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.

Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data.

BACKGROUND: In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. METHODS: A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. RESULTS: Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. CONCLUSIONS: Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. TRIAL REGISTRATION: PROSPERO, CRD42019128185.

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.

Survival of eight LLIN brands 6, 12, 24 and 36 months after a mass distribution campaign in rural and urban settings in Senegal.

BACKGROUND: Long lasting insecticidal nets (LLIN) are one of the core components of global malaria prevention and control. The lifespan of LLIN varies widely depending on the population or environment, and randomized studies are required to compare LLIN inaccording to arbitrary thresholds households under different field conditions. This study investigated survival of different LLIN brands in Senegal. METHODS: Ten thousand six hundred eight LLINs were distributed in five regions, each stratified by rural and urban setting. As part of the longitudinal follow-up, 2222 nets were randomly sampled and monitored from 6 to 36 months. Using random effects for households, Bayesian models were used to estimate independent survival by net type (Interceptor®, Life Net®, MAGNet™, Netprotect®, Olyset® Net, PermaNet® 2.0 R, PermaNet® 2.0 C, Yorkool® LN) and by area (rural/urban). In addition to survival, median survival time and attrition of each LLIN brand was determined. Attrition was defined as nets that were missing because they were reported given away, destroyed and thrown away, or repurposed. RESULTS: Three net types had a proportion of survival above 80% after 24 months: Interceptor®87.8% (95% CI 80-93.4); conical PermaNet® 2.0 86.9% (95% CI 79.3-92.4) and Life Net® 85.6% (95% CI 75-93). At 36 months, conical PermaNet® 2.0 maintained a good survival rate, 79.5% (95% CI 65.9-88.8). The attrition due to redistributed nets showed that the two conical net types (PermaNet® 2.0 and Interceptor®) were more often retained by households and their median retention time was well above 3 years (median survival time = 3.5 years for PermaNet® 2.0 and median survival time = 4 years for Interceptor®). Despite this good retention, Interceptor® had weak physical integrity and its median survival due to wear and tear was below 3 years (median survival time = 2.4 years). The odds ratio of survival was 2.5 times higher in rural settings than in urban settings (OR 2.5; 95% CI 1.7-3.7). CONCLUSIONS: Differences in survival among LLIN may be driven by brand, shape or environmental setting. In this study in Senegal, conical PermaNet® 2.0 were retained in households while rectangular PermaNet® 2.0 had lower retention, suggesting that net shape may play a role in retention and should be further investigated. Distribution of preferred LLIN shape, accompanied by good communication on care and repair, could lead to increased effective lifespan, and allow for longer intervals between universal coverage campaigns.

A data quality assessment of the first four years of malaria reporting in the Senegal DHIS2, 2014-2017.

BACKGROUND: As the global burden of malaria decreases, routine health information systems (RHIS) have become invaluable for monitoring progress towards elimination. The District Health Information System, version 2 (DHIS2) has been widely adopted across countries and is expected to increase the quality of reporting of RHIS. In this study, we evaluated the quality of reporting of key indicators of childhood malaria from January 2014 through December 2017, the first 4 years of DHIS2 implementation in Senegal. METHODS: Monthly data on the number of confirmed and suspected malaria cases as well as tests done were extracted from the Senegal DHIS2. Reporting completeness was measured as the number of monthly reports received divided by the expected number of reports in a given year. Completeness of indicator data was measured as the percentage of non-missing indicator values. We used a quasi-Poisson model with natural cubic spline terms of month of reporting to impute values missing at the facility level. We used the imputed values to take into account the percentage of malaria cases that were missed due to lack of reporting. Consistency was measured as the absence of moderate and extreme outliers, internal consistency between related indicators, and consistency of indicators over time. RESULTS: In contrast to public facilities of which 92.7% reported data in the DHIS2 system during the study period, only 15.3% of the private facilities used the reporting system. At the national level, completeness of facility reporting increased from 84.5% in 2014 to 97.5% in 2017. The percentage of expected malaria cases reported increased from 76.5% in 2014 to 94.7% in 2017. Over the study period, the percentage of malaria cases reported across all districts was on average 7.5% higher (P < 0.01) during the rainy season relative to the dry season. Reporting completeness rates were lower among hospitals compared to health centers and health posts. The incidence of moderate and extreme outlier values was 5.2 and 2.3%, respectively. The number of confirmed malaria cases increased by 15% whereas the numbers of suspected cases and tests conducted more than doubled from 2014 to 2017 likely due to a policy shift towards universal testing of pediatric febrile cases. CONCLUSIONS: The quality of reporting for malaria indicators in the Senegal DHIS2 has improved over time and the data are suitable for use to monitor progress in malaria programs, with an understanding of their limitations. Senegalese health authorities should maintain the focus on broader adoption of DHIS2 reporting by private facilities, the sustainability of district-level data quality reviews, facility-level supervision and feedback mechanisms at all levels of the health system.

Key informant perspectives on the challenges and opportunities for using routine health data for decision-making in Senegal.

BACKGROUND: Increasing the performance of routine health information systems (RHIS) is an important policy priority both globally and in Senegal. As RHIS data become increasingly important in driving decision-making in Senegal, it is imperative to understand the factors that determine their use. METHODS: Semi-structured interviews were conducted with 18 high- and mid-level key informants active in the malaria, tuberculosis and HIV programmatic areas in Senegal. Key informants were employed in the relevant divisions of the Senegal Ministry of Health or nongovernmental / civil society organizations. We asked respondents questions related to the flow, quality and use of RHIS data in their organizations. A framework approach was used to analyze the qualitative data. RESULTS: Although the respondents worked at the strategic levels of their respective organizations, they consistently indicated that data quality and data use issues began at the operational level of the health system before the data made its way to the central level. We classify the main identified barriers and facilitators to the use of routine data into six categories and attempt to describe their interrelated nature. We find that data quality is a central and direct determinant of RHIS data use. We report that a number of upstream factors in the Senegal context interact to influence the quality of routine data produced. We identify the sociopolitical, financial and system design determinants of RHIS data collection, dissemination and use. We also discuss the organizational and infrastructural factors that influence the use of RHIS data. CONCLUSIONS: We recommend specific prescriptive actions with potential to improve RHIS performance in Senegal, the quality of the data produced and their use. These actions include addressing sociopolitical factors that often interrupt RHIS functioning in Senegal, supporting and motivating staff that maintain RHIS data systems as well as ensuring RHIS data completeness and representativeness. We argue for improved coordination between the various stakeholders in order to streamline RHIS data processes and improve transparency. Finally, we recommend the promotion of a sustained culture of data quality assessment and use.

Molecular detection and quantification of Plasmodium falciparum gametocytes carriage in used RDTs in malaria elimination settings in northern Senegal.

BACKGROUND: Malaria surveillance requires powerful tools and strategies to achieve malaria elimination. Rapid diagnostic tests for malaria (RDTs) are easily deployed on a large scale and are helpful sources of parasite DNA. The application of sensitive molecular techniques to these RDTs is a modern tool for improving malaria case detection and drug resistance surveillance. Several studies have made it possible to extract the DNA of Plasmodium falciparum from RDTs. The knowledge of gametocyte carriage in the population is important to better assess the level of parasite transmission in elimination settings. The aim of this study was to detect P. falciparum gametocytes from used RDTs by quantitative PCR for molecular monitoring of malaria transmission. METHODS: DNA was extracted from 303 RDT devices (SD Bioline Malaria Pf) using the Chelex-100 protocol. qPCR was performed in a 20 µL reaction to detect and quantify transcripts of the pfs25 gene. The cycle threshold (Ct) was determined by the emission fluorescence corresponding to the initial amount of amplified DNA. RESULTS: The study found an overall prevalence of 53.47% with an average Ct of 32.12 ± 4.28 cycles. In 2018, the prevalence of gametocytes was higher in the Ranérou district (76.24%) than in the Saint-Louis district (67.33%) where an increase in the number of gametocyte carriers in 2018 was noted, in comparison with 2017. CONCLUSIONS: RDTs are a good source of DNA for molecular monitoring of gametocyte carriage. This method is a simple and effective tool to better understand the level of malaria transmission with a view to elimination.

Seasonal malaria chemoprevention combined with community case management of malaria in children under 10 years of age, over 5 months, in south-east Senegal: A cluster-randomised trial.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is recommended in the Sahel region of Africa for children under 5 years of age, for up to 4 months of the year. It may be appropriate to include older children, and to provide protection for more than 4 months. We evaluated the effectiveness of SMC using sulfadoxine-pyrimethamine plus amodiaquine given over 5 months to children under 10 years of age in Saraya district in south-east Senegal in 2011. METHODS AND FINDINGS: Twenty-four villages, including 2,301 children aged 3-59 months and 2,245 aged 5-9 years, were randomised to receive SMC with community case management (CCM) (SMC villages) or CCM alone (control villages). In all villages, community health workers (CHWs) were trained to treat malaria cases with artemisinin combination therapy after testing with a rapid diagnostic test (RDT). In SMC villages, CHWs administered SMC to children aged 3 months to 9 years once a month for 5 months. The study was conducted from 27 July to 31 December 2011. The primary outcome was malaria (fever or history of fever with a positive RDT). The prevalence of anaemia and parasitaemia was measured in a survey at the end of the transmission season. Molecular markers associated with resistance to SMC drugs were analysed in samples from incident malaria cases and from children with parasitaemia in the survey. SMC was well tolerated with no serious adverse reactions. There were 1,472 RDT-confirmed malaria cases in the control villages and 270 in the SMC villages. Among children under 5 years of age, the rate difference was 110.8/1,000/month (95% CI 64.7, 156.8; p < 0.001) and among children 5-9 years of age, 101.3/1,000/month (95% CI 66.7, 136.0; p < 0.001). The mean haemoglobin concentration at the end of the transmission season was higher in SMC than control villages, by 6.5 g/l (95% CI 2.0, 11; p = 0.007) among children under 5 years of age, and by 5.2 g/l (95% CI 0.4, 9.9; p = 0.035) among children 5-9 years of age. The prevalence of parasitaemia was 18% in children under 5 years of age and 25% in children 5-9 years of age in the control villages, and 5.7% and 5.8%, respectively, in these 2 age groups in the SMC villages, with prevalence differences of 12.5% (95% CI 6.8%, 18.2%; p < 0.001) in children under 5 years of age and 19.3% (95% CI 8.3%, 30.2%; p < 0.001) in children 5-9 years of age. The pfdhps-540E mutation associated with clinical resistance to sulfadoxine-pyrimethamine was found in 0.8% of samples from malaria cases but not in the final survey. Twelve children died in the control group and 14 in the SMC group, a rate difference of 0.096/1,000 child-months (95% CI 0.99, 1.18; p = 0.895). Limitations of this study include that we were not able to obtain blood smears for microscopy for all suspected malaria cases, such that we had to rely on RDTs for confirmation, which may have included false positives. CONCLUSIONS: In this study SMC for children under 10 years of age given over 5 months was feasible, well tolerated, and effective in preventing malaria episodes, and reduced the prevalence of parasitaemia and anaemia. SMC with CCM achieved high coverage and ensured children with malaria were promptly treated with artemether-lumefantrine. TRIAL REGISTRATION: www.clinicaltrials.gov NCT01449045.

Upper respiratory infections in a rural area with reduced malaria transmission in Senegal: a pathogens community study.

BACKGROUND: Acute Respiratory Infections (ARI) are common causes of febrile illnesses in many settings in Senegal. These infections are usually managed presumptively due to lack of appropriate diagnostic tools. This situation, can lead to poor management of febrile illness or antibiotic misuse. In addition, there are limited data on the spectrum of pathogens commonly responsible for these ARI. This study was conducted to explore the pathogens community among patients with acute respiratory infection in a rural area in Senegal. METHODS: A cross sectional study was conducted from August to December 2015. Children and adult patients attending Keur Socé health post for signs suggestive of acute respiratory infection were enrolled after providing inform consent. Eligible participants were recruited using a consecutive sampling method. Paired nose and throat swabs were collected for pathogen detection. Samples were processed using a multiplex PCR designed to identify 21 pathogens including both virus and bacteria. RESULTS: Two hundred and fifty patients participated in the study. Samples positivity rate was evaluated at 95.2% (238/250). Streptococcus pneumoniae was the predominant pathogen (74%) and was present in all months and all age-groups, followed by Staphylococcus aureus (28,8%) and rhinovirus (28,4%). Respiratory syncytial virus (RSV) was detected only among children under 5 years old in August and September while coronavirus was present in all age groups, during the months of October and December. CONCLUSION: This pilot study revealed a diversity of pathogens over the time and across all age groups, highlighting the need for further exploration. A pathogen community approach including both virus and bacteria at a larger scale becomes crucial for a better understanding of transmission dynamics at population level in order to help shape ARI control strategies.

Safety and Efficacy of Adding a Single Low Dose of Primaquine to the Treatment of Adult Patients With Plasmodium falciparum Malaria in Senegal, to Reduce Gametocyte Carriage: A Randomized Controlled Trial.

Introduction: More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common. Methods: Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7. Results: In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of -0.04 g/dL (95% confidence interval [CI] -0.23, 0.31), but the effect of primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI -0.08, 0.52) less in those who received primaquine (interaction P = .01). One G6PD normal patient who received primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received primaquine. Primaquine was associated with a 73% (95% CI 24-90) reduction in gametocyte carriage (P = .013). Conclusion: Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received primaquine than in those who did not and one patient who received primaquine developed moderately severe anemia. Clinical Trial registration: PACTR201411000937373 (www.pactr.org).

An epidemiological study to assess Plasmodium falciparum parasite prevalence and malaria control measures in Burkina Faso and Senegal.

BACKGROUND: Malariometric information is needed to decide how to introduce malaria vaccines and evaluate their impact in sub-Saharan African countries. METHODS: This cross-sectional study (NCT01954264) was conducted between October and November, 2013, corresponding to the high malaria transmission season, in four sites with Health and Demographic Surveillance Systems (DSS) [two sites with moderate-to-high malaria endemicity in Burkina Faso (Nouna and Saponé) and two sites with low malaria endemicity in Senegal (Keur Socé and Niakhar)]. Children (N = 2421) were randomly selected from the DSS lists of the study sites and were stratified into two age groups (6 months-4 years and 5-9 years). A blood sample was collected from each child to evaluate parasite prevalence of Plasmodium falciparum and other Plasmodium species and gametocyte density by microscopy, and rapid diagnosis test in the event of fever within 24 h. Case report forms were used to evaluate malaria control measures and other factors. RESULTS: Plasmodium falciparum was identified in 707 (29.2%) children, with a higher prevalence in Burkina Faso than Senegal (57.5 vs 0.9% of children). In Burkina Faso, prevalence was 57.7% in Nouna and 41.9% in Saponé in the 6 months-4 years age group, and 75.4% in Nouna and 70.1% in Saponé in the 5-9 years age group. Infections with other Plasmodium species were rare and only detected in Burkina Faso. While mosquito nets were used by 88.6-97.0 and 64.7-80.2% of children in Burkina Faso and Senegal, other malaria control measures evaluated at individual level were uncommon. In Burkina Faso, exploratory analyses suggested that use of malaria treatment or any other medication within 14 days, and use of insecticide spray within 7 days decreased the prevalence of malaria infection; older age, rural residence, natural floor, grass/palm roof, and unavailability of electricity in the house were factors associated with increased malaria occurrence. CONCLUSIONS: Plasmodium falciparum infection prevalence in children younger than 10 years was 57.5% in Burkina Faso and 0.9% in Senegal, and variability was observed, among others, by age, study site and malaria control measures.

Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.

BACKGROUND: Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age. METHODS AND FINDINGS: SMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3-59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN) use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC] was 0.90, 95% CI 0.68-1.2, p = 0.496). A reduction of 60% (95% CI 54%-64%, p < 0.001) in the incidence of malaria cases confirmed by a rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%-72%, p < 0.001) in the number of treatments for malaria (confirmed and unconfirmed) was observed in children. In areas where SMC was implemented, incidence of confirmed malaria in adults and in children too old to receive SMC was reduced by 26% (95% CI 18%-33%, p < 0.001) and the total number of treatments for malaria (confirmed and unconfirmed) in these older age groups was reduced by 29% (95% CI 21%-35%, p < 0.001). One hundred and twenty-three children were admitted to hospital with a diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas, showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%-68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at the end of the transmission season in SMC areas were 68% (95% CI 35%-85%) p = 0.002 in 2008, 84% (95% CI 58%-94%, p < 0.001) in 2009, and 30% (95% CI -130%-79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions attributable to SMC drugs. Vomiting was the most commonly reported mild adverse event but was reported in less than 1% of treatments. The average cost of delivery was US$0.50 per child per month, but varied widely depending on the size of the health post. Limitations included the low rate of mortality, which limited our ability to detect an effect on this endpoint. CONCLUSIONS: SMC substantially reduced the incidence of outpatient cases of malaria and of severe malaria in children, but no difference in all-cause mortality was observed. Introduction of SMC was associated with an overall reduction in malaria incidence in untreated age groups. In many areas of Africa with seasonal malaria, there is a substantial burden in older children that could be prevented by SMC. SMC in older children is well tolerated and effective and can contribute to reducing malaria transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712374.

Sero-epidemiological evaluation of Plasmodium falciparum malaria in Senegal.

BACKGROUND: In Senegal, a significant decrease of malaria transmission intensity has been noted the last years. Parasitaemia has become lower and, therefore, more difficult to detect by microscopy. In the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. Serological markers have been proposed as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria in two sentinel sites in Senegal. METHODS: Cross-sectional surveys were carried out in Velingara (south Senegal) and Keur Soce (central Senegal) between September and October 2010. Children under 10 years old, living in these areas, were enrolled using two-level, random sampling methods. P. falciparum infection was diagnosed using microscopy. P. falciparum antibodies against circumsporozoite protein (CSP), apical membrane protein (AMA1) and merozoite surface protein 1_42 (MSP1_42) were measured by ELISA method. A stepwise logistic regression analysis was done to assess factors associated with P. falciparum antibodies carriage. RESULTS: A total of 1,865 children under 10 years old were enrolled. The overall falciparum malaria prevalence was 4.99% with high prevalence in Velingara of 10.03% compared to Keur Soce of 0.3%. Symptomatic malaria cases (fever associated with parasitaemia) represented 17.37%. Seroprevalence of anti-AMA1, anti-MSP1_42 and anti-CSP antibody was 38.12, 41.55 and 40.38%, respectively. The seroprevalence was more important in Velingara and increased with age, active malaria infection and area of residence. CONCLUSION: The use of serological markers can contribute to improved malaria surveillance in areas with declining malaria transmission. This study provided useful baseline information about the sero-epidemiological situation of malaria in Senegal and can contribute to the identification of malaria hot spots in order to concentrate intervention efforts. TRIAL REGISTRATION NUMBER: PACTR201305000551876 ( http://www.pactr.org ).

Usefulness of MALDI-TOF Mass Spectrometry for Routine Identification of Candida Species in a Resource-Poor Setting.

BACKGROUND: Identification of fungal clinical isolates is essential for therapeutic management. In resource-limited settings, identification mostly relies on biochemical tests whose sensitivity and specificity are known to be insufficient for identification of closely related or newly described species. MALDI-TOF has been shown in favored countries to be a reliable and powerful tool for microorganism identification, including yeasts. The aim of this study was to compare MALDI-TOF with routine identification procedures in a resource-poor context. METHODS: A total of 734 clinical specimens (502 vaginal swabs, 147 oral swabs, 61 bronchoalveolar lavage fluids and 24 stool samples) have been tested in the mycology unit of Fann Hospital, Dakar, Senegal. Strains isolated from culture were identified by both conventional phenotypic methods (germ tube formation and biochemical panels) and MALDI-TOF Saramis/VITEK MS, bioMérieux, France. In addition to comparing the final identification, we determined the time of obtaining the results and the cost for both approaches. RESULTS: Overall, 218 (29.7 %) samples were positive for Candida. MALDI-TOF MS enabled the identification of 214 of the 218 strains isolated (98.1 %) at species level. Phenotypic approach yielded identification for 208 strains (95.4 %). Congruence between the tests was observed for 203 isolates. A discrepancy was observed for one isolate identified as Candida krusei with the phenotypic approach and Candida tropicalis with the MALDI-TOF. In addition, ten isolates identified at genus level by phenotypic methods were identified as C. glabrata (n = 8), C. tropicalis (n = 1) and C. parapsilosis (n = 1) by MALDI-TOF. The turnaround time for identification was <1 h using the MALDI-TOF compared to our routine procedures (48 h). The overall cost (reagents + expendables) per isolate was at 1.35 for the MALDI-TOF MS. CONCLUSION: MALDI-TOF clearly outperformed the diagnosis capacities of phenotypic methods by reducing the delay of results and giving accurate identification at species level. Moreover, this approach appears to be cost-effective and should be implemented especially in resource-poor context.

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.

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.

Understanding the role of household hygiene practices and foodborne disease risks in child stunting: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: Environmental hygiene and food safety are important determinants of child stunting. This research aims to explore the relationship between child stunting and household hygiene practices and behaviours, including the availability of water, sanitation and hygiene (WASH) facilities; the use of safe food and good quality drinking water (especially when used for complementary feeding); hygienic practices in food transport, storage and preparation and the control of cross-contamination from animals, their produce and waste. METHODS AND ANALYSIS: This study is part of a wider observational study which aims to investigate the interdisciplinary factors contributing to child stunting using a 'whole child' paradigm. The observational study recruits women during pregnancy in Hyderabad, India, Lombok, Indonesia and Kaffrine, Senegal, and dyads (ie, 500 mother-infant pairs per country) are followed longitudinally up to 24 months after birth. Within the interdisciplinary niche, the study here has developed tools to investigate the potential exposure pathways to environmental pathogen contamination of foods and water. Holistic WASH and food safety data collection tools have been developed to explore exposure pathways at the household level, including: (1) survey questionnaires; (2) spot-checks; (3) biological sampling of drinking water, food and domestic surfaces and (4) direct observation. An integrated analytical approach will be used to triangulate the evidence in order to examine the relationships between child stunting, WASH and food safety behaviours. ETHICS AND DISSEMINATION: Ethical approval of the study was granted by the ethics committee of the LSHTM, RVC, ILRI, ICMR, IIPHG, SEAMEO-RECFON, University of Cheikh Anta Diop. Findings of the study will be disseminated through publication in peer-reviewed journals, relevant international conferences, public engagement events, and policy-maker and stakeholder events.

Investigating market-based opportunities for the provision of nutritious and safe diets to prevent childhood stunting: a UKRI-GCRF action against stunting hub protocol paper.

BACKGROUND: Inadequate access to affordable, safe, desirable and convenient nutrient-dense food is one of the underlying causes of child stunting. While targeted nutrition-sensitive interventions (eg, backyard 'nutri-gardens') may increase dietary diversity within farming households, such interventions have limited scalability across the wider food system where markets remain underdeveloped. This research aims to develop and assess market-based interventions for key nutrient-dense foods to help improve the diets of women and children in the first 1000 days of life. METHODS: Data collection uses four parallel approaches in each of the three study countries (India, Indonesia and Senegal). (1) A novel food environment tool will be developed to characterise the accessibility and affordability of nutrient-dense foods in the study countries. The tool will be validated through pretesting using cognitive interviewing and piloting in purposively sampled households, 10 (cognitive interviewing) and 30 (piloting) households in each country; (2) stakeholder interviews (eg, with producers, intermediaries and retailers) will be conducted to map out nutrition-sensitive entry points of key value chains (eg, animal-sourced foods), before hotspots of potential food safety hazards will be identified from food samples collected along the chains; (3) the Optifood and Agrifood tools will be used to identify foods that can address food system nutrient gaps and engage key stakeholders to prioritise market interventions to improve nutrition outcomes. Optifood and Agrifood parameters will be informed by publicly available data, plus interviews and focus groups with value chain stakeholders; (4) informed by the previous three approaches and a campaign of participatory 'group model building', a novel system dynamics model will evaluate the impact of alternative market-based solutions on the availability and affordability of nutrient-dense foods over time. ETHICS AND DISSEMINATION: The study has received ethical approval in the United Kingdom, Senegal, Indonesia and India. Dissemination comprises peer-reviewed journals, international disciplinary conferences and multistakeholder dissemination workshops.

Acceptability by community health workers in Senegal of combining community case management of malaria and seasonal malaria chemoprevention.

BACKGROUND: Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs). METHODS: Sixty-one interviews and six focus group discussions were conducted nested in a cluster-randomized trial assessing the impact of combining CCMm and SMC in a rural area of Senegal. Participants consisted of: (i) members of village associations, (ii) members of families who had access to the interventions as well as members of families who did not access the interventions, (iii) CHWs, and (iv) community leaders, e g, religious guides and village chiefs. RESULTS: The interventions were acceptable to the local population and perceived as good strategy to make health care services available to community members and thus, to reduce the delays in access to anti-malarial treatment as well as expenses related to patients' transfer to the health post. The use of malaria rapid diagnostic test (RDT) contributed to improving CHWs diagnostic capacity as well as malaria treatment practices. Study participants notified RDT and drugs stock-out as the major risk for sustainability of the intervention at community level. CONCLUSION: Combining CCMm and SMC is a well accepted, community-based approach that can contribute to control malaria in areas where malaria transmission is seasonal.