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.

Fig 1. Single fluralaner treatment in a high prevalence region.

Proportions of dogs and bugs infected with T. cruzi after single administration of fluralaner treatment at equilibrium (27.4 years) in a region of high prevalence of endemic disease and domestic vectors was simulated.

Fig 2. Multiple fluralaner treatments in a high prevalence region.

Treatment scenarios were simulated for equilibrium populations of bugs and dogs in a region of high prevalence of endemic disease and domestic vectors. Annual administration of fluralaner for both 4 years (A) and 6 years (B) was simulated, as well as administration every 90 days (veterinary recommendation) for one year (C) and for two years (D).

Fig 3. Fluralaner treatment schemes in low prevalence regions.

Simulations were conducted to explore the effect of fluralaner treatment of regions of low prevalence of endemic disease and domestic vectors in equilibrium; we explored a range of dog average lifespan from 3 years (A-C) to 6 years (D-F). Treatment scenarios include one time treatment (A, D), annual treatment for 4 years (B, E), and treatment every 90 days for 1 year (C, F).

Fig 4. Fluralaner treatment schemes in low prevalence regions with semi-sylvatic transmission.

Simulations were conducted to explore the effect of fluralaner treatment of regions of low prevalence of endemic disease and domestic vectors as well as semi-sylvatic vectors in equilibrium; we explored a range of dog average lifespan from 3 years (A-C) to 6 years (D-F). Treatment scenarios include one time treatment (A, D), annual treatment for 4 years (B, E), and treatment every 90 days for 1 year (C, F).

Fig 5. Mathematical models of T. cruzi transmission dynamics between dogs and T. infestans in domestic and sylvatic cycles.

Dashed lines represent transmission events and solid lines represent transition between states. Prior to treatment, only vectorial transmission (blue lines) is considered to transition susceptible dogs (1-X) to infectious (X). Susceptible bugs (1-X) are replenished by a logistic birth rate. After administration of fluralaner, there are two transmission routes to infect susceptible dogs: vectorial transmission as before (blue line) and oral transmission (yellow line). In the sylvatic cycle, vectorial transmission is constant due to exposure to external infectious bugs (MM).