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Wiener klinische Wochenschrift

, Volume 122, Issue 5–6, pp 173–178 | Cite as

Efficacy and safety of a new pediatric artesunate-mefloquine drug formulation for the treatment of uncomplicated falciparum malaria in Gabon

  • Marielle K. Bouyou-Akotet
  • Michael Ramharter
  • Edgard Brice Ngoungou
  • Modeste Mabika Mamfoumbi
  • Mireille Pemba Mihindou
  • Michel A. Missinou
  • Florian Kurth
  • Sabine Bélard
  • Selidji T. Agnandji
  • Saadou Issifou
  • János L. Heidecker
  • Sonja Trapp
  • Peter G. Kremsner
  • Maryvonne KombilaEmail author
Original article

Summary

Pediatric drug formulations of artemisinin combination therapies are urgently needed for improving the treatment of children suffering from uncomplicated malaria. The aim of this clinical trial was to evaluate the efficacy, safety and tolerability of a novel pediatric fixed-dose granule formulation of artesunate-mefloquine and a new co-blister tablet formulation. A total of 71 children aged 1–13 years suffering from uncomplicated falciparum malaria were stratified into two groups according to weight: 10–20 kg, pediatric group (n = 41); 20–40 kg, tablet group (n = 30). All the children were treated once daily for three days: the pediatric group received the novel granule formulation, the tablet group received the co-blister tablets. The PCR-corrected cure rate on day 28 was evaluated. There was no reappearance of parasitemia during the follow-up period and the day-28 cure rate was therefore 100% in per-protocol analysis. In intention-to-treat analysis the cure rates were 95% in the pediatric group and 97% in the tablet group. The most frequent adverse events were vomiting (17%), abdominal pain (11%) and headache (17%). This study confirms the excellent efficacy and favorable safety and tolerability profile of a novel pediatric artesunate-mefloquine formulation for treatment in African children.

Keywords

Falciparum malaria Pediatric Artesunate-mefloquine 

Wirksamkeit, Verträglichkeit und Sicherheit einer neuen pädiatrischen Artesunat-Mefloquin Medikamentenformulierung zur Therapie der Malaria tropica

Zusammenfassung

Pädiatrische Medikamentenformulierungen sind ein wichtiger Fortschritt in der Therapie von afrikanischen Kindern, die an Malaria tropica erkrankt sind. In dieser klinischen Studie wurde die Wirksamkeit, Sicherheit und Verträglichkeit einer neuen pädiatrischen Artesunat-Mefloquin Koformulierung im Vergleich mit einer Tablettenformulierung evaluiert. Einundsiebzig pädiatrische Patienten am Albert Schweitzer Spital in Lambaréné, Gabun, die an unkomplizierter Malaria tropica litten, wurden nach Körpergewicht stratifiziert, um mit der pädiatrischen (10 – 20 kg; n = 41) oder der Tabletten-Formulierung (20 – 40 kg; n = 30) therapiert zu werden. Die PCR korrigierte Heilungsrate war 100 % am Tag 28. Die häufigsten Nebenwirkungen waren Erbrechen (17 %), abdominelle Schmerzen (11 %) und Cephalea (17 %). Diese Studie bestätigt die hervorragende Wirksamkeit und gute Verträglichkeit von Artesunat-Mefloquin zur Therapie pädiatrischer Patienten in Afrika.

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References

  1. World Health Organization (2006) Guidelines for the treatment of malaria. World Health Organization, Geneva. WHO/HTM/MAL/2006.1108Google Scholar
  2. Kremsner PG, Krishna S (2004) Antimalarial combinations. Lancet 364: 285–94CrossRefPubMedGoogle Scholar
  3. Ramharter M, Kurth FM, Bélard S, Bouyou-Akotet MK, Mamfoumbi MM, et al (2007) Pharmacokinetics of two paediatric artesunate mefloquine drug formulations in the treatment of uncomplicated falciparum malaria in Gabon. J Antimicrob Chemother 60: 1091–6CrossRefPubMedGoogle Scholar
  4. Abdulla S, Sagara I, Borrmann S, D'Alessandro U, González R, Hamel M, et al (2008) Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial. Lancet 372: 1819–27CrossRefPubMedGoogle Scholar
  5. Ramharter M, Kurth F, Schreier AC, Nemeth J, Glasenapp I, Bélard S, et al (2008) Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in paediatric patients in Gabon. J Infect Dis 198: 911–9CrossRefPubMedGoogle Scholar
  6. Matsiegui PB, Missinou MA, Necek M, Issifou S, Kremsner PG (2006) Short course of quinine plus a single dose of sulfadoxine/pyrimethamine for Plasmodium falciparum malaria. Wien Klin Wochenschr 118: 610–4CrossRefPubMedGoogle Scholar
  7. World Health Organization (2001) Antimalarial drug combination therapy. Report of a WHO technical consultation. World Health Organization, Geneva. WHO/CDS/RBM/2001.35Google Scholar
  8. Planche T, Krishna S, Kombila M, Engel K, Faucher JF, Ngou-Milama E, et al (2001) Comparison of methods for rapid laboratory assessment of children with malaria. Am J Trop Med Hyg 65: 599–602PubMedGoogle Scholar
  9. Ntoumi F, Contamin H, Rogier C, Bonnefoy S, Trape JF, Mercereau-Puijalon O (1995) Age-dependent carriage of multiple Plasmodium falciparum merozoite surface antigen-2 alleles in asymptomatic malaria infections. Am J Trop Med Hyg 52: 81–8PubMedGoogle Scholar
  10. World Health Organization (2003) Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. World Health Organizatopn, Geneva. WHO/HTM/RBM/2003.50Google Scholar
  11. Nosten F, Luxemburger C, ter Kuile FO, Woodrow C, Eh JP, Chongsuphajaisiddhi T, et al (1994) Treatment of multi-drug resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. J Infect Dis 170: 971–7PubMedGoogle Scholar
  12. Ramharter M, Wernsdorfer WH, Kremsner PG (2004) In vitro activity of quinolines against Plasmodium falciparum in Gabon. Acta Trop 90: 55–60CrossRefPubMedGoogle Scholar
  13. Massougbodji A, Kone M, Kinde-Gazard D, Same-Ekobo A, Cambon N, Mueller EA (2002) Randomised double blind study on the efficacy and safety of a practical 3 day regimen with artesunate and mefloquine for the treatment of uncomplicated malaria in Africa. Trans R Soc Trop Med Hyg 96: 655–9CrossRefPubMedGoogle Scholar
  14. Bhatt KM, Samia BM, Bhatt SM, Wasunna KM (2006) Efficacy and safety of an artesunate/mefloquine combination (Artequin) in the treatment of uncomplicated P. falciparum malaria in Kenya. East Afr Med J 83: 236–42PubMedGoogle Scholar
  15. Agomo PU, Meremikwu MM, Watila IM, Omalu IJ, Odey FA, Oguche S, et al (2008) Efficacy, safety and tolerability of artesunate-mefloquine in the treatment of uncomplicated Plasmodium falciparum malaria in four geographic zones of Nigeria. Malar J 7: 172CrossRefPubMedGoogle Scholar
  16. Sagara I, Diallo A, Kone M, Coulibaly M, Diawara SI, Guindo O (2008) A randomized trial of artesunate-mefloquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali. Am J Trop Med Hyg 79: 655–61PubMedGoogle Scholar
  17. Krudsood S, Looareesuwan S, Silachamroon U, Chalermrut K, Pittrow D, Cambon N, et al (2002) Artesunate and mefloquine given simultaneously for 3 days via a prepacked blister is equally effective and tolerated as a standard sequential treatment of uncomplicated malaria; randomized double-blind study in Thailand. Am J Trop Med Hyg 67: 465–72PubMedGoogle Scholar
  18. Smithuis F, Kyaw MK, Phe O, Aye KZ, Htet L, Barends M, et al (2006) Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison. Lancet 367: 2075–85CrossRefPubMedGoogle Scholar
  19. Ashley EA, Lwin KM, McGready R, Simon WH, Phaiphun L, Proux S, et al (2006) An open label randomized comparison of mefloquine-artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand. Trop Med Int Health 11: 1653–60CrossRefPubMedGoogle Scholar
  20. Faye B, Ndiaye JL, Ndiaye D, Dieng Y, Faye O, Gaye O (2007) Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal. Malar J 6: 80CrossRefPubMedGoogle Scholar
  21. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al (2009) Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455–67CrossRefPubMedGoogle Scholar
  22. Davis TM, Supanaranond W, Pukrittayakamee S, Crawley JC, Villaiwanna N, White NJ (1995) The effect of plasma free fatty acids and long-chain triglycerides on glucose metabolism in uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 89: 511–5CrossRefPubMedGoogle Scholar
  23. Mohanty S, Mishra SK, Das BS, Satpathy SK, Mohanty D, Patnaik JK, et al (1992) Altered plasma lipid pattern in falciparum malaria. Ann Trop Med Parasitol 86: 601–6PubMedGoogle Scholar
  24. Das BS, Patnaik JK, Mohanty S, Mishra SK, Mohanty D, Satpathy SK, et al (1993) Plasma antioxidants and lipid peroxidation products in falciparum malaria. Am J Trop Med Hyg 49: 720–5PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Marielle K. Bouyou-Akotet
    • 1
    • 2
  • Michael Ramharter
    • 3
    • 4
  • Edgard Brice Ngoungou
    • 1
    • 2
  • Modeste Mabika Mamfoumbi
    • 1
    • 2
  • Mireille Pemba Mihindou
    • 1
  • Michel A. Missinou
    • 3
    • 5
  • Florian Kurth
    • 3
  • Sabine Bélard
    • 3
  • Selidji T. Agnandji
    • 3
  • Saadou Issifou
    • 3
  • János L. Heidecker
    • 6
  • Sonja Trapp
    • 6
  • Peter G. Kremsner
    • 3
    • 5
  • Maryvonne Kombila
    • 1
    • 2
    Email author
  1. 1.Faculty of Medicine, Department of Parasitology, Mycology, and Tropical MedicineUniversité des Sciences de la SantéLibrevilleGabon
  2. 2.Malaria Clinical Research UnitCentre Hospitalier de Libreville-GabonLibrevilleGabon
  3. 3.Medical Research UnitAlbert Schweitzer HospitalLambarénéGabon
  4. 4.Division of Infectious Diseases and Tropical Medicine, Department of Medicine IMedical University of ViennaViennaAustria
  5. 5.Department for Parasitology, Institute for Tropical MedicineUniversity of TübingenTübingenGermany
  6. 6.Pharmaceutical ResearchDevelopment and Manufacture, Mepha LtdAeschSwitzerland

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