Efficacy of injectable versus topical formulation of ivermectin against Anopheles stephensi mosquitoes feeding on different body locations of treated Holstein calves

Abstract

Background: Malaria is a major public health concern and is transmitted to humans by the bite of infected Anopheles mosquitoes. One strategy to reduce populations of zoophagic Anopheles (i.e., likely to feed on other animals as well as humans) is the use of systemic veterinary parasiticides. The most widely systemic parasiticide used for this purpose is ivermectin. Ivermectin is available for livestock in two formulations; injectable and topical "pour-on." The purpose of this study was to evaluate the survival and fecundity of a zoophagic species, Anopheles stephensi, when fed on calves treated with different ivermectin formulations.

Methods: Three groups of four dairy calves were used; calves in one group received a single subcutaneous injection of commercial ivermectin, calves in another group were treated topically once with pour-on ivermectin, and the third group was left untreated. At various times after treatment, groups of mosquitoes were fed simultaneously on different parts of the body to determine if feeding location of mosquitoes influenced the efficacy of treatment. Engorged mosquitoes were maintained for 7 days to monitor survival and fecundity.

Results: Both formulations significantly reduced An. stephensi survival and fecundity for up to 9 and 14 days, respectively, following treatment of calves. Topical formulation of ivermectin applied to the back of the calves significantly reduced the survival of An. stephensi that fed on the back for up to 23 days after treatment, but not for mosquitoes that fed concurrently on the belly or the leg of the same calves, suggesting that a portion of topically applied ivermectin may remain at the site of application. Mosquitoes were less likely to feed on topically treated calves, implying that topical application may confer some mild repellency.

Conclusions: Determining the body location(s) where zoophagic Anopheles mosquitoes feed on livestock (e.g., legs) will allow targeted application and methods (e.g., foot baths) for more efficient use of topical formulations of ivermectin as part of an integrated zoophagic vector management strategy.

Keywords: Anopheles stephensi; Formulation; Ivermectin; Residual malaria.

Fig. 1

Survival curves for cohorts of Anopheles stephensi mosquitoes fed simultaneously on the back, belly, and leg of calves treated with injectable formulation of ivermectin (n = 4), topical formulation of ivermectin (n = 4), and untreated control calves (n = 4)

Fig. 2

Average (± SD) concentration of ivermectin (ng/mL) in the plasma of 6- to 8-week-old Holstein calves at 5, 9, 14, and 23 days after subcutaneous injection (white bars) or topical application of ivermectin (shaded bars). Predicted mortality of Anopheles stephensi mosquitoes as a function of plasma ivermectin is based on the dose–response equation of Dreyer et al. [20]. Actual mortality was quantified in mosquitoes fed directly on the calves from which plasma samples were collected

Fig. 3

Relationship between plasma concentration of ivermectin (log₁₀ ng/mL) at the time of mosquito feeding and subsequent mosquito mortality (probit scale) 7 days after feeding

Fig. 4

Odds ratios (with 95% confidence intervals) comparing the proportion of mosquitoes that blood-fed over a 23-day period on untreated calves (represented by the central dotted line; odds ratio = 1) versus calves treated with subcutaneous injection (open circles) or topical formulation (shaded circles) of ivermectin. Odds ratios greater than one indicate mosquito repellency