Evaluating the performance of Plasmodium falciparum genetic metrics for inferring National Malaria Control Programme reported incidence in Senegal.

BACKGROUND: Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. METHODS: This study examined parasites from 3147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. RESULTS: Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (< 10/1000/annual [‰]). CONCLUSIONS: When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence > 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was < 10‰, many of the correlations between parasite genetics and incidence were reversed, which may reflect the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

SARS-CoV-2 Seroprevalence and Vaccine Uptake among Pregnant Women at First Antenatal Care Visits in Malawi.

Many SARS-CoV-2 infections are asymptomatic, thus reported cases underestimate actual cases. To improve estimates, we conducted surveillance for SARS-CoV-2 seroprevalence among pregnant women attending their first antenatal care visit (ANC1) from June 2021 through May 2022. We administered a questionnaire to collect demographic, risk factors, and COVID-19 vaccine status information and tested dried blood spots for SARS-CoV-2 antibodies. Although <1% of ANC1 participants reported having had COVID-19, monthly SARS-CoV-2 seroprevalence increased from 15.4% (95% CI: 10.5-21.5) in June 2021 to 65.5% (95% CI: 55.5-73.7) in May 2022. Although COVID-19 vaccination was available in March 2021, uptake remained low, reaching a maximum of 9.5% (95% CI: 5.7-14.8) in May 2022. Results of ANC1 serosurveillance provided prevalence estimates helpful in understanding this population case burden that was available through self-report and national case reports. To improve vaccine uptake, efforts to address fears and misconceptions regarding COVID-19 vaccines are needed.

Systematic Review and Meta-Analysis of Seasonal Malaria Chemoprevention.

Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles.

Contextual Factors to Improve Implementation of Malaria Chemoprevention in Children: A Systematic Review.

Malaria remains a leading cause of childhood morbidity and mortality in sub-Saharan Africa, particularly among children under 5 years of age. To help address this challenge, the WHO recommends chemoprevention for certain populations. For children and infants, the WHO recommends seasonal malaria chemoprevention (SMC), perennial malaria chemoprevention (PMC; formerly intermittent preventive treatment in infants [IPTi]), and, more recently, intermittent preventive treatment in school children (IPTsc). This review describes the contextual factors, including feasibility, acceptability, health equity, financial considerations, and values and preferences, that impact implementation of these strategies. A systematic search was conducted on July 5, 2022, and repeated April 13, 2023, to identify relevant literature. Two reviewers independently screened titles for eligibility, extracted data from eligible articles, and identified and summarized themes. Of 6,295 unique titles identified, 65 were included. The most frequently evaluated strategy was SMC (n = 40), followed by IPTi (n = 18) and then IPTsc (n = 6). Overall, these strategies were highly acceptable, although with IPTsc, there were community concerns with providing drugs to girls of reproductive age and the use of nonmedical staff for drug distribution. For SMC, door-to-door delivery resulted in higher coverage, improved caregiver acceptance, and reduced cost. Lower adherence was noted when caregivers were charged with giving doses 2 and 3 unsupervised. For SMC and IPTi, travel distances and inclement weather limited accessibility. Sensitization and caregiver education efforts, retention of high-quality drug distributors, and improved transportation were key to improving coverage. Additional research is needed to understand the role of community values and preferences in chemoprevention implementation.

SEROPREVALENCE TO SCHISTOSOMA SOLUBLE EGG ANTIGEN AMONG NOMADIC PASTORALISTS RESIDING IN NORTHERN SENEGAL.

Urinary and intestinal schistosomiasis are endemic in Senegal, with prevalence heterogeneous throughout the country. Because of their way of life, nomadic pastoralists are not typically included in epidemiological surveys, and data on the prevalence of schistosomiasis in Senegalese nomadic populations are largely non-existent. The purpose of this study was to determine the seroprevalence of schistosomiasis in Senegalese nomadic pastoralists. A modified snowball sampling survey was conducted among 1,467 nomadic pastoralists aged 6 mo and older in 5 districts in northern Senegal. Dried blood spots from participants of all ages and data regarding demographics were collected to assess IgG antibody responses against Schistosoma mansoni soluble egg antigen (SEA) using a bead-based multiplex assay. Out of 1,467 study subjects, 1,464 (99.8%) provided IgG serological data that cleared quality assurance. Of the participants with appropriate data, 56.6% were male, the median age was 22 yr, and 31.6% were under 15 yr of age. The overall anti-SEA IgG seroprevalence was 19.1% (95% confidence interval [CI]: 17.1-21.1%) with the highest estimates observed in Dagana (35.9%) and the lowest observed in Podor nomadic groups (3.4%). Antibody responses increased significantly with age except for the oldest age groups (>40 yr of age), which saw lower levels of antibody response compared to younger adults. When controlling for age and location by multivariate regression, the male sex was associated with a 2-fold greater odds of anti-SEA IgG seropositivity (aPOR: 2.0; 95% CI: 1.5-2.7). Serosurveys for anti-SEA IgG among nomadic peoples in northern Senegal found a substantial percentage of individuals with evidence for current or previous Schistosoma spp. infection with the highest levels of exposure in the district adjacent to the Diama dam along the Senegal River. With IgG prevalence increased by age except in the older adults, and the male sex significantly associated with seropositivity, these data point toward sex-associated behavioral practices and human environmental modification as risk factors for Schistosoma exposure.

Evaluating the performance of Plasmodium falciparum genetics for inferring National Malaria Control Program reported incidence in Senegal.

Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programs (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. Here, we examined parasites from 3,147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, we constructed a series of Poisson generalized linear mixed-effects models to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. We compared the model-predicted incidence with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (<10/1000/annual [‰]). When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence >10 ‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was <10 ‰, we found that many of the correlations between parasite genetics and incidence were reversed, which we hypothesize reflects the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal.

We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study's goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure.

Two decades of molecular surveillance in Senegal reveal changes in known drug resistance mutations associated with historical drug use and seasonal malaria chemoprevention.

Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. We analyzed data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasite strains in Senegal to determine how historical changes in drug administration policy may have affected parasite evolution. We profiled several known drug resistance markers and their surrounding haplotypes using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole-genome sequence (WGS) based population genomics. We observed rapid changes in drug resistance markers associated with the withdrawal of chloroquine and introduction of sulfadoxine-pyrimethamine in 2003. We also observed a rapid increase in Pfcrt K76T and decline in Pfdhps A437G starting in 2014, which we hypothesize may reflect changes in resistance or fitness caused by seasonal malaria chemoprevention (SMC). Parasite populations evolve rapidly in response to drug use, and SMC preventive efficacy should be closely monitored.

Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal.

Parasite genetic surveillance has the potential to play an important role in malaria control. We describe here an analysis of data from the first year of an ongoing, nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal, intended to provide actionable information for malaria control efforts. Looking for a good proxy for local malaria incidence, we found that the best predictor was the proportion of polygenomic infections (those with multiple genetically distinct parasites), although that relationship broke down in very low incidence settings (r = 0.77 overall). The proportion of closely related parasites in a site was more weakly correlated ( r = -0.44) with incidence while the local genetic diversity was uninformative. Study of related parasites indicated their potential for discriminating local transmission patterns: two nearby study areas had similarly high fractions of relatives, but one area was dominated by clones and the other by outcrossed relatives. Throughout the country, 58% of related parasites proved to belong to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci as well as at one novel locus, reflective of ongoing selection pressure.

Routine Healthcare Facility- and Antenatal Care-Based Malaria Surveillance: Challenges and Opportunities.

Most monitoring and evaluation tools for measuring malaria burden, intervention coverage, and impact of interventions use periodic nationally representative cross-sectional household surveys. These provide advantages in terms of selecting a large, unbiased, population-based sample; however, they are infrequently conducted, are resource-intensive, and do not provide longitudinal data with sufficient granularity. Given the heterogeneity of malaria transmission within most endemic countries, systems with the capacity to provide more granular and frequent data would be more actionable by national malaria control programs and local implementing partners. There is increasing interest in using routine health facility data, usually from outpatient department visits, for monitoring malaria burden. Data from pregnant women attending antenatal care (ANC) could minimize bias related to fever care-seeking among outpatient department visits and provide more granular parasite prevalence data. Most pregnant women attend ANC at least once and are thus highly representative of the overall pregnant population. A growing body of evidence suggests that malaria parasitemia in pregnant women is correlated with parasitemia in children aged < 5 years in moderate to high transmission areas, allowing for monitoring parasitemia in real time. Additional data are needed to assess whether pregnant women are sufficiently representative of the overall population to yield valid malaria prevalence and intervention coverage estimates. Although use of routinely collected ANC data faces many of the same challenges experienced by other routinely collected health facility data, the opportunity to improve parasite prevalence monitoring and the associated health benefits to mothers and infants of early detection of parasitemia make these efforts valuable.

Surveillance as a Core Intervention to Strengthen Malaria Control Programs in Moderate to High Transmission Settings.

New tools are needed for malaria control, and recent improvements in malaria surveillance have opened the possibility of transforming surveillance into a core intervention. Implementing this strategy can be challenging in moderate to high transmission settings. However, there is a wealth of practical experience among national malaria control programs and partners working to improve and use malaria surveillance data to guide programming. Granular and timely data are critical to understanding geographic heterogeneity, appropriately defining and targeting interventions packages, and enabling timely decision-making at the operational level. Resources to be targeted based on surveillance data include vector control, case management commodities, outbreak responses, quality improvement interventions, and human resources, including community health workers, as they contribute to a more refined granularity of the surveillance system. Effectively transforming malaria surveillance into a core intervention will require strong global and national leadership, empowerment of subnational and local leaders, collaboration among development partners, and global coordination. Ensuring that national health systems include community health work can contribute to a successful transformation. It will require a strong supply chain to ensure that all suspected cases can be diagnosed and data reporting tools including appropriate electronic devices to provide timely data. Regular data quality audits, decentralized implementation, supportive supervision, data-informed decision-making processes, and harnessing technology for data analysis and visualization are needed to improve the capacity for data-driven decision-making at all levels. Finally, resources must be available to respond programmatically to these decisions.

Proactive community case management decreased malaria prevalence in rural Madagascar: results from a cluster randomized trial.

BACKGROUND: Malaria remains a leading cause of morbidity and mortality worldwide, with progress in malaria control stalling in recent years. Proactive community case management (pro-CCM) has been shown to increase access to diagnosis and treatment and reduce malaria burden. However, lack of experimental evidence may hinder the wider adoption of this intervention. We conducted a cluster randomized community intervention trial to assess the efficacy of pro-CCM at decreasing malaria prevalence in rural endemic areas of Madagascar. METHODS: Twenty-two fokontany (smallest administrative unit) of the Mananjary district in southeast Madagascar were selected and randomized 1:1 to pro-CCM (intervention) or conventional integrated community case management (iCCM). Residents of all ages in the intervention arm were visited by a community health worker every 2 weeks from March to October 2017 and screened for fever; those with fever were tested by a rapid diagnostic test (RDT) and treated if positive. Malaria prevalence was assessed using RDTs on all consenting study area residents prior to and following the intervention. Hemoglobin was measured among women of reproductive age. Intervention impact was assessed via difference-in-differences analyses using logistic regressions in generalized estimating equations. RESULTS: A total of 27,087 and 20,475 individuals participated at baseline and endline, respectively. Malaria prevalence decreased from 8.0 to 5.4% in the intervention arm for individuals of all ages and from 6.8 to 5.7% in the control arm. Pro-CCM was associated with a significant reduction in the odds of malaria positivity in children less than 15 years (OR = 0.59; 95% CI [0.38-0.91]), but not in older age groups. There was no impact on anemia among women of reproductive age. CONCLUSION: This trial suggests that pro-CCM approaches could help reduce malaria burden in rural endemic areas of low- and middle-income countries, but their impact may be limited to younger age groups with the highest malaria burden. TRIAL REGISTRATION: NCT05223933. Registered on February 4, 2022.

Sensitivity and specificity for malaria classification of febrile persons by rapid diagnostic test, microscopy, parasite DNA, histidine-rich protein 2, and IgG: Dakar, Senegal 2015.

OBJECTIVES: Different methods for detecting Plasmodium parasite infection or exposure are available, but a systematic comparison of all these methodologies to predict malaria infection is lacking. Understanding the characteristics of respective tests is helpful in choosing the most appropriate tests for epidemiological or research purposes. METHODS: We performed microscopy, rapid diagnostic tests (RDTs), and polymerase chain reaction (PCR) for 496 patients presenting with febrile illness in Dakar, Senegal, in 2015. Blood samples had laboratory multiplex assays performed for Immunoglobin G serology and detection of histidine-rich protein 2 (HRP2) antigen. Sensitivity (Se) and specificity (Sp) for different tests were calculated using PCR as the gold standard for detecting active infection. Modeling through latent class analysis compared each test to a modeled gold standard for Se/Sp estimates. RESULTS: Against PCR, Se/Sp were 95.2%/93.7% for RDT, 90.4%/100.0% for microscopy, and 97.9%/48.1% for laboratory HRP2 detection. Compared with the modeled gold standard, Se of microscopy was 93.5% and Se of RDT, PCR, and laboratory HRP2 detection were all greater than 99%. Se/Sp of Immunoglobin G serology were substantially lower for detecting active infection. CONCLUSIONS: Compared with single tests, a combinatorial latent class analysis approach of multiple biomarkers for detecting malaria infection from patient samples provides greater sensitivity and specificity for epidemiological estimates and research objectives.

Health inequities and clustering of fever, acute respiratory infection, diarrhoea and wasting in children under five in low- and middle-income countries: a Demographic and Health Surveys analysis.

BACKGROUND: Pneumonia, diarrhoea and malaria are responsible for over one third of all deaths in children under the age of 5 years in low and middle sociodemographic index countries; many of these deaths are also associated with malnutrition. We explore the co-occurrence and clustering of fever, acute respiratory infection, diarrhoea and wasting and their relationship with equity-relevant variables. METHODS: Multilevel, multivariate Bayesian logistic regression models were fitted to Demographic and Health Survey data from over 380,000 children in 39 countries. The relationship between outcome indicators (fever, acute respiratory infection, diarrhoea and wasting) and equity-relevant variables (wealth, access to health care and rurality) was examined. We quantified the geographical clustering and co-occurrence of conditions and a child's risk of multiple illnesses. RESULTS: The prevalence of outcomes was very heterogeneous within and between countries. There was marked spatial clustering of conditions and co-occurrence within children. For children in the poorest households and those reporting difficulties accessing healthcare, there were significant increases in the probability of at least one of the conditions in 18 of 21 countries, with estimated increases in the probability of up to 0.23 (95% CrI, 0.06-0.40). CONCLUSIONS: The prevalence of fever, acute respiratory infection, diarrhoea and wasting are associated with equity-relevant variables and cluster together. Via pathways of shared aetiology or risk, those children most disadvantaged disproportionately suffer from these conditions. This highlights the need for horizontal approaches, such as integrated community case management, with a focus on equity and targeted to those most at need.

Genetic evidence for imported malaria and local transmission in Richard Toll, Senegal.

BACKGROUND: Malaria elimination efforts can be undermined by imported malaria infections. Imported infections are classified based on travel history. METHODS: A genetic strategy was applied to better understand the contribution of imported infections and to test for local transmission in the very low prevalence region of Richard Toll, Senegal. RESULTS: Genetic relatedness analysis, based upon molecular barcode genotyping data derived from diagnostic material, provided evidence for both imported infections and ongoing local transmission in Richard Toll. Evidence for imported malaria included finding that a large proportion of Richard Toll parasites were genetically related to parasites from Thiès, Senegal, a region of moderate transmission with extensive available genotyping data. Evidence for ongoing local transmission included finding parasites of identical genotype that persisted across multiple transmission seasons as well as enrichment of highly related infections within the households of non-travellers compared to travellers. CONCLUSIONS: These data indicate that, while a large number of infections may have been imported, there remains ongoing local malaria transmission in Richard Toll. These proof-of-concept findings underscore the value of genetic data to identify parasite relatedness and patterns of transmission to inform optimal intervention selection and placement.

Proactive community case management in Senegal 2014-2016: a case study in maximizing the impact of community case management of malaria.

The Senegal National Malaria Control Programme (NMCP) introduced home-based malaria management for all ages, with diagnosis by rapid diagnostic test (RDT) and treatment with artemisinin-based combination therapy (ACT) in 2008, expanding to over 2000 villages nationwide by 2014. With prise en charge à domicile (PECADOM), community health workers (CHWs) were available for community members to seek care, but did not actively visit households to find cases. A trial of a proactive model (PECADOM Plus), in which CHWs visited all households in their village weekly during transmission season to identify fever cases and offer case management, in addition to availability during the week for home-based management, found that CHWs detected and treated more cases in intervention villages, while the number of cases detected weekly decreased over the transmission season. The NMCP scaled PECADOM Plus to three districts in 2014 (132 villages), to a total of six districts in 2015 (246 villages), and to a total of 16 districts in 2016 (708 villages). A narrative case study with programmatic results is presented. During active sweeps over approximately 20 weeks, CHWs tested a mean of 77 patients per CHW in 2014, 89 patients per CHW in 2015, and 90 patients per CHW in 2016, and diagnosed a mean of 61, 61 and 43 patients with malaria per CHW in 2014, 2015 and 2016, respectively. The number of patients who sought care between sweeps increased, with a 104% increase in the number of RDTs performed and a 77% increase in the number of positive tests and patients treated with ACT during passive case detection. While the number of CHWs increased 7%, the number of patients receiving an RDT increased by 307% and the number of malaria cases detected and treated by CHWs increased 274%, from the year prior to PECADOM Plus introduction to its first year of implementation. Based on these results, approximately 700 additional CHWs in 24 new districts were added in 2017. This case study describes the process, results and lessons learned from Senegal's implementation of PECADOM Plus, as well as guidance for other programmes considering introduction of this innovative strategy.

Analysis of anti-Plasmodium IgG profiles among Fulani nomadic pastoralists in northern Senegal to assess malaria exposure.

BACKGROUND: Northern Senegal is a zone of very low malaria transmission, with an annual incidence of < 5/1000 inhabitants. This area, where the Senegal National Malaria Control Programme has initiated elimination activities, hosts Fulani, nomadic, pastoralists that spend the dry season in the south where malaria incidence is higher (150-450/1000 inhabitants) and return to the north with the first rains. Previous research demonstrated parasite prevalence of < 1% in this Fulani population upon return from the south, similar to that documented in the north in cross-sectional surveys. METHODS: A modified snowball sampling survey of nomadic pastoralists was conducted in five districts in northern Senegal during September and October 2014. Demographic information and dried blood spots were collected. Multiplex bead-based assays were used to assess antibody responses to merozoite surface protein (MSP-119) antigen of the four primary Plasmodium species, as well as circumsporozoite protein (CSP) and liver stage antigen (LSA-1) of Plasmodium falciparum. RESULTS: In the five study districts, 1472 individuals were enrolled, with a median age of 22 years (range 1 to 80 years). Thirty-two percent of subjects were under 14 years and 57% were male. The overall seroprevalence of P. falciparum MSP-119, CSP and LSA-1 antibodies were 45, 12 and 5%, respectively. Plasmodium falciparum MSP-119 antibody responses increased significantly with age in all study areas, and were significantly higher among males. The highest seroprevalence to P. falciparum antigens was observed in the Kanel district (63%) and the lowest observed in Podor (28%). Low seroprevalence was observed for non-falciparum species in all the study sites: 0.4, 0.7 and 1.8%, respectively, for Plasmodium ovale, Plasmodium vivax and Plasmodium malariae MSP-1. Antibody responses to P. vivax were observed in all study sites except Kanel. CONCLUSION: Prevalence of P. falciparum MSP-119 antibodies and increases by study participant age provided data for low levels of exposure among this transient nomadic population. In addition, antibody responses to P. falciparum short half-life markers (CSP and LSA-1) and non-falciparum species were low. Further investigations are needed to understand the exposure of the Fulani population to P. vivax.

A Robust Estimator of Malaria Incidence from Routine Health Facility Data.

Routine incident malaria case data have become a pillar of malaria surveillance in sub-Saharan Africa. These data provide granular, timely information to track malaria burden. However, incidence data are sensitive to changes in care seeking rates, rates of testing of suspect cases, and reporting completeness. Based on a set of assumptions, we derived a simple algebraic formula to convert crude incidence rates to a corrected estimation of incidence, adjusting for biases in variable and suboptimal rates of care seeking, testing of suspect cases, and reporting completeness. We applied the correction to routine incidence data from Guinea and Mozambique, and aggregate data for sub-Saharan African countries from the World Malaria Report. We calculated continent-wide needs for malaria tests and treatments, assuming universal testing but current care seeking rates. Countries in southern and eastern Africa reporting recent increases in malaria incidence generally had lower overall corrected incidence than countries in Central and West Africa. Under current care seeking rates, the unmet need for malaria tests was estimated to be 160 million (M) (interquartile range [IQR]: 139-188) and for malaria treatments to be 37 M (IQR: 29-51). Maps of corrected incidence were more consistent with maps of community survey prevalence than was crude incidence in Guinea and Mozambique. Crude malaria incidence rates need to be interpreted in the context of suboptimal testing and care seeking rates, which vary over space and time. Adjusting for these factors can provide insight into the spatiotemporal trends of malaria burden.

Estimation of Malaria-Attributable Fever in Malaria Test-Positive Febrile Outpatients in Three Provinces of Mozambique, 2018.

Like most malaria-endemic countries, Mozambique relies on tabulation of confirmed malaria test-positive febrile patients to track incidence of malaria. However, this approach is potentially biased by incidental malaria parasitemia in patients with fever of another etiology. We compared pan-Plasmodium aldolase and lactate dehydrogenase and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) antigen concentrations measured using a laboratory bead-based assay of samples collected from 1,712 febrile and afebrile patients of all ages in Maputo, Zambézia, and Cabo Delgado provinces. We used a Bayesian latent class model to estimate the proportion of malaria-attributable fevers in malaria test-positive febrile patients. Depending on the antigen, estimated rates of malaria-attributable fever in malaria test-positive febrile patients were 100% in Maputo, 33-58% in Zambézia, and 63-74% in Cabo Delgado. Our findings indicate that most malaria test-positive febrile patients in the three provinces of Mozambique had a fever that was likely caused by the concurrent malaria infection. Counting malaria test-positive febrile patients for estimation of malaria incidence appears to be appropriate in this setting.

Serological Data Shows Low Levels of Chikungunya Exposure in Senegalese Nomadic Pastoralists.

The chikungunya virus (CHIKV) is spread by Aedes aegypti and Ae. albopictus mosquitos worldwide; infection can lead to disease including joint pain, fever, and rash, with some convalescent persons experiencing chronic symptoms. Historically, CHIKV transmission has occurred in Africa and Asia, but recent outbreaks have taken place in Europe, Indonesia, and the Americas. From September to October 2014, a survey was undertaken with nomadic pastoralists residing in the northeast departments of Senegal. Blood dried on filter paper (dried blood spots; DBS) were collected from 1465 participants of all ages, and assayed for Immunoglobulin G (IgG) antibodies against CHIKV E1 antigen by a bead-based multiplex assay. The overall seroprevalence of all participants to CHIKV E1 was 2.7%, with no persons under 10 years of age found to be antibody positive. Above 10 years of age, clear increases of seroprevalence and IgG levels were observed with increasing age; 7.6% of participants older than 50 years were found to be positive for anti-CHIKV IgG. Reported net ownership, net usage, and gender were all non-significant explanatory variables of seropositivity. These data show a low-level historical exposure of this pastoralist population to CHIKV, with no evidence of recent CHIKV transmission in the past decade.