Effectiveness and safety of artesunate-amodiaquine versus artemether-lumefantrine for home-based treatment of uncomplicated Plasmodium falciparum malaria among children 6-120 months in Yaoundé, Cameroon: a randomized trial

Peter Thelma Ngwa Niba, Akindeh Mbuh Nji, Innocent Mbulli Ali, Lawrence Fonyonga Akam, Cedric Hermann Dongmo, Jean Paul Kengne Chedjou, Calvino Tah Fomboh, William Dorian Nana, Ornella Laetitia Ayem Oben, Abdel Aziz Selly-Ngaloumo, Marcel N Moyeh, Jude Achidi Ngu, Ambassa Jean Ludovic, Pierre Martiniel Aboh, Marie Carine Enyegue Ambani, Pierrette Albertine Mbarga Omgba, Grâce Bissohong Kotcholi, Linus Moye Adzemye, Danielle Regine Abenkou Nna, Adèle Douanla, Ze Ango, Marie Sophie Ewane, Joel Tewara Ticha, Fritz Mbuh Tatah, Golwa Dinza, Valentine Nchafor Ndikum, Dorothy A Fosah, Jude D Bigoga, Michael Alifrangis, Wilfred F Mbacham, Peter Thelma Ngwa Niba, Akindeh Mbuh Nji, Innocent Mbulli Ali, Lawrence Fonyonga Akam, Cedric Hermann Dongmo, Jean Paul Kengne Chedjou, Calvino Tah Fomboh, William Dorian Nana, Ornella Laetitia Ayem Oben, Abdel Aziz Selly-Ngaloumo, Marcel N Moyeh, Jude Achidi Ngu, Ambassa Jean Ludovic, Pierre Martiniel Aboh, Marie Carine Enyegue Ambani, Pierrette Albertine Mbarga Omgba, Grâce Bissohong Kotcholi, Linus Moye Adzemye, Danielle Regine Abenkou Nna, Adèle Douanla, Ze Ango, Marie Sophie Ewane, Joel Tewara Ticha, Fritz Mbuh Tatah, Golwa Dinza, Valentine Nchafor Ndikum, Dorothy A Fosah, Jude D Bigoga, Michael Alifrangis, Wilfred F Mbacham

Abstract

Background: Many studies have reported high efficacy and safety of artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) when administered under direct observation in Cameroon. There is paucity of data to support their continuous use in home-based treatment of uncomplicated Plasmodium falciparum malaria in Cameroon. Hence, this study aimed to assess the effectiveness and safety of AS-AQ versus AL for home-based treatment of uncomplicated P. falciparum malaria among children 6-120 months in Yaoundé, Cameroon.

Methods: A two-arm, open-label, randomized, controlled trial comparing the equivalence of AS-AQ (experimental group) and AL (control group) was carried out from May 2019 to April 2020 at two secondary hospitals in Yaoundé. Participants were randomized to receive either AS-AQ or AL. After the first dose, antimalarial drugs were given at home, rather than under direct observation by a study staff. The conventional on-treatment and post-treatment laboratory and clinical evaluations were not done until day 3 of the full antimalarial treatment course. The evaluation of effectiveness was mainly based on per protocol polymerase chain reaction adjusted adequate clinical and parasitological response (PP PCR adjusted ACPR) on day 28 post-treatment. Safety was based on assessment of adverse events (AEs) and severe adverse events (SAEs) from day 1 to day 28.

Results: A total of 242 children were randomized to receive AS-AQ (n = 114) and AL (n = 128). The PP PCR adjusted day 28 cure rates were [AS-AQ = 96.9% (95% CI, 91.2-99.4) versus AL = 95.5% (95% CI, 89.9-98.5), P = 0.797]. Expected mild to moderate adverse events were reported in both arms [AS-AQ = 83 (84.7%) versus AL = 99 (86.1%), P = 0.774]. The most common adverse events included: transient changes of hematologic indices and fever.

Conclusions: This study demonstrated that AS-AQ and AL are effective and safe for home management of malaria in Yaoundé. The evidence from this study supports the parallel use of the two drugs in routine practice. However, the findings from this study do not describe the likely duration of antimalarial effectiveness in holoendemic areas where multiple courses of treatment might be required.

Trial registration: This study is a randomized controlled trial and it was retrospectively registered on 23/09/2020 at ClinicalTrials.gov with registration number NCT04565184.

Keywords: Artemether-lumefantrine; Artesunate-amodiaquine; Cameroon; Effectiveness; Malaria; Plasmodium falciparum; Safety.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Trial profile of effectiveness and safety study on artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) in Yaoundé, Cameroon. *Enrollment violation (1 participant had baseline parasitaemia > 200,000 parasites/µl, 2 had only positive results by malaria rapid diagnostic test and 2 had signs of severe malaria); Treatment violation (1 did not comply with the treatment procedure). **Enrollment violation (1 participant had baseline parasitaemia > 200,000 parasites/µl and 1 had only positive result by malaria rapid diagnostic test); Treatment violation (1 did not comply with the treatment procedure)

References

    1. WHO. World Malaria Report 2021. Geneva, World Health Organization. . Accessed on 26 Jan2022.
    1. WHO briefing on Malaria Treatment Guidelines and artemisinin monotherapies. . Accessed 20 Jul 2021.
    1. WHO. Geneva, World Health Organization 2009. Methods for surveillance of antimalarial drug efficacy. . Accessed 12 Feb 2019.
    1. WHO. Geneva, World Health Organization 2015. Guidelines for the treatment of malaria. Third edition. . Accessed15 Jul 2020.
    1. WHO. Geneva, World Health Organization. Tackling antimalarial drug resistance. . Accessed 3 May 2021.
    1. Sagara I, Beavogui AH, Zongo I, Soulama I, Borghini-Fuhrer I, Fofana B, et al. Pyronaridine–artesunate or dihydroartemisinin–piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b/4 trial. Lancet. 2018;391(10128):1378–1390. doi: 10.1016/S0140-6736(18)30291-5.
    1. Han KT, Lin K, Han ZY, Myint MK, Aye KH, Thi A, et al. Efficacy and safety of pyronaridine-artesunate for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Myanmar. Am J Trop Med Hyg. 2020;103(3):1088–1093. doi: 10.4269/ajtmh.20-0185.
    1. Cameroon National Malaria Control Program (NMCP) annual report of activities 2006.
    1. Cameroon National Malaria Control Program (NMCP) Annual Report of Activities 2016.
    1. Rathmes G, Rumisha SF, Lucas TCD, Twohig KA, Python A, Nguyen M, et al. Global estimation of anti-malarial drug effectiveness for the treatment of uncomplicated Plasmodium falciparum malaria 1991–2019. Malar J. 2020;19(1):374. doi: 10.1186/s12936-020-03446-8.
    1. van der Pluijm RW, Tripura R, Hoglund RM, Pyae Phyo A, Lek D, ul Islam A, et al. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. Lancet. 2020;395(10233):1345–60.
    1. Tahar R, Almelli T, Debue C, Foumane Ngane V, Djaman Allico J, Whegang Youdom S, et al. Randomized trial of artesunate-amodiaquine, atovaquone-proguanil, and artesunate-atovaquone-proguanil for the treatment of uncomplicated falciparum malaria in children. J Infect Dis. 2014;210(12):1962–1971. doi: 10.1093/infdis/jiu341.
    1. Nji AM, Ali IM, Moyeh MN, Ngongang E-O, Ekollo AM, Chedjou J-P, et al. Randomized non-inferiority and safety trial of dihydroartemisin-piperaquine and artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroonian children. Malar J. 2015;14:27. doi: 10.1186/s12936-014-0521-2.
    1. Lingani M, Bonkian LN, Yerbanga I, Kazienga A, Valéa I, Sorgho H, et al. In vivo/ex vivo efficacy of artemether-lumefantrine and artesunate-amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso. Malar J. 2020;19(1):8–8. doi: 10.1186/s12936-019-3089-z.
    1. Zongo I, Compaoré YD, Nikiéma F, Zongo M, Barry N, Somé FA, et al. Efficacy of artemether-lumefantrine and artesunate-amodiaquine as first line therapy of uncomplicated malaria in Burkina Faso 11 years after policy change. Pan Afr Med J. 2020 doi: 10.11604/pamj.2020.35.68.20849.
    1. Faucher J, Aubouy A, Adeothy A, Cottrell G, Doritchamou J, Gourmel B, et al. Comparison of sulfadoxine-pyrimethamine, unsupervised artemether-lumefantrine, and unsupervised artesunate-amodiaquine fixed-dose formulation for uncomplicated Plasmodium falciparum Malaria in Benin: a randomized effectiveness noninferiority trial. J Infect Dis. 2009;200(1):57–65. doi: 10.1086/599378.
    1. Ngasala BE, Malmberg M, Carlsson AM, Ferreira PE, Petzold MG, Blessborn D, et al. Efficacy and Effectiveness of Artemether-Lumefantrine after Initial and Repeated Treatment in Children <5 Years of Age with Acute Uncomplicated Plasmodium falciparum Malaria in Rural Tanzania A Randomized Trial. Clin Infect Dis. 2011;52(7):873–82. 10.1093/cid/cir066.
    1. Chatio S, Aborigo R, Adongo PB, Anyorigiya T, Dalinjong PA, Akweongo P, et al. Factors influencing adverse events reporting within the health care system: the case of artemisinin-based combination treatments in northern Ghana. Malar J. 2016;15(1):125. doi: 10.1186/s12936-016-1172-2.
    1. Ndagije HB, Nambasa V, Manirakiza L, Kusemererwa D, Kajungu D, Olsson S, et al. The burden of adverse drug reactions due to artemisinin-based antimalarial treatment in selected Ugandan health facilities: an active follow-up study. Drug Saf. 2018;41(8):753–765. doi: 10.1007/s40264-018-0659-x.
    1. Gasasira AF, Kamya MR, Achan J, Mebrahtu T, Kalyango JN, Ruel T, et al. High risk of neutropenia in HIV-infected children following treatment with artesunate plus amodiaquine for uncomplicated malaria in Uganda. Clin Infect Dis. 2008;46(7):985–991. doi: 10.1086/529192.
    1. Zwang J, D’Alessandro U, Ndiaye J-L, Djimdé AA, Dorsey G, Mårtensson AA, et al. Haemoglobin changes and risk of anaemia following treatment for uncomplicated falciparum malaria in sub-Saharan Africa. BMC Infect Dis. 2017;17(1):443–443. doi: 10.1186/s12879-017-2530-6.
    1. Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois A-C, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505(7481):50–55. doi: 10.1038/nature12876.
    1. Ménard D, Khim N, Beghain J, Adegnika AA, Shafiul-Alam M, Amodu O, et al. A worldwide map of Plasmodium falciparum K13-propeller polymorphisms. N Engl J Med. 2016;374(25):2453–2464. doi: 10.1056/NEJMoa1513137.
    1. Ocan M, Akena D, Nsobya S, Kamya MR, Senono R, Kinengyere AA, et al. K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors. Malar J. 2019;18(1):60. doi: 10.1186/s12936-019-2701-6.
    1. WHO. Geneva, World Health Organization. Report on antimalarial drug efficacy, resistance and response: 10 years of surveillance (2010–2019). . Accessed 3 May 2021.
    1. Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana S-I, Yamauchi M, et al. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med. 2021;385(13):1163–1171. doi: 10.1056/NEJMoa2101746.
    1. Bwire GM, Ngasala B, Mikomangwa WP, Kilonzi M, Kamuhabwa AAR. Detection of mutations associated with artemisinin resistance at k13-propeller gene and a near complete return of chloroquine susceptible falciparum malaria in Southeast of Tanzania. Sci Rep. 2020;10(1):3500. doi: 10.1038/s41598-020-60549-7.
    1. Uwimana A, Legrand E, Stokes BH, Ndikumana J-LM, Warsame M, Umulisa N, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020 doi: 10.1038/s41591-020-1005-2.
    1. Uwimana A, Umulisa N, Venkatesan M, Svigel SS, Zhou Z, Munyaneza T, et al. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: an open-label, single-arm, multicentre, therapeutic efficacy study. Lancet Infect Dis. 2021 doi: 10.1016/S1473-3099(21)00142-0.
    1. Boni MF, Smith DL, Laxminarayan R. Benefits of using multiple first-line therapies against malaria. Proc Natl Acad Sci U S A. 2008;105(37):14216–14221. doi: 10.1073/pnas.0804628105.
    1. Smith DL, Klein EY, McKenzie FE, Laxminarayan R. Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty. Malar J. 2010;9(1):217. doi: 10.1186/1475-2875-9-217.
    1. Ndiaye JL, Randrianarivelojosia M, Sagara I, Brasseur P, Ndiaye I, Faye B, et al. Randomized, multicentre assessment of the efficacy and safety of ASAQ—a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria. Malar J. 2009;8:125–125. doi: 10.1186/1475-2875-8-125.
    1. Faye B, Kuété T, Kiki-Barro CP, Tine RC, Nkoa T, Ndiaye JLA, et al. Multicentre study evaluating the non-inferiority of the new paediatric formulation of artesunate/amodiaquine versus artemether/lumefantrine for the management of uncomplicated Plasmodium falciparum malaria in children in Cameroon Ivory Coast and Senegal. Malar J. 2012;11:433–433. doi: 10.1186/1475-2875-11-433.
    1. Yaounde Climate and Temperature. . Accessed 18 May 2021.
    1. Antonio-Nkondjio C, Ndo C, Njiokou F, Bigoga JD, Awono-Ambene P, Etang J, et al. Review of malaria situation in Cameroon: technical viewpoint on challenges and prospects for disease elimination. Parasit Vectors. 2019;12(1):501. doi: 10.1186/s13071-019-3753-8.
    1. Sathian B, Sreedharan J, Baboo SN, Sharan K, Abhilash ES, Rajesh E. Relevance of sample size determination in medical research. Nepal J Epidemiol. 1970;1(1):4–10. doi: 10.3126/nje.v1i1.4100.
    1. Zhong B. How to calculate sample size in randomized controlled trial? J Thorac Dis. 2009;1(1):51–54.
    1. Sealed Envelope Ltd. 2019. Create a blocked randomisation list. . Accessed 7 May 2019.
    1. World Health Organization. UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Microscopy for the detection, identification and quantification of malaria parasites on stained thick and thin blood films in research settings (version 1.0): procedure: methods manual. Geneva: World Health Organization; 2015.
    1. Snounou G. Genotyping of Plasmodium spp.: Nested PCR. In: Doolan DL, editor. Malaria Methods and Protocols. New Jersey: Humana Press; 2002. pp. 103–116.
    1. Mohd Abd Razak MR, Sastu UR, Norahmad NA, Abdul-Karim A, Muhammad A, Muniandy PK, et al. Genetic diversity of Plasmodium falciparum populations in malaria declining areas of Sabah, East Malaysia. PLoS ONE. 2016 doi: 10.1371/journal.pone.0152415.
    1. WHO. Geneva. World Health Organization 2008. A practical handbook on the pharmacovigilance of antimalarial medicines. . Accessed 29 May 2020.
    1. Apinjoh T, Anchang-Kimbi J, Ajonina M, Njonguo E, Njua-Yafi C, Ngwai A, et al. In vivo efficacy of artesunate/sulphadoxine-pyrimethamine versus artesunate/amodiaquine in the treatment of uncomplicated P. falciparium malaria in children around the slope of mount cameroon: a randomized controlled trial. Biomedicines. 2016;4(1):5. doi: 10.3390/biomedicines4010005.
    1. Kobbe R, Klein P, Adjei S, Amemasor S, Thompson WN, Heidemann H, et al. A randomized trial on effectiveness of artemether-lumefantrine versus artesunate plus amodiaquine for unsupervised treatment of uncomplicated Plasmodium falciparum malaria in Ghanaian children. Malar J. 2008;7:261–261. doi: 10.1186/1475-2875-7-261.
    1. Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, et al. Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial. Lancet. 2005;365(9469):1474–1480. doi: 10.1016/S0140-6736(05)66417-3.
    1. Sondo P, Derra K, Diallo-Nakanabo S, Tarnagda Z, Zampa O, Kazienga A, et al. Effectiveness and safety of artemether-lumefantrine versus artesunate-amodiaquine for unsupervised treatment of uncomplicated falciparum malaria in patients of all age groups in Nanoro Burkina Faso: a randomized open label trial. Malar J. 2015;14(325):325. doi: 10.1186/s12936-015-0843-8.
    1. Ajayi IO, Browne EN, Bateganya F, Yar D, Happi C, Falade CO, et al. Effectiveness of artemisinin-based combination therapy used in the context of home management of malaria: a report from three study sites in sub-Saharan Africa. Malar J. 2008;7(1):190. doi: 10.1186/1475-2875-7-190.
    1. Tinto H, Diallo S, Zongo I, Guiraud I, Valea I, Kazienga A, et al. Effectiveness of artesunate-amodiaquine vs. artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Nanoro, Burkina Faso: a non-inferiority randomised trial. Trop Med Int Health. 2014;19(4):469–475. doi: 10.1111/tmi.12274.
    1. Abuaku B, Duah-Quashie NO, Quaye L, Matrevi SA, Quashie N, Gyasi A, et al. Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine combinations for uncomplicated malaria in 10 sentinel sites across Ghana: 2015–2017. Malar J. 2019;18(1):206. doi: 10.1186/s12936-019-2848-1.
    1. Diallo MA, Yade MS, Ndiaye YD, Diallo I, Diongue K, Sy SA, et al. Efficacy and safety of artemisinin-based combination therapy and the implications of Pfkelch13 and Pfcoronin molecular markers in treatment failure in Senegal. Sci Rep. 2020;10(1):8907. doi: 10.1038/s41598-020-65553-5.
    1. Ishengoma DS, Mandara CI, Francis F, Talundzic E, Lucchi NW, Ngasala B, et al. Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania. Malar J. 2019;18(1):88. doi: 10.1186/s12936-019-2730-1.
    1. Olivera MJ, Guerra AP, Cortes LJ, Horth RZ, Padilla J, Novoa J, et al. Artemether-lumefantrine efficacy for the treatment of uncomplicated Plasmodium falciparum malaria in choco, colombia after 8 years as first-line treatment. Am J Trop Med Hyg. 2020;102(5):1056–1063. doi: 10.4269/ajtmh.19-0954.
    1. Derbie A, Mekonnen D, Adugna M, Yeshitela B, Woldeamanuel Y, Abebe T. Therapeutic efficacy of artemether-lumefantrine (Coartem®) for the treatment of uncomplicated falciparum malaria in africa: a systematic review. J Parasitol Res. 2020 doi: 10.1155/2020/7371681.
    1. Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, Ruzagira E, et al. Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet. 2005;365(9469):1467–1473. doi: 10.1016/S0140-6736(05)66416-1.
    1. Depoortere E, Guthmann J-P, Presse J, Sipilanyambe N, Nkandu E, Balkan S, et al. Efficacy and effectiveness of the combination of sulfadoxine/pyrimethamine and a 3-day course of artesunate for the treatment of uncomplicated falciparum malaria in a refugee settlement in Zambia. Trop Med Int Health. 2005;10(2):139–145. doi: 10.1111/j.1365-3156.2004.01363.x.
    1. Dorsey G, Gasasira AF, Machekano R, Kamya MR, Staedke SG, Hubbard A. The impact of age, temperature, and parasite density on treatment outcomes from antimalarial clinical trials in Kampala. Uganda Am J Trop Med Hyg. 2004;71(5):531–536. doi: 10.4269/ajtmh.2004.71.531.
    1. Sangowawa AO, Amodu OK, Olaniyan SA, Amodu FA, Olumese PE, Omotade OO. Factors Associated with a Poor Treatment Outcome among Children Treated for Malaria in Ibadan, Southwest Nigeria. Wilson ML, editor. Epidemiol Res Int. 2014 doi: 10.1155/2014/974693.
    1. Kyabayinze DJ, Karamagi C, Kiggundu M, Kamya MR, Wabwire-Mangen F, Kironde F, et al. Multiplicity of Plasmodium falciparum infection predicts antimalarial treatment outcome in Ugandan children. Afr Health Sci. 2008;8(4):200–205.
    1. Muhindo Mavoko H, Kalabuanga M, Delgado-Ratto C, Maketa V, Mukele R, Fungula B, et al. Uncomplicated clinical malaria features, the efficacy of artesunate-amodiaquine and their relation with multiplicity of infection in the democratic republic of congo. PLoS ONE. 2016;11(6):e0157074–e0157074. doi: 10.1371/journal.pone.0157074.
    1. Borrmann S, Matsiegui P-B, Missinou MA, Kremsner PG. Effects of Plasmodium falciparum parasite population size and patient age on early and late parasitological outcomes of antimalarial treatment in children. Antimicrob Agents Chemother. 2008;52(5):1799–1805. doi: 10.1128/AAC.00755-07.
    1. Enevold A, Nkya WM, Theisen M, Vestergaard LS, Jensen AT, Staalsoe T, et al. Potential impact of host immunity on malaria treatment outcome in Tanzanian children infected with Plasmodium falciparum. Malar J. 2007;6(1):153. doi: 10.1186/1475-2875-6-153.
    1. Mutagonda RF, Kamuhabwa AAR, Minzi OMS, Massawe SN, Asghar M, Homann MV, et al. Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women. Malar J. 2017;16(1):267. doi: 10.1186/s12936-017-1914-9.
    1. St Jean PL, Koh GCKW, Breton JJ, Espino FEJ, Hien TT, Krudsood S, et al. Pharmacogenetic assessment of tafenoquine efficacy in patients with Plasmodium vivax malaria. Pharmacogenet Genomics. 2020;30(7):161–165. doi: 10.1097/FPC.0000000000000407.
    1. Borrmann S, Sallas WM, Machevo S, González R, Björkman A, Mårtensson A, et al. The effect of food consumption on lumefantrine bioavailability in African children receiving artemether-lumefantrine crushed or dispersible tablets (Coartem ® ) for acute uncomplicated Plasmodium falciparum malaria. Trop Med Int Health. 2010 doi: 10.1111/j.1365-3156.2010.02477.x.
    1. Faye B, Offianan AT, Ndiaye JL, Tine RC, Touré W, Djoman K, et al. Efficacy and tolerability of artesunate-amodiaquine (Camoquin plus®) versus artemether-lumefantrine (Coartem®) against uncomplicated Plasmodium falciparum malaria: multisite trial in Senegal and Ivory Coast. Trop Med Int Health. 2010 doi: 10.1111/j.1365-3156.2010.02487.x.
    1. Yavo W, Konaté A, Kassi FK, Djohan V, Angora EK, Kiki-Barro PC, et al. Efficacy and safety of artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in sentinel sites across Côte d’Ivoire, Krishna S, editor. Malar Res Treat. 2015 doi: 10.1155/2015/878132.
    1. Dorkenoo AM, Yehadji D, Agbo YM, Layibo Y, Agbeko F, Adjeloh P, et al. Therapeutic efficacy trial of artemisinin-based combination therapy for the treatment of uncomplicated malaria and investigation of mutations in k13 propeller domain in Togo, 2012–2013. Malar J. 2016;15(1):331. doi: 10.1186/s12936-016-1381-8.
    1. WWARN Gametocyte Study Group Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data. BMC Med. 2016;14:79–79. doi: 10.1186/s12916-016-0621-7.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere