Hamilton, J. G. | Search bioRxiv

bioRxiv2020

Odour of domestic dogs infected with Leishmania infantum is attractive to female but not male sand flies: evidence for parasite manipulation.

Globally visceral leishmaniasis (VL) causes thousands of human deaths every year. In South America, the etiologic agent, Leishmania infantum, is transmitted from an infected canine reservoir to human hosts by the blood-feeding activity of the sand fly vector, predominantly, Lutzomyia longipalpis. Previous evidence from model rodent systems have suggested that the odour of infected hosts is altered by the parasite making them more attractive to the vector leading to an increased biting rate and improved transmission prospects for the pathogen. However, the effect of Le. infantum infection on the attractiveness of naturally infected dogs which are integral to human infection, has not been assessed. Hair collected from infected and uninfected dogs residing in a VL endemic city in Brazil. was entrained to collect the volatile chemical odours present in the headspace. Female and male Lu. longipalpis sand flies were offered a choice of infected or uninfected odour in a series of behavioural experiments. Control experiments established that female and male Lu. longipalpis were equally attracted to uninfected dog odour, female Lu. longipalpis were significantly more attracted to infected dog odour than uninfected dog odour in all 15 experimental replicates (average 45.7{+/-}0.87 females attracted to infected odour; 23.9{+/-}0.82 to uninfected odour; paired T-test, P=0.000). Male Lu. longipalpis did not significantly prefer either infected or uninfected odour (average 36.1{+/-}0.4 males to infected odour; 35.7{+/-}0.6 to uninfected odour; paired T-test, P=0.722). A significantly greater proportion of females chose the infected dog odour compared to the males (paired T-test, P=0.000). The results show that dogs infected with Le. infantum are significantly more attractive to blood-feeding female than male sand flies. This is strong evidence for parasite manipulation of the host odour in a natural transmission system and indicates that infected dogs may have a disproportionate significance in maintaining infection in canine and human infection. Author SummaryVisceral leishmaniasis (VL) is a disease caused by the Protist parasite Leishmania infantum. In Brazil and other South and Central American countries, the parasite is transmitted by the blood-feeding activity of infected female Lutzomyia longipalpis sand flies. The disease leads to thousands of human cases and deaths every year. Domestic dogs are the reservoir of infection for humans therefore understanding the effect of infection on dogs is important in developing an understanding of the epidemiology of the disease. Although previous studies on rodent models of Le. infantum infection have shown that infected Golden Hamsters are more attractive to Lu. longipalpis the attractiveness of naturally infected dogs to the insect vector has not been previously been investigated. In this study we showed that the odour of infected dogs is significantly more attractive to female sand flies which can transmit the pathogen than to male sand flies which do not. This clear-cut difference in attraction of female and males suggests that the females are preferentially attracted by parasite infected hosts and may lead to enhanced infection and transmission opportunities for the parasite.

ecology↗

bioRxiv2019

Sand fly synthetic sex-aggregation pheromone co-located with insecticide reduces canine Leishmania infantum infection incidence: a stratified cluster randomised trial

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, and to reduce sand fly vector abundance. To compare the outcomes to those resulting from fitting deltamethrin-impregnated collars to the canine reservoir.\n\nMethodsA 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): pheromone + insecticide, insecticide-impregnated dog collars, or placebo control. Infection incidence was measured by seroconversion to anti-Leishmania 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.\n\nResultsA total 1,454 seronegative dogs were follow-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{middle dot}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{middle dot}5%), 48% (95% C.I. 0%, 73.4%) and 43% (95% C.I. 0%, 67.9%), respectively. Comparison of the outcomes 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 repellency onto humans or dogs.\n\nConclusionThe synthetic pheromone lure-and-kill approach provides protection particularly against 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, and human infection and clinical VL disease incidence, in different global regions. As a low-cost alternative or complimentary vector control tool, optimisation of best community deployment of the pheromone + insecticide are now underway.\n\nAuthor summaryThe sand fly vector of the intracellular parasite Leishmania infantum causing human and canine visceral leishmaniasis in the Americas is Lutzomyia longipalpis. Dogs are the proven reservoir. Vector control tools to reduce transmission suited to this predominantly exophilic vector are lacking. Insecticide-impregnated dog collars protect dogs against infectious bites from sand fly vectors, resulting in reductions of new infections in both dogs and humans. However, collars are costly particularly for endemic communities, and alternative approaches are needed. Recent bulk synthesis of a sex-aggregation pheromone produced by male Lu. longipalpis was shown to attract large numbers of conspecific females to lethal pyrethroid insecticides. This study, conducted in Brazil, evaluated the efficacy of this novel lure-and-kill approach to reduce seroconversion and infection incidence with L. infantum in the canine reservoir, in addition to measuring its impact on household abundance of Lu. longipalpis. Deployed in 14 stratified clusters, the outcomes were compared to those resulting attributed to the collars fitted to dogs in another 14 clusters; each intervention was compared to the 14 clusters that received placebo treatments. The beneficial effects of the lure-and-kill method were most noticeable on confirmed infection incidence and clinical parasite loads, and in reducing sand fly abundance. The overall effect of the two interventions were not statistically dissimilar, though the confidence intervals were broad. We conclude that the novel low-cost lure-and-kill approach should be added to the vector control toolbox against visceral leishmaniasis in the Americas.

microbiology↗