The impact of inclusion, dose and duration of pyrazinamide (PZA) on efficacy and safety outcomes in tuberculosis: systematic review and meta-analysis protocol.

BACKGROUND: Pyrazinamide (PZA) is a key component of current and future regimens for tuberculosis (TB). Inclusion of PZA at higher doses and for longer durations may improve efficacy outcomes but must be balanced against the potential for worse safety outcomes. METHODS: We will search for randomised and quasi-randomised clinical trials in adult participants with and without the inclusion of PZA in TB treatment regimens in the Cochrane infectious diseases group's trials register, Cochrane central register of controlled trials (CENTRAL), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) international clinical trials registry platform. One author will screen abstracts and remove ineligible studies (10% of which will be double-screened by a second author). Two authors will review full texts for inclusion. Safety and efficacy data will be extracted to pre-piloted forms by one author (10% of which will be double-extracted by a second author). The Cochrane risk of bias tool will be used to assess study quality. The study has three objectives: the association of (1) inclusion, (2) dose and (3) duration of PZA with efficacy and safety outcomes. Risk ratios as relative measures of effect for direct comparisons within trials (all objectives) and proportions as absolute measures of effect for indirect comparisons across trials (for objectives 2 and 3) will be calculated. If there is insufficient data for direct comparisons within trials for objective 1, indirect comparisons between trials will be performed. Measures of effect will be pooled, with corresponding 95% confidence intervals and p values. Meta-analysis will be performed using the generalised inverse variance method for fixed effects models (FEM) or the DerSimonian-Laird method for random effects models (REM). For indirect comparisons, meta-regression for absolute measures against dose and duration data will be performed. Heterogeneity will be quantified through the I2-statistic for direct comparisons and the τ2 statistic for indirect comparisons using meta-regression. DISCUSSION: The current use of PZA for TB is based on over 60 years of clinical trial data, but this has never been synthesised to guide rationale use in future regimens and clinical trials. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019138735.

Specific Interventions for Implementing a Patient-Centered Approach to TB Care in Low-Incidence Cities.

Background: According to the latest Guidelines from the World Health Organization, there is an increasing need for patient-centered tuberculosis disease management given the socio-economic factors influencing the tuberculosis epidemic. In the present study, we aimed to study TB in Barcelona city from an anthropological point of view and to devise a series of specific proposals to implement a patient-centered approach in our setting. Methods: We carried out a qualitative study using an anthropological approach in Barcelona in the period between November 2017 and November 2018 and proposed specific interventions based on our observations. Results: In practice, in our environment (a low-incidence European country where tuberculosis tends to present in patients with multiple social problems), and despite the goodwill of the care teams, there are no established and stable circuits, or specific tools to ensure that this is done routinely. Based on our observations, we have devised a series of specific proposals to implement a patient-centered approach. With these interventions we aim to (a) directly ameliorate TB patients well-being in any diagnostic/healthcare management center and (b) at more general level, to increase TB detection and treatment adherence. Conclusions: The patient-centered TB management recommended by the WHO might be essential for patients' well-being, but there is a lack of circuits or working protocols that ensure its implementation in a regulated manner. In the present manuscript we explain the various concrete measures that we propose in our region and which could be put into practice in other cities or geographic regions with similar epidemiological characteristics.

The missing voices of Indigenous Australians in the social, cultural and historical experiences of tuberculosis: a systematic and integrative review.

INTRODUCTION: Disparities in tuberculosis (TB) rates exist between Indigenous and non-Indigenous populations in many countries, including Australia. The social determinants of health are central to health inequities including disparities in TB rates. There are limitations in the dominant biomedical and epidemiological approaches to representing, understanding and addressing the unequal burden of TB for Indigenous peoples represented in the literature. This paper applies a social determinants of health approach and examines the structural, programmatic and historical causes of inequities for TB in Indigenous Australia. METHODS: Aboriginal Australians' families in northern New South Wales who are affected by TB initiated this investigation. A systematic search of published literature was conducted using PubMed, PsycINFO, Scopus and Informit ATSIhealth databases, the Australian Indigenous Health, InfoNet and Google. Ninety-five records published between 1885 and 2019 were categorised and graphed over time, inductively coded and thematically analysed. RESULTS: Indigenous Australians' voices are scarce in the TB literature and absent in the development of TB policies and programmes. Epidemiological reports are descriptive and technical and avoid analysis of social processes involved in the perpetuation of TB. For Indigenous Australians, TB is more than a biomedical diagnosis and treatment; it is a consequence of European invasion and a contributor to dispossession and the ongoing fight for justice. The introduction and spread of TB has resulted in the stealing of lives, family, community and cultures for Indigenous Australians. Racist policies and practices predominate in the experiences of individuals and families as consequences of, and resulting in, ongoing structural and systematic exclusion. CONCLUSION: Development of TB policies and programmes requires reconfiguration. Space must be given for Indigenous Australians to lead, be partners and to have ownership of decisions about how to eliminate TB. Shared knowledge between Indigenous Australians, policy makers and service managers of the social practices and structures that generate TB disparity for Indigenous Australians is essential.A social determinant of health approach will shift the focus to the social structures that cause TB. Collaboration with Indigenous partners in research is critical, and use of methods that amplify Indigenous peoples' voices and reconfigure power relations in favour of Indigenous Australians in the process is required.

The relationship between HbA1c control levels and antituberculosis treatment effects: a meta-analysis.

BACKGROUND: Multiple studies of tuberculosis (TB) treatment have indicated that patients with diabetes mellitus (DM) may experience poor outcomes. We performed a meta-analysis to summarize evidence for the relationship between HbA1c control levels and anti-TB treatment effects in patients afflicted with both TB and DM. METHODS: Both English and Chinese databases were searched. Chinese databases included CNKI, WanFang, SinoMed, and VIP. PubMed, Ovid MEDLINE, Embase, Cochrane Library, and Web of Science were searched for English articles. We included studies that were restricted to the relationship between HbA1c levels and anti-TB treatment effects (sputum conversion rate [SCR] and TB focus absorption) in diabetic patients receiving treatment for TB. We used RevMan 5.3 software to analyze the data. RESULTS: We included 12 studies, of which five reported SCR at 2 months, seven reported the conversion at 3 months, and seven reported TB focus absorption. According to the five studies which reported 2 months-SCR, patients with diabetes and TB had an odds ratio (OR) of 2.14 (95% CI: 0.84-5.43) for the 2 months-SCR between controlled (HbA1c <7.0) and uncontrolled diabetes (HbA1c ≥7.0). However, additional seven studies reporting 3 months-SCR showed that controlled diabetics had higher SCR than uncontrolled (OR 3.39, 95% CI: 2.12-5.43). Moreover, seven of the 12 studies demonstrated that there were differences in TB focus absorption between controlled and uncontrolled diabetes (OR 2.69, 95% CI: 1.91-3.79). CONCLUSION: HbA1c control levels influence the SCR at 3 months and the TB focus absorption at the end of the anti-TB intensive treatment phase. This study highlights a need for increased attention to HbA1c or glucose control in patients afflicted with both TB and DM.

Impact of multidrug-resistant tuberculosis and its medications on adverse maternal and perinatal outcomes: protocol for a systematic review and meta-analysis.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a common public health problem affecting pregnant women. However, the impact of MDR-TB and its medication on pregnancy and perinatal outcomes has been poorly understood and inconsistently reported. Therefore, using the available literature, we aim to determine whether MDR-TB and its medications during pregnancy impact maternal and perinatal outcomes. METHODS AND ANALYSIS: This systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches will be conducted in PubMed, Scopus and Web of Science on 10 February 2020 for studies that reported adverse maternal and perinatal outcomes due to MDR-TB and/or its medication. The search will be performed without language and time restrictions. Adverse birth outcomes include miscarriage or abortion, stillbirth, preterm birth, low birth weight, small and large for gestational age, and neonatal death. Two independent reviewers will screen search records, extract data and assess the quality of the studies. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the methodological quality of the included studies. In addition to a narrative synthesis, a random-effects meta-analysis will be conducted when sufficient data are available. I2 statistics will be used to assess the heterogeneity between studies. ETHICS AND DISSEMINATION: As it will be a systematic review and meta-analysis based on previously published evidence, there will be no requirement for ethical approval. Findings will be published in a peer-reviewed journal and will be presented at various conferences.

Epidemiological impact of targeted interventions for people with diabetes mellitus on tuberculosis transmission in India: Modelling based predictions.

INTRODUCTION: Diabetes mellitus (DM) is a leading driver of tuberculosis (TB) disease in TB-DM burdened countries. We aimed to assess the impact on TB disease of several intervention strategies targeting people with DM in India. METHODS: A previously validated TB-DM mathematical model was extended to include interventions targeting DM individuals. The model stratified the population by age, DM status, TB infection status and stage, TB disease form, treatment, recovery, and intervention status. RESULTS: By 2050, different TB vaccination strategies (coverage of 50 % and vaccine efficacies ranging between 50 %-60 %) reduced TB incidence and mortality rates by 4.5 %-20.8 % and 4.1 %-22.1 %, respectively, and averted 3.1 %-12.8 % of TB disease cases in the total population. Number of vaccinations needed to avert one TB case (effectiveness) was 14-105. Varying the coverage levels of latent TB treatment (coverage of 50 %-80 % and drug effectiveness of 90 %) reduced TB incidence and mortality rates by 7.1 %-11.3 % and 8.2 %-13.0 %, respectively, averting 4.2 %-6.7 % of TB cases, with effectiveness of 38-40. Different scenarios for dual and concurrent treatment of those with TB and DM, reduced TB incidence and mortality rates by 0.1 %-0.4 % and 1.3 %-4.8 %, respectively, averting 0.1 %-0.2 % of TB cases, with effectiveness of 28-107. Different scenarios for managing and controlling DM (regardless of TB status) reduced TB incidence and mortality rates by 4.5 %-16.5 % and 6.5 %-22.2 %, respectively, averting 2.9 %-10.8 % of TB cases, with effectiveness of 6-24. CONCLUSION: Gains can be attained by targeting DM individuals with interventions to reduce TB burden. Most strategies were effective with <50 intervention doses needed to avert one TB disease case, informing key updates of current treatment guidelines.

Effectiveness of vitamin D supplementation on the outcome of pulmonary tuberculosis treatment in adults: a meta-analysis of randomized controlled trials.

BACKGROUND: Tuberculosis (TB) is one of the most debilitating diseases worldwide. Current studies have shown that vitamin D plays a significant role in host immune defense against Mycobacterium tuberculosis, but clinical trials reported inconsistent results. Therefore, we systematically reviewed the literature to investigate whether vitamin D supplementation could improve the effect of anti-TB therapy. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from their inception to February 8th, 2019 for randomized controlled trials on vitamin D supplementation in patients with pulmonary TB receiving anti-TB therapy. The primary outcomes were time to sputum culture and smear conversion and proportion of participants with negative sputum culture. The secondary outcomes were clinical response to treatment and adverse events. A random-effects model was used to pool studies. Data were analyzed using RevMan 5.3 software. RESULTS: Five studies with a total of 1126 participants were included in our meta-analysis. Vitamin D supplementation did not shorten the time to sputum culture and smear conversion (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.89-1.23, P = 0.60; HR 1.15, 95% CI 0.93-1.41, P = 0.20, respectively) and did not lead to an increase in the proportion of participants with negative sputum culture (relative risk [RR] 1.04, 95% CI 0.97-1.11, P = 0.32). However, it reduced the time to sputum culture conversion in the sub-group of participants with TaqI tt genotype (HR 8.09, 95% CI 1.39-47.09, P = 0.02) and improved the multidrug-resistant (MDR) TB sputum culture conversion rate (RR 2.40, 95% CI 1.11-5.18, P = 0.03). There was no influence on secondary outcomes. CONCLUSIONS: Vitamin D supplementation had no beneficial effect on anti-TB treatment, but it reduced the time to sputum culture conversion in participants with tt genotype of the TaqI vitamin D receptor gene polymorphism and improved the MDR TB sputum culture conversion rate.

Multicenter evaluation of TB-SPRINT 59-Plex Beamedex®: accuracy and cost analysis.

BACKGROUND: Molecular tests can allow the rapid detection of tuberculosis (TB) and multidrug-resistant TB (MDR-TB). TB-SPRINT 59-Plex Beamedex® is a microbead-based assay developed for the simultaneous spoligotyping and detection of MDR-TB. The accuracy and cost evaluation of new assays and technologies are of great importance for their routine use in clinics and in research laboratories. The aim of this study was to evaluate the performance of TB-SPRINT at three laboratory research centers in Brazil and calculate its mean cost (MC) and activity-based costing (ABC). METHODS: TB-SPRINT data were compared with the phenotypic and genotypic profiles obtained using Bactec™ MGIT™ 960 system and Genotype® MTBDRplus, respectively. RESULTS: Compared with MGIT, the accuracies of TB-SPRINT for the detection of rifampicin and isoniazid resistance ranged from 81 to 92% and 91.3 to 93.9%, respectively. Compared with MTBDRplus, the accuracies of TB-SPRINT for rifampicin and isoniazid were 99 and 94.2%, respectively. Moreover, the MC and ABC of TB-SPRINT were USD 127.78 and USD 109.94, respectively. CONCLUSION: TB-SPRINT showed good results for isoniazid and rifampicin resistance detection, but still needs improvement to achieve In Vitro Diagnostics standards.

House-hold contact tuberculosis screening adherence and associated factors among tuberculosis patients attending at health facilities in Gondar town, northwest, Ethiopia.

BACKGROUND: Contacting patients with tuberculosis have a substantial risk of developing the disease. Household contact screening has recently been recommended as a strategy to enhance case detection in high-burden countries. But there is no enough information in Gondar town regarding household contact screening practice among TB patients. METHODS: An institution-based cross-sectional study was conducted from March 1 to 30, 2019 on 404 tuberculosis patients attending at health facilities in Gondar Town. Epi-Info version 7 for data entry and SPSS version 20 for data analysis were used. Descriptive statistics were carried out to illustrate the means, standard deviations, and frequencies. Bivariable and multivariable logistic regression analyses were used to identify significantly associated variables with the dependent variable. RESULTS: From 412 study populations, 404 were completed the study with 98.06% response rate. The overall household contact TB screening adherence was 47.5% (95% CI: 43.1, 52.5). In the multivariable analysis, having certificate and above educational level (AOR = 2.83, 95% CI:1.40,5.67), having sufficient knowledge about TB (AOR = 8.26, 95% CI:4.34,15.71), being satisfied with health care service (AOR = 3.26, 95% CI:1.58,6.76), health education given by health care workers (AOR = 2.60, 95% CI:1.54,4.40),and having HIV/AIDS co-infection (AOR = 3.54, 95% CI:1.70,7.39), were factors associated with household contact TB screening adherence. CONCLUSION: Compared to other previous studies, the current finding was high but it was low as compared with WHO and Ethiopian Ministry of Health recommendations (all persons having TB contact should be screened). Educational status, knowledge on TB, satisfaction with delivered health care service, health education given by HCWs about TB and HIV/AIDS co-infection were factors associated with household contact TB screening practice. Thus, strengthening household TB contact screening and educational programs regarding the risk of getting TB infection from household contacts is crucial.

IMPACT study on intervening with a manualised package to achieve treatment adherence in people with tuberculosis: protocol paper for a mixed-methods study, including a pilot randomised controlled trial.

INTRODUCTION: Compared with the rest of the UK and Western Europe, England has high rates of the infectious disease tuberculosis (TB). TB is curable, although treatment is for at least 6 months and longer when disease is drug resistant. If patients miss too many doses (non-adherence), they may transmit infection for longer and the infecting bacteria may develop resistance to the standard drugs used for treatment. Non-adherence may therefore risk both their health and that of others. Within England, certain population groups are thought to be at higher risk of non-adherence, but the factors contributing to this have been insufficiently determined, as have the best interventions to promote adherence. The objective of this study was to develop a manualised package of interventions for use as part of routine care within National Health Services to address the social and cultural factors that lead to poor adherence to treatment for TB disease. METHODS AND ANALYSIS: This study uses a mixed-methods approach, with six study components. These are (1) scoping reviews of the literature; (2) qualitative research with patients, carers and healthcare professionals; (3) development of the intervention; (4) a pilot randomised controlled trial of the manualised intervention; (5) a process evaluation to examine clinical utility; and (6) a cost analysis. ETHICS AND DISSEMINATION: This study received ethics approval on 24 December 2018 from Camberwell St. Giles Ethics Committee, UK (REC reference 18/LO/1818). Findings will be published and disseminated through peer-reviewed publications and conference presentations, published in an end of study report to our funder (the National Institute for Health Research, UK) and presented to key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN95243114 SECONDARY IDENTIFYING NUMBERS: University College London/University College London Hospitals Joint Research Office 17/0726.National Institute for Health Research, UK 16/88/06.

Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis.

BACKGROUND: Tuberculosis causes more deaths than any other infectious disease worldwide, with pulmonary tuberculosis being the most common form. Standard first-line treatment for drug-sensitive pulmonary tuberculosis for six months comprises isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) for two months, followed by HRE (in areas of high TB drug resistance) or HR, given over a four-month continuation phase. Many people do not complete this full course. Shortened treatment regimens that are equally effective and safe could improve treatment success. OBJECTIVES: To evaluate the efficacy and safety of shortened treatment regimens versus the standard six-month treatment regimen for individuals with drug-sensitive pulmonary tuberculosis. SEARCH METHODS: We searched the following databases up to 10 July 2019: the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE (PubMed); Embase; the Latin American Caribbean Health Sciences Literature (LILACS); Science Citation Index-Expanded; Indian Medlars Center; and the South Asian Database of Controlled Clinical Trials. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, the Clinical Trials Unit of the International Union Against Tuberculosis and Lung Disease, the UK Medical Research Council Clinical Trials Unit, and the Clinical Trials Registry India for ongoing trials. We checked the reference lists of identified articles to find additional relevant studies. SELECTION CRITERIA: We searched for randomized controlled trials (RCTs) or quasi-RCTs that compared shorter-duration regimens (less than six months) versus the standard six-month regimen for people of all ages, irrespective of HIV status, who were newly diagnosed with pulmonary tuberculosis by positive sputum culture or GeneXpert, and with presumed or proven drug-sensitive tuberculosis. The primary outcome of interest was relapse within two years of completion of anti-tuberculosis treatment (ATT). DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, and assessed risk of bias for the included trials. For dichotomous outcomes, we used risk ratios (RRs) with 95% confidence intervals (CIs). When appropriate, we pooled data from the included trials in meta-analyses. We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included five randomized trials that compared fluoroquinolone-containing four-month ATT regimens versus standard six-month ATT regimens and recruited 5825 adults with newly diagnosed drug-sensitive pulmonary tuberculosis from 14 countries with high tuberculosis transmission in Asia, Africa, and Latin Ameria. Three were multi-country trials that included a total of 572 HIV-positive people. These trials excluded children, pregnant or lactating women, people with serious comorbid conditions, and those with diabetes mellitus. Four trials had multiple treatment arms. Moxifloxacin replaced ethambutol in standard four-month, daily or thrice-weekly ATT regimens in two trials; moxifloxacin replaced isoniazid in four-month ATT regimens in two trials, was given daily in one trial, and was given with rifapentine instead of rifampicin daily for two months and twice weekly for two months in one trial. Moxifloxacin was added to standard ATT drugs for three to four months in one ongoing trial that reported interim results. Gatifloxacin replaced ethambutol in standard ATT regimens given daily or thrice weekly for four months in two trials. Follow-up ranged from 12 months to 24 months after treatment completion for the majority of participants. Moxifloxacin-containing four-month ATT regimens Moxifloxacin-containing four-month ATT regimens that replaced ethambutol or isoniazid probably increased the proportions who experienced relapse after successful treatment compared to standard ATT regimens (RR 3.56, 95% CI 2.37 to 5.37; 2265 participants, 3 trials; moderate-certainty evidence). For death from any cause, there was probably little or no difference between the two regimens (2760 participants, 3 trials; moderate-certainty evidence). Treatment failure was rare, and there was probably little or no difference in proportions with treatment failure between ATT regimens (2282 participants, 3 trials; moderate-certainty evidence). None of the participants given moxifloxacin-containing regimens developed resistance to rifampicin, and these regimens may not increase the risk of acquired resistance (2282 participants, 3 trials; low-certainty evidence). Severe adverse events were probably little or no different with moxifloxacin-containing four-month regimens that replaced ethambutol or isoniazid, and with three- to four-month regimens that augmented standard ATT with moxifloxacin, when compared to standard six-month ATT regimens (3548 participants, 4 trials; moderate-certainty evidence). Gatifloxacin-containing four-month ATT regimens Gatifloxacin-containing four-month ATT regimens that replaced ethambutol probably increased relapse compared to standard six-month ATT regimens in adults with drug-sensitive pulmonary tuberculosis (RR 2.11, 95% CI 1.56 to 2.84; 1633 participants, 2 trials; moderate-certainty evidence). The four-month regimen probably made little or no difference in death compared to the six-month regimen (1886 participants, 2 trials; moderate-certainty evidence). Treatment failure was uncommon and was probably little or no different between the four-month and six-month regimens (1657 participants, 2 trials; moderate-certainty evidence). Acquired resistance to isoniazid or rifampicin was not detected in those given the gatifloxacin-containing shortened ATT regimen, but we are uncertain whether acquired drug resistance is any different in the four- and six-month regimens (429 participants, 1 trial; very low-certainty evidence). Serious adverse events were probably no different with either regimen (1993 participants, 2 trials; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence to date does not support the use of shortened ATT regimens in adults with newly diagnosed drug-sensitive pulmonary tuberculosis. Four-month ATT regimens that replace ethambutol with moxifloxacin or gatifloxacin, or isoniazid with moxifloxacin, increase relapse substantially compared to standard six-month ATT regimens, although treatment success and serious adverse events are little or no different. The results of six large ongoing trials will help inform decisions on whether shortened ATT regimens can replace standard six-month ATT regimens. 9 December 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (10 Jul, 2019) were included.

Factors influencing active tuberculosis case-finding policy development and implementation: a scoping review.

OBJECTIVE: To explore antecedents, components and influencing factors on active case-finding (ACF) policy development and implementation. DESIGN: Scoping review, searching MEDLINE, Web of Science, the Cochrane Database of Systematic Reviews and the World Health Organization (WHO) Library from January 1968 to January 2018. We excluded studies focusing on latent tuberculosis (TB) infection, passive case-finding, childhood TB and studies about effectiveness, yield, accuracy and impact without descriptions of how this evidence has/could influence ACF policy or implementation. We included any type of study written in English, and conducted frequency and thematic analyses. RESULTS: Seventy-three articles fulfilled our eligibility criteria. Most (67%) were published after 2010. The studies were conducted in all WHO regions, but primarily in Africa (22%), Europe (23%) and the Western-Pacific region (12%). Forty-one percent of the studies were classified as quantitative, followed by reviews (22%) and qualitative studies (12%). Most articles focused on ACF for tuberculosis contacts (25%) or migrants (32%). Fourteen percent of the articles described community-based screening of high-risk populations. Fifty-nine percent of studies reported influencing factors for ACF implementation; mostly linked to the health system (eg, resources) and the community/individual (eg, social determinants of health). Only two articles highlighted factors influencing ACF policy development (eg, politics). Six articles described WHO's ACF-related recommendations as important antecedent for ACF. Key components of successful ACF implementation include health system capacity, mechanisms for integration, education and collaboration for ACF. CONCLUSION: We identified some main themes regarding the antecedents, components and influencing factors for ACF policy development and implementation. While we know much about facilitators and barriers for ACF policy implementation, we know less about how to strengthen those facilitators and how to overcome those barriers. A major knowledge gap remains when it comes to understanding which contextual factors influence ACF policy development. Research is required to understand, inform and improve ACF policy development and implementation.

[Disseminated tuberculosis mimicking metastatic gastric cancer - a case report]. / Disseminierte Tuberkulose imitiert metastasiertes Magenkarzinom ­ ein Fallbericht.

Increasing numbers of active tuberculosis in Germany were recorded in the last years. Thus, also extrapulmonary manifestations of tuberculosis gain clinical significance as differential diagnoses, especially when a metastatic tumor disease is suspected. We report the case of a 77-year-old male patient who presented with unilateral leg pain and B symptoms. Further investigations revealed an osteolytic mass in the sacrum as well as CT-morphological findings consistent with metastatic gastric cancer. However, transgastric biopsies showed necrotising granuloma with giant cells leading to molecular and cultural detection of Mycobacterium tuberculosis instead of suspected neoplastic tissue. A nine-month treatment regimen for suspected disseminated tuberculosis with bone involvement was initiated according to national guidelines. Clinical and radiological follow up examinations after treatment completion showed complete remission.

Neuropsychiatric reactions induced by cycloserine in the treatment of multidrug-resistant tuberculosis: what an Indian female patient tells us.

Multidrug-resistant tuberculosis continues to be a public health crisis. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people affected by drug-resistant tuberculosis. To implement tuberculosis control, in 2018, WHO recommended cycloserine as one of the Group B drugs. Following this recommendation, cycloserine should be generally included in the starting line-up in the longer regimen for the treatment of multidrug-resistant tuberculosis. However, neurological toxicity associated with this drug concerns clinicians and limits its use. In this paper, we present a case of a 48-year-old woman with a diagnosis of multidrug-resistant tuberculosis treated with cycloserine, who developed psychiatric adverse events after 3 months of administration. This case shows the need for close psychiatric follow-up to promptly detect adverse events in patients receiving regimens for multi-drug resistant tuberculosis.

Prevalence of tuberculosis, HIV/AIDS, and hepatitis; in a prison of Balochistan: a cross-sectional survey.

BACKGROUND: Human Immunodeficiency Virus (HIV), Hepatitis, and Tuberculosis (TB) are three primary communicable infections have the likely potential to cause severe morbidity in prison settings. The prison has the most favorable environment for the transmission of infections. We conducted this survey to determine the prevalence and feasibility of rapid diagnostic tests in an active screening of these infectious diseases in prison. METHODS: This cross-sectional survey conducted in central Jail Gaddani, one of the largest prisons in the Balochistan province of Pakistan. All prisoners, jail staffs, and staff's family members participated. Informed consent obtained from each participant before the screening. Van equipped with digital X-ray linked with Computer-Aided Detection for TB (CAD4TB) software used for testing. Sputum samples tested on Xpert for MTB/RIF assay and blood specimens collected for HIV and hepatitis serology. Diagnosed TB patients enrolled for treatment at Basic Management Unit (BMU), reactive on hepatitis Rapid Diagnostic Tools (RDTs) were referred for further testing and management, while HIV reactive referred to Anti Retro Viral (ARV) center for Anti Retro Viral Treatment (ART). RESULTS: A total of 567 participants offered screening, 63% (356) prisoners, 23% (129) staff's family members, and 14% (82) jail staffs. Among tested 10.3% (58/562) were hepatitis seropositive (Hepatitis-C 41 [7.29%] Hepatitis-B, 16 [2.84%] Hepatitis B&C both, 01 [0.17%]). In reactive participants, 49 were prisoners, 08 were jail staffs, and 01 was the staff's family member. HIV seropositive was 4% (24/566), and all were prisoners. Almost 99% (565/567) screened by digital X-ray, 172 (30%) were with abnormal CAD4TB suggestion (score > 50), out of them sputum of 26% (148) tested on Xpert, and 2% (03) found Mycobacterium tuberculosis Positive (MTB+). A total of five TB patients were detected; out of two were diagnosed clinically. Co-morbidities observed in 15 patients, (01 TB/HIV co-infected, 12 HIV/HCV, 01 HIV/HBV, and 01 HBV/HCV). CONCLUSION: The high frequency of infectious diseases in prison is alarming. For limiting the transmission of infections among prison and community, immediate steps are needed to be taken for improvement of prisons condition by application of recommended screening protocols at the time of the first entry of prisoners in prisons.

Detecting tuberculosis: rapid tools but slow progress.

The World Health Organization (WHO) currently recommends Xpert® MTB/RIF as the initial test for all people with presumptive tuberculosis (TB). A number of challenges have been reported, however, in using this technology, particularly in low-resource settings. Here we examine these challenges, and provide our perspective of the barriers to Xpert scale-up as assessed through a survey in 16 TB burden countries in which the Médecins Sans Frontières is present. We observed that the key barriers to scale-up include a lack of policy adoption and implementation of WHO recommendations for the use of Xpert, resulting from high costs, poor sensitisation of clinical staff and a high turnover of trained laboratory staff; insufficient service and maintenance provision provided by the manufacturer; and inadequate resources for sustainability and expansion. Funding is a critical issue as countries begin to transition out of support from the Global Fund. While it is clear that there is still an urgent need for research into and development of a rapid, affordable point-of-care test for TB that is truly adapted for use in low-resource settings, countries in the meantime need to develop functional and sustainable Xpert networks in order to close the existing diagnostic gap.

L'Organisation Mondiale de la Santé (OMS) recommande actuellement l'Xpert® MTB/RIF comme test initial pour toutes les personnes suspectes de tuberculose (TB). Le recours à cette technique s'est cependant heurté à un certain nombre de défis, particulièrement dans les contextes de faibles ressources. Nous examinons ici ces défis et proposons notre vision des contraintes à l'expansion comme l'a montré une enquête dans 16 pays très frappés par la TB où Médecins Sans Frontières est présent. Nous affirmons que les entraves majeures à l'expansion incluent un manque d'adoption politique et de mise en œuvre des recommandations de l'OMS relatives à l'utilisation de l'Xpert, résultant des coûts élevés, d'une sensibilisation insuffisante du personnel clinique et d'un taux élevé de renouvellement du personnel de laboratoire formé ; une offre insuffisante de service et de maintenance de la part du fabricant ; et des ressources insuffisantes pour la pérennité et l'expansion. Le financement est un problème crucial à mesure que les pays commencent leur transition vers l'arrêt du soutien du Fonds Mondial. Il est clair qu'il y a toujours un besoin urgent de recherche et de développement d'un test de TB rapide, abordable, réalisable sur place et réellement adapté à une utilisation dans des contextes de faibles ressources. Dans l'intervalle, les pays ont cependant besoin d'élaborer des réseaux d'Xpert fonctionnels et pérennisables de manière à combler le fossé existant en matière de diagnostic.

En la actualidad, la Organización Mundial de la Salud (OMS) recomienda como primer método diagnóstico la prueba Xpert® MTB/RIF en todas las personas con presunción clínica de tuberculosis (TB). Se ha comunicado, no obstante, una serie de dificultades con la utilización de esta técnica sobre todo en entornos con recursos limitados. En el presente estudio se examinan estas dificultades y se ofrece una perspectiva de los obstáculos a la ampliación de escala de la recomendación, a partir de una encuesta realizada en 16 países con carga de morbilidad por TB donde está presente Médicos Sin Fronteras. Los autores afirman que los principales obstáculos a la ampliación de escala son los siguientes: la falta de adopción de políticas en favor de las recomendaciones de la OMS sobre la utilización de la prueba Xpert y el refuerzo de su cumplimiento, debido a los costos altos, la escasa sensibilización del personal médico y una alta rotación del personal de laboratorio capacitado; la insuficiencia de la prestación de servicios y mantenimiento por parte del fabricante; y los recursos insuficientes para la sostenibilidad y la ampliación. El financiamiento constituye un elemento primordial a medida que los países dejan de percibir el apoyo del Fondo Mundial. Es evidente que existe una necesidad urgente de investigación y desarrollo de una prueba en el lugar de la consulta que sea asequible y efectivamente adaptada a los entornos con recursos escasos, pero mientras tanto, los países deben crear redes funcionales y sostenibles de la prueba Xpert a fin de subsanar las deficiencias actuales en el diagnóstico.

The high-quality health system 'revolution': Re-imagining tuberculosis infection prevention and control.

The Lancet Commission on High-Quality Health Systems called for a 'revolution' in the quality of care provided in low- and middle-income countries. We argue that this provides a helpful framework to demonstrate how effective tuberculosis infection prevention and control (TB IPC) implementation should be linked with health system strengthening, moving it from the silo of the national TB programmes. Using this framework, we identify and discuss links between TB IPC implementation and patient safety, human resources for health, prioritising person-centred care, building trust in health systems and refining the tools used to measure TB IPC implementation. Prioritising patient experience has been a recent addition to the definition of high-quality care. In high TB burden settings, the encounter with TB IPC measures may be a TB patient's initial contact with the healthcare system and may cause feelings of stigmatisation. We advocate for re-imagining the way we implement TB IPC, by drawing on the principles of person-centred care through incorporating the experiences of people using healthcare services. Health workers who developed occupational TB also offer a unique perspective: they have both experienced TB IPC and have played a role in implementing it in their workplace. They can be powerful advocates for person-centred TB IPC implementation. Through framing TB IPC as part of health system strengthening and consciously including person-centred perspectives in TB IPC design, measurement and guidelines, we hope to influence future TB IPC research and practice.

Quality of life with tuberculosis.

Tuberculosis diagnosis and treatment currently revolves around clinical features and microbiology. The disease however adversely affects patients' psychological, economic, and social well-being as well, and therefore our focus also additionally needs to shift towards quality of life (QOL). The disease influences all QOL domains and substantially adds to patient morbidity, and these complex and multidimensional interactions pose challenges in accurately quantifying impairment in QOL. For this review, PubMed database was queried using keywords like quality of life, health status and tuberculosis, and additional publications identified by a bibliographic review of shortlisted articles. Both generic and specific QOL scales show a wide variety of derangements in scores, and results vary across countries and patient groups. In particular, diminished capacity to work, social stigmatization, and psychological issues worsen QOL in patients with tuberculosis. Although QOL has been consistently shown to improve during standard anti-tubercular therapy, many patients continue to show residual impairment. It is also not clear if specific situations like presence of comorbid illnesses, drug resistance, or co-infection with human immunodeficiency virus additionally worsen QOL in these patients. There is a definite need to incorporate QOL assessment as adjunct outcome measures in tuberculosis control programs. Governments and program managers need to step up socio-cultural reforms and health education, and provide additional incentives to patients, to counter impairment in QOL.

Quality of TB care among people living with HIV: Gaps and solutions.

Tuberculosis (TB) is the leading infectious cause of death among people living with HIV, causing one third of AIDS-related deaths globally. The concerning number of missing TB cases, ongoing high TB mortality, slow reduction in TB incidence, and limited uptake of TB preventive treatment among people living with HIV, all indicate the urgent need to improve quality of TB services within HIV programs. In this mini-review we discuss major gaps in quality of TB care that impede achieving prevention and treatment targets within the TB-HIV care cascades, show approaches of assessing gaps in TB service provision, and describe outcomes from innovative quality improvement projects among HIV and TB programs. We also offer recommendations for measuring quality of TB care.

User-experience and patient satisfaction with quality of tuberculosis care in India: A mixed-methods literature review.

BACKGROUND: Tuberculosis affected 2.7 million people in India in 2017. The Revised National TB Control Programme has achieved milestones in coverage, however quality of TB care remains highly variable and often poor, with significant gaps in provider knowledge, practices, and patients consistently lost to follow-up. These quality gaps are largely informed by studies on provider practices or objective chart abstractions and case data. Per the knowledge of the author, no review has been conducted on first-hand patient perspectives on the quality of TB care they receive. This mixed-methods literature review aims to synthesize evidence on user-experience and patient satisfaction with TB care in India and inform areas for service quality improvement. METHODS: Five medical databases, including PubMed, EMBASE, Global Health (Ovid), Web of Science, and CINAHL were searched for empirical studies on patient perspectives on TB health services published between January 1st, 2000 to December 31st, 2017. Studies in English with adult patients with any form of TB in the public or private health system were included. Studies prior to entering the health system, on distance to health facilities and cost were excluded. Seven Indian journals were hand searched and a grey literature search was conducted in GoogleScholar. Studies were assessed for methodological quality and thematic analysis was conducted by categorizing data using NVivo 12. RESULTS: A total of 498 studies were screened, of which 23 met the inclusion criteria. 16 supplementary studies were identified from Indian journals and grey literature. Of the 39 total studies included most were quantitative (29; 74%), based in South India (17; 44%) and focused on drug-sensitive TB patients (19; 49%) within the public health system (25; 64%). Data collection methods were highly heterogenous which limited synthesis and comparisons across population demographics, health sectors, or regions. Overall quantitative patient satisfaction measured in seven studies was high. Two major themes identified were provider-related factors (n = 26 studies) and convenience (n = 25), and six minor themes were supplies and equipment availability (n = 12), confidence (n = 10), information and communication (n = 10), waiting time (n = 8), stigma (n = 4), and confidentiality (n = 4). Each reported positive and negative user-experiences. Most significantly, DOTS did not fit the daily needs and obligations of many patients, particularly due to conflicts with employment and frequency of visits; while positive provider support, information, and flexibility helped patients adhere to treatment. CONCLUSION: Although quantitative patient satisfaction was found to be high, data were not collected using robust, validated tools. Qualitative and quantitative user-experiences in each theme were variable, making them both barriers and facilitators of good quality TB care. Poor user-experiences were often responsible for patients interrupting treatment or dropping out of TB care. Patient-centeredness, or user-friendliness of TB care can be improved by introducing individualized or flexible DOTS that is responsive to user circumstances and needs. User-experience data should be systematically collected using a standardized, national tool for identification of specific bottlenecks and successes in quality of TB care from the patients' perspective.