Direct assessment in vivo of the efficacy of combined single-dose ivermectin and diethylcarbamazine against adult Wuchereria bancrofti

Abstract

When ivermectin and diethylcarbamazine (DEC) are given simultaneously in a single dose to persons with Wuchereria bancrofti infection, the resulting suppression of microfilaraemia is more profound and sustained than when either drug is given alone. To assess whether this effect is a result of enhanced macrofilaricidal efficacy, we used ultrasound to monitor the adult worms in the scrotal area of men with W. bancrofti microfilaraemia. Twenty-one men were treated simultaneously with DEC (6 mg/kg) and either 200 micrograms/kg or 400 micrograms/kg of ivermectin (11 and 10 men, respectively). Ten other men received a single 200 micrograms/kg dose of ivermectin followed 5 d later by a 6 mg/kg dose of DEC (sequential treatment). All men became amicrofilaraemic after treatment and all except one remained so for one year. Cessation of adult worm movement, indicative of death of all the adult worms in a given 'nest', was observed in none of 30 nests in men who received simultaneous treatment and in 3 of the 19 nests (16%) in the men who received sequential treatment (P = 0.05). Scrotal nodules were detected in 5 of 21 men (24%) who received simultaneous treatment and in 8 men (80%) who received sequential treatment (P < 0.01). Thus, co-administration of ivermectin with DEC seems to interfere with the macrofilaricidal action of DEC. These findings have implications both for treatment of the individual patient and for community-based drug distribution programmes designed to interrupt transmission of W. bancrofti.