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Summary Background Childhood immunisation is one of the most cost-effective health interventions. However, despite its known value, global access to vaccines remains far from complete. Although supply-side constraints lead to inadequate vaccine coverage in many health systems, there is no comprehensive analysis of the funding for immunisation. We aimed to fill this gap by generating estimates of funding for immunisation disaggregated by the source of funding and the type of activities in order to highlight the funding landscape for immunisation and inform policy making. Methods For this financial modelling study, we estimated annual spending on immunisations for 135 low-income and middle-income countries (as determined by the World Bank) from 2000 to 2017, with a focus on government, donor, and out-of-pocket spending, and disaggregated spending for vaccines and delivery costs, and routine schedules and supplementary campaigns. To generate these estimates, we extracted data from National Health Accounts, the WHO–UNICEF Joint Reporting Forms, comprehensive multi-year plans, databases from Gavi, the Vaccine Alliance, and the Institute for Health Metrics and Evaluation's 2019 development assistance for health database. We estimated total spending on immunisation by aggregating the government, donor, prepaid private, and household spending estimates. Findings Between 2000 and 2017, funding for immunisation totalled US$112·4 billion (95% uncertainty interval 108·5–118·5). Aggregated across all low-income and middle-income countries, government spending consistently remained the largest source of funding, providing between 60·0% (57·7–61·9) and 79·3% (73·8–81·4) of total immunisation spending each year (corresponding to between $2·5 billion [2·3–2·8] and $6·4 billion [6·0–7·0] each year). Across income groups, immunisation spending per surviving infant was similar in low-income and lower-middle-income countries and territories, with average spending of $40 (38–42) in low-income countries and $42 (39–46) in lower-middle-income countries, in 2017. In low-income countries and territories, development assistance made up the largest share of total immunisation spending (69·4% [64·6–72·0]; $630·2 million) in 2017. Across the 135 countries, we observed higher vaccine coverage and increased government spending on immunisation over time, although in some countries, predominantly in Latin America and the Caribbean and in sub-Saharan Africa, vaccine coverage decreased over time, while spending increased. Interpretation These estimates highlight the progress over the past two decades in increasing spending on immunisation. However, many challenges still remain and will require dedication and commitment to ensure that the progress made in the previous decade is sustained and advanced in the next decade for the Immunization Agenda 2030. Funding Bill & Melinda Gates Foundation.

Cancer mortality rates in low-income and middle-income countries (LMICs) are unacceptably high, requiring both collaborative global effort and in-country solutions. Experience has shown that working together in policy, clinical practice, education, training, and research leads to bidirectional benefit for LMICs and high-income countries. For over 60 years, the UK National Health Service has benefited from recruitment from LMICs, providing the UK with a rich diaspora of trained health-care professionals with links to LMICs. A grassroots drive to engage with partners in LMICs within the UK has grown from the National Health Service, UK academia, and other organisations. This drive has generated a model that rests on two structures: London Global Cancer Week and the UK Global Cancer Network, providing a high-value foundation for international discussion and collaboration. Starting with a historical perspective, this Series paper describes the UK landscape and offers a potential plan for the future UK's contribution to global cancer control. We also discuss the opportunities and challenges facing UK partnerships with LMICs in cancer control. The UK should harness the skills, insights, and political will from all partners to make real progress.

BACKGROUND The prevalence of landscape fires has increased, particularly in low-income and middle-income countries (LMICs). We aimed to assess the impact of exposure to landscape fire smoke (LFS) on the health of children. METHODS We conducted a sibling-matched case-control study and selected 552 155 children (aged

A number of organizations are producing resource stratified guidelines (RSGs) for cancer. Despite using similar definitions of resource levels, systemic treatment recommendations often differ between organizations. We systematically searched for RSGs focusing on solid tumors. We qualitatively compared the methods used to generate guidelines using the AGREE-II appraisal tool. We extracted systemic treatment recommendations and assessed interguideline concordance using the Gwet AC1 coefficient, stratified by resource level, treatment setting and cancer type. We identified 69 RSGs cancer covering 15 solid tumors produced by four organizations. Despite using common resource-level definitions (Basic, Core/Limited, Enhanced and Maximal), recommendations differed between organizations. Concordance for chemotherapy recommendations was poor in Basic (58.3%, Gwet 0.20), fair in Core (58.3%, Gwet 0.32) and excellent in Enhanced (92.4%, Gwet 0.92) and Maximal settings (95.4%, Gwet 0.95). Concordance rates for endocrine therapy were good in Basic (80% Gwet 0.61), and excellent in Core (90%, Gwet 0.87), Enhanced (90%, Gwet 0.89) and Maximal settings (90%, Gwet 0.89). There was moderate to excellent concordance in targeted therapy recommendations across all resource levels. Differences in recommendations appeared driven by different opinions among the chosen panel of experts regarding what is resource appropriate. Overall, we found that countries looking to base treatment and health-policy on RSGs will find conflicting information depending on which guidelines are used, particularly for chemotherapy in Basic and Core settings. Improved transparency regarding the methods used to determine the value of a therapy for a given resource level is needed.

Background Substance use remains a public health problem worldwide, and it is particularly concerning among adolescents because of its harmful effects. There is a need to better understand the factors associated with adolescents’ substance use to inform policies for effective prevention. Methods We used data from the Global School-based Student Health Surveys. Data were collected by anonymous self-report questionnaires. This study is based on three questions assessing substance use and four questions assessing psychological distress. Logistic regression models were used to analyse associations between substance use and psychological distress. We calculated the pooled overall and regional estimates by random-effects meta-analysis. Results We included 126,763 adolescents (boys, 44.7%; girls, 55.3%). Substance users tended to be older, male, physically attacked, in physical fighting, bullied; to experience psychological distress; and to have a higher socio-economic status. Alcohol use was consistently associated with medium and high psychological distress. In terms of four aspects of psychological distress, only suicidal ideation was consistently associated with the substance use components and all specific combinations of substance use. Additionally, the prevalence of alcohol use was higher than that of cigarette use and drug use. Region-wise analysis showed that substance use was associated with psychological distress in the African region, American region, South-East region and Western Pacific region. Limitations The cross-sectional data could not infer causality. Conclusions This study indicated that high levels of substance use were significantly associated with an increased likelihood of psychological distress among adolescents. In addition, age also had an effect on substance use.

Global child health has cemented itself as an important branch of global health. It is said that the development of a nation is gauged by its infant and under-5 mortality rates. Coordinated efforts by organizations such as the United Nations, the World Health Organization, and Governments are essential to maintain the momentum of improving the health of children across the world. Special focus needs to be put on areas such as Sub-Saharan Africa and conflict-prone regions where the initial positive gains are being erased. As we achieve success in controlling malaria, pneumonia, and diarrhea in many countries, we need to start focusing on areas such as cancer, accidents, climate change, and child abuse which will soon become important health problems in children in low- and middle-income countries.

Background Antimicrobial misuse is common in low-income and middle-income countries (LMICs), and this practice is a driver of antibiotic resistance. We compared community-based antibiotic access and use practices across communities in LMICs to identify contextually specific targets for interventions to improve antibiotic use practices. Methods We did quantitative and qualitative assessments of antibiotic access and use in six LMICs across Africa (Mozambique, Ghana, and South Africa) and Asia (Bangladesh, Vietnam, and Thailand) over a 2·5-year study period (July 1, 2016–Dec 31, 2018). We did quantitative assessments of community antibiotic access and use through supplier mapping, customer exit interviews, and household surveys. These quantitative assessments were triangulated with qualitative drug supplier and consumer interviews and discussions. Findings Vietnam and Bangladesh had the largest proportions of non-licensed antibiotic dispensing points. For mild illness, drug stores were the most common point of contact when seeking antibiotics in most countries, except South Africa and Mozambique, where public facilities were most common. Self-medication with antibiotics was found to be widespread in Vietnam (55·2% of antibiotics dispensed without prescription), Bangladesh (45·7%), and Ghana (36·1%), but less so in Mozambique (8·0%), South Africa (1·2%), and Thailand (3·9%). Self-medication was considered to be less time consuming, cheaper, and overall, more convenient than accessing them through health-care facilities. Factors determining where treatment was sought often involved relevant policies, trust in the supplier and the drug, disease severity, and whether the antibiotic was intended for a child. Confusion regarding how to identify oral antibiotics was revealed in both Africa and Asia. Interpretation Contextual complexities and differences between countries with different incomes, policy frameworks, and cultural norms were revealed. These contextual differences render a single strategy inadequate and instead necessitate context-tailored, integrated intervention packages to improve antibiotic use in LMICs as part of global efforts to combat antibiotic resistance. Funding Wellcome Trust and Volkswagen Foundation.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

Bilateral and multilateral development agencies spend a great deal of time, money, and effort trying to shape the reform priorities and processes of their counterpart countries. However, the means by which development agencies can achieve these ends are poorly understood. This article draws upon the first-hand experiences and observations of more than 1000 public sector officials from 70 low- and middle-income countries to better understand which external sources of reform advice and assistance are most and least useful to public sector decision-makers—and why. We find that donors more effectively shape reform priorities when they choose to deliver their funding through the public financial management systems of counterpart countries, rather than using channels of aid delivery—in particular, technical assistance programs—that bypass host governments and signal a lack of trust in the motivations and capabilities of the local authorities. This finding holds true even after controlling for institutional quality, or the trustworthiness of public sector institutions, in aid-receiving countries. As such, our results call attention to the fact that development agencies can amplify their policy influence by entrusting their counterpart governments with aid management responsibilities.

Background: Patients in low-income and middle-income countries (LMICs) have limited access to palliative care providers. In Myanmar, little is known about physician knowledge of or perceptions about palliative care. An assessment of physician practice and capacity to provide palliative care is needed. Objective: Our objective was to identify physician practice patterns, knowledge gaps, and confidence in providing palliative and end-of-life care in Myanmar. Design: This was a cross-sectional survey study. Setting/Subjects: Participants were physicians practicing in Myanmar who attended the Myanmar Emergency Medicine Updates Symposium on November 10 to 11, 2018 in Yangon, Myanmar (n = 89). Measurements: The survey used modified Likert scales to explore four aspects of palliative care practice and training: frequency of patient encounters, confidence in skills, previous training, and perceived importance of formal training. Results: Study participants were young (median age 27 years old); 89% cared for terminally ill patients monthly, yet 94% reported less than two weeks of training in common palliative care domains. Lack of training significantly correlated with lack of confidence in providing care. Priorities for improving palliative care services in Myanmar include better provider training and medication access. Conclusions: Despite limited training and low confidence in providing palliative care, physicians in Myanmar are treating patients with palliative needs on a monthly basis. Future palliative care education and advocacy in Myanmar and other LMICs could focus on physician training to improve end-of-life care, increase physician confidence, and reduce barriers to medication access.

BACKGROUND Both young and advanced maternal age have been associated with higher risks of neonatal mortality, but most studies are from high-income countries and the evidence from low- and middle-income countries (LMICs) is scarce. OBJECTIVE To investigate the association between maternal age at delivery and neonatal mortality in LMICs. METHODS This is a cross-sectional study using data from 159 Demographic and Health Surveys in 67 LMICs between 2000 and 2018. Maternal age at the time of the birth was the exposure variable, and neonatal mortality was the outcome. Multivariable logistic regression model taking into consideration complex survey design was performed with adjustments for maternal education level, paternal education level, rural/urban residence, country, and survey year. Subgroup analyses were performed by time of death, sex, the country's World Bank income classification, the World Health Organization region, and survey year. RESULTS A total of 1 395 746 mother-neonate pairs were included. Overall, compared with neonates born to mothers aged 25-29 years, those born to younger mothers aged 20-24, 16-19 and 12-15 years were at an increased risk of mortality (adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 1.17, 1.30; OR 1.81, 95% CI 1.71, 1.93; OR 2.29, 95% CI 1.96, 2.67, respectively). Neonates born to mothers aged 30-34, 35-39, 40-44, and ≥45 years were also at an increased risk of mortality (OR 1.09, 95% CI 1.03, 1.15; OR 1.30, 95% CI 1.21, 1.39; OR 1.50, 95% CI 1.38, 1.64; OR 1.84, 95% CI 1.54, 2.20, respectively). The results were consistent across most subgroup analyses. CONCLUSIONS Neonates born to younger (

The burden of stroke is higher in low-income and middle-income countries (LMICs) than in high-income countries and is rising. Even though there are global policies and guidelines for implementing stroke care, there are many challenges in setting up stroke services in LMICs. Despite these challenges, there are many models of stroke care available in LMICs-eg, multidisciplinary team care led by a stroke neurologist, specialist-led care by neurologists, physician-led care, hub and spoke models incorporating stroke telemedicine (ie, telestroke), and task sharing involving community health workers. Alternative strategies have been developed, such as reorganising the existing hospital infrastructure by training health professionals to implement protocol-driven care. The future challenge is to identify what elements of organised stroke care can be implemented to make the largest gain. Simple interventions such as swallowing assessments, bowel and bladder care, mobility assessments, and consistent secondary prevention can prove to be key elements to improving post-discharge morbidity and mortality in LMICs.

Microbial contamination of surface waters is of particular relevance in low-income and middle-income countries (LMICs) since they often represent the only available source of water for drinking and domestic use. In the recent years, a growing urbanization, profound demographic shifts and drastic climate events have greatly affected LMICs capacity to reach access to safe drinking water and sanitation practices, and to protect citizens’ health from risks associated to the exposure and use of contaminated water. Detailed phylogenetic and microbiological information on the exact composition of pathogenic organisms in urban and peri-urban water is scarce, especially in rapidly changing settings of sub-Saharan Africa. In this review we aim to highlight how large-scale water pathobiome studies can support the LMICs challenge to global access to safe water and sanitation practices.

Purpose of review To review the roles of enteric adenovirus types 40 and 41 and nonenteric adenoviruses in the global burden of pediatric diarrhea. Recent findings Large studies using highly sensitive, type-specific molecular diagnostics have demonstrated a substantial and previously under-estimated burden of pediatric diarrheal disease because of enteric infections with adenovirus types 40/41. However, the true epidemiology of adenovirus 40/41 remains incompletely understood. Similarly, additional adenovirus types may also be implicated as agents of community-acquired pediatric gastroenteritis but current data are too limited to elucidate their epidemiological role(s), if any. Summary Efforts at global diarrhea control in low-income and middle-income countries will require combating pediatric gastroenteritis because of enteric adenovirus infections. Future research in these settings using type-specific molecular diagnostics or strain genotyping to fully characterize the epidemiology of adenovirus 40/41 infections, identify non-40/41 adenoviruses significantly associated with gastroenteritis, and develop vaccines effective at preventing adenovirus diarrhea is warranted.

Low- and Middle-Income Countries suffer the large majority (93%) of global road crash deaths and face particular challenges in managing this crisis. This paper presents global data and trends revealing underlying features of the problem for LMICs. LMICs are commonly grouped and described together in road safety commentaries, yet appreciation of the substantial differences between LICs and MICs is vital. While global deaths per 100,000 people have stabilized during the UN Decade of Road Safety, the population rate has increased in LICs (by 8.2%), while decreasing in HIC and MIC. LICs have less resources to address road safety and younger populations adding to risk. Wide variations on road safety performance exist within country income groups, with some of this variance occurring systematically between regions. Absolute numbers of deaths are increasing due to increasing population and increasing vehicle fleets in LMICs compared with HICs. The capacity of MICs, and especially LICs, to manage road safety is hampered by poor crash data to guide action as well less available funding and resources to achieve safer road engineering, safer vehicles, and protect the large proportions of vulnerable road users. Road crash deaths and injuries are retarding the economic growth of LMICs and investing road safety is a costeffective means by which LMICs can move towards becoming HICs. Vital opportunities for cost-effective savings of lives and debilitating injuries in LMICs include better management of speed (especially through infrastructure), improving safety infrastructure for pedestrians, increasing seatbelt use, and shifting travel from motorcycles to buses through provision of Bus Rapid Transit systems.

NUTRITIONAL STATUS AND NUTRITIONAL SUPPORT IN CHILDREN WITH CONGENITAL MALFORMATIONS OF BRAIN IN UKRAINE: SINGLE-CENTER OBSERVATIONAL DESCRIPTIVE CROSS-SECTIONAL STUDY Riga O., Orlova N., Ishchenko T. In Ukraine, as one of low income and middle income countries (LMICs), PEM is detected and diagnosed not quite actively especially in children with neurologic impairment. Methods: Nutritive status and energy consumption was evaluated in 17 young and preschool children with congenital malformations of brain by anthropometry, 24-hour dietary recall and questionnaire of caregivers. Results: The study demonstrate nutritional disorders: Z-score BW for age in total cohort was -3.2, H/L for age was -2.7. The moderate PEM was diagnosed in 2/17 children, severe PEM in 12/17. The late appointment of nutritional support to such children has been demonstrated, its effect on increasing growth and body weight. Conclusion. The importance of drawing up individual plans for the energetic consumption of the children with congenital malformations of brain with training of caregivers and rehabilitative and palliative team was shown. Keywords: children, protein-energy malnutrition, congenital malformations of brain, LMICs. Резюме. ХАРЧОВИЙ СТАТУС І ХАРЧОВА ПІДТРИМКА ДІТЕЙ З ВРОДЖЕНИМИ ВАДАМИ РОЗВИТКУ МОЗКУ В УКРАЇНІ: ОДНОЦЕНТРОВЕ НАОЧНО-ОПИСОВЕ КРОС-СЕКЦІЙНЕ ДОСЛІДЖЕННЯ Ріга О.О., Орлова Н.В., Іщенко Т.Б. В Україні, як одна із країн з низьким рівнем доходу та середнього доходу (LMICs), БЕН виявляється та діагностується не досить активно, особливо у дітей з порушеннями неврології. Методи: Харчовий статус та споживання енергії було оцінено у 17 дітей молодшого та дошкільного віку з вродженими вадами розвитку головного мозку за допомогою антропометрії, цілодобової дієти та анкетування опікунів. Результати: Дослідження демонструє харчові розлади: показник Z-score BW за віком у загальній когорті становив -3,2, H/L для віку -2,7. Помірну БЕН було діагностовано у 2/17 дітей, тяжку БЕН у 12/17. Продемонстровано несвоєчасне призначення харчової підтримки таким дітям, його вплив на збільшення росту та маси тіла. Висновки. Показано важливість складання індивідуальних планів енергетичного споживання дітей з вродженими вадами розвитку мозку під час навчання опікунів та реабілітаційно-паліативного колективу. Ключові слова: діти, білково-енергетична недостатність, вроджені вади розвитку мозку, LMICs. Резюме. ПИЩЕВОЙ СТАТУС И ПИЩЕВАЯ ПОДДЕРЖКА ДЕТЕЙ С ВРОЖДЕННЫМИ ПОРОКАМИ РАЗВИТИЯ МОЗГА В УКРАИНЕ: ОДНОЦЕНТРОВОЕ НАГЛЯДНО-ОПИСАТЕЛЬНОЕ КРОСС-СЕКЦИОННОЕ ИССЛЕДОВАНИЕ Рига Е.А., Орлова Н.В., Ищенко Т.Б. В Украине, как одна из стран с низким уровнем дохода и среднего дохода (LMICs), БЄН оказывается и диагностируется недостаточно активно, особенно у детей с нарушениями неврологии. Методы: Пищевой статус и потребления энергии было оценено у 17 детей младшего и дошкольного возраста с врожденными пороками развития головного мозга с помощью антропометрии, круглосуточной диеты и анкетирования опекунов. Результаты: Исследование демонстрирует пищевые расстройства: показатель Z-score BW по возрасту в общей когорте составил -3,2, H/L для возраста -2,7. Умеренную БЄН было диагностировано у 2/17 детей, тяжелую БЄН у 12/17. Продемонстрировано несвоевременное назначение пищевой поддержки таким детям, его влияние на увеличение роста и массы тела. Выводы. Показана важность составления индивидуальных планов энергетического потребления детей с врожденными пороками развития мозга во время обучения опекунов и реабилитационно-паллиативного коллектива. Ключевые слова: дети, белково-энергетическая недостаточность, врожденные пороки развития мозга, LMICs.

Zoonotic and vector-borne parasites are important preventable risk factors for epilepsy. Three parasitic infections — cerebral malaria, Taenia solium cysticercosis and onchocerciasis — have an established association with epilepsy. Parasitoses are widely prevalent in low-income and middle-income countries, which are home to 80% of the people with epilepsy in the world. Once a parasitic infection has taken hold in the brain, therapeutic measures do not seem to influence the development of epilepsy in the long term. Consequently, strategies to control, eliminate and eradicate parasites represent the most feasible way to reduce the epilepsy burden at present. The elucidation of immune mechanisms underpinning the parasitic infections, some of which are parasite-specific, opens up new therapeutic possibilities. In this Review, we explore the pathophysiological basis of the link between parasitic infections and epilepsy, and we consider preventive and therapeutic approaches to reduce the burden of epilepsy attributable to parasitic disorders. We conclude that a concerted approach involving medical, veterinary, parasitological and ecological experts, backed by robust political support and sustainable funding, is the key to reducing this burden. Zoonotic and vector-borne parasites are important preventable risk factors for epilepsy. The authors explore the pathophysiological basis of the link between parasitic infections and epilepsy and consider preventive and therapeutic approaches to reduce the epilepsy burden associated with parasitic disorders.

BackgroundDiarrhoea is the second-leading infectious cause of death in children younger than age 5 years. The global burden of severe diarrhoeal disease is concentrated in Africa and Southeast Asia, where a significant percentage of the population resides in low-resource settings. We aimed to quantitatively examine whether extending the duration of legislated paid maternity leave affected the prevalence of childhood diarrhoea in low-income and middle-income countries (LMICs).MethodsWe merged longitudinal data measuring national maternity leave policies with information on the prevalence of bloody diarrhoea related to 884 517 live births occurring between 1996 and 2014 in 40 LMICs that participated at least twice in the Demographic and Health Surveys between 2000 and 2015. We used a difference-in-differences approach to compare changes in the percentage of children with bloody diarrhoea across eight countries that lengthened their paid maternity leave policy between 1995 and 2013 to the 32 countries that did not.ResultsThe prevalence of bloody diarrhoea in the past 2 weeks was 168 (SD=40) per 10 000 children under 5 years in countries that changed their policies and 136 (SD=15) in countries that did not. A 1-month increase in the legislated duration of paid maternity leave was associated with 61 fewer cases of bloody diarrhoea (95% CI −98.86 to −22.86) per 10 000 children under 5 years of age, representing a 36% relative reduction.ConclusionExtending the duration of paid maternity leave policy appears to reduce the prevalence of bloody diarrhoea in children under 5 years of age in LMICs.

Summary Prevalence of anaemia is high among children in low-income and middle-income countries. Anaemia is an important factor to consider preoperatively as low haemoglobin concentrations can have a negative effect on surgical outcomes and can also lead to surgeries being cancelled or postponed, which can have adverse health implications and stretch already limited resources in these countries. Additionally, blood transfusions to correct anaemia exposes children to safety issues. Therefore, where anaemia is known to be prevalent and resources are scarce, a contextually appropriate and relatively safe minimum haemoglobin concentration for proceeding to surgery could substantially improve patient management and efficiency of the health system. In this Review, we consider why paediatric anaemia is a major public health issue in low-income and middle-income countries, the value of preoperative testing of anaemia, and methods of optimising haemoglobin concentrations in the context of paediatric surgeries taking place in resource-limited settings.

OBJECTIVE: Many adolescents and young adults (AYA) have unmet HIV prevention needs. We describe the Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings (PATC(3)H) consortium organization, transition milestones, and youth engagement strategies. The PATC(3)H consortium focuses on reducing HIV incidence and related health disparities among AYA. DESIGN AND METHODS: Organizational data were obtained from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and supplemented with a brief survey completed by study principal investigators. Transition from the initial phase (years 1–2) to the subsequent phase (years 3–5) was contingent on meeting pre-specified milestones. We reviewed the structure and function of the research consortium, identified shared elements of transition milestones, and examined common youth engagement strategies. RESULTS: The PATC(3)H consortium supports eight research studies through a milestone transition mechanism. The consortium includes AYA HIV research studies in seven countries - Brazil, Kenya, Mozambique, Nigeria, South Africa, Uganda, and Zambia. The NIH request for applications required transition milestones that included early consultation with stakeholders. The transition milestones required by NIH for the eight studies included early consultation with health and policy stakeholders, pilot intervention data and commitment from national government stakeholders. All studies provided multiple pathways for AYA engagement, including AYA advisory boards and youth-led research studies. CONCLUSION: Data suggest that requiring milestones to transition to the final phase may have facilitated health and policy stakeholder engagement and enhanced formative assessment of regulatory protocols. These data have implications for designing engaged research studies in low and middle-income countries.

Summary Background Pathology and laboratory medicine diagnostics and diagnostic imaging are crucial to achieving universal health coverage. We analysed Service Provision Assessments (SPAs) from ten low-income and middle-income countries to benchmark diagnostic availability. Methods Diagnostic availabilities were determined for Bangladesh, Haiti, Malawi, Namibia, Nepal, Kenya, Rwanda, Senegal, Tanzania, and Uganda, with multiple timepoints for Haiti, Kenya, Senegal, and Tanzania. A smaller set of diagnostics were included in the analysis for primary care facilities compared with those expected at hospitals, with 16 evaluated in total. Surveys spanned 2004–18, including 8512 surveyed facilities. Country-specific facility types were mapped to basic primary care, advanced primary care, or hospital tiers. We calculated percentages of facilities offering each diagnostic, accounting for facility weights, stratifying by tier, and for some analyses, region. The tier-level estimate of diagnostic availability was defined as the median of all diagnostic-specific availabilities at each tier, and country-level estimates were the median of all diagnostic-specific availabilities of each of the tiers. Associations of country-level diagnostic availability with country income as well as (within-country) region-level availability with region-specific population densities were determined by multivariable linear regression, controlling for appropriate covariates including tier. Findings Median availability of diagnostics was 19·1% in basic primary care facilities, 49·2% in advanced primary care facilities, and 68·4% in hospitals. Availability varied considerably between diagnostics, ranging from 1·2% (ultrasound) to 76·7% (malaria) in primary care (basic and advanced) and from 6·1% (CT scan) to 91·6% (malaria) in hospitals. Availability also varied between countries, from 14·9% (Bangladesh) to 89·6% (Namibia). Availability correlated positively with log(income) at both primary care tiers but not the hospital tier, and positively with region-specific population density at the basic primary care tier only. Interpretation Major gaps in diagnostic availability exist in many low-income and middle-income countries, particularly in primary care facilities. These results can serve as a benchmark to gauge progress towards implementing guidelines such as the WHO Essential Diagnostics List and Priority Medical Devices initiatives. Funding Bill & Melinda Gates Foundation.

The COVAX Facility of the ACT Accelerator has agreements to access 2 billion doses of WHO prequalified vaccines during 2021, but this represents only 20% of the vaccine needs of participating countries Most low-income and middle-income countries (LMICs) face difficulties in accessing and delivering vaccines and therapeutics for COVID-19 to their populations For 80% of the populations in LMICs that will not benefit from COVAX-provided COVID-19 vaccines, finances for purchase or donations are needed Strengthening the capacity of LMICs to do clinical trials and promoting LMIC participation in research are also crucial Governments in LMICs with strong private health sectors, as those in high-income countries, will need to manage the inherent potential for inequity, whereby the rich could access COVID-19 vaccines before individuals with less access to private care who may be at increased risk of severe disease and death, such as older people and those with comorbidities The COVID-19 pandemic shows that no nation can stand alone We are all part of a common humanity that requires us to respect our diverse experiences, cultures, and countries and forge partnerships that better serve the interests of all (PsycInfo Database Record (c) 2021 APA, all rights reserved)

ObjectiveTo characterise the environmental presence of hepatitis A virus (HAV) in low- and middle-income countries (LMICs).DesignSystematic review and meta-analysis.Data sourcesEBSCOhost, PubMed, Scopus, ScienceDirect, Clinical Key and Web of Science were searched. Grey literature was sourced by searching the following electronic databases: Open Grey, National Health Research Database and Mednar.Eligibility criteria for including studiesCross-sectional and ecological studies reporting HAV environmental presence and conducted in LMICs between January 2005 and May 2019, irrespective of language of publication.Data extraction and data synthesisRelevant data were extracted from articles meeting the inclusion criteria, and two reviewers independently assessed the studies for risk of bias. High heterogeneity of the extracted data led to the results being reported narratively.ResultsA total of 2092 records were retrieved, of which 33 met the inclusion criteria. 21 studies were conducted in Tunisia, India and South Africa, and the rest were from Philippines, Pakistan, Morocco, Chad, Mozambique, Kenya and Uganda. In Tunisian raw sewage samples, the prevalence of HAV ranged from 12% to 68%, with an estimated average detection rate of 50% (95% CI 25 to 75), whereas HAV detection in treated sewage in Tunisia ranged from 23% to 65%, with an estimated average detection rate of 38% (95% CI 20 to 57). The prevalence of HAV detection in South African treated sewage and surface water samples ranged from 4% to 37% and from 16% to 76%, with an estimated average detection rates of 15% (95% CI 1 to 29) and 51% (95% CI 21 to 80), respectively. Over the review period, the estimated average detection rate of environmental HAV presence appeared to have declined by 10%.ConclusionThe quality of included studies was fair, but sampling issues and paucity of data limited the strength of the review findings.PROSPERO registration numberCRD42019119592.

BACKGROUND: Respiratory syncytial virus (RSV) represents a substantial burden of disease in young infants in low-income and middle-income countries (LMICs). Because RSV passive immunisations, including maternal vaccination and monoclonal antibodies, can only grant a temporary period of protection, their effectiveness and efficiency will be determined by the timing of the immunisation relative to the underlying RSV seasonality. We aimed to assess the potential effect of different approaches for passive RSV immunisation of infants in LMICs.METHODS: We included 52 LMICs in this study on the basis of the availability of RSV seasonality data and developed a mathematical model to compare the effect of different RSV passive immunisation approaches (seasonal approaches vs a year-round approach). For each candidate approach, we calculated the expected annual proportion of RSV incidence among infants younger than 6 months averted (effectiveness) and the ratio of per-dose cases averted between that approach and the year-round approach (relative efficiency).FINDINGS: 39 (75%) of 52 LMICs included in the study had clear RSV seasonality, defined as having more than 75% of annual RSV cases occurring in 5 or fewer months. In these countries with clear RSV seasonality, the seasonal approach in which monoclonal antibody administration began 3 months before RSV season onset was only a median of 16% (IQR 13-18) less effective in averting RSV-associated acute lower respiratory infection (ALRI) hospital admissions than a year-round approach, but was a median of 70% (50-97) more efficient in reducing RSV-associated hospital admissions per dose. The seasonal approach that delivered maternal vaccination 1 month before the season onset was a median of 27% (25-33) less effective in averting hospital admissions associated with RSV-ALRI than a year-round approach, but was a median of 126% (87-177) more efficient at averting these hospital admissions per dose.INTERPRETATION: In LMICs with clear RSV seasonality, seasonal approaches to monoclonal antibody and maternal vaccine administration might optimise disease prevention by dose given compared with year-round administration. More data are needed to clarify if seasonal administration of RSV monoclonal antibodies or maternal immunisation is programmatically suitable and cost effective in LMICs.FUNDING: The Bill & Melinda Gates Foundation, World Health Organization.

Background Priority setting process for the health care sector in low- and middle-income countries involves multiple agencies, each with their unique power, decision-making and funding mechanisms. Methods This paper developed and applied a new framework to analyze priority setting processes in Ethiopia, Nigeria, and Tanzania, from a scoping review of literature. Interviews were then conducted using a pre-determined interview guide developed by the research team. Transcripts were reviewed and coded based on the framework to identify what principles, players, processes, and products were considered during priority setting. Those elements were further used to identify where the potential capacity of local decision-makers could be harnessed. Results a framework was developed based on 40 articles selected from 6860 distinct search records. 21 interviews were conducted in three case countries from 12 institutions. Transcripts or meeting notes were analyzed to identify common practices and specific challenges faced by each country. We found that multiple stakeholders working around one national plan was the preferred approach used for priority setting in the countries studied. Conclusions Priority setting process can be further strengthened through better use of analytical tools, such as the one described in our study, to enhance local ownership and improve aid effectiveness.

Summary Background Mass deworming against soil-transmitted helminthiasis, which affects 1 billion of the poorest people globally, is one of the largest public health programmes for neglected tropical diseases, and is intended to be equitable. However, the extent to which treatment programmes for deworming achieve equitable coverage across wealth class and sex is unclear and the public health metric of national deworming coverage does not include representation of equity. This study aims to measure both coverage and equity in global, national, and subnational deworming to guide future programmatic evaluation, investment, and metric design. Methods We used nationally representative, geospatial, household data from Demographic and Health Surveys that measured mother-reported deworming in children of preschool age (12–59 months). Deworming was defined as children having received drugs for intestinal parasites in the previous 6 months before the survey. We estimated deworming coverage disaggregated by geography, wealth quintile, and sex, and computed an equity index. We examined trends in coverage and equity index across countries, within countries, and over time. We used a regression model to compute the household correlates of deworming and ecological correlates of equitable deworming. Findings Our study included 820 883 children living in 50 countries from Africa, the Americas, Asia, and Europe that are endemic for soil-transmitted helminthiasis using 77 Demographic and Health Surveys from December, 2003, to October, 2017. In these countries, the mean deworming coverage in preschool children was estimated at 33·0% (95% CI 32·9–33·1). The subnational coverage ranged from 0·5% to 87·5%, and within-country variation was greater than between-country variation. Of the 31 countries reporting that they reached the WHO goal of more than 75% national coverage, 30 had inequity in deworming, with treatment concentrated in wealthier populations. We did not detect systematic differences in deworming equity by sex. Interpretation Substantial inequities in mass deworming programmes are common as wealthier populations have consistently higher coverage than that of the poor, including in countries reporting to have reached the WHO goal of more than 75% national coverage. These inequities seem to be geographically heterogeneous, modestly improving over time, with no evidence of sex differences in inequity. Future reporting of deworming coverage should consider disaggregation by geography, wealth, and sex with incorporation of an equity index to complement the conventional public health metric of national deworming coverage. Funding Bill & Melinda Gates Foundation, Stanford University Medical Scientist Training Program.

To improve virological suppression and address the emerging threat of HIV drug resistance, many low-income and middle-income countries are moving away from non-nucleoside reverse transcriptase inhibitors (NNRTI) and transitioning to dolutegravir as part of a more affordable and standardised antiretroviral therapy (ART). Although this transition could decrease the effect of rising NNRTI resistance and yield improved ART outcomes, it also presents new challenges. First, current safety concerns for dolutegravir use in women of childbearing potential require alternative solutions. Second, pre-existing resistance to the co-administered nucleoside reverse transcriptase inhibitors might reduce effectiveness and durability of dolutegravir, particularly if there is scarce access to viral load tests to monitor treatment outcomes. Third, there is inadequate information on the genetic correlates of resistance to dolutegravir, particularly in patients infected with HIV-1 non-B subtypes. Finally, clinical management of patients with confirmed virological failure on a dolutegravir-based regimen can pose challenges because of uncertainty around whether dolutegravir resistance has actually developed and switching is needed, or whether only interventions to improve adherence without switching are sufficient. These considerations should be addressed to consolidate expected gains from widespread introduction of dolutegravir in low-income and middle-income countries.

Summary Background Between 2012 and 2016, development assistance for HIV/AIDS decreased by 20·0%; domestic financing is therefore critical to sustaining the response to HIV/AIDS. To understand whether domestic resources could fill the financing gaps created by declines in development assistance, we aimed to track spending on HIV/AIDS and estimated the potential for governments to devote additional domestic funds to HIV/AIDS. Methods We extracted 8589 datapoints reporting spending on HIV/AIDS. We used spatiotemporal Gaussian process regression to estimate a complete time series of spending by domestic sources (government, prepaid private, and out-of-pocket) and spending category (prevention, and care and treatment) from 2000 to 2016 for 137 low-income and middle-income countries (LMICs). Development assistance data for HIV/AIDS were from Financing Global Health 2018, and HIV/AIDS prevalence, incidence, and mortality were from the Global Burden of Disease study 2017. We used stochastic frontier analysis to estimate potential additional government spending on HIV/AIDS, which was conditional on the current government health budget and other finance, economic, and contextual factors associated with HIV/AIDS spending. All spending estimates were reported in 2018 US$. Findings Between 2000 and 2016, total spending on HIV/AIDS in LMICs increased from $4·0 billion (95% uncertainty interval 2·9–6·0) to $19·9 billion (15·8–26·3), spending on HIV/AIDS prevention increased from $596 million (258 million to 1·3 billion) to $3·0 billion (1·5–5·8), and spending on HIV/AIDS care and treatment increased from $1·1 billion (458·1 million to 2·2 billion) to $7·2 billion (4·3–11·8). Over this time period, the share of resources sourced from development assistance increased from 33·2% (21·3–45·0) to 46·0% (34·2–57·0). Care and treatment spending per year on antiretroviral therapy varied across countries, with an IQR of $284–2915. An additional $12·1 billion (8·4–17·5) globally could be mobilised by governments of LMICs to finance the response to HIV/AIDS. Most of these potential resources are concentrated in ten middle-income countries (Argentina, China, Colombia, India, Indonesia, Mexico, Nigeria, Russia, South Africa, and Vietnam). Interpretation Some governments could mobilise more domestic resources to fight HIV/AIDS, which could free up additional development assistance for many countries without this ability, including many low-income, high-prevalence countries. However, a large gap exists between available financing and the funding needed to achieve global HIV/AIDS goals, and sustained and coordinated effort across international and domestic development partners is required to end AIDS by 2030. Funding The Bill & Melinda Gates Foundation.

Summary box Affordable and equitable access to medical products and technologies have long been a challenge for health systems.1 The COVID-19 pandemic has further highlighted this critical challenge, making it a priority agenda issue for countries globally. Prices drive health expenditure and ultimately population-wide coverage and access to novel products. For example, DIME, an Inter-American Development Bank-funded project, estimated that Costa Rica, Ecuador and Mexico would have to allocate five times their annual immunisation budgets to cover their high-risk populations if prices recently announced for two leading vaccine candidates in high-income countries were held for these three countries.1 The high prices increase the financial burden for populations and governments.2 As part of a broader policymaking process, one role for government is developing and implementing well-planned pricing policies and guidelines to help ensure affordable and equitable access.3 The COVID-19 pandemic, however, limits pricing policy options. It is therefore necessary to consider what …

Background: In many units around the world, microsurgical free tissue transfer represents the gold standard for reconstruction of significant soft tissue defects following cancer, trauma or infection. However, many reconstructive units in low-income and middle-income countries (LMICs) do not yet have access to the resources, infrastructure or training required to perform any microsurgical procedures. Long-term international collaborations have been formed with annual short-term reconstructive missions conducting microsurgery. In the first instance, these provide reconstructive surgery to those who need it. In the longer-term, they offer an opportunity for teaching and the development of sustainable local services.Methods: A PRISMA-compliant systematic review and meta-analysis will be performed. A comprehensive, predetermined search strategy will be applied to the MEDLINE and Embase electronic databases from inception to December 2020. All clinical studies presenting sufficient data on free tissue transfer performed on short-term surgical missions (STSMs) in LMICs will be eligible for inclusion. The primary outcomes are rate of free flap failure, rate of emergency return to theatre for free flap salvage and successful salvage rate. The secondary outcomes include postoperative complications and any functional or patient reported outcome measures. Screening of studies, data extraction and assessments of study quality and bias will be conducted by two authors. Individual study quality will be assessed according to the Oxford Evidence-based Medicine Scales of Evidence 2, and risk of bias using either the ‘Revised Cochrane risk of bias tool for randomized trials’ (Rob2), or the ‘Risk of bias in non-randomized studies of interventions’ (ROBINS-I) tools. Overall strength of evidence will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.Discussion: To-date the outcomes of microsurgical procedures performed on STSMs to LMICs are largely unknown. Improved education, funding and allocation of resources are needed to support surgeons in LMICs to perform free tissue transfer. STSMs provide a vehicle for sustainable collaboration and training. Disseminating microsurgical skills could improve the care received by patients living with reconstructive pathology in LMICs, but this is poorly established. This study sets out a robust protocol for a systematic review designed to critically analyse outcomes. Systematic review registration: Submitted to PROSPERO (15/12/20 ID: 225613)

Objectives: This study aimed to analyze any reported antibiotic use for children aged