Characterization of the swarming behavior of Anopheles coluzzii and Anopheles gambiae (Diptera: Culicidae) populations in a hybrid zone of Senegal.

Anopheles gambiae and Anopheles coluzzii, often found in sympatry and synchronous, have undergone a premating reproductive isolation across their distribution range. However, in the Western coast of Africa, unexpected hybridization zones have been observed, and little is known about swarming behavior of these cryptic taxa. Here, we characterized the swarming behavior of An. coluzzii and An. gambiae to investigate its role in the high hybridization level in Senegal. The study was conducted in the south and central Senegal during the 2018 rainy season. Mating swarms of malaria vectors were surveyed at sunset and collected using an insect net. Meanwhile, indoor resting populations of malaria vectors were collected by pyrethrum spray catches. Upon collection, specimens were identified morphologically, and then members of the An. gambiae complex were identified at the species level by polymerase chain reaction (PCR). An. gambiae swarmed mainly over bare ground, whereas An. coluzzii were found swarming above various objects creating a dark-light contrast with the bare ground. The swarms height varied from 0.5 to 2.5 m. Swarming starting time was correlated with sunset whatever the months for both species, and generally lasted about 10 min. No mixed swarm of An. gambiae and An. coluzzii was found even in the high hybridization area. These results indicated a premating isolation between An. coluzzii and An. gambiae. However, the high hybridization rate in the sympatric area suggests that heterogamous mating is occurring, thus stressing the need for further extensive studies.

Diagnostic options for pulmonary fungal diseases in Africa.

Background: Fungal lung diseases are global in distribution and require specific tests for diagnosis. We report a survey of diagnostic service provision in Africa. Methods: A written questionnaire was followed by a video conference call with each respondent(s) and external validation. To disseminate the questionnaire, a snowball sample was used. Results: Data were successfully collected from 50 of 51 African countries with populations >1 million. The questionnaire was completed by respondents affiliated with 72 health facilities. Of these 72 respondents, 33 (45.8%) reported data for the whole country while others reported data for a specific region/province within their country. In the public sector, chest X-ray and computed tomography are performed often in 49 countries (98%) and occasionally in 37 countries (74%), and less often in the private sector. Bronchoscopy and spirometry were done often in 28 countries (56%) and occasionally in 18 countries (36%) in the tertiary health facilities of public sector. The most conducted laboratory diagnostic assay was fungal culture (often or occasionally) in 29 countries (58%). In collaboration with the Africa Centre for Disease Control and Prevention, regional webinars and individual country profiles provided further data validation. Conclusion: This survey has found a huge disparity of diagnostic test capability across the African continent. Some good examples of good diagnostic provision and very high-quality care were seen, but this was unusual. The unavailability of essential testing such as spirometry was noted, which has a high impact in the diagnosis of lung diseases. It is important for countries to implement tests based on the World Health Organization Essential Diagnostics List.

Residual malaria transmission and the role of Anopheles arabiensis and Anopheles melas in central Senegal.

Understanding the behavior and ecology of local malaria vectors is essential for the effectiveness of the commonly used vector-targeted malaria control tools in areas of low malaria transmission. This study was conducted to determine species composition, biting behavior and infectivity of the major Anopheles vectors of Plasmodium falciparum in low transmission settings in central Senegal. Adult mosquitoes were collected using human landing catches during 2 consecutive nights and Pyrethrum Spray Catches in 30-40 randomly selected rooms, from July 2017 to December 2018 in 3 villages. Anopheline mosquitoes were morphologically identified using conventional keys; their reproductive status assessed by ovary dissections, and a sub-sample of Anopheles gambiae s.l. were identified to species level using polymerase chain reaction (PCR). Plasmodium sporozoite infections were detected using real-time quantitative PCR. During this study 3684 Anopheles were collected of which 97% were An. gambiae s.l., 0.6% were Anopheles funestus, and 2.4% were Anopheles pharoensis. Molecular identification of 1,877 An. gambiae s.l. revealed a predominance of Anopheles arabiensis (68.7%), followed by Anopheles melas (28.8%), and Anopheles coluzzii (2.1%). The overall human-biting rate of An. gambiae s.l. was highest in the inland site of Keur Martin with 4.92 bites per person per night, while it was similar in the deltaic site, Diofior (0.51) and the coastal site, Mbine Coly (0.67). Parity rates were similar in An. arabiensis (45%) and An. melas (42%). Sporozoite infections were detected in both An. arabiensis and An. melas with the respective infection rates of 1.39% (N = 8) and 0.41% (N = 1). Results suggest that low residual malaria in central Senegal is transmitted by An. arabiensis and An. melas. Consequently, both vectors will need to be targeted as part of malaria elimination efforts in this area of Senegal.

Evolution of the Ace-1 and Gste2 Mutations and Their Potential Impact on the Use of Carbamate and Organophosphates in IRS for Controlling Anopheles gambiae s.l., the Major Malaria Mosquito in Senegal.

Widespread of insecticide resistance amongst the species of the Anopheles gambiae complex continues to threaten vector control in Senegal. In this study, we investigated the presence and evolution of the Ace-1 and Gste2 resistance genes in natural populations of Anopheles gambiae s.l., the main malaria vector in Senegal. Using historical samples collected from ten sentinel health districts, this study focused on three different years (2013, 2017, and 2018) marking the periods of shift between the main public health insecticides families (pyrethroids, carbamates, organophosphates) used in IRS to track back the evolutionary history of the resistance mutations on the Ace-1 and Gste2 loci. The results revealed the presence of four members of the Anopheles gambiae complex, with the predominance of An. arabiensis followed by An. gambiae, An. coluzzii, and An. gambiae-coluzzii hybrids. The Ace-1 mutation was only detected in An. gambiae and An. gambiae-coluzzii hybrids at low frequencies varying between 0.006 and 0.02, while the Gste2 mutation was found in all the species with a frequency ranging between 0.02 and 0.25. The Ace-1 and Gste2 genes were highly diversified with twenty-two and thirty-one different haplotypes, respectively. The neutrality tests on each gene indicated a negative Tajima's D, suggesting the abundance of rare alleles. The presence and spread of the Ace-1 and Gste2 resistance mutations represent a serious threat to of the effectiveness and the sustainability of IRS-based interventions using carbamates or organophosphates to manage the widespread pyrethroids resistance in Senegal. These data are of the highest importance to support the NMCP for evidence-based vector control interventions selection and targeting.

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.

The role of non-governmental organizations in strengthening healthcare systems in low- and middle-income countries: Lessons from Santé Diabète in Mali.

Non-governmental organizations play a vital part in the achievement of the Sustainable Development Goals as defined by the United Nations. These Goals also include targets related to noncommunicable diseases. However, non-governmental organizations have played a limited role in this area despite such diseases causing the bulk of morbidity and mortality worldwide. Through their activities, non-governmental organizations should aim to strengthen health systems, yet they often only support these for a single disease. Mali, like many other low- and middle-income countries, is facing an increasing burden of diabetes and a health system not adapted to address this challenge. Santé Diabète, a non-governmental organization based in Mali since 2003, has been working specifically on diabetes, and has developed a wide range of activities to improve the national health system. This paper describes changes in the diabetes environment in Mali between 2004 and 2018 based on two health system assessments carried out using a Rapid Assessment Protocol. Over this period, the health system was strengthened with regard to financing and access to medical products. Leadership and governance, service delivery and health workforce were all improved but still partially rely on sustained support from Santé Diabète. The key lesson from this study is that to be effective in changing the management of noncommunicable diseases in a low- and middle-income country, non-governmental organizations need to play a variety of roles, many of which may change over time.

Evolution of the Pyrethroids Target-Site Resistance Mechanisms in Senegal: Early Stage of the Vgsc-1014F and Vgsc-1014S Allelic Frequencies Shift.

The evolution and spread of insecticide resistance mechanisms amongst malaria vectors across the sub-Saharan Africa threaten the effectiveness and sustainability of current insecticide-based vector control interventions. However, a successful insecticide resistance management plan relies strongly on evidence of historical and contemporary mechanisms circulating. This study aims to retrospectively determine the evolution and spread of pyrethroid resistance mechanisms among natural Anopheles gambiae s.l. populations in Senegal. Samples were randomly drawn from an existing mosquito sample, collected in 2013, 2017, and 2018 from 10 sentinel sites monitored by the Senegalese National Malaria Control Programme (NMCP). Molecular species of An. gambiae s.l. and the resistance mutations at the Voltage-gated Sodium Channel 1014 (Vgsc-1014) locus were characterised using PCR-based assays. The genetic diversity of the Vgsc gene was further analyzed by sequencing. The overall species composition revealed the predominance of Anopheles arabiensis (73.08%) followed by An. gambiae s.s. (14.48%), Anopheles coluzzii (10.94%) and Anopheles gambiae-coluzii hybrids (1.48%). Both Vgsc-1014F and Vgsc-1014S mutations were found in all studied populations with a spatial variation of allele frequencies from 3% to 90%; and 7% to 41%, respectively. The two mutations have been detected since 2013 across all the selected health districts, with Vgsc-L1014S frequency increasing over the years while Vgsc-1014F decreasing. At species level, the Vgsc-1014F and Vgsc-1014S alleles were more frequent amongst An. gambiae s.s. (70%) and An. arabiensis (20%). The Vgsc gene was found to be highly diversified with eight different haplotypes shared between Vgsc-1014F and Vgsc-1014S. The observed co-occurrence of Vgsc-1014F and Vgsc-1014S mutations suggest that pyrethroid resistance is becoming a widespread phenomenon amongst malaria vector populations, and the NMCP needs to address this issue to sustain the gain made in controlling malaria.

Identification of High-Yielding Iron-Biofortified Open-Pollinated Varieties of Pearl Millet in West Africa.

Pearl millet is a predominant food and fodder crop in West Africa. This study was carried out to test the newly developed open-pollinated varieties (OPVs) for field performance and stability for grain yield, grain iron (Fe), and grain zinc (Zn) contents across 10 locations in West Africa (i.e., Niger, Nigeria, Mali, Burkina Faso, Senegal, and Ghana). The test material consisted of 30 OPVs, of which 8 are Fe/Zn biofortified. The experiment was conducted in a randomized complete block design in three replications. ANOVA revealed highly significant variability for grain yield and micronutrient traits. The presence of genotype × environment (G × E) indicated that the expressions of traits are significantly influenced by both genetic and G × E factors, for grain Fe and Zn contents. Days to 50% flowering and plant height showed less G × E, suggesting these traits are largely under genetic control. The genotypes CHAKTI (46 days), ICTP 8203 (46 days), ICMV 177002 (50 days), ICMV 177003 (48 days), and Moro (53 days) had exhibited early flowering across locations leading to early physiological maturity. CHAKTI (1.42 t/ha yield; 62.24 mg/kg of grain Fe, 47.29 mg/kg of grain Zn) and ICMP 177002 (1.19 t/ha yield, 62.62 mg/kg of grain Fe, 46.62 mg/kg of grain Zn) have performed well for grain yield and also for micronutrients, across locations, compared with the check. Additive Main Effect and Multiplicative Interaction (AMMI) ANOVA revealed the highly significant genotypic differences, the mean sum of squares of environment, and its interaction with the genotypes. Based on the AMMI stability value (ASV), the most stable genotype is SOSAT-C88 (ASV = 0.04) for grain yield and resistance to downy mildew; mean grain yield and stability rankings (YSI) revealed that the genotypes CHAKTI, SOSAT-C88, and ICMV IS 99001 were high yielding and expressed stability across regions. The strong correlation (r = 0.98∗∗) of grain Fe and Zn contents that merits Fe-based selection is highly rewarding. CHAKTI outperformed over other genotypes for grain yield (71% higher), especially with early maturing varieties in West Africa, such as GB 8735, LCIC 9702, and Jirani, and for grain Fe (16.11% higher) and Zn (7% higher) contents across locations, and made a candidate of high-iron variety to be promoted for combating the micronutrient malnutrition in West and Central Africa (WCA).

Mapping the breeding sites of Anopheles gambiae s. l. in areas of residual malaria transmission in central western Senegal.

Despite the deployment of several effective control interventions in central-western Senegal, residual malaria transmission is still occurring in some hotspots. To better tailor targeted control actions, it is critical to unravel the underlying environmental and geographical factors that cause the persistence infection in hotspot villages. "Hotspots villages" were defined in our study as those reporting more than six indigenous malaria cases during the previous year. A total of ten villages, including seven hotspots and three non-hotspots, were surveyed. All potential mosquito breeding sites identified in and around the ten study villages were regularly monitored between 2013 and 2017. Monitoring comprised the detection of anopheline larvae and the collection of epidemiological, hydrogeological, topographical, and biogeographical data. The number of larval breeding sites described and monitored during the study period ranged from 50 to 62. Breeding sites were more numerous in hotspot sites in each year of monitoring, with 90.3% (56/62) in 2013, 90.9% (50/55) in 2014, 90.3% (56/62) in 2015 and 86% (43/50) in 2017 (Fisher exact test; p = 1). In the non-hotspot areas, the data for the same years were, respectively, 9.7% (6/62), 9.1% (5/55), 9.7% (6/62) and 14% (7/50) (p = 1). The Hotspot villages were characterized mostly by saline or moderately saline hydro-morphic and halomorphic soils allowing water retention and a potential larval breeding sites. By contrast, non-hotspot villages were characterized mainly by a high proportion of extremely permeable sandy-textured soils, which due to their porosity had low water retention. The annual number of confirmed malaria cases was correlated with the frequency and extent of breeding sites. Malaria cases were significantly more frequent in the hamlets located near breeding sites of An. gambiae s.l., gradually decreasing with increasing remoteness. This study shows that the characteristics of larval breeding sites, as measured by their longevity, stability, proximity to human habitation, and their positivity in Anopheles larvae are likely determining factors in the persistence of malaria hotspots in central-western Senegal. The results of this study shed more light on the environmental factors underlying the residual transmission and should make it possible to better target vector control interventions for malaria elimination in west-central Senegal.

Novel Sources of Resistance to Phytophthora capsici on Pepper (Capsicum sp.) Landraces from Mexico.

Phytophthora capsici Leonian is a major pathogen of pepper worldwide and few resistance sources to this pathogen have been identified so far. The goals of this study were to identify new sources of resistance against P. capsici in Capsicum landraces and analyze the relationship between the resistance indicator of plant symptoms and some plant phenotype parameters of plant height, stem width, leaf length and leaf width. Thirtytwo landraces of pepper were collected from fourteen states in Mexico. From each population, 36 plants were inoculated with 10,000 zoospores of P. capsici under controlled conditions. This experiment was repeated twice. Out of the 32 landraces, six showed high level of resistance, four showed intermediate resistance and five showed low level of resistance when compared with the susceptible control 'Bravo' and the resistant control 'CM334', indicating that these landraces are promising novel sources of resistance to P. capsici. There was no correlation between the symptoms and plant phenotype parameters. However, these parameters were not affected in the group classified as highly resistant, indicating that P. capsici does not affect the growing of these resistant pepper landraces. The other resistant groups were significantly affected in a differently manner regarding their phenotype, indicating that this pathogen reduce their growth in different ways. This study reports novel resistance sources with great potential that could be used in breeding programs to develop new pepper cultivars with durable resistance to P. capsici.

GWAS unveils features between early- and late-flowering pearl millets.

BACKGROUND: Pearl millet, a nutritious food for around 100 million people in Africa and India, displays extensive genetic diversity and a high degree of admixture with wild relatives. Two major morphotypes can be distinguished in Senegal: early-flowering Souna and late-flowering Sanio. Phenotypic variabilities related to flowering time play an important role in the adaptation of pearl millet to climate variability. A better understanding of the genetic makeup of these variabilities would make it possible to breed pearl millet to suit regions with different climates. The aim of this study was to characterize the genetic basis of these phenotypic differences. RESULTS: We defined a core collection that captures most of the diversity of cultivated pearl millets in Senegal and includes 60 early-flowering Souna and 31 late-flowering Sanio morphotypes. Sixteen agro-morphological traits were evaluated in the panel in the 2016 and 2017 rainy seasons. Phenological and phenotypic traits related with yield, flowering time, and biomass helped differentiate early- and late-flowering morphotypes. Further, using genotyping-by-sequencing (GBS), 21,663 single nucleotide polymorphisms (SNPs) markers with more than 5% of minor allele frequencies were discovered. Sparse non-negative matrix factorization (sNMF) analysis confirmed the genetic structure in two gene pools associated with differences in flowering time. Two chromosomal regions on linkage groups (LG 3) (~ 89.7 Mb) and (LG 6) (~ 68.1 Mb) differentiated two clusters among the early-flowering Souna. A genome-wide association study (GWAS) was used to link phenotypic variation to the SNPs, and 18 genes were linked to flowering time, plant height, tillering, and biomass (P-value < 2.3E-06). CONCLUSIONS: The diversity of early- and late-flowering pearl millet morphotypes in Senegal was captured using a heuristic approach. Key phenological and phenotypic traits, SNPs, and candidate genes underlying flowering time, tillering, biomass yield and plant height of pearl millet were identified. Chromosome rearrangements in LG3 and LG6 were inferred as a source of variation in early-flowering morphotypes. Using candidate genes underlying these features between pearl millet morphotypes will be of paramount importance in breeding for resilience to climatic variability.

Evaluation of the effectiveness of a targeted community-based IRS approach for malaria elimination in an area of low malaria transmission of the central-western Senegal.

The implementation of effective malaria control strategies in the central-western Senegal, such as Indoor Residual Spraying (IRS), long-lasting insecticide-treated nets (LLIN), Seasonal malaria chemoprophylaxis (SMC) and appropriate management of malaria cases, has led to the decline of malaria transmission in the region. However, residual malaria transmission still occurring in some localities, known as hotspots villages, making challenging the achievement of the malaria elimination goal. A pilot study was undertaken between 2013 and 2014 to test the feasibility of a community-based IRS approach for malaria elimination in four targeted health districts of the Central Western Senegal. The residual efficacy of the Actellic® 300CS formulation on the sprayed surface was monitored using WHO cone test. Overall, 615 walls were tested over the two successive years, respectively 240 and 375 in 2013 and 2014 IRS campaigns. The residual efficacy of the IRS with Actellic®300 CS was longer in the second year due to the improvement of community agents spraying skill the second year thanks to the refreshing training and a better supervision by professional agent of the National Hygiene Service. The analysis of the Incidence Rate Ratio under the Poisson model shows no significant difference of IRS effectiveness according to the building type. In conclusion, the quality of training of community agents and good supervision of IRS activities play a key role in the quality and the residual efficacy of IRS campaigns. A good planning and implementation of IRS campaign ensure a high quality and a good effectiveness of spraying with the Actellic®300 CS formulation.

Entomological impact of indoor residual spraying with pirimiphos-methyl: a pilot study in an area of low malaria transmission in Senegal.

BACKGROUND: Scaling-up of effective anti-malarial control strategies in Central-West region of Senegal has resulted in the sharp decline in malaria prevalence in this area. However, despite these strategies, residual malaria transmission has been observed in some villages (hot spots). The objective of this study was to assess the impact of indoor residual spraying (IRS) with pirimiphos-methyl on malaria transmission in hot spot areas. METHODS: The malaria vector population dynamics were monitored in each of the six selected villages (4 of which used IRS, 2 were unsprayed control areas) using overnight human landing catches (HLC) and pyrethrum spray catches (PSC). The host source of blood meals from freshly fed females collected using PSC was identified using the direct ELISA method. Females caught through HLC were tested by ELISA for the detection of Plasmodium falciparum circumsporozoite protein and Anopheles gambiae complex was identified using PCR. RESULTS: Preliminary data shown that the densities of Anopheles populations were significantly lower in the sprayed areas (179/702) compared to the control. Overall, malaria transmission risk was 14 times lower in the intervention zone (0.94) compared to the control zone (12.7). In the control areas, three Anopheles species belonging to the Gambiae complex (Anopheles arabiensis, Anopheles coluzzii and Anopheles melas) maintained the transmission, while only An. coluzzii was infective in the sprayed areas. CONCLUSION: The preliminary data from this pilot study showed that IRS with the CS formulation of pirimiphos-methyl is likely very effective in reducing malaria transmission risk. However, additional studies including further longitudinal entomological surveys as well as ecological and ethological and genetical characterization of vectors species and their populations are needed to better characterize the entomological impact of indoor residual spraying with pirimiphos-methyl in the residual transmission areas of Senegal.

Epidemiology of malaria and elimination prospects in Maghreb Countries.

BACKGROUND: Faced with the challenges of immigration, the opening of the Trans-Saharan road and the increase in the volume of trade with sub-Saharan Africa, there is a steady increase in the number of malaria cases. An introduction of the disease in the Maghreb is possible. OBJECTIVE: The general objective is to take stock of the epidemiological situation and the malaria control strategy in the Maghreb countries. METHODS: This is a synthesis of data from a literature search on: PubMed (publications), International and national reports (epidemiology and strategies). RESULTS: In 1979, Tunisia became the second Maghreb country to eliminate malaria after Libya (the last local case in 1973). In 1997, when 76 cases were recorded, Morocco embarked on a new national strategy aimed at the elimination of indigenous malaria by the end of 2005. In Algeria, after a phase of control by existence of P. vivax and P. malaria microspheres, the country is in the maintenance phase and no cases were recorded between 2013 and 2016. In Mauritania, even though malaria transmission is generally low, this parasitosis remains a problem public health. And the strategies of struggle and the contribution of scientific research remain below expectations. CONCLUSION: With the exception of Mauritania, the countries of the Great Arab Maghreb have practically eradicated malaria, even though the maintenance phase is underway in Algeria and cases imported from sub-Saharan Africa continue to be registered.

Large-scale delivery of seasonal malaria chemoprevention to children under 10 in Senegal: an economic analysis.

Seasonal Malaria Chemoprevention (SMC) is recommended for children under 5 in the Sahel and sub-Sahel. The burden in older children may justify extending the age range, as has been done effectively in Senegal. We examine costs of door-to-door SMC delivery to children up to 10 years by community health workers (CHWs). We analysed incremental financial and economic costs at district level and below from a health service perspective. We examined project accounts and prospectively collected data from 405 CHWs, 46 health posts, and 4 district headquarters by introducing questionnaires in advance and completing them after each monthly implementation round. Affordability was explored by comparing financial costs of SMC to relevant existing health expenditure levels. Costs were disaggregated by administration month and by health service level. We used linear regression models to identify factors associated with cost variation between health posts. The financial cost to administer SMC to 180 000 children over one malaria season, reaching ∼93% of children with all three intended courses of SMC was $234 549 (constant 2010 USD) or $0.50 per monthly course administered. Excluding research-participation incentives, the financial cost was $0.32 per resident (all ages) in the catchment area, which is 1.2% of Senegal's general government expenditure on health per capita. Economic costs were 18.7% higher than financial costs at $278 922 or $0.59 per course administered and varied widely between health posts, from $0.38 to $2.74 per course administered. Substantial economies of scale across health posts were found, with the smallest health posts incurring highest average costs per monthly course administered. SMC for children up to 10 is likely to be affordable, particularly where it averts substantial curative care costs. Estimates of likely costs and cost-effectiveness of SMC in other contexts must account for variation in average costs across delivery months and health posts.

New Genetic Insights into Pearl Millet Diversity As Revealed by Characterization of Early- and Late-Flowering Landraces from Senegal.

Pearl millet (Pennisetum glaucum (L.) R. Br.) is a staple food and a drought-tolerant cereal well adapted to Sub-Saharan Africa agro-ecosystems. An important diversity of pearl millet landraces has been widely conserved by farmers and therefore could help copping with climate changes and contribute to future food security. Hence, characterizing its genetic diversity and population structure can contribute to better assist breeding programs for a sustainable agricultural productivity enhancement. Toward this goal, a comprehensive panel of 404 accessions were used that correspond to 12 improved varieties, 306 early flowering and 86 late-flowering cultivated landraces from Senegal. Twelve highly polymorphic SSR markers were used to study diversity and population structure. Two genes, PgMADS11 and PgPHYC, were genotyped to assess their association to flowering phenotypic difference in landraces. Results indicate a large diversity and untapped potential of Senegalese pearl millet germplasm as well as a genetic differentiation between early- and late-flowering landraces. Further, a fine-scale genetic difference of PgPHYC and PgMADS11 (SNP and indel, respectively) and co-variation of their alleles with flowering time were found among landraces. These findings highlight new genetic insights of pearl millet useful to define heterotic populations for breeding, genomic association panel, or crosses for trait-specific mapping.

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.

Population genomics of pearl millet (Pennisetum glaucum (L.) R. Br.): Comparative analysis of global accessions and Senegalese landraces.

BACKGROUND: Pearl millet is a staple food for people in arid and semi-arid regions of Africa and South Asia due to its high drought tolerance and nutritional qualities. A better understanding of the genomic diversity and population structure of pearl millet germplasm is needed to support germplasm conservation and genetic improvement of this crop. Here we characterized two pearl millet diversity panels, (i) a set of global accessions from Africa, Asia, and the America, and (ii) a collection of landraces from multiple agro-ecological zones in Senegal. RESULTS: We identified 83,875 single nucleotide polymorphisms (SNPs) in 500 pearl millet accessions, comprised of 252 global accessions and 248 Senegalese landraces, using genotyping by sequencing (GBS) of PstI-MspI reduced representation libraries. We used these SNPs to characterize genomic diversity and population structure among the accessions. The Senegalese landraces had the highest levels of genetic diversity (π), while accessions from southern Africa and Asia showed lower diversity levels. Principal component analyses and ancestry estimation indicated clear population structure between the Senegalese landraces and the global accessions, and among countries in the global accessions. In contrast, little population structure was observed across in the Senegalese landraces collections. We ordered SNPs on the pearl millet genetic map and observed much faster linkage disequilibrium (LD) decay in Senegalese landraces compared to global accessions. A comparison of pearl millet GBS linkage map with the foxtail millet (Setaria italica) and sorghum (Sorghum bicolor) genomes indicated extensive regions of synteny, as well as some large-scale rearrangements in the pearl millet lineage. CONCLUSIONS: We identified 83,875 SNPs as a genomic resource for pearl millet improvement. The high genetic diversity in Senegal relative to other regions of Africa and Asia supports a West African origin of this crop, followed by wide diffusion. The rapid LD decay and lack of confounding population structure along agro-ecological zones in Senegalese pearl millet will facilitate future association mapping studies. Comparative population genomics will provide insights into panicoid crop evolution and support improvement of these climate-resilient crops.