Modelling Sand Fly Lutzomyia longipalpis Attraction to Host Odour: Synthetic Sex-Aggregation Pheromone Dominates the Response

Zoontic visceral leishmaniasis (ZVL) due to Leishmania infantum is a potentially fatal protozoan parasitic disease of humans and dogs. In the Americas, dogs are the reservoir and the sand fly, Lutzomyia longipalpis, the principal vector. A synthetic version of the male sand fly produced sex-aggregation pheromone attracts both female and male conspecifics to co-located insecticide, reducing both reservoir infection and vector abundance. However the effect of the synthetic pheromone on the vector’s “choice“ of host (human, animal reservoir, or dead-end host) for blood feeding in the presence of the pheromone is less well understood. In this study, we developed a modelling framework to allow us to predict the relative attractiveness of the synthetic pheromone and potential alterations in host choice. Our analysis indicates that the synthetic pheromone can attract 53% (95% CIs: 39%–86%) of host-seeking female Lu. longipalpis and thus it out-competes competing host odours. Importantly, the results suggest that the synthetic pheromone can lure vectors away from humans and dogs, such that when co-located with insecticide, it provides protection against transmission leading to human and canine ZVL.

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

10.21203/rs.3.rs-52839/v1 ◽

2020 ◽

Author(s):

Vanessa Barbosa ◽

Cristian F Souza ◽

Derek Gatherer ◽

Reginaldo P Brazil ◽

James Gordon Campbell Hamilton

Keyword(s):

Aggregation Pheromone ◽

Leishmania Infantum ◽

Intervention Studies ◽

Potential Surface ◽

Lower Proportion ◽

Sand Fly ◽

Lutzomyia Longipalpis ◽

Sand Flies ◽

Synthetic Pheromone ◽

Canine Infection

Abstract Background: The sand fly, Lutzomyia longipalpis, is the main vector of Leishmania infantum in Brazil. A previous laboratory study showed that covering surfaces with insecticide-impregnated netting may provide an alternative method for killing sand flies. Synthetic male Lu. longipalpis sex/aggregation pheromone co-located with micro-encapsulated l-cyhalothrin demonstrated the potential of “lure-and-kill” to significantly reduce canine infection and sand fly densities. In this study we were interested to determine if insecticide impregnated netting could replace sprayed insecticide for Lu. longipalpis control.Methods: We placed synthetic pheromone in experimental and real chicken sheds treated with a 1m2 surface of either sprayed insecticide or insecticide-impregnated netting. Two experiments in experimental chicken sheds were carried out to determine the effect of the insecticide treatments on Lu. longipalpis over 1-week and 16-week periods. We counted the number of Lu. longipalpis collected overnight and dead at 24 hours. Two longitudinal intervention studies were carried in real chicken sheds and compared the numbers of Lu. longipalpis (collected and dead at 24h) before adding the intervention (either the netting or sprayed insecticide treatments) with the numbers collected 24h after the intervention. Results: In the first experiment all flies caught in the spray treated experimental chicken sheds were dead at 24 hours and in netting treated sheds 97% of females and 88% of males were dead at 24 hours (257 vs 225, Wilcoxon Signed Ranks Test P=0.043). The netting and spray treated traps were equally effective at killing both female and male Lu. longipalpis over the first 8-weeks however after 16-weeks both treatments killed a significantly lower proportion of females (64%vs 96%; P=0.000) and males 89%vs 100%; P=0.000) compared to the beginning. In the first of the longitudinal studies in real chicken sheds only the netting intervention significantly increased the proportion of females dead after 24h (60%vs81%; P=0.042). The subsequent study showed that both netting and spraying treatments had similarly significant impacts on the proportion of females dead after 24h (netting: 60%vs80%: P=0.0194 and spraying: 43%vs72%: P=0.0004).Conclusions: The netting and spray insecticide interventions (with synthetic sex/aggregation pheromone) have similar impacts on the Lu. longipalpis population.

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Studies on the Feeding Habits ofLutzomyia (Lutzomyia) longipalpis(Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) Populations from Endemic Areas of American Visceral Leishmaniasis in Northeastern Brazil

Journal of Tropical Medicine ◽

10.1155/2012/858657 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 28

Author(s):

Margarete Martins dos Santos Afonso ◽

Rosemere Duarte ◽

José Carlos Miranda ◽

Lindenbergh Caranha ◽

Elizabeth Ferreira Rangel

Keyword(s):

Visceral Leishmaniasis ◽

Feeding Habits ◽

Blood Feeding ◽

Northeastern Brazil ◽

Sand Fly ◽

Lutzomyia Longipalpis ◽

Elisa Technique ◽

Endemic Areas ◽

Feeding Sources

The aim of this study was to identify potential blood feeding sources ofL. (L.) longipalpisspecimens from populations in Northeastern Brazil, endemic areas of American Visceral Leishmaniasis (AVL) and its correlation with the transmission ofL. (L.) i. chagasi. The ELISA technique was applied using bird, dog, goat, opossum, equine, feline, human, sheep, and rodent antisera to analyze 609 females, resulting in an overall positivity of 60%. In all municipalities, females showed higher positivity for bird followed by dog antiserum and sand fly specimens were also positive for equine, feline, human, sheep, goat, opossum, and rodent antisera. The finding for 17 combinations of two or three types of blood in some females corroborates the opportunistic habit of this sand fly species. The results demonstrating the association betweenL. (L.) longipalpisand opossum suggest the need for further evaluation of the real role of this synanthropic mammal in the eco-epidemiology of AVL.

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Spatial modelling of sand fly vector’s response to a synthetic sex-aggregation pheromone: impact on the incidence of visceral leishmaniasis in rural and urban settings

10.1101/2020.10.18.20214569 ◽

2020 ◽

Author(s):

Renata Retkute ◽

Erin Dilger ◽

James GC Hamilton ◽

Matt J Keeling ◽

Orin Courtenay

Keyword(s):

Visceral Leishmaniasis ◽

Aggregation Pheromone ◽

Human Infection ◽

Urban Setting ◽

Sand Fly ◽

Mathematical Framework ◽

Urban Settings ◽

Infection Incidence ◽

Host Seeking ◽

Rural And Urban

AbstractBackgroundVisceral leishmaniasis (VL) is a potentially fatal protozoan parasitic disease of humans and dogs. In the Americas, dogs are the reservoir and Lutzomyia longipalpis is the sand fly vector. A synthetic version of the vector’s sex-aggregation pheromone attracts conspecifics to co-located lethal insecticide, reducing reservoir infection and vector abundance. Mathematical models of spatially deployed interventions are lacking, thus best practise using this novel lure-and-kill vector control approach to reduce infection incidence has not been fully explored.MethodsWe developed a predictive mathematical model of vector host-seeking behaviour combined with spatially explicit transmission models to evaluate changes in human and canine spatial infection incidence under variable pheromone implementation scenarios and demographic conditions.ResultsThe risk of human infection increased exponentially with canine incidence, but at different rates between rural and urban settings with spatial clustering of high forces of human infection related to their proximity to canine infected households. A predicted 70% household coverage using a cost-effective amount (50mg) of pheromone, plus insecticide, reduced rural and urban setting infection incidence by approximately 44% and 50% in dogs, and by 64% and 68% in humans, within 1-2 years. Near or complete transmission elimination in dogs and humans was achieved after 10 years intervention using 50mg of pheromone under 70% household coverage in urban settings when newly acquired (immigrant) dogs had no pre-existing infections, but in rural settings required 90% coverage using 500mg. The willingness to pay (WTP) price per 10mg unit of pheromone is likely to be <$3 USD, making it a cost-beneficial intervention compared to current alternative strategies.ConclusionsIntegrated stochastic and spatial models capturing vector host-seeking behaviour, is a useful mathematical framework to evaluate spatially dependent intervention methods, fine-scale transmission dynamics, and to identify best practise.

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Transmission potential of paromomycin-resistant Leishmania infantum and Leishmania donovani

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz517 ◽

2019 ◽

Vol 75 (4) ◽

pp. 951-957 ◽

Cited By ~ 3

Author(s):

S Hendrickx ◽

L Van Bockstal ◽

H Aslan ◽

J Sadlova ◽

L Maes ◽

...

Keyword(s):

Leishmania Infantum ◽

Leishmania Donovani ◽

Leishmania Species ◽

Blood Feeding ◽

Sand Fly ◽

Lutzomyia Longipalpis ◽

Transmission Potential ◽

Laboratory Rodents ◽

The Impact

Abstract Objectives Former studies demonstrated quick selection of paromomycin resistance for Leishmania infantum and Leishmania donovani accompanied by increased fitness. The present study aimed to interpret these findings in an epidemiological context by comparing infection of WT and experimentally derived paromomycin-resistant strains in the sand fly vector. Methods Depending on the Leishmania species, Lutzomyia longipalpis and Phlebotomus perniciosus or Phlebotomus argentipes sand flies were artificially infected with procyclic promastigotes of WT and paromomycin-resistant L. infantum (MHOM/FR/96/LEM3323-cl4) or L. donovani (MHOM/NP/03/BPK275/0-cl18). The infection rate and gut/stomodeal valve colonization were determined to monitor parasite phenotypic behaviour within the vector. The impact of the previously described gain of fitness in the vertebrate host on infectivity for the vector was assessed by feeding L. longipalpis on Syrian golden hamsters heavily infected with either WT or paromomycin-resistant parasites. Results WT and paromomycin-resistant Leishmania of both species behaved similarly in terms of infection and parasite location within the studied sand fly species. Blood feeding on infected hamsters did not reveal differences in acquisition of WT and paromomycin-resistant parasites, despite the higher organ burdens observed for the paromomycin-resistant strain. Strains remained resistant after passage in the vector. Conclusions Although paromomycin-resistant parasites show an increased parasite fitness in vitro and in laboratory rodents, the intrinsic infection potential of paromomycin-resistant parasites remains unaltered in the sand fly. Of importance is the fact that paromomycin-resistant Leishmania are able to complete development in the natural vectors and produce stomodeal infection with metacyclic forms, which clearly suggests their potential to spread and circulate in nature.

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Molecular signatures of sexual communication in the phlebotomine sand flies

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008967 ◽

2020 ◽

Vol 14 (12) ◽

pp. e0008967

Author(s):

Paul V. Hickner ◽

Nataliya Timoshevskaya ◽

Ronald J. Nowling ◽

Frédéric Labbé ◽

Andrew D. Nguyen ◽

...

Keyword(s):

Aggregation Pheromone ◽

Sexual Communication ◽

Gene Families ◽

Food Sources ◽

Sand Fly ◽

Gene Copy ◽

Lutzomyia Longipalpis ◽

Sand Flies ◽

Sympatric Populations ◽

Phlebotomine Sand Flies

Phlebotomine sand flies employ an elaborate system of pheromone communication wherein males produce pheromones that attract other males to leks (thus acting as an aggregation pheromone) and females to the lekking males (sex pheromone). In addition, the type of pheromone produced varies among populations. Despite the numerous studies on sand fly chemical communication, little is known of their chemosensory genome. Chemoreceptors interact with chemicals in an organism’s environment to elicit essential behaviors such as the identification of suitable mates and food sources. Thus, they play important roles during adaptation and speciation. Major chemoreceptor gene families, odorant receptors (ORs), gustatory receptors (GRs) and ionotropic receptors (IRs) together detect and discriminate the chemical landscape. Here, we annotated the chemoreceptor repertoire in the genomes of Lutzomyia longipalpis and Phlebotomus papatasi, major phlebotomine vectors in the New World and Old World, respectively. Comparison with other sequenced Diptera revealed a large and unique expansion where over 80% of the ~140 ORs belong to a single, taxonomically restricted clade. We next conducted a comprehensive analysis of the chemoreceptors in 63 L. longipalpis individuals from four different locations in Brazil representing allopatric and sympatric populations and three sex-aggregation pheromone types (chemotypes). Population structure based on single nucleotide polymorphisms (SNPs) and gene copy number in the chemoreceptors corresponded with their putative chemotypes, and corroborate previous studies that identified multiple populations. Our work provides genomic insights into the underlying behavioral evolution of sexual communication in the L. longipalpis species complex in Brazil, and highlights the importance of accounting for the ongoing speciation in central and South American Lutzomyia that could have important implications for vectorial capacity.

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Cooperative Blood-feeding and the Function and Implications of Feeding Aggregations in the Sand Fly, Lutzomyia longipalpis (Diptera: Psychodidae)

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0000503 ◽

2009 ◽

Vol 3 (8) ◽

pp. e503 ◽

Cited By ~ 10

Author(s):

Frédéric Tripet ◽

Simon Clegg ◽

Dia-Eldin Elnaiem ◽

Richard D. Ward

Keyword(s):

Blood Feeding ◽

Sand Fly ◽

Lutzomyia Longipalpis

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Community deployment of a synthetic pheromone of the sand fly Lutzomyia longipalpis co-located with insecticide reduces vector abundance in treated and neighbouring untreated houses: Implications for control of Leishmania infantum

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009080 ◽

2021 ◽

Vol 15 (2) ◽

pp. e0009080 ◽

Cited By ~ 1

Author(s):

Raquel Gonçalves ◽

Cristian F. de Souza ◽

Reila B. Rontani ◽

Alisson Pereira ◽

Katie B. Farnes ◽

...

Keyword(s):

Leishmania Infantum ◽

Negative Binomial ◽

Sand Fly ◽

Community Study ◽

Control Group ◽

Lutzomyia Longipalpis ◽

Potential Cost ◽

Intervention Effects ◽

Synthetic Pheromone ◽

Vector Abundance

Background The rising incidence of visceral leishmaniasis due to Leishmania infantum requires novel methods to control transmission by the sand fly vector. Indoor residual spraying of insecticide (IRS) against these largely exophilic / exophagic vectors may not be the most effective method. A synthetic copy of the male sex-aggregation pheromone of the key vector species Lutzomyia longipalpis in the Americas, was co-located with residual pyrethroid insecticide, and tested for its effects on vector abundance, hence potential transmission, in a Brazilian community study. Methods Houses within eight defined semi-urban blocks in an endemic municipality in Brazil were randomised to synthetic pheromone + insecticide or to placebo treatments. A similar number of houses located >100m from each block were placebo treated and considered as “True Controls” (thus, analysed as three trial arms). Insecticide was sprayed on a 2.6m2 surface area of the property boundary or outbuilding wall, co-located within one metre of 50mg synthetic pheromone in controlled-release dispensers. Vector numbers captured in nearby CDC light traps were recorded at monthly intervals over 3 months post intervention. Recruited sentinel houses under True Control and pheromone + insecticide treatments were similarly monitored at 7–9 day intervals. The intervention effects were estimated by mixed effects negative binomial models compared to the True Control group. Results Dose-response field assays using 50mg of the synthetic pheromone captured a mean 4.8 (95% C.L.: 3.91, 5.80) to 6.3 (95% C.L.: 3.24, 12.11) times more vectors (female Lu. longipalpis) than using 10mg of synthetic pheromone. The intervention reduced household female vector abundance by 59% (C.L.: 48.7, 66.7%) (IRR = 0.41) estimated by the cross-sectional community study, and by 70% (C.L.: 56.7%, 78.8%) estimated by the longitudinal sentinel study. Similar reductions in male Lu. longipalpis were observed. Beneficial spill-over intervention effects were also observed at nearby untreated households with a mean reduction of 24% (95% C.L.: 0.050%, 39.8%) in female vectors. The spill-over effect in untreated houses was 44% (95% C.L.: 29.7%, 56.1%) as effective as the intervention in pheromone-treated houses. Ownership of chickens increased the intervention effects in both treated and untreated houses, attributed to the suspected synergistic attraction of the synthetic pheromone and chicken kairomones. The variation in IRR between study blocks was not associated with inter-household distances, household densities, or coverage (proportion of total households treated). Conclusions The study confirms the entomological efficacy of the lure-and-kill method to reduce the abundance of this important sand fly vector in treated and untreated homesteads. The outcomes were achieved by low coverage and using only 1–2% of the quantity of insecticide as normally required for IRS, indicating the potential cost-effectiveness of this method. Implications for programmatic deployment of this vector control method are discussed.

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Micro-CT visualization of a promastigote secretory gel (PSG) and parasite plug in the digestive tract of the sand fly Lutzomyia longipalpis infected with Leishmania mexicana

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009682 ◽

2021 ◽

Vol 15 (8) ◽

pp. e0009682

Author(s):

Martin J. R. Hall ◽

Debashis Ghosh ◽

Daniel Martín-Vega ◽

Brett Clark ◽

Innes Clatworthy ◽

...

Keyword(s):

Blood Meal ◽

Blood Feeding ◽

Sand Fly ◽

Laboratory Model ◽

Lutzomyia Longipalpis ◽

Sand Flies ◽

Leishmania Mexicana ◽

Micro Computed Tomography ◽

The Tropics ◽

The Impact

Leishmaniasis is a debilitating disease of the tropics, subtropics and southern Europe caused by Leishmania parasites that are transmitted during blood feeding by phlebotomine sand flies (Diptera: Psychodidae). Using non-invasive micro-computed tomography, we were able to visualize the impact of the laboratory model infection of Lutzomyia longipalpis with Leishmania mexicana and its response to a second blood meal. For the first time we were able to show in 3D the plug of promastigote secretory gel (PSG) and parasites in the distended midgut of whole infected sand flies and measure its volume in relation to that of the midgut. We were also able to measure the degree of opening of the stomodeal valve and demonstrate the extension of the PSG and parasites into the pharynx. Although our pilot study could only examine a few flies, it supports the hypothesis that a second, non-infected, blood meal enhances parasite transmission as we showed that the thoracic PSG-parasite plug in infected flies after a second blood meal was, on average, more than twice the volume of the plug in infected flies that did not have a second blood meal.

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