Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment

Abstract

SUMMARYDuring a longitudinal study investigating the dynamics of malaria in Ugandan lakeshore communities, a consistently high malaria prevalence was observed in young children despite regular treatment. To explore the short-term performance of artemether-lumefantrine (AL), a pilot investigation into parasite carriage after treatment(s) was conducted in Bukoba village. A total of 163 children (aged 2–7 years) with a positive blood film and rapid antigen test were treated with AL; only 8·7% of these had elevated axillary temperatures. On day 7 and then on day 17, 40 children (26·3%) and 33 (22·3%) were positive by microscopy, respectively. Real-time PCR analysis demonstrated that multi-species Plasmodium infections were common at baseline, with 41·1% of children positive for Plasmodium falciparum/Plasmodium malariae, 9·2% for P. falciparum/ Plasmodium ovale spp. and 8·0% for all three species. Moreover, on day 17, 39·9% of children infected with falciparum malaria at baseline were again positive for the same species, and 9·2% of those infected with P. malariae at baseline were positive for P. malariae. Here, chronic multi-species malaria infections persisted in children after AL treatment(s). Better point-of-care diagnostics for non-falciparum infections are needed, as well as further investigation of AL performance in asymptomatic individuals.

Molecular Detection of Residual Parasitemia after Pyronaridine–Artesunate or Artemether–Lumefantrine Treatment of Uncomplicated Plasmodium falciparum Malaria in Kenyan Children

“…To conclude, this study demonstrates the detection of low-density parasitemia after microscopically successful ACT treatment, which confirms the findings from previous studies. [10][11][12][13]38,40 The data are relevant for the interpretation of clearance dynamics of both the relatively new PA and the commonly used AL. Both qPCR and db-PCR-NALFIA can be useful tools for patient follow-up after treatment, whereby in the clinical setting especially a negative db-PCR-NALFIA outcome at day 7 after treatment initiation may be a marker for an ACPR during further follow-up, keeping in mind that predictive values depend on the prevalence and may, thus, differ between settings.…”

“…9 Submicroscopic parasitemia after ACT treatment has been described in Sudan and Uganda. [10][11][12] In western Kenya, residual submicroscopic parasitemia was found to be common after ACT treatment and associated with increased gametocyte carriage, higher transmission potential to mosquitos, and an increased likelihood of recurrent parasitemia on day 28 or 42. 13 Extensive monitoring of parasite clearance dynamics after treatment is thus needed to determine whether responsiveness to ACT is changing.…”

Plasmodium Species Infecting Children Presenting with Malaria in Uganda

“…16 A study of children from eastern Uganda noted frequent mixed infections when malaria was diagnosed by molecular methods, with 41% of infections P. falciparum and P. malariae, 9% P. falciparum and P. ovale, and 8% all three of these species. 17 To gain further insights into the species composition in symptomatic malaria, we surveyed the prevalence of different plasmodial species in samples from children presenting with malaria at multiple sites in Uganda.…”

The consequences of mixed-species malaria parasite co-infections in mice and mosquitoes for disease severity, parasite fitness, and transmission success

“…Diagnostic techniques with improved sensitivities are revealing a greater prevalence of P. ovale and P. malariae in P. falciparum endemic areas than previously thought [7]. Intervention strategies such as anti-vector programs, and the development and employment of new drugs and vaccine will often be more effective against one species of parasite than they will against others [47,48]. In regions where P. falciparum prevalence is decreasing, the prevalence of non-falciparum malaria parasite species often becomes more apparent, highlighting the importance of mixed-species infections.…”