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.

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.

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.

Scaling up malaria intervention "packages" in Senegal: using cost effectiveness data for improving allocative efficiency and programmatic decision-making.

BACKGROUND: Senegal's National Malaria Control Programme (NMCP) implements control interventions in the form of targeted packages: (1) scale-up for impact (SUFI), which includes bed nets, intermittent preventive treatment in pregnancy, rapid diagnostic tests, and artemisinin combination therapy; (2) SUFI + reactive case investigation (focal test and treat); (3) SUFI + indoor residual spraying (IRS); (4) SUFI + seasonal malaria chemoprophylaxis (SMC); and, (5) SUFI + SMC + IRS. This study estimates the cost effectiveness of each of these packages to provide the NMCP with data for improving allocative efficiency and programmatic decision-making. METHODS: This study is a retrospective analysis for the period 2013-2014 covering all 76 Senegal districts. The yearly implementation cost for each intervention was estimated and the information was aggregated into a package cost for all covered districts. The change in the burden of malaria associated with each package was estimated using the number of disability adjusted life-years (DALYs) averted. The cost effectiveness (cost per DALY averted) was then calculated for each package. RESULTS: The cost per DALY averted ranged from $76 to $1591 across packages. Using World Health Organization standards, 4 of the 5 packages were "very cost effective" (less than Senegal's GDP per capita). Relative to the 2 other packages implemented in malaria control districts, the SUFI + SMC package was the most cost-effective package at $76 per DALY averted. SMC seems to make IRS more cost effective: $582 per DALY averted for SUFI + IRS compared with $272 for the SUFI + IRS + SMC package. The SUFI + focal test and treat, implemented in malaria elimination districts, had a cost per DALY averted of $1591 and was only "cost-effective" (less than three times Senegal's per capita GDP). CONCLUSION: Senegal's choice of deploying malaria interventions by packages seems to be effectively targeting high burden areas with a wide range of interventions. However, not all districts showed the same level of performance, indicating that efficiency gains are still possible.

Assessing whether universal coverage with insecticide-treated nets has been achieved: is the right indicator being used?

BACKGROUND/METHODS: Insecticide-treated nets (ITNs) are the primary tool for malaria vector control in sub-Saharan Africa, and have been responsible for an estimated two-thirds of the reduction in the global burden of malaria in recent years. While the ultimate goal is high levels of ITN use to confer protection against infected mosquitoes, it is widely accepted that ITN use must be understood in the context of ITN availability. However, despite nearly a decade of universal coverage campaigns, no country has achieved a measured level of 80% of households owning 1 ITN for 2 people in a national survey. Eighty-six public datasets from 33 countries in sub-Saharan Africa (2005-2017) were used to explore the causes of failure to achieve universal coverage at the household level, understand the relationships between the various ITN indicators, and further define their respective programmatic utility. RESULTS: The proportion of households owning 1 ITN for 2 people did not exceed 60% at the national level in any survey, except in Uganda's 2014 Malaria Indicator Survey (MIS). At 80% population ITN access, the expected proportion of households with 1 ITN for 2 people is only 60% (p = 0.003 R2 = 0.92), because individuals in households with some but not enough ITNs are captured as having access, but the household does not qualify as having 1 ITN for 2 people. Among households with 7-9 people, mean population ITN access was 41.0% (95% CI 36.5-45.6), whereas only 6.2% (95% CI 4.0-8.3) of these same households owned at least 1 ITN for 2 people. On average, 60% of the individual protection measured by the population access indicator is obscured when focus is put on the household "universal coverage" indicator. The practice of limiting households to a maximum number of ITNs in mass campaigns severely restricts the ability of large households to obtain enough ITNs for their entire family. CONCLUSIONS: The two household-level indicators-one representing minimal coverage, the other only 'universal' coverage-provide an incomplete and potentially misleading picture of personal protection and the success of an ITN distribution programme. Under current ITN distribution strategies, the global malaria community cannot expect countries to reach 80% of households owning 1 ITN for 2 people at a national level. When programmes assess the success of ITN distribution activities, population access to ITNs should be considered as the better indicator of "universal coverage," because it is based on people as the unit of analysis.

Modeling malaria genomics reveals transmission decline and rebound in Senegal.

To study the effects of malaria-control interventions on parasite population genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium falciparum collected in Thiès, Senegal between 2006 and 2013. The parasite samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the samples grouped into subsets with identical barcodes, varying in size by year and sometimes persisting across years. The barcodes also formed networks of related groups. Analysis of 164 completely sequenced parasites revealed extensive sharing of genomic regions. In at least two cases we found first-generation recombinant offspring of parents whose genomes are similar or identical to genomes also present in the sample. An epidemiological model that tracks parasite genotypes can reproduce the observed pattern of barcode subsets. Quantification of likelihoods in the model strongly suggests a reduction of transmission from 2006-2010 with a significant rebound in 2012-2013. The reduced transmission and rebound were confirmed directly by incidence data from Thiès. These findings imply that intensive intervention to control malaria results in rapid and dramatic changes in parasite population genomics. The results also suggest that genomics combined with epidemiological modeling may afford prompt, continuous, and cost-effective tracking of progress toward malaria elimination.

Assessment of the utility of a symptom-based algorithm for identifying febrile patients for malaria diagnostic testing in Senegal.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) enable point-of-care testing to be nearly as sensitive and specific as reference microscopy. The Senegal National Malaria Control Programme introduced RDTs in 2007, along with a case management algorithm for uncomplicated febrile illness, in which the first step stipulates that if a febrile patient of any age has symptoms indicative of febrile illness other than malaria (e.g., cough or rash), they would not be tested for malaria, but treated for the apparent illness and receive an RDT for malaria only if they returned in 48 h without improvement. METHODS: A year-long study in 16 health posts was conducted to determine the algorithm's capacity to identify patients with Plasmodium falciparum infection identifiable by RDT. Health post personnel enrolled patients of all ages with fever (≥37.5 °C) or history of fever in the previous 2 days. After clinical assessment, a nurse staffing the health post determined whether a patient should receive an RDT according to the diagnostic algorithm, but performed an RDT for all enrolled patients. RESULTS: Over 1 year, 6039 patients were enrolled and 58% (3483) were determined to require an RDT according to the algorithm. Overall, 23% (1373/6039) had a positive RDT, 34% (1130/3376) during rainy season and 9% (243/2661) during dry season. The first step of the algorithm identified only 78% of patients with a positive RDT, varying by transmission season (rainy 80%, dry 70%), malaria transmission zone (high 75%, low 95%), and age group (under 5 years 68%, 5 years and older 84%). CONCLUSIONS: In all but the lowest malaria transmission zone, use of the algorithm excludes an unacceptably large proportion of patients with malaria from receiving an RDT at their first visit, denying them timely diagnosis and treatment. While the algorithm was adopted within a context of malaria control and scarce resources, with the goal of treating patients with symptomatic malaria, Senegal has now adopted a policy of universal diagnosis of patients with fever or history of fever. In addition, in the current context of malaria elimination, the paradigm of case management needs to shift towards the identification and treatment of all patients with malaria infection.

Malaria prevalence, prevention and treatment seeking practices among nomadic pastoralists in northern Senegal.

BACKGROUND: Malaria transmission in Senegal is highly stratified, from low in the dry north to moderately high in the moist south. In northern Senegal, along the Senegal River Valley and in the Ferlo semi-desert region, annual incidence is less than five cases per 1000 inhabitants. Many nomadic pastoralists have permanent dwellings in the Ferlo Desert and Senegal River Valley, but spend dry season in the south with their herds, returning north when the rains start, leading to a concern that this population could contribute to ongoing transmission in the north. METHODS: A modified snowball sampling survey was conducted at six sites in northern Senegal to determine the malaria prevention and treatment seeking practices and parasite prevalence among nomadic pastoralists in the Senegal River Valley and the Ferlo Desert. Nomadic pastoralists aged 6 months and older were surveyed during September and October 2014, and data regarding demographics, access to care and preventive measures were collected. Parasite infection was detected using rapid diagnostic tests (RDTs), microscopy (thin and thick smears) and polymerase chain reaction (PCR). Molecular barcodes were determined by high resolution melting (HRM). RESULTS: Of 1800 participants, 61% were male. Sixty-four percent had at least one bed net in the household, and 53% reported using a net the night before. Only 29% had received a net from a mass distribution campaign. Of the 8% (142) who reported having had fever in the last month, 55% sought care, 20% of whom received a diagnostic test, one-third of which (n = 5) were reported to be positive. Parasite prevalence was 0.44% by thick smear and 0.50% by PCR. None of the molecular barcodes identified among the nomadic pastoralists had been previously identified in Senegal. CONCLUSIONS: While access to and utilization of malaria control interventions among nomadic pastoralists was lower than the general population, parasite prevalence was lower than expected and sheds doubt on the perception that they are a source of ongoing transmission in the north. The National Malaria Control Program is making efforts to improve access to malaria prevention and case management for nomadic populations.

Evidence of non-Plasmodium falciparum malaria infection in Kédougou, Sénégal.

BACKGROUND: Expanded malaria control efforts in Sénégal have resulted in increased use of rapid diagnostic tests (RDT) to identify the primary disease-causing Plasmodium species, Plasmodium falciparum. However, the type of RDT utilized in Sénégal does not detect other malaria-causing species such as Plasmodium ovale spp., Plasmodium malariae, or Plasmodium vivax. Consequently, there is a lack of information about the frequency and types of malaria infections occurring in Sénégal. This study set out to better determine whether species other than P. falciparum were evident among patients evaluated for possible malaria infection in Kédougou, Sénégal. METHODS: Real-time polymerase chain reaction speciation assays for P. vivax, P. ovale spp., and P. malariae were developed and validated by sequencing and DNA extracted from 475 Plasmodium falciparum-specific HRP2-based RDT collected between 2013 and 2014 from a facility-based sample of symptomatic patients from two health clinics in Kédougou, a hyper-endemic region in southeastern Sénégal, were analysed. RESULTS: Plasmodium malariae (n = 3) and P. ovale wallikeri (n = 2) were observed as co-infections with P. falciparum among patients with positive RDT results (n = 187), including one patient positive for all three species. Among 288 negative RDT samples, samples positive for P. falciparum (n = 24), P. ovale curtisi (n = 3), P. ovale wallikeri (n = 1), and P. malariae (n = 3) were identified, corresponding to a non-falciparum positivity rate of 2.5%. CONCLUSIONS: These findings emphasize the limitations of the RDT used for malaria diagnosis and demonstrate that non-P. falciparum malaria infections occur in Sénégal. Current RDT used for routine clinical diagnosis do not necessarily provide an accurate reflection of malaria transmission in Kédougou, Sénégal, and more sensitive and specific methods are required for diagnosis and patient care, as well as surveillance and elimination activities. These findings have implications for other malaria endemic settings where species besides P. falciparum may be transmitted and overlooked by control or elimination activities.

Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing.

The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata in a cross-sectional study of febrile patients and healthy controls in a low malaria burden area. Using 16S and untargeted sequencing, we detected viral, bacterial, or eukaryotic pathogens in 23% (38/163) of NMFI cases. Bacteria were the most common, with relapsing fever Borrelia and spotted fever Rickettsia found in 15.5% and 3.8% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed Plasmodium, including one putative P. ovale infection. We developed a logistic regression model that can distinguish Borrelia from NMFIs with similar presentation based on symptoms and vital signs (F1 score: 0.823). These results highlight the challenge and importance of improved diagnostics, especially for Borrelia, to support diagnosis and surveillance.

Safety monitoring of artemisinin combination therapy through a national pharmacovigilance system in an endemic malaria setting.

BACKGROUND: The National Malaria Control Programme in Senegal, introduced since 2006, artemisinin-based combination therapy (ACT administration) for the treatment of uncomplicated malaria cases. In this framework, an anti-malarial pharmacovigilance plan was developed and implemented in all public health services. This study investigated the occurrence of Adverse Drug Events (ADEs) after ACT. METHODS: The study was conducted between January 2007 and December 2009. It was based on spontaneous reports of ADEs in public health facilities. Data on patient demographic characteristics, dispensing facility, adverse signs and symptoms and causality were collected from a total of 123 patients. RESULTS: The age range of these patients was six months to 93 years with a mean of 25.9 years. Of the reported symptoms, 46.7% were related to the abdomen and the digestive system. Symptoms related to the nervous system, skin and subcutaneous tissue, circulatory and respiratory systems and general symptoms and signs were 7%, 9.7%, 3.5% and 31.3%, respectively. Causality results linked 14.3% of symptoms to Falcimon® (Artesunate-Amodiaquine) with certainty. Effects were classified as mild and severe in 69.1% and 7.3% of cases respectively while 23.6% were serious. All patients with serious ADEs were hospitalized. One death was reported in a patient who had taken 24 pills at once. CONCLUSION: These results confirm the need to develop and implement pharmacovigilance systems in malaria endemic countries in order to monitor the safety of anti-malarial treatments.

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.

Improving diagnosis of non-malarial fevers in Senegal: Borrelia and the contribution of tick-borne bacteria.

The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata from febrile patients and healthy controls in a low malaria burden area. Using 16S and unbiased sequencing, we detected viral, bacterial, or eukaryotic pathogens in 29% of NMFI cases. Bacteria were the most common, with relapsing fever Borrelia and spotted fever Rickettsia found in 15% and 3.7% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed Plasmodium, including one putative P. ovale infection. We developed a logistic regression model to distinguish Borrelia from NMFIs with similar presentation based on symptoms and vital signs. These results highlight the challenge and importance of improved diagnostics, especially for Borrelia, to support diagnosis and surveillance.

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.

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.

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.

Scale-up of home-based management of malaria based on rapid diagnostic tests and artemisinin-based combination therapy in a resource-poor country: results in Senegal.

BACKGROUND: Effective case management of malaria requires prompt diagnosis and treatment within 24 hours. Home-based management of malaria (HMM) improves access to treatment for populations with limited access to health facilities. In Senegal, an HMM pilot study in 2008 demonstrated the feasibility of integrated use of RDTs and ACT in remote villages by volunteer Home Care Providers (HCP). Scale-up of the strategy began in 2009, reaching 408 villages in 2009 and 861 villages in 2010. This paper reports the results of the scale-up in the targeted communities and the impact of the strategy on malaria in the formal health sector. METHODS: Data reported by the HCPs were used to assess their performance in 2009 and 2010, while routine malaria morbidity and mortality data were used to assess the impact of the HMM programme. Two high transmission regions where HMM was not implemented until 2010 were used as a comparison. RESULTS AND DISCUSSION: From July 2009 through May 2010, 12582 suspected cases were managed by HCPs, 93% (11672) of whom were tested with an RDT. Among those tested, 37% (4270) had a positive RDT, 97% (4126) of whom were reported treated and cured. Home care providers referred 6871 patients to health posts for management: 6486 with a negative RDT, 119 infants < 2 months, 105 pregnant women, and 161 severe cases. There were no deaths among these patients. In 2009 compared to 2008, incidence of suspected and confirmed malaria cases, all hospitalizations and malaria-related hospitalizations decreased in both intervention and comparison regions. Incidence of in-hospital deaths due to malaria decreased by 62.5% (95% CI 43.8-81.2) in the intervention regions, while the decrease in comparison regions was smaller and not statistically significant. CONCLUSION: Home-based management of malaria including diagnosis with RDT and treatment based on test results is a promising strategy to improve the access of remote populations to prompt and effective management of uncomplicated malaria and to decrease mortality due to malaria. When scaled-up to serve remote village communities in the regions of Senegal with the highest malaria prevalence, home care providers demonstrated excellent adherence to guidelines, potentially contributing to a decrease in hospital deaths attributed to malaria.

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.