Serological Markers of Sand Fly Exposure to Evaluate Insecticidal Nets against Visceral Leishmaniasis in India and Nepal: A Cluster-Randomized Trial

Abstract

BackgroundVisceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial.MethodsAs part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention.ResultsA total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83–0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80–1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi.ConclusionsThis trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions.

Human IgG Antibody Response to Aedes Nterm-34kDa Salivary Peptide, an Epidemiological Tool to Assess Vector Control in Chikungunya and Dengue Transmission Area

“…The human Ab response to vectors’ salivary proteins is a pertinent tool for evaluating the efficacy of vector control strategies, against malaria [20–22,28,40]. In the present study, a significant decrease of human IgG response to Nterm-34kDa peptide was observed just one week after VCI.…”

“…Recent studies have demonstrated the usefulness of anti-saliva Ab response for measuring exposure of humans to arthropods bites, such as, ticks [8] sand fly [9,10], Glossina [11] and mosquitoes [12–19]. Additionally, human Ab IgG response to whole saliva was identified as pertinent tool for evaluating efficacy of vector control against Anopheles [20,21], Phlebotomus [22] and Aedes albopictus [23]. However, the use of whole saliva is not an ideal indicator, because of: i) potential cross-reactivity with other vectors; ii) weak stability / fast degradation of proteins in wholes saliva and iii) poorly reproducible batches produced for large-scale studies.…”

Tissue Requirements for Establishing Long-Term CD4+ T Cell–Mediated Immunity following Leishmania donovani Infection

“…However, more recent work showed that CD4 + T cells from VL patients can respond to parasite Ag in whole-blood assays, suggesting that sample processing may have contributed to earlier results (42)(43)(44). Our results showing that CD4 + T cells were important for controlling parasite burden in chronically infected spleens of L. donovani-infected mice (Fig.…”

Salivary Antigen SP32 Is the Immunodominant Target of the Antibody Response to Phlebotomus papatasi Bites in Humans

“…Antibodies against saliva of sand flies have recently been evaluated as potential tools for measurement of exposure to sand fly bites [18], [19]. Current data provide evidence that the levels of specific antibodies correlate with variations in vector exposure [18] and could, thus, be used to evaluate vector control intervention [20]. Moreover, in endemic areas for cutaneous leishmaniasis, the presence of anti-saliva antibodies correlated with the risk of contracting disease [4], [7].…”