1921
Volume 91, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The efficacy of 3-day regimens of artemether-lumefantrine and artesunate-amodiaquine were evaluated in 747 children < 5 years of age with uncomplicated malaria from six geographical areas of Nigeria. Fever clearance was significantly faster ( = 0.006) and the proportion of children with parasitemia 1 day after treatment began was significantly lower ( = 0.016) in artesunate-amodiaquine—compared with artemether-lumefantrine-treated children. Parasite clearance times were similar with both treatments. Overall efficacy was 96.3% (95% confidence interval [CI] 94.5–97.6%), and was similar for both regimens. Polymerase chain reaction-corrected parasitologic cure rates on Day 28 were 96.9% (95% CI 93.9–98.2%) and 98.3% (95% CI 96.1–99.3%) for artemether-lumefantrine and artesunate-amodiaquine, respectively. Gametocyte carriage post treatment was significantly lower than pretreatment ( < 0.0001). In anemic children, mean time to recovery from anemia was 10 days (95% CI 9.04–10.9) and was similar for both regimens. Both treatments were well tolerated and are safe and efficacious treatments of uncomplicated falciparum malaria in young Nigerian children.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.13-0248
2014-11-05
2019-03-26
Loading full text...

Full text loading...

/deliver/fulltext/14761645/91/5/925.html?itemId=/content/journals/10.4269/ajtmh.13-0248&mimeType=html&fmt=ahah

References

  1. World Health Organization, 2001. Antimalarial Drug Combination Therapy: Report of a WHO Technical Consultation. Geneva: World Health Organization. [Google Scholar]
  2. Bosman A, Mendis KN, , 2007. A major transition in malaria treatment: the adoption and deployment of artemisinin-based combination therapies. Am J Trop Med Hyg 77 (Suppl 6): 193197. [Google Scholar]
  3. Wongsrichanalai C, Meshnick S, , 2008. Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia-Thailand border. Emerg Infect Dis 14: 716719.[Crossref] [Google Scholar]
  4. Lim P, Alker A, Khim N, Shah N, Incardona S, Doung S, Yi P, Bouth D, Boucher C, Mercereau P, Meshnick S, Wongsrichanalai C, Fandeur T, Bras J, Ringwald P, Ariey F, , 2009. Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia. Malar J 8: 11.[Crossref] [Google Scholar]
  5. Carrara VI, Zwang J, Ashley EA, Price RN, Stepniewka K, Marion B, Brockman A, Anderson T, McGready R, Phaiphun L, Stephane P, Vugt MV, Hutagalung R, Lwin KM, Phyo AP, Piyanuch P, Imwong M, Pukrittayakamee S, Singhasivanon P, White NJ, Nosten F, , 2009. Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS ONE 4: e511.[Crossref] [Google Scholar]
  6. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, , 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Eng Med 359: 26192620.[Crossref] [Google Scholar]
  7. Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, Moo C, Al-Saai S, Dondorp AM, Lwin KM, Singhasivanon P, Day N, White NJ, Anderson TM, Nosten F, , 2012. Emergence of arteminisin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379: 19601966.[Crossref] [Google Scholar]
  8. World Health Organization, 1973. Chemotherapy of Malaria and Resistance to Antimalarials. Geneva: World Health Organization. [Google Scholar]
  9. World Health Organization, 2003. Assessment and Monitoring of Antimalarials Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Geneva: World Health Organization. [Google Scholar]
  10. Federal Ministry of Health, 2005. National Antimalaria Treatment Guideline. Abuja, Nigeria: Federal Ministry of Health. [Google Scholar]
  11. World Health Organization, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 (Suppl 1): 190. [Google Scholar]
  12. Happi TC, Thomas SM, Gbotosho GO, Falade CO, Akinboye DO, Gerena L, Hudson T, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM, , 2003. Point mutations in the pfcrt and pfmdr-1 genes of Plasmodium falciparum and clinical response to chloroquine, among malaria patients from Nigeria. Ann Trop Med Parasitol 97: 439451.[Crossref] [Google Scholar]
  13. Happi CT, Gbotosho GO, Sowunmi A, Falade CO, Akinboye DO, Gerena L, Kyle DE, Milhous W, Wirth DF, Oduola AM, , 2004. Molecular analysis of Plasmodium falciparum recrudescent malaria infections in children treated with chloroquine in Nigeria. Am J Trop Med Hyg 70: 2026. [Google Scholar]
  14. Happi CT, Gbotosho GO, Folarin OA, Sowunmi A, Kyle DE, Bolaji OM, Fateye BA, Kyle DE, Milhous W, Wirth DF, Oduola AM, , 2006. Linkage disequilibrium between two distinct loci in chromosomes 5 and 7 of Plasmodium falciparum and in vivo chloroquine resistance in southwest Nigeria. Parasitol Res 100: 141148.[Crossref] [Google Scholar]
  15. Happi CT, Gbotosho GO, Folarin OA, Bolaji OM, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM, , 2006. Association between mutations in Plasmodium falciparum chloroquine resistance transporter and P. falciparum multidrug resistance 1 genes and in vivo amodaiquine resistance in P. falciparum malaria-infected children in Nigeria. Am J Trop Med Hyg 75: 155161. [Google Scholar]
  16. Sowunmi A, Balogun ST, Gbotosho GO, Happi CT, , 2008. Some features of primary and recrudescent amodiaquine-resistant Plasmodium falciparum infections in Nigerian children. Mem Inst Oswaldo Cruz 103: 754759.[Crossref] [Google Scholar]
  17. Anonymous, 1994. Epi info Version 6. A Word Processing DataBase and Statistics Programme for Public Health on IBM Compatible Microcomputers. Atlanta, GA: Centers for Disease Control and Prevention. [Google Scholar]
  18. Anonymous, 2008. SPSS for Windows Release 17.0 (Standard Version). Chicago, IL: SPSS Inc. [Google Scholar]
  19. Stepniewska K, Ashley E, Lee SJ, Antey N, Barne KJ, Binh TQ, D'Alessandro U, Day NP, de Vries PJ, Dorsey G, Guthmann JP, Mayxay M, Newton PN, Olliaro P, Osorio L, Price RN, Rowland M, Smithuis F, Taylor WR, Nosten F, White NJ, , 2010. In vivo parasitological measures of artemisinin susceptibility. J Infect Dis 201: 570579.[Crossref] [Google Scholar]
  20. Happi CT, Gbotosho GO, Folarin OA, Sowunmi A, Bolaji OM, Fateye BA, Kyle DE, Milhous W, Wirth DF, Oduola AM, , 2006. Linkage disequilibrium between two distinct loci in chromosome 5 and 7 of Plasmodium falciparum and in vivo chloroquine resistance in southwest Nigeria. Parasitol Res 100: 141148.[Crossref] [Google Scholar]
  21. Folarin OA, Bustamante C, Gbotosho GO, Sowunmi A, Zalis MG, Oduola AM, Happi CT, , 2011. In vitro amodiaquine resistance and its association with mutations in pfcrt and pfmdr1 genes of Plasmodium falciparum isolates from Nigeria. Acta Trop 120: 224230.[Crossref] [Google Scholar]
  22. Happi CT, Gbotosho GO, Sowunmi A, Falade CO, Akinboye DO, Gerena L, Kyle DE, Milhous W, Wirth DF, Oduola AM, , 2004. Molecular analysis of Plasmodium falciparum recrudescent malaria infections in children treated with chloroquine in Nigeria. Am J Trop Med Hyg 70: 2026. [Google Scholar]
  23. Folarin OA, Gbotosho GO, Sowunmi A, Olorunsogo OO, Happi TC, , 2008. Chloroquine-resistant Plasmodium falciparum in Nigeria: relationship between pfcrt and pfmdr-1 polymorphism, in vitro resistance and treatment outcome. Open Top Med J 1: 8492. [Google Scholar]
  24. Gbotosho GO, Folarin OA, Bustamante C, da Silva LH, Mesquita E, Sowunmi A, Zalis MG, Oduola AM, Happi CT, , 2012. Different patterns of pfcrt and pfmdr1 polymorphisms in P. falciparum isolates from Nigeria and Brazil: the potential role of antimalarial drug selection pressure. Am J Trop Med Hyg 86: 211213.[Crossref] [Google Scholar]
  25. Sowunmi A, Gbotosho GO, Happi CT, Adedeji AA, Fehintola FA, Folarin OA, Tambo E, Fateye BA, , 2007. Therapeutic efficacy and effects artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine on gametocyte carriage in children with uncomplicated Plasmodium falciparum malaria in southwest Nigeria. Am J Trop Med Hyg 77: 235241. [Google Scholar]
  26. Gbotosho GO, Sowunmi A, Happi CT, Okuboyejo TM, , 2011. Therapeutic efficacies of artemisinin-based combination therapies in Nigerian children with uncomplicated falciparum malaria during five years of adoption as first-line treatments. Am J Trop Med Hyg 84: 936943.[Crossref] [Google Scholar]
  27. Olliarro P, Mussano P, , 2003. Amodiaquine for treating malaria. Cochrane Database Syst Rev 2: CD000016. [Google Scholar]
  28. Gbotosho GO, Folarin OA, Bustamante C, da Silva LH, Mequita E, Sowunmi A, Zalis MG, Oduola AM, Happi CT, , 2012. Different patterns of pfcrt and pfmdr1 polymorphisms in P. falciparum isolates from Nigeria and Brazil: the potential role of antimalarial drug selection pressure. Am J Trop Med Hyg 86: 211213.[Crossref] [Google Scholar]
  29. Sa JM, Twu O, Hayton K, Reyes S, Fay MP, Ringwald P, Wellems TE, , 2008. Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine. Proc Natl Acad Sci USA 106: 1888318889.[Crossref] [Google Scholar]
  30. Sa JM, Twu O, , 2010. Protecting the malaria drug arsenal: halting the rise and spread of amodiaquine resistance by monitoring PfCRT SVMNT type. Malar J 9: 374.[Crossref] [Google Scholar]
  31. Suputtamongkol Y, Newton PN, Angus B, Teja-Isavadharm P, Keeratithakul D, Rasameesoraj M, Pukrittayakamee S, White NJ, , 2001. A comparison of oral artesunate and artemether antimalarial bioactivities in acute falciparum malaria. Br J Clin Pharmacol 52: 655661.[Crossref] [Google Scholar]
  32. Barnes KI, Watkins WM, White NJ, , 2008. Antimalarial dosing regimens and drug resistance. Trends Parasitol 24: 127134.[Crossref] [Google Scholar]
  33. Federal Ministry of Health, 2004. Antimalarial Treatment Policy. Abuja, Nigeria: Federal Ministry of Health. [Google Scholar]
  34. Ittarat W, Pickard AL, Rattanasinganchan P, Wilairatana P, Looareesuwan S, Emery K, Low J, Udomsangpetch R, Meshnick SR, , 2003. Recrudescence in artesunate-treated patients with falciparum malaria is dependent on parasite burden not on parasite factors. Am J Trop Med Hyg 68: 147152. [Google Scholar]
  35. Noedl H, Se Y, Sriwichai S, Schaecher K, Teja-Isavadharm P, Smith B, Rutvisuttinunt W, Bethell D, Surasri S, Fukuda MM, Socheat D, Cham Thap L, , 2010. Artemisinin resistance in Cambodia: a clinical trial designed to address an emerging problem in Southeast Asia. Clin Infect Dis 51: e82e89.[Crossref] [Google Scholar]
  36. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh K, Socheat D, White NJ, , 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467.[Crossref] [Google Scholar]
  37. Cheeseman IH, Miller BA, Nair S, Nkhoma S, Tan A, Tan JC, Saai SA, Phyo AP, Moo CL, Lwin KM, McGready R, Ashley E, Imwong M, Stepniewska K, Yi P, Dondorp AM, Mayxay M, Newton PN, White NJ, Nosten F, Ferdig MT, Anderson TJ, , 2012. A major genome region underlying artemisinin resistance in malaria. Science 336: 7982.[Crossref] [Google Scholar]
  38. Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, Lim P, Mao S, Sopha C, Sam B, Anderson JM, Duong S, Chuor CM, Taylor WR, Suon S, Mercereau-Puijalon O, Fairhurst RM, Menard D, , 2013. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo . Lancet Infect Dis 13: 10431049.[Crossref] [Google Scholar]
  39. Oduola AM, Sowunmi A, Milhous WK, Kyle DE, Martin RK, Walker O, Salako LA, , 1992. Innate resistance to new antimalarial drugs in Plasmodium falciparum from Nigeria. Trans R Soc Trop Med Hyg 86: 123126.[Crossref] [Google Scholar]
  40. Bustamante C, Onikepe AF, Gbotosho GO, Batista CN, Mesquita A, Brindeoro RM, Tanuri A, Struchiner CJ, Sowunmi A, Oduola A, Wirth DF, Zalis MG, Happi CT, , 2012. In vitro-reduced susceptibility to artemether in P. falciparum and its association with polymorphism on transporter genes. J Infect Dis 206: 324332.[Crossref] [Google Scholar]
  41. Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois A-C, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Ménard S, Rogers WO, Genton B, Fandeur T, Miotto O, Ringwald P, Le Bras J, Berry A, Barale J-C, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Ménard D, , 2014. A molecular maker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 5055.[Crossref] [Google Scholar]
  42. de Vries JP, Bich NN, Thien HV, Hung LN, Anh TK, Kager PA, Hiesterkamp SH, , 2000. Combinations of artemisinin and quinine for uncomplicated falciparum malaria: efficacy and pharmacodynamics. Antimicrob Agents Chemother 44: 13021308.[Crossref] [Google Scholar]
  43. Chotivanich K, Udomsangpetch R, Dondorp A, Williams T, Angus B, Simpson JA, Pukrittayakamee S, Looareesuwan S, Newbold CI, White NJ, , 2000. The mechanisms of parasite clearance after antimalarial treatment of Plasmodium falciparum malaria. J Infect Dis 182: 629633.[Crossref] [Google Scholar]
  44. Gbotosho GO, Okuboyejo T, Happi CT, Sowunmi A, , 2014. Fall in hematocrit per 1,000 parasites cleared from peripheral blood: a simple method for estimating drug-related fall in hematocrit after treatment of malaria infections. Am J Ther 21: 193197.[Crossref] [Google Scholar]
  45. Newton PN, Chotivanich K, Chierakul W, Ruangveerayuth R, Teerapong P, Silamut K, Looareesuwan S, White NJ, , 2001. A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes. Blood 98: 450457.[Crossref] [Google Scholar]
  46. Faye B, Offianan AT, Ndiaye JL, Tine RC, Toure W, Djoman K, Sylla K, Ndiaye PS, Penali L, Gaye O, , 2010. Efficacy and tolerability of artesunate-amodiaquine (camoquine plus) versus artemether-lumefantrine (coartem) against uncomplicated Plasmodium falciparum malaria: multisite trial in Senegal and Ivory Coast. Trop Med Int Health 15: 608613. [Google Scholar]
  47. Zwang J, Ndiaye J-L, Djimde A, Dorsey G, Mårtensson A, Karema C, Olliaro P, , 2012. Comparing changes in hematological parameters occurring in patients included in randomized controlled trial of artesunate-amodiaquine vs single and combination treatments of uncomplicated falciparum in sub-Saharan Africa. Malar J 11: 25.[Crossref] [Google Scholar]
  48. Sowunmi A, Walker O, Salako LA, , 1989. Pruritus and antimalarial drugs in Africans. Lancet 2: 213.[Crossref] [Google Scholar]
  49. Okafor HU, Shu EN, Oguonu T, , 2010. Therapeutic efficacy and effect on gametocyte carriage of an artemisinin and a non-based combination treatment in children with uncomplicated P. falciparum malaria, living in an area with high-level chloroquine resistance. J Trop Pediatr 56: 398406.[Crossref] [Google Scholar]
  50. Schramm B, Valeh P, Baudin C, Mazinda CS, Smith R, Pinoges L, Sundaygar T, Zolia YM, Jones JJ, Comte E, Bruneel A, Branger M, Jullien V, Cam G, Kiechel J-R, Ashley EA, Guérin PJ, , 2013. Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia. Malar J 12: 250.[Crossref] [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.13-0248
Loading
/content/journals/10.4269/ajtmh.13-0248
Loading

Data & Media loading...

  • Received : 08 May 2013
  • Accepted : 10 Jul 2014

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error