Plasmodium falciparum gametocyte-induced volatiles enhance attraction of Anopheles mosquitoes in the field

Abstract

Background: Plasmodium parasites manipulate the interaction between their mosquito and human hosts. Patients infected with gametocytes attract anopheline mosquitoes differentially compared to healthy individuals, an effect associated with an increased release of attractive volatile cues. This odour-driven manipulation is partly mediated by the gametocyte-specific metabolite, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which induces increased release of select aldehydes and terpenes from red blood cells and results in the enhanced attraction of host-seeking mosquitoes, which are vectors of malaria. This study investigates the effect of the HMBPP-induced volatiles on the attraction of wild Anopheles mosquitoes to humans under field conditions.

Methods: The efficacy of the HMBPP-induced odour blend to attract Anopheles was evaluated in a 4 × 6 Latin rectangular study design indoors using baited Suna traps. Furthermore, to assess the efficacy of the HMBPP-induced odour blend in (1) augmenting the attractiveness of human odour, and (2) attracting Anopheles mosquitoes in the absence of human odour, a two-choice assay using host decoy traps (HDTs) was used and evaluated using binomial generalized regression.

Results: Traps baited with the HMBPP-induced odour blend attracted and caught both Anopheles arabiensis and Anopheles pharoensis females in a dose-dependent manner in the presence of background human odour, up to 2.5 times that of an unbaited trap. Given a choice between human odour and human odour laden with the HMBPP-induced odour blend, mosquitoes differentially preferred traps augmented with the HMBPP-induced odour blend, which caught twice as many female An. arabiensis. Traps baited with the HMBPP-induced odour blend but lacking the background of human odour were not effective in attracting and catching mosquitoes.

Conclusion: The findings of the present study revealed that the HMBPP-induced odour blend, when augmented with human body odour, is attractive to anopheline mosquitoes and could be used as a complementary vector control tool along with existing strategies.

Keywords: (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate; Anopheles; Attraction; HMBPP; Mosquitoes.

Fig. 1

Map of the study area showing the districts in Ethiopia, the Gamo Gofa zone and the Arba Minch Zuria district, with the study site indicated

Fig. 2

The number of Anopheles arabiensis (a) and Anopheles pharoensis (b) caught in the HMBPP-induced odour-baited and control traps per night as depicted by box plots. The horizontal line within each box represents the median and the × represents the mean. The whiskers represent ± 1.5 times the inter-quartile range extending from the upper and lower quartile boundaries. The asterisks represent significant difference from the control at a level of α < 0.05 (N = 24; n = 72)

Fig. 3

a Photograph of the tent and one of the two BioGents AG host decoy traps connected by a polyvinylchloride (PVC) pipe. b Schematic representation of the two-choice behavioral assay, indicating the volunteer inside the tent. The human body odours were deployed to the host decoy traps via PVC pipes using two computer fans. The HMBPP-induced odour blend and the heptane control were introduced into either of the two PVC pipes by placing the dispensers in front of the fans. c The behavioral preference of Anopheles arabiensis to human odour, from two volunteers with or without augmentation by the HMBPP-induced odour blend is indicated by a choice index. In the absence of human odour, the host decoy traps caught 3 mosquitoes in the treatment and 4 in the control (data not shown). All experiments were replicated 8 times