Abstract
BackgroundUnsuccessful treatment outcomes among patients with multi-/extensively- drug resistant tuberculosis (TB) have hampered efforts involved in eradicating this disease. In order to better understand the etiology of this disease, we aimed to determine whether single or multiple strains of Mycobacterium tuberculosis (MTB) are localized within lung cavities of patients suffering from chronic progressive TB.Methodology/FindingsMultiple cavity isolates from lung of 5 patients who had undergone pulmonary resection surgery were analyzed on the basis of their drug susceptibility profile, and genotyped by spoligotyping and 24-loci MIRU-VNTR. The patients past history including treatment was studied. Three of the 5 patients had extensive drug resistant TB. Heteroresistance was also reported within different cavity isolates of the lung. Both genotyping methods reported the presence of clonal population of MTB strain within different cavities of the each patient, even those reporting heteroresistance. Four of the 5 patients were infected with a population of the Beijing genotype. Post-surgery they were prescribed a drug regimen consisting of cycloserine, a fluoroquinolone and an injectable drug. A 6 month post-surgery follow-up reported only 2 patients with positive clinical outcome, showing sputum conversion.ConclusionIdentical spoligotype patterns and MIRU-VNTR profiles between multiple cavities of each patient, characterize the presence of clonal population of MTB strains (and absence of multiple MTB infection).
Highlights
Infection due to a single strain of Mycobacterium tuberculosis (MTB) was considered as the cause of active tuberculosis (TB) until early 1970’s when phage typing reported the presence of more than one infecting strain in a single patient [1,2]
Few studies have shown the utility of 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR), a fingerprinting tool in detection of mixed infection and sub-clonal population [7,8]
To determine the presence/absence of multiple MTB strains within lung cavities of patients suffering from chronic progressive TB, we analyzed multiple cavities from lungs of each of the 5 patients who underwent pulmonary resection surgery by determining the drug susceptibility profile of each cavity isolate and further characterizing the bacterial populations present by both, spoligotyping and 24-loci MIRU-VNTR
Summary
Infection due to a single strain of Mycobacterium tuberculosis (MTB) was considered as the cause of active tuberculosis (TB) until early 1970’s when phage typing reported the presence of more than one infecting strain in a single patient [1,2]. Infection with different MTB strains each having different drug susceptibility pattern makes it difficult to effectively treat the patient with a correct combination of anti-tubercular drugs, leading to multi-/extensive- drug resistant (M/XDR) cases. In such cases, the tubercle bacilli overcomes the host immune defense system and does not respond to the anti-tubercular treatment (ATT) leading to chronic progressive disease with formation of cavities, fibrotic lesions and tissue necrosis in the lungs of patients. In order to better understand the etiology of this disease, we aimed to determine whether single or multiple strains of Mycobacterium tuberculosis (MTB) are localized within lung cavities of patients suffering from chronic progressive TB
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