Molecular epidemiological approach to understand and control the emergence and spread of drug resistant Mycobacterium tuberculosis strains in Lima, Peru

Francesca Barletta

Research output: ThesisDoctoral dissertation - Doctoral dissertation

Abstract

Although Peru accounts for only 3% of the population of the Americas, it has 9.5% of the region's tuberculosis (TB) cases. Lima reports 59% of all Peruvian TB cases, 82% of multi-drug resistant (MDR)-TB, and 93% of extremely-drug resistant (XDR)-TB cases. The most affected districts are located in the northeast and together represent 86% of the reported cases in the capital. San Juan de Lurigancho is one of the most concerned districts due to its high pulmonary TB incidence rate (193/100,000 inhabitants) and an overall MDR prevalence of 7%, exceeding the national averages. The aim of this thesis was to develop an affordable molecular diagnostic test and to gain insight in the population structure of M. tuberculosis for controlling the MDR-TB epidemic in the San Juan de Lurigancho district.

A fast TB diagnosis is key to start treatment. Therefore we developed a diagnostic in-house qPCR to be applied directly on sputum samples after a simple and cheap decontamination method and compared its performance against other methods commonly used in resource-poor settings. Our results showed that the qPCR proposed in this study, has a high specificity (99% CI 95-100%) and sensitivity (95% CI 89-98%), short turn-around time, and relatively low cost.

A pilot study to investigate second-line drugs profiles in identified MDR-TB strains showed that a relatively high proportion of MDR-TB strains was resistant to the injectable agents whereas all strains tested were found susceptible to FQs.

Finally, we combined clinical and molecular information (spoligotyping combined with MIRUVNTR-15 loci) about the infection episodes to better understand the TB transmission dynamics in the North-eastern of Lima where TB resistance has increased during the last years in spite of the national decrease of TB incidence and prevalence.

The MTBc population structure was diverse and showed a high clustering rate (69.7%), especially among Haarlem (72.6%) and Beijing (59.2%) families. However none of the first-line drugs were associated with recent transmission within this study population suggesting that the high MDR-TB rate is not primarily due to recent transmission among new TB cases.
Original languageEnglish
Place of PublicationAntwerpen
Publisher
Electronic ISBNs9781339313542
Publication statusPublished - 2015

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