Skip to main content
Top
Published in: Malaria Journal 1/2012

Open Access 01-12-2012 | Research

Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana

Authors: Benjamin Abuaku, Nancy Duah, Lydia Quaye, Neils Quashie, Kwadwo Koram

Published in: Malaria Journal | Issue 1/2012

Login to get access

Abstract

Background

In 2008, artemether - lumefantrine (AL) and dihydroartemisinin - piperaquine (DHAP) were added to artesunate - amodiaquine (AS-AQ) as first-line drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country.

Methods

The study was a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based 20/120 mg AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with fever.

Results

A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5% (95% CI: 92.1, 98.6) and 95.4% (95% CI: 90.3, 98.0), respectively, with statistically significant differences between the ecological zones. The 90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4) was significantly the lowest compared with 100% (95% CI: 93.2, 99.9) in the forest zone and 93.8% (95% CI: 77.8, 98.9) in the coastal zone (P = 0.017). Fever and parasite clearance were slower among children enrolled in the savannah zone. Gametocytaemia after day-3 post-treatment was rare in all the zones.

Conclusions

The study has shown that AL remains efficacious in Ghana with significant ecologic zonal differences. The savannah zone may be a potential zone for any emergence of resistant alleles as a result of the slower parasite clearance observed in the zone.
Appendix
Available only for authorised users
Literature
1.
go back to reference WHO: World Malaria Report 2011. 2011, Geneva: World Health Organization WHO: World Malaria Report 2011. 2011, Geneva: World Health Organization
2.
go back to reference Ministry of Health: National Malaria Control Programme. 2010, Annual Report Ministry of Health: National Malaria Control Programme. 2010, Annual Report
3.
go back to reference Koram KA: Mapping response of Plasmodium falciparum to chloroquine and other antimalarial drugs in Ghana, Project ID 980034. 2003, Accra: NMIMR, Final report submitted to MIM/TDR Koram KA: Mapping response of Plasmodium falciparum to chloroquine and other antimalarial drugs in Ghana, Project ID 980034. 2003, Accra: NMIMR, Final report submitted to MIM/TDR
4.
go back to reference WHO: Monitoring Antimalarial Drug Resistance: Report of a WHO Consultation. 3–5 December 2001. 2002, Geneva: World Health Organization WHO: Monitoring Antimalarial Drug Resistance: Report of a WHO Consultation. 3–5 December 2001. 2002, Geneva: World Health Organization
5.
go back to reference Koram KA, Abuaku B, Duah N, Quashie N: Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana. Acta Trop. 2005, 95: 194-203. 10.1016/j.actatropica.2005.06.018.CrossRefPubMed Koram KA, Abuaku B, Duah N, Quashie N: Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana. Acta Trop. 2005, 95: 194-203. 10.1016/j.actatropica.2005.06.018.CrossRefPubMed
6.
go back to reference Ghana Health Service: Final Draft. Antimalarial Drug Policy for Ghana. 2004, Accra: GHS Ghana Health Service: Final Draft. Antimalarial Drug Policy for Ghana. 2004, Accra: GHS
7.
go back to reference Ministry of Health: Guidelines for case management of malaria in Ghana. 2009, Accra: MOH Ministry of Health: Guidelines for case management of malaria in Ghana. 2009, Accra: MOH
8.
go back to reference WHO: Methods for surveillance of antimalarial drug efficacy. 2009, Geneva: World Health Organization WHO: Methods for surveillance of antimalarial drug efficacy. 2009, Geneva: World Health Organization
9.
go back to reference Ghana Statistical Service: 2010 population & housing census. Summary report of final results. 2012, GSS Ghana Statistical Service: 2010 population & housing census. Summary report of final results. 2012, GSS
11.
go back to reference Oduro AR, Koram KA, Rogers W, Atuguba F, Ansah P, Anyorigiya T, Ansah A, Anto F, Mensah N, Hodgson A, Nkrumah F: Severe falciparum malaria in young children of the Kassena-Nankana district of northern Ghana. Malar J. 2007, 6: 96-10.1186/1475-2875-6-96.PubMedCentralCrossRefPubMed Oduro AR, Koram KA, Rogers W, Atuguba F, Ansah P, Anyorigiya T, Ansah A, Anto F, Mensah N, Hodgson A, Nkrumah F: Severe falciparum malaria in young children of the Kassena-Nankana district of northern Ghana. Malar J. 2007, 6: 96-10.1186/1475-2875-6-96.PubMedCentralCrossRefPubMed
12.
go back to reference Abonuusum A, Owusu-Daako K, Tannich E, May J, Garms R, Kruppa T: Malaria transmission in two rural communities in the forest zone of Ghana. Parasitol Res. 2011, 108: 1465-1471. 10.1007/s00436-010-2195-1.CrossRefPubMed Abonuusum A, Owusu-Daako K, Tannich E, May J, Garms R, Kruppa T: Malaria transmission in two rural communities in the forest zone of Ghana. Parasitol Res. 2011, 108: 1465-1471. 10.1007/s00436-010-2195-1.CrossRefPubMed
13.
go back to reference Soulama I, Bigoga JD, Ndiaye M, Bougouma EC, Quagraine J, Casimiro PN, Stedman TT, Sirima SB: Genetic diversity of polymorphic vaccine candidate antigens (apical membrane antigen-1, merozoite surface protein-3, and erythrocyte binding antigen-175) in Plasmodium falciparum isolates from Western and Central Africa. Am J Trop Med Hyg. 2011, 84: 276-284. 10.4269/ajtmh.2011.10-0365.PubMedCentralCrossRefPubMed Soulama I, Bigoga JD, Ndiaye M, Bougouma EC, Quagraine J, Casimiro PN, Stedman TT, Sirima SB: Genetic diversity of polymorphic vaccine candidate antigens (apical membrane antigen-1, merozoite surface protein-3, and erythrocyte binding antigen-175) in Plasmodium falciparum isolates from Western and Central Africa. Am J Trop Med Hyg. 2011, 84: 276-284. 10.4269/ajtmh.2011.10-0365.PubMedCentralCrossRefPubMed
14.
go back to reference Adjei GO, Kurtzhals JA, Rodrigues OP, Alifrangis M, Hoegberg LC, Kitcher ED, Badoe EV, Lamptey R, Goka BQ: Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up. Malar J. 2008, 7: 127-10.1186/1475-2875-7-127.PubMedCentralCrossRefPubMed Adjei GO, Kurtzhals JA, Rodrigues OP, Alifrangis M, Hoegberg LC, Kitcher ED, Badoe EV, Lamptey R, Goka BQ: Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up. Malar J. 2008, 7: 127-10.1186/1475-2875-7-127.PubMedCentralCrossRefPubMed
15.
go back to reference Falade CO, Ogundele AO, Yusuf BO, Ademowo OG, Ladipo SM: High efficacy of two artemisinin-based combinations (artemether-lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria. Trop Med Int Health. 2008, 13: 635-643. 10.1111/j.1365-3156.2008.02043.x.CrossRefPubMed Falade CO, Ogundele AO, Yusuf BO, Ademowo OG, Ladipo SM: High efficacy of two artemisinin-based combinations (artemether-lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria. Trop Med Int Health. 2008, 13: 635-643. 10.1111/j.1365-3156.2008.02043.x.CrossRefPubMed
16.
go back to reference Faye B, Ndiaye JL, Ndiaye D, Dieng Y, Faye O, Gaye O: Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal. Malar J. 2007, 6: 80-10.1186/1475-2875-6-80.PubMedCentralCrossRefPubMed Faye B, Ndiaye JL, Ndiaye D, Dieng Y, Faye O, Gaye O: Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal. Malar J. 2007, 6: 80-10.1186/1475-2875-6-80.PubMedCentralCrossRefPubMed
17.
go back to reference Sagara I, Dicko A, Djimde A, Guindo O, Kone M, Tolo Y, Thera MA, Sogoba M, Fofana M, Ouattara A, Sissoko M, Jansen HF, Doumbo OK: A randomized trial of artesunate-sulfamethoxypyrazine-pyrimethamine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali. Am J Trop Med Hyg. 2006, 75: 630-636.PubMed Sagara I, Dicko A, Djimde A, Guindo O, Kone M, Tolo Y, Thera MA, Sogoba M, Fofana M, Ouattara A, Sissoko M, Jansen HF, Doumbo OK: A randomized trial of artesunate-sulfamethoxypyrazine-pyrimethamine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali. Am J Trop Med Hyg. 2006, 75: 630-636.PubMed
18.
go back to reference Sowunmi A, Gbotosho GO, Happi CT, Adedeji AA, Fehintola FA, Folarin OA, Tambo E, Fateye BA: Therapeutic efficacy and effects of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine on gametocyte carriage in children with uncomplicated Plasmodium falciparum Malaria in Southwestern Nigeria. Am J Trop Med Hyg. 2007, 77: 235-241.PubMed Sowunmi A, Gbotosho GO, Happi CT, Adedeji AA, Fehintola FA, Folarin OA, Tambo E, Fateye BA: Therapeutic efficacy and effects of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine on gametocyte carriage in children with uncomplicated Plasmodium falciparum Malaria in Southwestern Nigeria. Am J Trop Med Hyg. 2007, 77: 235-241.PubMed
19.
go back to reference Fanello CI, Karema C, Doren WV, Overmeir CV, Ngamije D, D’Alessandro U: A randomized trial to assess the safety and efficacy of artemether-lumfantrine (Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwanda. Trans R Soc Trop Med Hyg. 2007, 101: 344-350. 10.1016/j.trstmh.2006.06.010.CrossRefPubMed Fanello CI, Karema C, Doren WV, Overmeir CV, Ngamije D, D’Alessandro U: A randomized trial to assess the safety and efficacy of artemether-lumfantrine (Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwanda. Trans R Soc Trop Med Hyg. 2007, 101: 344-350. 10.1016/j.trstmh.2006.06.010.CrossRefPubMed
20.
go back to reference Guthmann JP, Cohuet S, Rigutto C, Fortes F, Saraiva N, Kiguli J, Kyomuhendo J, Francis M, Noel F, Mulemba M, Balkan S: High efficacy of two artemisinin-based combinations (artesunate + amodiaquine and artemether + lumefantrine) in Caala, Central Angola. Am J Trop Med Hyg. 2006, 75 (1): 143-145.PubMed Guthmann JP, Cohuet S, Rigutto C, Fortes F, Saraiva N, Kiguli J, Kyomuhendo J, Francis M, Noel F, Mulemba M, Balkan S: High efficacy of two artemisinin-based combinations (artesunate + amodiaquine and artemether + lumefantrine) in Caala, Central Angola. Am J Trop Med Hyg. 2006, 75 (1): 143-145.PubMed
21.
go back to reference Färnert A, Ursing J, Tolfvenstam T, Rono J, Karlsson L, Sparrelid E, Lindegårdh N: Artemether-lumefantrine treatment failure despite adequate lumefantrine day 7 concentration in a traveler with Plasmodium falciparum malaria after returning from Tanzania. Malar J. 2012, 11: 176-10.1186/1475-2875-11-176.PubMedCentralCrossRefPubMed Färnert A, Ursing J, Tolfvenstam T, Rono J, Karlsson L, Sparrelid E, Lindegårdh N: Artemether-lumefantrine treatment failure despite adequate lumefantrine day 7 concentration in a traveler with Plasmodium falciparum malaria after returning from Tanzania. Malar J. 2012, 11: 176-10.1186/1475-2875-11-176.PubMedCentralCrossRefPubMed
22.
go back to reference Michael OS, Gbotosho GO, Folarin OA, Okuboyejo T, Sowunmi A, Oduola AM, Happi CT: Early variations in Plasmodium falciparum dynamics in Nigerian children after treatment with two artemisinin-based combinations: implications on delayed parasite clearance. Malar J. 2010, 9: 335-10.1186/1475-2875-9-335.PubMedCentralCrossRefPubMed Michael OS, Gbotosho GO, Folarin OA, Okuboyejo T, Sowunmi A, Oduola AM, Happi CT: Early variations in Plasmodium falciparum dynamics in Nigerian children after treatment with two artemisinin-based combinations: implications on delayed parasite clearance. Malar J. 2010, 9: 335-10.1186/1475-2875-9-335.PubMedCentralCrossRefPubMed
23.
go back to reference McIntosh HM, Olliaro P: Artemisinin derivatives for treating severe malaria. Cochrane Database Syst Rev. 2000, 2: CD000527-PubMed McIntosh HM, Olliaro P: Artemisinin derivatives for treating severe malaria. Cochrane Database Syst Rev. 2000, 2: CD000527-PubMed
24.
go back to reference Sowunmi A, Adewoye EO, Gbotsho GO, Happi CT, Sijuade A, Folarin OA, Okuboyejo TM, Michael OS: Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children. Malar J. 2010, 9: 53-10.1186/1475-2875-9-53.PubMedCentralCrossRefPubMed Sowunmi A, Adewoye EO, Gbotsho GO, Happi CT, Sijuade A, Folarin OA, Okuboyejo TM, Michael OS: Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children. Malar J. 2010, 9: 53-10.1186/1475-2875-9-53.PubMedCentralCrossRefPubMed
25.
go back to reference WHO: Antimalarial drug combination therapy. Report of a WHO Technical consultation, 4 – 5 April 2001. 2001, Geneva: World Health Organization WHO: Antimalarial drug combination therapy. Report of a WHO Technical consultation, 4 – 5 April 2001. 2001, Geneva: World Health Organization
26.
go back to reference Mulenga M, JP Vg, Mwananyanda L, Chalwe V, Moerman F, Chilengi R, Overmeir CV, Dujardin JC, D’Alessandro U: Safety and efficacy of lumefantrine-artemether (Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults. Malar J. 2006, 5: 73-10.1186/1475-2875-5-73.PubMedCentralCrossRefPubMed Mulenga M, JP Vg, Mwananyanda L, Chalwe V, Moerman F, Chilengi R, Overmeir CV, Dujardin JC, D’Alessandro U: Safety and efficacy of lumefantrine-artemether (Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults. Malar J. 2006, 5: 73-10.1186/1475-2875-5-73.PubMedCentralCrossRefPubMed
27.
go back to reference Owusu-Agyei S, Asante KP, Owusu R, Adjuik M, Amenga-Etego S, Dosoo DK, Gyapong J, Greenwood B, Chandramohan D: An open label, randomized trial of artesunate + amodiaquine, artesunate + chlorproguanil-dapsone and artemether-lumefantrine for the treatment of uncomplicated malaria. PLoS ONE. 2008, 3: e2530-10.1371/journal.pone.0002530.PubMedCentralCrossRefPubMed Owusu-Agyei S, Asante KP, Owusu R, Adjuik M, Amenga-Etego S, Dosoo DK, Gyapong J, Greenwood B, Chandramohan D: An open label, randomized trial of artesunate + amodiaquine, artesunate + chlorproguanil-dapsone and artemether-lumefantrine for the treatment of uncomplicated malaria. PLoS ONE. 2008, 3: e2530-10.1371/journal.pone.0002530.PubMedCentralCrossRefPubMed
28.
go back to reference Boni MF, Smith DL, Laxminarayan R: Benefits of using multiple first-line therapies against malaria. Proc Natl Acad Sci USA. 2008, 105: 14216-14221. 10.1073/pnas.0804628105.PubMedCentralCrossRefPubMed Boni MF, Smith DL, Laxminarayan R: Benefits of using multiple first-line therapies against malaria. Proc Natl Acad Sci USA. 2008, 105: 14216-14221. 10.1073/pnas.0804628105.PubMedCentralCrossRefPubMed
29.
go back to reference 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: 217-10.1186/1475-2875-9-217.PubMedCentralCrossRefPubMed 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: 217-10.1186/1475-2875-9-217.PubMedCentralCrossRefPubMed
Metadata
Title
Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana
Authors
Benjamin Abuaku
Nancy Duah
Lydia Quaye
Neils Quashie
Kwadwo Koram
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2012
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-11-388

Other articles of this Issue 1/2012

Malaria Journal 1/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine