Safety and Effectiveness of an All-Oral, Bedaquiline-Based, Shorter Treatment Regimen for Rifampicin-Resistant Tuberculosis in High Human Immunodeficiency Virus (HIV) Burden Rural South Africa: A Retrospective Cohort Analysis.

BACKGROUND: At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9-12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. METHODS: We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database. RESULTS: Our cohort included 117 patients; 68.4% (95% confidence interval [CI]: 59.3-76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50-57). Treatment success was achieved in 75.2% (95% CI: 66.5-82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8-20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range [IQR] 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8-34.5) of participants. CONCLUSIONS: An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs.

One Step Forward: Successful End-of-Treatment Outcomes of Patients With Drug-Resistant Tuberculosis Who Received Concomitant Bedaquiline and Delamanid in Mumbai, India.

BACKGROUND: The Médecins Sans Frontières Clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. METHODS: This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included. RESULTS: Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients. CONCLUSIONS: The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.

Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis.

BACKGROUND: HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. METHODS: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. FINDINGS: We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. INTERPRETATION: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Partner Notification Approaches for Sex Partners and Children of Human Immunodeficiency Virus Index Cases in Côte d'Ivoire.

BACKGROUND: Four partner notification approaches were introduced in health facilities in Côte d'Ivoire to increase human immunodeficiency virus (HIV) testing uptake among the type of contacts (sex partners and biological children younger than 15 years). The study assessed the 4 approaches: client referral (index cases refer the contacts for HIV testing), provider referral (health care providers refer the contacts), contract referral (index case-provider hybrid approach), and dual referral (both the index and their partner are tested simultaneously). METHODS: Program data were collected at 4 facilities from October 2018 to March 2019 from index case files and HIV testing register. We compared uptake of the approaches, uptake of HIV testing, and HIV positivity percentages, stratified by contact type and gender. RESULTS: There were 1089 sex partners and 469 children from 1089 newly diagnosed index cases. About 90% of children were contacted through client referral: 85.2% of those were tested and 1.4% was positive. Ninety percent of the children came from female index cases. The provider referral brought in 56.3% of sex partners, of whom 97.2% were HIV-tested. The client referral brought in 30% of sex partners, of whom only 81.5% were HIV-tested. The HIV positivity percentages were 75.5% and 72.7%, respectively, for the 2 approaches. Male index cases helped to reach twice as many HIV-positive sexual contacts outside the household (115) than female index cases (53). The contract and dual referrals were not preferred by index cases. CONCLUSIONS: Provider referral is a successful and acceptable strategy for bringing in sex partners for testing. Client referral is preferred for children.

Setting up a nurse-led model of care for management of hypertension and diabetes mellitus in a high HIV prevalence context in rural Zimbabwe: a descriptive study.

BACKGROUND: In the light of the increasing burden of non-communicable diseases (NCDs) on health systems in low- and middle-income countries, particularly in Sub-Saharan Africa, context-adapted, cost-effective service delivery models are now required as a matter of urgency. We describe the experience of setting up and organising a nurse-led Diabetes Mellitus (DM) and Hypertension (HTN) model of care in rural Zimbabwe, a low-income country with unique socio-economic challenges and a dual disease burden of HIV and NCDs. METHODS: Mirroring the HIV experience, we designed a conceptual framework with 9 key enablers: decentralization of services, integration of care, simplification of management guidelines, mentoring and task-sharing, provision of affordable medicines, quality assured laboratory support, patient empowerment, a dedicated monitoring and evaluation system, and a robust referral system. We selected 9 primary health care clinics (PHC) and two hospitals in Chipinge district and integrated DM and HTN either into the general out-patient department, pre-existing HIV clinics, or an integrated chronic care clinic (ICCC). We provided structured intensive mentoring for staff, using simplified protocols, and disease-specific education for patients. Free medication with differentiated periodic refills and regular monitoring with point of care (POC) glycosylated haemoglobin (HbA1c) were provided. RESULTS: Nurses in 7 PHC facilities and one hospital developed sufficient knowledge and skills to diagnose, initiate treatment and monitor DM and HTN patients, and 3094 patients were registered in the programme (188 with DM only, 2473 with HTN only, 433 with both DM and HTN). Major lessons learned from our experience include: the value of POC devices in the management of diabetes; the pressure on services of the added caseload, exacerbated by the availability of free medications in supported health facilities; and the importance of leadership in the successful implementation of care in health facilities. CONCLUSION: Our experience demonstrates a model for nurse-led decentralized integrated DM and HTN care in a high HIV prevalence rural, low-income context. Developing a context-adapted efficient model of care is a dynamic process. We present our lessons learned with the intention of sharing experience which may be of value to other public health programme managers.

Preparedness of outpatient health facilities for ambulatory treatment with all-oral short DR-TB treatment regimens in Zhytomyr, Ukraine: a cross-sectional study.

BACKGROUND: Ukraine has a high burden of drug-resistant tuberculosis (DR-TB). Mental health problems, including alcohol use disorder, are common co-morbidities. One in five DR-TB patients has human immunodeficiency virus (HIV). As part of health reform, the country is moving from inpatient care to ambulatory primary care for tuberculosis (TB). In Zhytomyr oblast, Médecins Sans Frontières (MSF) is supporting care for DR-TB patients on all-oral short DR-TB regimens. This study describes the preparedness of ambulatory care facilities in Zhytomyr oblast, Ukraine, to provide good quality ambulatory care. METHODS: This is a retrospective analysis of routinely collected programme data. Before discharge of every patient from the hospital, MSF teams assess services available at outpatient facilities using a standardised questionnaire. The assessment evaluates access, human resources, availability of medicines, infection control measures, laboratory and diagnostic services, and psychosocial support. RESULTS: We visited 68 outpatient facilities in 22 districts between June 2018 and September 2019. Twenty-seven health posts, 24 TB-units, 13 ambulatories, two family doctors and one polyclinic, serving 30% of DR-TB patients in the oblast by September 2019, were included. All facilities provided directly observed treatment, but only seven (10%) provided weekend-services. All facilities had at least one medical staff member, but TB-training was insufficient and mostly limited to TB-doctors. TB-treatment and adequate storage space were available in all facilities, but only five (8%) had ancillary medicines. HIV-positive patients had to visit a separate facility to access HIV-care. Personal protective equipment was unavailable in 32 (55%) facilities. Basic laboratory services were available in TB-units, but only four (17%) performed audiometry. Only ten (42%) TB-units had psychosocial support available, and nine (38%) offered psychiatric support. CONCLUSION: Outpatient facilities in Zhytomyr oblast are not yet prepared to provide comprehensive care for DR-TB patients. Capacity of all facilities needs strengthening with trainings, infection control measures and infrastructure. Integration of psychosocial services, treatment of co-morbidities and adverse events at the same facility are essential for successful decentralisation. The health reform is an opportunity to establish quality, patient-centred care.

Treatment Outcomes in Global Systematic Review and Patient Meta-Analysis of Children with Extensively Drug-Resistant Tuberculosis.

Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (<15 years of age) with bacteriologically confirmed XDR TB in 11 countries. These patients were managed during 1999-2013. For the 37 children, median age was 11 years, 32 (87%) had pulmonary TB, and 29 had a recorded HIV status; 7 (24%) were infected with HIV. Median treatment duration was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, 1 (3%) failed treatment, and 2 (5%) did not complete treatment. We found a high proportion of favorable treatment outcomes among children, with mortality rates markedly lower than for adults. Regimens and duration of treatment varied considerably. Evaluation of new regimens in children is required.

Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Are they there yet? Linkage of patients with tuberculosis to services for tobacco cessation and alcohol abuse - a mixed methods study from Karnataka, India.

BACKGROUND: Tobacco use and alcohol abuse are associated with higher risk of tuberculosis (TB) infection, progression to active TB and adverse treatment outcomes among patients with TB. Revised National Tuberculosis Control Programme (RNTCP) treatment guidelines (2016) require the documentation of tobacco and alcohol use among patients with TB and their linkage to tobacco and alcohol abuse treatment services. This study aimed to assess the extent of documentation of tobacco and alcohol usage data in the TB treatment card and to explore in-depth, the operational issues involved in linkage. METHODS: A convergent parallel mixed methods study was conducted. All new TB treatment cards of adult patients registered under RNTCP between January and June 2017 in Dakshina Kannada district were reviewed to assess documentation. Document review was done to understand the process of linkage (directing patients to tobacco and alcohol abuse treatment services). In-depth interview of health care providers (n = 7) and patients with TB (n = 5) explored into their perspectives on linkage. RESULTS: Among 413 treatment cards reviewed, tobacco use was documented in 322 (78%), of whom 86 (21%) were documented as current tobacco users. Sixteen (19%) out of these 86 patients were linked to tobacco cessation services. Alcohol usage status was documented in 319 (77%) cards of whom 71(17%) were documented as alcohol users. Eleven (16%) out of these 71 patients were linked to alcohol abuse treatment services. The questions in the treatment card lacked clarity. Guidelines on eliciting history of substance abuse and criteria for linkage were not detailed. Perceived enablers for linkage included family support, will power of the patients and fear of complications. Challenges included patient's lack of motivation, financial and time constraints, inadequate guidelines and lack of co-ordination mechanisms between TB programme and tobacco/alcohol abuse treatment services. CONCLUSION: Documentation was good but not universally done. Clear operational guidelines on linkage and treatment guidelines for health care providers to appropriately manage the patients with comorbidities are lacking. Lack of coordination between the TB treatment programme and tobacco cessation as well as alcohol treatment services was considered a major challenge in effective implementation of the linkage services.

Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis.

BACKGROUND: An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. METHODS AND FINDINGS: To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%-19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%-48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15-20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0-8.3, p = 0.041 and aOR 5.9, 95% CI 1.7-20.5, p = 0.007, respectively). These findings for high-dose isoniazid may have been affected by site effect, as the majority of patients came from Cape Town. Limitations of this study include the difficulty of estimating the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician's perception of illness, with resulting potential for bias. CONCLUSIONS: This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated.

Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa.

Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa.This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF).Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation >500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred.This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options.

Alarming prevalence and clustering of modifiable noncommunicable disease risk factors among adults in Bhutan: a nationwide cross-sectional community survey.

BACKGROUND: Bhutan is currently facing a double burden of non-communicable (NCDs) and communicable diseases, with rising trends of NCDs. The 2014 STEPS survey identified high prevalence of several NCD risk factors; however, associations with socio-demographic characteristics as well as clustering of risk factors were not assessed. This study aimed to determine the distribution and clustering of modifiable NCD risk factors among adults in Bhutan and their demographic and social determinants. METHODS: This was secondary analysis of data from NCD Risk Factors WHO STEPS Survey 2014 in Bhutan. A weighted analysis was conducted to calculate the prevalence of NCD risk factors, and associations were explored using weighted log-binomial regression models. RESULTS: This study included 2822 Bhutanese aged 18-69 years; 52% were 18-39 years, 62% were female, and 69% were rural resident. Prevalence of high salt intake, unhealthy diet and tobacco use were 99, 67 and 25% respectively. Raised blood pressure was the commonest (36%) modifiable biological risk factor followed by overweight (33%). The median NCD risk factors per person was 3 (Inter Quartile Range: 2-4); 52.5%% had > = 3 risk factors. A statistically significant difference was found between male vs. female in alcohol consumption(aPR 0.71, 95% CI: 0.53-0.97), low physical activity(aPR 2.06, 95% CI: 1.54-2.75), impaired fasting glycaemia(aPR 1.24, 95% CI: 1.01-1.52), and being overweight(aPR 1.46, 95% CI: 1.31-1.63). Low physical activity was more common among those with secondary and above education level vs. those without any formal education(aPR 1.71, 95% CI: 1.24-2.35), and among those residing in urban areas vs. those in rural(aPR 3.43, 95% CI: 2.27-5.18). Older participants and urban residents were more likely to have > = 3 NCD risk factors compared to younger(aPR 1.46, 95% CI: 1.35-1.58) and rural residents(aPR 1.21, 95% CI: 1.10-1.32). CONCLUSION: Lifestyle modifications at the population level are urgently required in Bhutan as several NCD risk factors such as high salt intake, unhealthy diet, overweight, and high blood pressure were alarmingly high and frequently clustered. Moreover there is a need to consider policy and socio-political and economic factors that have undermined global and national progress to address the rise of NCDs and their risk factors in Bhutan as elsewhere.

Effect of previous utilization and out-of-pocket expenditure on subsequent utilization of a state led public-private partnership scheme "Chiranjeevi Yojana" to promote facility births in Gujarat, India.

BACKGROUND: In Gujarat, India, a state led public private partnership scheme to promote facility birth named Chiranjeevi Yojana (CY) was implemented in 2005. Institutional birth is provided free of cost at accredited private health facilities to women from socially disadvantaged groups (eligible women). CY has contributed in increasing facility birth and providing substantially subsidized (but not totally free) birth care; however, the retention of mothers in this scheme in subsequent child birth is unknown. Therefore, we conducted a study aimed to determine the effect of previous utilization of the scheme and previous out of pocket expenditure on subsequent child birth among multiparous eligible women in Gujarat. METHODS: This was a retrospective cohort study of multiparous eligible women (after excluding abortions and births at public facility). A structured questionnaire was administered by trained research assistant to those with recent delivery between Jan and Jul 2013. Outcome of interest was CY utilization in subsequent child birth (Jan-Jul 2013). Explanatory variables included socio-demographic characteristics (including category of eligibility), pregnancy related characteristics in previous child birth, before Jan 2013, (including CY utilization, out of pocket expenditure) and type of child birth in subsequent birth. A poisson regression model was used to assess the association of factors with CY utilization in subsequent child birth. RESULTS: Of 997 multiparous eligible women, 289 (29%) utilized and 708 (71%) did not utilize CY in their previous child birth. Of those who utilized CY (n = 289), 182 (63%) subsequently utilized CY and 33 (11%) gave birth at home; whereas those who did not utilize CY (n = 708) had four times higher risk (40% vs. 11%) of subsequent child birth at home. In multivariable models, previous utilization of the scheme was significantly associated with subsequent utilization (adjusted Relative Risk (aRR): 2.7; 95% CI: 2.2-3.3), however previous out of pocket expenditure was not found to be associated with retention in the CY scheme. CONCLUSION: Women with previous CY utilization were largely retained; therefore, steps to increase uptake of CY are expected to increase retention of mothers within CY in their subsequent child birth. To understand the reasons for subsequent child birth at home despite previous CY utilization and previous zero/minimal out of pocket expenditure, future research in the form of systematic qualitative enquiry is recommended.

Infection Control for Drug-Resistant Tuberculosis: Early Diagnosis and Treatment Is the Key.

Multidrug-resistant (MDR) tuberculosis, "Ebola with wings," is a significant threat to tuberculosis control efforts. Previous prevailing views that resistance was mainly acquired through poor treatment led to decades of focus on drug-sensitive rather than drug-resistant (DR) tuberculosis, driven by the World Health Organization's directly observed therapy, short course strategy. The paradigm has shifted toward recognition that most DR tuberculosis is transmitted and that there is a need for increased efforts to control DR tuberculosis. Yet most people with DR tuberculosis are untested and untreated, driving transmission in the community and in health systems in high-burden settings. The risk of nosocomial transmission is high for patients and staff alike. Lowering transmission risk for MDR tuberculosis requires a combination approach centered on rapid identification of active tuberculosis disease and tuberculosis drug resistance, followed by rapid initiation of appropriate treatment and adherence support, complemented by universal tuberculosis infection control measures in healthcare facilities. It also requires a second paradigm shift, from the classic infection control hierarchy to a novel, decentralized approach across the continuum from early diagnosis and treatment to community awareness and support. A massive scale-up of rapid diagnosis and treatment is necessary to control the MDR tuberculosis epidemic. This will not be possible without intense efforts toward the implementation of decentralized, ambulatory models of care. Increasing political will and resources need to be accompanied by a paradigm shift. Instead of focusing on diagnosed cases, recognition that transmission is driven largely by undiagnosed, untreated cases, both in the community and in healthcare settings, is necessary. This article discusses this comprehensive approach, strategies available, and associated challenges.

Utilization of the state led public private partnership program "Chiranjeevi Yojana" to promote facility births in Gujarat, India: a cross sectional community based study.

BACKGROUND: "Chiranjeevi Yojana (CY)", a state-led large-scale demand-side financing scheme (DSF) under public-private partnership to increase institutional delivery, has been implemented across Gujarat state, India since 2005. The scheme aims to provide free institutional childbirth services in accredited private health facilities to women from socially disadvantaged groups (eligible women). These services are paid for by the state to the private facility with the intention of service being free to the user. This community-based study estimates CY uptake among eligible women and explores factors associated with non-utilization of the CY program. METHODS: This was a community-based cross sectional survey of eligible women who gave birth between January and July 2013 in 142 selected villages of three districts in Gujarat. A structured questionnaire was administered by trained research assistant to collect information on socio-demographic details, pregnancy details, details of childbirth and out-of-pocket (OOP) expenses incurred. A multivariable inferential analysis was done to explore the factors associated with non-utilization of the CY program. RESULTS: Out of 2,143 eligible women, 559 (26 %) gave birth under the CY program. A further 436(20 %) delivered at free public facilities, 713(33 %) at private facilities (OOP payment) and 435(20 %) at home. Eligible women who belonged to either scheduled tribe or poor [aOR = 3.1, 95 % CI:2.4 - 3.8] or having no formal education [aOR = 1.6, 95 % CI:1.1, 2.2] and who delivered by C-section [aOR = 2.1,95 % CI: 1.2, 3.8] had higher odds of not utilizing CY program. Of births at CY accredited facilities (n = 924), non-utilization was 40 % (n = 365) mostly because of lack of required official documentation that proved eligibility (72 % of eligible non-users). Women who utilized the CY program overall paid more than women who delivered in the free public facilities. CONCLUSION: Uptake of the CY among eligible women was low after almost a decade of implementation. Community level awareness programs are needed to increase participation among eligible women. OOP expense was incurred among who utilized CY program; this may be a factor associated with non-utilization in next pregnancy which needs to be studied. There is also a need to ensure financial protection of women who have C-section.

Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India.

BACKGROUND: There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen. METHODS: This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART). RESULTS: 102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4-18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse. CONCLUSIONS: In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients.

Caseload, management and treatment outcomes of patients with hypertension and/or diabetes mellitus in a primary health care programme in an informal setting.

OBJECTIVE: In three primary health care clinics run by Médecins Sans Frontières in the informal settlement of Kibera, Nairobi, Kenya, we describe the caseload, management and treatment outcomes of patients with hypertension (HT) and/or diabetes mellitus (DM) receiving care from January 2010 to June 2012. METHOD: Descriptive study using prospectively collected routine programme data. RESULTS: Overall, 1465 patients were registered in three clinics during the study period, of whom 87% were hypertensive only and 13% had DM with or without HT. Patients were predominantly female (71%) and the median age was 48 years. On admission, 24% of the patients were obese, with a body mass index (BMI) > 30 kg/m2. Overall, 55% of non-diabetic hypertensive patients reached their blood pressure (BP) target at 24 months. Only 28% of diabetic patients reached their BP target at 24 months. For non-diabetic patients, there was a significant decrease in BP between first consultation and 3 months of treatment, maintained over the 18-month period. Only 20% of diabetic patients with or without hypertension achieved glycaemic control. By the end of the study period,1003 (68%) patients were alive and in care, one (<1%) had died, eight (0.5%) had transferred out and 453 (31%) were lost to follow-up. CONCLUSION: Good management of HT and DM can be achieved in a primary care setting within an informal settlement. This model of intervention appears feasible to address the growing burden of non-communicable diseases in developing countries.

Correction: Prevalence and risk factors for hepatitis C virus infection in an informal settlement in Karachi, Pakistan.

[This corrects the article DOI: 10.1371/journal.pgph.0002076.].

Correction: Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

[This corrects the article DOI: 10.1371/journal.pone.0264442.].