Tuberculosis in ageing: high rates, complex diagnosis and poor clinical outcomes.

BACKGROUND: worldwide, the frequency of tuberculosis among older people almost triples that observed among young adults. OBJECTIVE: to describe clinical and epidemiological consequences of pulmonary tuberculosis among older people. METHODS: we screened persons with a cough lasting more than 2 weeks in Southern Mexico from March 1995 to February 2007. We collected clinical and mycobacteriological information (isolation, identification, drug-susceptibility testing and IS6110-based genotyping and spoligotyping) from individuals with bacteriologically confirmed pulmonary tuberculosis. Patients were treated in accordance with official norms and followed to ascertain treatment outcomes, retreatment, and vital status. RESULTS: eight hundred ninety-three tuberculosis patients were older than 15 years of age; of these, 147 (16.5%) were 65 years of age or older. Individuals ≥ 65 years had significantly higher rates of recently transmitted and reactivated tuberculosis. Older age was associated with treatment failure (OR=5.37; 95% CI: 1.06-27.23; P=0.042), and death due to tuberculosis (HR=3.52; 95% CI: 1.78-6.96; P<0.001) adjusting for sociodemographic and clinical variables. CONCLUSIONS: community-dwelling older individuals participate in chains of transmission indicating that tuberculosis is not solely due to the reactivation of latent disease. Untimely and difficult diagnosis and a higher risk of poor outcomes even after treatment completion emphasise the need for specific strategies for this vulnerable group.

Indoor pollution as an occupational risk factor for tuberculosis among women: a population-based, gender oriented, case-control study in Southern Mexico.

BACKGROUND: Indoor air pollution produced by biomass cooking fuels in developing countries has been associated with acute and chronic lower respiratory diseases, but has not been identified as an occupational exposure among women. OBJECTIVE: To examine the relationship between the use of biomass cooking fuels (mainly wood) and tuberculosis (TB) among women living in rural areas in Southern Mexico. METHODS: We conducted a population based case-control study in the health jurisdiction of Orizaba, Mexico. Cases were all incident female pulmonary TB patients, with Mycobacterium tuberculosis in sputum, living in communities with fewer than 15,000 inhabitants, diagnosed between March 1995 and April 2003. Woodsmoke exposure was assessed by applying a standardized questionnaire (ATS-DLD-78 questionnaire). Controls were randomly selected from sex-matched neighbors. Appropriate IRB approval was obtained. RESULTS: 42 TB cases and 84 community controls were recruited. Multivariate assessment showed that more than 20 years of exposure to smoke from biomass fuels was three times more frequent among cases than among controls [Odds ratio (OR): 3.3, 95% confidence interval (CI):1.06-10.30, p = 0.03], after controlling for age, body mass, household crowding, years of formal education and tobacco use. CONCLUSIONS: We found a strong association between the use of biomass cooking fuels and tuberculosis among women in a community-based, case-control study. Results of this study are intended to provide evidence to policy makers, community leaders and the general public on the importance of implementing gender oriented interventions that decrease the use of biomass fuels in poor communities in developing countries.

Molecular analysis of Mycobacterium tuberculosis strains with an intact pks15/1 gene in a rural community of Mexico.

BACKGROUND: Mycobacterium tuberculosis (MTB) is one of the leading causes of morbidity and mortality worldwide and infects approximately 1/3 of the human population, but only 10% of all infected individuals will ever develop the disease and half of these may result in a rapid progression to disease during the first 2 years after being infected. On the other hand, some phenotypic differences among mycobacterial strains contribute to variations in the outcome of the infection, e.g., the hypervirulent phenotype described in the Beijing family has been associated with the production of a phenolic glycolipid, which reduces the production of Th1 cytokines in the experimental model and requires the activity of a polyketide synthase enzyme encoded by the pks15/1 gene. METHODS: We analyzed clinical isolates characterized by recent transmission and rapid progression to disease to identify factors that may influence such behavior from a rural and semi-urban community in eastern Mexico. RESULTS: Using various typing tools, we were able to identify intrafamilial clusters which belonged to the East Asian lineage of MTB isolates (Beijing family) and another that belonged to the Indo-Oceanic lineage (Manila family). All isolates within these two clusters showed an intact pks15/1 gene sequence. Additionally, we identified three more family clusters that belonged to the Euro-American lineage and showed the typical 7-bp deletion of the pks15/1 gene. This 7-bp deletion was also found in the remaining 23 cases from non-family clusters. CONCLUSIONS: This is the first report of cases caused by strains with an intact pks15/1 gene in Mexico. Interestingly, we identified the three main mycobacterial lineages described so far: East-Asian, Indo-Oceanic, and Euro-American in a human population with almost no present-day migration.

Does DOTS work in populations with drug-resistant tuberculosis?

BACKGROUND: Directly observed therapy (DOTS) is the main strategy for prevention and control of tuberculosis worldwide. However, its effect on tuberculosis transmission in populations with moderate rates of drug-resistant disease is not known. METHODS: This population-based prospective study in southern Mexico between March, 1995, and February, 2000, was based on passive case finding and detection of acid-fast bacilli in sputum samples to diagnose pulmonary tuberculosis. We also used cultures, drug-susceptibility testing, bacterial genotyping, and monitoring of treatment outcomes. FINDINGS: We enrolled 436 patients; the HIV seroprevalence rate was 2%. We used three indicators to monitor continuing tuberculosis transmission: the incidence rate of pulmonary tuberculosis, which decreased by 54.4% between 1995 and 2000, from 42.1 to 19.2 per 10(5) population (p=0.00048); the percentage of clustered pulmonary tuberculosis cases, which decreased by 62.6% from 22% to 8% (p=0.02); and the rate of primary drug resistance, which decreased by 84.0% from 9.4 to 1.5 per 10(5) population (p=0.004). Rates of multidrug-resistant (MDR) tuberculosis also decreased (p<0.0001). The case-fatality ratio was 12% for MDR tuberculosis (five of 41), 7% for strains resistant to at least one drug after exclusion of MDR (four of 55), and 3% for pansusceptible strains (nine of 272). There were 13 treatment failures (11%) in 1995 and one (2%) in 2000 (p=0.012). INTERPRETATION: Even in settings with moderate rates of MDR tuberculosis, DOTS can rapidly reduce the transmission and incidence of both drug-susceptible and drug-resistant tuberculosis. However, further interventions, such as drug-susceptibility testing and standardised or individualised treatment regimens, are needed to reduce mortality rates for MDR tuberculosis.

Changes in the geographical distribution of tuberculosis patients in Veracruz, Mexico, after reinforcement of a tuberculosis control programme.

OBJECTIVE: Geographical information systems are valuable tools for studying tuberculosis (TB) epidemiology, but have been underused for the evaluation of TB control programs. We aimed to compare the geographical distribution of TB before and after the five elements of directly observed therapy, short course (DOTS) were strengthened in a Health Jurisdiction in Mexico in response to recommendations made by the WHO Global Tuberculosis Program. METHODS: All consenting persons detected by passive case finding between March 1995 and February 2000 who were confirmed to have acid-fast bacilli (AFB) in sputum underwent clinical and laboratory evaluation. A TB 'episode' was defined as the period of time between bacteriological diagnosis and treatment discharge by the local control programme. Distances of TB episodes from the nearest urban centre were determined according to recent transmission and multidrug resistance (MDR). RESULTS: During the first half of the study period, MDR episodes were located a median distance of 1.24 km from urban centres, which did not differ significantly from non-MDR episodes (1.14 km, P=0.56). In contrast, the median distance of MDR episodes increased 55% to 1.92 km during the second half, which placed them significantly further away out than non-MDR episodes (1.08 km, P=0.01). No changes in location were detected for recent transmission. CONCLUSION: While reinforcing the TB control programme reduced the incidence of MDR, the remaining episodes were located in poorer and more remote areas.

Tuberculosis and diabetes in southern Mexico.

OBJECTIVE: To determine the impact of diabetes on the rates of tuberculosis in a region where both diseases are prevalent. RESEARCH DESIGN AND METHODS: Data from a population-based cohort of patients with pulmonary tuberculosis undergoing clinical and mycobacteriologic evaluation (isolation, identification, drug-susceptibility testing, and IS6110-based genotyping and spoligotyping) were linked to the 2000 National Health Survey (ENSA2000), a national probabilistic, polystage, stratified, cluster household survey of the civilian, noninstitutionalized population of Mexico. RESULTS: From March 1995 to March 2003, 581 patients with Mycobacterium tuberculosis culture and fingerprint were diagnosed, 29.6% of whom had been diagnosed previously with diabetes by a physician. According to the ENSA2000, the estimated prevalence of diabetes in the study area was 5.3% (95% CI 4.1-6.5). The estimated rates of tuberculosis for the study area were greater for patients with diabetes than for nondiabetic individuals (209.5 vs. 30.7 per 100000 person-years, P < 0.0001). CONCLUSIONS: In this setting, the rate of tuberculosis was increased 6.8-fold (95% CI 5.7-8.2, P < 0.0001) in patients with diabetes due to increases in both reactivated and recently transmitted infection. Comorbidity with diabetes may increase tuberculosis rates as much as coinfection with human immunodeficiency virus (HIV), with important implications for the allocation of health care resources.

Rapid identification and susceptibility testing of Mycobacterium tuberculosis from MGIT cultures with luciferase reporter mycobacteriophages.

In a prospective study conducted in a diagnostic laboratory in Mexico City, luciferase reporter mycobacteriophages (LRPs) were evaluated for their utility and performance in identification and antibiotic-susceptibility testing of Mycobacterium tuberculosis complex (MTC) isolates from MGIT-960 cultures. Eighty-four consecutive MGIT cultures recovered from 54 patients were included in this study. The LRPs confirmed mycobacterial growth in 79 (94 %) of 84 MGIT cultures. Failure to confirm growth was due to low inoculum (n = 1) or growth with non-tuberculous mycobacteria (n = 4). The median time to confirmation of MGIT cultures was 1 day (range 1-55). Confirmed cultures were identified with p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP), a selective inhibitor of MTC species, and results obtained with LRPs were compared with those obtained by BACTEC-460. The sensitivity and specificity of the LRP NAP test were respectively 97 and 100 %, and the median turnaround time for identification was 3 days with both methods. The accuracy and speed of the LRPs for susceptibility testing with rifampicin, streptomycin, isoniazid and ethambutol were compared with BACTEC-460 and discrepant results were tested by the conventional agar proportion method. In total, 72 MTC cultures were tested. The overall agreement between the LRPs and BACTEC-460 was 98.6 %. Four isolates (5.6 %) were falsely identified as ethambutol-resistant. The median turnaround time for susceptibility testing was 3 days (range 3-57) with the LRPs and 9 days (range 7-29) with BACTEC-460. LRPs offer an accurate and rapid approach for identification and susceptibility testing of M. tuberculosis from MGIT-960 cultures.