Drug resistance in Mexico: results from the National Survey on Drug-Resistant Tuberculosis.

OBJECTIVE: To present estimations obtained from a population-level survey conducted in Mexico of prevalence rates of mono-, poly- and multidrug-resistant strains among newly diagnosed cases of pulmonary tuberculosis (TB), as well as the main factors associated with multidrug resistance (combined resistance to isoniazid and rifampicin). DESIGN: Study data came from the National Survey on TB Drug Resistance (ENTB-2008), a nationally representative survey conducted during 2008-2009 in nine states with a stratified cluster sampling design. Samples were obtained for all newly diagnosed cases of pulmonary TB in selected sites. Drug susceptibility testing (DST) was performed for anti-tuberculosis drugs. RESULTS: DST results were obtained for 75% of the cases. Of these, 82.2% (95%CI 79.5-84.7) were susceptible to all drugs. The prevalence of multidrug-resistant TB (MDR-TB) was estimated at 2.8% (95%CI 1.9-4.0). MDR-TB was associated with previous treatment (OR 3.3, 95%CI 1.1-9.4). CONCLUSIONS: The prevalence of drug resistance is relatively low in Mexico. ENTB-2008 can be used as a baseline for future follow-up of drug resistance.

Multidrug-resistant pulmonary tuberculosis in Los Altos, Selva and Norte regions, Chiapas, Mexico.

OBJECTIVES: To analyse the proportion of multidrug-resistant tuberculosis (MDR-TB) in cultures performed during the period 2000-2002 in Los Altos, Selva and Norte regions, Chiapas, Mexico, and to analyse MDR-TB in terms of clinical and sociodemographic indicators. METHODS: Cross-sectional study of patients with pulmonary tuberculosis (PTB) from the above regions. Drug susceptibility testing results from two research projects were analysed, as were those of routine sputum samples sent in by health personnel for processing (n = 114). MDR-TB was analysed in terms of the various variables of interest using bivariate tests of association and logistic regression. RESULTS: The proportion of primary MDR-TB was 4.6% (2 of 43), that of secondary MDR-TB was 29.2% (7/24), while among those whose history of treatment was unknown the proportion was 14.3% (3/21). According to the logistic regression model, the variables most highly associated with MDR-TB were as follows: having received anti-tuberculosis treatment previously, cough of >3 years' duration and not being indigenous. CONCLUSIONS: The high proportion of MDR cases found in the regions studied shows that it is necessary to significantly improve the control and surveillance of PTB.

Evaluation of new external quality assessment guidelines involving random blinded rechecking of acid-fast bacilli smears in a pilot project setting in Mexico.

SETTING: Laboratories in Mexico that support the national tuberculosis (TB) control program have been involved in an acid-fast bacilli (AFB) microscopy external quality assurance program which includes rechecking 100% of smears identified as AFB-positive by the local laboratories and 10% of smears identified as AFB-negative. Very few errors have been detected in Mexico using non-random selection and unblinded rechecking of the slides. OBJECTIVE: To evaluate the results from a 1-year pilot program involving blinded rechecking of randomly selected AFB slides from local TB laboratories in two Mexican states and determine its feasibility for future implementation. DESIGN: To reduce potential bias, laboratory staff from the National TB Laboratory, Institute for Epidemiological Diagnosis and Reference (InDRE), performed quarterly statistical sampling of AFB smears and on-site evaluations in local laboratories in each state. AFB smears were rechecked at the respective state laboratories with discordant results resolved at InDRE. RESULTS: A significantly greater percentage of errors was detected on the randomly selected, blinded AFB smears than on the non-randomly selected, unblinded smears. CONCLUSION: Random blinded rechecking provides more accurate estimates of AFB microscopy results, resulting in improved diagnosis and monitoring of treatment response.

[Drug resistance of Mycobacterium tuberculosis in Orizaba, Veracruz. Implications for the tuberculosis prevention and control program]. / Resistencia de Mycobacterium tuberculosis a los antimicrobianos en Orizaba, Veracruz. Implicaciones para el Programa de Prevención y Control de la Tuberculosis.

BACKGROUND: Tuberculosis, declared a global emergency by the World Health Organization, continues to be an important public health problem in Mexico, included in the first twenty causes of death. OBJECTIVE: To know the impact of drug resistance of Mycobacterium tuberculosis on treatment outcome, need of re-treatment and mortality in a cohort of patients with pulmonary tuberculosis receiving directly observed therapy, short course (DOTS). METHODS: We conducted a population-based study in a suburban region in Southern Mexico. People who had been coughing for more than two weeks underwent sputum acid-fast bacilli smear. Patients with a positive smear were recruited and underwent clinical exam, chest X-ray, HIV testing, and sputum cultures. Identification, drug susceptibility testing and restriction fragment length polymorphism analysis (RFLP) were performed in all isolates. Patients were followed every 12 months for new episodes of tuberculosis and vital status. Patients were referred for clinical care to the local program of tuberculosis. Deaths were corroborated with death certificates. Informed consent was obtained from participants. RESULTS: Between March 1995 and February 1999, tuberculosis was diagnosed in 371 patients who were followed for an average of 32 months. M. tuberculosis was cultured from 316 patients; resistance to any drug occurred in 25.0% of isolates (primary 18.8%, acquired 49.2%); only to isoniazid in 6.8% (primary 7.3%, acquired 4.8%); to isoniazid and rifampin in 6.2% (primary 1.6%, acquired 23.8%). Patients with drug resistance had a higher probability of treatment failure (OR = 16.9, CI 95% 4.5-63.0) and patients with MDR strains had a higher probability of need of re-treatment (RR = 24.4, CI 95% 8.8-67.6), and of death (RR = 4.0, CI 95% 1.5-10.7). Additional variables were found to be associated with subsequent episodes of disease and mortality: Cocaine use, chronic disease, type of radiological lesions, HIV co-infection, non-compliance and treatment delay, as well as RFLP clustering. CONCLUSIONS: In this study, we observed that drug resistance showed a severe impact on the outcome and survival; drug-resistance was the most significant factor for these negative outcomes; DOTS may not be sufficient in areas where drug resistance is considerable, and patient follow-up for longer periods of time, as compared to evaluation at the end of treatment, provides additional information which is useful for prevention and control programs.

Survey of drug resistance of Mycobacterium tuberculosis in 3 Mexican states, 1997.

BACKGROUND: Drug resistance threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Mexico. OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Mexico. METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in the states of Baja California, Sinaloa, and Oaxaca, Mexico. We performed cultures and drug susceptibility testing on M tuberculosis isolates from patients with newly diagnosed, smear-positive TB from April 1 to October 31, 1997. RESULTS: Mycobacterium tuberculosis was isolated from 460 (75%) of the 614 patients. Levels of resistance in new and retreatment TB cases to 1 or more of the 3 current first-line drugs used in Mexico (isoniazid, rifampin, and pyrazinamide) were 12.9% and 50.5%, respectively; the corresponding levels of multi-drug-resistant TB were 2.4% and 22.4%. Retreatment cases were significantly more likely than new cases to have isolates resistant to 1 or more of the 3 first-line drugs (relative risk [RR], 3.9; 95% confidence interval [CI], 2.8-5.5), to have isoniazid resistance (RR, 3.6; 95% CI, 2.5-5.2), and to have multi-drug-resistant TB (RR, 9.4; 95% CI, 4.3-20.2). CONCLUSIONS: This population-based study of M tuberculosis demonstrates moderately high levels of drug resistance. Important issues to consider in the national strategy to prevent M tuberculosis resistance in Mexico include consideration of the most appropriate initial therapy in patients with TB, the treatment of patients with multiple drug resistance, and surveillance or periodic surveys of resistance among new TB patients to monitor drug resistance trends.

Comparison among three methods for mycobacteria identification.

OBJECTIVE: To compare three methods: Biochemical tests, high-performance liquid chromatography (HPLC) and polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP), for the identification of mycobacteria, and to perform a cost-benefit analysis to define an optimum identification algorithm. MATERIAL AND METHODS: One-hundred-and-seven mycobacteria isolates were identified by the three methods at Instituto de Diagnóstico y Referencia Epidemiológicos, between February of 1999 and January of 2000 and the results were compared with those of a reference laboratory using the Q-Cochran statistical test. RESULTS: PCR-RFLP was the most rapid and specific procedure but also the most expensive; biochemical tests excelled for identification of Mycobacterium tuberculosis, but were lengthy and expensive for other mycobacteria; HPLC ranked in the middle for price, speed and specificity. CONCLUSIONS: Considering the expected proportion of M. tuberculosis, the following algorithm was proposed: Initially, biochemical tests should be performed; if the results indicate a non-tuberculous mycobacteria, the isolate should be analyzed with HPLC; if results are unclear, the isolate should be analyzed using PCR-RFLP. Isolates showing a previously undescribed PCR-RFLP pattern should be characterized by DNA sequencing.