Persistence of mRNA indicative of Plasmodium falciparum ring-stage parasites 42 days after artemisinin and non-artemisinin combination therapy in naturally infected Malians

Background Malaria control in sub-Saharan Africa relies upon prompt case management with artemisinin-based combination therapy (ACT). Ring-stage parasite mRNA, measured by sbp1 quantitative reverse-transcriptase PCR (qRT-PCR), was previously reported to persist after ACT treatment and hypothesized to reflect temporary arrest of the growth of ring-stage parasites (dormancy) following exposure to artemisinins. Here, the persistence of ring-stage parasitaemia following ACT and non-ACT treatment was examined. Methods Samples were used from naturally infected Malian gametocyte carriers who received dihydroartemisinin–piperaquine (DP) or sulfadoxine–pyrimethamine (SP–AQ) with or without gametocytocidal drugs. Gametocytes and ring-stage parasites were quantified by qRT-PCR during 42 days of follow-up. Results At baseline, 89% (64/73) of participants had measurable ring-stage parasite mRNA. Following treatment, the proportion of ring-stage parasite-positive individuals and estimated densities declined for all four treatment groups. Ring-stage parasite prevalence and density was generally lower in arms that received DP compared to SP–AQ. This finding was most apparent days 1, 2, and 42 of follow-up (p < 0.01). Gametocytocidal drugs did not influence ring-stage parasite persistence. Ring-stage parasite density estimates on days 14 and 28 after initiation of treatment were higher among individuals who subsequently experienced recurrent parasitaemia compared to those who remained free of parasites until day 42 after initiation of treatment (pday 14 = 0.011 and pday 28 = 0.068). No association of ring-stage persistence with gametocyte carriage was observed. Conclusions The current findings of lower ring-stage persistence after ACT without an effect of gametocytocidal partner drugs affirms the use of sbp1 as ring-stage marker. Lower persistence of ring-stage mRNA after ACT treatment suggests the marker may not reflect dormant parasites whilst it was predictive of re-appearance of parasitaemia.

Persistence of P. Falciparum Ring-stage Parasites 42 Days After Artemisinin and Non-artemisinin Combination Therapy in Naturally Infected Malians

BackgroundMalaria control in sub-Saharan Africa relies upon prompt case management with artemisinin-based combination therapy (ACT). Ring-stage parasites, measured by sbp1 quantitative reverse-transcriptase PCR (qRT-PCR), were previously reported to persist after ACT treatment and hypothesized to reflect temporary arrest of the growth of ring-stage parasites (dormancy) following exposure to artemisinins. Here, the persistence of ring-stage parasitemia following ACT and non-ACT treatment was examined. MethodsSamples were used from naturally infected Malian gametocyte carriers who received dihydroartemisinin-piperaquine (DP) or sulfadoxine-pyrimethamine (SP-AQ) with or without gametocytocidal drugs. Gametocytes and ring-stage parasites were quantified by qRT-PCR during 42 days of follow-up. ResultsAt baseline, 89% (64/73) of participants had measurable ring-stage parasites. Following treatment, the proportion of ring-stage parasite-positive individuals and ring-stage parasite densities declined for all four treatment groups. Participants who received DP had 81% lower post-treatment ring-stage parasite density compared to participants who received SP-AQ (p<0.001). Gametocytocidal drugs did not influence ring-stage parasite persistence. Ring-stage parasite densities on days 14 and 28 after initiation of treatment were higher among individuals who subsequently experienced recurrent parasitemia compared to those who remained free of parasites until day 42 after initiation of treatment (pday 14=0.011 and pday 28=0.068). No association of ring-stage persistence with gametocyte carriage was observed. Conclusions Our findings of lower ring-stage persistence after ACT treatment without an effect of gametocytocidal partner drugs affirms the use of sbp1 as ring-stage marker. Lower persistence of ring-stage parasites after ACT treatment suggests the marker may not reflect dormant parasites whilst it was predictive of re-appearance of parasitemia.

Persistence of P. Falciparum Ring-Stage Parasites 42 Days After Artemisinin and Non-Artemisinin Combination Therapy in Naturally Infected Malians

Background: Malaria control in sub-Saharan Africa relies upon prompt case management with artemisinin-based combination therapy (ACT). Ring-stage parasites, measured by sbp1 quantitative reverse-transcriptase PCR (qRT-PCR), were previously reported to persist after ACT treatment and hypothesized to reflect temporary arrest of the growth of ring-stage parasites (dormancy) following exposure to artemisinins. Here, we examined the persistence of ring-stage parasitemia following ACT and non-ACT treatment. Methods: We used samples from naturally infected Malian gametocyte carriers who received dihydroartemisinin-piperaquine (DP) or sulfadoxine-pyrimethamine (SP-AQ) with or without gametocytocidal drugs. Gametocytes and ring-stage parasites were quantified by qRT-PCR during 42 days of follow-up. Results: At baseline, 89% (64/73) of participants had measurable ring-stage parasites. Following treatment, the proportion of ring-stage parasite-positive individuals and ring-stage parasite densities declined for all four treatment groups. Participants who received DP had 81% lower post-treatment ring-stage parasite density compared to participants who received SP-AQ (p<0.001). Gametocytocidal drugs did not influence ring-stage parasite persistence. Ring-stage parasite densities on days 14 and 28 after initiation of treatment were higher among individuals who subsequently experienced recurrent parasitemia compared to those who remained free of parasites until day 42 after initiation of treatment (pday 14=0.011 and pday 28=0.068). We observed no association of ring-stage persistence with gametocyte carriage. Conclusions: Our findings of lower ring-stage persistence after ACT treatment without an effect of gametocytocidal partner drugs affirms the use of sbp1 as ring-stage marker and argues against preferential persistence of low densities of rings following ACT treatment. The implications of our findings for monitoring drug sensitivity require further study.