Determinants of multidrug-resistant tuberculosis in São Paulo-Brazil: a multilevel Bayesian analysis of factors associated with individual, community and access to health services.

OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) remains a serious public health problem worldwide. Accordingly, this study sought to identify individual, community and access to health services risk factors for MDR-TB. METHODS: Retrospective cohort of all TB cases diagnosed between 2006 and 2016 in the state of São Paulo. A Bayesian spatial hierarchical analysis with a multilevel design was carried out. RESULTS: It was identified that the history of previous TB treatment (Odds Ratios [OR]:13.86, 95% credibility interval [95% CI]:12.06-15.93), positive sputum culture test (OR: 5.26, 95% CI: 4.44-6.23), diabetes mellitus (OR: 2.34, 95% CI: 1.87-2.91), residing at a standard address (OR: 2.62, 95% CI: 1.91-3.60), positive sputum smear microscopy (OR: 1.74, 95% CI: 1.44-2.12), cavitary pulmonary TB (OR: 1.35, 95% CI: 1.14-1.60) and diagnosis performed due to spontaneous request (OR: 1.26; 95% CI: 1.10-1.46) were associated with MDR-TB. Furthermore, municipalities that performed HIV tests in less than 42.65% of patients with TB (OR: 1.50, 95% CI: 1.25-1.79), that diagnosed TB cases only after death (OR: 1.50, 95% CI: 1.17-1.93) and that had more than 20.16% of their population with income between » and ½ of one minimum wage (OR: 1.56, 95% CI: 1.30-1.87) were also related to the MDR-TB. CONCLUSIONS: Knowledge of these predictive factors may help to develop more comprehensive disease prevention strategies for MDR-TB, avoiding the risks expressed regarding drug resistance expansion.

OBJECTIF: La tuberculose multirésistante (TB-MDR) reste un grave problème de santé publique dans le monde. Cette étude visait à identifier les facteurs de risque individuels, communautaires et d'accès aux services de santé pour la TB-MDR. MÉTHODES: Analyse de cohorte rétrospective de tous les cas de TB diagnostiqués entre 2006 et 2016 dans l'Etat de São Paulo par analyse bayésienne spatiale à plusieurs niveaux. RÉSULTATS: Les antécédents de traitements antituberculeux (Rapports de cotes [OR]: 13,86, Intervalle de confiance à 95% [IC95%]: 12.06-15.93), un test de culture d'expectorations positif (OR: 5,26, IC95%: 4,44-6,23), le diabète sucré (OR: 2,34, IC95%: 1,87-2,91), la résidence à une adresse standard (OR: 2,62, IC95%: 1,91-3,60), la microscopie à frottis positif (OR: 1,74, IC95%: 1,44-2,12), la TB pulmonaire (OR: 1,35, IC95%: 1,14-1,60) et le diagnostic réalisé en raison d'une demande spontanée (OR: 1,26; IC95%: 1,10-1,46) étaient associés à la TB-MDR. Les municipalités qui ont effectué des tests de dépistage du VIH chez moins de 42,65% des patients atteints de TB (OR: 1,50, IC95%: 1,25-1,79), qui ont diagnostiqué des cas de TB uniquement après le décès (OR: 1,50, IC95%: 1,17-1,93) et qui avaient plus de 20,16% de leur population avec un revenu entre » et ½ d'un salaire minimum (OR: 1,56, IC95%: 1,30-1,87) étaient également associées à la TB-MDR. CONCLUSIONS: La connaissance de ces facteurs prédictifs peut aider à développer des stratégies plus complètes de prévention des maladies pour la TB-MDR, en évitant les risques d'extension de la résistance aux médicaments.

First insights into the genetic diversity of Mycobacterium tuberculosis isolates from HIV-infected Mexican patients and mutations causing multidrug resistance.

BACKGROUND: The prevalence of infections with Mycobacterium tuberculosis (MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the Mycobacterium tuberculosis complex strains, to determine their drug resistance profiles by colorimetric microplate Alamar Blue assay (MABA), and finally, to detect mutations present in katG, rpoB and inhA genes, resulting in isoniazid (INH) and rifampin (RIF) resistance. RESULTS: Of the 67 mycobacterial strains isolated, 48 were identified as MTb, 9 as M. bovis, 9 as M. avium and 1 as M. intracellulare. IS6110-RFLP of 48 MTb strains showed 27 profiles. Spoligotyping of the 48 MTb strains yielded 21 patterns, and 9 M. bovis strains produced 7 patterns. Eleven new spoligotypes patterns were found. A total of 40 patterns were produced from the 48 MTb strains when MIRU-VNTR was performed. Nineteen (39.6%) MTb strains were resistant to one or more drugs. One (2.1%) multidrug-resistant (MDR) strain was identified. A novel mutation was identified in a RIF-resistant strain, GAG --> TCG (Glu --> Ser) at codon 469 of rpoB gene. CONCLUSIONS: This is the first molecular analysis of mycobacteria isolated from HIV-infected patients in Mexico, which describe the prevalence of different mycobacterial species in this population. A high genetic diversity of MTb strains was identified. New spoligotypes and MIRU-VNTR patterns as well as a novel mutation associated to RIF-resistance were found. This information will facilitate the tracking of different mycobacterial species in HIV-infected individuals, and monitoring the spread of these microorganisms, leading to more appropriate measures for tuberculosis control.

Multidrug-resistant Mycobacterium tuberculosis in HIV-infected persons, Peru.

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima, Peru, and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%) of 965 patients who were HIV-negative or of unknown HIV status (p<0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB.