Sand fly synthetic sex-aggregation pheromone co-located with insecticide reduces the incidence of infection in the canine reservoir of visceral leishmaniasis: A stratified cluster randomised trial

Abstract

ObjectiveTo evaluate the efficacy of a synthetic sex-aggregation pheromone of the sand fly vector Lu. longipalpis, co-located with residual insecticide, to reduce the infection incidence of Leishmania infantum in the canine reservoir.MethodsA stratified cluster randomised trial was designed to detect a 50% reduction in canine incident infection after 24 months in 42 recruited clusters, randomly assigned to one of three intervention arms (14 cluster each): synthetic pheromone + insecticide, insecticide-impregnated dog collars, or placebo control. Infection incidence was measured by seroconversion to anti-Leishmania serum antibody, Leishmania parasite detection and canine tissue parasite loads. Changes in relative Lu. longipalpis abundance within households were measured by setting three CDC light traps per household.ResultsA total 1,454 seronegative dogs were followed-up for a median 15.2 (95% C.I.s: 14.6, 16.2) months per cluster. The pheromone + insecticide intervention provided 13% (95% C.I. 0%, 44.0%) protection against anti-Leishmania antibody seroconversion, 52% (95% C.I. 6.2%, 74·9%) against parasite infection, reduced tissue parasite loads by 53% (95% C.I. 5.4%, 76.7%), and reduced household female sand fly abundance by 49% (95% C.I. 8.2%, 71.3%). Variation in the efficacy against seroconversion varied between trial strata. Equivalent protection attributed to the impregnated-collars were 36% (95% C.I. 14.4%, 51.8%), 23% (95% C.I. 0%, 57·5%), 48% (95% C.I. 0%, 73.4%) and 43% (95% C.I. 0%, 67.9%), respectively. Comparison of the two interventions showed no statistically consistent differences in their efficacies; however, the errors were broad for all outcomes. Reductions in sand fly numbers were predominant where insecticide was located (chicken and dog sleeping sites), with no evidence of insecticide-induced repellence onto humans or dogs.ConclusionThe synthetic pheromone co-located with insecticide provides protection particularly against canine L. infantum parasite transmission and sand fly vector abundance. The effect estimates are not dissimilar to those of the insecticide-impregnated collars, which are documented to reduce canine infection incidence, human infection and clinical VL disease incidence, in different global regions. The trialled novel lure-and-kill approach is a low-cost potential vector control tool against ZVL in the Americas.

Significant reduction in abundance of peridomestic mosquitoes (Culicidae) and Culicoides midges (Ceratopogonidae) after insecticide intervention in western São Paulo, Brazil

“…longipalpis it would only attract that species [22]. It is unsurprising that the reductions in the biting Diptera was related to the presence of insecticide; the current analyses demonstrate the potential additional bene t of such insecticidal interventions against sand ies [18] and other vectors (i.e. Culicoides and mosquitoes) of other important diseases.…”

“…Data were statistically analysed for impact of insecticide intervention (abundance and distribution) and climatic variables (temperature and rainfall). Household covariate data, the abundance of people, dogs, and chickens were collected separately from Diptera abundance, being recorded once per round as part of routine trial activities [18]. As such, the per household covariate data recorded on the date closest to that of Diptera capture was assumed to be representative for each household.…”

“…Recently, a new vector control approach using a synthetic version of a Lu. longipalpis sex pheromone (9methylgermacrene-B) co-located with microencapsulated lambda-cyhalothrin to reduce vector densities and canine Leishmania infantum infection incidence in dogs, was tested in a large-scale, long-term strati ed randomised control trial (sRCT) in the Araçatuba region of Western São Paulo State, Brazil [18,19]. The trial which also investigated the use of Scalibor ® deltamethrin-impregnated dog collars, an established sand y control device, was carried out in 33 municipalities and 9 districts of Araçatuba.…”

Insecticide-impregnated netting as a potential surface treatment: an alternative to insecticide spraying for control of the leishmaniasis vector Lutzomyia longipalpis (Diptera: Psychodidae)?

“…More extensive trials that co-locate insecticide impregnated net and synthetic sex/aggregation pheromone are required to determine the effectiveness of this approach in an "attract-and-kill" strategy to improve sand y control. A trial of synthetic (±)-9-methylgermacrene-B [25] formulated in a long-lasting controlled release device [26,27] co-located with microencapsulated l-cyhalothrin in chicken roosting sites signi cantly reduced Lu. longipalpis densities, canine Leishmania parasite infection incidence, tissue loads and canine seroconversion incidence [23] indicating the potential of this strategy for reducing disease incidence however replacing the sprayed insecticide application with a netting application could improve the cost of the application and therefore coverage.…”

“…A trial of the synthetic sex/aggregation, (S)-9methylgermacrene-B [24], formulated in a long-lasting controlled release device [20,21] co-located with microencapsulated l-cyhalothrin in chicken roosting sites signi cantly reduced Lu. longipalpis densities, canine Leishmania parasite infection incidence, tissue loads and canine seroconversion incidence establishing the potential for this strategy to reduce disease incidence [25].…”