Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence

Abstract

Background: Parasite clearance time after artemisinin-based combination therapy (ACT) may be increasing in Asian and African settings. The association between parasite clearance following ACT and transmissibility is currently unknown.

Methods: We determined parasite clearance dynamics by duplex quantitative polymerase chain reaction (qPCR) in samples collected in the first 3 days after treatment of uncomplicated malaria with ACT. Gametocyte carriage was determined by Pfs25 quantitative nucleic acid sequence-based amplification assays; infectiousness to mosquitoes by membrane-feeding assays on day 7 after treatment.

Results: Residual parasitemia was detected by qPCR in 31.8% (95% confidence interval [CI], 24.6-39.8) of the children on day 3 after initiation of treatment. Residual parasitemia was associated with a 2-fold longer duration of gametocyte carriage (P = .0007), a higher likelihood of infecting mosquitoes (relative risk, 1.95; 95% CI, 1.17-3.24; P = .015), and a higher parasite burden in mosquitoes (incidence rate ratio, 2.92; 95% CI, 1.61-5.31; P < .001). Children with residual parasitemia were also significantly more likely to experience microscopically detectable parasitemia during follow-up (relative risk, 11.25; 95% CI, 4.08-31.01; P < .001).

Conclusions: Residual submicroscopic parasitemia is common after ACT and is associated with a higher transmission potential. Residual parasitemia may also have consequences for individual patients because of its higher risk of recurrent parasitemia.

Keywords: PCR; anopheles; artemisinin; infectivity; resistance; submicroscopic; transmission.

Figure 1.

Plasmodium falciparum parasite prevalence and relative density by duplex quantitative polymerase chain reaction (qPCR), by treatment arm. Left y-axis, qPCR parasite prevalence (bars) for children treated with artemether-lumefantrine (AL; n = 84) or dihydroartemisinin-piperaquine (DP; n = 70). Error bars indicate the upper limit of the 95% confidence interval. Right y-axis, median relative parasite density relative to starting infection is plotted (line) for PCR-positive individuals treated with AL (solid line) or DP (dashed line). All samples were collected between 10 am and 12 pm (day 0) or between 8 am and 12 pm (days 1, 2, and 3).

Figure 2.

Plasmodium falciparum gametocyte prevalence by quantitative nucleic acid sequence–based amplification for children whose infection cleared or who had residual parasitemia detected by duplex quantitative polymerase chain reaction on day 3 after treatment with artemether-lumefantrine or dihydroartemisinin-piperaquine. Error bars indicate the upper limit of the 95% confidence interval.