Controle de populações de Triatoma infestans resistentes a piretróides, principal vetor do Trypanosoma cruzi, por meio do tratamento de cães com fluralaner no Chaco argentino / Control de poblaciones de Triatoma infestans resistente a piretroides, principal vector de Trypanosoma cruzi, mediante tratamiento de plantas con fluralaner en el Chaco argentino / Control of populations of pyrethroid-resistant Triatoma infestans, the main vector of Trypanosoma cruzi, through treatment of plants with fluralaner in the Argentine Chaco

We assessed whether fluralaner administered to outbred healthy dogs reduced or supressed site infestation and abundance of pyrethroid-resistant populations of Triatoma infestans Klug (Heteroptera: Reduviidae). We conducted a placebo-controlled before-and-after efficacy trial in 28 infested sites in Castelli (Argentine Chaco) over 10 months. All 72 dogs initially present received either an oral dose of fluralaner (treated group) or placebo (control group) at month 0 posttreatment (MPT). Preliminary results justified treating all 38 control-house dogs with fluralaner 1 month later, and 71 of 78 existing dogs at 7 MPT. Site-level infestation and triatomine abundance were evaluated using timed manual searches with a dislodging aerosol. In the fluralaner-treated group, infestation dropped significantly from 100% at baseline to 19% over 6-10 MPT whereas mean abundance fell highly significantly from 5.5 to 0.8-0.9 triatomines per unit effort. In the placebo group, site infestation and mean abundance remained stable between 0 and 1 MPT, and strongly declined after fluralaner administration from 13.0-14.7 - triatomines at 0-1 MPT to 4.0-4.2 over 6-10 MPT. Only one of 81 noninfested sites before fluralaner treatment became infested subsequently. Fluralaner significantly reduced the site-level infestation and abundance of pyrethroid-resistant T. infestans and should be tested more widely in Phase III efficacy trials.

Control of pyrethroid-resistant populations of Triatoma infestans, the main vector of Trypanosoma cruzi, by treating dogs with fluralaner in the Argentine Chaco

We assessed whether fluralaner administered to outbred healthy dogs reduced or supressed site infestation and abundance of pyrethroid-resistant populations of Triatoma infestans Klug (Heteroptera: Reduviidae). We conducted a placebo-controlled before-and-after efficacy trial in 28 infested sites in Castelli (Argentine Chaco) over 10 months. All 72 dogs initially present received either an oral dose of fluralaner (treated group) or placebo (control group) at month 0 posttreatment (MPT). Preliminary results justified treating all 38 control-house dogs with fluralaner 1 month later, and 71 of 78 existing dogs at 7 MPT. Site-level infestation and triatomine abundance were evaluated using timed manual searches with a dislodging aerosol. In the fluralaner-treated group, infestation dropped significantly from 100% at baseline to 19% over 6-10 MPT whereas mean abundance fell highly significantly from 5.5 to 0.8-0.9 triatomines per unit effort. In the placebo group, site infestation and mean abundance remained stable between 0 and 1 MPT, and strongly declined after fluralaner administration from 13.0-14.7 - triatomines at 0-1 MPT to 4.0-4.2 over 6-10 MPT. Only one of 81 noninfested sites before fluralaner treatment became infested subsequently. Fluralaner significantly reduced the site-level infestation and abundance of pyrethroid-resistant T. infestans and should be tested more widely in Phase III efficacy trials.

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

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.

Insecticidal efficacy of fluralaner (Bravecto®) against Triatoma brasiliensis, a major vector of Trypanosoma cruzi in Brazil

Background: Triatomines are responsible for the vector transmission of the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Triatoma brasiliensis is the main vector of the parasite in Brazil, and dogs are an important reservoir of the parasite. The aim of this study was to evaluate the insecticidal effect of fluralaner (Bravecto®) on T. brasiliensis after a blood meal in treated dogs. Methods: Healthy mongrel dogs (n = 8) were recruited from the Zoonoses Control Center (ZCC) in the city of Natal, Rio Grande do Norte, Brazil, and randomized into two groups, a fluralaner (Bravecto®)-treated group (n = 4) and a control group (n = 4). Colony-reared third-, fourth- and fifth-instar nymphs of T. brasiliensis nymphs (n = 10) were allowed to feed on dogs from both groups for 30-40 min, once monthly, for up to 12 months. Bug mortality was observed up to 5 days after each blood meal. Results: Mortality in triatomines which had a blood meal on fluralaner (Bravecto®)-treated dogs was 100% for up to 7 months after treatment, with mortality decreasing to 66.4% after 8 months, 57% after 9 months, 35% after 10 months, 10% after 11 months and 0% after 12 months. The mortality of triatomines that fed on non-treated control dogs was always ≤ 2.5%. Conclusions: Our results suggest that fluralaner (Bravecto®) treatment of dogs induces long-term mortality of T. brasiliensis after the blood meal. This is a potential approach to be used to control vector transmission of T. cruzi, the etiological agent of Chagas disease, especially in endemic areas.

Insecticidal efficacy of fluralaner (Bravecto®) against Triatoma brasiliensis, a major vector of Trypanosoma cruzi in Brazil

Background: Triatomines are responsible for the vector transmission of the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Triatoma brasiliensis is the main vector of the parasite in Brazil, and dogs are an important reservoir of the parasite. The aim of this study was to evaluate the insecticidal efect of furalaner (Bravecto®) on T. brasiliensis after a blood meal in treated dogs. Methods: Healthy mongrel dogs (n=8) were recruited from the Zoonoses Control Center (ZCC) in the city of Natal, Rio Grande do Norte, Brazil, and randomized into two groups, a furalaner (Bravecto®)-treated group (n=4) and a control group (n=4). Colony-reared third-, fourth- and ffth-instar nymphs of T. brasiliensis nymphs (n=10) were allowed to feed on dogs from both groups for 30­40 min, once monthly, for up to 12 months. Bug mortality was observed up to 5 days after each blood meal. Results: Mortality in triatomines which had a blood meal on furalaner (Bravecto®)-treated dogs was 100% for up to 7 months after treatment, with mortality decreasing to 66.4% after 8 months, 57% after 9 months, 35% after 10 months, 10% after 11 months and 0% after 12 months. The mortality of triatomines that fed on non-treated control dogs was always ≤ 2.5%. Conclusions: Our results suggest that furalaner (Bravecto®) treatment of dogs induces long-term mortality of T. brasiliensis after the blood meal. This is a potential approach to be used to control vector transmission of T. cruzi, the etiological agent of Chagas disease, especially in endemic areas.

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 (50­70%) 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.