Impact of transmission intensity on the accuracy of genotyping to distinguish recrudescence from new infection in antimalarial clinical trials
| Autor: | Alan Hubbard, Grant Dorsey, Philip J. Rosenthal, Bryan Greenhouse, Christian Dokomajilar |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Genetic Markers
medicine.medical_specialty Heterozygote Genotype Plasmodium falciparum Protozoan Proteins Antigens Protozoan Amodiaquine Biology DNA Satellite Clinical Therapeutics law.invention chemistry.chemical_compound Antimalarials law Recurrence Internal medicine medicine Animals Humans Pharmacology (medical) Typing Treatment Failure Malaria Falciparum Genotyping Genotyping Techniques Alleles Merozoite Surface Protein 1 Pharmacology Clinical Trials as Topic Homozygote Clinical trial Infectious Diseases Transmission (mechanics) chemistry Artesunate Immunology medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 51(9) |
| ISSN: | 0066-4804 |
| Popis: | Antimalarial clinical trials use genotyping techniques to distinguish new infection from recrudescence. In areas of high transmission, the accuracy of genotyping may be compromised due to the high number of infecting parasite strains. We compared the accuracies of genotyping methods, using up to six genotyping markers, to assign outcomes for two large antimalarial trials performed in areas of Africa with different transmission intensities. We then estimated the probability of genotyping misclassification and its effect on trial results. At a moderate-transmission site, three genotyping markers were sufficient to generate accurate estimates of treatment failure. At a high-transmission site, even with six markers, estimates of treatment failure were 20% for amodiaquine plus artesunate and 17% for artemether-lumefantrine, regimens expected to be highly efficacious. Of the observed treatment failures for these two regimens, we estimated that at least 45% and 35%, respectively, were new infections misclassified as recrudescences. Increasing the number of genotyping markers improved the ability to distinguish new infection from recrudescence at a moderate-transmission site, but using six markers appeared inadequate at a high-transmission site. Genotyping-adjusted estimates of treatment failure from high-transmission sites may represent substantial overestimates of the true risk of treatment failure. |
| Databáze: | OpenAIRE |
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