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Patients with Active Tuberculosis often Have Different Strains in the Same Sputum Specimen

Medical Research Council Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, and Centre for Tuberculosis Research and Education, Department of Child Health and Paediatrics, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa

Correspondence and requests for reprints should be addressed to Robin M. Warren, M.D., MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, Stellenbosch University, P.O. Box 19063, Tygerberg, South Africa 7505. E-mail: rw1{at}sun.ac.za

It is generally accepted that tuberculosis results from a single infection with a single Mycobacterium tuberculosis strain. Such infections are thought to confer protective immunity against exogenous reinfection. In this study, a novel polymerase chain reaction method was developed to specifically identify M. tuberculosis strains belonging to the Beijing and non-Beijing evolutionary lineages in sputum specimens collected from tuberculosis patients resident in an epidemiologic field site in Cape Town, South Africa. The sensitivity and specificity of the polymerase chain reaction–based strain classification method were 100% (95% confidence interval, 85–100%) when compared with DNA fingerprinting and spacer oligotyping (spoligotyping). Application of this method showed that 19% of all patients were simultaneously infected with Beijing and non-Beijing strains, and 57% of patients infected with a Beijing strain were also infected with a non-Beijing strain. Multiple infections were more frequent in retreatment cases (23%) as compared with new cases (17%), but were not associated with sex, age, or smear grading. These results suggest that multiple infections are frequent, implying high reinfection rates and the absence of efficient protective immunity conferred by the initial infection. This finding could influence our understanding of the epidemiology of disease in high-incidence regions and our understanding for vaccine development.

Key Words: multiple infection • Mycobacterium tuberculosis • reinfection

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