This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aubouy, A.
Right arrow Articles by Deloron, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aubouy, A.
Right arrow Articles by Deloron, P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2003, p. 231-237, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.231-237.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Combination of Drug Level Measurement and Parasite Genotyping Data for Improved Assessment of Amodiaquine and Sulfadoxine-Pyrimethamine Efficacies in Treating Plasmodium falciparum Malaria in Gabonese Children

Agnès Aubouy,1 Mohamed Bakary,2 Annick Keundjian,3 Bernard Mbomat,2 Jean Ruffin Makita,2 Florence Migot-Nabias,1,4 Michel Cot,5 Jacques Le Bras,6 and Philippe Deloron1,5*

Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville,1 Bakoumba Hospital, Bakoumba, Gabon,2 Institut de Recherche pour le Développement, UR010 Mother and Child Health in the Tropics, Faculté de Pharmacie, Laboratoire de Parasitologie, 75006 Paris,5 IMTSSA, Laboratoire de Parasitologie, 13998 Marseille,3 Hôpital Bichat-Claude Bernard, Laboratoire de Parasitologie, 75877 Paris, France,6 IRD UR010, Dakar, Senegal4

Received 8 April 2002/ Returned for modification 29 July 2002/ Accepted 23 October 2002

Many African countries currently use a sulfadoxine-pyrimethamine combination (SP) or amodiaquine (AQ) to treat uncomplicated Plasmodium falciparum malaria. Both drugs represent the last inexpensive alternatives to chloroquine. However, resistant P. falciparum populations are largely reported in Africa, and it is compulsory to know the present situation of resistance. The in vivo World Health Organization standard 28-day test was used to assess the efficacy of AQ and SP to treat uncomplicated falciparum malaria in Gabonese children under 10 years of age. To document treatment failures, molecular genotyping to distinguish therapeutic failures from reinfections and drug dosages were undertaken. A total of 118 and 114 children were given AQ or SP, respectively, and were monitored. SP was more effective than AQ, with 14.0 and 34.7% of therapeutic failures, respectively. Three days after initiation of treatment, the mean level of monodesethylamodiaquine (MdAQ) in plasma was 149 ng/ml in children treated with amodiaquine. In those treated with SP, mean levels of sulfadoxine and pyrimethamine in plasma were 100 µg/ml and 212 ng/ml, respectively. Levels of the three drugs were higher in patients successfully treated with AQ (MdAQ plasma levels) or SP (sulfadoxine and pyrimethamine plasma levels). Blood concentration higher than breakpoints of 135 ng/ml for MdAQ, 100 µg/ml for sulfadoxine, and 175 ng/ml for pyrimethamine were associated with treatment success (odds ratio: 4.5, 9.8, and 11.8, respectively; all P values were <0.009). Genotyping of merozoite surface proteins 1 and 2 demonstrated a mean of 4.0 genotypes per person before treatment. At reappearance of parasitemia, both recrudescent parasites (represented by common bands in both samples) and newly inoculated parasites (represented by bands that were absent before treatment) were present in the blood of most (51.1%) children. Only 3 (6.4%) therapeutic failures were the result not of treatment inefficacy but of new infection. In areas where levels of drug resistance and complexity of infections are high, drug dosage and parasite genotyping may be of limited interest in improving the precision of drug efficacy measurement. Their use should be weighted according to logistical constraints.

* Corresponding author. Mailing address: IRD UR010, Faculté de Pharmacie, Laboratoire de Parasitologie, 4 Avenue de l'Observatoire, 75006 Paris, France. Phone: 33 1 53 73 96 21. Fax: 33 1 42 16 26 54. E-mail: philippe.deloron{at}ird.fr.

Antimicrobial Agents and Chemotherapy, January 2003, p. 231-237, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.231-237.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Adjei, G. O., Kristensen, K., Goka, B. Q., Hoegberg, L. C. G., Alifrangis, M., Rodrigues, O. P., Kurtzhals, J. A. L. (2008). Effect of Concomitant Artesunate Administration and Cytochrome P4502C8 Polymorphisms on the Pharmacokinetics of Amodiaquine in Ghanaian Children with Uncomplicated Malaria. Antimicrob. Agents Chemother. 52: 4400-4406 [Abstract] [Full Text]  
  • Johnson, J. D., Dennull, R. A., Gerena, L., Lopez-Sanchez, M., Roncal, N. E., Waters, N. C. (2007). Assessment and Continued Validation of the Malaria SYBR Green I-Based Fluorescence Assay for Use in Malaria Drug Screening. Antimicrob. Agents Chemother. 51: 1926-1933 [Abstract] [Full Text]  
  • AYALA, E., LESCANO, A. G., GILMAN, R. H., CALDERON, M., PINEDO, V. V., TERRY, H., CABRERA, L., VINETZ, J. M. (2006). POLYMERASE CHAIN REACTION AND MOLECULAR GENOTYPING TO MONITOR PARASITOLOGICAL RESPONSE TO ANTI-MALARIAL CHEMOTHERAPY IN THE PERUVIAN AMAZON. Am J Trop Med Hyg 74: 546-553 [Abstract] [Full Text]  
  • YARDLEY, V., CROFT, S. L., DE DONCKER, S., DUJARDIN, J.-C., KOIRALA, S., RIJAL, S., MIRANDA, C., LLANOS-CUENTAS, A., CHAPPUIS, F. (2005). THE SENSITIVITY OF CLINICAL ISOLATES OF LEISHMANIA FROM PERU AND NEPAL TO MILTEFOSINE. Am J Trop Med Hyg 73: 272-275 [Abstract] [Full Text]  
  • Cassera, M. B., Gozzo, F. C., D'Alexandri, F. L., Merino, E. F., del Portillo, H. A., Peres, V. J., Almeida, I. C., Eberlin, M. N., Wunderlich, G., Wiesner, J., Jomaa, H., Kimura, E. A., Katzin, A. M. (2004). The Methylerythritol Phosphate Pathway Is Functionally Active in All Intraerythrocytic Stages of Plasmodium falciparum. J. Biol. Chem. 279: 51749-51759 [Abstract] [Full Text]  
  • AUBOUY, A., MAYOMBO, J., KEUNDJIAN, A., BAKARY, M., LE BRAS, J., DELORON, P. (2004). SHORT REPORT: LACK OF PREDICTION OF AMODIAQUINE EFFICACY IN TREATING PLASMODIUM FALCIPARUM MALARIA BY IN VITRO TESTS. Am J Trop Med Hyg 71: 294-296 [Abstract] [Full Text]  
  • Aubouy, A., Jafari, S., Huart, V., Migot-Nabias, F., Mayombo, J., Durand, R., Bakary, M., Le Bras, J., Deloron, P. (2003). DHFR and DHPS genotypes of Plasmodium falciparum isolates from Gabon correlate with in vitro activity of pyrimethamine and cycloguanil, but not with sulfadoxine-pyrimethamine treatment efficacy. J Antimicrob Chemother 52: 43-49 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»