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1.
PLoS Comput Biol ; 19(5): e1011115, 2023 05.
Article in English | MEDLINE | ID: mdl-37155680

ABSTRACT

BACKGROUND: Chagas disease, a vector-borne parasitic disease caused by Trypanosoma cruzi, affects millions in the Americas. Dogs are important reservoirs of the parasite. Under laboratory conditions, canine treatment with the systemic insecticide fluralaner demonstrated efficacy in killing Triatoma infestans and T. brasiliensis, T. cruzi vectors, when they feed on dogs. This form of pest control is called xenointoxication. However, T. cruzi can also be transmitted orally when mammals ingest infected bugs, so there is potential for dogs to become infected upon consuming infected bugs killed by the treatment. Xenointoxication thereby has two contrasting effects on dogs: decreasing the number of insects feeding on the dogs but increasing opportunities for exposure to T. cruzi via oral transmission to dogs ingesting infected insects. OBJECTIVE: Examine the potential for increased infection rates of T. cruzi in dogs following xenointoxication. DESIGN/METHODS: We built a deterministic mathematical model, based on the Ross-MacDonald malaria model, to investigate the net effect of fluralaner treatment on the prevalence of T. cruzi infection in dogs in different epidemiologic scenarios. We drew upon published data on the change in percentage of bugs killed that fed on treated dogs over days post treatment. Parameters were adjusted to mimic three scenarios of T. cruzi transmission: high and low disease prevalence and domestic vectors, and low disease prevalence and sylvatic vectors. RESULTS: In regions with high endemic disease prevalence in dogs and domestic vectors, prevalence of infected dogs initially increases but subsequently declines before eventually rising back to the initial equilibrium following one fluralaner treatment. In regions of low prevalence and domestic or sylvatic vectors, however, treatment seems to be detrimental. In these regions our models suggest a potential for a rise in dog prevalence, due to oral transmission from dead infected bugs. CONCLUSION: Xenointoxication could be a beneficial and novel One Health intervention in regions with high prevalence of T. cruzi and domestic vectors. In regions with low prevalence and domestic or sylvatic vectors, there is potential harm. Field trials should be carefully designed to closely follow treated dogs and include early stopping rules if incidence among treated dogs exceeds that of controls.


Subject(s)
Chagas Disease , Insecticides , Triatoma , Trypanosoma cruzi , Animals , Dogs , Insect Vectors , Chagas Disease/epidemiology , Chagas Disease/prevention & control , Chagas Disease/veterinary , Triatoma/parasitology , Insecticides/pharmacology , Mammals
2.
medRxiv ; 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36747723

ABSTRACT

Background: Chagas disease, a vector-borne parasitic disease caused by Trypanosoma cruzi , affects millions in the Americas. Dogs are important reservoirs of the parasite. Under laboratory conditions, canine treatment with the systemic insecticide fluralaner demonstrated efficacy in killing Triatoma infestans and T. brasiliensis, T. cruzi vectors, when they feed on dogs. This form of pest control is called xenointoxication. However, T. cruzi can also be transmitted orally when mammals ingest infected bugs, so there is potential for dogs to become infected upon consuming infected bugs killed by the treatment. Xenointoxication thereby has two contrasting effects on dogs: decreasing the number of insects feeding on the dogs but increasing opportunities for exposure to T. cruzi via oral transmission to dogs ingesting infected insects. Objective: Examine the potential for increased infection rates of T. cruzi in dogs following xenointoxication. Design/Methods: We built a deterministic mathematical model, based on the Ross-MacDonald malaria model, to investigate the net effect of fluralaner treatment on the prevalence of T. cruzi infection in dogs in different epidemiologic scenarios. We drew upon published data on the change in percentage of bugs killed that fed on treated dogs over days post treatment. Parameters were adjusted to mimic three scenarios of T. cruzi transmission: high and low disease prevalence and domestic vectors, and low disease prevalence and sylvatic vectors. Results: In regions with high endemic disease prevalence in dogs and domestic vectors, prevalence of infected dogs initially increases but subsequently declines before eventually rising back to the initial equilibrium following one fluralaner treatment. In regions of low prevalence and domestic or sylvatic vectors, however, treatment seems to be detrimental. In these regions our models suggest a potential for a rise in dog prevalence, due to oral transmission from dead infected bugs. Conclusion: Xenointoxication could be a beneficial and novel One Health intervention in regions with high prevalence of T. cruzi and domestic vectors. In regions with low prevalence and domestic or sylvatic vectors, there is potential harm. Field trials should be carefully designed to closely follow treated dogs and include early stopping rules if incidence among treated dogs exceeds that of controls. Author summary: Chagas disease, caused by the parasite Trypanosoma cruzi , is transmitted via triatomine insect vectors. In Latin America, dogs are a common feeding source for triatomine vectors and subsequently an important reservoir of T. cruzi . One proposed intervention to reduce T. cruzi transmission is xenointoxication: treating dogs with oral insecticide to kill triatomine vectors in order to decrease overall T. cruzi transmission. Fluralaner, commonly administered to prevent ectoparasites such as fleas and ticks, is effective under laboratory conditions against the triatomine vectors. One concern with fluralaner treatment is that rapid death of the insect vectors may make the insects more available to oral ingestion by dogs; a more effective transmission pathway than stercorarian, the usual route for T. cruzi transmission. Using a mathematical model, we explored 3 different epidemiologic scenarios: high prevalence endemic disease within a domestic T. cruzi cycle, low prevalence endemic disease within a domestic T. cruzi cycle, and low prevalence endemic disease within a semi-sylvatic T. cruzi cycle. We found a range of beneficial to detrimental effects of fluralaner xenointoxication depending on the epidemiologic scenario. Our results suggest that careful field trials should be designed and carried out before wide scale implementation of fluralaner xenointoxication to reduce T. cruzi transmission.

3.
Hum Genet ; 140(11): 1505-1515, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33547946

ABSTRACT

Vast progress has been made in the clinical diagnosis and molecular basis of hereditary diseases and genetic predisposition in companion animals. The purpose of this report is to provide an update on the availability of DNA testing for hereditary diseases and genetic predispositions in dogs and cats utilizing the WSAVA-PennGen DNA Testing Database web resource (URL: http://research.vet.upenn.edu/WSAVA-LabSearch ). Information on hereditary diseases, DNA tests, genetic testing laboratories and afflicted breeds added to the web-based WSAVA-PennGen DNA Testing Database was gathered. Following verification through original research and clinical studies, searching various databases on hereditary diseases in dogs and cats, and contacting laboratories offering DNA tests, the data were compared to the resource reported on in 2013. The number of molecularly defined Mendelian inherited diseases and variants in companion animals listed in the WSAVA-PennGen DNA Testing Database in 2020 drastically increased by 112% and 141%, respectively. The number of DNA variant tests offered by each laboratory has also doubled for dogs and cats. While the overall number of laboratories has only slightly increased from 43 to 47, the number of larger corporate laboratories increased, while academic laboratories have declined. In addition, there are now several laboratories that are offering breed-specific or all-breed panel tests rather than single-DNA tests for dogs and cats. This unique regularly updated searchable web-based database allows veterinary clinicians, breeders and pet owners to readily find available DNA tests, laboratories performing these DNA tests worldwide, and canine and feline breeds afflicted and also serves as a valuable resource for comparative geneticists.


Subject(s)
Cat Diseases/genetics , Dog Diseases/genetics , Genetic Diseases, Inborn/veterinary , Genetic Predisposition to Disease , Genetic Testing/veterinary , Internet , Animals , Cats , Databases, Factual , Dogs , Genetic Diseases, Inborn/genetics
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