Tuberculosis in Ukrainian War Refugees and Migrants in the Czech Republic and Slovakia: A Molecular Epidemiological Study.

BACKGROUND: The war in Ukraine has led to significant migration to neighboring countries, raising public health concerns. Notable tuberculosis (TB) incidence rates in Ukraine emphasize the immediate requirement to prioritize approaches that interrupt the spread and prevent new infections. METHODS: We conducted a prospective genomic surveillance study to assess migration's impact on TB epidemiology in the Czech Republic and Slovakia. Mycobacterium tuberculosis isolates from Ukrainian war refugees and migrants, collected from September 2021 to December 2022 were analyzed alongside 1574 isolates obtained from Ukraine, the Czech Republic, and Slovakia. RESULTS: Our study revealed alarming results, with historically the highest number of Ukrainian tuberculosis patients detected in the host countries. The increasing number of cases of multidrug-resistant TB, significantly linked with Beijing lineage 2.2.1 (p < 0.0001), also presents substantial obstacles to control endeavors. The genomic analysis identified the three highly related genomic clusters, indicating the recent TB transmission among migrant populations. The largest clusters comprised war refugees diagnosed in the Czech Republic, TB patients from various regions of Ukraine, and incarcerated individuals diagnosed with pulmonary TB specialized facility in the Kharkiv region, Ukraine, pointing to a national transmission sequence that has persisted for over 14 years. CONCLUSIONS: The data showed that most infections were likely the result of reactivation of latent disease or exposure to TB before migration rather than recent transmission occurring within the host country. However, close monitoring, appropriate treatment, careful surveillance, and social support are crucial in mitigating future risks, though there is currently no evidence of local transmission in EU countries.

Strain structure analysis of Mycobacterium tuberculosis circulating among HIV negative, positive and drug resistant TB patients attending chest clinics in Western Kenya.

BACKGROUND: Despite global tuberculosis (TB) interventions, the disease remains one of the major public health concerns. Kenya is ranked 15th among 22 high burden TB countries globally. METHODS: A cross-sectional study was conducted in Western Kenya, which comprises 10 counties. A multistage sampling method was used where a single sub-county was randomly selected followed by sampling two high volume health facility from each sub-county. Identification of spoligotype profiles and their family distribution and lineage level were achieved by comparison with SITVIT database. RESULTS: Lineage distribution pattern revealed that the most predominant lineage was CAS 220 (39.8%) followed by Beijing 128 (23.1%). The other lineages identified were T, LAM, H, X, S and MANU which were quantified as 87 (15.7%), 67 (12.1%), 16 (2.8%), 10 (1.8%), 8 (1.4%) and 5 (0.9%) respectively. CAS and Beijing strains were the most predominant lineage in both HIV negative and positive TB patients. The Beijing lineage was also the most predominant in resistant M. tuberculosis strains as compared to wild type. A total of 12 (2.0%) were orphaned M. tuberculosis strains which were spread across all the 10 counties of the study site. In multivariate logistic regression adjusting for potential cofounders three potential risk factors were significant. HIV status (OR = 1.52, CI = 0.29-3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43-3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49-3.87 and P value = 0.026). Most M. tuberculosis clinical isolates showed genetic clustering with multivariate logistic regression indicating three potential risk factors to clustering. HIV status (OR = 1.52, CI = 0.29-3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43-3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49-3.87 and P value = 0.026). CONCLUSION: There exist diverse strains of M. tuberculosis across the 10 counties of Western Kenya. Predominant distribution of clustered genotype points to the fact that most TB cases in this region are as a result of resent transmission other than activation of latent TB.

Profil épidémiologique et mortalité due à la tuberculose dans la zone de Santé de Kamina, Province du Haut-Lomami, en Démocratique du Congo / Epidemiological profile and deaths related to TB disease in the Kamina´s Health Zone, Haut-Lomami Province, Democratic Republic of the Congo

Introduction: Était de décrire le profil épidémiologique, clinique et évolutif des patients tuberculeux suivis dans le milieu urbano-rural de Kaminaen République Démocratique du Congo (RDC). Méthodes: il s´agit d´une étude transversale par analyse rétrospective de dossiers des patients suivis pour tuberculose sur une période allant du 1er Janvier 2018 au 31 Décembre 2021. Résultats: sur un total de 612 échantillons analysés, 216 cas de tuberculose ont été confirmés par le laboratoire, soit une fréquence de 35,3 %. Notre échantillon était constitué de 138 hommes et 78 femmes, soit un sex-ratio de 1,77. L´âge moyen était de 35,37±18,14 années. La majorité des patients était dans la tranche d´âge comprise entre 21-40 ans. La profession libérale représentait 94,4 % de notre effectif, soit 204 patients. Il y a eu 63,4% des patients souffraient d´une tuberculose pulmonaire dont 70,9 % était guéris. La sérologie VIH était positive chez 6 patients, soit un taux de séroprévalence VIH de 2,77 %. Au total, 27 malades sont décédés sur les 612, soit un taux de mortalité de 4,41 %. C´est la tranche d´âge de malades ages de plus de 60 ans qui a connu une mortalitéélévée, soit 5 cas sur 20 (25 %), suivie de celle des malades ages de moins de 20 ans, 11 cas sur 49 (22,4 %). D´autre part, le résultat a montré un taux de mortalité plus élévé chez les tuberculeux séropositif, 33,3 %, contre 11.9 % chez les séronégatifs. Conclusion: ce rapport montre un taux élevé de tuberculose dans la zone de santé de Kamina ; il confirme le fait que la TB est endémique dans la région. Il est nécessaire d'améliorer les conditions de vie de la population et le système de santé local en ce qui concerne la prévention et la gestion de la TB afin de réduire sa morbi-mortalité.

Introduction: the purpose of this study was to describe the epidemiological, clinical and evolutionary profile of patients with tuberculosis followed in the urban-rural area of Kamina, Democratic Republic of the Congo (DRC). Methods: we conducted a cross-sectional study based on a retrospective analysis of the medical records of patients followed for tuberculosis over the period January 1, 2018 -December 31, 2021. Results: out of 612 samples analysed, 216 cases had received lab confirmation of tuberculosis, reflecting a rate of 35.3%. Our sample consisted of 78 women and 138 men (sex ratio 1.77). The average age of patients was 35,37±18.14 years. The majority of patients were in the age range 21-40 years. Self-employed people accounted for 94.4% of our workforce (204 patients); 63.4% of patients suffered from pulmonary tuberculosis, 70.9% of whom were cured. Serology test for HIV was positive in 6 patients (i.e. an HIV seroprevalence rate of 2.77%). In total, 27 patients out of 612 died, (i.e. a mortality rate of 4.41%). Patients aged over 60 had higher mortality rates (5 out of 20 cases; 25%), followed by patients under 20 (11 out of 49 cases; 22.4%). On the other hand, our results showed a higher mortality rate among HIV-positive patients with tuberculosis (33.3%, compared to 11.9% among HIV-negative patients). Conclusion: this study shows a high rate of tuberculosis in the Kamina health zone, confirming the fact that TB is endemic in the region. There is a need to improve the living conditions of the population and the local health system with regard to the prevention and management of TB in order to reduce morbidity and mortality

Self-reported Engagement in Care among U.S. Residents with Latent Tuberculosis Infection: 2011-2012.

Rationale: A central strategy of tuberculosis (TB) control in the United States is reducing the burden of latent TB infection (LTBI) through targeted testing and treatment of persons with untreated LTBI. Objectives: The objective of the study was to provide estimates of and risk factors for engagement in LTBI care in the overall U.S. population and among specific risk groups. Methods: We used nationally representative data from 7,080 participants in the 2011-2012 National Health and Nutrition Examination Survey. Engagement in LTBI care was assessed by estimating the proportion with a history of testing, diagnosis, treatment initiation, and treatment completion. Weighted methods were used to account for the complex survey design and to derive national estimates. Results: Only 1.4 million (10%) of an estimated 14.0 million individuals with an LTBI had previously completed treatment. Of the 12.6 million who did not complete LTBI treatment, 3.7 million (29%) had never been tested and 7.2 million (57%) received testing but had no history of diagnosis. High-risk groups showed low levels of engagement, including contacts of individuals with TB and persons born outside the United States. Conclusions: There is a reservoir of more than 12 million individuals in the United States who may be at risk for progression to TB disease and potential transmission. TB control programs and community providers should consider focused efforts to increase testing, diagnosis, and treatment for LTBI.

Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission.

Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission.

Temporal trend of tuberculosis incidence and its spatial distribution in Macapá - Amapá / Tendência temporal da incidência de tuberculose e sua distribuição espacial em Macapá-AP

ABSTRACT OBJECTIVE: To evaluate the temporal trend of tuberculosis incidence after the implementation of the rapid molecular test (RMT-TB), to identify whether tuberculosis presents seasonal variation and to classify the territory according to case density and risk areas in Macapá, Amapá. METHODS: Ecological study of tuberculosis cases registered in the Sistema de Informação de Agravos de Notificação (SINAN - Information System for Notifiable Diseases) between 2001 and 2017. We used the Prais-Winsten test to classify the temporal trend of incidence and the interrupted time series to identify changes in the temporal trend before and after the implementation of the rapid molecular test, and to verify seasonality in the municipality. The Kernel estimator was used to classify case density and scan statistics to identify areas of tuberculosis risk. RESULTS: A total of 1,730 cases were identified, with a decreasing temporal trend of tuberculosis incidence (−0.27% per month, 95%CI −0.13 to −0.41). The time series showed no change in level after the implementation of the GeneXpert®MTB/RIF molecular test; however, the incidence increased in the post-test period (+2.09% per month, 95%CI 0.92 to 3.27). Regarding the seasonal variation, it showed growth (+13.7%/month, 95%CI 4.71 to 23.87) from December to June, the rainy season - called amazon winter season -, and decrease (−9.21% per month, CI95% −1.37 to −16.63) in the other periods. We classified areas with high density of cases in the Central and Northern districts using Kernel and identified three protection clusters, SC1 (RR = 0.07), SC2 (RR = 0.23) and SC3 (RR = 0.36), and a high-risk cluster, SC4 (RR = 1.47), with the scan statistics. CONCLUSION: The temporal trend of tuberculosis incidence was decreasing in the time series; however, detection increased after the introduction of RMT-TB, and tuberculosis showed seasonal behavior. The case distribution was heterogeneous, with a tendency to concentrate in vulnerable and risk territories, evidencing a pattern of disease inequality in the territory.

RESUMO OBJETIVO: Avaliar a tendência temporal da incidência da tuberculose após a implementação do teste rápido molecular, identificar se a tuberculose apresenta variação sazonal e classificar o território de acordo com a densidade de casos e as áreas de risco em Macapá-AP. MÉTODOS: Estudo ecológico composto por casos de tuberculose registrados no SINAN entre 2001 e 2017. Foi utilizado o teste Prais-Winsten para classificar a tendência temporal da incidência e a Série Temporal Interrompida para identificar mudanças na tendência temporal antes e depois da implementação do teste rápido molecular, além de verificar a sazonalidade no município. Utilizou-se o estimador de Kernel para classificar a densidade de casos e estatística de varredura para identificar áreas de risco da tuberculose. RESULTADOS: Foram identificados 1730 casos, observando-se que a tendência temporal da incidência de tuberculose foi decrescente (-0,27% por mês, IC95% −0,13 a −0,41). Não houve mudança de nível na série temporal após a implantação do teste molecular GeneXpert® MTB/RIF, porém, o período pós teste foi classificado como crescente em termos da incidência (+2,09% por mês, IC95% 0,92 a 3,27). Quanto à variação sazonal, apresentou crescimento (+13,7%/mês, IC95% 4,71 a 23,87) nos meses de dezembro a junho, referente ao período de chuvas - chamado inverno amazônico - e decréscimo (-9,21% por mês, IC95% −1,37 a −16,63) nos demais períodos. Por meio de Kernel, foram classificadas áreas com alta densidade de casos nos distritos Central e Norte e, com a estatística de varredura, foram identificados três aglomerados de proteção, AE1 (RR = 0,07), AE2 (RR = 0,23) e AE3 (RR = 0,36), e um aglomerado de alto risco, AE4 (RR = 1,47). CONCLUSÃO: A tendência temporal da incidência de tuberculose se revelou decrescente na série temporal, todavia, um crescimento na detecção foi observado após introdução do TRM-TB, e ainda se evidenciou que há comportamento sazonal da tuberculose. A distribuição dos casos foi heterogênea, com tendência de concentração em territórios vulneráveis e de risco, evidenciando um padrão de desigualdade da doença no território.

Tuberculosis in Brazil: one country, multiple realities / Tuberculose no Brasil: um país, múltiplas realidades

ABSTRACT Objective: To identify the determinants of tuberculosis-related variables in the various regions of Brazil and evaluate trends in those variables over the ten-year period preceding the end of the timeframe defined for the United Nations Millennium Development Goals (MDGs). Methods: This was an ecological analytical study in which we utilized eight national public databases to investigate the 716,971 new tuberculosis cases reported between 2006 and 2015. Results: Over the study period, there were slight reductions in the prevalence, incidence, and mortality associated with tuberculosis. Brazil did not reach the MDG for tuberculosis-related mortality. Among the performance indicators of tuberculosis control, there were improvements only in those related to treatment and treatment abandonment. In terms of the magnitude of tuberculosis, substantial regional differences were observed. The tuberculosis incidence rate was highest in the northern region, as were the annual mean temperature and relative air humidity. That region also had the second lowest human development index, primary health care (PHC) coverage, and number of hospitalizations for tuberculosis. The northeastern region had the highest PHC coverage, number of hospitalizations for primary care-sensitive conditions, and tuberculosis-related mortality rate. The southern region showed the smallest reductions in epidemiological indicators, together with the greatest increases in the frequency of treatment abandonment and retreatment. The central-west region showed the lowest overall magnitude of tuberculosis and better monitoring indicators. Conclusions: The situation related to tuberculosis differs among the five regions of Brazil. Those differences can make it difficult to control the disease in the country and could explain the fact that Brazil failed to reach the MDG for tuberculosis-related mortality. Tuberculosis control measures should be adapted to account for regional differences.

RESUMO Objetivo: Identificar os determinantes das variáveis da tuberculose nas diversas regiões do Brasil e avaliar as tendências dessas variáveis ao longo dos dez anos anteriores ao término do prazo definido para os Objetivos de Desenvolvimento do Milênio (ODM) das Nações Unidas. Métodos: Estudo analítico ecológico no qual utilizamos oito bancos de dados públicos nacionais para investigar os 716.971 casos novos de tuberculose notificados entre 2006 e 2015. Resultados: Durante o período estudado, houve ligeiras reduções na prevalência, incidência e mortalidade associadas à tuberculose. O Brasil não atingiu o ODM de mortalidade por tuberculose. Entre os indicadores de desempenho no controle da tuberculose, houve melhora apenas naqueles relacionados a tratamento e abandono de tratamento. Em termos da magnitude da tuberculose, foram observadas diferenças regionais substanciais. A taxa de incidência de tuberculose foi maior na região Norte, assim como a temperatura média anual e a umidade relativa do ar. Essa região também apresentou a segunda menor média do índice de desenvolvimento humano, a menor cobertura de atenção primária à saúde (APS) e o menor número de hospitalizações por tuberculose. A região Nordeste apresentou a maior cobertura de APS, o maior número de hospitalizações por condições sensíveis à atenção primária e a maior taxa de mortalidade por tuberculose. A região Sul apresentou as menores reduções nos indicadores epidemiológicos, juntamente com os maiores aumentos na frequência de abandono de tratamento e de retratamento. A região Centro-Oeste apresentou a menor magnitude geral de tuberculose e melhores indicadores de monitoramento. Conclusões: A situação da tuberculose difere entre as cinco regiões do Brasil. Essas diferenças podem dificultar o controle da doença no país e podem explicar o fato de o Brasil não ter atingido o ODM de mortalidade por tuberculose. As medidas de controle da tuberculose devem ser adaptadas para dar conta das diferenças regionais.

The potential impact of the COVID-19 response related lockdown on TB incidence and mortality in India.

India has the highest burden of incident tuberculosis (TB) cases and deaths globally. TB is strongly associated with poverty and this risk is largely mediated by undernutrition in India. COVID-19 response related lockdown has resulted in an economic crisis which may double levels of poverty, has exacerbated food insecurity, and disrupted TB services. These developments may have serious implications for TB progression and transmission in India. The nutritional status of a population is a strong determinant of the TB incidence, and undernutrition in adults alone accounts for 32-44% of TB incidence in India. A systematic review has shown that a 14% increase in TB incidence can occur per one unit decrease in body mass index (BMI), across the BMI range of 18.5-30 kg/m2. We believe that one unit decrease in BMI (corresponding to a 2-3 kg weight loss) may result in the poor in India as a result of the lockdown and its aftermath. This may result in an increase in estimated (uncertainty interval) incident TB by 185 610 (180 230, 190 990) cases. A 59% reduction in TB case detection between end March and May 2020, may result in an estimated (uncertainty interval) additional 87 711 (59 998, 120 630) TB deaths [19.5% increase (14.5, 24.7)] in 2020. Disadvantaged social groups and those living in states with higher levels of poverty, under-nutrition,and migrant workers are at particular risk. We suggest enhanced rations including pulses through the public distribution system and direct cash transfers to the poor pending restoration of livelihoods. TB services should be resumed immediately with enhanced efforts at case detection including active case finding. To prevent deaths among TB detected within the national TB programme, systemic identification, referral and management of severe disease at notification should be considered.

Population Attributable Risk of Tuberculosis Vulnerabilities in Kerala, India.

BACKGROUND: A robust disaggregated understanding of the determinants of tuberculosis (TB) in each local setting is essential for effective health system and policy action to control TB. OBJECTIVES: The objective of the study was to identify population attributable risk (PAR) for TB disease based on the locally available evidences for Kerala, India. METHODS: Systematic review was done for risk factors of TB in the state. The second set of searches was done to understand the prevalence of the identified risk factors in general population in Kerala. With all available studies and reports, an expert group consensus was made to finalize state-specific prevalence of risk factors. Population attributable fractions were calculated for identified risk factors. RESULTS: PAR for TB disease in Kerala obtained was 24% for undernutrition, 15% for diabetes, 15% for tobacco use, and 1% for HIV. CONCLUSION: Kerala state's PAR for TB was comparatively lower for HIV but higher for diabetes mellitus. Similar exercises for summarizing population risk factors need to happen at all states for making plans to effectively combat TB.

Children as sentinels of tuberculosis transmission: disease mapping of programmatic data.

BACKGROUND: Identifying hotspots of tuberculosis transmission can inform spatially targeted active case-finding interventions. While national tuberculosis programs maintain notification registers which represent a potential source of data to investigate transmission patterns, high local tuberculosis incidence may not provide a reliable signal for transmission because the population distribution of covariates affecting susceptibility and disease progression may confound the relationship between tuberculosis incidence and transmission. Child cases of tuberculosis and other endemic infectious disease have been observed to provide a signal of their transmission intensity. We assessed whether local overrepresentation of child cases in tuberculosis notification data corresponds to areas where recent transmission events are concentrated. METHODS: We visualized spatial clustering of children < 5 years old notified to Peru's National Tuberculosis Program from two districts of Lima, Peru, from 2005 to 2007 using a log-Gaussian Cox process to model the intensity of the point-referenced child cases. To identify where clustering of child cases was more extreme than expected by chance alone, we mapped all cases from the notification data onto a grid and used a hierarchical Bayesian spatial model to identify grid cells where the proportion of cases among children < 5 years old is greater than expected. Modeling the proportion of child cases allowed us to use the spatial distribution of adult cases to control for unobserved factors that may explain the spatial variability in the distribution of child cases. We compare where young children are overrepresented in case notification data to areas identified as transmission hotspots using molecular epidemiological methods during a prospective study of tuberculosis transmission conducted from 2009 to 2012 in the same setting. RESULTS: Areas in which childhood tuberculosis cases are overrepresented align with areas of spatial concentration of transmission revealed by molecular epidemiologic methods. CONCLUSIONS: Age-disaggregated notification data can be used to identify hotspots of tuberculosis transmission and suggest local force of infection, providing an easily accessible source of data to target active case-finding intervention.

Investigation of a rapidly spreading tuberculosis outbreak using whole-genome sequencing.

This paper describes the application of whole-genome sequencing (WGS) to investigate an outbreak of Mycobacterium tuberculosis occurring in Aragon, Spain, where strains have been submitted to genotyping since 2004. The responsible outbreak strain appeared in our region first in 2014 and it spread to 14 patients in the following three years. WGS found low variability between the isolates with none of the SNPs differences detected more than once, all of which were attributed to a recent transmission. Although two ambiguous bases linked two cases with those who presented the SNP in the same position, the establishment of a definitive transmission route was not possible. The epidemiological data supported the existence of a super-spreader, probably responsible for the majority of the cases involved since there was a two-year delay in diagnoses among cases. This fact would also help explaining the low variability found. The index case was not identified, possibly because it was not diagnosed in Aragon. In addition WGS characterised the strain as a Linage 4.3.3/LAM family and corroborated the susceptibility to anti-tuberculosis drugs observed by the clinical laboratories. This work shows the need to have epidemiological data to support the genomic data in order to clarify the evolution of tuberculosis outbreaks.

Incidence of tuberculosis in patients receiving anti-TNF therapy for rheumatic diseases: a systematic review.

INTRODUCTION: The TNF inhibitors were the first immunobiologicals used to treat rheumatic diseases, but their use is associated with an increased risk of tuberculosis. The primary objective is to estimate the incidence of tuberculosis in patients with rheumatic diseases exposed to anti-TNF therapy. The secondary objectives are to evaluate the incidence of tuberculosis by region and subgroups of diseases, to review the presentation of tuberculosis in these patients, and to assess the time elapsed between onset of anti-TNF therapy and development of active granulomatous disease. METHODS: A systematic review of the literature was conducted in MEDLINE, the Cochrane Library, and LILACS. The primary endpoint was described as incidence and secondary outcomes, through subgroup analyses and comparisons of means. RESULTS: We included 52 observational studies. Among the exposed patients, 947 cases of tuberculosis were documented (62.2% pulmonary), with a cumulative incidence of 9.62 cases per 1000 patients exposed. TB incidence across different continents was distributed as follows: South America, 11.75 cases/1000 patients exposed; North America, 4.34 cases/1000 patients exposed; Europe, 6.28 cases/1000 patients exposed; and Asia, 13.47 cases/1000 patients exposed. There were no significant differences in TB incidence among the described diseases. The mean time elapsed from start of anti-TNF therapy until the endpoint was 18.05 months. CONCLUSION: The incidence of TB in patients with rheumatic diseases exposed TNF inhibitor considering all countries was 9.62 cases per 1000 patients exposed. TB incidence was higher in South America and Asia compared with North America and Europe. Most cases occurred in the first XX months of use, and the pulmonary form predominated.Key Points• Higher incidence of tuberculosis in patients exposed to anti-TNF compared with the general population.• Higher incidence of TB in countries of South America and Asia compared with North America and Europe.

Impact of Advocacy, Communication, Social Mobilization and Active Case Finding on TB Notification in Jharkhand, India.

Community-level benefits of screening for active tuberculosis (TB) disease remain uncertain. Project Axshya (meaning free of TB) conducted advocacy, communication, social mobilization, and active case finding among vulnerable/marginalized populations of India. Among 15 districts of Jharkhand state, the project was initiated in 36 subdistrict level administrative units - tuberculosis units (TUs) in a staggered manner between April 2013 and September 2014, and continued till the end of 2015. Seven TUs did not implement the project. We assessed the relative change in the quarterly TB case finding indicators (n = 4) after inclusion of a TU within the project. By fitting four multilevel models (mixed-effects maximum likelihood regression using random intercept), we adjusted for secular (over previous five quarters) and seasonal trends, baseline differences within Axshya and non-Axshya TUs, and population size and clustering within districts and within TUs. After inclusion of a TU within the project, we found a significant increase [95% confidence interval (CI)] in TU-level presumptive TB sputum examination rate, new sputum-positive TB Case Notification Rate (CNR), sputum-positive TB CNR, and all forms TB CNR by 12 (5.5, 18.5), 1.1 (0.5, 1.7), 1.3 (0.6, 2.0), and 1.2 (0.1, 2.2) per 100,000 population per quarter, respectively. Overall, the project resulted in an increase (95% CI) in sputum examination and detection of new sputum-positive TB, sputum-positive TB and all forms of TB patients by 22,410 (10,203, 34,077), 2066 (923, 3210), 2380 (1162, 3616), and 2122 (203, 4059), respectively. This provides evidence for implementing project Axshya over and above the existing passive case finding.

Characterization of clinical isolates of Mycobacterium tuberculosis from indigenous peoples of Colombia / Caracterización de aislamientos clínicos de Mycobacterium tuberculosis de pueblos indígenas de Colombia

ABSTRACT Introduction: Tuberculosis continues to be a public health priority. Indigenous peoples are vulnerable groups with cultural determinants that increase the risk of the disease. Objective: To determine molecular epidemiology and phenotypical features and of Mycobacterium tuberculosis isolates from indigenous people in Colombia during the period from 2009 to 2014. Materials and methods: We conducted an analytical observational study; we analyzed 234 isolates to determine their patterns of sensitivity to antituberculosis drugs and their molecular structures by spoligotyping. Results: The isolates came from 41 indigenous groups, predominantly the Wayúu (13.10%) and Emberá Chamí (11.35%). We found 102 spoligotypes distributed among seven genetic families (37.2% LAM, 15.8% Haarlem, 8.1% T, 3.4% U, 2.6% S, 2.1% X, and 0.9%, Beijing). The association analysis showed that the non-clustered isolates were related to prior treatment, relapse, orphan spoligotypes, and the Beijing family. The H family presented an association with the Arhuaco and Camëntŝá indigenous groups, the U family was associated with the Wounaan group, and the T family was associated with the Motilón Barí group. Conclusions: This is the first national study on M. tuberculosis characterization in indigenous groups. The study evidenced that diagnosis in indigenous people is late. We described 53% of orphan patterns that could be typical of the Colombian indigenous population. The high percentage of grouping by spoligotyping (62%) could indicate cases of active transmission, a situation that should be corroborated using a second genotyping marker. A new Beijing spoligotype (Beijing-like SIT 406) was identified in Colombia.

RESUMEN Introducción. La tuberculosis es prioridad de salud pública. Los pueblos indígenas son vulnerables debido a los factores culturales determinantes que aumentan el riesgo de tuberculosis. Objetivo. Determinar la epidemiologia molecular y las características fenotípicas de los aislamientos de Mycobacterium tuberculosis de pueblos indígenas de Colombia entre 2009 y 2014. Materiales y métodos. Se hizo un estudio observacional analítico; se analizaron 234 aislamientos para determinar la sensibilidad a los fármacos antituberculosos y la estructura molecular usando spoligotyping. La información epidemiológica se recolectó utilizando el formato único de vigilancia de micobacterias. Resultados. Los aislamientos provenían de 41 grupos indígenas, principalmente los wayúu (13,10 %) y emberá chamí (11,35 %). Se encontraron 102 genotipos distribuidos en siete familias genéticas (37,2 %, LAM; 15,8 %, Haarlem; 8,1 %, T; 3,4 %, U; 2,6 %, S; 2,1 %, X, y 0,9%, Beijing). El análisis de asociación mostró que los aislamientos no agrupados se asociaron con el tratamiento previo, las recaídas, los genotipos huérfanos y la familia Beijing. La familia H presentó una asociación con los grupos indígenas arhuaco y camëntŝá, la familia U se asoció con el grupo wounaan y la familia T con el grupo motilón barí. Conclusiones. Este es el primer estudio nacional de caracterización de M. tuberculosis en grupos indígenas. Se evidenció que el diagnóstico en indígenas es tardío, y que 53 % de los patrones huérfanos podrían ser típicos de la población indígena colombiana. El alto porcentaje de agrupamiento por spoligotyping (62%) podría indicar casos de transmisión activa, una situación que debe ser corroborada usando un segundo marcador de genotipificación. Se identificó un nuevo genotipo (Beijing-like SIT 406) en Colombia.

Bone and articular impairment in tuberculosis. An important extrapulmonary involvement: a review

This is a literature review on the pathogenesis and epidemiology of bone tuberculosis (BTB). Full-text papers from 2001 to 2017 were included. After inclusion criteria were met, 23 papers were selected for analysis. Results show that in most cases of BTB, the spine is the main site involved, regardless of the geographical regions analyzed; hip and knee involvement are also frequent. These three sites are the most prevalent, totaling approximately 70 - 80% of infections. The major forms of involvement are tuberculous spondylitis, tuberculous osteomyelitis, primarily in areas of long-bone growth, as well as cases of chronic disease leading to tuberculous arthritis, mainly in endemic areas. The results also indicated that bone involvement is still prevalent, being the fifth cause of extrapulmonary disease involvement in Brazil. This review highlights the role of tuberculosis in public health, especially in economically active groups where BTB is most prevalent

Spatial Cluster Analysis Of New And Relapsed Cases Of Pulmonary Tuberculosis By District: Pakistan 2015.

Tuberculosis (TB) is a major public health problem in Pakistan. There are no studies in Pakistan on TB disease mapping and spatial analysis at the country level. This study was conducted to map and identify clusters of TB incidence rates at the district level for all provinces of Pakistan, including Islamabad for all new and relapsed cases of pulmonary TB, for the year 2015. The district level TB rate for new and relapsed cases ranged from 4.7 to 422.6 per 100,000. Global Moran's I was 0.25238, with a pseudo pvalue of 0.001, indicating clustering in the data. Local Moran's I, i.e., Local indicators of Spatial Association identified 11 districts as high-high clusters, and 20 districts as low-low clusters. Better understanding of these hot and cold spot districts would be helped by the availability and analysis of TB data at the more granular level of Union Councils in the country.

Trends in tuberculosis mortality in Brazil (1990-2015): joinpoint analysis / Tendência da mortalidade por tuberculose no Brasil (1990-2015): análise por pontos de inflexão

ABSTRACT The objective of this study was to analyze trends in the tuberculosis mortality rate in Brazil (1990-2015) in an ecological time-series analysis. The indicators were obtained from the Brazilian National Ministry of Health. A joinpoint regression model was applied for the temporal analysis, with a level of significance of 5%. During the period in question, there was a trend toward a reduction in mortality in the country as a whole (p < 0.001) and in each of its five regions. The states with the highest tuberculosis mortality rates were Rio de Janeiro (7.0/100,000 population) and Pernambuco (5.0/100,000 population). Eleven states and the Federal District of Brasília showed downward trends. Only the state of Alagoas showed a significant increase (p < 0.001). The temporal behavior observed indicates that tuberculosis continues to be a major public health problem in Brazil.

RESUMO Objetivou-se analisar a tendência da taxa de mortalidade por tuberculose no Brasil (1990-2015) em um estudo ecológico de séries temporais. Os indicadores foram obtidos do Ministério da Saúde. Aplicou-se o modelo por pontos de inflexão para a análise temporal. Houve uma tendência significativa de redução da mortalidade no Brasil (p < 0,001) e em suas cinco regiões no período estudado. Os estados com as maiores taxas foram Rio de Janeiro (7,0/100.000 habitantes) e Pernambuco (5,0/100.000 habitantes). Onze estados e o Distrito Federal apresentaram tendência de redução da taxa. Somente Alagoas mostrou um crescimento significativo (p < 0,001). O comportamento temporal verificado indica que a tuberculose ainda figura como um importante problema de saúde pública no país.

Risk factors of multidrug-resistant tuberculosis: A global systematic review and meta-analysis.

OBJECTIVES: Since the risk of multidrug-resistant tuberculosis (MDR-TB) may depend on the setting, we aimed to determine the associations of risk factors of MDR-TB across different regions. METHODS: A systematic review and meta-analysis was performed with Pubmed and Embase databases. Information was retrieved on 37 pre-defined risk factors of MDR-TB. We estimated overall Mantel-Haenszel odds ratio as a measure of the association. RESULTS: Factors of previous TB disease and treatment are the most important risk factors associated with MDR-TB. There was also a trend towards increased risk of MDR-TB for patients 40 years and older, unemployed, lacking health insurance, smear positive, with non-completion and failure of TB treatment, showing adverse drug reaction, non-adherent, HIV positive, with COPD and with M. Tuberculosis Beijing infection. Effect modification by geographical area was identified for several risk factors such as male gender, married patients, urban domicile, homelessness and history of imprisonment. CONCLUSIONS: Assessment of risk factors of MDR-TB should be conducted regionally to develop the most effective strategy for MDR-TB control. Across all regions, factors associated with previous TB disease and treatment are essential risk factors, indicating the appropriateness of diagnosis, treatment and monitoring are an important requirements.