A population-based study of first and second-line drug-resistant tuberculosis in a high-burden area of the Mexico/United States border

The resistance of 139 Mycobacterium tuberculosis (MTB) isolates from the city of Monterrey, Northeast Mexico, to first and second-line anti-TB drugs was analysed. A total of 73 isolates were susceptible and 66 were resistant to anti-TB drugs. Monoresistance to streptomycin, isoniazid (INH) and ethambutol was observed in 29 cases. Resistance to INH was found in 52 cases and in 29 cases INH resistance was combined with resistance to two or three drugs. A total of 24 isolates were multidrug-resistant (MDR) resistant to at least INH and rifampicin and 11 MDR cases were resistant to five drugs. The proportion of MDR-TB among new TB cases in our target population was 0.72% (1/139 cases). The proportion of MDR-TB among previously treated cases was 25.18% (35/139 cases). The 13 polyresistant and 24 MDR isolates were assayed against the following seven second-line drugs: amikacin (AMK), kanamycin (KAN), capreomycin (CAP), clofazimine (CLF), ethionamide (ETH), ofloxacin (OFL) and cycloserine (CLS). Resistance to CLF, OFL or CLS was not observed. Resistance was detected to ETH (10.80%) and to AMK (2.70%), KAN (2.70%) and CAP (2.70%). One isolate of MDR with primary resistance was also resistant to three second-line drugs. Monterrey has a high prevalence of MDR-TB among previously treated cases and extensively drug-resistant-MTB strains may soon appear.

Asociación de la tuberculosis pulmonar con los antígenos del sistema HLA en el Noreste de México / Association of pulmonar tuberculosis with HLA system antigens in Northeastern Mexico

Antecedentes: La susceptibilidad genética a tuberculosis pulmonar (TbP) ha sido asociada al sistema HLA (antígenos de los leucocitos humanos) del MHC (complejo mayor de histocompatibilidad), principalmente con los antígenos HLA-DR y -DQ. Dado lo anterior, el objetivo de este estudio caso-control no pareado, fue determinar la asociación de TbP con los antígenos HLA-DR y -DQ en pacientes que asistían a una unidad médica del IMSS. Métodos: Los fenotipos del sistema HLA de casos (n=50) y controles (n=417), se definieron serológicamente por la técnica de microlinfocitotoxicidad dependiente de complemento. Los linfocitos B fueron obtenidos utilizando inmunoperlas. Las frecuencias alélicas y haplotípicas, equilibrio de Hardy-Weinberg y el desequilibrio de ligamiento, se determinaron mediante el programa computacional Arlequín versión 3.01, y el riesgo relativo (RR) mediante el programa Epimax Table Calculator. Resultados: Los alelos HLA-DR11(5), -DR16(2) y -DQ7(3) y los haplotipos /DR11(5)-DQ7(3), /DR14(6)-DQ5(1) y /DR16(2)-DQ7(3) fueron más frecuentes en casos que en controles (RR>1, p<0.05). Los alelos HLA-DR17(3) y DQ8(3) y los haplotipos /DR17(3)-DQ2 y /DR4-DQ8(3) fueron más frecuentes en controles que en casos (RR<1, p<0.05). Conclusiones: Estos resultados sugieren asociación entre TbP y HLA-DR y -DQ en esta población mestiza mexicana y son similares a los encontrados en otros estudios caso-control no pareados a nivel mundial.

BACKGROUND: Genetic susceptibility to pulmonary tuberculosis (PTb) has been associated with the HLA (Antigens of the Human Leukocytes) system of the MHC (Major Histocompatibility Complex), mainly with HLA-DR and-DQ antigens. Based on this assumption we carried out a case control study to determine the association of PTb with the HLA-DR and-DQ antigens among a sample of patients attending a medical unit belonging to the Mexican Social Security System (IMSS). METHODS: HLA system phenotypes from cases (n=50) and controls (n=417), were defined serologically using a complement dependent microlymphocytotoxic assay. B lymphocytes were obtained using immunobeads. The allele and haplotype frequencies were determined using the Arlequin version 3.01 computer software. Relative risk (RR) was calculated with the Epimax Table Calculator. RESULTS: The alelles HLA-DR11(5), -DR16(2) and -DQ7(3) and haplotypes /DR11(5)-DQ7(3), /DR14(6)-DQS(1) and /DR16(2)-DQ7(3) had a higher frequency in cases than in controls (RR>1, p<0.05). The HLA-DR17(3) and DQ8(3) alelles and /DR17(3)-DQ2 and /DR4-DQ8(3) haplotypes had a higher frequency among controls than among cases (RR<1, p<.05). CONCLUSIONS: These results indicate an association between PTb with the HLA-DR and -DQ antigens in a Mexican sample. Our results are similar to those found in the international literature.