Modelling of reinvasion efficiency in Plasmodium falciparum cultures

Oosthuizen, Maria Magdalena (2017-03)

Thesis (MSc)--Stellenbosch University, 2017.

Thesis

ENGLISH SUMMARY: The virulence and severity of the malaria disease within a human host is dependent on how efficient daughter merozoites reinvade red blood cells. Traditionally estimating the efficiency of erythrocytic invasion of P.falciparum parasites has been approached with microscopic methods by counting the number of released merozoites and following the parasitaemia subsequently. We aimed to study the reinvasion from a metabolic viewpoint, i.e. macroscopically, by measuring the lactate production of infected red blood cell cultures over two subsequent life cycles. Mathematical equations describing the lactate production of uninfected and infected red blood cells in terms of the change in parasitic biomass over time were used to obtain a reinvasion model. The model was fitted to experimental data to identify unknown parameters like the reinvasion efficiency factor. Subsequently the average number of merozoites was calculated with an average of 16plus-minus4, in agreement with literature findings. Using the lactate production to study the reinvasion is a complete new approach and is advantageous as the whole cultures are studied in stead of a few hundred cells under microscopes and we gain mechanistic insight into the process. The model can now be used further to study the impact of various factors on the reinvasion more quantitatively.

AFRIKAANSE OPSOMMING: Die virulensie en felheid van 'n malaria infeksie in 'n menslike gasheer is afhanklik van hoe effektief dogter merozoïte rooibloedselle binnedring. Kwantitatiewe insigte oor die effektiwiteit van indringing van die P.falciparum-parasiete tydens bloedfases is nog baie beperk. Voorheen is hierdie probleem benader deur van mikroskopiemetodes gebruik te maak om die aantal ontwikkelende merozoïte te tel en die gevolglike toename in parasetemie te volg. Die fokus van hierdie studie was om parasietindringing makroskopies te bestudeer van uit 'n metaboliese oogpunt, deur die laktaatproduksie van ongeïnfekteerde en geïnfekteerde rooibloedselle beskryf in terme van die verandering in parasitiese biomassa met verloop van tyd. Die model is instaat daartoe om eksperimentele data te gebruik om onbekende parameters, soos die faktor van herindringingsdoeltreffendheid te identifiseer. Daarna is die gemiddelde aantal merozoïte berekend met 'n gemiddeld van 16 plus-minus 4, wat deur literatuurbevindings ondersteun word. Deur die laktaatproduksie te bestudeer is 'n totaal nuwe benadering tot die onderwerp gevolg. 'n Studie van heelkulture, in plaas van slegs 'n paar honderd selle onder 'n mikroskoop laat ons toe om 'n beter meganistiese insig oor herindringing te bekom. Die model kan nou gebruik word om die impak van verskeie faktore op herindringing meer kwantitatief te bestudeer.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/101364
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