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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.

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.

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.

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

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 (β)  = -0.660, (95% confidence interval (CI), -0.96 to -0.35); and β = -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.