Insecticide Resistance Profiling of Anopheles coluzzii and Anopheles gambiae Populations in the Southern Senegal: Role of Target Sites and Metabolic Resistance Mechanisms.

The emergence and spread of insecticide resistance among the main malaria vectors is threatening the effectiveness of vector control interventions in Senegal. The main drivers of this resistance in the Anopheles gambiae complex (e.g., An. gambiae and Anopheles coluzzii) remains poorly characterized in Senegal. Here we characterized the main target site and metabolic resistances mechanisms among the An. gambiae and An. coluzzii populations from their sympatric and allopatric or predominance area in Senegal. Larvae and pupae of An. gambiae s.l. were collected, reared to adulthood, and then used for insecticides susceptibility and synergist assays using the WHO (World Health Organisation) test kits for adult mosquitoes. The TaqMan method was used for the molecular characterization of the main target site insecticide resistance mechanisms (Vgsc-1014F, Vgsc-1014S, N1575Y and G119S). A RT-qPCR (Reverse Transcriptase-quantitative Polymerase Chaine Reaction) was performed to estimate the level of genes expression belonging to the CYP450 (Cytochrome P450) family. Plasmodium infection rate was investigated using TaqMan method. High levels of resistance to pyrethroids and DDT and full susceptibility to organophosphates and carbamates where observed in all three sites, excepted a probable resistance to bendiocarb in Kedougou. The L1014F, L1014S, and N1575Y mutations were found in both species. Pre-exposure to the PBO (Piperonyl butoxide) synergist induced a partial recovery of susceptibility to permethrin and full recovery to deltamethrin. Subsequent analysis of the level of genes expression, revealed that the CYP6Z1 and CYP6Z2 genes were over-expressed in wild-resistant mosquitoes compared to the reference susceptible strain (Kisumu), suggesting that both the metabolic resistance and target site mutation involving kdr mutations are likely implicated in this pyrethroid resistance. The presence of both target-site and metabolic resistance mechanisms in highly pyrethroid-resistant populations of An. gambiae s.l. from Senegal threatens the effectiveness and the sustainability of the pyrethroid-based tools and interventions currently deployed in the country. The Kdr-west mutation is widely widespread in An. coluzzii sympatric population. PBO or Duo nets and IRS (Indoor Residual Spraying) with organophosphates could be used as an alternative measure to sustain malaria control in the study area

Toxicity assessment and analgesic activity investigation of aqueous acetone extracts of <it>Sida acuta </it> Burn f <it>.</it> and <it>Sida cordifolia </it> L. (Malvaceae), medicinal plants of Burkina Faso

<p>Abstract</p> <p>Background</p> <p><it>Sida acuta </it> Burn f. and <it>Sida cordifolia </it> L. (Malvaceae) are traditionally used in Burkina Faso to treat several ailments, mainly pains, including abdominal infections and associated diseases. Despite the extensive use of these plants in traditional health care, literature provides little information regarding their toxicity and the pharmacology. This work was therefore designed to investigate the toxicological effects of aqueous acetone extracts of <it>Sida acuta </it> Burn f. and <it>Sida cordifolia </it> L. Furthermore, their analgesic capacity was assessed, in order to assess the efficiency of the traditional use of these two medicinal plants from Burkina Faso.</p> <p>Method</p> <p>For acute toxicity test, mice were injected different doses of each extract by intraperitoneal route and the LD50 values were determined. For the subchronic toxicity evaluation, Wistar albinos rats were treated by gavage during 28 days at different doses of aqueous acetone extracts and then haematological and biochemical parameters were determined. The analgesic effect was evaluated in mice by the acetic-acid writhing test and by the formalin test.</p> <p>Results</p> <p>For the acute toxicity test, the LD50 values of 3.2 g/kg and 3.4 g/kg respectively for <it>S. acuta </it> Burn f. and <it>S. cordifolia </it> L. were obtained. Concerning the haematological and biochemical parameters, data varied widely (increase or decrease) according to dose of extracts and weight of rats and did not show clinical correlations. The extracts have produced significant analgesic effects by the acetic acid writhing test and by the hot plate method (p <0.05) and a dose-dependent inhibition was observed.</p> <p>Conclusion</p> <p>The overall results of this study may justify the traditional uses of <it>S. acuta </it> and <it>S. cordifolia </it>.</p