As redes vivas na produção do cuidado com o usuário na centralidade do tratamento para tuberculose multidroga resistente / Las redes vivas en la producción del cuidado con el usuario en la centralidad del tratamiento para la tuberculosis multidrogo resistente / Live networks in care production with the user at the center of the treatment for multidrugresistant tuberculosis

Vivenciamos a trajetória de uma usuária-guia no tratamento para tuberculose multidroga resistente (TB-MDR). As narrativas das redes vivas na produção de cuidado apontam para os seguintes itens: 1) cuidar no ato de viver: suplantar os estigmas e cultivar vínculos que ajudem a superar os discursos fomentados pelo medo, preconceitos, exclusão e invisibilidade dos sujeitos; 2) redes vivas de cuidado: os entremeios da norma; e 3) as interfaces de atenção usuário-trabalhador da saúde: como desmistificar o julgamento dos trabalhadores da saúde, que, subordinados a protocolos limitantes, muitas vezes estigmatizam o usuário como "abandonador de tratamento"?. A usuária-guia vislumbrou que cuidar é se desterritorializar, é colocar os desejos como potência para transformação, saindo do modus operandi rumo à criatividade, tendo o usuário no centro do processo. (AU)

Presenciamos la trayectoria de una usuaria-guía en el tratamiento para tuberculosis multidrogo resistente (TB-MDR). Las narrativas de las Redes Vivas en la producción de cuidado señalan: 1) cuidar en el acto de vivir: suplantar los estigmas y cultivar vínculos que ayuden a superar los discursos fomentados por el miedo, prejuicios, exclusión e invisibilidad de los sujetos. 2) Redes Vivas de cuidado: los entresijos de la norma y 3) las interfaces de atención usuario-trabajador de la salud: ¿cómo desmistificar el juicio de los trabajadores de la salud quienes, subordinados a protocolos limitantes, muchas veces estigmatizan al usuario como "abandonador de tratamiento"? La usuaria-guía vislumbró que cuidar es desterritorializarse, es colocar los deseos como potencia para trasformación, saliendo del modus operandi rumbo a la creatividad, colocando al usuario en el centro del proceso. (AU)

We followed the trajectory of a guiding user undergoing treatment for multidrug-resistant tuberculosis (MDR-TB). The narratives of Live Networks in care production showed: 1) Caring in the act of living: Overcoming stigmas and cultivating bonds that help overcome discourses fostered by fear, prejudice, exclusion and invisibility of subjects; 2) Live Networks of care: The in-betweens of the norm; and 3) Interfaces of user-health worker care: How can we demystify the judgment of health workers who, subordinated to limiting protocols, often stigmatize the user as someone who "abandons the treatment"? The guiding user perceived that caring means deterritorializing oneself, expressing one's desires as power for transformation, and leaving the modus operandi towards creativity, with the user at the center of the process. (AU)

Cost analysis of GenoType® MTBDRplus and GenoType® MTBDRsl at the State Laboratory of São Paulo, Brazil.

BACKGROUND: We aimed to evaluate the costs of GenoType® MTBDRplus and MTBDRsl incurred during the diagnosis of first- and second-line drug-resistant tuberculosis (TB) in São Paulo, Brazil. METHODS: Mean and activity-based costs of GenoType® were calculated in a referral laboratory for TB in Brazil. RESULTS: The mean cost value and activity-based cost of GenoType® MTBDRplus were USD 19.78 and USD 35.80 and those of MTBDRsl were USD 54.25 and USD 41.85, respectively. CONCLUSIONS: The cost of GenoType® MTBDRplus was reduced owing to the high number of examinations performed and work optimization.

Nontuberculous mycobacteria in patients of a specialty hospital.

The incidence and clinical characteristics of NTM diseases in Brazil remain relatively unknown. The present study describes the diagnosis of NTM isolates, the clinical presentation and treatment outcomes. We analyzed NTM isolates in patients of a tertiary hospital in the Southeast region of Brazil, from January 2008 to July 2019. The ATS/IDSA criteria for diagnosis and treatment of these patients was applied. Mycobacterium kansasii were identified in 13/113 (11.5%) patients. In 59/113 (52.2%) patients who met the ATS criteria for disease, 29/59 (49.1%) received treatment, and 22/29 (75.8%) were cured. The major species identified was M. kansasii. The most frequent symptoms among the treated patients were dyspnea and cough, and the proportion of cured patients was high.

REDbox: a comprehensive semantic framework for data collection and management in tuberculosis research.

Clinical research outcomes depend on the correct definition of the research protocol, the data collection strategy, and the data management plan. Furthermore, researchers often need to work within challenging contexts, as is the case in tuberculosis services, where human and technological resources for research may be scarce. Electronic Data Capture Systems mitigate such risks and enable a reliable environment to conduct health research and promote result dissemination and data reusability. The proposed solution is based on needs pinpointed by researchers, considering the need for an accommodating solution to conduct research in low-resource environments. The REDbox framework was developed to facilitate data collection, management, sharing, and availability in tuberculosis research and improve the user experience through user-friendly, web-based tools. REDbox combines elements of the REDCap and KoBoToolbox electronic data capture systems and semantics to deliver new valuable tools that meet the needs of tuberculosis researchers in Brazil. The framework was implemented in five cross-institutional, nationwide projects to evaluate the users' perceptions of the system's usefulness and the information and user experience. Seventeen responses (representing 40% of active users) to an anonymous survey distributed to active users indicated that REDbox was perceived to be helpful for the particular audience of researchers and health professionals. The relevance of this article lies in the innovative approach to supporting tuberculosis research by combining existing technologies and tailoring supporting features.

The effect of BCG vaccination on infection and antibody levels against SARS-CoV-2-The results of ProBCG: a multicenter randomized clinical trial in Brazil.

OBJECTIVES: Evatuate if Bacillus Calmette-Guérin (BCG) vaccine could be used as a tool against SARS-CoV-2 based on the concept of trained immunity. METHODS: A multicenter, double-blinded, randomized clinical trial recruited health care workers (HCWs) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCWs receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac or COVISHIELD) was analyzed. Cox proportional hazard and linear mixed effect modeling were used. RESULTS: A total of 264 volunteers were included for analysis (BCG = 134 and placebo = 130). The placebo group presented a COVID-19 cumulative incidence of 0.75% vs 0.52% of BCG. The Moreau strain also presented a higher incidence rate (1.60% × 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log (immunoglobulin G) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance. CONCLUSION: Our results suggest that BCG has a tendency of protection against SARS-CoV-2 and higher immunoglobulin G levels than placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941).

Nontuberculous mycobacteria in patients of a specialty hospital

ABSTRACT The incidence and clinical characteristics of NTM diseases in Brazil remain relatively unknown. The present study describes the diagnosis of NTM isolates, the clinical presentation and treatment outcomes. We analyzed NTM isolates in patients of a tertiary hospital in the Southeast region of Brazil, from January 2008 to July 2019. The ATS/IDSA criteria for diagnosis and treatment of these patients was applied. Mycobacterium kansasii were identified in 13/113 (11.5%) patients. In 59/113 (52.2%) patients who met the ATS criteria for disease, 29/59 (49.1%) received treatment, and 22/29 (75.8%) were cured. The major species identified was M. kansasii. The most frequent symptoms among the treated patients were dyspnea and cough, and the proportion of cured patients was high.

Cost analysis of GenoType® MTBDRplus and GenoType® MTBDRsl at the State Laboratory of São Paulo, Brazil

ABSTRACT Background: We aimed to evaluate the costs of GenoType® MTBDRplus and MTBDRsl incurred during the diagnosis of first- and second-line drug-resistant tuberculosis (TB) in São Paulo, Brazil. Methods: Mean and activity-based costs of GenoType® were calculated in a referral laboratory for TB in Brazil. Results: The mean cost value and activity-based cost of GenoType® MTBDRplus were USD 19.78 and USD 35.80 and those of MTBDRsl were USD 54.25 and USD 41.85, respectively. Conclusions: The cost of GenoType® MTBDRplus was reduced owing to the high number of examinations performed and work optimization.

Clinical, laboratory, and radiographic aspects of patients with pulmonary tuberculosis and dysglycemia and tuberculosis treatment outcomes.

OBJECTIVE: To analyze the association of dysglycemia with clinical, laboratory, and radiographic characteristics of patients with pulmonary tuberculosis (PTB), as well as with their tuberculosis treatment outcomes. METHODS: This was a longitudinal study involving 140 patients diagnosed with PTB (positive cultures for Mycobacterium tuberculosis or positive Xpert MTB/RIF results from sputum samples). Patients were evaluated at diagnosis (M0), after completing the second month of treatment (M2), and at the end of treatment (MEND). At M0, the patients were classified into three groups: normoglycemia+PTB (NGTB); pre-diabetes mellitus+PTB (PDMTB), and diabetes mellitus+PTB (DMTB), in accordance with glycated hemoglobin levels (< 5.7%, 5.7%-6.4%, and ≥ 6.5%, respectively). Treatment outcomes were classified as favorable (cure or treatment completion) and unfavorable (death, loss to follow-up, or treatment failure). RESULTS: In our sample, 76 patients (61.4%) had dysglycemia, 20 of whom (14.3%) had DM at M0. The patients with dysglycemia, in comparison with those in the NGTB group, more frequently presented with positive sputum smear microscopy (94.2% vs. 75.9%; p = 0.003); cavities (80.2% vs. 63.0%; p = 0.03); bilateral lesions (67.4% vs. 46.0%; p = 0.02); and higher median of affected thirds of the lungs (3.0 vs. 2.0; p = 0.03) on chest radiography. No significant differences regarding outcomes were found among the groups, but tuberculosis lethality was higher in the DMTB group than in the PDMTB and NGTB groups (20% vs. 2.2%). CONCLUSIONS: PTB patients with dysglycemia had laboratory and radiographic manifestations indicative of more advanced disease, and the risk of death was higher in the DMTB group. These findings reinforce the recommendation for early screening for DM in patients with newly diagnosed tuberculosis in order to reduce the risk of death during treatment.

String test: a potentially useful tool in the diagnosis of pulmonary tuberculosis in Brazilian children and adolescents.

This study investigated the potential use of the String Test (ST) for the diagnosis of pulmonary tuberculosis (PTB) in children and adolescents. This is a case series of patients aged 4-15 years presenting with clinically presumed PTB and submitted to ST in three pediatric TB referral centers in Brazil, between November 2017 and July 2020. The ST was performed in the morning, after 4-12 h of fasting, followed by ingestion of the capsule by the patient, which was attached to the patient's malar region. The material was collected for simultaneous smear microscopy (acid-fast bacilli - AFB), culture and the molecular investigation by the GeneXpert MTB/RIF®. Thirty-three patients with presumed PTB were included and ST was performed in 26 (78.8%) of them and 7 (21.2%) patients could not swallow the cord. The diagnosis of PTB was established in 11 (42.3%) of the 26 patients who underwent the ST. The diagnosis of PTB was confirmed (by culture or GeneXpert MTB/RIF®) in 5 patients, 4 of whom were also positive by the ST. Two of them showed positivity by the GeneXpert MTB/RIF® only in the ST sample. Two other patients had a positive ST following the induced sputum test (AFB, GeneXpert MTB/RIF®, and positive culture in both specimens). Thus, ST was positive in 36.4% of the patients in whom PTB was diagnosed. ST could be a useful test for diagnosing PTB in children and adolescents.

Comparison of 68Ga-DOTATOC and 18F-FDG Thoracic Lymph Node and Pulmonary Lesion Uptake Using PET/CT in Postprimary Tuberculosis.

Tuberculosis (TB) remains one of the world's leading infectious cause of morbidity and mortality. Positron emission tomography (PET) associated with computed tomography (CT) allows a structural and metabolic evaluation of TB lesions, being an excellent noninvasive alternative for understanding its pathogenesis. DOTATOC labeled with gallium-68 (68Ga-DOTATOC) can bind to somatostatin receptors present in activated macrophages and lymphocytes, cells with a fundamental role in TB pathogenesis. We describe 68Ga-DOTATOC uptake distribution and patterns in thoracic lymph nodes (LN) and pulmonary lesions (PL) in immunocompetent patients with active postprimary TB, analyze the relative LN/PL uptake, and compare this two tracer's uptake. High uptake of both radiotracers in PL and LN was demonstrated, with higher LN/PL ratio on 68Ga-DOTATOC (P < 0.05). Considering that LN in immunocompetent patients are poorly studied, 68Ga-DOTATOC can contribute to the understanding of the complex immunopathogenesis of TB.

Gene-Xpert Ultra for the diagnosis of extrapulmonary tuberculosis in children and adolescents.

This prospective study describes the use of Gene-Xpert Ultra for the diagnosis of extrapulmonary tuberculosis (EPTB) in children and adolescents, in Rio de Janeiro, Brazil. Eighteen patients were studied; the final diagnosis of EPTB was established in 13 (72%). Gene-Xpert Ultra results showed detection in 10/13 (77%) of EPTB cases (7 of these 10 with trace-positive results). Gene-Xpert Ultra proved to be a promising method for the diagnosis of childhood EPTB.

Clinical, laboratory, and radiographic aspects of patients with pulmonary tuberculosis and dysglycemia and tuberculosis treatment outcomes / Aspectos clínicos, laboratoriais e radiográficos de pacientes com tuberculose pulmonar e disglicemia e desfechos do tratamento da tuberculose

ABSTRACT Objective: To analyze the association of dysglycemia with clinical, laboratory, and radiographic characteristics of patients with pulmonary tuberculosis (PTB), as well as with their tuberculosis treatment outcomes. Methods: This was a longitudinal study involving 140 patients diagnosed with PTB (positive cultures for Mycobacterium tuberculosis or positive Xpert MTB/RIF results from sputum samples). Patients were evaluated at diagnosis (M0), after completing the second month of treatment (M2), and at the end of treatment (MEND). At M0, the patients were classified into three groups: normoglycemia+PTB (NGTB); pre-diabetes mellitus+PTB (PDMTB), and diabetes mellitus+PTB (DMTB), in accordance with glycated hemoglobin levels (< 5.7%, 5.7%-6.4%, and ≥ 6.5%, respectively). Treatment outcomes were classified as favorable (cure or treatment completion) and unfavorable (death, loss to follow-up, or treatment failure). Results: In our sample, 76 patients (61.4%) had dysglycemia, 20 of whom (14.3%) had DM at M0. The patients with dysglycemia, in comparison with those in the NGTB group, more frequently presented with positive sputum smear microscopy (94.2% vs. 75.9%; p = 0.003); cavities (80.2% vs. 63.0%; p = 0.03); bilateral lesions (67.4% vs. 46.0%; p = 0.02); and higher median of affected thirds of the lungs (3.0 vs. 2.0; p = 0.03) on chest radiography. No significant differences regarding outcomes were found among the groups, but tuberculosis lethality was higher in the DMTB group than in the PDMTB and NGTB groups (20% vs. 2.2%). Conclusions: PTB patients with dysglycemia had laboratory and radiographic manifestations indicative of more advanced disease, and the risk of death was higher in the DMTB group. These findings reinforce the recommendation for early screening for DM in patients with newly diagnosed tuberculosis in order to reduce the risk of death during treatment.

RESUMO Objetivo: Analisar a associação de disglicemia e características clínicas, laboratoriais e radiográficas em pacientes com tuberculose pulmonar (TBP), bem como a associação de disglicemia e desfechos do tratamento da tuberculose. Métodos: Estudo longitudinal com 140 pacientes com diagnóstico de TBP (culturas de escarro positivas para Mycobacterium tuberculosis ou resultados positivos do teste Xpert MTB/RIF em amostras de escarro). Os pacientes foram avaliados no momento do diagnóstico (M0), após dois meses de tratamento (M2) e no fim do tratamento (MFIM). Em M0, os pacientes foram divididos em três grupos: normoglicemia+TBP (NGTB); pré-diabetes mellitus+TBP (PDMTB) e diabetes mellitus+TBP (DMTB), de acordo com os níveis de hemoglobina glicada (< 5,7%, 5,7%-6,4% e ≥ 6,5%, respectivamente). Os desfechos do tratamento foram classificados em favoráveis (cura ou conclusão do tratamento) e desfavoráveis (óbito, perda de seguimento ou falência do tratamento). Resultados: Em nossa amostra, 76 pacientes (61,4%) apresentavam disglicemia, 20 (14,3%) dos quais apresentavam DM em M0. Os pacientes com disglicemia, em comparação com os do grupo NGTB, apresentaram mais frequentemente baciloscopia de escarro positiva (94,2% vs. 75,9%; p = 0,003); cavidades (80,2% vs. 63,0%; p = 0,03); lesões bilaterais (67,4% vs. 46,0%; p = 0,02) e maior mediana de terços pulmonares acometidos (3,0 vs. 2,0; p = 0,03) na radiografia de tórax. Não foram observadas diferenças significativas entre os grupos quanto aos desfechos, mas a letalidade da tuberculose foi maior no grupo DMTB do que nos grupos PDMTB e NGTB (20% vs. 2,2%). Conclusões: Pacientes com TBP e disglicemia apresentaram manifestações laboratoriais e radiográficas indicativas de doença mais avançada, e o risco de óbito foi maior no grupo DMTB. Esses achados reforçam a recomendação de detecção precoce de DM em pacientes com tuberculose recém-diagnosticada, a fim de reduzir o risco de óbito durante o tratamento.

Gene-Xpert Ultra for the diagnosis of extrapulmonary tuberculosis in children and adolescents

ABSTRACT This prospective study describes the use of Gene-Xpert Ultra for the diagnosis of extrapulmonary tuberculosis (EPTB) in children and adolescents, in Rio de Janeiro, Brazil. Eighteen patients were studied; the final diagnosis of EPTB was established in 13 (72%). Gene-Xpert Ultra results showed detection in 10/13 (77%) of EPTB cases (7 of these 10 with trace-positive results). Gene-Xpert Ultra proved to be a promising method for the diagnosis of childhood EPTB.

[Factors associated with underreporting of cases of multidrug-resistant tuberculosis in the state of Rio de Janeiro, Brazil: probabilistic database linkage]. / Fatores associados à subnotificação de casos de tuberculose multirresistente no Estado do Rio de Janeiro, Brasil: relacionamento probabilístico entre sistemas de informação.

This study estimated the proportion of underreporting of multidrug-resistant tuberculosis (MDR-TB) and associated factors in the State of Rio de Janeiro, Brazil, as well as the proportion of deaths in this group. A retrospective cohort study was conducted using probabilistic database linkage. Cases with the results of the drug sensitivity test (DST) with MDR-TB pattern recorded in the Laboratory Environment Management System (GAL) from 2010 to 2017 were linked to cases reported to the Special TB Treatments System (SITETB). Simple and multiple logistic regressions were performed to estimate factors associated with underreporting. Death was verified by search for cases in the Mortality Information System (SIM) and in the portal of the Rio de Janeiro State Court of Justice. Of the 651 cases of MDR-TB in the GAL, 165 had not been reported to the SITETB, meaning an underreporting rate of 25.4% in the sample. Among the unreported cases, 61 (37%) were identified in the death records. In the multiple analysis, the fact that the test was ordered by a hospital (OR = 2.86; 95%CI: 1.72-4.73) was associated with underreporting. Overall, the mean turnaround time between ordering the test and releasing the result was 113 days. Among reported cases, the mean time between ordering the test and initiating treatment was 169 days. The results underline the urgent need to strengthen epidemiological surveillance activities for MDR-TB, establish and monitor hospital surveillance centers and routine TB reporting in hospitals, review operational stages, and integrate various information systems to make them more agile and integrated.

Neste estudo, estimou-se a proporção e os fatores associados à subnotificação da tuberculose multirresistente (TB-MDR) no Estado do Rio de Janeiro, Brasil, assim como a proporção de óbitos nesse grupo. Realizou-se um estudo de coorte retrospectiva, utilizando a técnica de relacionamento probabilístico entre sistemas de informação. Os casos com resultado do teste de sensibilidade às drogas (TSA) com padrão TB-MDR registrados no Sistema Gerenciador de Ambiente Laboratorial (GAL), no período 2010 a 2017, foram relacionados com casos notificados no Sistema de Tratamentos Especiais de Tuberculose (SITETB). Regressões logísticas simples e múltipla foram realizadas para estimar os fatores associados à subnotificação. Para verificar o óbito, foi realizada a busca dos casos no Sistema de Informações sobre Mortalidade (SIM) e no portal do Tribunal de Justiça do Estado do Rio de Janeiro. Dos 651 casos TB-MDR no GAL, 165 não haviam sido notificados no SITETB, perfazendo uma subnotificação de 25,4% na amostra. Entre os casos subnotificados, 61 (37%) foram encontrados nos registros de óbito. Na análise múltipla, ter o exame solicitado por um hospital (OR = 2,86; IC95%: 1,72-4,73) esteve associado à subnotificação. No geral, o tempo médio entre a solicitação do exame e a liberação do resultado foi de 113 dias. Entre os casos notificados, o tempo médio entre a solicitação do exame e o início do tratamento foi de 169 dias. Diante disso, é urgente fortalecer as ações de vigilância epidemiológica na TB-MDR, estabelecer e monitorar núcleos de vigilância hospitalar e as rotinas de notificação de TB nos hospitais, rever etapas operacionais, além de unificar os diversos sistemas de informação tornando-os mais ágeis e integrados.

En este estudio se estimó la proporción y los factores asociados a la subnotificación de la tuberculosis resistente a múltiples fármacos (TB-MDR) en el Estado de Río de Janeiro, Brasil, así como la proporción de óbitos en ese grupo. Se realizó un estudio de cohorte retrospectiva, utilizando la técnica de relación probabilística entre sistemas de información. Los casos con resultado del test de sensibilidad a las drogas (TSA) con patrón TB-MDR, registrados en el Sistema Gerenciador de Ambiente Laboratorial (GAL), en el período 2010 a 2017, se relacionaron con casos notificados en el Sistema de Tratamientos Especiales de Tuberculosis (SITETB). Se realizaron regresiones logísticas simples y múltiples para estimar los factores asociados a la subnotificación. Para verificar el óbito, se realizó la búsqueda de los casos en el Sistema de Información sobre Mortalidad (SIM) y en el portal del Tribunal de Justicia del Estado de Río de Janeiro. De los 651 casos TB-MDR en el GAL, 165 no habían sido notificados en el SITETB, lo que equivale a una subnotificación de un 25,4% en la muestra. Entre los casos subnotificados, 61 (37%) se encontraron en los registros de óbito. En el análisis múltiple, que el examen haya sido solicitado por un hospital (OR = 2,86; IC95%: 1,72-4,73) estuvo asociado a la subnotificación. En general, el tiempo medio entre la solicitud del examen y la llegada del resultado fue de 113 días. Entre los casos notificados, el tiempo medio entre la solicitud del examen y el inicio del tratamiento fue de 169 días. Ante esto, es urgente fortalecer las acciones de vigilancia epidemiológica en la TB-MDR, establecer y supervisar núcleos de vigilancia hospitalaria y las rutinas de notificación de TB en los hospitales, revisar etapas operacionales, además de unificar los diversos sistemas de información haciéndolos más ágiles e integrados.

Cost analysis for patients with presumed pulmonary tuberculosis attended in the public health system of rio de janeiro, Brazil.

Background: In last years, few attention has given to the patient's prediagnostic costs when evaluating the introduction of new technologies for tuberculosis (TB) and in this context, this study evaluated patient's costs and cost-effectiveness incurred with TB diagnosis comparing BactecTMMGITTM960 system (MGIT) to the Löwestein-Jensen (LJ) culture in a health center and in a university hospital, in Rio de Janeiro City, Brazil. Methods: Patient's mean costs were evaluated during the diagnosis process and cost-effectiveness based on mean time in days for the adoption of appropriate clinical anti-TB treatment in two health units comparing culture by means LJ and MGIT. Results: The mean cost of LJ and MGIT in the health center was U. S. dollars (US$) 26.6 and US$ 45.13, respectively, and in university hospital was US$ 206.87 and US$ 285.48, respectively. Comparing the two approaches for TB diagnosis incurred by the patients, the incremental cost-effectiveness of MGIT compared to LJ was US$ 0.88 and US$ 4.03 per patient, respectively, to reduce the average time to adopt appropriate treatment. Conclusions: The culture method directly impacts patient costs while waiting for the correct diagnosis and contributing to aggravating costs with patients with TB.

Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil.

Genomic-based surveillance on the occurrence of drug resistance and its transmission dynamics has emerged as a powerful tool for the control of tuberculosis (TB). A whole-genome sequencing approach, phenotypic testing and clinical-epidemiological investigation were used to undertake a retrospective population-based study on drug-resistant (DR)-TB in Rio Grande do Sul, the largest state in Southern Brazil. The analysis included 305 resistant Mycobacterium tuberculosis strains sampled statewide from 2011 to 2014, and covered 75.7% of all DR-TB cases identified in this period. Lineage 4 was found to be predominant (99.3%), with high sublineage-level diversity composed mainly of 4.3.4.2 [Latin American and Mediterranean (LAM)/RD174], 4.3.3 (LAM/RD115) and 4.1.2.1 (Haarlem/RD182) sublineages. Genomic diversity was also reflected in resistance of the variants to first-line drugs. A large number of distinct resistance-conferring mutations, including variants that have not been reported previously in any other setting worldwide, and 22 isoniazid-monoresistant strains with mutations described as disputed in the rpoB gene but causing rifampicin resistance generally missed by automated phenotypic tests as BACTEC MGIT. Using a cut-off of five single nucleotide polymorphisms, the estimated recent transmission rate was 55.1%, with 168 strains grouped into 28 genomic clusters. The most worrying fact concerns multi-drug-resistant (MDR) strains, of which 73.4% were clustered. Different resistance profiles and acquisition of novel mutations intraclusters revealed important amplification of resistance in the region. This study described the diversity of M. tuberculosis strains, the basis of drug resistance, and ongoing transmission dynamics across the largest state in Southern Brazil, stressing the urgent need for MDR-TB transmission control state-wide.

Tuberculosis among children and adolescents in Rio de Janeiro, Brazil - Focus on extrapulmonary disease.

OBJECTIVE: To compare the socio-demographic, clinical, and diagnostic characteristics and treatment outcomes between extrapulmonary tuberculosis (EPTB) and pulmonary tuberculosis (PTB) in children and adolescents in Rio de Janeiro, a high TB-burdened Brazilian city. METHODS: This retrospective study used data from patients with EPTB and PTB aged 0 - 18 years, notified on two national databases from 2014 to 2016. RESULTS: Among the 1008 patients, 144 (14.2%) had EPTB. Patients with EPTB showed higher odds of hospital-based diagnosis (odds ratio (OR): 6.76 [95% confidence interval (95% CI): 4.62-9.90]; p < 0.001), no laboratory confirmation (OR: 4.9 2.14 [95% CI: 3.07 - 7.85]; p < 0.001), and being <14 years old (OR: 3.13 [95% CI: 2.18-4.49]) than those with PTB. A diagnosis without laboratory investigation was observed among 301/864 (34.8%) patients with PTB, 48/144 (33.3%) with EPTB, and among those aged under five years with EPTB (15/27 [55.6%]). TB deaths were more frequent in patients with EPTB (5/144 [3.5%]) than in those with PTB (4/864[0.5%]) (p = 0.001); 4/5 (80%) TB deaths were due to TB meningitis; 50% died within 14 days of diagnosis. CONCLUSIONS: EPTB remains a clinical diagnostic challenge that needs to be addressed to fully benefit from the higher sensitivity laboratory investigations.

Fatores associados à subnotificação de casos de tuberculose multirresistente no Estado do Rio de Janeiro, Brasil: relacionamento probabilístico entre sistemas de informação / Factors associated with underreporting of cases of multidrug-resistant tuberculosis in the state of Rio de Janeiro, Brazil: probabilistic database linkage / Factores asociados a la subnotificación de casos de tuberculosis resistente a múltiples fármacos en el estado de Río de Janeiro, Brasil: relación probabilística entre sistemas de información

Neste estudo, estimou-se a proporção e os fatores associados à subnotificação da tuberculose multirresistente (TB-MDR) no Estado do Rio de Janeiro, Brasil, assim como a proporção de óbitos nesse grupo. Realizou-se um estudo de coorte retrospectiva, utilizando a técnica de relacionamento probabilístico entre sistemas de informação. Os casos com resultado do teste de sensibilidade às drogas (TSA) com padrão TB-MDR registrados no Sistema Gerenciador de Ambiente Laboratorial (GAL), no período 2010 a 2017, foram relacionados com casos notificados no Sistema de Tratamentos Especiais de Tuberculose (SITETB). Regressões logísticas simples e múltipla foram realizadas para estimar os fatores associados à subnotificação. Para verificar o óbito, foi realizada a busca dos casos no Sistema de Informações sobre Mortalidade (SIM) e no portal do Tribunal de Justiça do Estado do Rio de Janeiro. Dos 651 casos TB-MDR no GAL, 165 não haviam sido notificados no SITETB, perfazendo uma subnotificação de 25,4% na amostra. Entre os casos subnotificados, 61 (37%) foram encontrados nos registros de óbito. Na análise múltipla, ter o exame solicitado por um hospital (OR = 2,86; IC95%: 1,72-4,73) esteve associado à subnotificação. No geral, o tempo médio entre a solicitação do exame e a liberação do resultado foi de 113 dias. Entre os casos notificados, o tempo médio entre a solicitação do exame e o início do tratamento foi de 169 dias. Diante disso, é urgente fortalecer as ações de vigilância epidemiológica na TB-MDR, estabelecer e monitorar núcleos de vigilância hospitalar e as rotinas de notificação de TB nos hospitais, rever etapas operacionais, além de unificar os diversos sistemas de informação tornando-os mais ágeis e integrados.

This study estimated the proportion of underreporting of multidrug-resistant tuberculosis (MDR-TB) and associated factors in the State of Rio de Janeiro, Brazil, as well as the proportion of deaths in this group. A retrospective cohort study was conducted using probabilistic database linkage. Cases with the results of the drug sensitivity test (DST) with MDR-TB pattern recorded in the Laboratory Environment Management System (GAL) from 2010 to 2017 were linked to cases reported to the Special TB Treatments System (SITETB). Simple and multiple logistic regressions were performed to estimate factors associated with underreporting. Death was verified by search for cases in the Mortality Information System (SIM) and in the portal of the Rio de Janeiro State Court of Justice. Of the 651 cases of MDR-TB in the GAL, 165 had not been reported to the SITETB, meaning an underreporting rate of 25.4% in the sample. Among the unreported cases, 61 (37%) were identified in the death records. In the multiple analysis, the fact that the test was ordered by a hospital (OR = 2.86; 95%CI: 1.72-4.73) was associated with underreporting. Overall, the mean turnaround time between ordering the test and releasing the result was 113 days. Among reported cases, the mean time between ordering the test and initiating treatment was 169 days. The results underline the urgent need to strengthen epidemiological surveillance activities for MDR-TB, establish and monitor hospital surveillance centers and routine TB reporting in hospitals, review operational stages, and integrate various information systems to make them more agile and integrated.

En este estudio se estimó la proporción y los factores asociados a la subnotificación de la tuberculosis resistente a múltiples fármacos (TB-MDR) en el Estado de Río de Janeiro, Brasil, así como la proporción de óbitos en ese grupo. Se realizó un estudio de cohorte retrospectiva, utilizando la técnica de relación probabilística entre sistemas de información. Los casos con resultado del test de sensibilidad a las drogas (TSA) con patrón TB-MDR, registrados en el Sistema Gerenciador de Ambiente Laboratorial (GAL), en el período 2010 a 2017, se relacionaron con casos notificados en el Sistema de Tratamientos Especiales de Tuberculosis (SITETB). Se realizaron regresiones logísticas simples y múltiples para estimar los factores asociados a la subnotificación. Para verificar el óbito, se realizó la búsqueda de los casos en el Sistema de Información sobre Mortalidad (SIM) y en el portal del Tribunal de Justicia del Estado de Río de Janeiro. De los 651 casos TB-MDR en el GAL, 165 no habían sido notificados en el SITETB, lo que equivale a una subnotificación de un 25,4% en la muestra. Entre los casos subnotificados, 61 (37%) se encontraron en los registros de óbito. En el análisis múltiple, que el examen haya sido solicitado por un hospital (OR = 2,86; IC95%: 1,72-4,73) estuvo asociado a la subnotificación. En general, el tiempo medio entre la solicitud del examen y la llegada del resultado fue de 113 días. Entre los casos notificados, el tiempo medio entre la solicitud del examen y el inicio del tratamiento fue de 169 días. Ante esto, es urgente fortalecer las acciones de vigilancia epidemiológica en la TB-MDR, establecer y supervisar núcleos de vigilancia hospitalaria y las rutinas de notificación de TB en los hospitales, revisar etapas operacionales, además de unificar los diversos sistemas de información haciéndolos más ágiles e integrados.