Strengthening Multidrug-Resistant Tuberculosis Epidemiological Surveillance in Rio de Janeiro: a multidimensional analysis.

This study aimed to reinforce the importance of the epidemiological surveillance of multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State (RJ). Here, we reviewed seven articles we published between 2018 and 2022. This study had two phases. The quantitative phase where frequency was used to describe patient characteristics and regressions were used to evaluate the relationship between treatment outcomes and covariates. The qualitative phase where content analysis of the narratives was performed. Secondary (electronic systems) and primary (semi-structured interviews) data were used. We analyzed 2,269 MDR-TB, 58.1% MDR-TB, and 18.6% extensively drug-resistant TB (XDR-TB) cases, of which 44.3% exhibited unfavorable outcomes. Among the 140 patients with XDR-TB, 29.3% had not undergone prior treatment for MDR-TB. The primary resistance rate in MDR-TB cases was 14.7%, revealing significant demographic and clinical disparities, particularly among women, Caucasians, and those with higher education levels. The number of cases increased from 7.69% in 2000 to 38.42% in 2018, showing an increasing trend (AAPC = 9.4; 95% CI 1.4-18.0, p < 0.001), with 25.4% underreporting. A qualitative study confirmed a high proportion of primary resistance (64.5%) and delayed diagnosis of MDR-TB. In RJ, the diagnostic and therapeutic cascade of MDR-TB must be improved using molecular tests to achieve an early diagnosis of resistance and immediate initiation of appropriate treatment, promote social protection for MDR/XDR-TB patients and their families, enhance TB contact tracing, establish and monitor hospital surveillance centers integrated with Primary Care, and unify various information systems through interoperability for better integration.

Pre-extensively drug-resistant and extensively drug-resistant tuberculosis in Latin America and the Caribbean: A systematic review and meta-analysis.

BACKGROUND: The growing threat from pre-extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) poses a major public health concern in Latin America and the Caribbean (LAC). Therefore, this study aimed to summarize the available evidence on the prevalence of pre-XDR-TB and XDR-TB among patients with multidrug-resistant tuberculosis in LAC. METHODS: A systematic review was conducted in the following databases on June 3, 2023: PubMed, Scopus, Ovid Medline, Web of Science, Scielo and LILACS. We estimated pooled proportions using a random effects model (Dersimonian and Laird). The 95% confidence intervals (95% CI) were calculated using the binomial exact method (Clopper-Pearson Method). Subgroup (by time period and country) and sensitivity analyses were performed. RESULTS: Twenty-nine studies were eligible for qualitative synthesis and 27 for meta-analysis (n = 15,565). The pooled prevalence of XDR-TB in the study participants was 5% (95% CI: 3%-6%), while that of pre-XDR-TB was 10% (95% CI 7%-14%). Cuba (6%, 95% CI 0%-17%) and Peru (6%, 95% CI 5%-7%) had the highest pooled prevalence of XDR-TB. Regarding pre-XDR-TB, Brazil (16%, 95% CI 11%-22%) and Peru (13%, 95% CI: 9%-16%) showed the highest prevalence. CONCLUSIONS: The pooled prevalence of pre-XDR-TB and XDR-TB in LAC was 10% and 5%, respectively. Governments should strengthen drug-resistance surveillance and TB programs.

Laboratory-based study of drug resistance and genotypic profile of multidrug-resistant tuberculosis isolates in Salvador, Bahia, Brazil.

BACKGROUND: Surveillance of multidrug resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB) is essential to guide disease dissemination control measures. Brazil contributes to a significant fraction of tuberculosis (TB) cases worldwide, but only few reports addressed MDR/XDR-TB in the country. METHODS: This cross-sectional, laboratory-based study describes the phenotypic resistance profiles of isolates obtained between January 2008 and December 2011 in Bahia, Brazil, and sociodemographic, epidemiological, and clinical characteristics (obtained from mandatory national registries) of the corresponding 204 MDR/XDR-TB patients. We analyzed the mycobacterial spoligotyping and variable number of tandem repeats of mycobacterial interspersed repetitive units in 12-loci profiles obtained from Salvador. RESULTS: MDR/XDR-TB patients were predominantly male, had a median age of 43 years, belonged to black ethnicity, and failed treatment before MDR-TB diagnosis. Nearly one-third of the isolates had phenotypic resistance (evaluated by mycobacteria growth indicator tube assay) to second-line anti-TB drugs (64/204, 31%), of which 22% cases (14/64) were diagnosed as XDR-TB. Death was a frequent outcome among these individuals and was associated with resistance to second-line anti-TB drugs. Most isolates successfully genotyped belonged to the Latin-American Mediterranean (LAM) Family, with an unprecedented high proportion of LAM10-Cameroon subfamily bacilli. More than half of these isolates were assigned to a unique cluster by the genotyping methods performed. Large clusters of identical genotypes were also observed among LAM SIT42 and SIT376 strains. CONCLUSIONS: We highlight the need for strengthening local and national efforts to perform early detection of TB drug resistance and to prevent treatment discontinuation to limit the emergence of drug-resistant strains.

K-mer applied in Mycobacterium tuberculosis genome cluster analysis.

According to studies carried out, approximately 10 million people developed tuberculosis in 2018. Of this total, 1.5 million people died from the disease. To study the behavior of the genome sequences of Mycobacterium tuberculosis (MTB), the bacterium responsible for the development of tuberculosis (TB), an analysis was performed using k-mers (DNA word frequency). The k values ranged from 1 to 10, because the analysis was performed on the full length of the sequences, where each sequence is composed of approximately 4 million base pairs, k values above 10, the analysis is interrupted, as consequence of the program's capacity. The aim of this work was to verify the formation of the phylogenetic tree in each k-mer analyzed. The results showed the formation of distinct groups in some k-mers analyzed, taking into account the threshold line. However, in all groups, the multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains remained together and separated from the other strains.

Clinical and epidemiological features of tuberculosis isolated from critically ill patients / Tuberculosis en la unidad de cuidados intensivos: características clínicas y epidemiológicas

Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p;<;0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p;<;0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis.

La tuberculosis (TB) aún representa un problema mayor de salud pública. En Uruguay, contrariamente a la tendencia mundial, se ha observado un incremento en el número de casos desde 2006. Aunque la incidencia de casos de multidrogorresistencia (MDR) es baja y no se han reportados casos de resistencia a fármacos de primera y segunda línea de tratamiento (XDR), se ha observado un incremento en el número de casos con TB grave, que requieren internación en unidad de terapia intensiva (CTI). Como primer objetivo del presente trabajo, se analizó la estructura genética de cepas de Mycobacterium tuberculosis aisladas de pacientes internados en CTI. Comparamos estos resultados con los obtenidos con cepas circulantes en la comunidad. Observamos un incremento estadísticamente significativo del genotipo Haarlem en los pacientes internados en CTI (53,3 vs. 34,7%; p;<;0,05). Además, investigamos la asociación del desenlace clínico con el genotipo, y encontramos una mayor incidencia de disfunción hepática en los pacientes infectados con la cepa Haarlem (p;<;0,05). La cohorte presentada en este trabajo corresponde a una de las series con mayor número de pacientes con tuberculosis que requirieron internación en CTI.

Clinical and epidemiological features of tuberculosis isolated from critically ill patients.

Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p<0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p<0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis.

Putative extensive and pre-extensive drug resistant-tuberculosis associated with unusual genotypes on the Thailand-Myanmar border.

Extensive drug-resistant tuberculosis (XDR-TB) is highly life threatening and its diagnosis is usually difficult and time-consuming. Here we present the first two cases of XDR and pre-XDR-TB diagnosed in 2018 on the Thailand-Myanmar border, more specifically in Tak province. Rapid detection of XDR-TB was performed by loop-mediated isothermal amplification (LAMP), Xpert MTB/RIF, and line probe assays. Mutation analyses targeting rpoB, katG, inhA, gyrA and rrs genes showed an association with drug-resistant phenotypes, except for rifampicin resistance. Spoligotyping revealed uncommon Beijing and T2 genotypes and the analysis of M. tuberculosis interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) showed the presence of more polymorphisms. This report highlights the importance of the early detection of drug-resistant tuberculosis by molecular tests followed by phenotyping assays. Based on the up-to-date definition of XDR- and pre-XDR-TB, the susceptibility testing for bedaquiline and linezolid is required and the two reported cases may correspond to putative XDR-TB.

Whole genome analysis of extensively drug resistant Mycobacterium tuberculosis strains in Peru.

Peru has the highest burden of multidrug-resistant tuberculosis in the Americas region. Since 1999, the annual number of extensively drug-resistant tuberculosis (XDR-TB) Peruvian cases has been increasing, becoming a public health challenge. The objective of this study was to perform genomic characterization of Mycobacterium tuberculosis strains obtained from Peruvian patients with XDR-TB diagnosed from 2011 to 2015 in Peru. Whole genome sequencing (WGS) was performed on 68 XDR-TB strains from different regions of Peru. 58 (85.3%) strains came from the most populated districts of Lima and Callao. Concerning the lineages, 62 (91.2%) strains belonged to the Euro-American Lineage, while the remaining 6 (8.8%) strains belonged to the East-Asian Lineage. Most strains (90%) had high-confidence resistance mutations according to pre-established WHO-confident grading system. Discordant results between microbiological and molecular methodologies were caused by mutations outside the hotspot regions analysed by commercial molecular assays (rpoB I491F and inhA S94A). Cluster analysis using a cut-off ≤ 10 SNPs revealed that only 23 (34%) strains evidenced recent transmission links. This study highlights the relevance and utility of WGS as a high-resolution approach to predict drug resistance, analyse transmission of strains between groups, and determine evolutionary patterns of circulating XDR-TB strains in the country.

Metabolic profiles of multidrug resistant and extensively drug resistant Mycobacterium tuberculosis unveiled by metabolomics.

Although treatable with antibiotics, tuberculosis is a leading cause of death. Mycobacterium tuberculosis antibiotic resistance is becoming increasingly common and disease control is challenging. Conventional drug susceptibility testing takes weeks to produce results, and treatment is often initiated empirically. Therefore, new methods to determine drug susceptibility profiles are urgent. Here, we used mass-spectrometry-based metabolomics to characterize the metabolic landscape of drug-susceptible (DS), multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis. Direct infusion mass spectrometry data showed that DS, MDR, and XDR strains have distinct metabolic profiles, which can be used to predict drug susceptibility and resistance. This was later confirmed by Ultra-High-Performance Liquid Chromatography and High-Resolution Mass Spectrometry, where we found that levels of ions presumptively identified as isoleucine, proline, hercynine, betaine, and pantothenic acid varied significantly between strains with different drug susceptibility profiles. We then confirmed the identification of proline and isoleucine and determined their absolute concentrations in bacterial extracts, and found significantly higher levels of these amino acids in DS strains, as compared to drug-resistant strains (combined MDR and XDR strains). Our results advance the current understanding of the effect of drug resistance on bacterial metabolism and open avenues for the detection of drug resistance biomarkers.

Predictive factors for unfavourable treatment in MDR-TB and XDR-TB patients in Rio de Janeiro State, Brazil, 2000-2016.

SETTING: The State of Rio de Janeiro stands out as having the second highest incidence and the highest mortality rate due to TB in Brazil. This study aims at identifying the factors associated with the unfavourable treatment of MDR/XDR-TB patients in that State. METHOD: Data on 2269 MDR-TB cases reported in 2000-2016 in Rio de Janeiro State were collected from the Tuberculosis Surveillance System. Bivariate and multivariate logistic regressions were run to estimate the factors associated with unfavourable outcomes (failure, default, and death) and, specifically, default and death. RESULTS: The proportion of unfavourable outcomes was 41.9% among MDR-TB and 81.5% among XDR-TB. Having less than 8 years of schooling, and being an Afro-Brazilian, under 40 years old and drug user were associated with unfavourable outcome and default. Bilateral disease, HIV positive, and comorbidities were associated with death. XDR-TB cases had a 4.7-fold higher odds of an unfavourable outcome, with 29.3% of such cases being not treated for multidrug resistance in the past. CONCLUSION: About 30% of XDR-TB cases may have occurred by primary transmission. The high rates of failure and death in this category reflect the limitation of treatment options. This highlights the urgency to incorporate new drugs in the treatment.

Barriers to access and adherence to tuberculosis services, as perceived by patients: A qualitative study in Mozambique

Tuberculosis (TB) continues to be a leading cause of death in Sub-Saharan Africa, including Mozambique. While diagnostic methods and total notifications are improving, significant gaps remain between total numbers of TB cases annually, and the number that are notified. The purpose of this study was to elicit Mozambican patients with drug sensitive TB (DS-TB), TB/HIV and Multi drug resistant tuberculosis (MDR-TB) understanding and assessment of the quality of care for DS-TB, HIV/TB and MDR-TB services in Mozambique, along with challenges to effectively preventing, diagnosing and treating TB. Materials and methods: Qualitative data was collected via separate focus group discussions consisting of patients with DS-TB, TB/HIV and MDR-TB at four health centers in Sofala and Manica Province, Mozambique, to describe knowledge on TB, HIV and MDR-TB, and identify barriers to access and adherence to services and their recommendations for improvement. A total of 51 patients participated in 11 discussions. Content analysis was done and main themes were identified. Results: Focus groups shared a number of prominent themes. Respondents identified numerous challenges including delays in diagnosis, stigma related with diagnosis and treatment, long waits at health facilities, the absence of nutritional support for patients with TB, the absence of a comprehensive psychosocial support program, and the lack of overall knowledge about TB or multi drug resistant TB in the community. Discussion: TB patients in central Mozambique identified many challenges to effectively preventing, diagnosing and treating tuberculosis. Awareness strengthening in the community, continuous quality monitoring and in-service training is needed to increase screening, diagnosis and treatment for TB, HIV/TB and MDR-TB

A significant therapeutic effect of silymarin administered alone, or in combination with chemotherapy, in experimental pulmonary tuberculosis caused by drug-sensitive or drug-resistant strains: In vitro and in vivo studies.

For many years, tuberculosis (TB) has been a major public health problem worldwide. Advances for treatment and eradication have been very limited. Silymarin (Sm) is a natural product with antioxidant and hepatoprotective activities that has been proposed as a complementary medicine to reduce the liver injury produced by the conventional anti-TB chemotherapy. Sm also has immunoregulatory and microbicide properties. In this study, we determined the effect of Sm on the growth control of mycobacteria. In vitro studies showed that Sm and Silibinin (the principal active compound of Sm) have microbicidal activity against drug-sensitive and multidrug-resistant (MDR) mycobacteria, induce the production of protective cytokines from infected macrophages, and improve the growth control of mycobacteria (p ≤ 0.0001). Studies in vivo using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive or MDR mycobacteria have shown that Sm induces significant expression of Th-1 cytokines such as IFN-γ and IL-12 as well as TNFα, which produce significant therapeutic activity when administered alone and apparently have a synergistic effect with chemotherapy. These results suggest that Sm has a bactericidal effect and can contribute to the control and establishment of a TH1 protective immune response against mycobacterial infection. Thus, it seems that this flavonoid has a promising potential as adjuvant therapy in the treatment of TB.

4H-1,3-Benzothiazin-4-one a Promising Class Against MDR/XDR-TB.

Nowadays, tuberculosis (TB) is an important global public health problem, being responsible for millions of TB-related deaths worldwide. Due to the increased number of cases and resistance of Mycobacterium tuberculosis to all drugs used for the treatment of this disease, we desperately need new drugs and strategies that could reduce treatment time with fewer side effects, reduced cost and highly active drugs against resistant strains and latent disease. Considering that, 4H-1,3-benzothiazin-4-one is a promising class of antimycobacterial agents in special against TB-resistant strains being the aim of this review the discussion of different aspects of this chemical class such as synthesis, mechanism of action, medicinal chemistry and combination with other drugs.

Tuberculosis congénita pre-extensivamente resistente a drogas: reporte de caso / Pre-extensively drug-resistant congenital tuberculosis: case report

RESUMEN La tuberculosis en el lactante es un cuadro de difícil diagnóstico por las pruebas diagnósticas que muchas veces resultan negativas y por la dificultad de identificar la fuente de transmisión. Se presenta el caso de un lactante varón de un mes de vida que presenta irritabilidad, taquipnea, fiebre, pobre ganancia de peso desde el nacimiento y hepatomegalia, además, tiene el antecedente materno de tuberculosis pre-extensivamente resistente a drogas y reacción granulomatosa tuberculoide con tinción auramina positiva para bacilos ácido-alcohol resistentes en la histopatología de placenta. Ante la sospecha de tuberculosis congénita, es referido al Instituto Nacional de Salud del Niño para estudio diagnóstico y tratamiento; el paciente presenta una evolución clínica favorable y sin reacciones adversas al tratamiento. El diagnóstico de tuberculosis congénita debe considerarse en lactantes con signos clínicos sugestivos de la enfermedad y mantener la sospecha ante la presencia del antecedente materno de infección por Mycobacterium tuberculosis.

ABSTRACT Tuberculosis in infants is a clinical case difficult to diagnose by regular testing which often yield negative results; additionally, the source of transmission is difficult to identify. This work presents the case of a one-month old nursing boy presenting irritability, tachypnea, fever, poor gain weight from birth, and hepatomegaly. Additionally, he had the maternal history of pre-extensively drug- resistant tuberculosis and tuberculoid granulomatosis reaction with positive auramine tincture for acid-alcohol resistant bacilli at histopathology of the placenta. With a suspected congenital tuberculosis, he was referred to the National Children's Health Institute for diagnosis and treatment. The patient showed a favorable clinical evolution and no adverse reactions to treatment. The diagnosis of congenital tuberculosis must be considered in infants with suggestive clinical signs of the disease and such suspicion must be maintained with the presence of a maternal history of Mycobacterium tuberculosis infection.

Programmatic management of patients with pre-extensively drug-resistant tuberculosis in Peru, 2011-2014.

BACKGROUND: In Peru, a treatment approach for extensively drug-resistant tuberculosis (XDR-TB) incorporating World Health Organization Group 5 drugs and patient-centred care has achieved 65% success. To extend this approach to pre-XDR-TB patients, we evaluated this population separately. OBJECTIVE: To assess programmatic management of pre-XDR-TB. METHOD: Retrospective study using the official national registry from 2011 to 2014. Cases were separately evaluated according to resistance to fluoroquinolones (FQs) (pre-XDR-F) or to second-line injectables (SLIs) (pre-XDR-I). RESULTS: Of 610 pre-XDR-TB patients, 120 (20%) had pre-XDR-F and 490 (80%) had pre-XDR-I. Pre-XDR-F cases were older (34 years vs. 28 years, P < 0.001) and a higher proportion had previously received two or more regimens (70% vs. 38%, P < 0.001). Among the 452 patients who started treatment in 2011-2013, treatment success was 43.3%, 26.5% were lost to follow-up, 12.1% died and 13.7% failed treatment. Success was higher in pre-XDR-I (48.5%) than pre-XDR-F (21.4%) patients. History of previous treatment (OR 2.23, 95%CI 1.52-3.38) and pre-XDR-F (OR 2.39, CI 1.18-4.83) were associated with unsuccessful outcomes. CONCLUSION: Programmatic management of pre-XDR-TB has not been successful, particularly in pre-XDR-F patients, with lower rates of success than those achieved in the same setting for XDR-TB. The strategy used for XDR-TB should be extended to pre-XDR-TB patients in Peru.

New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis.

Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the "white plague", and promising results are being reported.

New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis / Novos fármacos e fármacos repropostos para o tratamento da tuberculose multirresistente e extensivamente resistente

ABSTRACT Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the "white plague", and promising results are being reported.

RESUMO A tuberculose multirresistente (TB-MDR, do inglês multidrug-resistant) e a extensivamente resistente (TB-XDR, do inglês extensively drug-resistant) continuam representando um desafio para os clínicos e as autoridades de saúde pública. Infelizmente, embora haja relatos encorajadores de taxas de sucesso maiores, a taxa global de desfechos favoráveis do tratamento da TB-MDR/XDR é de apenas 54%, ou muito menor quando o espectro de resistência aos fármacos vai além do da TB-XDR. O tratamento da TB-MDR/XDR continua sendo uma tarefa difícil, em razão da alta incidência de eventos adversos, do longo tempo de tratamento, do alto culto dos esquemas utilizados e da drenagem dos recursos de saúde. Diversos ensaios e estudos foram realizados recentemente (alguns já publicados e outros em andamento), todos visando a melhorar os desfechos do tratamento da TB-MDR/XDR por meio da alteração da abordagem geral, redução do tempo de tratamento e desenvolvimento de um esquema universal. O objetivo desta revisão foi resumir o que se conseguiu até o momento, no que se refere a novos fármacos e fármacos repropostos, dando foco especial para delamanid, bedaquilina, pretomanida, clofazimina, carbapenêmicos e linezolida. Após mais de 40 anos de negligência, recentemente foi dada mais atenção á necessidade de novos fármacos para se combater a "praga branca", e resultados promissores estão sendo relatados.

Prevalence, associated factors, outcomes and transmission of extensively drug-resistant tuberculosis among multidrug-resistant tuberculosis patients in São Paulo, Brazil: a cross-sectional study.

OBJECTIVES: To describe the prevalence, associated factors, treatment outcomes and transmission of extensively drug-resistant (XDR) tuberculosis (TB) in the state of São Paulo, Brazil, for 2011 to 2013. METHODS: Drug susceptibility testing to first- and second-line drugs was performed by BACTEC MGIT 960 and molecular typing, by IS6110 restriction fragment length polymorphism. Clinical, epidemiologic and demographic data were obtained from surveillance information systems for TB. Patients were divided into three groups: multidrug resistant (MDR) TB (resistance to at least isoniazid and rifampicin), pre-XDR-TB (MDR-TB resistant to a fluoroquinolone or to at least one of the second-line injectable drugs) and XDR-TB (MDR-TB resistant to a fluoroquinolone and to at least one of the second-line injectables). RESULTS: Among the 313 MDR-TB patients identified, the prevalence of XDR-TB and pre-XDR-TB was 10.2% (n = 32) and 19.2% (n = 60), respectively. Compared to MDR-TB patients, XDR-TB patients were more likely to be female (odds ratio (OR) = 2.74, 95% confidence interval (CI), 1.29-5.83), have a history of TB (OR = 5.16; 95% CI, 1.52-17.51) and present higher death rates (OR= 3.74; 95% CI 1.70-8.25). XDR-TB transmission was observed in households, between neighbours and between a patient and a healthcare worker in a hospital. CONCLUSIONS: The prevalence of XDR-TB in the state of São Paulo is close to that estimated globally. Most of the XDR-TB patients were treated previously for TB and presented the lowest successful outcome rates. Because transmission of XDR-TB occurred, it is important that timely diagnosis of drug resistance is performed.

[Pre-extensively drug-resistant congenital tuberculosis: case report]. / Tuberculosis congénita pre-extensivamente resistente a drogas: reporte de caso.

Tuberculosis in infants is a clinical case difficult to diagnose by regular testing which often yield negative results; additionally, the source of transmission is difficult to identify. This work presents the case of a one-month old nursing boy presenting irritability, tachypnea, fever, poor gain weight from birth, and hepatomegaly. Additionally, he had the maternal history of pre-extensively drug- resistant tuberculosis and tuberculoid granulomatosis reaction with positive auramine tincture for acid-alcohol resistant bacilli at histopathology of the placenta. With a suspected congenital tuberculosis, he was referred to the National Children's Health Institute for diagnosis and treatment. The patient showed a favorable clinical evolution and no adverse reactions to treatment. The diagnosis of congenital tuberculosis must be considered in infants with suggestive clinical signs of the disease and such suspicion must be maintained with the presence of a maternal history of Mycobacterium tuberculosis infection.

La tuberculosis en el lactante es un cuadro de difícil diagnóstico por las pruebas diagnósticas que muchas veces resultan negativas y por la dificultad de identificar la fuente de transmisión. Se presenta el caso de un lactante varón de un mes de vida que presenta irritabilidad, taquipnea, fiebre, pobre ganancia de peso desde el nacimiento y hepatomegalia, además, tiene el antecedente materno de tuberculosis pre-extensivamente resistente a drogas y reacción granulomatosa tuberculoide con tinción auramina positiva para bacilos ácido-alcohol resistentes en la histopatología de placenta. Ante la sospecha de tuberculosis congénita, es referido al Instituto Nacional de Salud del Niño para estudio diagnóstico y tratamiento; el paciente presenta una evolución clínica favorable y sin reacciones adversas al tratamiento. El diagnóstico de tuberculosis congénita debe considerarse en lactantes con signos clínicos sugestivos de la enfermedad y mantener la sospecha ante la presencia del antecedente materno de infección por Mycobacterium tuberculosis.

An updated systematic review and meta-analysis for treatment of multidrug-resistant tuberculosis.

This systematic review aimed to update the current evidence for multidrug-resistant tuberculosis (MDR-TB) treatment.We searched for studies that reported treatment information and clinical characteristics for at least 25 patients with microbiologically confirmed pulmonary MDR-TB and either end of treatment outcomes, 6-month culture conversion or severe adverse events (SAEs). We assessed the association of these outcomes with patients' characteristics or treatment parameters. We identified 74 studies, including 17 494 participants.The pooled treatment success was 26% in extensively drug-resistant TB (XDR-TB) patients and 60% in MDR-TB patients. Treatment parameters such as number or duration and individual drugs were not associated with improved 6-month sputum culture conversion or end of treatment outcomes. However, MDR-TB patients that received individualised regimens had higher success than patients who received standardised regimens (64% versus 52%; p<0.0.01). When reports from 20 cohorts were pooled, proportions of SAE ranged from 0.5% attributed to ethambutol to 12.2% attributed to para-aminosalicylic acid. The lack of significant associations of treatment outcomes with specific drugs or regimens may reflect the limitations of pooling the data rather than a true lack of differences in efficacy of regimens or individual drugs.This analysis highlights the need for stronger evidence for treatment of MDR-TB from better-designed and reported studies.