Bromide is a surprisingly potent larvicide for Anopheles gambiae in the laboratory

Mosquito-borne diseases remain a major global health burden, and novel approaches to vector control are urgently needed as resistance to conventional insecticides spreads. Most mosquitoes breed in freshwater but can tolerate low levels of halogen salts. Whether specific halides exhibit selective toxicity toward mosquito larvae has not been systematically investigated. We now report on a survey focusing on Anopheles gambiae, the primary vector for malaria in sub-Saharan Africa. Bromide is selectively and potently toxic to Anopheles larvae with an LC₅₀ below 10 µM for its sodium potassium salt. This sensitivity is more than 10-fold greater than that observed for the sodium salts of fluoride, chloride and iodide. Bromide toxicity is stage-specific with An. gambiae larvae displaying 300-fold greater sensitivity than adults while eggs and pupae remain unaffected by 5 mM sodium bromide. Anopheles stephensi larvae exhibit similar sensitivity, whereas Aedes aegypti and Culex quinquefasciatus larvae are approximately 10-fold more tolerant of sodium bromide. Mechanistically, bromide toxicity operates independently of pathways targeted by conventional insecticides. Co-administration of diflubenzuron or spinosad neither suppressed nor enhanced bromide's effects. Bromide exposure induced overexpression of GluCl and CCC-2 ion channels without affecting Rdl, Best, or KCC expression. Chloride also protected against bromide toxicity, suggesting these halides share a common receptor. Thoracic swelling in dying larvae indicates that bromide disrupts osmotic or hydration balance. These findings are unexpected given that bromide is generally considered non-toxic to aquatic and terrestrial organisms, revealing a previously unknown vulnerability specific to Anopheles mosquitoes. The selective toxicity of bromide toward Anopheles larvae, combined with its independence from existing insecticide resistance mechanisms, may serve as a new lead for controlling malaria vectors. Targeting this bromide-sensitive pathway may complement current larvicidal approaches and provide an alternative for populations resistant to standard insecticides. The use of bromide itself will still require significant environmental and field-based studies prior to its possible application.