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1. Systemic veterinary drugs for control of the common bed bug, Cimex lectularius, in poultry farms

   https://doi.org/10.1186/s13071-022-05555-6  

   González-Morales, Maria A. ; Thomson, Andrea E. ; Petritz, Olivia A. ; Crespo, Rocio ; Haija, Ahmed ; Santangelo, Richard G. ; Schal, Coby ( November 2022 , Parasites & Vectors)

   The common bed bug,CimexlectulariusL., is a hematophagous ectoparasite that was a common pest in poultry farms through the 1960s. Dichlorodiphenyltrichloroethane (DDT) and organophosphates eradicated most infestations, but concurrent with their global resurgence as human ectoparasites, infestations of bed bugs have been reappearing in poultry farms. Although the impact of bed bugs on chicken health has not been quantified, frequent biting and blood-feeding are expected to cause stress, infections and even anemia in birds. Bed bug control options are limited due to the sensitive nature of the poultry environment, limited products labeled for bed bug control and resistance of bed bug populations to a broad spectrum of active ingredients. Veterinary drugs are commonly used to control endo- and ectoparasites in animals. In this study, we evaluated the effects of two common veterinary drugs on bed bugs by treating the host with systemic antiparasitic drugs.

   We conducted dose–response studies of ivermectin and fluralaner against several bed bug strains using a membrane feeding system. Also, different doses of these drugs were given to chickens and two delivery methods (topical treatment and ingestion) were used to evaluate the efficacy of ivermectin and fluralaner on bed bug mortality.

   Using an artificial feeding system, both ivermectin and fluralaner caused high mortality in insecticide-susceptible bed bugs, and fluralaner was found to be effective on pyrethroid- and fipronil-resistant bed bugs. Ivermectin was ineffective in chickens either by the topical treatment or ingestion, whereas bed bugs that fed on chickens which had ingested fluralaner suffered high mortality when feeding on these chickens for up to 28 days post treatment.

   These findings suggest that systemic ectoparasitic drugs have great potential for practical use to control bed bug infestations in poultry farms. These findings also demonstrate the efficacy of fluralaner (and potentially other isoxazolines) as a potent new active ingredient for bed bug control.

    

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2. Comparison of the variability in mortality data generated by CDC bottle bioassay, WHO tube test, and topical application bioassay using Aedes aegypti mosquitoes

   https://doi.org/10.1186/s13071-022-05583-2  

   Althoff, Rachel A. ; Huijben, Silvie ( December 2022 , Parasites & Vectors)

   Insecticide resistance remains a major public health problem. Resistance surveillance is critical for effective vector control and resistance management planning. Commonly used insecticide susceptibility bioassays for mosquitoes are the CDC bottle bioassay and the WHO tube test. Less commonly used in the field but considered the gold standard for assessing insecticide susceptibility in the development of novel insecticides is the topical application bioassay. Each of these bioassays has critical differences in how they assess insecticide susceptibility that impacts their ability to differentiate between resistant and susceptible populations or determine different levels of resistance intensity.

   We compared the CDC bottle bioassay, the WHO tube test, and the topical application bioassay in establishing the dose–response against deltamethrin (DM) using the DM-resistantAedes aegyptistrain MC1. Mosquitoes were exposed to a range of insecticide concentrations to establish a dose–response curve and assess variation around model predictions. In addition, 10 replicates of 20–25 mosquitoes were exposed to a fixed dose with intermediate mortality to assess the degree of variation in mortality.

   The topical application bioassay exhibited the lowest amount of variation in the dose–response data, followed by the WHO tube test. The CDC bottle bioassay had the highest level of variation. In the fixed-dose experiment, a higher variance was similarly found for the CDC bottle bioassay compared with the WHO tube test and topical application bioassay.

   These data suggest that the CDC bottle bioassay has the lowest power and the topical application bioassay the highest power to differentiate between resistant and susceptible populations and assess changes over time and between populations. This observation has significant implications for the interpretation of surveillance results from different assays. Ultimately, it will be important to discuss optimal insecticide resistance surveillance tools in terms of the surveillance objective, practicality in the field, and accuracy of the tool to reach that objective.

    

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3. Resistance to Fipronil in the Common Bed Bug (Hemiptera: Cimicidae)

   https://doi.org/10.1093/jme/tjab040  

   González-Morales, María A ; DeVries, Zachary ; Sierras, Angela ; Santangelo, Richard G ; Kakumanu, Madhavi L ; Schal, Coby ( April 2021 , Journal of Medical Entomology)

   Hribar, Lawrence (Ed.)

   Abstract Cimex lectularius L. populations have been documented worldwide to be resistant to pyrethroids and neonicotinoids, insecticides that have been widely used to control bed bugs. There is an urgent need to discover new active ingredients with different modes of action to control bed bug populations. Fipronil, a phenylpyrazole that targets the GABA receptor, has been shown to be highly effective on bed bugs. However, because fipronil shares the same target site with dieldrin, we investigated the potential of fipronil resistance in bed bugs. Resistance ratios in eight North American populations and one European population ranged from 1.4- to >985-fold, with highly resistant populations on both continents. We evaluated metabolic resistance mechanisms mediated by cytochrome P450s, esterases, carboxylesterases, and glutathione S-transferases using synergists and a combination of synergists. All four detoxification enzyme classes play significant but variable roles in bed bug resistance to fipronil. Suppression of P450s and esterases with synergists eliminated resistance to fipronil in highly resistant bed bugs. Target-site insensitivity was evaluated by sequencing a fragment of the Rdl gene to detect the A302S mutation, known to confer resistance to dieldrin and fipronil in other species. All nine populations were homozygous for the wild-type genotype (susceptible phenotype). Highly resistant populations were also highly resistant to deltamethrin, suggesting that metabolic enzymes that are responsible for pyrethroid detoxification might also metabolize fipronil. It is imperative to understand the origins of fipronil resistance in the development or adoption of new active ingredients and implementation of integrated pest management programs. 

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4. Pharmacokinetics of fluralaner as a systemic drug to control infestations of the common bed bug, Cimex lectularius, in poultry facilities

   https://doi.org/10.1186/s13071-023-05962-3  

   González-Morales, Maria A. ; Thomson, Andrea E. ; Yeatts, James ; Enomoto, Hiroko ; Haija, Ahmed ; Santangelo, Richard G. ; Petritz, Olivia A. ; Crespo, Rocio ; Schal, Coby ; Baynes, Ronald ( September 2023 , Parasites & Vectors)

   Bed bug infestations are re-emerging in the poultry industry throughout the USA. Although the impacts of bed bugs on birds’ health and welfare are poorly understood, adverse outcomes are expected, including stress, anemia, infections and lower production rates. Worker welfare is also an important consideration in commercial poultry farms. A limited number of insecticides are available for use in the complex spatial environment of commercial farms. Systemic drugs have the potential to overcome the limitations of existing pest management tactics. A recent study showed that fluralaner administered to chickens caused high levels of mortality in bed bugs.

   To further understand the efficacy of this approach, we evaluated the pharmacokinetics of an oral solid formulation of fluralaner in 11 chickens and quantified its plasma concentration in chickens using UPLC/MS. We administered fluralaner to chickens with two doses of Bravecto^®(each 0.5 mg/kg body mass) via gavage 1 week apart and evaluated its efficacy on bed bugs that fed on medicated chickens for up to 28 days post-treatment.

   Bed bugs that fed on fluralaner-treated chickens experienced > 50% mortality within 30 min of the administration of Bravecto and 100% mortality 2 days post-treatment. Mortality slowly declined to 66.6% by day 28. Fluralaner was quantifiable in the hens’ plasma for at least 28 days post-treatment. The treatment resulted in maximal plasma concentrations (C_max) of 106.4 ng/ml around day 9.0 (T_max), substantially higher than the LC₉₀, the concentration needed to kill 90% of the bed bugs.

   Fluralaner appears to be a promising candidate for bed bug control in poultry farms, with a treatment effect lasting at least 28 days.

    

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5. A deltamethrin crystal polymorph for more effective malaria control

   https://doi.org/10.1073/pnas.2013390117  

   Yang, Jingxiang ; Erriah, Bryan ; Hu, Chunhua T. ; Reiter, Ethan ; Zhu, Xiaolong ; López-Mejías, Vilmalí ; Carmona-Sepúlveda, Isis Paola ; Ward, Michael D. ; Kahr, Bart ( October 2020 , Proceedings of the National Academy of Sciences)

   Pyrethroid contact insecticides are mainstays of malaria control, but their efficacies are declining due to widespread insecticide resistance inAnophelesmosquito populations, a major public health challenge. Several strategies have been proposed to overcome this challenge, including insecticides with new modes of action. New insecticides, however, can be expensive to implement in low-income countries. Here, we report a simple and inexpensive method to improve the efficacy of deltamethrin, the most active and most commonly used pyrethroid, by more than 10 times againstAnophelesmosquitoes. Upon heating for only a few minutes, the commercially available deltamethrin crystals, form I, melt and crystallize upon cooling into a polymorph, form II, which is much faster acting against fruit flies and mosquitoes. Epidemiological modeling suggests that the use of form II in indoor residual spraying in place of form I would significantly suppress malaria transmission, even in the presence of high levels of resistance. The simple preparation of form II, coupled with its kinetic stability and markedly higher efficacy, argues that form II can provide a powerful, timely, and affordable malaria control solution for low-income countries that are losing protection in the face of worldwide pyrethroid resistance.

    

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