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

Abstract

T uberculosis (TB) is among the top 10 causes of death in the global ranking (1). Although Peru accounts for only 3% of the population of the Americas, it has 9.5% of the region's TB cases. According to the World Health Organization (WHO), 21,916 new cases of pulmonary TB were reported in Peru between January and November 2013 (2). Urban areas are more affected, with 59% of all Peruvian TB cases, 82% of multidrug-resistant (MDR) TB cases, and 93% of extensively drug-resistant (XDR) TB cases occurring in Lima. Within the capital area, TB cases are heterogeneously distributed. The most affected districts are located in the northeast and together represent 86% of the reported cases in the capital (3, 4). San Juan de Lurigancho is the most populated district in this area, with 1,004,339 inhabitants (5), and reports a pulmonary TB incidence rate of 193 cases per 100,000 inhabitants, a smear-positive TB incidence rate of 126 cases per 100,000 inhabitants (6), and an overall MDR prevalence of 7% (7), exceeding the national averages for the three indicators of 103 cases per 100,000 inhabitants, 62 cases per 100,000 inhabitants, and 5.3%, respectively (8). The HIV prevalence among TB patients in this setting is similar to the national prevalence, which in 2008 was 2.6% (9).Peru has been considered a good example of the beneficial effects of implementing directly observed therapy short course (DOTS) in a country's health system (10). Nevertheless, national surveys from 1996 and 2006 have shown increases in MDR rates from 2.4% to 5.3% among new cases and from 15.7% to 23.6% among previously treated cases (11). This paradox of improved TB management and worsening resistance prevalence has been explained by increases in the notified cases, i.e., in case detection, although treatment outcomes remain poor (12). Basically, the observed increases in MDR-TB rates may result from two factors, i.e., transmission of MDR-TB and acquired resistance due to ineffective TB treatment selecting for spontaneous mutations in specific genes associated with drug resistance (13,14).Molecular strain typing (genotyping) has significantly contributed worldwide to the understanding of TB epidemiology and transmission dynamics (15,16), by confirming outbreaks (17) and identifying the clonal spread of successful strains, including MDR strains (18,19). Furthermore, molecular typing has shown that the Mycobacterium tuberculosis complex (MTBc) has a diverse population structure, being composed of seven lineages of human

Molecular epidemiology and drug resistance patterns ofMycobacterium tuberculosiscomplex isolates from university students and the local community in Eastern Ethiopia

“…The predominant MTBC lineages in this study were lineage 4 followed by lineage 3; findings that are similar to other studies conducted in Ethiopia [10, 19, 22]. We also demonstrate that local sub-linages such as the newly described “Ethiopia_4” and the closely related to Ethiopia_3 (both part of lineage 4 and related to TUR genotype strains) dominate among Ethiopian TB cases but do not play a major role in the global TB epidemic.…”

“…A cluster was defined as two or more MTBC isolates sharing identical 24-loci MIRU/VNTR and spoligotyping patterns. Samples with no PCR amplicon at only one locus in the 24-loci MIRU/VNTR analysis were included for further analysis by considering missing data at the respective locus [19].…”

Drug resistance and population structure of M.tuberculosis isolates from prisons and communities in Ethiopia

“…Heterogeneous isolates with double alleles at only one locus were included in the cluster analysis (both patterns were compared). Isolates with no PCR amplicon at only one locus were treated as missing data at the respective locus and also were included, whereas isolates lacking amplicons at two or more loci were excluded [28, 30]. …”

Identification of the Mycobacterium tuberculosis Beijing lineage in Ecuador

“…Genotyping techniques are useful for the identification of isolate clusters, and they provide researchers and clinicians with a better understanding of the transmission dynamics of this pathogen in different settings (2)(3)(4), allowing the differentiation of M. tuberculosis lineages as well. Some of them, such as the Beijing lineage, are considered to be more "successful" due to their virulence, transmissibility and acquisition of resistance (5,6).…”