Modeling the impact of xenointoxication in dogs to halt Trypanosoma cruzi transmission

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.

Effectiveness of Systemic Insecticide Dog Treatment for the Control of Chagas Disease in the Tropics

“…These interventions have the potential to be cost-effective in reducing T. cruzi infection in humans [ 35 ]. Annual treatment of dogs with fluralaner may be effective in reducing infection rates in high transmission settings, but caution is needed in low transmission settings [ 36 ]. However, there is a potential counterproductive effect as dogs may ingest treated infected triatomines, increasing infection rates in the dog population.…”

“…The Ross-MacDonald theory has made significant contributions to the advancement of quantitative theory and basic principles of epidemiology, particularly in the context of vector-borne diseases [ 37 , 38 ]. Mathematical models have been developed to study and better understand the dynamics of T. cruzi transmission with an emphasis on protecting human health [ 36 , 39 , 40 , 41 , 42 , 43 ]. Mathematical modeling techniques provide valuable insights into the cycle of T. cruzi transmission and the potential impacts of host-targeted interventions.…”