RESUMO
BACKGROUND: In most low income countries there are twice as many cases of tuberculosis (TB) reported among men than among women, a difference commonly attributed to biological and epidemiological characteristics as well as socioeconomic and cultural barriers in access to health care. The World Health Organization has encouraged gender specific comparisons in TB rates to determine whether women with TB are less likely than men with TB to be diagnosed, reported, and treated. A study was undertaken to identify gender based differences in patients with pulmonary TB and to use this information to improve TB control efforts. METHODS: Individuals with a cough for more than 2 weeks in southern Mexico were screened from March 1995 to April 2003. Clinical and mycobacteriological information (isolation, identification, drug susceptibility testing and IS6110 based genotyping, and spoligotyping) was collected from those with bacteriologically confirmed pulmonary TB. Patients were treated in accordance with official norms and followed to ascertain treatment outcome, retreatment, and vital status. RESULTS: 623 patients with pulmonary TB were enrolled. The male:female incidence rate ratio for overall, reactivated, and recently transmitted disease was 1.58 (95% CI 1.34 to 1.86), 1.64 (95% CI 1.36 to 1.98), and 1.41 (95% CI 1.01 to 1.96), respectively. Men were more likely than women to default from treatment (adjusted OR 3.30, 95% CI 1.46 to 7.43), to be retreated (hazard ratio (HR) 3.15, 95% CI 1.38 to 7.22), and to die from TB (HR 2.23, 95% CI 1.25 to 3.99). CONCLUSIONS: Higher rates of transmitted and reactivated disease and poorer treatment outcomes among men are indicators of gender differentials in the diagnosis and treatment of pulmonary TB, and suggest specific strategies in endemic settings.
Assuntos
Doenças Endêmicas/estatística & dados numéricos , Fatores Sexuais , Tuberculose Pulmonar/transmissão , Métodos Epidemiológicos , Feminino , Humanos , Masculino , México/epidemiologia , Distribuição por Sexo , Escarro/microbiologia , Resultado do Tratamento , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologiaRESUMO
Helicobacter pylori (HP) infection can cause hypochlorhydria, a positive risk factor for Mycobacterium tuberculosis (MTB) infection. This study examined the association between HP and MTB infections among persons attending the Policlinico Peruano Japonés Gastrointestinal Clinic in Lima, Peru. From 23 June 2000 to 18 August 2000, consenting 18-55 year olds who attended the clinic for gastric biopsy gave blood for HP serologic testing, underwent tuberculin skin testing (TST) and completed a social and medical history. Of 128 participating patients, 78 (61%) were TST positive for MTB, and 107 (84%) were infected with HP by serology. Of the patients who were HP positive, 67 (63%) developed positive TST reactions compared to 11 (52%) of 21 HP-seronegative subjects (OR 1.29; 95% CI 0.54-3.11; P = 0.6). There was no association after adjusting for covariates of H. pylori infection (OR 0.78; 95% CI 0.23-2.71; P = 0.7). However, study power was limited by high prevalence of the two infections.
Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Fatores de Confusão Epidemiológicos , Feminino , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Peru/epidemiologia , Prevalência , Fatores de Risco , Testes Cutâneos , Inquéritos e Questionários , Tuberculose Pulmonar/complicaçõesRESUMO
The use of polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) to study rpoB gene mutations in rifampin-resistant (RIFr) Mycobacterium tuberculosis has yielded contradictory results. To determine the sensitivity of this method, we analyzed 35 RIFr strains and 11 rifampin-susceptible (RIFs) strains, using the DNA sequencing of the core region of rpoB for comparison. Of the RIFr, 24 had a PCR-SSCP pattern identical to that of H37Rv; the other 11 had four different patterns. The 11 RIFs had PCR-SSCP patterns identical to that of H37Rv. The sensitivity of the assay was 31.4%; its specificity was 100%. We observed a strong correlation between the degree of resistance and the type of mutation.
Assuntos
Antibióticos Antituberculose/farmacologia , RNA Polimerases Dirigidas por DNA/genética , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , DNA Bacteriano/análise , Farmacorresistência Bacteriana , Humanos , Mutagênese , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNARESUMO
The utility of luciferase reporter mycobacteriophages (LRPs) for detection, identification, and antibiotic susceptibility testing of Mycobacterium tuberculosis was prospectively evaluated in a clinical microbiology laboratory in Mexico City, Mexico. Five hundred twenty-three consecutive sputum samples submitted to the laboratory during a 5-month period were included in this study. These specimens were cultivated in Middlebrook 7H9 (MADC), MGIT, and Löwenstein-Jensen (LJ) media. Of the 71 mycobacterial isolates recovered with any of the three media, 76% were detected with the LRPs, 97% were detected with the MGIT 960 method, and 90% were detected with LJ medium. When contaminated specimens were excluded from the analysis, the LRPs detected 92% (54 of 59) of the cultures. The median time to detection of bacteria was 7 days with both the LRPs and the MGIT 960 method. LRP detection of growth in the presence of p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) was used for selective identification of M. tuberculosis complex (MTC) and compared to identification with BACTEC 460. Using the LRP NAP test, 47 (94%) out of 50 isolates were correctly identified as tuberculosis complex. The accuracy and speed of LRP antibiotic susceptibility testing with rifampin, streptomycin, isoniazid, and ethambutol were compared to those of the BACTEC 460 method, and discrepant results were checked by the conventional proportion method. In total, 50 MTC isolates were tested. The overall agreement between the LRP and BACTEC 460 results was 98.5%. The median LRP-based susceptibility turnaround time was 2 days (range, 2 to 4 days) compared to 10.5 days (range, 7 to 16 days) by the BACTEC 460 method. Phage resistance was not detected in any of the 243 MTC isolates tested. Mycobacteriophage-based approaches to tuberculosis diagnostics can be implemented in clinical laboratories with sensitivity, specificity, and rapidity that compare favorably with those of the MGIT 960 and BACTEC 460 methods. The phages currently provide the fastest phenotypic assay for susceptibility testing.
Assuntos
Antituberculosos/farmacologia , Genes Reporter , Luciferases/genética , Micobacteriófagos/genética , Mycobacterium tuberculosis , Meios de Cultura , Humanos , México , Testes de Sensibilidade Microbiana , Micobacteriófagos/fisiologia , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/virologia , Tuberculose/microbiologiaRESUMO
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.
Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/prevenção & controle , Adulto , Antituberculosos/farmacologia , Resistência Microbiana a Medicamentos , Feminino , Humanos , Masculino , México/epidemiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/prevenção & controle , Tuberculose Pulmonar/mortalidadeRESUMO
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.
Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/transmissão , Adulto , Antituberculosos/uso terapêutico , Análise por Conglomerados , Resistência Microbiana a Medicamentos , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Retratamento , Fatores de Risco , Falha de Tratamento , Tuberculose Pulmonar/epidemiologiaRESUMO
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.
Assuntos
Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/transmissão , Análise por Conglomerados , Impressões Digitais de DNA , Feminino , Humanos , Masculino , Programas de Rastreamento , México/epidemiologia , Epidemiologia Molecular , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Escarro/microbiologia , Tuberculose Pulmonar/genéticaRESUMO
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.
Assuntos
Mycobacterium tuberculosis/classificação , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Impressões Digitais de DNA , DNA Bacteriano/genética , Resistência Microbiana a Medicamentos/genética , Resistência a Múltiplos Medicamentos/genética , Feminino , Humanos , Modelos Logísticos , Masculino , México/epidemiologia , Mycobacterium tuberculosis/genética , Modelos de Riscos Proporcionais , Estudos Prospectivos , Taxa de Sobrevida , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
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.
Assuntos
Tuberculose/prevenção & controle , Adolescente , Adulto , Idoso , Análise de Variância , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/organização & administração , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População/métodos , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose/epidemiologiaRESUMO
STUDY OBJECTIVE: To determine the epidemiology and clinical consequences of drug-resistant TB in Guatemala. DESIGN: A prospective study conducted for 12 months. SETTING: A thoracic referral hospital in western Guatemala. PATIENTS: Three hundred and seventy-six patients with confirmed TB. RESULTS: Of 376 confirmed cases, 335 (89%) were culture-positive. Tests of drug sensitivities to four first-line antituberculous drugs were performed in 172 (51%) of the culture-positive cases. Fifty-one patients (30%) were resistant to at least one antimicrobial agent, and 26 (15%) were resistant to at least two drugs. In a multivariate model of clinically available patient characteristics, only cavitary disease (odds ratio=2.1; 95% confidence interval, 1.1-6.6) and a history of taking anti-TB medication for >2 weeks (OR=3.0; 95% CI, 1.5-10.3) were independent predictors of resistance to two or more anti-TB agents. Resistance to two or more anti-TB drugs was the single independent predictor of treatment failure (OR=6.4; 95% CI, 2.3-17.8). Twenty-four of 172 patients (14%) who denied having received prior anti-TB therapy were infected with resistant organisms, suggesting ongoing transmission of drug-resistant strains. Although 84% (69 of 82 cases) of patients with fully susceptible organisms and 89% (17 of 19 cases) with singly resistant organisms were cured, only 45% of patients (10 of 22 cases) infected with organisms resistant to two or more agents were successfully treated. CONCLUSIONS: At this sentinel site for complicated TB, a substantial subset of cases who are infected with drug-resistant bacteria cannot be easily identified or treated.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Criança , Feminino , Guatemala/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/transmissãoRESUMO
SETTING: San Francisco, California. OBJECTIVE: To determine the relative contributions of infection acquired in San Francisco and reactivation of tuberculous infection acquired elsewhere in Mexican-born persons who developed tuberculosis in San Francisco, and to determine the frequency of transmission leading to secondary cases of tuberculosis in other persons. DESIGN: The study population consisted of all Mexican-born tuberculosis patients reported in San Francisco from 1991 through June 1995. All patients had positive cultures for Mycobacterium tuberculosis and DNA fingerprinting of isolates using IS6110 with more than two bands. Patients were classified as infected in San Francisco or infected elsewhere based on pre-defined criteria that included a second DNA fingerprinting technique (polymorphic guanine-cytosine-rich sequence), chart reviews, and selected patient interviews. RESULTS: Of the 43 Mexican-born patients studied, nine (21%) met the definition of infection acquired in San Francisco and 34 (79%) met the definition of reactivation of infection acquired elsewhere. Only one of the 43 cases resulted in two secondary cases in US-born persons. CONCLUSION: One-fifth of the Mexican-born patients who developed tuberculosis in San Francisco acquired their tuberculous infection in San Francisco; transmission from Mexican-born persons leading to tuberculosis in other persons is uncommon.