Defining operational research priorities to improve malaria control and elimination in sub-Saharan Africa: results from a country-driven research prioritization setting process.

BACKGROUND: In order to reignite gains and accelerate progress toward improved malaria control and elimination, policy, strategy, and operational decisions should be derived from high-quality evidence. The U.S. President's Malaria Initiative (PMI) Insights project together with the Université Cheikh Anta Diop of Dakar, Senegal, conducted a broad stakeholder consultation process to identify pressing evidence gaps in malaria control and elimination across sub-Saharan Africa (SSA), and developed a priority list of country-driven malaria operational research (OR) and programme evaluation (PE) topics to address these gaps. METHODS: Five key stakeholder groups were engaged in the process: national malaria programmes (NMPs), research institutions in SSA, World Health Organization (WHO) representatives in SSA, international funding agencies, and global technical partners who support malaria programme implementation and research. Stakeholders were engaged through individual or small group interviews and an online survey, and asked about key operational challenges faced by NMPs, pressing evidence gaps in current strategy and implementation guidance, and priority OR and PE questions to address the challenges and gaps. RESULTS: Altogether, 47 interviews were conducted with 82 individuals, and through the online survey, input was provided by 46 global technical partners. A total of 33 emergent OR and PE topics were identified through the consultation process and were subsequently evaluated and prioritized by an external evaluation committee of experts from NMPs, research institutions, and the WHO. The resulting prioritized OR and PE topics predominantly focused on generating evidence needed to close gaps in intervention coverage, address persistent challenges faced by NMPs in the implementation of core strategic interventions, and inform the effective deployment of new tools. CONCLUSION: The prioritized research list is intended to serve as a key resource for informing OR and PE investments, thereby ensuring future investments focus on generating the evidence needed to strengthen national strategies and programme implementation and facilitating a more coordinated and impactful approach to malaria operational research.

Malaria-associated risk factors among adolescents living in areas with persistent transmission in Senegal: a case-control study.

BACKGROUND: In Senegal, malaria morbidity has sharply decreased over these past years. However, malaria epidemiology remains heterogeneous with persistent transmission in the southeastern part of the country and many cases among older children and adolescents. Little is known about factors associated with clinical malaria among this group. A better understanding of malaria transmission among this newly emerging vulnerable group will guide future interventions targeting this population group. This study aimed to identify factors associated with clinical malaria among adolescents in Senegal. METHODS: A case-control study was conducted from November to December 2020 in four health posts located in the Saraya district. Cases were defined as adolescents (10-19 years) with an uncomplicated malaria episode with fever (temperature > 37.5°) or a history of fever and positive malaria rapid diagnostic test (RDT). Controls were from the same age group, living in the neighbourhood of the case, presenting a negative RDT. A standardized, pre-tested questionnaire was administered to each study participant followed by a home visit to assess the participant's living conditions. Factors associated with clinical malaria were assessed using stepwise logistic regression analysis. RESULTS: In total, 492 individuals were recruited (246 cases and 246 controls). In a multivariate analysis, factors associated with clinical malaria included non-use of long-lasting insecticidal net (LLIN) (aOR = 2.65; 95% CI 1.58-4.45), non-use of other preventive measures (aOR = 2.51; 95% CI 1.53-4.11) and indoor sleeping (aOR = 3.22; 95% CI 1.66-6.23). Protective factors included 15-19 years of age (aOR = 0.38; 95% CI 0.23-0.62), absence of stagnant water around the house (aOR = 0.27; 95% CI 0.16-0.44), having a female as head of household (aOR = 0.47; 95% CI 0.25-0.90), occupation such as apprentice (OR = 0.24; 95% CI 0.11-0.52). CONCLUSIONS: The study revealed that environmental factors and non-use of malaria preventive measures are the main determinants of malaria transmission among adolescents living in areas with persistent malaria transmission in Senegal. Strategies aimed at improving disease awareness and access to healthcare interventions, such as LLINs, are needed to improve malaria control and prevention among these vulnerable groups.

Malaria prevalence and use of control measures in an area with persistent transmission in Senegal.

INTRODUCTION: In Senegal, the widespread use of vector control measures has resulted in a significant reduction in the malaria burden and led the country to consider the possibility of elimination. Given this shift and changing context, it is important to characterize the malaria burden across all age groups to guide decision-making on programmatic interventions to interrupt transmission and ultimately eradicate the disease. In Senegal, there is a lack of information on malaria prevalence among certain populations, particularly among adolescents and adults. This study sought to assess the magnitude of malaria infections in all age groups, as well as malaria associated factors in an area of persistent transmission in Senegal. METHODS: A cross-sectional household survey was conducted in four health posts (Khossanto, Mamakhona, Diakhaling and Sambrambougou), of the health district of Saraya, in November 2021, among individuals over 6 months of age. Households were selected using multistage sampling. Consented participants were screened for malaria parasites by microscopic examination of blood smears, and hemoglobin levels were measured using the Hemocue HB 301TM analyzer. Socio-demographic information of the participants, household heads, household assets, and information on ownership and use of preventive measures were collected using a structured questionnaire. Weighted generalized mixed effects logistic regression model was used to identify factors associated with microscopically confirmed malaria infection. RESULTS: A total of 1759 participants were enrolled in the study. Overall, about 21% of participants were classified as having Plasmodium infection; children aged 5-10 years old (26.6%), adolescents aged 10-19 years old (24.7%), and children under five years of age (20.5%) had higher rates of infection compared to adults (13.5%). Plasmodium falciparum accounted for 99.2% of the malaria infections, and most infections (69%) were asymptomatic. Around one-third of study participants had anemia (hemoglobin level <11.0 g/dl), with under five children bearing the highest burden (67.3%). Multivariate analysis showed that the odds of having a malaria infection were around 2 times higher among participants in Khossanto compared to Diakhaling (aOR = 1.84, 95% CI:1.06-3.20). Participants aged 5-9 years were more likely to have malaria infection compared to under five children (aOR = 1.40, 95% CI:1.02-1.91). Factors associated with anemia were P. falciparum infection (aOR = 1.36, p = 0.027), females (aOR = 2.16, p = 0.000), under-five age group (aOR = 13.01, p = 0.000). CONCLUSION: Malaria burden was considerable among adolescents and under ten children living in an area of persistent transmission, with adolescents more commonly presenting as asymptomatic. Interventions tailored to this specific group of the population are needed to better control the disease and reduce its burden.

Developing a data repository to support interdisciplinary research into childhood stunting: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: As a topic of inquiry in its own right, data management for interdisciplinary research projects is in its infancy. Key issues include the inability of researchers to effectively query diverse data outputs and to identify potentially important synergies between discipline-specific data. Equally problematic, few semantic ontologies exist to better support data organisation and discovery. Finally, while interdisciplinary research is widely regarded as beneficial to unpacking complex problems, non-researchers such as policy-makers and planners often struggle to use and interrogate the related datasets. To address these issues, the following article details the design and development of the UKRI GCRF Action Against Stunting Hub (AASH)'s All-Hub Data Repository (AHDR). METHODS AND ANALYSIS: The AHDR is a single application, single authentication web-based platform comprising a data warehouse to store data from across the AASH's three study countries and to support data querying. Four novel components of the AHDR are described in the following article: (1) a unique data discovery tool; (2) a metadata catalogue that provides researchers with an interface to explore the AASH's data outputs and engage with a new semantic ontology related to child stunting; (3) an interdisciplinary aid to support a directed approach to identifying synergies and interactions between AASH data and (4) a decision support tool that will support non-researchers in engaging with the wider evidence-based outputs of the AASH. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by institutional ethics committees in the UK, India, Indonesia and Senegal. Results will be disseminated via publications in peer-reviewed journals; presentations at international conferences and community-level public engagement events; key stakeholder meetings; and in public repositories with appropriate Creative Commons licences allowing for the widest possible use.

Prevalence of Malaria Infection in Pregnant Women Attending Antenatal Clinics in Southern Senegal.

Despite marked progress in Senegal, three regions in the southeast part continue to have a high burden of malaria, but there have been no recent studies assessing the prevalence of malaria associated with pregnancy. This study aimed to determine the prevalence of malaria infection in pregnant women attending antenatal clinics in Senegal. During the malaria transmission season of 2019, pregnant women attending 11 health care facilities for a scheduled visit and those presenting unwell with signs of malaria were invited to participate in a malaria screening study. A finger prick blood sample was taken for malaria diagnosis by rapid diagnosis test (RDT) and polymerase chain reaction (PCR). A total of 877 pregnant women were enrolled, 787 for a scheduled antenatal consultation and 90 for an unscheduled consultation with signs of malaria. The prevalence of Plasmodium falciparum among the first group was 48% by PCR and 20% by RDT, and that among the second group was 86% by PCR and 83% by RDT. RDT sensitivity in capturing asymptomatic, PCR-positive infections was 9.2% but ranged from 83% to 94% among febrile women. The prevalence of infection by PCR in women who reported having received at least three doses of sulfadoxine pyrimethamine (SP) was 41.9% compared with 58.9% in women who reported they had not received any SP doses (prevalence ratio adjusted for gravidity and gestational age, 0.54; 95% CI, 0.41-0.73). The burden of P. falciparum infections remains high among pregnant women, the majority of which are not captured by RDT. More effective measures to prevent malaria infection in pregnancy are needed.

Monitoring the progress and impact of a multicountry, interdisciplinary research project on childhood stunting: the UKRI GCRF Action Against Stunting Hub MEL protocol.

INTRODUCTION: Monitoring, Evaluation and Learning (MEL) is an integral part of research, programme and policy development and implementation. However, MEL methods used to monitor and evaluate interdisciplinary research projects are often informal and under-reported. This article describes the MEL protocol of the UKRI GCRF Action Against Stunting Hub (AASH). METHODS AND ANALYSIS: The AASH conducts interdisciplinary research into childhood stunting in India, Indonesia and Senegal across 23 distinct work packages. Project-specific MEL framework and methods will be implemented. A logframe will be developed to monitor and evaluate the research activities across the field sites including the number of participants recruited, questionnaires, measurements and procedures completed. MEL dashboards using Tableau and Glasscubes will be used to track and report progress, milestones and outcomes of the project. Dashboard outputs will be reported as numbers and percentages, with additional graphs/charts for easy visualisation. A 'learning' framework will be developed to outline appropriate pipelines for the dissemination of the research findings. This includes a theory of change explicating the overarching ambitions of the project in influencing policy, practice and research, and strategic engagement of relevant stakeholders to evaluate knowledge, attitudes and best practices for impactful engagement and dissemination of the research findings. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee of the London School of Hygiene & Tropical Medicine (17915/RR/17513); National Institute of Nutrition (ICMR)-Ministry of Health and Family Welfare, Government of India (CR/04/I/2021); Health Research Ethics Committee, University of Indonesia and Cipto Mangunkusumo Hospital (KET-887/UN2.F1/ETIK/PPM.00.02/2019); and the National Ethics Committee for Health Research (CNERS), Senegal (Protocole SEN19/78). Findings from this work will be published in peer-reviewed journals, presented in conferences and disseminated to policy makers and research communities.

Malaria prevention knowledge, attitudes, and practices (KAP) among adolescents living in an area of persistent transmission in Senegal: Results from a cross-sectional study.

INTRODUCTION: While malaria morbidity has sharply declined in several areas in Senegal, it remains an important problem in the southern part of the country, particularly among adolescents. Understanding adolescents' knowledge, attitudes, prevention and care-seeking practices is important to inform more targeted interventions aimed at optimizing adolescents' uptake of malaria prevention and control measures. This study assessed malaria-related knowledge, attitudes, and practices (KAP) among adolescents living in a highly persistent transmission area in Senegal. METHODS: A community-based cross-sectional survey was conducted among 391 adolescents living in the Saraya health district. A multistage random sampling technique was used to select households. An electronic questionnaire developed on Open Data Kit (ODK), was used to collect data on socio-demographic characteristics, household assets, adolescents' knowledge of malaria, as well as their attitudes with regards to malaria prevention, and care-seeking behaviors. Bivariate and multivariate analyses were performed to assess factors associated with adolescents' KAP towards malaria. RESULTS: Nearly, one-third of the participants had good knowledge of malaria (34.4%) and good practice in regards to malaria preventive measures (32.8%) while 59.0% had a positive attitude and 73.8% had good care-seeking behavior regarding malaria. Multivariate analysis revealed that a primary (aOR = 5.43, p = 0.002) or secondary level of education (aOR = 10.41, p = 0.000) was associated with good knowledge of malaria transmission, signs, and prevention measures. Male individuals had lower knowledge compared to female ones (aOR = 0.40, p = 0.001). Individuals belonging to households from the highest wealth quintile were more likely to have a positive attitude towards malaria compared to those from households in the lowest wealth quintile (aOR = 3.49, p = 0.004). The odds of positive attitude towards malaria decreased among participants with koranic and primary education level, respectively (aOR = 0.14, p = 0.005) and (aOR = 0.24, p = 0.019). A positive attitude was 1.89 more likely to be (aOR = 1.89, p = 0.026) associated with good practice of prevention measures compared to adolescents who demonstrated negative attitudes. Individuals from households in the fourth (aOR = 0.42, p = 0.024), middle (aOR = 0.34, P = 0.005), and second (aOR = 0.42, p = 0.027) wealth quintiles were less likely to use malaria prevention measures compared to those from households in the highest wealth quintile. CONCLUSION: The study revealed that adolescents, generally have poor levels of malaria knowledge and low uptake of malaria prevention and control interventions. Targeted interventions for high-risk adolescents are needed, that focus on improving their knowledge of the disease and effective preventive measures, and on increasing their access to health care services and LLINs.

Effectiveness of seasonal malaria chemoprevention administered in a mass campaign in the Kedougou region of Senegal in 2016: a case-control study.

Background: Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) is a malaria prevention strategy recommended since 2012 by the World Health Organization (WHO) for children under 5 years. In Senegal, the scaling up of SMC started in 2013 in the south-eastern regions of the country with an extension of the target to 10 years old children. The scaling up of SMC requires regular evaluation of the strategy as recommended by the WHO. This study was conducted to evaluate the effectiveness of SMC. Methods: A case-control study was conducted in some villages of the health districts of Saraya and Kedougou in the Kedougou region from July to December 2016. A case was a sick child, aged 3 months to 10 years, seen in consultation and with a positive malaria rapid diagnostic test (RDT). The control was a child of the same age group with a negative RDT and living in the same compound as the case or in a neighbouring compound. Each case was matched with two controls. Exposure to SMC was assessed by interviewing the mothers/caretakers and by checking the SMC administration card. Results: Overall, 492 children, including 164 cases and 328 controls, were recruited in our study. Their mean ages were 5.32 (+/- 2.15) and 4.44 (+/-2.25) years for cases and controls, respectively. The number of boys was higher in both cases (55.49%; CI 95%=47.54-63.24%) and controls (51,22%; CI 95%=45.83-56.58%). Net ownership was 85.80% among cases and 90.85% among controls (p=0,053). The proportion of controls who received SMC was higher than that of cases (98.17% vs 85.98% and p=1.10 -7). The protective effectiveness of SMC was 89% (OR= 0.12 (CI 95%=0.04-0.28)). Conclusions: SMC is an effective strategy in the control of malaria in children. Case-control studies are a good approach for monitoring the efficacy of drugs administered during SMC.

Malaria parasite carriage before and two years after the implementation of seasonal malaria chemoprevention: a case study of the Saraya health district, southern Senegal.

Background : Seasonal malaria chemoprevention (SMC) has been adopted and implemented in the southern regions of Senegal in children aged between three and 120 months since 2013. Scaling up this strategy requires its evaluation to assess the impact. This study was carried out to determine the dynamics of Plasmodium falciparum carriage before and after two years of SMC implementation. Methods : Four household surveys were conducted in villages in the health district of Saraya, which is a SMC implementation area in Senegal. These villages were selected using probability proportional to size sampling. Each selected village was divided into segments containing at least 50 children. In each segment, a household questionnaire was administered to the parents or legal representatives of children aged three to 120 months. Blood smears were collected to determine P. falciparum prevalence by microscopy one month before the first round of SMC, one month after the last round of the first SMC campaign and two years after the start of the implementation. Results : A total of 2008 children were included with a mean average age of 4.81 (+/-2.73) years. Of the study population, 50.33% were more than five years old and 50.3% were male. In 2013, mosquito net ownership was 99.4 % before the SMC campaign and 97.4% after. In 2015, it was 36.6% before and 45.8% after the campaign. In 2013, the prevalence of plasmodium carriage was 11.8% before and 6.1% after the SMC campaign. In 2015, the prevalence was 4.9% before the administration of SMC and this increased up to 15.3% after. Malaria prevalence was high among children over five years old and in boys. Conclusions : The decrease in Plasmodium falciparum parasite prevalence, which subsequently increased after two years of SMC implementation in this study, suggests adding an extra cycle of the SMC or adjusting the administration period.

Reduction in neural-tube defects after folic acid fortification in Canada.

BACKGROUND: In 1998, folic acid fortification of a large variety of cereal products became mandatory in Canada, a country where the prevalence of neural-tube defects was historically higher in the eastern provinces than in the western provinces. We assessed changes in the prevalence of neural-tube defects in Canada before and after food fortification with folic acid was implemented. METHODS: The study population included live births, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces from 1993 to 2002. On the basis of published results of testing of red-cell folate levels, the study period was divided into prefortification, partial-fortification, and full-fortification periods. We evaluated the relationship between baseline rates of neural-tube defects in each province and the magnitude of the decrease after fortification was implemented. RESULTS: A total of 2446 subjects with neural-tube defects were recorded among 1.9 million births. The prevalence of neural-tube defects decreased from 1.58 per 1000 births before fortification to 0.86 per 1000 births during the full-fortification period, a 46% reduction (95% confidence interval, 40 to 51). The magnitude of the decrease was proportional to the prefortification baseline rate in each province, and geographical differences almost disappeared after fortification began. The observed reduction in rate was greater for spina bifida (a decrease of 53%) than for anencephaly and encephalocele (decreases of 38% and 31%, respectively). CONCLUSIONS: Food fortification with folic acid was associated with a significant reduction in the rate of neural-tube defects in Canada. The decrease was greatest in areas in which the baseline rate was high.

Spina bifida before and after folic acid fortification in Canada.

BACKGROUND: In 1998, fortification of a large variety of cereal products with folic acid became mandatory in Canada. A multicentric study was carried out to assess the impact of this policy on the frequency of NTDs. The present analysis focused on spina bifida. METHODS: The study population included approximately 2 million livebirths, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces, from 1993 to 2002. Spina bifida cases were divided according to the upper limit of the defect: upper (cranial, cervical, or thoracic) and lower (lumbar or sacral) defects. Based on published results of red blood cell folate tests, the study period was divided into prefortification, partial fortification, and full fortification periods. RESULTS: A total of 1,286 spina bifida cases were identified: 51% livebirths, 3% stillbirths, and 46% terminations. Prevalence decreased from 0.86/1,000 in the prefortification to 0.40 in the full fortification period, while the proportion of upper defects decreased from 32% to 13%. Following fortification, regional variations in the prevalence and distribution of sites almost disappeared. CONCLUSIONS: Results confirmed the etiologic heterogeneity of spina bifida and the more pronounced effect of folic acid in decreasing the risk of the more severe clinical presentations.

Impact of folic acid food fortification on the birth prevalence of lipomyelomeningocele in Canada.

BACKGROUND: Recent studies reported no reduction in the frequency of lipomeningomyelocele (LMMC) in Hawaii and Nova Scotia after the implementation of a folic acid food fortification policy in 1998, while a marked reduction in the prevalence of other NTDs was observed. This study was performed to assess the prevalence of LMMC in Canada in relation to the timing of food fortification. METHODS: The study population included livebirths, stillbirths, and terminations of pregnancies because of fetal anomaly to women residing in seven Canadian provinces, from 1993 to 2002. In each province, the ascertainment of NTD cases relied on multiple sources, and in addition all medical charts were reviewed. The study period was divided into pre-, partial, and full fortification periods, based on results of red cell folate tests published in the literature. RESULTS: A total of 86 LMMC cases were recorded among approximately 1.9 million live births. The average birth prevalence rate was 0.05/1,000, ranging from a minimum of 0.01/1,000 in 2002 to a maximum of 0.08/1,000 in 1999. There was statistical heterogeneity between years (p = .01), but no pattern compatible with a decrease following fortification. Comparing the full fortification period with the prefortification period, there was a slight but not statistically significant decrease in LMMC birth prevalence. CONCLUSIONS: LMMC seems to be pathogenically distinct from myelomeningocele and more studies are needed to understand the embryologic mechanisms leading to this condition, and the environmental and genetic factors involved in its etiology.

Evaluation of Two Strategies for Community-Based Safety Monitoring during Seasonal Malaria Chemoprevention Campaigns in Senegal, Compared with the National Spontaneous Reporting System.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine has been introduced in 12 African countries. Additional strategies for safety monitoring are needed to supplement national systems of spontaneous reporting that are known to under represent the incidence of adverse reactions. OBJECTIVES: This study aimed to determine if adverse event (AE) reporting could be improved using a smartphone application provided to village health workers, or by active follow-up using a symptom card provided to caregivers. METHODS: Two strategies to improve reporting of AEs during SMC campaigns were evaluated, in comparison with the national system of spontaneous reporting, in 11 health post areas in Senegal. In each health post, an average of approximately 4000 children under 10 years of age received SMC treatment each month for 3 months during the 2015 malaria transmission season-a total of 134,000 treatments. In three health posts (serving approximately 14,000 children), caregivers were encouraged to report any adverse reactions to the nurse at the health post or to a community health worker (CHW) in their village, who had been trained to use a smartphone application to report the event (enhanced spontaneous reporting). In two health posts (approximately 10,000 children), active follow-up of children at home was organized after each SMC campaign to ask about AEs that caregivers had been asked to record on a symptom card (active surveillance). Six health posts (approximately 23,000 children) followed the national system of spontaneous reporting using the national reporting (yellow) form. Each AE report was assessed by a panel to determine likely association with SMC drugs. RESULTS: The incidence of reported AEs was 2.4, 30.6, and 21.6 per 1000 children treated per month, using the national system, enhanced spontaneous reporting, and active surveillance, respectively. The most commonly reported symptoms were vomiting, fever, and abdominal pain. The incidence of vomiting, known to be caused by amodiaquine, was similar using both innovative methods (10/1000 in the first month, decreasing to 2.5/1000 in the third month). Despite increased surveillance, no serious adverse drug reactions were detected. CONCLUSION: Training CHWs in each village and health facility staff to report AEs using a mobile phone application led to much higher reporting rates than through the national system. This approach is feasible and acceptable, and could be further improved by strengthening laboratory investigation and the collection of control data immediately prior to SMC campaigns.

Validity of death and stillbirth certificates and hospital discharge summaries for the identification of neural tube defects in Quebec City.

The objectives of this study were 1) to assess the validity of different databases which identify neural tube defect (NTD) cases in the population, and 2) to examine the temporal trends in NTD rates and the impact of prenatal diagnoses among pregnancies referred to a tertiary care hospital in Quebec City, Canada, from 1993 to 2002. Infant death and stillbirth certificates were a highly reliable source for ascertaining NTD cases, but their overall sensitivity was poor (13 percent). Med-Echo had very good sensitivity (92 percent), but there were many coding errors in the database and some diagnostic categories were not specific for NTD. The average NTD prevalence proportion was 6.5/1,000 births during the entire study period, decreasing from 12.2/1,000 in 1993 to 3.9/1,000 in 2002. Overall, 78.6 percent of NTD cases were diagnosed prenatally and the pregnancy was terminated in 52.6 percent of these. These two proportions were stable over the study years. To conclude, the combination of hospital discharge summaries and infant death and stillbirth certificates is a highly sensitive method for the ascertainment of NTD cases, including terminations of pregnancies, but medical records must be reviewed to exclude coding errors and to clarify unspecific diagnostic categories.