Biology subjects

Drakeley, C.

Publications and source records attributed to Drakeley, C..

23 records · Page 2Linked to original sources

bioRxiv2018

A systematic review and meta-analysis of the human blood index of the major African malaria vectors

BACKGROUNDThe proportion of mosquito blood-meals that are of human origin, referred to as the human blood index or HBI, is a key determinant of malaria transmission. We conducted a systematic review of the HBI for the major African malaria vectors.\n\nRESULTSEvidence is presented for higher HBI among Anopheles gambiae (M/S forms and An. coluzzii/An. gambiae s.s. are not distinguished for most studies and therefore combined) as well as An. funestus when compared with An. arabiensis (prevalence odds ratio adjusted for collection location [i.e. indoor or outdoor]: 1.62; 95%CI 1.09-2.42; 1.84; 95%CI 1.35-2.52, respectively). This finding is keeping with the entomological literature which describes An. arabiensis to be more zoophagic than the other major African vectors. However, analysis also revealed that HBI was more associated with location of mosquito captures (R2=0.29) than with mosquito (sibling) species (R2=0.11).\n\nCONCLUSIONSOur findings call into question the appropriateness of current methods of assessing host preferences among disease vectors and have important implications for strategizing vector control.

ecology↗

bioRxiv2018

Taking sharper pictures of malaria with CAMERAs: Combined Antibodies to Measure Exposure Recency Assays

Antibodies directed against malaria parasites are easy and inexpensive to measure but remain an underutilized surveillance tool due to a lack of consensus on what to measure and how to interpret results. High throughput screening of antibodies from well-characterized cohorts offers a means to substantially improve existing assays by rationally choosing the most informative sets of responses and analytical methods. Recent data suggest that high-resolution data on malaria exposure can be obtained from a small number of samples by measuring a handful of properly chosen antibody responses. In this review, we will discuss how standardized multi-antibody assays can be developed and efficiently integrated into existing surveillance activities, with great potential to greatly augment the breadth and quality of information available to direct and monitor malaria control and elimination efforts.

epidemiology↗

bioRxiv2017

Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Plasmodium gametocytes are the sexual forms of the malaria parasite essential for transmission to mosquitoes. To better understand how gametocytes differ from asexual blood-stage parasites, we performed a systematic analysis of available omics data for P. falciparum and other Plasmodium species. 18 transcriptomic and proteomic data sets were evaluated for the presence of curated \"gold standards\" of 41 gametocyte-specific versus 46 non-gametocyte genes and integrated using Bayesian probabilities, resulting in gametocyte-specificity scores for all P. falciparum genes.\n\nTo illustrate the utility of the gametocyte score, we explored newly predicted gametocyte-specific genes as potential biomarkers of gametocyte carriage and exposure. We analyzed the humoral immune response in field samples against 30 novel gametocyte-specific antigens and found five antigens to be differentially recognized by gametocyte carriers as compared to malaria-infected individuals without detectable gametocytes. We also validated the gametocyte-specificity of 15 identified gametocyte transcripts on culture material and samples from naturally infected individuals, resulting in eight transcripts that were >1000-fold higher expressed in gametocytes compared to asexual parasites and whose transcript abundance allowed gametocyte detection in naturally infected individuals. Our integrated genome-wide gametocyte-specificity scores provide a comprehensive resource to identify targets and monitor P. falciparum gametocytemia.

microbiology↗

bioRxiv2017

Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure

Malaria immunity is complex and multi-faceted, and fundamental gaps remain in our understanding of how it develops. Here, we use detailed clinical and entomological data from three parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomatic Plasmodium falciparum as a function of age and transmission intensity. We focus on: anti-parasite immunity (i.e; ability to control parasite densities) and anti-disease immunity (i.e; ability to tolerate higher parasite densities without fever). Our findings suggest a strong effect of age on both types of immunity, that remains significant after adjusting for cumulative exposure. They also show a non-linear effect of transmission intensity, where children experiencing the lowest transmission appear to develop immunity faster than those experiencing higher transmission. These findings illustrate how anti-parasite and anti-disease immunity develop in parallel, reducing the probability of experiencing symptomatic malaria upon each subsequent P. falciparum infection.

epidemiology↗

bioRxiv2016

A structural variant encoding hybrid glycophorins is associated with resistance to severe malaria

Plasmodium falciparum invades human red blood cells by a series of interactions between host and parasite surface proteins. Here we analyse whole genome sequence data from worldwide human populations, including 765 new genomes from across sub-Saharan Africa, and identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA and GYPB. We find that a nearby reported association with severe malaria is explained by a complex structural variant that involves the loss of GYPB and gain of two hybrid genes, each with a GYPB extracellular domain and GYPA intracellular domain. This variant reduces the risk of severe malaria by 40% and has recently risen in frequency in parts of Kenya. We show that the structural variant encodes the Dantu blood group antigen, and therefore a serologically distinct red cell phenotype. These findings demonstrate that structural variation of red blood cell invasion receptors is associated with natural resistance to P. falciparum malaria.

genomics↗