[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.

Factors associated with tuberculin reactivity in two general hospitals in Mexico.

OBJECTIVE: To identify risk factors associated with tuberculin reactivity in healthcare workers (HCWs). DESIGN: Cross-sectional survey of tuberculin reactivity (2 TU of purified protein derivative (PPD) RT23, using the Mantoux two-step test). SETTING: Two general hospitals located in a region with a high prevalence of tuberculosis and high bacille Calmette-Guerin (BCG) coverage. PARTICIPANTS: Volunteer sample of HCWs. RESULTS: 605 HCWs were recruited: 71.2% female; mean age, 36.4 (standard deviation [SD], 8.2) years; 48.9% nurses, 10.4% physicians, 26.8% administrative personnel; mean time of employment, 10.9 (SD, 6.7) years. PPD reactivity (> or =10 mm) was found in 390 (64.5%). Multivariate analysis revealed an association of tuberculin reactivity with occupational exposure in the hospital: participation in autopsies (odds ratio [OR], 9.3; 95% confidence interval [CI95], 2.1-40.5; P=.003.), more than 1 year of employment (OR, 2.4; CI95, 1.1-5.0; P=.02), work in the emergency or radiology departments (OR, 2.0; CI95, 1.03-3.81; P=.04), being physicians or nurses (OR, 1.5; CI95, 1.04-2.11; P=.03), age (OR, 1.04; CI95, 1.02-1.07 per year of age; P<.001), and BCG scar (OR, 2.1; CI95, 1.2-3.4; P=.005). CONCLUSIONS: Although the studied population has a high baseline prevalence of tuberculosis infection and high coverage of BCG vaccination, nosocomial risk factors associated with PPD reactivity were identified as professional risks; strict early preventive measures must be implemented accordingly.

Underestimation of Mycobacterium tuberculosis infection in HIV-infected subjects using reactivity to tuberculin and anergy panel.

BACKGROUND: This study aimed to evaluate purified protein derivative (PPD) reactivity and its interrelationship with anergy panel and CD4+ lymphocytes in HIV-infected subjects as compared to PPD reactivity in HIV-uninfected individuals in a tuberculosis endemic and high Bacillus Calmette-Guérin (BCG) coverage environment. METHODS: Clients of four Mexico City HIV detection centres were screened for HIV-1 antibodies (ELISA or haemagglutination, Western Blot); reactivity to PPD (Mantoux PPD, 5TU RT-23), Candida (1:1000, 0.1 ml), and tetanus toxoid (10Lf, 0.1 ml); and CD4+ T cells. Active tuberculosis was excluded. Informed consent was obtained. RESULTS: From 5130 clients 1168 subjects were enrolled; of these 801 (68.6%) were HIV positive. Reactivity to PPD among HIV-positive subjects was found in 174 (22%), 261 (32.6%), and 296 (37%), at PPD cutoff levels of > or =10 mm, > or =5 mm, and > or =2 mm as compared to 224 (61%) of 367 HIV-negative individuals' reactors to PPD (> or =10 mm) (P < 0.001). After exclusion of anergic individuals using two cutoff levels for cutaneous allergens (< or =2 mm and < or =5 mm), PPD reactivity between HIV-infected and uninfected individuals continued to be significantly different. Only HIV-infected individuals with CD4+ T cells > or =500 cells/mm3 had similar reactivity to PPD as HIV-uninfected individuals. Variables associated with PPD reactivity were CD4+ T cell counts, BCG scar, HIV infection and age. CONCLUSIONS: PPD reactivity was useful to diagnose tuberculosis infection only among HIV-infected individuals with CD4+ counts > or =500 cells/mm3. Among individuals with lower counts, lowering cutoff levels or using anergy panel did not permit comparable reactivity as that observed among HIV-uninfected individuals.

Clinical consequences and transmissibility of drug-resistant tuberculosis in southern Mexico.

BACKGROUND: Consequences of drug-resistant tuberculosis (TB) in developing countries using directly observed treatment, short-course (DOTS), are not well defined. OBJECTIVE: To determine the impact of drug resistance on clinical outcome and transmission of TB under programmatic conditions. PATIENTS AND METHODS: A prospective cohort and molecular epidemiologic study was conducted in southern Mexico. Between March 1995 and February 1998 all patients with persistent cough whose sputa had acid-fast bacilli (AFB) underwent clinical and mycobacteriologic evaluation (species identification, drug susceptibility testing, and IS6110-based genotyping). Treatment was provided in accordance with Mexico's National Tuberculosis Program. Clinical and microbiologic outcomes and molecular epidemiologically defined transmission were measured. RESULTS: Mycobacterium tuberculosis was isolated from 238 of the 284 AFB smear-positive persons. The overall rate of resistance was 28.4% (new, 20.7%; retreated, 54.7%), and 10.8% (new, 3.3%; retreated, 35.8%) had multi-drug-resistant TB (ie, resistance to isoniazid and rifampin). After treatment, 75% (new, 81.0%; retreated, 52.8%) were cured, 8% (new, 7.8%; retreated, 7.5%) abandoned therapy, 9% (new, 3.9%; retreated, 28.3%) had treatment failure, and 4% (new, 3.3%; retreated, 7.5%) died. Another 2% of patients relapsed, and 9% died during a median of 24.4 months of follow-up. Drug-resistance was a strong independent risk factor for treatment failure. Being infected with multi-drug-resistant TB was the only factor associated with a decreased likelihood of being in a restriction fragment length polymorphism cluster. CONCLUSIONS: Despite the use of DOTS, patients with drug-resistant TB had a dramatically increased probability of treatment failure and death. Although multi-drug-resistant TB may have a decreased propensity to spread and cause disease, it has a profoundly negative impact on TB control.

The role of core groups in transmitting Mycobacterium tuberculosis in a high prevalence community in Southern Mexico.

SETTING: A community in Southern Mexico with a high prevalence of tuberculosis. OBJECTIVE: To characterize the transmission dynamics in a region with a DOTS-based tuberculosis control program. DESIGN: Community-based screening of chronic coughers between 1 March 1995 and 31 August 1996. Individuals with acid-fast bacilli (AFB) in their sputum were enrolled, interviewed, and had mycobacterial cultures and fingerprinting performed. In-depth interviews were conducted on all persons with DNA fingerprinting. RESULTS: AFB smears were performed on 1424 individuals, 124 of whom were microbiologically confirmed. Of the 95 cases for whom bacterial DNA fingerprints were available, 38 were in clusters. The largest cluster involved seven individuals who were members of a social network centered on a series of unlicensed bars. CONCLUSION: This population-based molecular epidemiologic study showed that a focus of transmission within a social network accounted for one fourth of transmission which rapidly progressed to disease. These observations raise questions about the potential benefit of targeted tuberculosis control interventions in health jurisdictions approaching WHO-defined DOTS benchmarks.

Mycobacterium tuberculosis drug resistance in a suburban community in southern Mexico.

OBJECTIVE: To determine the impact of drug resistance (DR) on the clinical outcome and transmission of tuberculosis under programmatic conditions. METHODS: Prospective cohort and molecular epidemiologic study in the Orizaba Health Jurisdiction of Mexico. Between March 1995 and July 1999, chronic coughers with positive acid-fast bacilli (AFB) detected in sputum smear underwent clinical and mycobacteriologic evaluation (species identification, drug susceptibility testing and IS6110-based genotyping). Treatment was provided in accordance with official norms. RESULTS: Mycobacterium tuberculosis was isolated from 326/387 AFB-positive cases. The rate of DR was 24.2% and that of multidrug resistance (MDR, defined as resistance to both isoniazid and rifampin at least) was 7.7%; 78% were cured, 8% abandoned treatment, 6% failed treatment, and 5% died. An additional 13.5% received retreatment and 8.9% died during a median 28.6 months of follow up. Factors associated with DR by multivariate analysis were chronicity of tuberculosis (OR 4.8, 95%CI 2.7-8.4, P < 0.001), age >40 years (OR 1.9, 95%CI 1.1-3.2, P = 0.02) and indigenous origin (OR 0.3, 95%CI 0.13-0.75, P = 0.01). Cox-adjusted relative risks showed that MDR (RR 2.5, 95%CI 1.02-6.16, P = 0.04), HIV infection (RR 31.3, 95%CI 11.6-84.8, P < 0.001), and chronicity of tuberculosis (RR 2.1, 95%CI 1.0-4.4, P = 0.06) were associated with mortality, controlling for age. Predictors of retreatment were DR (not including MDR) (RR 2.2 95%CI 0.89-5.31, P < 0.087), MDR (RR 12.6, 95%CI 5.46-28.88, P < 0.001), and living in a household with an earthen floor (RR 2.8, 95%CI 1.27-6.13, P = 0.011). Being infected with MDR-TB was the only factor associated with a decreased likelihood of being in an RFLP cluster (OR 0.31, 95%CI 0.12-0.81, P = 0.02). CONCLUSIONS: Although MDR-TB may have a decreased propensity to spread and cause disease, it has a profoundly negative impact on tuberculosis control.

Tuberculosis epidemiology and control in Veracruz, Mexico.

BACKGROUND: Tuberculosis (TB) rates remain high in regions of Southern Mexico despite the existence of a National Tuberculosis Program. Understanding TB epidemiology in such settings would assist in the design of improved TB control and highlight the challenges confronting TB control in developing countries. METHODS: We conducted a retrospective review of treatment control cards from 1991 to 1994 in five municipalities in a semiurban region of Southern Mexico. RESULTS: The relatively high rate of TB observed, 42.6 per 100,000 inhabitants, did not change significantly during the study period. Cure rates among new cases were 79% and significantly lower among retreatment cases (62%). Directly observed therapy (DOT) was administered to 84% of patients. Approximately one-half of the retreatment cases who were not cured were compliant with therapy, suggesting that drug resistance contributed to these poor results. Of particular concern was a core group of 16 patients who had received at least three treatments. CONCLUSIONS: This region of Mexico has persistently high TB rates despite a DOT-based TB control programme which achieves an overall cure rate of 77%. There exist many retreatment cases for whom cure rates are significantly lower. These cases may serve as a core group for the dissemination of drug resistant TB. The control programme is being reinforced by a nominal register of patients, decreasing administrative barriers for drug supply to individual patients and the availability of mycobacteria cultures. In addition to these measures, in regions which are approaching the levels of efficacy recommended by the WHO it may be appropriate to consider focusing efforts on the identification and treatment of chronic cases.

[Efficacy and efficiency of antitubercular treatment in health jurisdictions of Morelos]. / Eficacia y eficiencia del tratamiento antituberculoso en jurisdicciones sanitarias de Morelos.

OBJECTIVE: To evaluate the efficacy and efficiency of tuberculosis treatment administered by the Secretaría de Salud (SSA) in the sanitary jurisdictions of Cuernavaca and Cuautla, Morelos, for the 1992-1996 period by retrospectively reviewing tuberculosis treatment control cards. MATERIAL AND METHODS: Official Norm for Tuberculosis Prevention and Control in Primary Care Units outcome definitions were used. Data was collected on standardized forms and analyzed with SAS and Epi Info programs; 149 primary care units and 4 hospitals in the study area were visited. RESULTS: There were found 288 patients cards, of which 260 were new cases. These patients received 311 treatments of which 85% were directly observed. Reviewed cards represented 60% of SSA notified cases for this period. There were analyzed 246 treatments of which 32% were bacteriological cures, 26% probable cures, 18% dropouts, 1% failures and 3% deaths. In 20% of treatments the outcome was unknown. Cure rate was better in new cases (61%) than in retreatments (38%), p < 0.01. Efficacy of treatment was 71% and efficiency 58%. Patients receiving retreatment abandoned it more frequently (32%) than new cases (16%), p < 0.01. A statistically significant association was found between abandoned treatment and being retreated (OR = 3.3, CI 95% 1.3-8.5, p = 0.01) or belonging to a lower socioeconomic level (OR = 2.3, CI 95% 1.0-4.9, p = 0.04). In the 34 retreatment programs, 22 were initiated after abandonment, failure or relapse. CONCLUSIONS: Proportion of cure rate (58%) compares unfavorably with WHO recommendations (85%). Implications of a high dropout rate and probability of circulation of resistant strains of M tuberculosis are discussed. Creative strategies to reinforce patient compliance which take into account the patient and not only the health services, extension of cultures to known M. tuberculosis drug resistance and evaluation of modifications to drug regimens are proposed. Review of treatment control cards is a useful tool for program evaluation.

[Tuberculosis and AIDS in Mexico]. / Tuberculosis y SIDA en México.

Tuberculosis (TB) still is an important health problem in Mexico. According to reported figures, an excess in the number of cases has occurred during recent years, mainly among young adults of both sexes. The present estimated rate of TB is 51.7 cases/100,000 inhabitants. This is the most frequent endemic infection among AIDS patients, ranking third among infectious diseases after candidiasis and P. carinii pneumoniae. A total of 8.3% of the 19,352 AIDS cases notified to July 1994, presented TB as the initial manifestation. According to sentinel surveillance carried out since 1990 in 17 states, HIV seroprevalence among TB patients has been 3.1% (0-6.5%) in males and 1.0% (0-2.3%) in females. Results of epidemiologic research in the field of TB prevention and characteristics of drug sensitivity of strains of M. tuberculosis isolated from HIV/AIDS patients are also described. Finally, perspectives of TB prevention and control are discussed.

[Education of Mexican health personnel on AIDS]. / Educación del personal de salud de México sobre el SIDA.

We describe the epidemiology of AIDS as it pertains to health workers in Mexico. Of the 12,151 cases notified in adults up until 1993, 2.9% occurred among such workers. Two cases of occupational transmission have been documented. Seroprevalence surveys have shown an infection rate of less than 0.1%. Nonetheless, the frequency with which hepatitis B viral markers are present (11.8% of anti-HBs antibody carriers and 2% of anti-HBsAg antibody carriers) points to the fact that mechanisms for the transmission of both types of viruses are at work. Surveys conducted among health workers to explore their knowledge and attitudes on the subject of AIDS indicate that they share many false notions about the disease and that they stigmatize its victims. Educational campaigns have improved knowledge about the illness but have not modified people's attitudes significantly. Holding workshops has proved to be the most useful strategy for attitude modification. We describe a few strategies that may be useful for changing negative attitudes among health personnel. When calculating the frequency with which biosafety measures are implemented, it has been noted that their application is erratic. Epidemiologic studies have confirmed the existence of an association between the time of occupational exposure and the presence of hepatitis B viral markers. Many people reject adopting certain measures, such as anti-hepatitis vaccination. Finally, we analyze the need for continuous training and supplies if increased biosafety measures are to be adopted.

HIV-1 seropositivity and behavioral and sociological risks among homosexual and bisexual men in six Mexican cities.

We report on the epidemiology of sexual behaviors, HIV-1 seroprevalence, and condom use in gay and bisexual men in six Mexican cities in 1988 and test the extent to which variations in sexual behavior and sociological risks are responsible for variations in prevalence. Seroprevalence rates among samples in six cities ranged from 2% to 25%. In multiple logistic regression models controlling for city, insertive/receptive behavior (IRB), and meeting partners in bathhouses, the following were independently related to seropositivity (p less than 0.05): city, IRB, syphilis, sex with a person with AIDS, and meeting partners in bathouses. The independent risks associated with categories of IRB were no or almost no activity (odds ratio 1.0), only insertive (3.0), mostly insertive (4.9), mixed (6.0), mostly receptive (3.3), and only receptive (0.9). The condom use rate on last sexual encounter was 30%. The main sexual risk for HIV-1 infection is not exclusively receptive anal sex, but rather mixed behavior. This association may be explained by the infectious state of the partner pools. The sociologic risk variables (national and local partner pools) are better predictors of seroprevalence than behavioral variables, such as the number of partners or use of condoms. These results imply that more effective individual strategies for risk reduction are needed, including better knowledge concerning the risk status of partners.