Indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are the main methods used to control mosquito populations for malaria prevention. The efficacy of these strategies is threatened by the spread of insecticide resistance (IR), limiting the success of malaria control. Studies of the genetic evolution leading to insecticide resistance could enable the identification of molecular markers that can be used for IR surveillance and an improved understanding of the molecular mechanisms associated with IR. This study used a weighted gene co-expression network analysis (WGCNA) algorithm, a systems biology approach, to identify genes with similar co-expression patterns (modules) and hub genes that are potential molecular markers for insecticide resistance surveillance in Kenya and Benin. A total of 20 and 26 gene co-expression modules were identified via average linkage hierarchical clustering from Anopheles arabiensis and An. gambiae, respectively, and hub genes (highly connected genes) were identified within each module. Three specific genes stood out: serine protease, E3 ubiquitin-protein ligase, and cuticular proteins, which were top hub genes in both species and could serve as potential markers and targets for monitoring IR in these malaria vectors. In addition to the identified markers, we explored molecular mechanisms using enrichment maps that revealed a complex process involving multiple steps, from odorant binding and neuronal signaling to cellular responses, immune modulation, cellular metabolism, and gene regulation. Incorporation of these dynamics into the development of new insecticides and the tracking of insecticide resistance could improve the sustainable and cost-effective deployment of interventions.

Trade-offs between evolutionary gain and loss are prevalent in nature, yet their genetic basis is not well resolved. The evolution of insect resistance to insecticide is often associated with strong fitness costs; however, how the fitness trade-offs operates remains poorly understood. Here, we show that the mitogen-activated protein kinase (MAPK) pathway and its upstream and downstream actors underlie the fitness trade-offs associated with insecticide resistance in the whitefly Bemisia tabaci. Specifically, we find a key cytochrome P450 gene CYP6CM1, that confers neonicotinoids resistance to in B. tabaci, is regulated by the MAPKs p38 and ERK through their activation of the transcription factor cAMP-response element binding protein. However, phosphorylation of p38 and ERK also leads to the activation of the transcription repressor Cap \"n\" collar isoform C (CncC) that negatively regulates exuperantia (Ex), vasa (Va), and benign gonial cell neoplasm (Bg), key genes involved in oogenesis, leading to abnormal ovary growth and a reduction in female fecundity. We further demonstrate that the transmembrane G protein-coupled receptor (GPCR) neuropeptide FF receptor 2 (NPFF2) triggers the p38 and ERK pathways via phosphorylation. Additionally, a positive feedback loop between p38 and NPFF2 leads to the continuous activation of the MAPK pathways, thereby constitutively promoting neonicotinoids resistance but with a significant reproductive cost. Collectively, these findings provide fundamental insights into the role of cis-trans regulatory networks incurred by GPCR-MAPK signaling pathways in evolutionary trade-offs and applied knowledge that can inform the development of strategies for the sustainable pest control.

BACKGROUND: The emergence of pyrethroid resistance has threatened the elimination of Triatoma infestans from the Gran Chaco ecoregion. We investigated the status and spatial distribution of house infestation with T. infestans and its main determinants in Castelli, a municipality of the Argentine Chaco with record levels of triatomine pyrethroid resistance, persistent infestation over 2005-2014, and limited or no control actions over 2015-2020.
METHODS: We conducted a 2-year longitudinal survey to assess triatomine infestation by timed manual searches in a well-defined rural section of Castelli including 14 villages and 234 inhabited houses in 2018 (baseline) and 2020, collected housing and sociodemographic data by on-site inspection and a tailored questionnaire, and synthetized these data into three indices generated by multiple correspondence analysis.
RESULTS: The overall prevalence of house infestation in 2018 (33.8%) and 2020 (31.6%) virtually matched the historical estimates for the period 2005-2014 (33.7%) under recurrent pyrethroid sprays. While mean peridomestic infestation remained the same (26.4-26.7%) between 2018 and 2020, domestic infestation slightly decreased from 12.2 to 8.3%. Key triatomine habitats were storerooms, domiciles, kitchens, and structures occupied by chickens. Local spatial analysis showed significant aggregation of infestation and bug abundance in five villages, four of which had very high pyrethroid resistance approximately over 2010-2013, suggesting persistent infestations over space-time. House bug abundance within the hotspots consistently exceeded the estimates recorded in other villages. Multiple regression analysis revealed that the presence and relative abundance of T. infestans in domiciles were strongly and negatively associated with indices for household preventive practices (pesticide use) and housing quality. Questionnaire-derived information showed extensive use of pyrethroids associated with livestock raising and concomitant spillover treatment of dogs and (peri) domestic premises.
CONCLUSIONS: Triatoma infestans populations in an area with high pyrethroid resistance showed slow recovery and propagation rates despite limited or marginal control actions over a 5-year period. Consistent with these patterns, independent experiments confirmed the lower fitness of pyrethroid-resistant triatomines in Castelli compared with susceptible conspecifics. Targeting hotspots and pyrethroid-resistant foci with appropriate house modification measures and judicious application of alternative insecticides with adequate toxicity profiles are needed to suppress resistant triatomine populations and prevent their eventual regional spread.

According to the World Health Organization vector-borne diseases account for more than 17% of all infectious diseases, causing more than 700,000 deaths annually. Vectors are organisms that are able to transmit infectious pathogens between humans, or from animals to humans. Many of these vectors are hematophagous insects, which ingest the pathogen from an infected host during a blood meal, and later transmit it into a new host. Malaria, dengue, African trypanosomiasis, yellow fever, leishmaniasis, Chagas disease, and many others are examples of diseases transmitted by insects.Both the diet and the infection with pathogens trigger changes in many metabolic pathways, including lipid metabolism, compared to other insects. Blood contains mostly proteins and is very poor in lipids and carbohydrates. Thus, hematophagous insects attempt to efficiently digest and absorb diet lipids and also rely on a large de novo lipid biosynthesis based on utilization of proteins and carbohydrates as carbon source. Blood meal triggers essential physiological processes as molting, excretion, and oogenesis; therefore, lipid metabolism and utilization of lipid storage should be finely synchronized and regulated regarding that, in order to provide the necessary energy source for these events. Also, pathogens have evolved mechanisms to hijack essential lipids from the insect host by interfering in the biosynthesis, catabolism, and transport of lipids, which pose challenges to reproduction, survival, fitness, and other insect traits.In this chapter, we have tried to collect and highlight the current knowledge and recent discoveries on the metabolism of lipids in insect vectors of diseases related to the hematophagous diet and pathogen infection.

The insecticide resistance is becoming increasingly severe in malaria vectors and has become one of the most important threats to global malaria elimination. Currently, malaria vectors not only have developed high resistance to conventional insecticides, including organochlorine, organophosphates, carbamates, and pyrethroids, but also have been resistant to recently used neonicotinoids and pyrrole insecticides. This article describes the current status of global insecticide resistance in malaria vectors and global insecticide resistance management strategies, analyzes the possible major challenges in the insecticide resistance management, and proposes the response actions, so as to provide insights into global insecticide resistance management and contributions to global malaria elimination.
［摘要］ 传疟媒介杀虫剂抗性问题日益严峻, 已成为全球消除疟 疾面临的最重要挑战之一。目前, 传疟媒介不仅对有机氯、有机 磷、氨基甲酸酯和拟除虫菊酯类等传统杀虫剂产生了高度抗性, 而且对近年来新使用的新烟碱类和吡咯类杀虫剂亦产生了抗性。 本文对当前全球传疟媒介杀虫剂抗性现状和相关抗性治理策略 进行了梳理, 并就杀虫剂抗性治理中存在的主要问题进行了分 析, 提出了下一步应对措施, 旨在为全球传疟媒介杀虫剂抗性治 理提供科学参考, 助力全球消除疟疾。.

BACKGROUND: The Dual-Active Ingredient long-lasting insecticidal nets (Dual-AI LLIN) have been developed to counteract the reduced efficacy of pyrethroid (PY)-only nets due to widespread pyrethroid insecticide resistance in malaria vector mosquitoes. They constitute half of the nets distributed in sub-Saharan Africa between 2022 and 2024. However, their effectiveness once they develop holes is unclear, particularly in pyrethroid-resistant settings. This study evaluates the textile integrity of three dual- AI LLINs compared to standard PY LLN, over 3 years of use in a community in Tanzania and the associated impact on malaria prevalence and incidence.
METHODS: A secondary analysis of data from a randomized controlled trial (RCT) in North-western Tanzania was conducted to evaluate the effectiveness of α-cypermethrin only; pyriproxyfen and α-cypermethrin (PPF-PY); chlorfenapyr and α-cypermethrin (chlorfenapyr-PY); and the synergist piperonyl butoxide and permethrin (PBO-PY) LLINs on malaria infection prevalence and case incidence. The association between the net textile condition and 1/malaria prevalence over 3 years of use between 2019 and 2022, and 2/malaria case incidence in a cohort of children over 2 years of follow-up was assessed between 2019 and 2021.
RESULTS: There was no significant association between damaged (OR 0.98, 95% CI 0.71-1.37, p-value  = 0.655) and too-torn (OR 1.07, 95% CI 0.77-1.47, p-value = 0.694) compared to intact nets on malaria prevalence for all net types. However, there were reduced rates of malaria case incidence in children sleeping under a net in good condition compared to too-torn nets (incidence rate ratio (IRR) 0.76 [95% CI 0.63-0.92], p = 0.005). Malaria incidence was also consistently lower in too-torn PBO-PY LLIN (IRR = 0.37 [95% CI 0.19-0.72], p = 0.003) and chlorfenapyr-PY LLIN (IRR = 0.45 [95% CI 0.33-0.97], p = 0.053) compared to an intact PY-only LLIN during the first year of follow up. In year 2, the incidence was only significantly lower in intact chlorfenapyr-PY LLIN (IRR = 0.49 [95% CI 0.29-0.81], p = 0.006) compared to intact PY LLIN.
CONCLUSIONS: The study confirmed that sleeping under a chlorfenapyr-PY LLIN or PBO-PY LLIN offered superior protection to pyrethroid-only nets even when torn. Preventing the development of holes is essential as they impact the level of protection offered against malaria infection.
BACKGROUND: ClinicalTrials.gov, number (NCT03554616).

BACKGROUND: Phosphine resistance in Tribolium castaneum challenges grain storage. This study investigates the impact of cytochrome P450 (CYP) enzymes and CYP346 family genes on phosphine resistance in Indian Tribolium castaneum populations.
METHODS: Seven field populations of T. castaneum were compared with Lab- susceptible population for their resistance to phosphine. The levels of cytochrome P450 enzyme and expression of certain CYP346 family genes were tracked in these populations.
RESULTS: The highly resistant Patiala population showed significantly increased CYP450 activity (11.26 ± 0.14 nmol/min/mg protein, 7.41-fold higher) compared to the lab-susceptible population (1.52 ± 0.09 nmol/min/mg protein) when assayed using 8 mM p-nitroanisole as the substrate. The mRNA expression was measured relative to the standard gene RPS18 and revealed significant upregulation of CYP346B1 and CYP346B3 in highly resistant populations Moga and Patiala (CYP346B1: 12.09 ± 2.19 to 21.74 ± 3.82; CYP346B3: 59.097 ± 10.265 to 50.148 ± 8.272). Patiala\'s CYP346B1 exhibited an impressive 685.76-fold change, and Moga\'s CYP346B3 showed a 361.893-fold change compared to lab-susceptible. Linear regression confirmed robust fits for each gene (R2: 0.693 to 0.756). Principal component analysis (PCA) demonstrated a strong positive correlation between CYP346 genes expression; and cytochrome P450 activity. Patiala, Moga, and Hapur populations showed conformity, associating higher resistance with increased P450 activity and CYP346 gene expression. Cluster analysis highlighted a potential correlation between CYP346B1, CYP346B2, and CYP346B3 and P450 activity, with Patiala and Moga clustering together.
CONCLUSIONS: Variability in CYP346B1 and CYP346B3 in strong resistance populations may contribute to adaptation and resistance mechanisms. The study provides insights into specific CYP346 family genes associated with phosphine resistance, emphasizing the intricate interaction between CYP450 detoxifying enzymes, CYP346 family genes, and resistance mechanisms. The upregulation of CYP346 genes suggests a survival advantage for T. castaneum against phosphine, diminishing phosphine\'s efficacy as a pest control measure.

UNASSIGNED: Despite significant progress in malaria control throughout India, Chhattisgarh state continues to be a significant contributor to both malaria morbidity and mortality. This study aims to identify key factors associated with malaria endemicity, with a goal of focusing on these factors for malaria elimination by 2030.
METHODS: We employed an analysis and narrative review methodology to summarize the existing evidence on malaria epidemiology in Chhattisgarh. Data encompassing environmental conditions, dominant malaria vectors and their distribution, and the impact of previous interventions on malaria control, were extracted from published literature using PubMed and Google Scholar. This information was subsequently correlated with malaria incidence data using appropriate statistical and geographical methods.
RESULTS: Much of the malaria burden in Chhattisgarh state is concentrated in a few specific districts. The primary malaria vectors in these regions are Anopheles culicifacies and An. fluviatilis. High transmission areas are found in tribal belts which are challenging to access and are characterized by densely forested areas that provide a conducive habitat for malaria vectors.
UNASSIGNED: Conducive environmental conditions characterized by high forest cover, community behavior, and insurgency, contribute to high malaria endemicity in the area. Challenges include insecticide resistance in malaria vectors and asymptomatic malaria. Allocating additional resources to high-endemic districts is crucial. Innovative and focused malaria control programs of the country, such as DAMAN and Malaria Mukt Abhiyan, hold immense importance.

Insects are the most diverse form of life, and as such, they interact closely with humans, impacting our health, economy, and agriculture. Beneficial insect species contribute to pollination, biological control of pests, decomposition, and nutrient cycling. Pest species can cause damage to agricultural crops and vector diseases to humans and livestock. Insects are often exposed to toxic xenobiotics in the environment, both naturally occurring toxins like plant secondary metabolites and synthetic chemicals like herbicides, fungicides, and insecticides. Because of this, insects have evolved several mechanisms of resistance to toxic xenobiotics, including sequestration, behavioral avoidance, and enzymatic degradation, and in many cases had developed symbiotic relationships with microbes that can aid in this detoxification. As research progresses, the important roles of these microbes in insect health and function have become more apparent. Bacterial symbionts that degrade plant phytotoxins allow host insects to feed on otherwise chemically defended plants. They can also confer pesticide resistance to their hosts, especially in frequently treated agricultural fields. It is important to study these interactions between insects and the toxic chemicals they are exposed to in order to further the understanding of pest insect resistance and to mitigate the negative effect of pesticides on nontarget insect species like Hymenopteran pollinators.

The house fly Musca domestica L. is one of the most common insects of veterinary and medical importance worldwide; its ability to develop resistance to a large number of insecticides is well known. Many studies support the involvement of cytochrome P-450-dependent monooxygenases (P450) in the development of resistance to pyrethroids, neonicotinoids, carbamates, and organophosphates among insects. In this paper, the monooxygenase activity and expression level of CYP6D1 were studied for the first time in a chlorfenapyr-resistant strain of house fly. Our studies demonstrated that P450 activity in adults of the susceptible strain (Lab TY) and chlorfenapyr-resistant strain (ChlA) was 1.56-4.05-fold higher than that in larvae. In females of the Lab TY and ChlA strains, this activity was 1.53- and 1.57-fold higher, respectively (p < 0.05), than that in males, and in contrast, the expression level of CYP6D1 was 21- and 8-fold lower, respectively. The monooxygenase activity did not vary between larvae of the susceptible strain Lab TY and the chlorfenapyr-resistant strain ChlA. Activity in females and males of the ChlA strain exceeded that in the Lab TY strain specimens by 1.54 (p = 0.08) and 1.83 (p < 0.05) times, respectively, with the same level of CYP6D1 expression. PCR-RFLP analysis revealed a previously undescribed mutation in the promoter region of the CYP6D1 gene in adults of the Lab TY and ChlA strains, and it did not affect the gene expression level. The obtained results show that the development of resistance to chlorfenapyr in M. domestica is accompanied by an increase in P450-monooxygenase activity without changes in CYP6D1 expression.