BioMalPar XVI Virtual Conference “Biology and Pathology of the Malaria Parasite” – 2020: Day 2

MESA Correspondents bring you cutting-edge coverage from the BioMalPar XIX: biology and pathology of the malaria parasite

Virtual Session 4 – Epidemiology & surveillance

Mario Recker (University of Exeter, UK) presented malaria infection data from a longitudinal, systemsimmunological cohort study conducted in a study site in Kenya between 2010 and 2018. He defined an immune response pattern that distinguishes children with frequent malaria episodes and those with an average number of episodes. After describing the time-spatial trends in cumulative malaria exposure (year of birth), Recker investigated whether malaria susceptibility could be predicted. The data showed high heterogeneity in the rate at which children experience clinical malaria and no persistent hotspots were found within the study area. The rate of acquired clinical episodes was similar between older and younger individuals and the number of experienced episodes seemed to depend more on the year of birth rather than age. Against their expectation, the probability of clinical episodes in the upcoming transmission season increased with previous exposure while no geographic trend could be determined. From these findings, Recker concluded that there might be differences in susceptibility phenotypes in the population and raised the concern that the high inter-annual and inter-individual heterogeneity likely affect results from ‘epidemiological snapshots’.

Manuella Carrasquilla (Harvard T.H. Chan School of Public Health, USA) highlighted the important aspects of malaria epidemiology in a study area in the Pacific coast of South America, Guapi. The de novo emergence of PfKelch13 C580Y mutation in Guapi, a regional hotspot of drug resistance, suggests high level of mutation occurring in local Pf populations. Carrasquilla performed whole-genome sequencing of 151 Pf clinical samples from the locality of Guapi. Population structure analysis was performed with all allele frequencies revealing five distinct ancestral populations. This is driven by the history of antimalarial selection, human migration and neutral drift. Also, identity-by-descent (IBT) analysis showed variation in the level of relatedness and a large number of clonal clusters in Guapi. Spatial and temporal dynamics of clonal clusters reveal mining sites as main drivers of malaria transmission. The impact of selection antimalarial on population structure showed dihydrofolate reductase (DHFR) haplotypes, possible ongoing antifolates selection, and migration. Ultimately, Carrasquilla pointed out evidence of transfer of Pfmdr1 haplotype between clonal clusters in addition to an increasingly level of recombination events with time.

Reduction in malaria burden has been associated with increased control interventions as shown by prevalence and cases estimates over time. Simon Kigozi (London School of Hygiene and Tropical Medicine, UK) evaluated the age distribution of malaria cases in order to determine the progress of control interventions. To address this issue, Kigozi compared routine surveillance data over a period of about ten-years (January 2009 – July 2018) from four sentinel health districts (HDs) in Uganda. These HDs have undergone mass distribution of LLINs and/or IRS during the study period. Over the study period, Kigozi observed an overall change in the age distribution of suspected and confirmed malaria cases with a shift from younger to older age groups. Age distributions were very similar to baseline data for not suspected and negative malaria patients with a marginal decline across the intervention period. These findings are therefore indicative of immunity, behavioural, occupational factors and the success of control interventions.

Virtual Session 5 – Pathogenesis & immunology

In Africa, most malaria case fatalities in pediatric patients are caused by Plasmodium falciparum (Pf) cerebral infections and failure in response to available therapeutics. Brittany Riggle (National Institutes of Health, USA), in charge of the keynote of the session, investigated the role of CD8+ T cells in this severe disease form. Using a mouse model, Riggle induced a similar pathogenesis as observed during pediatric cerebral malaria (CM) and noted a significant expression of Pf specific CD8+ T cells in the brain following a DON (6-Diazo-5-oxo-L-norleucine) treatment administered to experimental mice 4 to 8 days’ post-infection, however, CD8+ T cells were not found in peripheral tissues. Similar observations were made in post-mortem brains from pediatric patients with or without CM and with known HIV status engaging CD3+ and CD8+ into cerebro- and perivasculature. These data provide a rationale for investigating CD3+ CD8+ T cells as the target of an adjunctive therapy for cerebral malaria.

Carola Schaefer (Seattle Children’s Research Institute, USA) developed a unique humanized mouse model to investigate the transition of Pv infection to blood stages and to test blood stage interventions. In the model, human liver-chimeric FRGN huHep mice were infected with P. vivax sporozoites and infused with human reticulocytes. The model demonstrated successful parasites developed into all asexual stages (erythrocytic forms within their physiological 48-hour life cycle in vivo). A successful expression of gametocyte antigen Pvs16 was also detected. The developed model was found adequate to test blood stage interventions and provides a proof of principle that gametocytes mature and can be transmitted to mosquitoes. A promising step towards maintaining a whole life-cycle in the lab.

Virtual Session 6 – Transmission biology

The findings of Dennis Klug’s (INSERM, France) “cast new light” on the interactions between malaria parasites, their vectors and the interplay of factors during mosquitoes’ immune response of. In his talk Klug focused on the role of the Thioesther-containing protein 12 (TEP12) in the early phase of immune response of Anopheles against Plasmodium infection and compared it with TEP1, the most studied protein and major anti-parasitic factor across the TEP family. Several experiments were carried out using Anopheles stephensi and A. coluzzi, infected with Plasmodium berghei or Plasmodium falciparum. When TEP12 was knocked down, some increase in parasite load was observed in A. stephensi infected by Plasmodium berghei. When an engineered A. coluzzi strains was used, results indicated that absence of TEP12 also allowed for increase in P. berghei infections, but the opposite effect was observed in P. falciparum where knocked down of TEP12 led to a decrease in mosquito infection. Finally, TEP 12 was the first anti-plasmodial TEP present in all sequenced Anopheles species.

The closing remarks by the emeritus steering group of the EMBL Virtual BioMalPar 2020 were moderated by Julian Rayner (Wellcome Sanger Institute, UK) who gave the floor to Andy Walters (University of Glasgow, UK) for a brief In Memoriam talk, remembering Shahid Khan for his brilliant contributions in characterizing malaria parasite using OMICs tools. Rayner further thanked the organizing committee for their invaluable commitment and ‘superhuman efforts’ to make the virtual event possible and the great experiment they did with this first virtual BioMalPar. Finally, he thanked all conference participants for the wonderful experience shared and active communication.

* MESA only reported the talks that had the approval of the speaker.