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      A Preliminary Report Showing Spinosad and Fluralaner Are Able to Incapacitate Cimex lectularius L., the Common Bed Bug

      research-article
      1 ,
      ,
      Cureus
      Cureus
      bed bug, cimex lectularius, fluralaner, spinosad, bedbug, drug, treatment, veterinary, xenointoxication

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          Abstract

          Cimex lectularius L., the common bed bug, is a hematophagous human ectoparasite. The veterinary drugs, spinosad and fluralaner, were studied for their ability to incapacitate C. lectularius when administered in a blood meal using an artificial feeding system under laboratory conditions. Tested drug doses were based on the reported peak blood levels in animals given the drugs. Spinosad at doses 1,000 ng/mL or higher resulted in 75% or greater bed bug incapacitation (defined as death or immobility). Fluralaner at doses 500 ng/mL or higher had 100% bed bug incapacitation. Both drugs were significantly more effective than controls at these doses ( < 0.001).

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          Bed bugs: clinical relevance and control options.

          Since the late 1990s, bed bugs of the species Cimex lectularius and Cimex hemipterus have undergone a worldwide resurgence. These bed bugs are blood-sucking insects that readily bite humans. Cutaneous reactions may occur and can start out as small macular lesions that can develop into distinctive wheals of around 5 cm in diameter, which are accompanied by intense itching. Occasionally, bullous eruptions may result. If bed bugs are numerous, the patient can present with widespread urticaria or eythematous rashes. Often, bites occur in lines along the limbs. Over 40 pathogens have been detected in bed bugs, but there is no definitive evidence that they transmit any disease-causing organisms to humans. Anemia may result when bed bugs are numerous, and their allergens can trigger asthmatic reactions. The misuse of chemicals and other technologies for controlling bed bugs has the potential to have a deleterious impact on human health, while the insect itself can be the cause of significant psychological trauma. The control of bed bugs is challenging and should encompass a multidisciplinary approach utilizing nonchemical means of control and the judicious use of insecticides. For accommodation providers, risk management procedures should be implemented to reduce the potential of bed bug infestations.
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            Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases

            Reduction in clinical cases of vector-borne diseases is strongly dependent on the ability to reduce the number of infectious insect bites. Here we describe a treatment concept based on single-dose administration of an insecticidal isoxazoline drug to a human population, which leads to killing of blood-fed insect vectors and a predicted sharp decline in disease transmission. Based on the long half-life observed in preclinical species, a single human dose of <500 mg is predicted to provide plasma exposure above the insecticidal threshold for longer than 2 months. Importantly, we show that isoxazolines are active against a range of vector species, which holds promise for expanding the concept of drug-based vector control from malaria to leishmaniasis and arboviral diseases. Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite control in companion animals. Here we propose their use in humans for the reduction of vector-borne disease incidence. Fluralaner and afoxolaner rapidly killed Anopheles , Aedes , and Culex mosquitoes and Phlebotomus sand flies after feeding on a drug-supplemented blood meal, with IC 50 values ranging from 33 to 575 nM, and were fully active against strains with preexisting resistance to common insecticides. Based on allometric scaling of preclinical pharmacokinetics data, we predict that a single human median dose of 260 mg (IQR, 177–407 mg) for afoxolaner, or 410 mg (IQR, 278–648 mg) for fluralaner, could provide an insecticidal effect lasting 50–90 days against mosquitoes and Phlebotomus sand flies. Computational modeling showed that seasonal mass drug administration of such a single dose to a fraction of a regional population would dramatically reduce clinical cases of Zika and malaria in endemic settings. Isoxazolines therefore represent a promising new component of drug-based vector control.
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              Systemic insecticide treatment of the canine reservoir of Trypanosoma cruzi induces high levels of lethality in Triatoma infestans, a principal vector of Chagas disease

              Background Despite large-scale reductions in Chagas disease prevalence across Central and South America, Trypanosoma cruzi infection remains a considerable public health problem in the Gran Chaco region where vector-borne transmission persists. In these communities, peridomestic animals are major blood-meal sources for triatomines, and household presence of infected dogs increases T. cruzi transmission risk for humans. To address the pressing need for field-friendly, complementary methods to reduce triatomine infestation and interrupt T. cruzi transmission, this study evaluated the systemic activity of three commercial, oral, single dose insecticides Fluralaner (Bravecto®), Afoxolaner (NexGard®) and Spinosad (Comfortis®) in canine feed-through assays against Triatoma infestans, the principal domestic vector species in the Southern Cone of South America. Methods Twelve healthy, outbred dogs were recruited from the Zoonosis Surveillance and Control Program in Santa Cruz, Bolivia, and randomized to three treatment groups, each containing one control and three treated dogs. Following oral drug administration, colony-reared second and third stage T. infestans instars were offered to feed on dogs for 30 min at 2, 7, 21, 34 and 51 days post-treatment. Results Eighty-five per cent (768/907) of T. infestans successfully blood-fed during bioassays, with significantly higher proportions of bugs becoming fully-engorged when exposed to Bravecto® treated dogs (P < 0.001) for reasons unknown. Exposure to Bravecto® or NexGard® induced 100% triatomine mortality in fully- or semi-engorged bugs within 5 days of feeding for the entire follow-up period. The lethality effect for Comfortis® was much lower (50–70%) and declined almost entirely after 51 days. Instead Comfortis® treatment resulted in substantial morbidity; of these, 30% fully recovered whereas 53% remained morbid after 120 h, the latter subsequently unable to feed 30 days later. Conclusions A single oral dose of Fluralaner or Afoxolaner was safe and well tolerated, producing complete triatomine mortality on treated dogs over 7.3 weeks. While both drugs were highly efficacious, more bugs exposed to Fluralaner took complete blood-meals, and experienced rapid knock-down. Coupled with its longer residual activity, Fluralaner represents an ideal insecticide for development into a complementary, operationally-feasible, community-level method of reducing triatomine infestation and potentially controlling T. cruzi transmission, in the Gran Chaco region.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                3 April 2020
                April 2020
                : 12
                : 4
                : e7529
                Affiliations
                [1 ] Emergency Medicine, Mayo Clinic, Jacksonville, USA
                Author notes
                Article
                10.7759/cureus.7529
                7198093
                32377477
                75b2b3ad-8dde-43e6-9775-40d4f77ef5a0
                Copyright © 2020, Sheele et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 December 2019
                : 27 January 2020
                Categories
                Miscellaneous
                Infectious Disease
                Public Health

                bed bug,cimex lectularius,fluralaner,spinosad,bedbug,drug,treatment,veterinary,xenointoxication

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