Growth rate differences in human malaria parasites - Why do some parasites grow more quickly in the body, and cause more severe forms of malaria disease?

 

Supervisor: Lisa Ranford-Cartwright, School of Biodiversity, One Health & Veterinary Medicine

There are over 240 million cases of malaria caused by P. falciparum per year, and around 600,000 people die of severe forms of the disease. Identifying and targeting better health care to those individuals most at risk of severe disease and death is a priority to reduce mortality rates, but at present there is no clear marker, either in the host or parasite, associated with increased risk of mortality. Higher parasite growth rates in the blood, leading to increased parasite burdens, are associated with higher morbidity and mortality [1,2]. Previous work in my lab using a quantitative trait locus analysis [3] in a genetic cross between two P. falciparum clones identified genomic regions (qtl) contributing to asexual growth rate differences that differ in their invasion efficiency. Our overall aim for this project is to identify the genes in the human malaria parasite Plasmodium falciparum that determine differential rates of intraerythrocytic growth, and thus suggest biomarkers for the development of severe disease.

We have very recently culture-adapted a set of new parasites from people living in Mali (unpublished). Some children presented with a form of severe malaria known as hyperparasitaemia, where there are very high numbers of parasites in the blood, possibly as a result of fast growth- but this is not understood. During the rotation project, you will characterise the growth rates of these parasites, plus controls from individuals presenting with lower parasitaemia. You will analyse variation in the genes within the qtl regions we identified, and see if variation in these genes correlates with high growth rates. Is there good evidence to link growth rate with the occurrence of hyperparasitaemia?

The work would involve culturing the new malaria parasites, and measuring their growth rates (length of intra-erythrocytic cycle, number offspring per cycle, invasion efficacy). This would be coupled with some bioinformatics (sequencing). The project has plenty of scope to develop into different areas to explore these novel isolates.

References

  1. Chotivanich K, Udomsangpetch R, Simpson J, Newton P, Pukrittayakamee S, Looareesuwan S, White N (2000) Parasite Multiplication Potential and the Severity of Falciparum Malaria. J Inf Dis 181: 1206-1209.
  2. Tripathy R, Parida S, Das L, Mishra DP, Tripathy D, Das MC, Chen H, Maguire JH, Panigrahi P (2007) Clinical manifestations and predictors of severe malaria in Indian children. Pediatrics 120: e454-e460.
  1. Ranford-Cartwright LC, Mwangi JM (2012) Analysis of malaria parasite phenotypes using experimental genetic crosses of Plasmodium falciparum. Int J Parasitol 42: 529-534.

 webpages: https://www.gla.ac.uk/schools/bohvm/staff/lisaranford-cartwright/