Effectiveness of fluralaner treatment regimens for the control of canine Chagas disease: A mathematical modeling study

Abstract

Background: Canine Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and transmitted by insect triatomine vectors known as kissing bugs. The agent can cause cardiac damage and long-term heart disease and death in humans, dogs, and other mammals. In laboratory settings, treatment of dogs with systemic insecticides has been shown to be highly efficacious at killing triatomines that feed on treated dogs.

Method: We developed compartmental vector-host models of T. cruzi transmission between the triatomine and dog population accounting for the impact of seasonality and triatomine migration on disease transmission dynamics. We considered a single vector-host model without seasonality, and model with seasonality, and a spatially coupled model. We used the models to evaluate the effectiveness of the insecticide fluralaner with different durations of treatment regimens for reducing T. cruzi infection in different transmission settings.

Results: In low and medium transmission settings, our model showed a marginal difference between the 3-month and 6-month regimens for reducing T. cruzi infection among dogs. The difference increases in the presence of seasonality and triatomine migration from a sylvatic transmission setting. In high transmission settings, the 3-month regimen was substantially more effective in reducing T. cruzi infections in dogs than the other regimens. Our model showed that increased migration rate reduces fluralaner effectiveness in all treatment regimens, but the relative reduction in effectiveness is minimal during the first years of treatment. However, if an additional 10% or more of triatomines killed by dog treatment were eaten by dogs, treatment could increase T. cruzi infections in the dog population at least during the first year of treatment.

Conclusion: Our analysis shows that treating all peridomestic dogs every three to six months for at least five years could be an effective measure to reduce T. cruzi infections in dogs and triatomines in peridomestic transmission settings. However, further studies at the local scale are needed to better understand the potential impact of routine use of fluralaner treatment on increasing dogs' consumption of dead triatomines.

Fig 1. Single vector-host population model structure.

Fig 2. Model structure with treatment.

TS_b1 and TI_b1 is the density of susceptible and infected adult bugs that feed on fluralaner-treated dogs and will die from fluralaner intoxication.

Fig 3. Effectiveness of systemic insecticide treatment of dogs with fluralaner for the control of canine Chagas in a high transmission setting with 3-month, 6-month, 9-month, and 12-month treatment regimens using Model 1.

(A) Reduction of total population density (blue) and T. cruzi infections in triatomines (red), (B) Reduction of T. cruzi infection prevalence (red) and incidence in dogs (blue). Effectiveness is evaluated using the single vector-host model without seasonality.

Fig 4. Relative effectiveness of dog treatment regimen for reducing T.

cruzi infections among dogs and triatomines compared to a 12-month treatment regimen using Model 1. Effectiveness is computed using the single host-vector model without seasonality. (A) Cumulative additional dog infections averted under the 3-month, 6-month, and 9-month regimen relative to the 12-month regimen in the low, medium, and high transmission settings. (B) Cumulative additional triatomine infections averted under the 3-month, 6-month, and 9-month regimen relative to the 12-month regimen in the low, medium, and high transmission settings.

Fig 5. Effectiveness of systemic insecticide treatment of dogs with fluralaner for the control of canine Chagas in a high transmission setting with 3-month, 6-month, 9-month, and 12-month treatment regimens using Model 2.

(A) Reduction of total population density (blue) and T. cruzi infections in triatomines (red), (B) Reduction of T. cruzi infection prevalence (red) and incidence in dogs (blue). Effectiveness is evaluated using the single vector-host model with seasonality.

Fig 6. Relative effectiveness of dog treatment regimen for reducing T.

cruzi infections among dogs and triatomines compared to a 12-month treatment regimen using Model 2. Effectiveness is computed using the single host-vector model with seasonality. (A) Cumulative additional dog infections averted under the 3-month, 6-month, and 9-month regimen relative to the 12-month regimen in the low, medium, and high transmission settings. (B) Cumulative additional triatomine infections averted under the 3-month, 6-month, and 9-month regimen relative to the 12-month regimen in the low, medium, and high transmission settings.

Fig 7. Effectiveness of systemic insecticide treatment of dogs with fluralaner for the control of canine Chagas in a high transmission setting with 3-month, 6-month, 9-month, and 12-month treatment regimens using Model 3.

(A) Reduction of total population density (blue) and T. cruzi infections in triatomines (red), (B) Reduction of T. cruzi infection prevalence (red) and incidence in dogs (blue). Effectiveness is evaluated using the spatially coupled model.

Fig 8. Relative effectiveness of dog treatment regimen for reducing T.

cruzi infections among dogs and triatomines compared to a 12-month treatment regimen using Model 3. Effectiveness is computed using the spatially coupled model. (A) Cumulative additional dog infections averted under the 3-month, 6-month, and 9-month regimen relative to the 12-month regimen in the low, medium, and high transmission settings. (B) Cumulative additional triatomine infections averted under the 3-month, 6-month, and 9-month regimen relative to the 12-month regimen in the low, medium, and high transmission settings.

Fig 9. Impact of triatomine migration rate between sylvatic and peridomestic communities on the effectiveness of fluralaner treatment regimens for reducing dog T. cruzi prevalence.

Fig 10. Impact of increased consumption of dead triatomines by dogs on the effectiveness of fluralaner treatment regimens for reducing dog T. cruzi prevalence.

We consider four scenarios: 1) no increased consumption of dead bugs, 2) 10% of bugs killed by fluralaner treatment are eaten by dogs, and 3) 30% of bugs killed by fluralaner treatment are eaten by dogs, and 4) 50% of bugs killed by fluralaner treatment are eaten by dogs.