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Abstract Background Retrospective and descriptive molecular epidemiology studies have shown that Mycobacterium tuberculosis whole genome sequencing can identify outbreaks and disease transmission events with higher resolution than conventional epidemiological investigations. Those studies have strengthened our understanding of genomic polymorphisms correlating with person-to-person transmission and helped resolve putative transmission clusters. To date, systematic genomic surveillance programs implemented for M. tuberculosis were only implemented in low-incidence settings. The purpose of this study is to determine whether there is an impact of routine M. tuberculosis whole genome sequencing on tuberculosis case detection in a high-incidence setting. Methods A cluster randomized controlled trial will be performed. Forty-eight rural village groups (or Fokontany) in the Vohibato district of Madagascar will be randomized to one of three interventions arms. Arm 1 (standard of care) involves healthcare facility-based passive case detection with smear microscopy testing. Arm 2 (best practice) consists of active case finding and Xpert MTB/RIF Ultra PCR testing followed by household contact investigations. Arm 3 (novel intervention) includes the same interventions as arm 2, with addition of sputum culture and M. tuberculosis whole genome sequencing for all newly diagnosed cases. In arm 3, molecular suggested putative outbreaks are investigated, and additional TB suspects are appropriately tested. The intervention observational period will be 2 years. The primary outcome will be the number of detected cases/100,000/year in each arm after 1 year of intervention. Discussion This study is designed to determine whether there is an impact of prospective whole genome sequencing-based molecular typing on tuberculosis case detection in high-incidence settings. Investigating potential outbreaks and focusing active case finding in spatiotemporal settings where disease transmission is suggested by genomic typing is hypothesized to improve case detection in rural communities. Trial registration ClinicalTrials.gov NCT05406453 . Retrospectively registered on June 6, 2022.

Abstract Not receiving a DPT-containing vaccine in early childhood indicates an absence of routine immunization, which puts children at an elevated risk of mortality, morbidity, and worse human development over the life course. We estimated the percentage of children 12–35 months who did not receive a dose of DPT-containing vaccine (termed zero-dose children) using household surveys from 81 low- and middle-income countries conducted between 2014 and 2023. For 68 countries with more than one survey (with the earlier survey conducted 2000–2013), we estimated the average annual percentage point change in prevalence of zero-dose children between the earliest and latest surveys. We also explored the association of zero-dose prevalence with postneonatal and child mortality, health expenditure, and Gavi-eligibility. Overall, 16% of children in our pooled sample had not received a dose of DPT-containing vaccine. There was a 0.8% point decline in zero-dose prevalence per year on average across the period studied. A single percentage point average annual decline in zero-dose prevalence was associated with an average annual decrease of 1.4 deaths in the postneonatal and childhood period per 1000 live births. Gavi-eligible countries had a much faster decline in zero-dose prevalence than other countries. Large gains have been made in reducing the percentage of children who did not receive a DPT-containing vaccine. Efforts to reduce the number of zero-dose children should focus on countries with high prevalence to achieve the Immunization Agenda 2030. Healthcare spending could be prioritized so that the prevalence of zero-dose children is reduced.

Objective Cluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time.Design A systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews.Data sources We searched MEDLINE between 1 January 2017 and 17 August 2022.Eligibility criteria for selecting studies We included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022.Data extraction and synthesis Data were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country’s economic level or publication year.Results Among 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country’s economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time.Conclusion Our findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed.

Promotive social protection programs aim to increase income and capabilities and could help address structural drivers of HIV-vulnerability like poverty, lack of education and gender inequality. Unemployed and out-of-school young women bear the brunt of HIV infection in Botswana, but rarely benefit from such economic empowerment programs. Using a qualitative exploratory study design and a participatory research approach, we explored factors affecting perceived program benefit and potential solutions to barriers. Direct stakeholders (n = 146) included 87 unemployed and out-of-school young women and 59 program and technical officers in five intervention districts. Perceived barriers were identified in 20 semi-structured interviews (one intervention district) and 11 fuzzy cognitive maps. Co-constructed improvement recommendations were generated in deliberative dialogues. Analysis relied on Framework and the socioecological model. Overall, participants viewed existing programs in Botswana as ineffective and inadequate to empower vulnerable young women socially or economically. Factors affecting perceived program benefit related to programs, program officers, the young women, and their social and structural environment. Participants perceived barriers at every socioecological level. Young women's lack of life and job skills, unhelpful attitudes, and irresponsible behaviors were personal-level barriers. At an interpersonal level, competing care responsibilities, lack of support from boyfriends and family, and negative peer influence impeded program benefit. Traditional venues for information dissemination, poverty, inequitable gender norms, and lack of coordination were community- and structural-level barriers. Improvement recommendations focused on improved outreach and peer approaches to implement potential solutions. Unemployed and out-of-school young women face multidimensional, interacting barriers that prevent benefit from available promotive social protection programs in Botswana. To become HIV-sensitive, these socioeconomic empowerment programs would need to accommodate or preferentially attract this key population. This requires more generous and comprehensive programs, a more client-centered program delivery, and improved coordination. Such structural changes require a holistic, intersectoral approach to HIV-sensitive social protection.

The study explored women's experiences of their community reintegration process after surgical repair of obstetric fistula at Jean Paul 2 Hospital in Conakry, Guinea. The study examined how lived experiences of the disease impacted on the community reintegration of treated women. Using a qualitative research methodology, ten women participated after giving informed consent. Semi- structured interviews, lasting an average of 30 to 60 minutes were guided by an interview guide. The main themes covered were experiences with the disease, perceived social support and reintegration into the community. According to the participants, delays in obstetric care were the main cause of obstetric fistula. Socio- economic, cultural and medical factors such as early marriage, lack of education and poverty contributed to these delays. Even after surgical repair, women continued to endure the physical and psychosocial consequences of the disease, exposing them to stigma, discrimination and even rejection within the community. Study participants also reported a lack of social support. The little support perceived by these women concerned food and medical needs. This made the women dependent on their families. Reintegration into the community also proved difficult due to the persistent silence and stigma surrounding their situation. The study results highlight the complexity of the challenges faced by women with obstetric fistula in their journey towards integration. Effective management of obstetric fistula requires a holistic approach victims, their communities, health professionals and decision-makers in solving this problem. So, to improve women's reintegration after treatment for obstetric fistula, it is vital to raise awareness of the causes and consequences of the disease among the women concerned and their families, and to provide rapid access to emergency obstetric care, reinforce social support and set up economic empowerment programs.

Introduction ‘Zero-dose’ children (infants who fail to receive the first dose of diphtheria-tetanus-pertussis-containing vaccine) face substantial adversity in early childhood and may be at risk of failure to thrive. To inform a new global policy, we studied the relationship between zero-dose vaccination status in early childhood and learning attainment in preadolescence, and considered whether community socioeconomic development moderated these relationships.Methods We constructed a population cohort from the 2019 India Human Development Survey panel dataset to study the comparative performance of zero-dose versus vaccinated children identified in wave I (2004–2005) on basic learning tests at ages 8–11 in wave II (2011–2012). The outcome was a sum of reading, writing and math scores ranging from 0 (no knowledge) to 8. We fit three linear regression models examining whether child zero-dose status predicts learning attainment: a crude model, a main effects model including all prespecified covariates, and a model including an interaction between child zero-dose status and community development level.Results The analytic sample included 3781 children from 3781 households in 1699 communities, representing 18.2 million children. Predicted learning attainment scores for zero-dose children were lower than those for vaccinated children by −1.698 (95% CI −2.02 to −1.37; p

Objective. To document the evolution of socioeconomic and geographical inequalities in childhood vaccination in Mexico from 2012 to 2021. Methods. Repeated cross-sectional analysis using three rounds of National Health and Nutrition Surveys (2012, 2018, and 2021). Dichotomous variables were created to identify the proportion of children who received no dose of each vaccine included in the national immunization schedule (BCG; diphtheria, pertussis, and tetanus-containing; rotavirus; pneumococcal conjugate; and measles, mumps, and rubella [MMR]), and the proportion completely unvaccinated. The distribution of unvaccinated children was analyzed by state, and by socioeconomic status using the concentration index. Results. The prevalence of completely unvaccinated children in Mexico was low, with 0.3% children in 2012 and 0.8% children in 2021 receiving no vaccines (p = 0.070). Notwithstanding, for each vaccine, an important proportion of children missed receiving any dose. Notably, the prevalence of MMR unvaccinated children was 10.2% (95% CI 9.2–11.1) in 2012, 22.3% (95% CI 20.9–23.8) in 2018, and 29.1% (95% CI 26.3–31.8) in 2021 (p < 0.001 for the difference between 2012 and 2021). The concentration index indicated pro-rich inequalities in non-vaccination for 2 of 5 vaccines in 2012, 3 of 5 vaccines in 2018, and 4 of 5 vaccines in 2021. There were marked subnational variations. The percentage of MMR unvaccinated children ranged from 3.3% to 17.9% in 2012, 5.5% to 36.5% in 2018, and 13.1% to 72.5% in 2021 across the 32 states of Mexico. Conclusions. Equitable access to basic childhood vaccines in Mexico has deteriorated over the past decade. Vigilant equity monitoring coupled with tailored strategies to reach those left out is urgently required.

Poverty, lack of education and gender inequality make unemployed and out-of-school young women extremely vulnerable to HIV infection. Promotive social protection programmes aim to increase livelihood and capabilities and could empower this priority population to act on HIV prevention choices. In Botswana, they rarely benefit from such programmes. A modified Policy Delphi engaged a panel of 22 unemployed and out-of-school young women and eight frontline service providers to consider alternative policy and practice options, and tailor available programmes to their own needs and social situation. The panel assessed the desirability and feasibility of improvement proposals and, in a second round, ranked them for relative importance. Nearly all 40 improvement proposals were considered very desirable and definitely, or possibly, feasible, and panellists prioritised a wide range of proposals. Frontline service providers stressed foundational skills, like life skills and second chance education. Young women preferred options with more immediate benefits. Overall, panellists perceived positive role models for programme delivery, access to land and water, job skills training, and stipends as most important to empower HIV-vulnerable young women. Results suggest ample policy space to make existing social protection programmes in Botswana more inclusive of unemployed and out-of-school young women, hence more HIV-sensitive.

Abstract Background The Tika Vaani intervention, an initiative to improve basic health knowledge and empower beneficiaries to improve vaccination uptake and child health for underserved rural populations in India, was assessed in a pilot cluster randomized trial. The intervention was delivered through two strategies: mHealth (using mobile phones to send vaccination reminders and audio-based messages) and community mobilization (face-to-face meetings) in rural Indian villages from January to September 2018. We assessed acceptability and implementation fidelity to determine whether the intervention delivered in the pilot trial can be implemented at a larger scale. Methods We adapted the Conceptual Framework for implementation fidelity to assess acceptability and fidelity of the pilot interventions using a mixed methods design. Quantitative data sources include a structured checklist, household surveys, and mobile phone call patterns. Qualitative data came from field observations, intervention records, semi-structured interviews and focus groups with project recipients and implementers. Quantitative analyses assessed whether activities were implemented as planned, using descriptive statistics to describe participant characteristics and the percentage distribution of activities. Qualitative data were analyzed using content analysis and in the light of the implementation fidelity model to explore moderating factors and to determine how well the intervention was received. Results Findings demonstrated high (86.7%) implementation fidelity. A total of 94% of the target population benefited from the intervention by participating in a face-to-face group meeting or via mobile phone. The participants felt that the strategies were useful means for obtaining information. The clarity of the intervention theory, the motivation, and commitment of the implementers as well as the periodic meetings of the supervisors largely explain the high level of fidelity obtained. Geographic distance, access to a mobile phone, level of education, and gender norms are contextual factors that contributed to heterogeneity in participation. Conclusions Although the intervention was evaluated in the context of a randomized trial that could explain the high level of fidelity obtained, this evaluation provides confirmatory evidence that the results of the study reflect the underlying theory. The mobile platform coupled with community mobilization was well-received by the participants and could be a useful way to improve health knowledge and change behavior. Trial registration ISRCTN 44840759 (22 April 2018)

Abstract Background Social, behavioural and community engagement (SBCE) interventions are essential for global maternal, newborn and child health (MNCH) strategies. Past efforts to synthesise research on SBCE interventions identified a need for clear priorities to guide future research. WHO led an exercise to identify global research priorities for SBCE interventions to improve MNCH. Methods We adapted the Child Health and Nutrition Research Initiative method and combined quantitative and qualitative methods to determine MNCH SBCE intervention research priorities applicable across different contexts. Using online surveys and meetings, researchers and programme experts proposed up to three research priorities and scored the compiled priorities against four criteria – health and social impact, equity, feasibility, and overall importance. Priorities were then ranked by score. A group of 29 experts finalised the top 10 research priorities for each of maternal, newborn or child health and a cross-cutting area. Results A total of 310 experts proposed 867 research priorities, which were consolidated into 444 priorities and scored by 280 experts. Top maternal and newborn health priorities focused on research to improve the delivery of SBCE interventions that strengthen self-care/family care practices and care-seeking behaviour. Child health priorities focused on the delivery of SBCE interventions, emphasising determinants of service utilisation and breastfeeding and nutrition practices. Cross-cutting MNCH priorities highlighted the need for better integration of SBCE into facility-based and community-based health services. Conclusions Achieving global targets for MNCH requires increased investment in SBCE interventions that build capacities of individuals, families and communities as agents of their own health. Findings from this exercise provide guidance to prioritise investments and ensure that they are best directed to achieve global objectives. Stakeholders are encouraged to use these priorities to guide future research investments and to adapt them for country programmes by engaging with national level stakeholders.

Reaching zero-dose (ZD) children, operationally defined as children who have not received a first dose of the diphtheria, tetanus, and pertussis (DTP1) vaccine, is crucial to increase equitable immunisation coverage and access to primary health care. However, little is known about the approaches already taken by countries to improve immunisation equity. We reviewed all Health System Strengthening (HSS) proposals submitted by Gavi-supported countries from 2014 to 2021 inclusively and extracted information on interventions favouring equity. Pro-equity interventions were mapped to an analytical framework representing Gavi 5.0 programmatic guidance on reaching ZD children and missed communities. Data from keyword searches and manual screening were extracted into an Excel database. Open format responses were analysed using inductive and deductive thematic coding. Data analysis was conducted using Excel and R. Of the 56 proposals included, 51 (91%) included at least one pro-equity intervention. The most common interventions were conducting outreach sessions, tailoring the location of service delivery, and partnerships. Many proposals had “bundles” of interventions, most often involving outreach, microplanning and community-level education activities. Nearly half prioritised remote-rural areas and only 30% addressed gender-related barriers to immunisation. The findings can help identify specific interventions on which to focus future evidence syntheses, case studies and implementation research and inform discussions on what may or may not need to change to better reach ZD children and missed communities moving forward.

Summary: Background: Reaching zero-dose children (infants who receive no routine vaccinations) is a global strategic priority. We studied zero-dose children in India over 24 years to clarify aggregate trends and the contribution of large-scale social, economic, and geographical inequalities to these. Methods: We did a multilevel, geospatial analysis of repeated cross-sectional surveys of all four rounds (1992–2016) of India's National Family Health Survey to study the prevalence, distribution, and drivers of zero-dose (no first dose of diphtheria, tetanus, and pertussis) vaccination status. We included all children born to participating women who were aged 12–23 months at the time of the survey, as this is the standard age at which immunisation data are assessed. Children who died before the survey and those missing data on key outcomes or correlates were excluded. The outcome was child zero-dose vaccination status. We also compared the prevalence of nutritional deficits among zero-dose versus vaccinated children. For the most recent survey, we produced geospatial estimates identifying the prevalence of zero-dose children across states and districts and used these to project head count. Findings: We examined 393 167 children for eligibility. 72 848 children were included in the final analytic data set. The proportion of zero-dose children in India declined from 33·4% (95% CI 32·5–34·2) in 1992 to 10·1% (9·8–10·4) in 2016. Progress notwithstanding, in 2016, zero-dose children remained concentrated among disadvantaged groups (prevalence in the bottom wealth quintile 15·3%, 95% CI 14·6–16·0; prevalence among mothers with no education 16·8%, 16·1–17·4). Compared with vaccinated children, zero-dose children were more likely to suffer from malnutrition in all survey rounds (prevalence of severe stunting in 1992: zero dose 41·3%, 95% CI 39·2–43·8 vs vaccinated 28·5%, 27·2–29·7; 2016: zero dose 24·9%, 23·6–26·2 vs vaccinated 18·7%, 18·3–19·1). In 2016, there were an estimated 2·88 (95% CI 2·86–2·89) million zero-dose children in India, concentrated in less developed states and districts and several urban areas. Interpretation: Over a 24-year period in India, child zero-dose status was shaped by large-scale social inequalities and remained a consistent marker of generalised vulnerability. Interventions that address this cycle of intergenerational inequities should be prioritised. Funding: None. Translations: For the French, Spanish, and Hindi translations of the abstract see Supplementary Materials section.

Background: Global immunization inequities persist, reflected in the 25 million underimmunized and 18 million zero-dose children in 2021. To identify country approaches to reach underimmunized and zero-dose children, we undertook a structured synthesis of pro-equity strategies across 61 countries receiving programmatic support from Gavi, the Vaccine Alliance. Methods: We extracted data from 174 Country Joint Appraisals and Multi-Stakeholder Dialogue reports (2016–2020). We identified strategies via a targeted keyword search, informed by a determinants of immunization coverage framework. Strategies were synthesized into themes consolidated from UNICEF’s Journey to Health and Immunization (JTHI) and the Global Routine Immunization Strategies and Practices (GRISP) frameworks. Results: We found 607 unique strategies across 61 countries and 24 themes. Strategies to improve care at the point of service (44%); to improve knowledge, awareness and beliefs (25%); and to address preparation, cost and effort barriers (13%) were common. Fewer strategies targeted experience of care (8%), intent, (7%) and after-service (3%). We also identified strategies addressing gender-related barriers to immunization and targeting specific types of communities. Conclusions: We summarize the range of pro-equity immunization strategies employed in Gavi-supported countries and interpret them thematically. Findings are incorporated into a searchable database which can be used to inform equity-driven immunization programs, policies and decision-making which target underimmunized and zero-dose communities.

Abstract Introduction Social protection programmes are considered HIV‐sensitive when addressing risk, vulnerability or impact of HIV infection. Socio‐economic interventions, like livelihood and employability programmes, address HIV vulnerabilities like poverty and gender inequality. We explored the HIV‐sensitivity of socio‐economic interventions for unemployed and out‐of‐school young women aged 15 to 30 years, in East and Southern Africa, a key population for HIV infection. Methods We conducted a systematic review using a narrative synthesis method and the Mixed Methods Appraisal Tool for quality appraisal. Interventions of interest were work skills training, microfinance, and employment support. Outcomes of interest were socio‐economic outcomes (income, assets, savings, skills, (self‐) employment) and HIV‐related outcomes (behavioural and biological). We searched published and grey literature (January 2005 to November 2019; English/French) in MEDLINE, Scopus, Web of Science and websites of relevant international organizations. Results We screened 3870 titles and abstracts and 188 full‐text papers to retain 18 papers, representing 12 projects. Projects offered different combinations of HIV‐sensitive social protection programmes, complemented with mentors, safe space and training (HIV, reproductive health and gender training). All 12 projects offered work skills training to improve life and business skills. Six offered formal (n = 2) or informal (n = 5) livelihood training. Eleven projects offered microfinance, including microgrants (n = 7), microcredit (n = 6) and savings (n = 4). One project offered employment support in the form of apprenticeships. In general, microgrants, savings, business and life skills contributed improved socio‐economic and HIV‐related outcomes. Most livelihood training contributed positive socio‐economic outcomes, but only two projects showed improved HIV‐related outcomes. Microcredit contributed little to either outcome. Programmes were effective when (i) sensitive to beneficiaries' age, needs, interests and economic vulnerability; (ii) adapted to local implementation contexts; and (iii) included life skills. Programme delivery through mentorship and safe space increased social capital and may be critical to improve the HIV‐sensitivity of socio‐economic programmes. Conclusions A wide variety of livelihood and employability programmes were leveraged to achieve improved socio‐economic and HIV‐related outcomes among unemployed and out‐of‐school young women. To be HIV‐sensitive, programmes should be designed around their interests, needs and vulnerability, adapted to local implementation contexts, and include life skills. Employment support received little attention in this literature.

Abstract Background Village Health and Nutrition Days (VHNDs) are a cornerstone of the Government of India’s strategy to provide first-contact primary health care to rural areas. Recent government programmes such as the Janani Suraksha Yojana (JSY) and Mission Indradhanush (MI) have catalysed important changes impacting VHNDs. To learn how VHNDs are currently being delivered, we assessed the fidelity of services provided as compared to government norms in a priority district of Uttar Pradesh. Methods We fielded a cross-sectional study of VHNDs to provide a snapshot of health services functioning. Process evaluation data were collected via administrative sources, non-participant observation using a standardised form, and structured questionnaires. Questionnaires were designed using a framework to assess implementation fidelity. Key respondents were VHND participants, front-line workers involved in VHND delivery, and VHND non-participants (pregnant women due for antenatal care or children due for vaccination as per administrative records). Results were summarised as counts, frequencies, and proportions. Results In the 30 villages randomly selected for inclusion, 36 VHNDs were scheduled but four (11.1%) were cancelled and one VHND was not surveyed. Vaccination and antenatal care were offered at 96.8% (30/31) and child weighing at 83.9% (26/31) of VHNDs. Other normed services were infrequently provided or completely absent. Health education and promotion were particularly weak; institutional delivery was the only topic discussed in a majority of VHNDs. The true proportion of any serious problem impeding vaccine delivery was 47.2% (17/36), comprising 4 VHND cancellations and 13 VHNDs experiencing vaccine shortages. Of the 13 incidents of vaccine shortage, 11 related to an unexpected global shortage of injectable polio vaccine (IPV). Over the 31 VHNDs, 37.8% (171 of the 452 scheduled beneficiaries) did not participate. Analysis of missed opportunities for vaccination highlighted inaccuracies in beneficiary identification and tracking and demand side-factors. Conclusions The transformative potential of VHNDs to improve population health is only partially being met. A core subset of high-priority services for antenatal care, institutional delivery, and vaccination associated with high-priority government programmes (JSY, MI) is now being provided quite successfully. Other basic health promotion and prevention services are largely not provided, constituting a critical missed opportunity.

Abstract Background Cluster randomised trials (CRTs) are a key instrument to evaluate public health interventions. Fidelity assessment examines study processes to gauge whether an intervention was delivered as initially planned. Evaluation of implementation fidelity (IF) is required to establish whether the measured effects of a trial are due to the intervention itself and may be particularly important for CRTs of complex interventions conducted in low- and middle-income countries (LMICs). However, current CRT reporting guidelines offer no guidance on IF assessment. The objective of this review was to study current practices concerning the assessment of IF in CRTs of public health interventions in LMICs. Methods CRTs of public health interventions in LMICs that planned or reported IF assessment in either the trial protocol or the main trial report were included. The MEDLINE/PubMed, CINAHL and EMBASE databases were queried from January 2012 to May 2016. To ensure availability of a study protocol, CRTs reporting a registration number in the abstract were included. Relevant data were extracted from each study protocol and trial report by two researchers using a predefined screening sheet. Risk of bias for individual studies was assessed. Results We identified 90 CRTs of public health interventions in LMICs with a study protocol in a publicly available trial registry published from January 2012 to May 2016. Among these 90 studies, 25 (28%) did not plan or report assessing IF; the remaining 65 studies (72%) addressed at least one IF dimension. IF assessment was planned in 40% (36/90) of trial protocols and reported in 71.1% (64/90) of trial reports. The proportion of overall agreement between the trial protocol and trial report concerning occurrence of IF assessment was 66.7% (60/90). Most studies had low to moderate risk of bias. Conclusions IF assessment is not currently a systematic practice in CRTs of public health interventions carried out in LMICs. In the absence of IF assessment, it may be difficult to determine if CRT results are due to the intervention design, to its implementation, or to unknown or external factors that may influence results. CRT reporting guidelines should promote IF assessment. Trial Registration Protocol published and available at: https://doi.org/10.1186/s13643-016-0351-0

Abstract Background Decreasing trends in measles mortality have been reported in recent years. However, such estimates of measles mortality have depended heavily on assumed regional measles case fatality risks (CFRs) and made little use of mortality data from low- and middle-income countries in general and India, the country with the highest measles burden globally, in particular. Methods We constructed a dynamic model of measles transmission in India with parameters that were empirically inferred using spectral analysis from a time series of measles mortality extracted from the Million Death Study, an ongoing longitudinal study recording deaths across 2.4 million Indian households and attributing causes of death using verbal autopsy. The model was then used to estimate the measles CFR, the number of measles deaths, and the impact of vaccination in 2000–2015 among under-five children in India and in the states of Bihar and Uttar Pradesh (UP), two states with large populations and the highest numbers of measles deaths in India. Results We obtained the following estimated CFRs among under-five children for the year 2005: 0.63% (95% confidence interval (CI): 0.40–1.00%) for India as a whole, 0.62% (0.38–1.00%) for Bihar, and 1.19% (0.80–1.75%) for UP. During 2000–2015, we estimated that 607,000 (95% CI: 383,000–958,000) under-five deaths attributed to measles occurred in India as a whole. If no routine vaccination or supplemental immunization activities had occurred from 2000 to 2015, an additional 1.6 (1.0–2.6) million deaths for under-five children would have occurred across India. Conclusions We developed a data- and model-driven estimation of the historical measles dynamics, CFR, and vaccination impact in India, extracting the periodicity of epidemics using spectral and coherence analysis, which allowed us to infer key parameters driving measles transmission dynamics and mortality.

Abstract Background Widespread increases in caesarean section (CS) rates have sparked concerns about risks to mothers and infants and rising healthcare costs. A multicentre, two-arm, cluster-randomized trial in Quebec, Canada assessed whether an audit and feedback intervention targeting health professionals would reduce CS rates for pregnant women compared to usual care, and concluded that it reduced CS rates without adverse effects on maternal or neonatal health. The effect was statistically significant but clinically small. We assessed cost-effectiveness to inform scale-up decisions. Methods A prospective economic evaluation was undertaken using individual patient data from the Quality of Care, Obstetrics Risk Management, and Mode of Delivery (QUARISMA) trial (April 2008 to October 2011). Analyses took a healthcare payer perspective. The time horizon captured hospital-based costs and clinical events for mothers and neonates from labour onset to 3 months postpartum. Resource use was identified and measured from patient charts and valued using standardized government sources. We estimated the changes in CS rates and costs for the intervention group (versus controls) between the baseline and post-intervention periods. We examined heterogeneity between clinical subgroups of high-risk versus low-risk pregnancies and estimated the joint uncertainty in cost-effectiveness over 20,000 trial simulations. We decomposed costs to identify drivers of change. Results The intervention group experienced per-patient reductions of 0.005 CS (95% confidence interval (CI): −0.015 to 0.004, P = 0.09) and $180 (95% CI: −$277 to − $83, P

Objective: To determine whether an intervention based on patient-practitioner communication is more effective than usual care in improving diabetes self-management in patients with type 2 diabetes with low educational level. Methods: 12-month, pragmatic cluster randomised controlled trial. Nine physicians and 184 patients registered at two practices in a deprived area of Granada (Andalusia, Spain) participated in the study. Adult patients with type 2 diabetes, low educational level and glycated haemoglobin (HbA1c) > 7% (53.01 mmol/mol) were eligible. The physicians in the intervention group received training on communication skills and the use of a tool for monitoring glycaemic control and providing feedback to patients. The control group continued standard care. The primary outcome was difference in HbA1c after 12 months. Dyslipidaemia, blood pressure, body mass index and waist circumference were also assessed as secondary outcomes. Two-level (patient and provider) regression analyses controlling for sex, social support and comorbidity were conducted. Results: The HbA1c levels at 12 months decreased in both groups. Multilevel analysis showed a greater improvement in the intervention group (between-group HbA1c difference= 0.16; p = 0.049). No statistically significant differences between groups were observed for dyslipidaemia, blood pressure, body mass index and waist circumference. Conclusions: In this pragmatic study, a simple and inexpensive intervention delivered in primary care showed a modest benefit in glycaemic control compared with usual care, although no effect was observed in the secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients.

Resumen Objetivo: investigar qué estrategias para aumentar la demanda de vacunación son efectivas a la hora de incrementar la cobertura de vacunación infantil en países de ingresos bajos y medios. Metodología: se realizaron búsquedas en las bases de datos de MEDLINE, EMBASE, Cochrane Library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science y Scopus para encontrar estudios pertinentes, publicados en alemán, español, francés, hindi, inglés y portugués hasta el 25 de marzo de 2014. Se incluyeron estudios de intervenciones que tenían como objetivo incrementar la demanda de vacunación infantil de rutina. Los estudios fueron considerados elegibles si se realizaron en países de ingresos bajos y medios y utilizaron un diseño de ensayo controlado aleatorizado, ensayo controlado no aleatorizado, estudio controlado antes y después o de series temporales interrumpidas. Se estimó un riesgo de sesgo mediante las directrices de colaboración de Cochrane y se realizaron metaanálisis de efectos aleatorios. Resultados: se identificaron 11 estudios que abarcan cuatro ensayos controlados aleatorizados, seis ensayos controlados aleatorizados por conglomerados y un estudio controlado antes y después, publicados en inglés entre 1996 y 2013. En general, los participantes fueron padres de niños pequeños expuestos a una intervención elegible. Seis estudios demostraron un bajo riesgo de sesgo y cinco estudios presentaron un riesgo de sesgo entre moderado y elevado. Se realizó un análisis agrupado teniendo en cuenta los 11 estudios, con datos de 11.512 participantes. Las intervenciones enfocadas en la demanda se relacionaron con una recepción de las vacunas significativamente superior, riesgo relativo (RR): 1,30, (intervalo de confianza, IC, del 95%: 1,17–1,44). Los análisis de los subgrupos también demostraron efectos importantes de siete estudios de educación y traslación de conocimientos, RR: 1,40 (IC del 95%: 1,20–1,63) y de cuatro estudios que utilizaron incentivos, RR: 1,28 (IC del 95%: 1,12–1,45). Conclusión: las intervenciones enfocadas en la demanda conducen a mejoras significativas en la cobertura de vacunación infantil en países de ingresos bajos y medios. Asimismo, los enfoques educativos y el uso de incentivos fueron estrategias efectivas. / Abstract Objective: To investigate which strategies to increase demand for vaccination are effective in increasing child vaccine coverage in low- and middle-income countries. Methodology: We searched MEDLINE, EMBASE, Cochrane library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science and Scopus databases for relevant studies, published in English, French, German, Hindi, Portuguese and Spanish up to 25 March 2014. We included studies of interventions intended to increase demand for routine childhood vaccination. Studies were eligible if conducted in low- and middle-income countries and employing a randomized controlled trial, non-randomized controlled trial, controlled before-and-after or interrupted time series design. We estimated risk of bias using Cochrane collaboration guidelines and performed random-effects metaanalysis. Results: it was identified 11 studies comprising four randomized controlled trials, six cluster randomized controlled trials and one controlled before-and-after study published in English between 1996 and 2013. Participants were generally parents of young children exposed to an eligible intervention. Six studies demonstrated low risk of bias and five studies had moderate to high risk of bias. We conducted a pooled analysis considering all 11 studies, with data from 11 512 participants. Demand-side interventions were associated with significantly higher receipt of vaccines, relative risk (RR): 1.30, (95% confidence interval, CI: 1.17–1.44). Subgroup analyses also demonstrated significant effects of seven education and knowledge translation studies, RR: 1.40 (95% CI: 1.20–1.63) and of four studies which used incentives, RR: 1.28 (95% CI: 1.12–1.45). Conclusion: Demand-side interventions lead to significant gains in child vaccination coverage in low- and middle-income countries. Educational approaches and use of incentives were both effective strategies.

ContextRecent randomised controlled trials in Bangladesh and Kenya concluded that household water treatment, alone or in combination with upgraded sanitation and handwashing, did not reduce linear growth faltering or improve other child growth outcomes. Whether these results are applicable in areas with distinct constellations of water, sanitation and hygiene (WaSH) risks is unknown. Analysis of observational data offers an efficient means to assess the external validity of trial findings. We studied whether a water quality intervention could improve child growth in a rural Indian setting with higher levels of circulating pathogens than the original trial sites.MethodsWe analysed a cross-sectional dataset including a microbiological measure of household water quality. All households accessed water from an improved source. We applied propensity score methods to emulate a randomised trial investigating the hypothesis that receipt of drinking water meeting Sustainable Development Goal (SDG) 6.1 quality standards for absence of faecal contamination leads to improved growth. Growth outcomes (stunting, underweight, wasting, and their corresponding Z-scores) were assessed in children 12-23 months of age. For each outcome, we estimated the mean and 95% confidence interval of the absolute risk difference between treatment groups.FindingsOf 1088 households, 442 (40.62%) received drinking water meeting SDG 6.1 standards. The adjusted risk of child underweight was 7.4% (1.3% to 13.4%) lower among those drinking water satisfying SDG 6.1 norms than among controls. Evidence concerning the relationship of drinking water meeting SDG 6.1 norms to length-for-age and weight-for-age was inconclusive, and there was no apparent relationship with stunting or wasting.ConclusionsIn contexts characterised by high pathogen transmission, water quality improvements have the potential to reduce the proportion of underweight children, but are unlikely to impact stunting or wasting. Further research is required to assess how these modelled benefits can best be achieved in real world settings.

Abstract Objective To investigate which strategies to increase demand for vaccination are effective in increasing child vaccine coverage in low- and middle-income countries. Methods We searched MEDLINE, EMBASE, Cochrane library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science and Scopus databases for relevant studies, published in English, French, German, Hindi, Portuguese and Spanish up to 25 March 2014. We included studies of interventions intended to increase demand for routine childhood vaccination. Studies were eligible if conducted in low- and middle-income countries and employing a randomized controlled trial, non-randomized controlled trial, controlled before-and-after or interrupted time series design. We estimated risk of bias using Cochrane collaboration guidelines and performed random-effects meta-analysis. Findings We identified 11 studies comprising four randomized controlled trials, six cluster randomized controlled trials and one controlled before-and-after study published in English between 1996 and 2013. Participants were generally parents of young children exposed to an eligible intervention. Six studies demonstrated low risk of bias and five studies had moderate to high risk of bias. We conducted a pooled analysis considering all 11 studies, with data from 11 512 participants. Demand-side interventions were associated with significantly higher receipt of vaccines, relative risk (RR): 1.30, (95% confidence interval, CI: 1.17-1.44). Subgroup analyses also demonstrated significant effects of seven education and knowledge translation studies, RR: 1.40 (95% CI: 1.20-1.63) and of four studies which used incentives, RR: 1.28 (95% CI: 1.12-1.45). Conclusion Demand-side interventions lead to significant gains in child vaccination coverage in low- and middle-income countries. Educational approaches and use of incentives were both effective strategies.

Objective To estimate the impact on maternal and child mortality after eliminating user fees for pregnant women and for children less than five years of age in Burkina Faso. Methods Two health districts in the Sahel region eliminated user fees for facility deliveries and curative consultations for children in September 2008. To compare health-care coverage before and after this change, we used interrupted time series, propensity scores and three independent data sources. Coverage changes were assessed for four variables: women giving birth at a health facility, and children aged 1 to 59 months receiving oral rehydration salts for diarrhoea, antibiotics for pneumonia and artemesinin for malaria. We modelled the mortality impact of coverage changes in the Lives Saved Tool using several scenarios. Findings Coverage increased for all variables, however, the increase was not statistically significant for antibiotics for pneumonia. For estimated mortality impact, the intervention saved approximately 593 (estimate range 168–1060) children’s lives in both districts during the first year. This lowered the estimated under-five mortality rate from 235 deaths per 1000 live births in 2008 to 210 (estimate range 189–228) in 2009. If a similar intervention were to be introduced nationwide, 14 000 to 19 000 (estimate range 4000–28 000) children's lives could be saved annually. Maternal mortality showed a modest decrease in all scenarios. Conclusion In this setting, eliminating user fees increased use of health services and may have contributed to reduced child mortality.

Diabetes mellitus (DM) is one of the most burdensome chronic diseases and is associated with shorter lifetime, diminished quality of life and economic burdens on the patient and society as a result of healthcare, medication, and reduced labor market participation. We aimed to estimate the direct (medical and non-medical) and indirect costs of DM and compare them with those of people without DM (ND), as well as the cost predictors.Observational retrospective case-control study performed in Mali. Participants were identified and randomly selected from diabetes registries. We recruited 500 subjects with DM and 500 subjects without DM, matched by sex and age. We conducted structured, personal interviews. Costs were expressed for a 90-day period. Direct medical costs comprised: inpatient stays, ICU, laboratory tests and other hospital visits, specialist and primary care doctor visits, others, traditional practitioners, and medication. Direct non-medical costs comprised travel for treatment and paid caregivers. The indirect costs include the productivity losses by patients and caregivers, and absenteeism. We estimate a two-part model by type of service and a linear multiple regression model for the total cost. We found that total costs of persons with DM were almost 4 times higher than total cost of people without DM. Total costs were $77.08 and $281.92 for ND and DM, respectively, with a difference of $204.84.Healthcare use and costs were dramatically higher for people with DM than for people with normal glucose tolerance and, in relative terms, much higher than in developed countries.

Objective. To summarize key findings of economic evaluations of lifestyle interventions for the primary prevention of type 2 diabetes (T2D) in high-risk subjects. Methods. We conducted a systematic review of peer-reviewed original studies published since January 2009 in English, French, and Spanish. Eligible studies were identified through relevant databases including PubMed, Medline, National Health Services Economic Evaluation, CINHAL, EconLit, Web of sciences, EMBASE, and the Latin American and Caribbean Health Sciences Literature. Studies targeting obesity were also included. Data were extracted using a standardized method. The BMJ checklist was used to assess study quality. The heterogeneity of lifestyle interventions precluded a meta-analysis. Results. Overall, 20 studies were retained, including six focusing on obesity control. Seven were conducted within trials and 13 using modeling techniques. T2D prevention by physical activity or diet or both proved cost-effective according to accepted thresholds, except for five inconclusive studies, three on diabetes prevention and two on obesity control. Most studies exhibited limitations in reporting results, primarily with regard to generalizability and justification of selected sensitivity parameters. Conclusion. This confirms that lifestyle interventions for the primary prevention of diabetes are cost-effective. Such interventions should be further promoted as sound investment in the fight against diabetes.

Children unreached by vaccination are at higher risk of poor health outcomes and India accounts for nearly a quarter of unvaccinated children worldwide. The objective of this study was to investigate compositional and contextual determinants of non-receipt of childhood vaccines in India using multilevel modelling.We studied characteristics of unvaccinated children using the District Level Health and Facility Survey 3, a nationally representative probability sample containing 65 617 children aged 12-23 months from 34 Indian states and territories. We developed four-level Bayesian binomial regression models to examine the determinants of non-vaccination. The analysis considered two outcomes: completely unvaccinated (CUV) children who had not received any of the eight vaccine doses recommended by India's Universal Immunization Programme, and children who had not received any dose from routine immunisation services (no RI). The no RI category includes CUV children and those who received only polio doses administered via mass campaigns. Overall, 4.83% (95% CI: 4.62-5.06) of children were CUV while 12.01% (11.68-12.35) had received no RI. Individual compositional factors strongly associated with CUV were: non-receipt of tetanus immunisation for mothers during pregnancy (OR = 3.65 [95% CrI: 3.30-4.02]), poorest household wealth index (OR = 2.44 [1.81-3.22] no maternal schooling (OR = 2.43 [1.41-4.05]) and no paternal schooling (OR = 1.83 [1.30-2.48]). In rural settings, the influence of maternal illiteracy disappeared whereas the role of household wealth index was reinforced. Factors associated with no RI were similar to those for CUV, but effect sizes for individual compositional factors were generally larger. Low maternal education was the strongest risk factor associated with no RI in all models. All multilevel models found significant variability at community, district, and state levels net of compositional factors.Non-vaccination in India is strongly related to compositional characteristics and is geographically distinct. Tailored strategies are required to overcome current barriers to immunisation.

Background. Point-of-care (POC) diagnostics for syphilis can contribute to epidemic control by offering a timely knowledge of serostatus. Although accuracy data on POC syphilis tests have been widely published, few studies have evaluated broader outcomes beyond accuracy that impact patients and health systems. We comprehensively reviewed evidence and reporting of these implementation research outcomes (IROs), and proposed a framework to improve their quality. Methods. Three reviewers systematically searched 6 electronic databases from 1980 to 2014 for syphilis POC studies reporting IROs. Data were abstracted and findings synthesised narratively. Results. Of 71 studies identified, 38 documented IROs. IROs were subclassified into preference (7), acceptability (15), feasibility (15), barriers and challenges (15), impact (13), and prevalence (23). Using our framework and definitions, a pattern of incomplete documentation, inconsistent definitions, and lack of clarity was identified across all IROs. Conclusion. Although POC screening tests for syphilis were generally favourably evaluated across a range of outcomes, the quality of evidence was compromised by inconsistent definitions, poor methodology, and documentation of outcomes. A framework for standardized reporting of outcomes beyond accuracy was proposed and considered a necessary first step towards an effective implementation of these metrics in POC diagnostics research.