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Despite recent progress in the fight against malaria, it still remains a global health challenge necessitating development of intervention strategies. However, the search for malaria vaccine(s) has so far been very challenging. Multiple targets have been tested and so far only a few show promise with one having been endorsed by the WHO. In this study we explore the development of immunity in a low transmission setting, with very few documented re-infections, in order to understand the kinetics of the development and waning of immunity to current and novel blood-stage vaccine candidate antigens. To do this we performed a high-throughput measurement of natural acquired immunity against P. falciparum antigens utilizing a well-established micro-array platform based on the mammalian protein expression system. This large panel of known and novel recombinant full length ectodomain P. falciparum merozoite vaccine candidates were differently recognized by the immune system. Based on the overal spread of the data, some of these antigens induced the acquisition of high levels (1st tertile) of antibodies, among which included novel antigens such as PF3D7_1025300, PF3D7_1105800, PF3D7_1334400, PF3D7_0911300, PF3D7_1252300, PF3D7_1460600, PF3D7_1453100, PF3D7_0831400 and some induced low levels of antibodies (3rd tertile) while others induced moderate levels (4th tertile). In this longitudinal cohort with low level of malaria endemicity, acquisition of humoral immunity to these full length ectodomains P. falciparum antigens demonstrate different dynamics over-time, whereby it was either not acquired or if it was acquired it was either maintained or lost at different rates. These various identified novel antigens are potentially ideal candidates to be prioritized for further functional and or serological studies.

Molecular data and analysis outputs are being integrated into malaria surveillance efforts to provide valuable programmatic insights for national malaria control programs (NMCPs). A plethora of studies from diverse geographies have demonstrated that malaria parasite genetic data can be an important tool for drug resistance monitoring, species identification, outbreak analysis, and transmission characterization. Despite many successful research efforts, there are still important knowledge gaps hindering practical translation of each of these use cases for NMCPs. Here, we leverage epidemiological modeling and time-series data of 2035 genetic sequences collected in Thiès, Senegal from 2006-2018 to provide a quantitative and setting-specific assessment of the levels, trends, and connectivity of malaria transmission. We also identify the genetic features that are the most informative for inferring transmission in Thiès, such as the fraction of the population with multiple infections and the persistence of parasite lineages across multiple transmission seasons. The model fitting and uncertainty quantification framework also reveals a significant decrease in the level of malaria transmission around 2013. This difference coincides with a large-scale drought and bed net campaign by the NMCP and USAID and is independently corroborated by geo-spatial models of incidence in Thiès. We find that genetically identical samples are more likely to be geographically clustered even at the neighborhood scale; and moreover, these lineages propagate non-randomly around the city. Our approach and results provide quantitative guidance for the interpretation of malaria parasite genetic data from Thiès, Senegal and indicates the value of increased malaria genomic surveillance for NMCPs.

Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.

Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal—a region of exceptionally low malaria transmission (entomological inoculation rate (EIR) less than 1). Genetic identity (identity by state) was established using a 24 single nucleotide polymorphism molecular barcode and a multivariable linear regression model was used to establish genetic and spatial relationships. Our results show clustering of genetically similar parasites within households and a decline in genetic similarity of parasites with increasing distance. One household showed extremely high diversity and warrants further investigation as to the source of these diverse genetic types. This study illustrates the utility of genomic data with traditional epidemiological approaches for surveillance and detection of trends and patterns in malaria transmission not only by neighborhood but also by household. This approach can be implemented regionally and countrywide to strengthen and support malaria control and elimination efforts.

Dengue virus is a major and rapidly growing public health concern in tropic and subtropic regions across the globe. In late 2018, Senegal experienced its largest dengue virus outbreak to date, covering several regions. However, little is known about the genetic diversity of dengue virus (DENV) in Senegal. Here we used molecular tools including metagenomic sequencing to identify 19 previously undetected dengue virus cases from the city of Thiès and assemble 17 complete virus genomes. DENV3 was the most frequent serotype; 11 sequences (65%) were DENV3, 4 sequences were DENV2 and 2 were DENV1. Sequences were closest to recent sequences from West Africa, suggesting ongoing local circulation of viral populations; however, detailed inference is limited by the scarcity of available genomic data. We did not find clear associations with reported clinical signs or symptoms, highlighting the importance of testing for diagnosing febrile diseases. Overall, these findings expand the known range of DENV in Senegal, and underscore the need for better genomic characterization of DENV in West Africa.

BackgroundCharacterization of malaria parasite populations in different endemic settings (from low to high) could be helpful for ascertaining the progress of malaria interventions in endemic settings. The present study aims to compare Plasmodium falciparum parasite population structure between two West African countries with very different level of endemicity using P. falciparum allelic polymorphic markers: msp1 and msp2.MethodsParasite genomic DNA was extracted from 187 dried blood spot collected from confirmed uncomplicated P. falciparum malaria infected patients in Senegal (94) being at the pre-elimination stage in most part of the country and Nigeria (93) which is still at the control stage. Allelic polymorphism of msp1 and msp2 genes were assessed by nested PCR.ResultsIn Senegal as well as in Nigeria, K1 and IC3D7 allelic families were the most represented for msp1 and msp2 genes respectively. A higher multiplicity of infection (MOI) was found in both study sites in Senegal (Thies:1.51/2.53; Kedougou:2.2/2.0 for msp 1/2) than from sites in Nigeria (Gbagada: 1.39/1.96; Oredo: 1.35/1.75]). The heterozygosity of msp 1 gene was higher in P. falciparum isolates from Senegal (Thies: 0.62; Kedougou: 0.53) than isolates from Nigeria (Gbagada: 0.55; Oredo: 0.50). In Senegal, K1 alleles were associated with heavy (28) than with moderate (18) infections, in Nigeria however, equal proportions of K1 were observed in both infection types. The IC3D7 subtype allele of the msp 2 family showed high occurrence in heavily infected individuals from both countries (Senegal- 32; Nigeria- 26) than in the moderately infected participants.ConclusionWith the unusual high genetic diversity obtained in low endemic setting in Senegal and low genetic diversity in a high endemic Nigerian setting, multiple holistic approach should be employed in evaluating the actual transmission of a place in order to effectively direct control measures.

As transmission intensity has declined in Senegal, so has the genetic complexity of circulating Plasmodium falciparum parasites, resulting in specific genotypes emerging and persisting over years. We address whether changes in parasite genetic signatures can alter the immune repertoire to variant surface antigens, and whether such responses can influence the expansion or contraction of specific parasite genotypes in the population. We characterize parasites within genotypic clusters, defined as identical by a 24-SNP molecular barcode and a haplotype identifier for other highly polymorphic loci; we measure expression of variant surface antigens (VSA) such as PfEMP-1 by transcript expression typing and expressed var DBL1α sequencing in ex vivo and short-term adapted RNA samples; and we measure IgG responses against VSAs from short-term adapted parasites. We find that parasites within genotypic clusters are genetically identical at other highly polymorphic loci. These parasites express similar Ups var classes and largely the same dominant var DBL1α sequences ex vivo. These parasites are recognized similarly by anti-VSA antibodies after short-term adaptation to culture; however, antibody responses do not correlate with genotype frequencies over time. Both genotype-specific and multiple genotype-reactive surface IgG responses are observed in this population. Parasites with identical genomes are extremely similar in their expression and host antibody recognition of VSAs. Monitoring changes in population-level parasite genomics and transmission dynamics is critical, as fluctuations will influence the breadth of resulting host immune responses to circulating parasite genotypes. These findings suggest shared immune recognition of genetically similar parasites, which has implications for both our understanding of immunity and vaccine development strategies in malaria elimination settings.