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Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials

BACKGROUND: Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antim...

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Autores principales: Sowunmi, Akintunde, Fatunmbi, Bayo, Akano, Kazeem, Wewe, Olubunmi A., Agomo, Chimere, Finomo, Finomo, Ebenebe, Joy, Jiya, Nma, Ambe, Jose, Wammanda, Robinson, Ntadom, Godwin, Mokuolu, Olugbenga, Emechebe, George, Ezeigwe, Nnenna, Ayede, Adejumoke I., Adewoye, Elsie O., Gbotosho, Grace O., Folarin, Onikepe A., Happi, Christian T., Oguche, Stephen, Oyibo, Wellington A., Useh, Francis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738206/
https://www.ncbi.nlm.nih.gov/pubmed/29258448
http://dx.doi.org/10.1186/s12879-017-2876-9
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author Sowunmi, Akintunde
Fatunmbi, Bayo
Akano, Kazeem
Wewe, Olubunmi A.
Agomo, Chimere
Finomo, Finomo
Ebenebe, Joy
Jiya, Nma
Ambe, Jose
Wammanda, Robinson
Ntadom, Godwin
Mokuolu, Olugbenga
Emechebe, George
Ezeigwe, Nnenna
Ayede, Adejumoke I.
Adewoye, Elsie O.
Gbotosho, Grace O.
Folarin, Onikepe A.
Happi, Christian T.
Oguche, Stephen
Oyibo, Wellington A.
Useh, Francis
author_facet Sowunmi, Akintunde
Fatunmbi, Bayo
Akano, Kazeem
Wewe, Olubunmi A.
Agomo, Chimere
Finomo, Finomo
Ebenebe, Joy
Jiya, Nma
Ambe, Jose
Wammanda, Robinson
Ntadom, Godwin
Mokuolu, Olugbenga
Emechebe, George
Ezeigwe, Nnenna
Ayede, Adejumoke I.
Adewoye, Elsie O.
Gbotosho, Grace O.
Folarin, Onikepe A.
Happi, Christian T.
Oguche, Stephen
Oyibo, Wellington A.
Useh, Francis
author_sort Sowunmi, Akintunde
collection PubMed
description BACKGROUND: Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children. METHODS: Malarious <5 year-olds randomized to artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine treatments were followed up clinically for 6 weeks. Anaemia was defined as haematocrit <30%; Malaria-attributable fall in haematocrit (MAFH) as the difference between haematocrit 28–42 days post- and pre-treatment; Total MAFH (TMAFH) as the difference between days 28–42 haematocrit and the lowest haematocrit recorded in the first week post-treatment initiation; Drug-attributable fall in haematocrit (DAFH) as the difference between MAFH and TMAFH; Early appearing anaemia (EAA) as haematocrit <30% occurring within 1 week in children with normal haematocrit pre-treatment. Predictors of anaemia pre-treatment, EAA, MAFH or DAFH >4% were evaluated by stepwise multiple logistic regression models. Survival analysis and kinetics of DAFH were evaluated by Kaplan-Meier estimator and non-compartment model, respectively. RESULTS: Pre-treatment, 355 of 959 children were anaemic. Duration of illness >2 days and parasitaemia ≤10,000 μL(−1) were independent predictors of anaemia pre-treatment. EAA occurred in 301 of 604 children. Predictors of EAA were age ≤ 15 months, history of fever pre-treatment and enrolment haematocrit ≤35%. The probabilities of progression from normal haematocrit to EAA were similar for all treatments. MAFH >4% occurred in 446 of 694 children; its predictors were anaemia pre-treatment, enrolment parasitaemia ≤50,000 μL(−1), parasitaemia one day post-treatment initiation and gametocytaemia. DAFH >4% occurred in 334 of 719 children; its predictors were history of fever pre-and fever 1 day post-treatment initiation, haematocrit ≥37%, and parasitaemia >100,000 μL(−1). In 432 children, declines in DAFH deficits were monoexponential with overall estimated half-time of 2.2d (95% CI 1.9–2.6). Area under curve of deficits in DAFH versus time and estimated half-time were significantly higher in non-anaemic children indicating greater loss of haematocrit in these children. CONCLUSION: After ten years of adoption of ACTs, anaemia is common pre-and early post-treatment, falls in haematocrit attributable to a single infection is high, and DAFH >4% is common and significantly lower in anaemic compared to non-anaemic Nigerian children. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR) [PACTR201709002064150, 1 March 2017].
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spelling pubmed-57382062017-12-21 Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials Sowunmi, Akintunde Fatunmbi, Bayo Akano, Kazeem Wewe, Olubunmi A. Agomo, Chimere Finomo, Finomo Ebenebe, Joy Jiya, Nma Ambe, Jose Wammanda, Robinson Ntadom, Godwin Mokuolu, Olugbenga Emechebe, George Ezeigwe, Nnenna Ayede, Adejumoke I. Adewoye, Elsie O. Gbotosho, Grace O. Folarin, Onikepe A. Happi, Christian T. Oguche, Stephen Oyibo, Wellington A. Useh, Francis BMC Infect Dis Research Article BACKGROUND: Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children. METHODS: Malarious <5 year-olds randomized to artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine treatments were followed up clinically for 6 weeks. Anaemia was defined as haematocrit <30%; Malaria-attributable fall in haematocrit (MAFH) as the difference between haematocrit 28–42 days post- and pre-treatment; Total MAFH (TMAFH) as the difference between days 28–42 haematocrit and the lowest haematocrit recorded in the first week post-treatment initiation; Drug-attributable fall in haematocrit (DAFH) as the difference between MAFH and TMAFH; Early appearing anaemia (EAA) as haematocrit <30% occurring within 1 week in children with normal haematocrit pre-treatment. Predictors of anaemia pre-treatment, EAA, MAFH or DAFH >4% were evaluated by stepwise multiple logistic regression models. Survival analysis and kinetics of DAFH were evaluated by Kaplan-Meier estimator and non-compartment model, respectively. RESULTS: Pre-treatment, 355 of 959 children were anaemic. Duration of illness >2 days and parasitaemia ≤10,000 μL(−1) were independent predictors of anaemia pre-treatment. EAA occurred in 301 of 604 children. Predictors of EAA were age ≤ 15 months, history of fever pre-treatment and enrolment haematocrit ≤35%. The probabilities of progression from normal haematocrit to EAA were similar for all treatments. MAFH >4% occurred in 446 of 694 children; its predictors were anaemia pre-treatment, enrolment parasitaemia ≤50,000 μL(−1), parasitaemia one day post-treatment initiation and gametocytaemia. DAFH >4% occurred in 334 of 719 children; its predictors were history of fever pre-and fever 1 day post-treatment initiation, haematocrit ≥37%, and parasitaemia >100,000 μL(−1). In 432 children, declines in DAFH deficits were monoexponential with overall estimated half-time of 2.2d (95% CI 1.9–2.6). Area under curve of deficits in DAFH versus time and estimated half-time were significantly higher in non-anaemic children indicating greater loss of haematocrit in these children. CONCLUSION: After ten years of adoption of ACTs, anaemia is common pre-and early post-treatment, falls in haematocrit attributable to a single infection is high, and DAFH >4% is common and significantly lower in anaemic compared to non-anaemic Nigerian children. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR) [PACTR201709002064150, 1 March 2017]. BioMed Central 2017-12-19 /pmc/articles/PMC5738206/ /pubmed/29258448 http://dx.doi.org/10.1186/s12879-017-2876-9 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sowunmi, Akintunde
Fatunmbi, Bayo
Akano, Kazeem
Wewe, Olubunmi A.
Agomo, Chimere
Finomo, Finomo
Ebenebe, Joy
Jiya, Nma
Ambe, Jose
Wammanda, Robinson
Ntadom, Godwin
Mokuolu, Olugbenga
Emechebe, George
Ezeigwe, Nnenna
Ayede, Adejumoke I.
Adewoye, Elsie O.
Gbotosho, Grace O.
Folarin, Onikepe A.
Happi, Christian T.
Oguche, Stephen
Oyibo, Wellington A.
Useh, Francis
Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials
title Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials
title_full Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials
title_fullStr Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials
title_full_unstemmed Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials
title_short Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials
title_sort factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738206/
https://www.ncbi.nlm.nih.gov/pubmed/29258448
http://dx.doi.org/10.1186/s12879-017-2876-9
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