Therapeutic efficacy and effects of artesunate-amodiaquine and artemetherlumefantrine on malaria-associated anaemia in Nigerian children aged two years and under

Background:Artemisinin-based combination therapies are recommended as first-line treatments for uncomplicated falciparum malaria,but there is little evaluation of their efficacy and effects on uncomplicated malaria-associated anaemia in children aged 2 years and under.Methods:Parasitological efficacy and effects on malaria-associated anaemia were evaluated in 250 malarious children aged 2 years and under,and efficacy was evaluated in 603 malarious children older than two but younger than 5 years of age following treatment with artesunate-amodiaquine(AA)or artemether-lumefantrine(AL).Kinetics of the disposition of parasitaemia following treatment were evaluated using a non-compartment model.Late-appearing anaemia(LAA)was diagnosed using the following criteria:clearance of parasitaemia,fever and other symptoms occurring within 7 days of starting treatment,adequate clinical and parasitological response on days 28–42,haematocrit(HCT)≥30%at 1 and/or 2 weeks,a fall in HCT to<30%occurring at 3–6 weeks,absence of concomitant illness at 1–6 weeks,and absence of asexual parasitaemia detected using both microscopy and polymerase chain reaction(PCR)at 1–6 weeks.Results:Overall,in children aged 2 years and under,the PCR-corrected parasitological efficacy was 97.2%(95%CI 92.8–101.6),which was similar for both treatments.In children older than 2 years,parasitological efficacy was also similar for both treatments,but parasite prevalence 1 day after treatment began was significantly higher,and fever and parasite clearance times were significantly faster in the AA-treated children compared with the AL-treated children.Declines in parasitaemia were monoexponential with an estimated elimination half-time of 1 h.Elimination half-times were similar for both treatments.In children aged 2 years and under who were anaemic at presentation,the mean anaemia recovery time was 12.1 days(95%CI 10.6–13.6,n=127),which was similar for both treatments.Relatively asymptomatic LAA occurred in 11 children(4.4%)aged 2 years and under,the recovery from which was uneventful.Conclusion:This study showed that AA and AL are efficacious treatments for uncomplicated falciparum malaria in Nigerian children aged 2 years and under,and that AA clears parasitaemia and fever significantly faster than AL in children older than 2 years.Both treatments may cause a relatively asymptomatic LAA with uneventful recovery in a small proportion of children aged 2 years and under.Trials registration:Pan African Clinical Trial Registry PACTR201508001188143,3 July 2015;PACTR201510001189370,3 July 2015;PACTR201508001191898,7 July 2015 and PACTR201508001193368,8 July 2015 http://www.pactr.org.