Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments.
BACKGROUND
Artemisinin-based combination treatments (ACTs) are the first-line treatments of uncomplicated Plasmodium falciparum malaria in many endemic areas but there are few evaluation of their efficacy in anaemic malarious children.


METHODS
Therapeutic efficacy of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine was evaluated in 437 anaemic and 909 non-anaemic malarious children following treatment during a seven-year period (2008-2014). Patterns of temporal changes in haematocrit were classified based on haematocrit values <30% and ≥30%. Kinetics of the disposition of the deficit in haematocrit from 30% following treatment were evaluated using a non-compartment model.


RESULTS
PCR-corrected parasitological efficacy 28 days after start of treatment was significantly higher in artesunate-amodiaquine- compared to artemether-lumefantrine-treated children [97% (95%CI: 92.8-100) versus 96.4% (95%CI: 91.3-99.4), P = 0.02], but it was similar in non-anaemic and anaemic children. Fall in haematocrit/1 000 asexual parasites cleared from peripheral blood was significantly greater at lower compared to higher parasitaemias (P < 0.0001), and in non-anaemic compared to anaemic children (P = 0.007). In anaemic children at presentation, mean anaemia recovery time (AnRT) was 15.4 days (95%CI: 13.3-17.4) and it did not change over the years. Declines in haematocrit deficits from 30% were monoexponential with mean estimated half-time of 1.4 days (95%CI: 1.2-1.6). Anaemia half-time (t½anaemia) correlated positively with AnRT in the same patients (r = 0.69, P < 0.0001). Bland-Altman analysis of 10 multiples of t½anaemiaand AnRT showed narrow limit of agreement with insignificant bias (P = 0.07) suggesting both can be used interchangeably in the same patients.


CONCLUSIONS
Artesunate-amodiaquine and artemether-lumefantrine remain efficacious treatments of uncomplicated P. falciparum infections in non-anaemic and anaemic Nigerian children in the last 7 years of adoption as first-line treatments. These ACTs may also conserve haematocrit at high parasitaemias and in anaemic children.


BACKGROUND
Pan African Clinical Trial Registry PACTR201508001188143 , 3 July 2015; PACTR201510001189370 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015.
Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria. akinsowunmi@hotmail.com.|Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria. akinsowunmi@hotmail.com.|Department of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria. akinsowunmi@hotmail.com.
Akintunde
A
Sowunmi
Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria.
Kazeem
K
Akano
National Malaria Elimination Programme, Federal Ministry of Health, Abuja, Nigeria.
Godwin
G
Ntadom
Department of Paediatrics, University of Ibadan, Ibadan, Nigeria.
Adejumoke I
AI
Ayede
Department of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria.
Folasade O
FO
Ibironke
Department of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria.
Temitope
T
Aderoyeje
Department of Physiology, University of Ibadan, Ibadan, Nigeria.
Elsie O
EO
Adewoye
World Health Organization, Regional Office for the Western Pacific, Khan Daun Penh, Phnom Penh, Cambodia.
Bayo
B
Fatunmbi
Department of Paediatrics, University of Jos, Jos, Nigeria.
Stephen
S
Oguche
Department of Paediatrics, Institute of Child Health, University of Nigeria Teaching Hospital, Enugu, Nigeria.
Henrietta U
HU
Okafor
Department of Paediatrics, Specialist Hospital, Maiduguri, Borno Sate, Nigeria.
Ismaila
I
Watila
Department of Paediatrics, University of Calabar, Calabar, Cross Rivers State, Nigeria.
Martin
M
Meremikwu
Nigeria Institute of Medical Research, Yaba, Lagos, Nigeria.
Philip
P
Agomo
Department of Paediatrics, Ahmadu Bello University, Zaria, Nigeria.
William
W
Ogala
Nigeria Institute of Medical Research, Yaba, Lagos, Nigeria.
Chimere
C
Agomo
Department of Biological Sciences, Redeemer's University, Ede, Osun State, Nigeria.
Onikepe A
OA
Folarin
Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria.|Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Grace O
GO
Gbotosho
Department of Biological Sciences, Redeemer's University, Ede, Osun State, Nigeria.
Christian T
CT
Happi
D000293:Adolescent; D000655:Amodiaquine / Q000627:therapeutic use*; D000740:Anemia / Q000473:pathology*; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D006400:Hematocrit; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D009549:Nigeria; D016896:Treatment Outcome
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine
Artemisinin-based combination treatments; Children; Malaria-associated anaemia; Nigeria; “Haematocrit conservation”