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Published ahead of print on December 30, 2003, doi:10.1164/rccm.200305-714OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 5, March 2004, 610-614

A more recent version of this article appeared on March 1, 2004
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Submitted on June 9, 2003
Accepted on December 19, 2003

Patients with Active Tuberculosis Often have Different Strains in the Same Sputum Specimen

Robin M Warren1*, Thomas C Victor1, Elizabeth M Streicher1, Madalene Richardson1, Nulda Beyers2, Nicolaas C Gey van Pittius1, and Paul D van Helden1

1 MRC Centre for Molecular and Cellular Biology, Medical Biochemistry, Stellenbosch University, Tygerberg, South Africa, 2 Centre for TB Research and Education, Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa

* To whom correspondence should be addressed. 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 a protective immunity against exogenous reinfection. In this study, a novel PCR method to 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 epidemiological field site in Cape Town, South Africa. The sensitivity and specificity of the PCR-based strain classification method was 100% (95%CI 85 -100%) when compared to DNA fingerprinting and spoligotyping. Application of this method, showed that 19% of all patients were simultaneously infected with Beijing and non-Beijing strains, while 57% of patients infected with a Beijing strain were also infected with a non-Beijing strain. Multiple infections were more frequent in retreatment cases (25%) as compared to new cases (17%), but were not associated with gender, age or smear grading. These results suggest that multiple infections are frequent, implying high reinfection rates and the absence of an 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: Mycobacterium tuberculosis, reinfection, multiple infection




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