Entomological impact of mass administration of ivermectin and dihydroartemisinin-piperaquine in The Gambia: a cluster-randomized controlled trial

Abstract

Background Vector control interventions in sub-Saharan Africa rely on insecticide-treated nets and indoor residual spraying. Insecticide resistance, poor coverage of interventions, poor quality nets and changes in vector behavior threaten the effectiveness of these interventions and, consequently, alternative tools are needed. Mosquitoes die after feeding on humans or animals treated with ivermectin (IVM). Mass drug administration (MDA) with IVM could reduce vector survival and decrease malaria transmission. The entomological impact of MDA of combined IVM and dihydroartemisinin-piperaquine was assessed in a community-based, cluster-randomized trial. Methods A cluster-randomized trial was implemented in 2018 and 2019 in 32 villages in the Upper River Region, The Gambia. The with the inhabitants of 16 intervention villages eligible to receive three monthly rounds of MDA at the beginning of the malaria transmission season. Entomological surveillance with light traps and human landing catches (HLC) was carried out during a 7- to 14-day period after each round of MDA, and then monthly until the end of the year. The mosquitocidal effect of IVM was determined by direct membrane feeding assays. Results Of the 15,017 mosquitoes collected during the study period, 99.65% (n = 14,965) were Anopheles gambiae sensu lato (An. gambiae s.l.), comprising Anopheles arabiensis (56.2%), Anopheles coluzzii (24.5%), Anopheles gambiae sensu stricto (An. gembiae s.s.; 16.0%) and Anopheles funestus sensu lato (An. funestus s.l.; 0.35%). No effect of the intervention on vector parity was observed. Vector density determined on light trap collections was significantly lower in the intervention villages in 2019 (adjusted incidence rate ratio: 0.39; 95% confidence interval [CI]: 0.20, 0.74; P = 0.005) but not in 2018. However, vector density determined in HLC collections was similar in both the intervention and control villages. The entomological inoculation rate was significantly lower in the intervention villages than in the control villages (odds ratio: 0.36, 95% CI: 0.19, 0.70; P = 0·003). Mosquito mortality was significantly higher when blood fed on IVM-treated individuals up to 21 days post-treatment, particularly in adults and individuals with a higher body mass index. Conclusion Mass drug administration with IVM decreased vector density and the entomological inoculation rate while the effect on vector parity was less clear. Survival of mosquitoes fed on blood collected from IVM-treated individuals was significantly lower than that in mosquitoes which fed on controls. The influence of host characteristics on mosquito survivorship indicated that dose optimization could improve IVM efficacy. Future detailed entomological evaluation trials in which IVM is administered as stand-alone intervention may elucidate the contribution of this drug to the observed reduction in transmission. Graphical Abstract

Cost-effectiveness of Precision Guided SIT for Control ofAnopheles gambiaein the Upper River Region, The Gambia

“…The modeling framework was calibrated to malaria prevalence data from The Gambia (Dabira et al 2022), and informed by local entomological data (Soumare et al 2022) and rainfall data sourced from Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS, https://www.chc.ucsb.edu/data/chirps). The model was also calibrated with existing coverage of artemisinin-based combination treatment (ACTs), LLINS, and IRS with insecticides specific to the Upper River region based on data from the Malaria Atlas Project (Pfeffer et al 2018).…”

“…The model was also calibrated with existing coverage of artemisinin-based combination treatment (ACTs), LLINS, and IRS with insecticides specific to the Upper River region based on data from the Malaria Atlas Project (Pfeffer et al 2018). The seasonal carrying capacity of the environment for A. gambiae larvae was determined from the CHIRPS rainfall data, entomological data suggesting that dry season larval carrying capacity was ∼10% that of the peak rainy season (Soumare et al 2022), and for consistency with human malaria prevalence data from a recent randomized controlled trial conducted in the Upper River region (Dabira et al 2022). Further bionomic parameters for the A. gambiae population were sourced from the literature and are summarized in Table S1 .…”

“…The study found a baseline malaria prevalence in the URR of ~18% at the beginning of the rainy season, which we aligned with the simulation output. Furthermore, entomological data from the URR (Soumare et al 2022) suggested vector breeding sites in this region are substantially more abundant in the rainy season than in the dry season, so we assumed that larval carrying capacity in the dry season was 10% that of the peak rainy season. The malaria model calibration took place in the context of model parameterization with existing levels of coverage of ACTs, LLINs, and IRS with insecticides, which modify the transition rates between human infectious states and life history parameters of the mosquito vector population, respectively.…”

Exposure of gut bacterial isolates to the anthelminthic drugs, ivermectin and moxidectin, leads to antibiotic-like phenotypes of growth inhibition and adaptation

“…To our knowledge, only limited data regarding antibacterial activity of IV and MX against gut bacterial isolates have been published to date [21,23]. A causal relationship between bacterial sensitivity profiles and IV or MX treatment would raise serious concerns in light of the extensive use of IV and MX in the livestock industry and the increase in distribution and administration for helminth infections and malaria transmission control [24][25][26]. Thus, it is crucial to anticipate potential off-target effects of these two anthelminthics.…”

“…The copyright holder for this preprint this version posted January 18, 2024. ; https://doi.org/10.1101/2024.01.17.575993 doi: bioRxiv preprint administration for helminth infections and malaria transmission control [24][25][26]. Thus, it is crucial to anticipate potential off-target effects of these two anthelminthics.…”