Research paperMolecular characterization of multidrug-resistant Mycobacterium tuberculosis isolates from high prevalence tuberculosis states in Mexico
Introduction
The 2015 World Health Organization (WHO) Tuberculosis (TB) Report estimated 9.6 million new cases of TB in 2014 and 1.5 million deaths caused by the disease. Mismanagement of patients and inadequate administration of antimicrobial therapy are the most important factors contributing to the development of tuberculosis drug resistance (DR-TB). According to the WHO, DR-TB has become a major public health problem in several countries. It is estimated that close to half a million cases exhibit simultaneous resistance to isoniazid and rifampicin, an aggravated form of TB resistance defined as MDR-TB. Recently, the emergence of a more aggressive form of MDR-TB showing additional resistance to any fluoroquinolone and at least one of the three second-line injectable drugs (i.e. amikacin, capreomycin, or kanamycin) has been reported. This form has been labeled extensively drug-resistant TB (XDR-TB) and possess a major threat to TB control (WHO, 2015).
According to the 2014 Report on TB by the National Mycobacteriosis Program, out of the 19,000 cases of pulmonary TB diagnosed each year in Mexico, close to 200 (1.3%) are caused by drug resistant strains. The number of MDR-TB and XDR-TB cases reported is increasing especially in five states: Nuevo Leon, Tamaulipas, Guerrero, Veracruz, and Baja California, the former three contributing with 50%, and the latter two with 80% of the total number of DR-TB and MDR-TB cases (Castellanos-Joya, 2014).
Recent reports on the characterization of genotypic features and mutations associated with resistance to rifampicin (rpoB); isoniazid (katG and inhA); fluoroquinolones (gyrA and gyrB); as well as to kanamycin, amikacin, and capreomycin (rrs, eis and tlyA) in MDR-TB and XDR-TB isolates show variations among geographical regions (Bhembe et al., 2014, Chaoui et al., 2009, Chen et al., 2014, Feuerriegel et al., 2009, Flores-Trevino et al., 2014, Jugheli et al., 2009, Morlock et al., 2003, Perdigao et al., 2010, Sandgren et al., 2009, Sekiguchi et al., 2007, Siddiqi et al., 2002, Sowajassatakul et al., 2014, Surcouf et al., 2011, Zenteno-Cuevas et al., 2009). In addition, description of genotypes and polymorphisms in genes related to drug resistance in TB isolates from Mexico is somewhat limited (Flores-Trevino et al., 2014, Martinez-Guarneros et al., 2013, Nava-Aguilera et al., 2011, Ramaswamy et al., 2004, Zenteno-Cuevas et al., 2015, Zenteno-Cuevas et al., 2009). For these reasons, the goal of this work was to determine the genotypes and polymorphisms presented in genes associated to first and second line drugs in a set of MDR-TB isolates from Veracruz and Baja California, two of the states with the highest prevalence and incidence of DR-TB and MDR-TB in Mexico.
Section snippets
Collection of clinical samples, isolation of Mycobacterium tuberculosis and drug susceptibility test
Fifty-four sputum samples from the same number of patients confirmed as MDR-TB cases by the tuberculosis state programs from Veracruz and Baja California were collected from January 2010 to July 2013. The samples were processed by standard methods (N-acetyl-l-cysteine-sodium hydroxide), and their isolates were recovered in Löwenstein-Jensen media. Drug susceptibility against first-line drugs—streptomycin (S), isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (Z)—was confirmed by the
Population characteristics
In this study, 54 MDR isolates of M. tuberculosis were recovered. Baja California provided 22 (41%) samples and Veracruz the remaining 32 (59%). The average age of the population was 43 ± 15 years and 57% (31) of individuals were male. The most frequent co-morbidities were type 2 diabetes mellitus with 26% (14), followed by HIV with 14% (8). Only 7% (4) of patients mentioned alcohol consumption. 54% (29) mentioned TB as primary diagnosis and 35% (19) reported a previous drug treatment. The average
Discussion
Mexico has the fourth place for incidence of TB and TB-DR in Latin America. Official reports indicate that out of the 19,000 TB cases annually reported, near to 1.5% are DR-TB, 0.4% are MDR-TB and 0.04% are XDR-TB. In addition, Veracruz and Baja California are placed within the first five states with the highest number of MDR-TB cases (Castellanos-Joya, 2014). This figures place to the DR-TB in Mexico as a growing problem that require immediate attention.
Among the individuals exhibiting MDR-TB
Competing interests
The authors declare that they have no competing interests.
Acknowledgements
This work was supported by the Consejo Nacional de Ciencia y Tecnología-Proyecto de desarrollo científico para atender problemas nacionales No. 213712: Desarrollo de un sistema de vigilancia epidemiológico molecular de TB. CONACyT grant No. 166624 “Epidemiología molecular de Mycobacterium tuberculosis en la frontera Noroeste México-Estados Unidos”. The authors would like to thank Andres Beltrán-Ureña for his technical support.
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