Mycobacterium tuberculosis ecology in Venezuela: epidemiologic correlates of common spoligotypes and a large clonal cluster defined by MIRU-VNTR-24

Abstract

BackgroundTuberculosis remains an endemic public health problem, but the ecology of the TB strains prevalent, and their transmission, can vary by country and by region. We sought to investigate the prevalence of Mycobacterium tuberculosis strains in different regions of Venezuela. A previous study identified the most prevalent strains in Venezuela but did not show geographical distribution nor identify clonal genotypes. To better understand local strain ecology, we used spoligotyping to analyze 1298 M. tuberculosis strains isolated in Venezuela from 1997 to 2006, predominantly from two large urban centers and two geographically distinct indigenous areas, and then studied a subgroup with MIRU-VNTR 24 loci.ResultsThe distribution of spoligotype families is similar to that previously reported for Venezuela and other South American countries: LAM 53%, T 10%, Haarlem 5%, S 1.9%, X 1.2%, Beijing 0.4%, and EAI 0.2%. The six most common shared types (SIT's 17, 93, 605, 42, 53, 20) accounted for 49% of the isolates and were the most common in almost all regions, but only a minority were clustered by MIRU-VNTR 24. One exception was the third most frequent overall, SIT 605, which is the most common spoligotype in the state of Carabobo but infrequent in other regions. MIRU-VNTR homogeneity suggests it is a clonal group of strains and was named the "Carabobo" genotype. Epidemiologic comparisons showed that patients with SIT 17 were younger and more likely to have had specimens positive for Acid Fast Bacilli on microscopy, and patients with SIT 53 were older and more commonly smear negative. Female TB patients tended to be younger than male patients. Patients from the high incidence, indigenous population in Delta Amacuro state were younger and had a nearly equal male:female distribution.ConclusionSix SIT's cause nearly half of the cases of tuberculosis in Venezuela and dominate in nearly all regions. Strains with SIT 17, the most common pattern overall may be more actively transmitted and SIT 53 strains may be less virulent and associated with reactivation of past infections in older patients. In contrast to other common spoligotypes, strains with SIT 605 form a clonal group centered in the state of Carabobo.

Predominant Mycobacterium tuberculosis Families and High Rates of Recent Transmission among New Cases Are Not Associated with Primary Multidrug Resistance in Lima, Peru

“…In contrast to previous reports from Latin America in which LAM was the most common family (11,(36)(37)(38)(39)(40), our results demonstrated a predominance of the Haarlem family among new cases in the district of San Juan de Lurigancho.…”

Mycobacterium tuberculosis Strains Potentially Involved in the TB Epidemic in Sweden a Century Ago

“…In a molecular analysis of M. tuberculosis DNA from a family of 18th century Hungarians two spoligotypes were identified, corresponding to SIT50 and SIT53 [25]. As in our study SIT53 is found in elderly patients in other parts of the world: in a study from Venezuela, patients with SIT53 had a significantly higher mean age compared to all other patients [26], and in Mexico SIT53 was significantly more prevalent in elderly patients, especially in females [27]. Polymorphism in the direct repeat region in clinical isolates appears to be the result of successive deletions of single discrete direct variant repeats (DVRs) or of multiple contiguous DVRs from a primordial direct repeat region [28].…”

Population Structure among Mycobacterium tuberculosis Isolates from Pulmonary Tuberculosis Patients in Colombia

“…This sublineage, although described for the first time in 1998 in this Colombian seaport city, has only been reported since then from patients whose origin is from this same city, or patients with the same origin but diagnosed in the country's inland major urban settings [38]–[40]. In agreement with these data, despite the human migration from Asia, where the Beijing isolates are very frequent, they represent a proportion about 5% or less of isolates in Latin America, according to several reports [20]–[25].…”