Martins, A. d. J. | bioRxiv Science

bioRxiv2025

Wolbachia introgression in Rio de Janeiro remains at sub-optimal levels 30 months after its crash: challenges in the sustainability of wMel interventions for dengue control

The deployment of the Wolbachia wMel strain is currently underway in multiple dengue-endemic municipalities across Brazil. The efficacy of this strategy in Rio de Janeiro remains uncertain, primarily due to the difficulty in sustaining high wMel prevalence in regions previously subjected to large-scale releases. A key contributing factor was the routine rotation of insecticides within the framework of Integrated Vector Management (IVM), which led to the use of the larvicide Spinosad for Aedes control in urban areas. This compound was associated with a precipitous decline in Aedes aegypti mosquitoes, regardless the wMel infection status. While wMel-uninfected population recovered within weeks, wMel-infected population remained at low levels likely due to the fitness costs imposed by wMel on egg viability. To assess the long-term persistence of wMel following this demographic collapse, we conducted mosquito sampling across 12 neighborhoods in Rio de Janeiro, 30 months after mosquito populations crashed. Our findings reveal that wMel introgression remains suboptimal, with a mean frequency of 9.87% across the sampled areas. Only two neighborhoods exhibited wMel frequencies exceeding 15%, likely reflecting ongoing localized releases. The reduced prevalence underscores the challenges of achieving self-sustaining wMel establishment in complex urban environments and highlight critical considerations for the implementation of Wolbachia-based dengue control programs in endemic regions. SponsorshipThis study was supported by grants from the CNPq - Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (312282/2022-2, 307209/2023-7) and by FAPERJ - Fundacao Carlos Chagas Filho de Amparo a Pesquisa no Estado do Rio de Janeiro (E-26/211.159/2019, E-26/204.108/2024, E26/2001.844/2017, E-26/210.335/2022, E-26/210.537/2024).

ecology↗

bioRxiv2019

On the use of inhibitors of 4-hydroxyphenylpyruvate dioxygenase as a vector-selective insecticide in the control of mosquitoes

Blood-sucking insects incorporate many times their body weight of blood in a single meal. As proteins are the major component of vertebrate blood, its digestion in the gut of hematophagous insects generates extremely high concentrations of free amino acids. Previous reports showed that the tyrosine degradation pathway plays an essential role in adapting these animals to blood feeding. Inhibiting 4-hydroxyphenylpyruvate dioxygenase (HPPD), the rate-limiting step of tyrosine degradation, results in the death of insects after a blood meal. Therefore, it was suggested that compounds that block the catabolism of tyrosine could act selectively on blood-feeding insects. Here we have evaluated the toxicity against mosquitoes of three HPPD inhibitors currently used as herbicides and in human health. Among the compounds tested, nitisinone (NTBC) proved to be more potent than mesotrione (MES) and isoxaflutole (IFT) in Aedes aegypti. NTBC was lethal to Ae. aegypti in artificial feeding assays (LD50: 4.36 {micro}M), as well as in topical application (LD50: 0.0033 nmol/mosquito). NTBC was also lethal to Ae. aegypti populations that were resistant to neurotoxic insecticides, and it was lethal to other mosquito species (Anopheles and Culex). Therefore, HPPD inhibitors, particularly NTBC, represent promising new drugs for mosquito control. Since they only affect blood-feeding organisms, they would represent a safer and more environmentally friendly alternative to conventional neurotoxic insecticides.\n\nAuthor SummaryThe control of mosquitoes has been pursued in the last decades by the use of neurotoxic insecticides to prevent the spreading of dengue, zika and malaria, among other diseases. However, the selection and propagation of different mechanisms of resistance hinder the success of these compounds. New methodologies are needed for their control. Hematophagous arthropods, including mosquitoes, ingest quantities of blood that represent many times their body weight in a single meal, releasing huge amounts of amino acids during digestion. Recent studies showed that inhibition of the tyrosine catabolism pathway could be a new selective target for vector control. Thus we tested three different inhibitors of the second enzyme in the tyrosine degradation pathway as tools for mosquito control. Results showed that Nitisinone (NTBC), an inhibitor used in medicine, was the most potent of them. NTBC was lethal to Aedes aegypti when it was administered together with the blood meal and when it was topically applied. It also caused the death of Anopheles aquasalis and Culex quinquefasciatus mosquitoes, as well as field-collected Aedes populations resistant to neurotoxic insecticides, indicating that there is no cross-resistance. We discuss the possible use of NTBC as a new insecticide.

physiology↗