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 (LAM) 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.