Declining malaria transmission differentially impacts on the maintenance of humoral immunity to Plasmodium falciparum in children

BACKGROUND We investigated the poorly understood impact of declining malaria transmission on maintenance of antibodies to P. falciparum merozoite antigens and infected erythrocytes (IEs), including functional immunity. METHODS In a 3-year longitudinal cohort of 300 Kenyan children, antibodies to different merozoite AMA1 and MSP2 alleles, IE surface antigens, and antibody functional activities were quantified. RESULTS Over a period in which malaria transmission declined markedly, AMA1 and MSP2 antibodies decreased substantially; estimated half-lives of antibody duration were 0.8 and 1-3 years, respectively. However, 69-74% of children maintained their sero-positivity to AMA1 alleles and 42-52% to MSP2 alleles. Levels and prevalence of anti-merozoite antibodies were consistently associated with increasing age and concurrent parasitaemia. Antibodies promoting opsonic phagocytosis of merozoites declined rapidly (half-life 0.15 years). In contrast, complement-fixing antibodies to merozoites did not decline and antibodies to IE surface antigens expressing virulent phenotypes were much better maintained (half-life 4-10 years). CONCLUSIONS A decline in malaria transmission is associated with reduction in naturally-acquired immunity. However, loss of immunity is not universal; some key functional responses and antibodies to IEs were better maintained and these may continue to provide some protection. Findings have implications for malaria surveillance and control measures and informing vaccine development

Declining malaria transmission differentially impacts the maintenance of humoral immunity to Plasmodium falciparum in children

Background We investigated the poorly understood impact of declining malaria transmission on maintenance of antibodies to Plasmodium falciparum merozoite antigens and infected erythrocytes (IEs), including functional immunity. Methods In a 3-year longitudinal cohort of 300 Kenyan children, antibodies to different AMA1 and MSP2 alleles of merozoites, IE surface antigens, and antibody functional activities were quantified. Results Over a period in which malaria transmission declined markedly, AMA1 and MSP2 antibodies decreased substantially; estimated half-lives of antibody duration were 0.8 year and 1–3 years, respectively. However, 69%–74% of children maintained their seropositivity to AMA1 alleles and 42%–52% to MSP2 alleles. Levels and prevalence of antimerozoite antibodies were consistently associated with increasing age and concurrent parasitemia. Antibodies promoting opsonic phagocytosis of merozoites declined rapidly (half-life, 0.15 years). In contrast, complement-fixing antibodies to merozoites did not decline and antibodies to IE surface antigens expressing virulent phenotypes were much better maintained (half-life, 4–10 years). Conclusions A decline in malaria transmission is associated with reduction in naturally acquired immunity. However, loss of immunity is not universal; some key functional responses and antibodies to IEs were better maintained and these may continue to provide some protection. Findings have implications for malaria surveillance and control measures and informing vaccine development.</p

Deep Learning Model for Grading Metastatic Epidural Spinal Cord Compression on Staging CT

10.3390/cancers14133219Cancers14133219

Transcriptome sequencing and annotation of the microalgae Dunaliella tertiolecta: Pathway description and gene discovery for production of next-generation biofuels

Background Biodiesel or ethanol derived from lipids or starch produced by microalgae may overcome many of the sustainability challenges previously ascribed to petroleum-based fuels and first generation plant-based biofuels. The paucity of microalgae genome sequences, however, limits gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for the non-model microalgae species, Dunaliella tertiolecta, and identify pathways and genes of importance related to biofuel production. Results Next generation DNA pyrosequencing technology applied to D. tertiolecta transcripts produced 1,363,336 high quality reads with an average length of 400 bases. Following quality and size trimming, ~ 45% of the high quality reads were assembled into 33,307 isotigs with a 31-fold coverage and 376,482 singletons. Assembled sequences and singletons were subjected to BLAST similarity searches and annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology (KO) identifiers. These analyses identified the majority of lipid and starch biosynthesis and catabolism pathways in D. tertiolecta. Conclusions The construction of metabolic pathways involved in the biosynthesis and catabolism of fatty acids, triacylglycrols, and starch in D. tertiolecta as well as the assembled transcriptome provide a foundation for the molecular genetics and functional genomics required to direct metabolic engineering efforts that seek to enhance the quantity and character of microalgae-based biofuel feedstock.National Science Foundation (U.S.) (Grant #0854322)National Institutes of Health (U.S.) (NIH Grant# RR19895)Biomedical High Performance Computing Cente