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Background Reliable surveillance systems are essential for identifying disease outbreaks and allocating resources to ensure universal access to diagnostics and treatment for endemic diseases. Yet, most countries with high disease burdens rely entirely on facility-based passive surveillance systems, which miss the vast majority of cases in rural settings with low access to health care. This is especially true for malaria, for which the World Health Organization estimates that routine surveillance detects only 14% of global cases. The goal of this study was to develop a novel method to obtain accurate estimates of disease spatio-temporal incidence at very local scales from routine passive surveillance, less biased by populations' financial and geographic access to care. Methods We use a geographically explicit dataset with residences of the 73,022 malaria cases confirmed at health centers in the Ifanadiana District in Madagascar from 2014 to 2017. Malaria incidence was adjusted to account for underreporting due to stock-outs of rapid diagnostic tests and variable access to healthcare. A benchmark multiplier was combined with a health care utilization index obtained from statistical models of non-malaria patients. Variations to the multiplier and several strategies for pooling neighboring communities together were explored to allow for fine-tuning of the final estimates. Separate analyses were carried out for individuals of all ages and for children under five. Cross-validation criteria were developed based on overall incidence, trends in financial and geographical access to health care, and consistency with geographic distribution in a district-representative cohort. The most plausible sets of estimates were then identified based on these criteria. Results Passive surveillance was estimated to have missed about 4 in every 5 malaria cases among all individuals and 2 out of every 3 cases among children under five. Adjusted malaria estimates were less biased by differences in populations' financial and geographic access to care. Average adjusted monthly malaria incidence was nearly four times higher during the high transmission season than during the low transmission season. By gathering patient-level data and removing systematic biases in the dataset, the spatial resolution of passive malaria surveillance was improved over ten-fold. Geographic distribution in the adjusted dataset revealed high transmission clusters in low elevation areas in the northeast and southeast of the district that were stable across seasons and transmission years. Conclusions Understanding local disease dynamics from routine passive surveillance data can be a key step towards achieving universal access to diagnostics and treatment. Methods presented here could be scaled-up thanks to the increasing availability of e-health disease surveillance platforms for malaria and other diseases across the developing world.

COVID-19 has wreaked havoc globally with particular concerns for sub-Saharan Africa (SSA), where models suggest that the majority of the population will become infected. Conventional wisdom suggests that the continent will bear a higher burden of COVID-19 for the same reasons it suffers from other infectious diseases: ecology, socio-economic conditions, lack of water and sanitation infrastructure, and weak health systems. However, so far SSA has reported lower incidence and fatalities compared to the predictions of standard models and the experience of other regions of the world. There are three leading explanations, each with different implications for the final epidemic burden: (1) low case detection, (2) differences in epidemiology (e.g. lowR(0)), and (3) policy interventions. The low number of cases have led some SSA governments to relaxing these policy interventions. Will this result in a resurgence of cases? To understand how to interpret the lower-than-expected COVID-19 case data in Madagascar, we use a simple age-structured model to explore each of these explanations and predict the epidemic impact associated with them. We show that the incidence of COVID-19 cases as of July 2020 can be explained by any combination of the late introduction of first imported cases, early implementation of non-pharmaceutical interventions (NPIs), and low case detection rates. We then re-evaluate these findings in the context of the COVID-19 epidemic in Madagascar through August 2020. This analysis reinforces that Madagascar, along with other countries in SSA, remains at risk of a growing health crisis. If NPIs remain enforced, up to 50,000 lives may be saved. Even with NPIs, without vaccines and new therapies, COVID-19 could infect up to 30% of the population, making it the largest public health threat in Madagascar for the coming year, hence the importance of clinical trials and continually improving access to healthcare.

Background 50% of Malagasy children have moderate to severe stunting. In 2016, a new 10 year National Nutrition Action Plan (PNAN III) was initiated to help address stunting and developmental delay. We report factors associated with risk of developmental delay in 3 and 4 year olds in the rural district of Ifanadiana in southeastern Madagascar in 2016. Methods The data are from a cross-sectional analysis of the 2016 wave of IHOPE panel data (a population-representative cohort study begun in 2014). We interviewed women ages 15-49 using the MICS Early Child Development Indicator (ECDI) module, which includes questions for physical, socio-emotional, learning and literacy/numeracy domains. We analyzed ECDI data using standardized z scores for relative relationships for 2 outcomes: at-risk-for-delay vs. an international standard, and lower-development-than-peers if ECDI z scores were > 1 standard deviation below study mean. Covariates included demographics, adult involvement, household environment, and selected child health factors. Variables significant at alpha of 0.1 were included a multivariable model; final models used backward stepwise regression, clustered at the sampling level. Results Of 432 children ages 3 and 4 years, 173 (40%) were at risk for delay compared to international norms and 68 children (16.0%) had lower-development than peers. This was driven mostly by the literacy/numeracy domain, with only 7% of children considered developmentally on track in that domain. 50.5% of children had moderate to severe stunting. 76 (17.6%) had > = 4 stimulation activities in past 3 days. Greater paternal engagement (OR 1.5 (1.09, 2.07)) was associated with increased delay vs. international norms. Adolescent motherhood (OR. 4.09 (1.40, 11.87)) decreased children's development vs. peers. Engagement from a non-parental adult reduced odds of delay for both outcomes (OR (95%CI = 0.76 (0.63, 0.91) & 0.27 (0.15, 0 48) respectively). Stunting was not associated with delay risk (1.36 (0.85, 2.15) or low development (0.92 (0.48, 1.78)) when controlling for other factors. Conclusions In this setting of high child malnutrition, stunting is not independently associated with developmental risk. A low proportion of children receive developmentally supportive stimulation from adults, but non-parent adults provide more stimulation in general than either mother or father. Stimulation from non-parent adults is associated with lower odds of delay.

Author summary Why was this study done? One of the largest contributors to preventable deaths in low- and middle-income countries is poor quality of care delivered by the public health system. Yet, given the multiple dimensions of care quality, there are currently no standard measures to evaluate impacts in this domain. While health system strengthening (HSS) initiatives strive to simultaneously increase access to healthcare and improve care quality, few studies have evaluated the impact of HSS initiatives on both targets. Our study sought to determine whether an HSS intervention in a rural health district of Madagascar, one of the world's poorest countries, improved the quality of maternal and child care at the population level. What did the researchers do and find? We used data from a district-representative open longitudinal cohort that followed over 1,500 households between 2014 and 2016, in order to compare trends in the content of care as a proxy for care quality, inside and outside the intervention catchment, through difference-in-differences analyses. We also analysed data from a Service Availability and Readiness Assessment (SARA) conducted in health facilities supported by the HSS intervention. Our data set included self-reported information on health seeking behaviors and care content for common illnesses of children under five ( = 657 in 2014; 411 in 2016), and for maternal care before and during live births that occurred in the previous two years ( = 552 in 2014; 524 in 2016). nnWe found that compared to the non-intervention group, the intervention group experienced a larger improvement in most care content outputs for childhood illnesses (e.g., 24.4% more children with diarrhea were prescribed oral rehydration therapy after two years than in the non-intervention area) and for perinatal care, whereas trends in antenatal care content were more similar in both populations. Despite progress, there remained important gaps in the provision of essential health services for individuals in both the intervention and non-intervention groups. What do these findings mean? The study provides evidence that HSS initiatives can successfully increase access to healthcare in target populations while also improving the quality of certain primary care services provided. The approach used here can be adapted to other local HSS initiatives to stimulate more comprehensive impact evaluations. Evidence from this study can help guide investments in integrated primary care systems that are needed globally to improve maternal and child care. The interpretation of the study findings is limited by the absence of randomization in the allocation of the intervention's programs and by the reliance on self-reported answers. Background In order to reach the health-related Sustainable Development Goals (SDGs) by 2030, gains attained in access to primary healthcare must be matched by gains in the quality of services delivered. Despite the broad consensus around the need to address quality, studies on the impact of health system strengthening (HSS) have focused predominantly on measures of healthcare access. Here, we examine changes in the content of maternal and child care as a proxy for healthcare quality, to better evaluate the effectiveness of an HSS intervention in a rural district of Madagascar. The intervention aimed at improving system readiness at all levels of care (community health, primary health centers, district hospital) through facility renovations, staffing, equipment, and training, while removing logistical and financial barriers to medical care (e.g., ambulance network and user-fee exemptions). Methods and findings We carried out a district-representative open longitudinal cohort study, with surveys administered to 1,522 households in the Ifanadiana district of Madagascar at the start of the HSS intervention in 2014, and again to 1,514 households in 2016. We examined changes in healthcare seeking behavior and outputs for sick-child care among children

Introduction A global strategy of mass drug administration (MDA) has greatly reduced the burden of lymphatic filariasis (LF) in endemic countries. In Madagascar, the National Programme to eliminate LF has scaled-up annual MDA of albendazole and diethylcarbamazine across the country in the last decade, but its impact on LF transmission has never been reported. The objective of this study was to evaluate progress towards LF elimination in southeastern Madagascar. Methods Three different surveys were carried out in parallel in four health districts of the Vatovavy Fitovinany region in 2016: i) a school-based transmission assessment survey (TAS) in the districts of Manakara Atsimo, Mananjary, and Vohipeno (following a successful pre-TAS in 2013); ii) a district-representative community prevalence survey in Ifanadiana district; and iii) a community prevalence survey in sentinel and spot-check sites of these four districts. LF infection was assessed using the Alere Filariasis Test Strips, which detect circulating filarial antigens (CFA) of adult worms. A brief knowledge, attitudes and practices questionnaire was included in the community surveys. Principal findings None of the 1,825 children sampled in the TAS, and only one in 1,306 children from sentinel and spot-check sites, tested positive to CFA. However, CFA prevalence rate in individuals older than 15 years was still high in two of these three districts, at 3.5 and 9.7% in Mananjary and Vohipeno, respectively. Overall CFA prevalence in sentinel and spot-check sites of these three districts was 2.80% (N = 2,707), but only two individuals had detectable levels of microfilaraemia (0.06%). Prevalence rate estimates for Ifanadiana were substantially higher in the district-representative survey (15.8%; N = 545) than in sentinel and spot-check sites (0.8%; N = 618). Only 51.2% of individuals surveyed in these four districts reported taking MDA in the last year, and 42.2% reported knowing about LF. Conclusions Although TAS results suggest that MDA can be stopped in three districts of southeastern Madagascar, the adult population still presents high CFA prevalence levels. This discordance raises important questions about the TAS procedures and the interpretation of their results.

Introduction The Sustainable Development Goals framed an unprecedented commitment to achieve global convergence in child and maternal mortality rates through 2030. To meet those targets, essential health services must be scaled via integration with strengthened health systems. This is especially urgent in Madagascar, the country with the lowest level of financing for health in the world. Here, we present an interim evaluation of the first 2 years of a district-level health system strengthening (HSS) initiative in rural Madagascar, using estimates of intervention coverage and mortality rates from a district-wide longitudinal cohort. Methods We carried out a district representative household survey at baseline of the HSS intervention in over 1500 households in Ifanadiana district. The first follow-up was after the first 2 years of the initiative. For each survey, we estimated maternal, newborn and child health (MNCH) coverage, healthcare inequalities and child mortality rates both in the initial intervention catchment area and in the rest of the district. We evaluated changes between the two areas through difference-in-differences analyses. We estimated annual changes in health centre per capita utilisation from 2013 to 2016. Results The intervention was associated with 19.1% and 36.4% decreases in under-five and neonatal mortality, respectively, although these were not statistically significant. The composite coverage index (a summary measure of MNCH coverage) increased by 30.1%, with a notable 63% increase in deliveries in health facilities. Improvements in coverage were substantially larger in the HSS catchment area and led to an overall reduction in healthcare inequalities. Health centre utilisation rates in the catchment tripled for most types of care during the study period. Conclusion At the earliest stages of an HSS intervention, the rapid improvements observed for Ifanadiana add to preliminary evidence supporting the untapped and poorly understood potential of integrated HSS interventions on population health.

Background Several studies have suggested a survival benefit of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head. Data concerning NAT for PDAC located in pancreatic body or tail are lacking. Methods Post hoc analysis of an international multicenter retrospective cohort of distal pancreatectomy for PDAC in 34 centers from 11 countries (2007–2015). Patients who underwent resection after NAT were matched (1:1 ratio), using propensity scores based on baseline characteristics, to patients who underwent upfront resection. Median overall survival was compared using the stratified log-rank test. Results Among 1236 patients, 136 (11.0%) received NAT, most frequently FOLFIRINOX (25.7%). In total, 94 patients receiving NAT were matched to 94 patients undergoing upfront resection. NAT was associated with less postoperative major morbidity (Clavien–Dindo ≥ 3a, 10.6% vs. 23.4%, P = 0.020) and pancreatic fistula grade B/C (9.6% vs. 21.3%, P = 0.026). NAT did not improve overall survival [27 (95% CI 14–39) versus 31 months (95% CI 19–42), P = 0.277], as compared with upfront resection. In a sensitivity analysis of 251 patients with radiographic tumor involvement of splenic vessels, NAT (n = 37, 14.7%) was associated with prolonged overall survival [36 (95% CI 18–53) versus 20 months (95% CI 15–24), P = 0.049], as compared with upfront resection. Conclusion In this international multicenter cohort study, NAT for resected PDAC in pancreatic body or tail was associated with less morbidity and pancreatic fistula but similar overall survival in comparison with upfront resection. Prospective studies should confirm a survival benefit of NAT in patients with PDAC and splenic vessel involvement.

Importance: The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.Objective: To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.Design, Setting, and Participants: This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded.Exposures: The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise.Results: We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73).Conclusions and Relevance: These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.