Two modes of sand fly transmission under the influence of dose and the biological inputs that influence them.

<p>Flies feeding on mammalian hosts with a high parasite load are infected with a high dose of parasites, generating infections with a high frequency of metacyclic promastigotes that are transmitted to a second mammalian host with high efficiency and in larger numbers, resulting in more severe disease [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006571#ppat.1006571.ref054" target="_blank">54</a>]. Higher dose infections in the mammalian host result in more severe acute disease but with more complete resolution and lower parasite loads in the chronic phase. Lower dose infections result in mild acute disease but chronic moderate disease [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006571#ppat.1006571.ref058" target="_blank">58</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006571#ppat.1006571.ref059" target="_blank">59</a>]. High acute parasite loads act as highly efficient reservoirs for disease, while low chronic parasite loads are very poor reservoirs for disease, and chronic moderate parasite loads are moderate reservoirs for disease [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006571#ppat.1006571.ref058" target="_blank">58</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006571#ppat.1006571.ref060" target="_blank">60</a>]. Individuals with high parasite loads are mammalian “super-spreaders” by virtue of their high reservoir potential, while sand flies with high parasite loads are sand fly “super-spreaders” by virtue of their highly efficient transmission of parasites.</p

Estimates of the sensitivity of rK39 RDTs to detect asymptomatic <i>Leishmania infantum</i> infection in dogs.

1<p>CC – case-control; XS – cross-sectional;</p>2<p>Inbios International Inc, WA, USA; Cypress Diagnostic Company, Belgium; Intersep DiaSys Europe Ltd; Diamed AG, Switzerland;</p>3<p>data from first time-point of a cohort study;</p>4<p>crude antigen.</p

Factors associated with a positive rK39 RDT result in samples from infected Brazilian dogs.

<p>Odds Ratios (95% CI) were estimated using general estimating equations with robust standard errors, to account for the non-independence of repeat samples from the same dog. All analyses included time since confirmed infection (months and months²) as covariates.</p

Estimates of the sensitivity of rK39 RDTs to detect <i>Leishmania infantum</i> infection in dogs.

1<p>CC – case-control; XS – cross-sectional;</p>2<p>Inbios International Inc, WA, USA; Corixa, USA; Cypress Diagnostic Company, Belgium; Intersep DiaSys Europe Ltd; Diamed AG, Switzerland;</p>3<p>data from first time-point of a cohort study;</p>4<p>crude antigen.</p

Proportion of dogs positive by rK39 RDT according to anti-CLA IgG concentrations.

<p>IgG concentrations expressed as arbitrary units/mL relative to positive control serum, by ELISA. Each point represents 31–32 samples. Dashed line indicates the CLA ELISA cut-off.</p

Estimates of the specificity of rK39 RDTs in dogs.

1<p>CC – case-control; XS – cross-sectional;</p>2<p>Inbios International Inc, WA, USA; Cypress Diagnostic Company, Belgium; Intersep DiaSys Europe Ltd; Diamed AG, Switzerland;</p>3<p>NEC non-endemic controls, EC endemic controls, OD other diseases;</p>4<p>data from first time-point of a cohort study;</p>5<p>not stated;</p>6<p>clinically suspect dogs.</p

Proportion of infected dogs positive by CLA ELISA and rK39 RDT according to parasite density in bone marrow.

<p>Parasite density expressed as number of parasites/mL of bone marrow biopsy by quantitative kDNA PCR. Key: CLA ELISA (open circles); rK39 RDT (closed circles). Each point represents 25 samples.</p

Specificity of rK39 RDTs in various groups of control dogs.

<p>Specificity of rK39 RDTs in various groups of control dogs.</p

Flow diagram for study inclusion in meta-analysis.

<p>Flow diagram for study inclusion in meta-analysis.</p

Sensitivity of rK39 RDT and CLA ELISA in samples from infected and uninfected dogs.

<p>The percentage of dogs positive (95% CI) by each test for different classes of dogs was estimated using general estimating equations with robust standard errors, to account for the non-independence of repeat samples from the same dog. n – number of samples; N – number of dogs.</p>1<p>as defined by CLA ELISA.</p