BackgroundInsecticide resistance in major malaria vectors poses severe challenges for stakeholders responsible for controlling the disease. During the 2013/14 season, malaria vector sentinel sites in Mutare and Mutasa Districts, Zimbabwe, experienced high presence of gravid malaria vector mosquitoes resting indoors in recently pyrethroid-sprayed structures. Subsequently, an evaluation of insecticide resistance in Anopheles funestus populations, the major malaria vector, was conducted to better inform the Zimbabwe National Malaria Control Programme.MethodsIndoor-resting mosquitoes were collected in randomly selected pyrethroid-sprayed houses around Burma Valley and Zindi sentinel sites in Mutare and Mutasa Districts, respectively, using prokopac aspirator in February 2014. A. funestus mosquitoes were identified in the field using morphological keys and divided into two cohorts. One cohort was used immediately for WHO susceptibility tests and the other batch was transferred to the National Institute of Health Research insectary in Harare for oviposition. Susceptibility and intensity resistance assays were carried out on polymerase chain reaction-assayed, 3–5 days old, A. funestus s.s. F1 progeny females.ResultsEight-hundred and thirty-six A. funestus and seven Anopheles gambiae complex mosquitoes were collected resting inside living structures. Wild caught females showed resistance to lambda-cyhalothrin (3.3 % mortality), deltamethrin (12.9 % mortality), etofenprox (9.2 % mortality), and bendiocarb (11.7 % mortality). F1 A. funestus female progeny indicated resistance to deltamethrin (14.5 % mortality), lambda-cyhalothrin (6.9 % mortality), etofenprox (8.3 % mortality), and bendiocarb (16.8 % mortality). Wild caught and female progeny were susceptible to DDT and pirimiphos-methyl (100 % mortality). Intensity resistance assay to bendiocarb was 100 % mortality, while deltamethrin, lambda-cyhalothrin, and etofenprox had increased knockdown times with mortalities ranging between 66.7 and 92.7 % after 24-h exposures.ConclusionThis study is the first report of pyrethroid and carbamate resistance in A. funestus populations from Burma Valley and Zindi areas and indicates a major threat to the gains made in malaria vector control in Zimbabwe. In view of the current extension and intensity of such resistance, there is urgent need to set up a periodic and systematic insecticide resistance-monitoring programme which will form the basis for guiding the selection of insecticides for indoor residual spraying and distribution of pyrethroid-treated mosquito nets.
Phenotypic TB drug resistance, also known as drug tolerance, has been previously attributed to slowed bacterial growth in vivo. The increased activity and expression of efflux systems can lower the intracellular concentration of many antibiotics thus reducing their efficacy. We hypothesized that efflux pump activation and expression could be a risk factor for TB drug tolerance in patients initiated on treatment. Analyses of gene expression levels of six select efflux pumps associated with drug tolerance in Mycobacterium tuberculosis and its correlation with the cell’s ability to efflux ethidium bromide (a common efflux substrate) were assayed. Efflux pump gene expression differed significantly between the strains from treatment failures and treatment successes. Efflux of ethidium bromide by M. tuberculosis isolates revealed that isolates from treatment failures rapidly efflux ethidium bromide more than isolates from treatment successes or the H37Rv control strains. The efflux pumps efpA, jefA (Rv2459c), Rv1258c, p55 and mmpL7 may have a role in TB drug tolerance. Quantifying the expression levels of M. tuberculosis efflux pump genes may be a new method to diagnose clinically persistent tuberculosis. High efflux pump activity and expression at baseline can be associated with tuberculosis treatment failure even when the Mycobacterium tuberculosis does not have established resistance mutations.Journal of Medical and Biomedical Sciences (2017) 6(1), 8-17Keywords: drug resistance, Efflux, Mycobacterium tuberculosis, expression, treatment outcome
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