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.

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.

Micobacteriosis diseminada asomciada al complejo Mycobacterium avium-intracellulare (MAI), en paciente infectado con el virus de inmunodeficiencia humana / Disseminated mycobacteriosis associated with the Mycobacterium avium-intracellulare (MAI) complex in HIV infected patients

Se estudiaron diferentes tipos de muestras procedentes de una paciente de 27 años, diagnosticada como paciente SIDA luego de haber presentado un cuadro respiratorio agudo provocado por Pneumocistis carinii en 1997. A partir de ese momento la paciente siguió presentando cuadros respiratorios a repetición, hasta que ingresó en el Instituto de Medicina Tropical ôPedro Kouríö con cuadro diarreico crónico, pérdida de peso importante y anorexia extrema, acompañada de una constante tos húmeda, fiebre, etc. Se le realizaron los exámenes complementarios necesarios donde se resalta, un mantoux hiperérgico y niveles de células CD4 muy bajos (por debajo de 200 células/m3, conjuntamente se realizan estudios microbiológicos a partir de muestras de esputos, hemocultivos y líquido cefalorraquídeo, para descartar la presencia de bacilos ácido-alcohol resistentes. Como resultado de estos estudios se logró el aislamiento repetitivo en todos los tipos de muestras trabajadas de una cepa de crecimiento lento, cremosa no pigmentada, perteneciente al grupo III de Runyon, la cual fue clasificada como perteneciente al complejo Mycobacterium avium-intracellulare. La paciente fue sometida a tratamiento con 4 drogas antibacilares, sin obtener resultado, pues a las 4 semanas de tratamiento falleció a causa de la diseminación total de esta infección. Se debe destacar que este ha sido el primer caso reportado y diagnosticado microbiológicamente de mycobacteriosis generalizada en paciente VIH+ por Mycobacterium avium-intracellulare

Micobacteriosis diseminada asomciada al complejo Mycobacterium avium-intracellulare (MAI), en paciente infectado con el virus de inmunodeficiencia humana / Disseminated mycobacteriosis associated with the Mycobacterium avium-intracellulare (MAI) complex in HIV infected patients

Se estudiaron diferentes tipos de muestras procedentes de una paciente de 27 años, diagnosticada como paciente SIDA luego de haber presentado un cuadro respiratorio agudo provocado por Pneumocistis carinii en 1997. A partir de ese momento la paciente siguió presentando cuadros respiratorios a repetición, hasta que ingresó en el Instituto de Medicina Tropical “Pedro Kourí” con cuadro diarreico crónico, pérdida de peso importante y anorexia extrema, acompañada de una constante tos húmeda, fiebre, etc. Se le realizaron los exámenes complementarios necesarios donde se resalta, un mantoux hiperérgico y niveles de células CD4 muy bajos (por debajo de 200 células/m3, conjuntamente se realizan estudios microbiológicos a partir de muestras de esputos, hemocultivos y líquido cefalorraquídeo, para descartar la presencia de bacilos ácido-alcohol resistentes. Como resultado de estos estudios se logró el aislamiento repetitivo en todos los tipos de muestras trabajadas de una cepa de crecimiento lento, cremosa no pigmentada, perteneciente al grupo III de Runyon, la cual fue clasificada como perteneciente al complejo Mycobacterium avium-intracellulare. La paciente fue sometida a tratamiento con 4 drogas antibacilares, sin obtener resultado, pues a las 4 semanas de tratamiento falleció a causa de la diseminación total de esta infección. Se debe destacar que este ha sido el primer caso reportado y diagnosticado microbiológicamente de mycobacteriosis generalizada en paciente VIH+ por Mycobacterium avium-intracellulare(AU)