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Parasite. 2019;26:56. doi: 10.1051/parasite/2019058. Epub 2019 Sep 13.

Clinical illness and outcomes in Nigerian children with persistent early-appearing anaemia following initiation of artemisinin-based combination treatments of uncomplicated falciparum malaria.

Author information

1
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Biological Sciences and African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede 232102, Nigeria - Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan 200212, Nigeria.
2
World Health Organization, Country Office, Kampala, Uganda.
3
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria.
4
Department of Paediatrics, University of Ibadan, Ibadan 200284, Nigeria.
5
Department of Clinical Pharmacology, University College Hospital, Ibadan 200212, Nigeria.
6
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria.
7
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria - Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Ibadan, Ibadan 200284, Nigeria.
8
Department of Biological Sciences and African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede 232102, Nigeria.
9
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Paediatrics, Nnamdi Azikiwe University, Awka 420110, Nigeria.
10
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Paediatrics, University of Maiduguri, Maiduguri 600230, Nigeria.
11
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Paediatrics, Ahmadu Bello University, Zaria 810001, Nigeria.
12
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Paediatrics, Usman Dan Fodio University, Sokoto 840001, Nigeria.
13
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Paediatrics, Federal Medical Centre, Yenagoa 560231, Nigeria.
14
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Paediatrics, Imo State University Teaching Hospital, Orlu 473212, Nigeria.
15
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Paediatrics and Child Health, University of Ilorin, Ilorin 240003, Nigeria.
16
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Medical Laboratory Science, University of Lagos, Lagos 100254, Nigeria.
17
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Paediatrics, University of Jos, Jos 930222, Nigeria.
18
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Department of Biological Sciences and African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede 232102, Nigeria.
19
Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja 900211, Nigeria - Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan 200212, Nigeria - Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria - Department of Clinical Pharmacology, University College Hospital, Ibadan 200212, Nigeria.

Abstract

In non-anaemic children with malaria, early-appearing anaemia (EAA) is common following artemisinin-based combination treatments (ACTs) and it may become persistent (PEAA). The factors contributing to and kinetics of resolution of the deficit in haematocrit from baseline (DIHFB) characteristic of ACTs-related PEAA were evaluated in 540 consecutive children with malaria treated with artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine. Asymptomatic PEAA occurred in 62 children. In a multiple logistic regression model, a duration of illness ≤3 days before presentation, haematocrit <35% before and <25% one day after treatment initiation, drug attributable fall in haematocrit ≥6%, and treatment with dihydroartemisinin-piperaquine independently predicted PEAA. Overall, mean DIHFB was 5.7% (95% CI 4.8-6.6) 7 days after treatment initiation and was similar for all treatments. Time to 90% reduction in DIHFB was significantly longer in artemether-lumefantrine-treated children compared with other treatments. In a one compartment model, declines in DIHFB were monoexponential with overall mean estimated half-time of 3.9 days (95% CI 2.6-5.1), Cmax of 7.6% (95% CI 6.7-8.4), and Vd of 0.17 L/kg (95% CI 0.04-0.95). In Bland-Altman analyses, overall mean anaemia recovery time (AnRT) of 17.4 days (95% CI 15.5-19.4) showed insignificant bias with 4, 5 or 6 multiples of half-time of DIHFB. Ten children after recovery from PEAA progressed to late-appearing anaemia (LAA). Progression was associated with female gender and artesunate-amodiaquine treatment. Asymptomatic PEAA is common following ACTs. PEAA or its progression to LAA may have implications for case and community management of anaemia and for anaemia control efforts in sub-Saharan Africa where ACTs have become first-line antimalarials. Trial registration: Pan Africa Clinical Trial Registration PACTR201709002064150, 1 March 2017 http://www.pactr.org.

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