Population genetics of concurrent selection with albendazole and ivermectin or diethylcarbamazine on the possible spread of albendazole resistance in Wuchereria bancrofti.
The Global Program for the Elimination of Lymphatic Filariasis (GPELF) intends to achieve its aims through yearly mass treatments with albendazole (ABZ) combined with ivermectin (IVM) or diethylcarbamazine (DEC). The use of ABZ and IVM separately to combat parasites of veterinary importance has, on many occasions, resulted in widespread drug resistance. In order to help predict the spread of potential ABZ resistance alleles through a population of Wuchereria bancrofti, we have developed a mathematical model that incorporates population genetics into EPIFIL, a model which examines the transmission dynamics of the parasite. Our model considers the effect of the combined treatments on the frequency of a recessive allele, which confers ABZ resistance. The model predicts that after 10 yearly treatments with ALB and DEC, 85% coverage and an initial resistance allele frequency of 5%, the frequency of the resistance genotype will increase from 0.25 to 12.7%. If non-random mating is assumed, the initial genotype frequency will be 2.34% and will increase to 62.7%. ABZ and IVM combination treatment may lead to weaker selection for this genotype. Treatment coverage, initial allele frequencies and number of treatments also affect the rate of selection.
Schwab
A E
AE
Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec, Canada, H9X 3V9.
Churcher
T S
TS
Schwab
A J
AJ
Basáñez
M-G
MG
Prichard
R K
RK
D015766:Albendazole / Q000494:pharmacology* / Q000627:therapeutic use; D000483:Alleles; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology* / Q000627:therapeutic use; D000977:Antiparasitic Agents / Q000494:pharmacology / Q000627:therapeutic use; D009033:Culicidae / Q000469:parasitology; D004049:Diethylcarbamazine / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics*; D004359:Drug Therapy, Combination; D005368:Filariasis / Q000188:drug therapy / Q000469:parasitology*; D005369:Filaricides / Q000494:pharmacology* / Q000627:therapeutic use; D005787:Gene Frequency / Q000235:genetics; D005828:Genetics, Population; D007559:Ivermectin / Q000494:pharmacology* / Q000627:therapeutic use; D008954:Models, Biological; D012641:Selection, Genetic; D013997:Time Factors; D014958:Wuchereria bancrofti / Q000187:drug effects / Q000235:genetics*
D000871:Anthelmintics; D000977:Antiparasitic Agents; D005369:Filaricides; D007559:Ivermectin; D015766:Albendazole; D004049:Diethylcarbamazine