Skip to main content

Free Content Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub-Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness

Download Article:

You have access to the full text article on a website external to Ingenta Connect.

Please click here to view this article on Wiley Online Library.

You may be required to register and activate access on Wiley Online Library before you can obtain the full text. If you have any queries please visit Wiley Online Library


Molecular genotyping of baseline and post-treatment recurrent Plasmodium falciparum is recommended to distinguish recrudescent from new infections. However, genotyping performance and adjustment of treatment outcomes have not been evaluated in large field trials. Parasitological outcomes were assessed in nine double-blinded trials of uncomplicated P. falciparum malaria in African children treated with artesunate/placebo plus standard monotherapies. Day 28 failure rates were adjusted by stepwise genotyping the P. falciparum glutamate rich protein (glurp), merozoite surface protein 1 (msp1) and 2 (msp2). We calculated overall and laboratory genotyping performance and compared unadjusted (crude) and PCR-adjusted outcomes. 3455 (93.6%) of 3691 enrolled patients were evaluable by Day 28. 767 (22%) had post-Day 14 recurrent parasitemias of which 686 could be genotyped: 246 were recrudescences, 286 new infections and 154 unresolved. The overall and laboratory genotyping performance were 69 (12–100)% and 78 (50–100)%, respectively. The mean Day 28 crude parasitological failure rate was 44 (range 3–87)%. PCR-adjusted rates were 36 (range 2–86)% if unresolved infections were counted as failures or 33 (range 2–86)% if excluded from analysis. The overall difference between crude Day 28 and Day 14 failure rates was 22% (95% CI 20.3, 24.6) but decreased to 14% (95% CI 12.1, 16.3) if unresolved infections are counted as failures, or to 11% (95% CI 9.8, 16.3) if unresolved infections are excluded from the analysis. Genotyping refined treatment outcomes but diligence is needed in sample collection and analysis to improve its performance. Our findings support the WHO recommendation of PCR genotyping in malaria clinical trials and suggest that stepwise genotyping of only two loci (msp2 and msp1 or glurp) can reliably discriminate recrudescences from new infections.
No References
No Citations
No Supplementary Data
No Data/Media
No Metrics

Keywords: PCR-adjusted antimalarial treatment outcomes; drug trials; molecular genotyping

Document Type: Research Article

Affiliations: 1:  Navrongo Health Research Centre, Navrongo, Ghana 2:  Pasteur Institute, Paris, France 3:  Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon 4:  UNICEF/UNDP/WORLD BANK/WHO Special Programme for Research and Training in Tropical Diseases, Geneva, Switzerland 5:  Ifakara Health Research and Development Centre, Ifakara, Tanzania 6:  Swiss Tropical Institute, Basel, Switzerland

Publication date: 2006-09-01

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more