Poster Presentation First Malaria World Congress 2018

Extreme diversity and population structure of var genes can explain why immunity to the blood stages of Plasmodium falciparum is non-sterilizing (#377)

Shazia Ruybal-Pesántez 1 , Kathryn E Tiedje 1 , Gerry Tonkin-Hill 2 , Shai Pilosof 3 , Abraham R Oduro 4 , Michael F Duffy 1 , Kwadwo A Koram 5 , Mercedes Pascual 3 , Karen P Day 1
  1. University of Melbourne/Bio21 Institute, Parkville, VIC, Australia
  2. Walter and Eliza Hall Institute, Melbourne, Australia
  3. Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA
  4. Navrongo Health Research Centre, Navrongo, Ghana
  5. Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana

PfEMP1 is encoded by the var multi-gene family and is a major target of naturally acquired immunity. Variation in PfEMP1 underlies parasite fitness, measured as the ability to evade the host immune response and establish a chronic infection to optimize transmission. We investigated the extent of var sequence diversity and population structure in the asymptomatic P. falciparum reservoir in an area with seasonal transmission in Bongo District (BD), Ghana. We sampled individuals across all ages with asymptomatic P. falciparum infections (both microscopic and, for the first time, submicroscopic infections) to examine the entire parasite reservoir. With the aim to define the transmission dynamics of P. falciparum through the lens of var genomics, we set out to describe seasonal and age-specific patterns of var diversity at the var type and repertoire level, within-host infection complexity, temporal var dynamics, and population structure. Our analysis of 1,099 P. falciparum isolates across two transmission seasons revealed 42,399 var types circulating in the population. Strikingly, this extensive diversity was uniquely structured into var repertoires that had minimal overlap regardless of season and infection complexity. Through the lens of var genes, we explain several key epidemiological features of P. falciparum malaria in endemic areas and demonstrate that the transmission system in BD is extremely complex. Despite this complexity, three key features of the molecular epidemiology emerge: (i) extremely high var sequence diversity, (ii) limited overlap of var repertoires in both seasons, and (iii) rapid turnover of repertoires yet maintenance of certain var types between seasons. The absence of related parasites was demonstrated by pairwise type sharing and most isolate repertoires shared <10% of their var types. Using computational experiments, this highly diverse parasite population with non-overlapping var repertoires was shown to explain age-specific patterns of immunity and the epidemiology of P. falciparum in high transmission areas.