Barriers to engagement in the care cascade for tuberculosis disease in India: A systematic review of quantitative studies.

BACKGROUND: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. METHODS AND FINDINGS: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. CONCLUSIONS: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade.

Epidemiology of antimicrobial resistance in bacteria isolated from inpatient and outpatient samples, Ecuador, 2018.

Objective: To compare the epidemiology of antimicrobial resistance in bacteria isolated from inpatient and outpatient samples in Ecuador. Methods: A secondary analysis was done of data on bacteria isolated from inpatient and outpatient samples. Data were taken from the 2018 national antimicrobial resistance surveillance database of the National Reference Center for Antimicrobial Resistance. The variables included were: age, sex, inpatient versus outpatient setting, type of specimen, bacterial species identified, pattern of resistance to antibiotics, and geographic area. Results: Data from 57 305 bacterial isolates were included in the study: 48.8% were from hospitalized patients, 55.7% were from women, and 60.1% were from patients older than 45 years. Urine (42.9%) and blood (12.4%) were the most common clinical samples. Overall, 77.1% of bacterial isolates were gram-negative (83% and 71% in outpatients and inpatients, respectively). The most common gram-positive and gram-negative species were Staphylococcus aureus and Escherichia coli, respectively. Antimicrobial resistance levels were high (up to 80% for some antimicrobial drugs), and were higher in hospitalized patients compared with outpatients. A variety of carbapenemases were found to confer resistance to carbapenems (antibiotics of last resort) in gram-negative bacteria. Conclusions: The study findings provide an important baseline on antimicrobial resistance in Ecuador. This will allow the strengthening of guidelines of the surveillance system, the creation of public policies for standardization of laboratory methodologies, the proper handling of information, and the development of empirical therapy guidelines based on local epidemiology.

Treatment success rates among tuberculosis patients notified from the private sector in West Bengal, India.

In India, an estimated 50% of tuberculosis (TB) patients are diagnosed and managed by private providers (PPs). However, there is limited information on treatment outcomes among those treated by PPs largely because of a lack of systems for patient follow-up and documentation of the outcomes. Tuberculosis Health Action Learning Initiative (THALI) project implemented in six districts of West Bengal, supported PPs in managing TB patients and systematically documented the TB treatment outcomes of such patients. This provided us an opportunity to describe the treatment outcomes and assess factors associated with 'unsuccessful outcomes' among TB patients notified by PPs from January to April 2018. This was a retrospective cohort study using routinely collected data. During the study reference period, 2347 patients were notified from 389 PPs. The patient's mean (SD) age was 39.9 (17.2) years and 61% were males. Of the total, about 86% had pulmonary TB, 95% were new cases, and 23% were microbiologically confirmed (either on sputum smear microscopy or Xpert assay). Among 2347 patients, 19% received free drugs from the National Tuberculosis Program (NTP) under the supervision of PPs while the rest purchased anti-TB drugs from the private pharmacies. The 'successful outcomes' (cured and treatment completed) were seen in 86.1% (95% confidence interval (CI), 84.6%-87.4%) patients and 8.6% were 'not evaluated'. The patients who received free NTP drugs (adjusted relative risk-4.0 (95% CI: 3.1-5.0)) had a higher risk of 'unsuccessful outcomes' than those who availed of drugs from private pharmacies. The high 'successful outcomes' among TB patients treated by PPs are promising. However, higher 'unsuccessful outcomes' among patients on free NTP drugs need to be explored, and suitable corrective actions have to be taken.

Constructing care cascades for active tuberculosis: A strategy for program monitoring and identifying gaps in quality of care.

The cascade of care is a model for evaluating patient retention across sequential stages of care required to achieve a successful treatment outcome. This approach was first used to evaluate HIV care and has since been applied to other diseases. The tuberculosis (TB) community has only recently started using care cascade analyses to quantify gaps in quality of care. In this article, we describe methods for estimating gaps (patient losses) and steps (patients retained) in the care cascade for active TB disease. We highlight approaches for overcoming challenges in constructing the TB care cascade, which include difficulties in estimating the population-level burden of disease and the diagnostic gap due to the limited sensitivity of TB diagnostic tests. We also describe potential uses of this model for evaluating the impact of interventions to improve case finding, diagnosis, linkage to care, retention in care, and post-treatment monitoring of TB patients.

Coprevalence of type 2 diabetes mellitus and tuberculosis in low-income and middle-income countries: A systematic review.

Increasing coprevalence of diabetes mellitus (DM) and tuberculosis (TB) in low-income and middle-income countries (LMICs) indicates a rising threat to the decades of progress made against TB and requires global attention. This systematic review provides a summary of type 2 diabetes and tuberculosis coprevalence in various LMICs. We searched PubMed, Ovid Medline, Embase, and PsychINFO databases for studies that provided estimates of TB-DM coprevalence in LMICs published between 1990 and 2016. Studies that were non-English and exclusively conducted in multidrug resistant-tuberculosis or type 1 diabetes and inpatient settings were excluded. We reviewed 84 studies from 31 countries. There were huge diversity of study designs and diagnostic methods used to estimate coprevalence, and this precluded pooling of the results. Most studies (n = 78) were from small, localized settings. The DM prevalence among TB patients in various LMICs varied from 1.8% to 45%, with the majority (n = 44) between 10% and 30%. The TB prevalence among people with DM ranged from 0.1% to 6.0% with most studies (n = 9) reporting prevalences less than 2%. Coprevalence of TB-DM was higher than general population prevalence of either diseases in these countries. This study underscores the need for intervention and more focused research on TB DM bidirectional screening programs in low-income and middle-income countries as well as integrated chronic disease management.

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.

Initiation of antiretroviral therapy or antiretroviral prophylaxis in pregnant women living with HIV registered in five townships of Mandalay, Myanmar: A cross sectional study.

BACKGROUND: A series of interventions are required to prevent mother to child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) starting from HIV testing of pregnant women, initiating antiretroviral therapy (ART) or antiretroviral prophylaxis to HIV-positive pregnant women to providing HIV prophylaxis to newborn babies. Gaps in each step can significantly affect the effectiveness of PMTCT interventions. We aimed to determine the gap in initiation of ART/antiretroviral prophylaxis for pregnant women living with HIV, delay in initiation of ART/antiretroviral prophylaxis and factors associated with the delay. METHODS: This is a cross sectional study using routinely collected programme data from five health facilities providing PMTCT services located at Township Health Departments (THD) of Mandalay, Myanmar. RESULTS: There were 363 pregnant women living with HIV enrolled between January 2012 and December 2017. Sixty (16%) women were excluded from the study due to missing data on dates of HIV diagnosis. Of 303 (84%) women included in the study, 89/303 (29%) and 214/303 (71%) were diagnosed with HIV before and during current pregnancy respectively. Among 214 women, 180 (84%) women were started on ART by the censor date (31st March 2018). Among those who started ART, 109 (61%) women had a delay of starting ART > 2 weeks from diagnosis. Women residing in township 4 had a significantly higher risk of delay in initiation of ART/antiretroviral prophylaxis compared to women residing in township 1 [adjusted prevalence ratio 4.2 (95% confidence interval 1.2-14.8]. CONCLUSIONS: We found that one in four women living with HIV knew their HIV status before current pregnancy. Although the rate of ART/antiretroviral prophylaxis initiation was high among pregnant women living with HIV, there was a delay. Early initiation of ART/antiretroviral prophylaxis among newly HIV diagnosed pregnant women needs to be strengthened.

Use of Verbal Autopsy to Determine Underlying Cause of Death during Treatment of Multidrug-Resistant Tuberculosis, India.

Of patients with multidrug-resistant tuberculosis (MDR TB), <50% complete treatment. Most treatment failures for patients with MDR TB are due to death during TB treatment. We sought to determine the proportion of deaths during MDR TB treatment attributable to TB itself. We used a structured verbal autopsy tool to interview family members of patients who died during MDR TB treatment in India during January-December 2016. A committee triangulated information from verbal autopsy, death certificate, or other medical records available with the family members to ascertain the underlying cause of death. For 66% of patient deaths (47/71), TB was the underlying cause of death. We assigned TB as the underlying cause of death for an additional 6 patients who died of suicide and 2 of pulmonary embolism. Deaths during TB treatment signify program failure; accurately determining the cause of death is the first step to designing appropriate, timely interventions to prevent premature deaths.

Variations in the quality of tuberculosis care in urban India: A cross-sectional, standardized patient study in two cities.

BACKGROUND: India has the highest burden of tuberculosis (TB). Although most patients with TB in India seek care from the private sector, there is limited evidence on quality of TB care or its correlates. Following our validation study on the standardized patient (SP) method for TB, we utilized SPs to examine quality of adult TB care among health providers with different qualifications in 2 Indian cities. METHODS AND FINDINGS: During 2014-2017, pilot programs engaged the private health sector to improve TB management in Mumbai and Patna. Nested within these projects, to obtain representative, baseline measures of quality of TB care at the city level, we recruited 24 adults to be SPs. They were trained to portray 4 TB "case scenarios" representing various stages of disease and diagnostic progression. Between November 2014 and August 2015, the SPs visited representatively sampled private providers stratified by qualification: (1) allopathic providers with Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees or higher and (2) non-MBBS providers with alternative medicine, minimal, or no qualifications. Our main outcome was case-specific correct management benchmarked against the Standards for TB Care in India (STCI). Using ANOVA, we assessed variation in correct management and quality outcomes across (a) cities, (b) qualifications, and (c) case scenarios. Additionally, 2 micro-experiments identified sources of variation: first, quality in the presence of diagnostic test results certainty and second, provider consistency for different patients presenting the same case. A total of 2,652 SP-provider interactions across 1,203 health facilities were analyzed. Based on our sampling strategy and after removing 50 micro-experiment interactions, 2,602 interactions were weighted for city-representative interpretation. After weighting, the 473 Patna providers receiving SPs represent 3,179 eligible providers in Patna; in Mumbai, the 730 providers represent 7,115 eligible providers. Correct management was observed in 959 out of 2,602 interactions (37%; 35% weighted; 95% CI 32%-37%), primarily from referrals and ordering chest X-rays (CXRs). Unnecessary medicines were given to nearly all SPs, and antibiotic use was common. Anti-TB drugs were prescribed in 118 interactions (4.5%; 5% weighted), of which 45 were given in the case in which such treatment is considered correct management. MBBS and more qualified providers had higher odds of correctly managing cases than non-MBBS providers (odds ratio [OR] 2.80; 95% CI 2.05-3.82; p < 0.0001). Mumbai non-MBBS providers had higher odds of correct management than non-MBBS in Patna (OR 1.79; 95% CI 1.06-3.03), and MBBS providers' quality of care did not vary between cities (OR 1.15; 95% CI 0.79-1.68; p = 0.4642). In the micro-experiments, improving diagnostic certainty had a positive effect on correct management but not across all quality dimensions. Also, providers delivered idiosyncratically consistent care, repeating all observed actions, including mistakes, approximately 75% of the time. The SP method has limitations: it cannot account for patient mix or care-management practices reflecting more than one patient-provider interaction. CONCLUSIONS: Quality of TB care is suboptimal and variable in urban India's private health sector. Addressing this is critical for India's plans to end TB by 2025. For the first time, we have rich measures on representative levels of care quality from 2 cities, which can inform private-sector TB interventions and quality-improvement efforts.

Uptake of antiretroviral therapy in HIV-positive women ever enrolled into 'prevention of mother to child transmission' programme, Mandalay, Myanmar-a cohort study.

BACKGROUND: Early initiation and longer duration of anti-retroviral therapy either as prophylaxis (pARV) or lifelong treatment (ART) in HIV-positive pregnant women prior to delivery has a huge impact in reducing mother to child transmission (MTCT) of HIV, maternal morbidity, mortality and increasing retention in care. In this study, we aimed to determine the following in a 'prevention of mother-to-child transmission' (PMTCT) programme in Central Women Hospital, Mandalay, Myanmar: i) uptake of ART and factors associated with the uptake ii) duration of ART/ pARV received by HIV-positive pregnant women prior to delivery, iii) factors associated with ART/ pARV initiation after delivery and iv) factors associated with shorter duration of ART/ pARV (≤ 8 weeks prior to delivery). METHOD: This was a retrospective cohort study using routinely collected data from PMTCT programme. We used multivariable Cox proportional Hazard model or log binomial models to assess the association between socio-demographic and clinical factors with a) uptake of ART/pARV, b) initiation of ART/pARV after delivery, c) shorter (≤8 weeks) duration of ART/PARV prior to delivery. RESULTS: Of the 670 ART naïve HIV-positive women enrolled to PMTCT programme between March 2011 and December 2016, 588 (88%) were initiated on ART/pARV. In adjusted analysis, only pregnancy stage at enrolment was significantly associated with initiation of ART/pARV. Of 585 who had delivered babies on or before the censor date, 522 (89%) were on ART/pARV. Women who lived outside Mandalay were more likely to be initiated on ART after delivery (i.e., delayed ART initiation in those on ART). Among women who were initiated on ART/pARV before delivery (n = 468), only 59% got ART/pARV for > 8 weeks before delivery. Women whose spouses' HIV status was not recorded had 40% higher risk of short duration of ART/pARV. CONCLUSIONS: This study shows high uptake of ART/pARV among those enrolled into the PMTCT programme. However, about one in eight pregnant women did not receive ART before delivery. Among those initiated on ART/pARV before delivery, nearly half of them received ART/pARV for less than 8 weeks prior to delivery. These aspects need to be improved in order to eliminate mother-to-child transmission of HIV.

The Tuberculosis Cascade of Care in India's Public Sector: A Systematic Review and Meta-analysis.

BACKGROUND: India has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world's "missing" patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The "cascade of care" is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions. METHODS AND FINDINGS: The care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India's TB patients. We define the TB cascade as including the following patient populations: total prevalent active TB patients in India, TB patients who reach and undergo evaluation at RNTCP diagnostic facilities, patients successfully diagnosed with TB, patients who start treatment, patients retained to treatment completion, and patients who achieve 1-y recurrence-free survival. We estimate each step of the cascade for 2013 using data from two World Health Organization (WHO) reports (2014-2015), one WHO dataset (2015), and three RNTCP reports (2014-2016). In addition, we conduct three targeted systematic reviews of the scientific literature to identify 39 unique articles published from 2000-2015 that provide additional data on five indicators that help estimate different steps of the TB cascade. We construct separate care cascades for the overall population of patients with active TB and for patients with specific forms of TB-including new smear-positive, new smear-negative, retreatment smear-positive, and multidrug-resistant (MDR) TB. The WHO estimated that there were 2,700,000 (95%CI: 1,800,000-3,800,000) prevalent TB patients in India in 2013. Of these patients, we estimate that 1,938,027 (72%) TB patients were evaluated at RNTCP facilities; 1,629,906 (60%) were successfully diagnosed; 1,417,838 (53%) got registered for treatment; 1,221,764 (45%) completed treatment; and 1,049,237 (95%CI: 1,008,775-1,083,243), or 39%, of 2,700,000 TB patients achieved the optimal outcome of 1-y recurrence-free survival. The separate cascades for different forms of TB highlight different patterns of patient attrition. Pretreatment loss to follow-up of diagnosed patients and post-treatment TB recurrence were major points of attrition in the new smear-positive TB cascade. In the new smear-negative and MDR TB cascades, a substantial proportion of patients who were evaluated at RNTCP diagnostic facilities were not successfully diagnosed. Retreatment smear-positive and MDR TB patients had poorer treatment outcomes than the general TB population. Limitations of our analysis include the lack of available data on the cascade of care in the private sector and substantial uncertainty regarding the 1-y period prevalence of TB in India. CONCLUSIONS: Increasing case detection is critical to improving outcomes in India's TB cascade of care, especially for smear-negative and MDR TB patients. For new smear-positive patients, pretreatment loss to follow-up and post-treatment TB recurrence are considerable points of attrition that may contribute to ongoing TB transmission. Future multisite studies providing more accurate information on key steps in the public sector TB cascade and extension of this analysis to private sector patients may help to better target interventions and resources for TB control in India.

The importance of implementation strategy in scaling up Xpert MTB/RIF for diagnosis of tuberculosis in the Indian health-care system: a transmission model.

BACKGROUND: India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. METHODS AND FINDINGS: We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: -1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: -5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research. CONCLUSIONS: The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary.

Research to policy and practice change: is capacity building in operational research delivering the goods?

OBJECTIVES: Between 2009 and 2012, eight operational research capacity building courses were completed in Paris (3), Luxembourg (1), India (1), Nepal (1), Kenya (1) and Fiji (1). Courses had strict milestones that were subsequently adopted by the Structured Operational Research and Training InitiaTive (SORT IT) of the World Health Organization. We report on the numbers of enrolled participants who successfully completed courses, the number of papers published and their reported effect on policy and/or practice. DESIGN: Retrospective cohort study including a survey. METHODS: Participant selection criteria ensured that only those proposing specific programme-related and relevant operational research questions were selected. Effects on policy and/or practice were assessed in a standardised manner by two independent reviewers. RESULTS: Of 93 enrolled participants from 31 countries (14 in Africa, 13 in Asia, two in Latin America and two in South Pacific), 83 (89%) completed their courses. A total of 96 papers were submitted to scientific journals of which 89 (93%) were published and 88 assessed for effect on policy and practice. There was a reported effect in 65 (74%) studies including changes to programme implementation (27), adaptation of monitoring tools (24) and changes to existing guidelines (20). CONCLUSION: Three quarters of published operational research studies from these structured courses had reported effects on policy and/or practice. It is important that this type of tracking becomes a standard component of operational research and research in general.

HIV- related knowledge, attitude, practices, and stigma among healthcare providers caring for HIV in Jordan: Identification of several organizational challenges.

Background: There is a paucity of data on Healthcare Providers (HCPs) caring for people living with HIV in Jordan. Objective: We aimed to understand HCPs' knowledge, attitude, stigma, and practices, to assess the gaps in HIV care in Jordan. Methods: We conducted recorded in-depth interviews with all five HCPs working at the only HIV Service Center in Jordan, using semi-structured questions in 2021. Content analysis was performed. Results: Several organizational challenges were identified. Only one had received HIV training. All were uncertain of updated recommendations with little knowledge of international guidelines, vertical transmission, contraception, sexually transmitted infections (STIs), non-communicable diseases (NCDs), and prophylaxis. Four HCPs perform counseling, focusing on easing anxieties, risk modification, and the importance of treatment adherence. However, their counseling on contraception, risk of transmission, STIs, and NCDs is inadequate, and they have little-to-no experience with prophylaxis. Most had a positive attitude towards people living with HIV, especially HCPs working at the center the longest, encouraging marriage and reproduction. Most do not approve of mandatory testing, or of breaching patient confidentiality. They repetitively described risky behavior as 'immoral behavior', empathizing more with patients who caught HIV through blood transfusion or birth, and demonstrating embedded stigmatized beliefs. They reported people living with HIV experience anticipated stigma and stigma by their general community including by other HCPs. Conclusion: This is the first study on HCPs caring for people living with HIV in Jordan. It highlights the suboptimal knowledge, practices, and stigma which improve with greater participatory exposure to HIV care. HCPs had an overall positive attitude, more evident in HCPs working at the clinic the longest.

Tuberculosis-related knowledge, practices, perceived stigma and discrimination among patients with tuberculosis: a cross-sectional study in Jordan.

BACKGROUND: Tuberculosis knowledge, practices, and perceived stigma and discrimination among patients with tuberculosis are key factors for the management of the disease. OBJECTIVES: The objectives of the study were to assess knowledge, practices, perceived stigma and discrimination, perceived family and health workers support, perceived level of satisfaction with healthcare services, delay in diagnosis/treatment and reasons for delay among patients with tuberculosis in Jordan. METHODS: A cross-sectional study was conducted among patients who were under treatment for tuberculosis in Jordan in 2021. RESULTS: This study included a total of 452 patients with tuberculosis. About 91.4% of patients had low to moderate overall tuberculosis-related knowledge score and 8.6% had high knowledge score. Almost two-thirds of patients (67.5%) had perceived a low level of stigma, 61 (13.5%) perceived a moderate level of stigma, and 86 (19.0%) perceived a high level of stigma. The majority (84.5%) of patients with tuberculosis thought that there was a delay in diagnosis and/or treatment of tuberculosis. CONCLUSION: Our study showed gaps in tuberculosis knowledge and practices, high perceived stigma and discrimination, and perceived delay in diagnosis and treatment initiation,. Efforts within the national tuberculosis control program should be made to increase public awareness about the symptoms of tuberculosis and the importance of seeking early care.

Evaluation of the National Tuberculosis Program and Tuberculosis Surveillance System, Jordan 2021.

Objectives: Evaluate and determine the gaps in the National Tuberculosis Program and Tuberculosis Surveillance System in Jordan. Methods: A concurrent embedded mixed quantitative/qualitative methods study was conducted to assess the National Tuberculosis Program and Tuberculosis Surveillance System in Jordan. A semi-structured questionnaire was developed based on the Updated CDC Guideline for Evaluating Public Health Surveillance System to collect necessary information from service providers and other stakeholders. Results: The National Tuberculosis Program and Tuberculosis Surveillance System encounter various gaps and challenges across several critical domains, including infrastructure, human resources, National Tuberculosis Program functions, surveillance system performance, coordination, case findings, and data collection and notification. Regrettably, not all of the Tuberculosis Surveillance System's objectives were successfully achieved in the past. Coordination of tuberculosis services has been repeatedly reported as inadequate. This deficiency manifests in the delay in diagnosing tuberculosis patients and, in some instances, misdiagnoses. The root cause is often traced back to insufficient knowledge of tuberculosis case definitions among healthcare providers at peripheral tuberculosis clinics. Additionally, a structured approach to active case finding is conspicuously absent. Furthermore, the tuberculosis management guidelines remain unfamiliar to many healthcare providers in tuberculosis centers, leaving them inadequately equipped to handle tuberculosis cases effectively. The utilization and analysis of the system's data are also far from optimal. A glaring concern is the delay in tuberculosis case notifications received from the stakeholders involved in the Tuberculosis Surveillance System. Conclusions: Our study showed different gaps in the National Tuberculosis Program and Tuberculosis Surveillance Systems across several areas. The structure of National Tuberculosis Program and the clinical expertise of human resources do not support tuberculosis elimination. An electronic data collection and notification system is essential to facilitate tuberculosis case detection, reporting, and follow-up. Decision-makers should push the tuberculosis epidemic on the national health agenda. Jordan should focus on allocating national and international resources for tuberculosis control programs.

Modeling the impact of alternative strategies for rapid molecular diagnosis of tuberculosis in Southeast Asia.

Novel diagnostic tests hold promise for improving tuberculosis (TB) control, but their epidemiologic impact remains uncertain. Using data from the World Health Organization (2011-2012), we developed a transmission model to evaluate the deployment of 3 hypothetical TB diagnostic tests in Southeast Asia under idealized scenarios of implementation. We defined diagnostics by their sensitivity for smear-negative TB and proportion of patients testing positive who initiate therapy ("point-of-care amenability"), with tests of increasing point-of-care amenability having lower sensitivity. Implemented in the public sector (35% of care-seeking attempts), each novel test reduced TB incidence by 7%-9% (95% uncertainty range: 4%-13%) and mortality by 20%-22% (95% uncertainty range: 14%-27%) after 10 years. If also deployed in the private sector (65% of attempts), these tests reduced incidence by 13%-16%, whereas a perfect test (100% sensitivity and treatment initiation) reduced incidence by 20%. Annually detecting 20% of prevalent TB cases through targeted screening (70% smear-negative sensitivity, 85% treatment initiation) also reduced incidence by 19%. Sensitivity and point-of-care amenability are equally important considerations when developing novel diagnostic tests for TB. Novel diagnostics can substantially reduce TB incidence and mortality in Southeast Asia but are unlikely to transform TB control unless they are deployed actively and in the private sector.

Tuberculosis-related knowledge, behaviors, stigmatizing attitude, and discrimination among refugees, migrants, and the general population in Jordan.

Objective: A better understanding of tuberculosis-related knowledge, attitude, practices in the community, and other issues can help in implementing evidence-driven activities to control tuberculosis in Jordan. This study aimed to assess tuberculosis-related knowledge, attitude, and behaviors among refugees, migrants, and general population, and assess their stigmatizing and discrimination attitudes toward tuberculosis patients, social behavior toward tuberculosis, and healthcare-seeking behaviors. Methods: A cross-sectional study was conducted among Jordanians, Syrian refugees, and migrants living in four governorates including Amman, Zarqa, Mafraq, and Irbid during the study period of June to September 2021. A structured questionnaire was developed to collect data via face-to-face interviews. Descriptive statistics, chi-square test, and general linear model procedure were used to analyze data. Results: A total of 2302 (27.7% Jordanians, 25.7% urban refugees, 22.1% camp refugees, and 24.5% migrants) participated in this study. Of the total, 90.1% of participants reported that they have heard of tuberculosis. However, 88.9% of Jordanians, 92.8% of urban refugees, 92% of camp refugees, and 90.5% of migrants had low level of tuberculosis-related knowledge. About 62.0% of urban refugees, 54.8% of Jordanians, 43.0% of camp refugees, and 55.4% of migrants had moderate to high stigmatizing attitude toward tuberculosis patients. About 15.1% of Jordanians, 10.6% of urban refugees, 23.7% of camp refugees, and 16.1% of migrants had moderate to high level of discriminating attitude toward tuberculosis patients. Camp refugees had a significantly higher level of discriminating attitude toward tuberculosis patients than the other groups. Conclusion: This study identified significant gaps in tuberculosis-related knowledge among the targeted groups. Moderate to high level of stigmatizing attitude was reported by a considerable proportion of the study participants. This suggests a need for public health education programs to educate people on tuberculosis causes, signs, symptoms, mode of transmission, and address related stigma, especially among the most disadvantaged and affected communities in Jordan.

Tuberculosis Notification in Jordan, 2016-2020.

The burden of tuberculosis (TB) in Jordan is largely unknown due to the paucity of high-quality data, under-reporting, and a lack of good quality vital registration system. This study aimed to assess the characteristics of TB patients in Jordan, determine the TB notification rate and assess the trend of TB notification in Jordan between 2016 and 2020. Methods: This study analyzed the TB Surveillance data in Jordan for the period 2016-2020. The obtained data included information on age, gender, nationality, marital status, date of symptoms onset and date of diagnosis, and site of TB. Results: During the period 2016-2020, a total of 1711 patients (989 women and 722 men) were diagnosed with and treated for tuberculosis. The mean (SD) age of patients was 30.1 (17.2) years. Almost half of them (48.4%) were Jordanians. The majority of non-Jordanian patients were from Syria, Philippines, and Bangladesh. Two thirds of patients (66.0%) had pulmonary TB and 34.0% had extra-pulmonary TB. Almost half (50.7%) of the patients were diagnosed within one month of the symptoms' onset. The average annual TB notification rate during 2016-2020 was 3.32 per 100,000 pop (4.08 per 100,000 women and 2.64 per 100,000 men). The average annual standardized notification rate was 4.13 per 100,000 pop (4.52 per 100,000 women and 3.52 per 100,000 men). The overall age-standardized notification rate increased from 3.88 per 100,000 pop in 2016 to 4.58 per 100,000 pop in 2019 and declined to 2.46 per 100,000 pop in 2020. The trend in TB notification differed significantly according to gender. While the notification increased in the last three years among women, it decreased significantly among men. Conclusions: While TB notification increased in the last three years among women, it decreased significantly among men. There is a need to ensure that the national TB plans set clear targets for reducing the burden of TB.

Time to Treatment and Risk Factors for Unsuccessful Treatment Outcomes among People Who Started Second-Line Treatment for Rifampicin-Resistant or Multi-Drug-Resistant Tuberculosis in the Kyrgyz Republic, 2021.

The Kyrgyz Republic is a high-burden country for rifampicin resistant/multi-drug resistant tuberculosis (RR/MDR-TB). TB control efforts rely on early diagnosis and initiation of people on effective regimens. We studied the interval from diagnosis of RR-TB to starting treatment and risk factors for unsuccessful outcomes among people who started RR/MDR-TB treatment in 2021. We conducted a cohort study using country-wide programme data and used binomial regression to determine associations between unsuccessful outcomes and predictor variables. Of the 535 people included in the study, three-quarters were in the age category 18-59 years, and 68% had past history of TB. The median (IQR) time from onset of TB symptoms to diagnosis was 30 (11-62) days, 1 (0-4) days from diagnosis to starting treatment, and 35 (24-65) days from starting treatment to receipt of second-line drug susceptibility test (SL-DST) results. Overall, 136 (25%) had unsuccessful outcomes. Risk factors for unsuccessful outcomes were being homeless, fluroquinolone resistance, having unknown HIV status, past TB treatment, male gender and being unemployed. Treatment outcomes and the interval from diagnosis to starting treatment were commendable. Further reductions in unsuccessful outcomes by be achieved through ensuring timely diagnosis and access to SL-DSTs and by reducing the proportion of people who are lost to follow-up.