Delayed mortality effects cut the malaria transmission potential of insecticide-resistant mosquitoes

Abstract

Malaria transmission has been substantially reduced across Africa through the distribution of long-lasting insecticidal nets (LLINs). However, the emergence of insecticide resistance within mosquito vectors risks jeopardizing the future efficacy of this control strategy. The severity of this threat is uncertain because the consequences of resistance for mosquito fitness are poorly understood: while resistant mosquitoes are no longer immediately killed upon contact with LLINs, their transmission potential may be curtailed because of longer-term fitness costs that persist beyond the first 24 h after exposure. Here, we used a Bayesian state-space model to quantify the immediate (within 24 h of exposure) and delayed (>24 h after exposure) impact of insecticides on daily survival and malaria transmission potential of moderately and highly resistant laboratory populations of the major African malaria vector Anopheles gambiae Contact with LLINs reduced the immediate survival of moderately and highly resistant An. gambiae strains by 60-100% and 3-61%, respectively, and delayed mortality impacts occurring beyond the first 24 h after exposure further reduced their overall life spans by nearly one-half. In total, insecticide exposure was predicted to reduce the lifetime malaria transmission potential of insecticide-resistant vectors by two-thirds, with delayed effects accounting for at least one-half of this reduction. The existence of substantial, previously unreported, delayed mortality effects within highly resistant malaria vectors following exposure to insecticides does not diminish the threat of growing resistance, but posits an explanation for the apparent paradox of continued LLIN effectiveness in the presence of high insecticide resistance.

Keywords: Anopheles gambiae; insecticide resistance; long-lasting insecticidal nets; state-space models; transmission potential.

Fig. 1.

Experimental data. Top panels show the observed daily survival curves, i.e., the proportion of mosquitoes from day x − 1 alive at day x for each exposure regime (across panels), strain (different colors), and treatment (filled vs. open symbols) combination. Vertical dotted lines correspond to the time of exposure. Middle panels show the immediate mortality rate of each group, i.e., within 24 h of exposure to pyrethroids. Replicates shown with different shades of the same color. Bottom panels show the delayed mortality rate of each group, i.e., 24–72 h after exposure to pyrethroids.

Fig. S1.

Model fit of the binomial survival model. Comparison of the observed (points) and model-fitted survival curves (lines with shaded 95% credible intervals) of each exposure regime (columns), strain, and treatment group (row).

Fig. 2.

Estimated impact of delayed effects of exposure to insecticides on mosquito daily survival of moderately (blue) and highly (red) resistant strains. The dotted line corresponds to the baseline daily survival (and controls) of both strains and the shaded area to the 95% credible interval.

Fig. 3.

Modeled daily survival curves of An. gambiae after different exposure regimes to LLINs. Full lines represent the curve estimated from fitting the binomial model to the data, and the dotted lines represent the counterfactual curve predicted with no delayed effects. Lines correspond to the median prediction with shaded 95% credible intervals.

Fig. 4.

Contour plots of the mean number of infectious bites per mosquito of TOR (blue upper panels) and TIA (red bottom panels) strains obtained for mosquitoes exposed to untreated (control) and insecticide-treated nets with and without delayed effects across varying probabilities of biting (x axis) and exposure (y axis).