Seroprevalence of measles antibodies and factors associated with susceptibility: a national survey in Mexico using a plaque reduction neutralization test.

Measles continues to be one of the leading causes of child mortality worldwide, even though a highly effective vaccine has existed for more than 40 years. We aimed to describe the seroprevalence of measles antibodies in Mexico in 2012 and the risk factors associated with susceptibility. A total of 7,785 serum samples were analyzed from the National Health and Nutrition Survey in Mexico. This national survey is representative of the general population, including noninstitutionalized adult, adolescent, and child populations. Antibody titers were classified into protective (> 120 mIU/mL) or susceptible (≤ 120 mIU/mL) levels. The weighted seroprevalence and susceptibility of the overall population were 99.37% (95% CI 99.07-99.58) and 0.63% (95% CI 0.42-0.93), respectively. Among 1-to-4-year-old children, 2.18% (95% CI 1.36-3.48) were susceptible to measles. Among adolescents and young adults, the prevalence of susceptibility was as follows: those 15-19 years of age had a prevalence of 0.22% (95% CI 0.09-0.57), and those 30-39 years of age had a prevalence of 1.17% (95% CI 0.47-2.85). Susceptibility was associated with young age, living in Mexico City, living in crowded households and unknown or nonvaccinated status among 1- to 5-year-old children. Although the overall sample population seroprevalence for measles is above 95%, increased susceptibility among younger children signals the importance of the timely administration of the first vaccine dose at 12 months of age. Furthermore, increased susceptibility among specific subgroups indicates the need to reinforce current vaccination policies, including the immunization of unvaccinated or incompletely vaccinated individuals from 10 to 39 years of age.

Seroprevalence of Poliomyelitis Antibodies Among Children Aged 1 to 4 Years Old and Factors Associated With Poliovirus Susceptibility; Mexican Health and Nutrition Survey, 2012.

Background: An essential component of the "Polio Eradication and Endgame Strategic Plan 2013-2018" is the evaluation of population immunity. Mexico introduced the inactivated polio vaccine (IPV) into its routine immunization schedule in 2007 but continued to give trivalent oral polio vaccine OPV twice a year during National Health Weeks through 2016. Methods: To describe the seroprevalence of poliomyelitis among children one to four years old in Mexico and analyze risk factors for susceptibility. We detected antibodies to poliovirus type 1 by microneutralization test in 966 serum samples randomly selected from the National Health and Nutrition Survey, 2012. We assessed variables associated with susceptibility using multivariable logistic regression. Results: The overall weighted seroprevalence of the general population was 98.39% (95% confidence interval [CI] 96.76-99.21). We found significant differences of prevalence according to age (94.39%, 95% CI 87.56-97.58; 99.02%, 95% CI 95.68-99.79; 99.82%, 95% CI 98.77-99.98; and 100% among children 1, 2, 3, and 4 years old respectively) and number of IPV doses (96.91%, 95% CI 90.55-99.44; 100%; 97.85%, 95% CI 94.46-99.18; and 99.92%, 95% CI 99.45-99.98 for 1 2, 3, and 4 number of doses, respectively). Multivariate analyses showed that susceptibility was associated with younger age, fewer doses of IPV, and certain socioeconomic levels. Conclusions: Overall seroprevalence was high. However, we found susceptible children among younger ages and children with fewer or unknown IPV doses belonging to certain socioeconomic strata. Results are relevant for countries transitioning from OPV to IPV and underline the importance of achieving high coverage with IPV.

Protocol Paper: Oral Poliovirus Vaccine Transmissibility in Communities After Cessation of Routine Oral Poliovirus Vaccine Immunization.

Background: We aimed to elucidate household and community-level shedding and transmission of trivalent oral polio vaccine (tOPV) in communities with inactivated polio vaccine (IPV) routine immunization after tOPV is administered during a national health week (NHW). Methods: We conducted a 3-arm, randomized trial with data collected at baseline through 10 weeks post-NHW in households with at least 1 child <5 years old in 3 semi-rural communities in Orizaba, Mexico. Selected communities were geographically isolated but socio-demographically similar. Each community was assigned an oral polio vaccine (OPV) immunization rate: 10, 30, or 70% of participating households. From 2653 households in the 3 communities, ~150 households per community were selected, for 466 in total. Households were randomized as vaccinated or unvaccinated, with only 1 child under 5 in the vaccinated household receiving OPV during the February 2015 NHW. No other community members received OPV during this NHW. Stool samples were collected up to 10 weeks post-vaccination for all members of the 466 study households and were analyzed for the presence of OPV serotypes using a multiplex polymerase chain reaction assay. Results: We will report on the factors associated with, and incidence and duration of, household and community shedding and transmission of OPV. The secondary outcomes will characterize temporal and geospatial OPV serotype shedding patterns. Conclusions: The current global polio eradication plan relies on transitioning away from OPV to IPV. This study contributes to understanding patterns of OPV shedding and transmission dynamics in communities with primary IPV immunity, in order to optimize the reduction of OPV transmission.

Characterization of Household and Community Shedding and Transmission of Oral Polio Vaccine in Mexican Communities With Varying Vaccination Coverage.

Background: The World Health Assembly 2012 Polio Eradication and Endgame Strategic Plan calls for the eventual cessation of all oral polio vaccines (OPVs), to be replaced with inactivated polio vaccine (IPV); however, IPV induces less robust mucosal immunity than OPV. This study characterized household and community OPV shedding and transmission after OPV vaccination within primarily IPV-vaccinated communities. Methods: Households in 3 IPV-vaccinated Mexican communities were randomized to receive 3 levels of OPV vaccination coverage (70%, 30%, or 10%). Ten stool samples were collected from all household members over 71 days. Analysis compared vaccinated subjects, household contacts of vaccinated subjects, and subjects in unvaccinated households. Logistic and Cox regression models were fitted to characterize transmission of OPV by coverage and household vaccination status. Results: Among 148 vaccinated children, 380 household contacts, and 1124 unvaccinated community contacts, 78%, 18%, and 7%, respectively, shed OPV. Community and household contacts showed no differences in transmission (odds ratio [OR], 0.67; 95% confidence interval [CI], .37-1.20), in shedding trajectory (OR, 0.61; 95% CI, .35-1.07), or in time to shedding (hazard ratio, 0.68; 95% CI, .39-1.19). Transmission began as quickly as 1 day after vaccination and persisted as long as 71 days after vaccination. Transmission within unvaccinated households differed significantly across vaccination coverage communities, with the 70% community experiencing the most transmissions (15%), and the 10% community experiencing the least (4%). These trends persisted over time and in the time to first shedding analyses. Conclusions: Transmission did not differ between household contacts of vaccinees and unvaccinated households. Understanding poliovirus transmission dynamics is important for postcertification control.

Genotyping and spatial analysis of pulmonary tuberculosis and diabetes cases in the state of Veracruz, Mexico.

BACKGROUND: Genotyping and georeferencing in tuberculosis (TB) have been used to characterize the distribution of the disease and occurrence of transmission within specific groups and communities. OBJECTIVE: The objective of this study was to test the hypothesis that diabetes mellitus (DM) and pulmonary TB may occur in spatial and molecular aggregations. MATERIAL AND METHODS: Retrospective cohort study of patients with pulmonary TB. The study area included 12 municipalities in the Sanitary Jurisdiction of Orizaba, Veracruz, México. Patients with acid-fast bacilli in sputum smears and/or Mycobacterium tuberculosis in sputum cultures were recruited from 1995 to 2010. Clinical (standardized questionnaire, physical examination, chest X-ray, blood glucose test and HIV test), microbiological, epidemiological, and molecular evaluations were carried out. Patients were considered "genotype-clustered" if two or more isolates from different patients were identified within 12 months of each other and had six or more IS6110 bands in an identical pattern, or < 6 bands with identical IS6110 RFLP patterns and spoligotype with the same spacer oligonucleotides. Residential and health care centers addresses were georeferenced. We used a Jeep hand GPS. The coordinates were transferred from the GPS files to ArcGIS using ArcMap 9.3. We evaluated global spatial aggregation of patients in IS6110-RFLP/ spoligotype clusters using global Moran´s I. Since global distribution was not random, we evaluated "hotspots" using Getis-Ord Gi* statistic. Using bivariate and multivariate analysis we analyzed sociodemographic, behavioral, clinic and bacteriological conditions associated with "hotspots". We used STATA® v13.1 for all statistical analysis. RESULTS: From 1995 to 2010, 1,370 patients >20 years were diagnosed with pulmonary TB; 33% had DM. The proportion of isolates that were genotyped was 80.7% (n = 1105), of which 31% (n = 342) were grouped in 91 genotype clusters with 2 to 23 patients each; 65.9% of total clusters were small (2 members) involving 35.08% of patients. Twenty three (22.7) percent of cases were classified as recent transmission. Moran`s I indicated that distribution of patients in IS6110-RFLP/spoligotype clusters was not random (Moran`s I = 0.035468, Z value = 7.0, p = 0.00). Local spatial analysis showed statistically significant spatial aggregation of patients in IS6110-RFLP/spoligotype clusters identifying "hotspots" and "coldspots". GI* statistic showed that the hotspot for spatial clustering was located in Camerino Z. Mendoza municipality; 14.6% (50/342) of patients in genotype clusters were located in a hotspot; of these, 60% (30/50) lived with DM. Using logistic regression the statistically significant variables associated with hotspots were: DM [adjusted Odds Ratio (aOR) 7.04, 95% Confidence interval (CI) 3.03-16.38] and attending the health center in Camerino Z. Mendoza (aOR18.04, 95% CI 7.35-44.28). CONCLUSIONS: The combination of molecular and epidemiological information with geospatial data allowed us to identify the concurrence of molecular clustering and spatial aggregation of patients with DM and TB. This information may be highly useful for TB control programs.

Assessing the individual risk of fecal poliovirus shedding among vaccinated and non-vaccinated subjects following national health weeks in Mexico.

BACKGROUND: Mexico introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in 2007 but continued to give trivalent oral polio vaccine (tOPV) twice a year during national health weeks (NHW) through 2015. OBJECTIVES: To evaluate individual variables associated with poliovirus (PV) shedding among children with IPV-induced immunity after vaccination with tOPV and their household contacts. MATERIALS AND METHODS: We recruited 72 children (both genders, ≤30 months, vaccinated with at least two doses of IPV) and 144 household contacts (both genders, 2 per household, children and adults) between 08/2010 and 09/2010 in Orizaba, Veracruz. Three NHW took place (one before and two after enrollment). We collected fecal samples monthly for 12 months, and tested 2500 samples for polioviruses types 1, 2 and 3 with three serotype-specific singleplex real-time RT-PCR (rRT-PCR) assays. In order to increase the specificity for OPV virus, all positive and 112 negative samples were also processed with a two-step, OPV serotype-specific multiplex rRT-PCR. ANALYSIS: We estimated adjusted hazard ratios (HR) and 95% CI using Cox proportional hazards regression for recurrent events models accounting for individual clustering to assess the association of individual variables with the shedding of any poliovirus for all participants and stratifying according to whether the participant had received tOPV in the month of sample collection. RESULTS: 216 participants were included. Of the 2500 collected samples, using the singleplex rRT-PCR assay, PV was detected in 5.7% (n = 142); PV1 in 1.2% (n = 29), PV2 in 4.1% (n = 103), and PV3 in 1.9% (n = 48). Of the 256 samples processed by multiplex rRT-PCR, PV was detected in 106 (PV1 in 16.41% (n = 42), PV2 in 21.09% (n = 54), and PV3 in 23.05% (n = 59). Both using singleplex and multiplex assays, shedding of OPV among non-vaccinated children and subjects older than 5 years of age living in the same household was associated with shedding of PV2 by a household contact. All models were adjusted by sex, age, IPV vaccination and OPV shedding by the same individual during the previous month of sample collection. CONCLUSION: Our results provide important evidence regarding the circulation of poliovirus in a mixed vaccination context (IPV+OPV) which mimics the "transitional phase" that occurs when countries use both vaccines simultaneously. Shedding of OPV2 by household contacts was most likely the source of infection of non-vaccinated children and subjects older than 5 years of age living in the same household.

Molecular clustering of patients with diabetes and pulmonary tuberculosis: A systematic review and meta-analysis.

INTRODUCTION: Many studies have explored the relationship between diabetes mellitus (DM) and tuberculosis (TB) demonstrating increased risk of TB among patients with DM and poor prognosis of patients suffering from the association of DM/TB. Owing to a paucity of studies addressing this question, it remains unclear whether patients with DM and TB are more likely than TB patients without DM to be grouped into molecular clusters defined according to the genotype of the infecting Mycobacterium tuberculosis bacillus. That is, whether there is convincing molecular epidemiological evidence for TB transmission among DM patients. Objective: We performed a systematic review and meta-analysis to quantitatively evaluate the propensity for patients with DM and pulmonary TB (PTB) to cluster according to the genotype of the infecting M. tuberculosis bacillus. MATERIALS AND METHODS: We conducted a systematic search in MEDLINE and LILACS from 1990 to June, 2016 with the following combinations of key words "tuberculosis AND transmission" OR "tuberculosis diabetes mellitus" OR "Mycobacterium tuberculosis molecular epidemiology" OR "RFLP-IS6110" OR "Spoligotyping" OR "MIRU-VNTR". Studies were included if they met the following criteria: (i) studies based on populations from defined geographical areas; (ii) use of genotyping by IS6110- restriction fragment length polymorphism (RFLP) analysis and spoligotyping or mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) or other amplification methods to identify molecular clustering; (iii) genotyping and analysis of 50 or more cases of PTB; (iv) study duration of 11 months or more; (v) identification of quantitative risk factors for molecular clustering including DM; (vi) > 60% coverage of the study population; and (vii) patients with PTB confirmed bacteriologically. The exclusion criteria were: (i) Extrapulmonary TB; (ii) TB caused by nontuberculous mycobacteria; (iii) patients with PTB and HIV; (iv) pediatric PTB patients; (v) TB in closed environments (e.g. prisons, elderly homes, etc.); (vi) diabetes insipidus and (vii) outbreak reports. Hartung-Knapp-Sidik-Jonkman method was used to estimate the odds ratio (OR) of the association between DM with molecular clustering of cases with TB. In order to evaluate the degree of heterogeneity a statistical Q test was done. The publication bias was examined with Begg and Egger tests. Review Manager 5.3.5 CMA v.3 and Biostat and Software package R were used. RESULTS: Selection criteria were met by six articles which included 4076 patients with PTB of which 13% had DM. Twenty seven percent of the cases were clustered. The majority of cases (48%) were reported in a study in China with 31% clustering. The highest incidence of TB occurred in two studies from China. The global OR for molecular clustering was 0.84 (IC 95% 0.40-1.72). The heterogeneity between studies was moderate (I2 = 55%, p = 0.05), although there was no publication bias (Beggs test p = 0.353 and Eggers p = 0.429). CONCLUSION: There were very few studies meeting our selection criteria. The wide confidence interval indicates that there is not enough evidence to draw conclusions about the association. Clustering of patients with DM in TB transmission chains should be investigated in areas where both diseases are prevalent and focus on specific contexts.

Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010.

BACKGROUND: Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. OBJECTIVE: To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. MATERIALS AND METHODS: We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. RESULTS: Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15-2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08-6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38-45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00-10.84). All the models were adjusted for socio-demographic and clinical variables. CONCLUSIONS: The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings.

Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series.

BACKGROUND: Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART) programs and epidemiology of infectious diseases. OBJECTIVE: To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS. MATERIAL AND METHODS: We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions. RESULTS: We studied 308 patients, of whom 206 (66.9%) had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm3 [interquartile range (IQR): 30-150]. Seventy-five (24.4%) cases had received HAART for more than 180 days. Pneumocystis jirovecii pneumonia (PJP) (n = 142), tuberculosis (n = 63), and bacterial community-acquired pneumonia (n = 60) were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR): 0.245, 95% Confidence Interval (CI): 0.08-0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06-0.75) of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses. CONCLUSIONS: HAART for 180 days or more was associated with 79% decrease in all-cause in-hospital mortality and lower frequency of PJP as discharge diagnosis. The prevalence of poorly controlled HIV was high, regardless of whether HIV was diagnosed before or during admission. HIV diagnosis and treatment resources should be improved, and strengthening of HAART program needs to be promoted.

Association of Pulmonary Tuberculosis and Diabetes in Mexico: Analysis of the National Tuberculosis Registry 2000-2012.

BACKGROUND: Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years. OBJECTIVE: To describe the trends of incidence rates of pulmonary TB associated with DM and not associated with DM and to compare the results of treatment outcomes in patients with and without DM. MATERIALS AND METHODS: We analysed the National Tuberculosis Registry from 2000 to 2012 including patients with pulmonary TB among individuals older than 20 years of age. The association between DM and treatment failure was analysed using logistic regression, accounting for clustering due to regional distribution. RESULTS: In Mexico from 2000 to 2012, the incidence rates of pulmonary TB associated to DM increased by 82.64%, (p<0.001) in contrast to rates of pulmonary TB rate without DM, which decreased by 26.77%, (p<0.001). Patients with a prior diagnosis of DM had a greater likelihood of failing treatment (adjusted odds ratio, 1.34 (1.11-1.61) p<0.002) compared with patients who did not have DM. There was statistical evidence of interaction between DM and sex. The odds of treatment failure were increased in both sexes. CONCLUSION: Our data suggest that the growing DM epidemic has an impact on the rates of pulmonary TB. In addition, patients who suffer from both diseases have a greater probability of treatment failure.

Effect of isoniazid on antigen-specific interferon-γ secretion in latent tuberculosis.

Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes. We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays of in vitro interferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed. During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy. The in vitro IFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection.

Results of the implementation of a pilot model for the bidirectional screening and joint management of patients with pulmonary tuberculosis and diabetes mellitus in Mexico.

BACKGROUND: Recently, the World Health Organisation and the International Union Against Tuberculosis and Lung Disease published a Collaborative Framework for the Care and Control of Tuberculosis (TB) and Diabetes (DM) (CFTB/DM) proposing bidirectional screening and joint management. OBJECTIVE: To evaluate the feasibility and effectiveness of the CFTB/DM in Mexico. DESIGN: Prospective observational cohort. SETTING: 15 primary care units in 5 states in Mexico. PARTICIPANTS: Patients aged ≥20 years diagnosed with DM or pulmonary TB who sought care at participating clinics. INTERVENTION: The WHO/Union CFTB/DM was adapted and implemented according to official Mexican guidelines. We recruited participants from July 2012 to April 2013 and followed up until March 2014. Bidirectional screening was performed. Patients diagnosed with TB and DM were invited to receive TB treatment under joint management. MAIN OUTCOME MEASURES: Diagnoses of TB among DM, of DM among TB, and treatment outcomes among patients with DM and TB. RESULTS: Of 783 DM patients, 11 (1.4%) were unaware of their TB. Of 361 TB patients, 16 (4.4%) were unaware of their DM. 95 TB/DM patients accepted to be treated under joint management, of whom 85 (89.5%) successfully completed treatment. Multiple linear regression analysis with change in HbA1c and random capillary glucose as dependent variables revealed significant decrease with time (regression coefficients (ß)  = -0.660, (95% confidence interval (CI), -0.96 to -0.35); and ß = -1.889 (95% CI, -2.77 to -1.01, respectively)) adjusting by sex, age and having been treated for a previous TB episode. Patients treated under joint management were more likely to experience treatment success than patients treated under routine DM and TB programs as compared to historical (adjusted OR (aOR), 2.8, 95%CI 1.28-6.13) and same period (aOR 2.37, 95% CI 1.13-4.96) comparison groups. CONCLUSIONS: Joint management of TB and DM is feasible and appears to improve clinical outcomes.

Impact of cigarette smoking on rates and clinical prognosis of pulmonary tuberculosis in Southern Mexico.

OBJECTIVES: To examine the relationship between cigarette smoking and incidence and mortality rates of pulmonary tuberculosis (TB) and treatment outcomes. MATERIALS: From 1995 to 2010, we analyzed data from 1062 patients with TB and from 2001 to 2004, 2951 contacts in Southern Mexico. Patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and mycobacteriological evaluation and received treatment by the local DOTS program. RESULTS: Consumers of 1-10 (LS) or 11 or more (HS) cigarettes per day incidence (1.75 and 11.79) and mortality (HS, 17.74) smoker-non-smoker rate ratios were significantly higher for smokers. Smoker population was more likely to experience unfavorable treatment outcomes (HS, adjusted OR 2.36) and retreatment (LS and HS, adjusted hazard ratio (HR) 2.14 and 2.37). Contacts that smoked had a higher probability of developing active TB (HR 2.38) during follow up. CONCLUSIONS: Results indicate the need of incorporating smoking prevention and cessation, especially among men, into international TB control strategies.

Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes.

OBJECTIVE: To determine the clinical consequences of pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM). METHODS: We conducted a prospective study of patients with TB in Southern Mexico. From 1995 to 2010, patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. Annual follow-ups were performed to ascertain treatment outcome, recurrence, relapse and reinfection. RESULTS: The prevalence of DM among 1262 patients with pulmonary TB was 29.63% (n=374). Patients with DM and pulmonary TB had more severe clinical manifestations (cavities of any size on the chest x-ray, adjusted OR (aOR) 1.80, 95% CI 1.35 to 2.41), delayed sputum conversion (aOR 1.51, 95% CI 1.09 to 2.10), a higher probability of treatment failure (aOR 2.93, 95% CI 1.18 to 7.23), recurrence (adjusted HR (aHR) 1.76, 95% CI 1.11 to 2.79) and relapse (aHR 1.83, 95% CI 1.04 to 3.23). Most of the second episodes among patients with DM were caused by bacteria with the same genotype but, in 5/26 instances (19.23%), reinfection with a different strain occurred. CONCLUSIONS: Given the growing epidemic of DM worldwide, it is necessary to add DM prevention and control strategies to TB control programmes and vice versa and to evaluate their effectiveness. The concurrence of both diseases potentially carries a risk of global spreading, with serious implications for TB control and the achievement of the United Nations Millennium Development Goals.

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.