Adult Control I
Adult Control I
Insecticide resistance among malaria vector species is now a pervasive problem, which threatens to jeopardize global disease control efforts. In sub-Saharan Africa, novel vector control tools, including long-lasting insecticidal nets (LLINs) incorporating new active ingredients (A.I.s), with different modes of action, are urgently needed to delay the evolution and spread of resistance. During a three-year, four-arm cluster-randomised controlled trial in Tanzania, evaluating the effectiveness of three dual-A.I. LLINs compared to pyrethroid-LLINs (PY-LLINs), we measured longitudinal phenotypic and genotypic insecticide resistance profiles among 47,258 female Anopheles mosquitoes collected over 36 months. In the PY-LLIN arm, a significant increase in alpha-cypermethrin and permethrin resistance intensity and concomitant decline in mortality, following exposure to the synergist PBO,was observed in An. funestus s.l. (the predominant vector species complex) over 24 months. A similar phenomenon was apparent in the pyriproxyfen-PY LLIN arm over three years, with the greatest escalation in resistance intensity evidenced in the PBO-PY LLIN arm. The chlorfenapyr-PY LLIN arm had no significant effecton pyrethroid resistance, supported by minimal reductions in chlorfenapyr susceptibility. By comparison, An.funestus s.l. populations displayed limited sterility following pyriproxyfen exposure. Highly over-expressed detoxification enzymes presented dynamic patterns of selection throughout the trial. Phenotypic data strengthened clinical trial epidemiological findings; chlorfenapyr-PY LLINs provided superior protection from malaria across multiple transmission seasons, with little impact on insecticide resistance. Rapid fifty-fold pyrethroid resistance intensification in the PBO-PY LLIN arm and pre-existing tolerance of vector populations to pyriproxyfen in the trial site may explain the poorer performance of these two interventions on malaria outcomes. Ongoing work is elucidating potential mechanisms driving cross-resistance between pyrethroids and novel A.I.s, to better inform pragmatic design of resistance management schemes.