Abstract
BackgroundGrowth rate of malaria parasites in the blood of infected subjects is an important measure of efficacy of drugs and vaccines.MethodsWe used log-linear and sine-wave models to estimate the parasite growth rate of the 3D7 strain of Plasmodium falciparum using data from 177 subjects from 14 induced blood stage malaria (IBSM) studies conducted at QIMR Berghofer. We estimated parasite multiplication rate per 48 hour (PMR48), PMR per life-cycle (PMRLC), and parasite life-cycle duration. We compared these parameters to those from studies conducted elsewhere with infections induced by IBSM (n=66), sporozoites via mosquito bite (n=336) or injection (n=51).ResultsThe parasite growth rate of 3D7 in QIMR Berghofer studies was 0.75/day (95% CI: 0.73–0.77/day), PMR48 was 31.9 (95% CI: 28.7–35.4), PMRLC was 16.4 (95% CI: 15.1–17.8) and parasite life-cycle was 38.8 hour (95% CI: 38.3–39.2 hour). These parameters were similar to estimates from IBSM studies elsewhere (0.71/day, 95% CI: 0.67–0.75/day; PMR48 26.6, 95% CI: 22.2–31.8), but significantly higher (P < 0.001) than in sporozoite studies (0.47/day, 95% CI: 0.43–0.50/day; PMR48 8.6, 95% CI: 7.3–10.1).ConclusionsParasite growth rates were similar across different IBSM studies and higher than infections induced by sporozoite.
Highlights
Growth rate of malaria parasites in the blood of infected subjects is an important measure of efficacy of drugs and vaccines
Accurate estimation of the parasite life-cycle in the induced blood stage malaria (IBSM) model would s allow estimation of parasite multiplication rate (PMR) per life-cycle (PMRLC). nu In this study, we analyzed data from IBSM studies conducted at QIMR Berghofer (QIMR-B) a in which subjects were inoculated with P. falciparum 3D7 under similar experimental M conditions [20,21,22,23,24,25,26,27,28,29,30,31,32] and parasitemia quantitated by a validated quantitative PCR assay d [33]
The log10 parasite growth rate t estimated fitting QIMR-B IBSM parasitemia data overall using a sine-wave model was ip 0.75/day, the amplitude was estimated as 0.63 log10 parasites (95% cr confidence intervals (CI): 0.59–0.66 log10 parasites) and the parasite life-cycle was estimated as 38.8 h
Summary
The growth rate of Plasmodium parasites in the blood of infected individuals is a major determinant of parasite biomass and the pathology of malaria [1]. PMR48 has been e estimated using parasitemia data from volunteer infection studies (VIS) – otherwise known as c Controlled Human Malaria Infection (CHMI) studies – conducted to evaluate efficacy of Ac blood stage vaccines. We estimated the parasite growth rate and parasite life-cycle of P. falciparum 3D7, to te calculate PMR48 and PMRLC We compared these estimates with our estimates using p data from IBSM studies conducted by other research groups [14, 15, 34,35,36,37], from mosquito e bite sporozoite studies [17, 19, 34, 38], and from cryopreserved sporozoite studies [8, 10, 39Acc 42]
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