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

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

Infectious Diseases of Poverty, July 2016

27384596

Akintunde Sowunmi, Kazeem Akano, Adejumoke I. Ayede, Godwin Ntadom, Elsie O. Adewoye, Bayo Fatunmbi, Temitope Aderoyeje

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. 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. 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. 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. 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 .