Combining epidemiology with basic biology of sand flies, parasites, and hosts to inform leishmaniasis transmission dynamics and control

Abstract

Quantitation of the nonlinear heterogeneities in Leishmania parasites, sand fly vectors, and mammalian host relationships provides insights to better understand leishmanial transmission epidemiology towards improving its control. The parasite manipulates the sand fly via production of promastigote secretory gel (PSG), leading to the “blocked sand fly” phenotype, persistent feeding attempts, and feeding on multiple hosts. PSG is injected into the mammalian host with the parasite and promotes the establishment of infection. Animal models demonstrate that sand flies with the highest parasite loads and percent metacyclic promastigotes transmit more parasites with greater frequency, resulting in higher load infections that are more likely to be both symptomatic and efficient reservoirs. The existence of mammalian and sand fly “super-spreaders” provides a biological basis for the spatial and temporal clustering of clinical leishmanial disease. Sand fly blood-feeding behavior will determine the efficacies of indoor residual spraying, topical insecticides, and bed nets. Interventions need to have sufficient coverage to include transmission hot spots, especially in the absence of field tools to assess infectiousness. Interventions that reduce sand fly densities in the absence of elimination could have negative consequences, for example, by interfering with partial immunity conferred by exposure to sand fly saliva. A deeper understanding of both sand fly and host biology and behavior is essential to ensuring effectiveness of vector interventions.

Spatio-temporal modelling ofLeishmania infantuminfection among domestic dogs: a simulation study and sensitivity analysis applied to rural Brazil

“…Accordingly, finding greater sensitivity 297 on infection prevalence when altering the parameters related to sand fly dynamics versus the 298 majority of parameters conditioned solely on dogs is not unexpected and is in agreement with 299 prior studies displaying the sensitivity of Leishmania transmission models to sand fly parameter 300 values [13,38]. Furthermore, the importance of understanding sand fly biology and biting be-301 haviours in relation to transmission probability and control has been underpinned by laboratory 302 experiments and observations in nature [32,[39][40][41][42].…”

“…A reported 3,500 human VL cases occur in the country per year, 90% of all VL 39 cases reported in the Americas [1,3], with the actual incidence (allowing for under-reporting) 40 estimated annually to be between 4,200 and 6,300 [1]. Accordingly, in Brazil importance is 41 attached to the management of infection prevalence among domestic dogs to diminish the public 42 health VL risk [22,23]. 43 To this end, we herein develop a novel spatio-temporal mechanistic modelling framework for L. 44 infantum infection in domestic dogs.…”

“…307 Studies of domestic dog migration are few, but in most dog populations losses and replacements 308 appear relatively stable with estimates from Brazil of the percentage of new dogs being immi-309 grants ranging from 37% to 50%, with up to 15% of immigrant dogs being Leishmania seropos-310 itive on arrival [43][44][45]. Given the heterogeneities in sand fly abundance and infection [42], even 311 in highly endemic regions such as Marajó, migration of infected dogs between villages can have 312 a significant impact on transmission as demonstrated here.…”

Parasite infections in a social carnivore: Evidence of their fitness consequences and factors modulating infection load

“…Juveniles that shed high Cystoisospora oocyst loads may act as “super‐shedders” for infection. “Super‐shedders” are thought to be important for disease transmission in several pathogens (Courtenay, Peters, Rogers, & Bern, ; Lloyd‐Smith, Schreiber, Kopp, & Getz, ; Paull et al, ). Because adult females in our study clans give birth throughout the year (East et al, ; Hofer & East, ), for a substantial proportion of each year, communal dens are likely to contain the young juveniles (Figure b) that typically shed high oocyst loads.…”

“…Hyena communal den sites are locations of high use by both adults and juveniles ( Figure 7) and thus can act as hot spots for the spread of pathogens, similar to bird feeders (Adelman, Moyers, Farine, & Hawley, 2015) and savannah waterholes (Stommel et al, 2016). Both super-spreaders and hot spots of infection are important for the spread and maintenance of pathogens in host populations (Adelman et al, 2015;Courtenay et al, 2017;Lloyd-Smith et al, 2005;Paull et al, 2011). Juvenile hyenas with high infection loads at communal dens may be important for the spread and maintenance of not only Cystoisospora and Ancylostoma (this study) but other parasite such as Dipylidium (East et al, 2013).…”