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Parasite reduction ratio one day after initiation of artemisinin-based combination therapies and its relationship with parasite clearance time in acutely malarious children

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Infectious Diseases of Poverty 2018年第1期7卷 1270-1283页

作者： kazeem Akano Godwin Ntadom Chimere Agomo Christian T.Happi Onikepe A.Folarin Grace O.Gbotosho Olugbenga Mokuolu Finomo Finomo Joy C.Ebenebe Nma Jiya Jose Ambe Robinson Wammanda George Emechebe oluwabunmi k.basorun Olubunmi A.Wewe Sikiru Amoo Nnenna Ezeigwe Stephen Oguche Bayo Fatunmbi Akintunde Sowunmi Department of Pharmacology and Therapeutics University of IbadanIbadanNigeria Antimalarial Therapeutic Efficacy Monitoring Group National Malaria Elimination ProgrammeThe Federal Ministry of HealthAbujaNigeria Department of Medical Laboratory Science University of LagosLagosNigeria Department of Biological Sciences and African Centre of Excellence for Genomics of Infectious Diseases(ACEGID) Redeemer UniversityEdeNigeria Institute for Medical Research and Training University of IbadanIbadanNigeria Department of Pharmacology and Toxicology Faculty of PharmacyUniversity of IbadanIbadanNigeria Department of Paediatrics University of IlorinIlorinNigeria Department of Paediatrics Federal Medical CentreYenagoaNigeria Department of Paediatrics Nnamdi Azikiwe UniversityAwkaNigeria Department of Paediatrics Uthman Dan Fodio UniversitySokotoNigeria Department of Paediatrics University of MaiduguriMaiduguriNigeria Department of Paediatrics Ahmadu Bello UniversityZariaNigeria Department of Paediatrics Imo State University Teaching HospitalOrluNigeria Department of Paediatrics University of JosJosNigeria World Health Organization Country OfficeKampalaUganda

Background:In acute falciparum malaria,asexual parasite reduction ratio two days post-treatment initiation(PRRD2)≥10000 per cycle has been used as a measure of the rapid clearance of parasitaemia and efficacy of artemisinin derivatives.However,there is little evaluation of alternative measures;for example,parasite reduction ratio one day after treatment initiation(PRRD1)and its relationship with parasite clearance time(PCT)or PRRD2.This study evaluated the use of PRRD1 as a measure of responsiveness to antimalarial drugs.Methods:In acutely malarious children treated with artesunate-amodiaquine(AA),artemether-lumefantrine(AL)or dihydroartemisinin-piperaquine(DHP),the relationships between PRRD1 or PRRD2 and PCT,and between PRRD1 and PRRD2 were evaluated using linear regression.Agreement between estimates of PCT using PRRD1 and PRRD2 linear regression equations was evaluated using the Bland-Altman analysis.Predictors of PRRD1>5000 per half cycle and PRRD2≥10000 per cycle were evaluated using stepwise multiple logistic regression models.Using the linear regression equation of the relationship between PRRD1 and PCT previously generated in half of the DHP-treated children during the early study phase,PCT estimates were compared in a prospective blinded manner with PCTs determined by microscopy during the later study phase in the remaining half.Results:In 919 malarious children,PRRD1 was significantly higher in DHP-and AA-treated compared with AL-treated children(P15months,parasitaemia>10000/μl and DHP treatment independently predicted PRRD1>5000 per half cycle,while age>30months,haematocrit≥31%,body temperature>37.4°C,parasitaemia>100000/μl,PRRD1 value>1000 and no gametoc

关键词： Falciparum malaria Artemisinin-based combination therapies Parasite clearance Children Nigeria

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Declining responsiveness of childhood Plasmodium falciparum infections to artemisinin-based combination treatments ten years following deployment as first-line antimalarials in Nigeria

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Infectious Diseases of Poverty 2019年第4期8卷 96-97页

作者： Akintunde Sowunmi Godwin Ntadom kazeem Akano Folasade O.Ibironke Adejumoke I.Ayede Chimere Agomo Onikepe A.Folarin Grace O.Gbotosho Christian Happi Stephen Oguche Henrietta U.Okafor Martin Meremikwu Philip Agomo William Ogala Ismaila Watila Olugbenga Mokuolu Finomo Finomo Joy C.Ebenebe Nma Jiya Jose Ambe Robinson Wammanda George Emechebe Wellington Oyibo Francis Useh Temitope Aderoyeje Titilope M.Dokunmu Omobolaji T.Alebiosu Sikiru Amoo oluwabunmi k.basorun Olubunmi A.Wewe Chukwuebuka Okafor Odafe Akpoborie Bayo Fatunmbi Elsie O.Adewoye Nnenna M.Ezeigwe Ayoade Oduola Antimalarial Therapeutic Efficacy Monitoring Group National Malaria Elimination ProgrammeThe Federal Ministry of HealthAbujaNigeria Department of Pharmacology and Therapeutics University of IbadanIbadanNigeria 不详

Background:The development and spread of artemisinin-resistant Plasmodium falciparum malaria in Greater Mekong Subregion has created impetus for continuing global monitoring of efficacy of artemisinin-based combination therapies(ACTs). This post analyses is aimed to evaluate changes in early treatment response markers 10 years after the adoption of ACTs as first-line treatments of uncomplicated falciparum malaria in Nigeria.Methods: At 14 sentinel sites in six geographical areas of Nigeria, we evaluated treatment responses in 1341 children under 5 years and in additional 360 children under 16 years with uncomplicated malaria enrolled in randomized trials of artemether-lumefantrine versus artesunate-amodiaquine at 5-year interval in 2009-2010 and 2014-2015 and at 2-year interval in 2009-2010 and 2012-2015, respectively after deployment in 2005.Results: Asexual parasite positivity 1 day after treatment initiation (APPD1) rose from 54 to 62% and 2 days after treatment initiation from 5 to 26% in 2009-2010 to 2014-2015(P=0.002 and P 75 000 μl^-1, haematocrit > 27% 1 day post-treatment initiatiortreatment with artemether-lumefantrine and enrolment in 2014-2015 independently predicted APPD1. In paralle , kaplan-Meier estimated risk of recurrent infections by day 28 rose from 8 to 14% (P=0005) and from 9 to 15%(P=0.02) with artemether-lumefantrine and artesunate-amodiaquine, respectively. Mean asexual parasitaemia half-life increased significantly from 1.1 h to 1.3h within 2 years (P<0.0001).Conclusions:These data indicate declining parasitological responses through time to the two ACTs may be due to emergence of parasites with reduced susceptibility or decrease in immunity to

关键词： Declining responsiveness Falciparum malaria Children Artemisinin-based combination treatment Nigeria

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