Corrigendum to: A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection

Plasmodium falciparum sexual conversion rates can be affected by artemisinin-based treatment in naturally infected malaria patients

“…Two recent studies showed that the relative transcript levels of pfap2-g and SRBs such as surfin13.1 and surfin1.2 correlate with sexual conversion rates in natural infections, 21,23 and a study using controlled human malaria infection (CHMI) showed that pfap2-g relative transcript levels correlate with peak mature gametocytes density one to two weeks later. 88 Furthermore, in untreated naturally infected asymptomatic patients, pfap2-g and gexp5 relative transcript levels were positively associated with mature gametocyte carriage two weeks later. 28 Here we report the use of pfap2-g and other SRBs to study the effect of drugs on sexual conversion rates in natural infections.…”

“…Previous studies reported changes in mature gametocyte carriage after drug treatment, but the effect of the drugs on sexual conversion rates could not be disentangled from their effect on other processes. 10,61À63 Here we characterised the impact of ART treatment on sexual conversion rates using samples from three different cohorts with regular sampling every 12 h after treatment, and taking advantage of the recent validation of transcripts of pfap2-g and several other genes as in vivo markers for sexual rings, 21,23,28,88 the only early sexual stage present in the circulation. 20À23,61 Our results for this primary outcome of the study revealed increased relative transcript levels of pfap2-g and other SRBs soon after ART-based treatment in many patients, suggesting that parasites can enhance their sexual conversion rates in response to treatment.…”

“…On the other hand, SRBs have been shown to predict the future infectious potential of an individual, if not receiving antimalarial treatment. 28,88 The discovery of SRBs expressed by circulating sexual rings also enables the assessment of the effect of human host conditions or drug treatment on sexual conversion rates. Two recent studies showed that the relative transcript levels of pfap2-g and SRBs such as surfin13.1 and surfin1.2 correlate with sexual conversion rates in natural infections, 21,23 and a study using controlled human malaria infection (CHMI) showed that pfap2-g relative transcript levels correlate with peak mature gametocytes density one to two weeks later.…”

“…The density of sexual rings, estimated from the transcript levels of pfap2-g or other SRBs, predicts the future density of mature gametocytes if an infection is left untreated. 28,88 To estimate the relative (between samples) density of sexual rings in our cohorts before treatment or 12 h after treatment, we multiplied the total parasitaemia (quantified by qPCR) by the relative pfap2g transcript levels (pfap2-g/uce). There was no statistically significant correlation between mature gametocyte density (day 7-14) and estimated relative density of sexual rings before or just after treatment (Supplementary Figure 8), except for the Mozambique cohort before treatment and day 7 gametocytes (r = 0.39, p = 0.013).…”

Safety, Tolerability, and Parasite Clearance Kinetics in Controlled Human Malaria Infection after Direct Venous Inoculation of Plasmodium falciparum Sporozoites: A Model for Evaluating New Blood-Stage Antimalarial Drugs

“…9,10,16 CHMI studies have also been used to study antimalarial immunity and other aspects of host-parasite biology. [25][26][27][28][29][30][31] There are three main methods of establishing malaria infection in CHMI: intravenous administration of parasitized erythrocytes (pRBCs), [8][9][10][11][31][32][33][34] transmission of P. falciparum sporozoites (PfSPZ) via bites from infected mosquitoes, [12][13][14][15][16]30,[34][35][36][37][38][39][40][41] or the use of cryopreserved infectious PfSPZ (PfSPZ Challenge), which are introduced via intradermal injection, 17,[42][43][44][45] intramuscular injection, [45][46][47] intravenous injection, 48 or by direct venous inoculation (DVI). [16][17][18][19][20][21]…”