Xenointoxication of a Rabbit for the Control of the Common Bed Bug Cimex lectularius L. Using Ivermectin

Abstract

Human bed bug infestations have undergone a recent global resurgence. The human antiparasitic drug ivermectin has been proposed as a strategy to help control bed bug infestations, but in vivo data are lacking. We allowed separate populations of the common bed bug, Cimex lectularius L., to feed once on a rabbit before and after it was injected subcutaneously with 0.3 mg/kg of ivermectin, and bed bug morbidity and mortality were recorded. Ivermectin levels in the rabbit were measured using high-performance liquid chromatography and mass spectroscopy. Ivermectin blood levels of ∼2 ng/mL caused reductions in bed bug fecundity, and levels of >8 ng/mL caused bed bug death and long-term morbidity including reductions in refeeding, mobility, reproduction, and molting. Gut bacterial cultures from the fed bed bugs showed that ivermectin altered the bed bug gut microbiome.

Ivermectin and Moxidectin Can Incapacitate Different Strains of the Common Bed Bug Cimex lectularius L.: A Study

“…Laboratory strains of bed bugs were used and pyrethroid-resistance could have waned over time without repeated exposure to pyrethroids. Lastly, all the life stages of the bed bugs were not recorded; so we were unable to ascertain from these experiments if ivermectin and moxidectin adversely affected all life stages similarly; however, this has been examined previously [5,7,[9][10].…”

“…The drug was still detectable in the insect one month after the feeding. The long-term persistence of ivermectin in the bed bug may help explain why the insects that survive a sublethal dose of ivermectin can manifest long-term morbidity [6,7,[9][10]. The ivermectin fed to bed bugs in our experiments was diluted in DMSO, an aprotic solvent miscible in many organic solvents and water; hence, future experiments should ideally measure ivermectin levels in bed bugs for longer periods of time, from multiple C. lectularius strains, and from in vivo ivermectin blood meals.…”

“…Ivermectin is administered to about 250 million people annually, mostly as part of mass drug administration programs in developing countries [3]. The antiparasitic drugs ivermectin and moxidectin have limited human toxicity at therapeutic doses, and both have been shown to kill bed bugs that consume blood meals spiked with these drugs in a dose-dependent manner [4][5][6][7][8][9][10]. Bed bugs that survive blood meals containing ivermectin or moxidectin suffer long-term harm including reduced fecundity, inhibition of nymphal molting, delays in blood meal digestion, and reduced locomotion [5][6][7][8][9][10].…”

“…The antiparasitic drugs ivermectin and moxidectin have limited human toxicity at therapeutic doses, and both have been shown to kill bed bugs that consume blood meals spiked with these drugs in a dose-dependent manner [4][5][6][7][8][9][10]. Bed bugs that survive blood meals containing ivermectin or moxidectin suffer long-term harm including reduced fecundity, inhibition of nymphal molting, delays in blood meal digestion, and reduced locomotion [5][6][7][8][9][10]. However, previous research on ivermectin has involved laboratory-adapted bed bugs with an unknown sensitivity to the pyrethroids and neonicotinoids; and there has only been one study using moxidectin and the Irvington stain, which is known to have moderate resistance to pyrethroids [6][7][8].…”

“…Ivermectin is known to act at the invertebrate glutamate-gated chloride channel, causing nerve and muscle hyperpolarization [12]. The pharmacotoxicity of a sublethal dose of ivermectin against C. lectularius is unknown but could be multifactorial including the persistence of ivermectin in the insect, changes in gene expression, or damage to C. lectularius organs [6][7][8][9][10]. Therefore, an additional objective was to quantify ivermectin levels in fed bed bugs.…”