Transinfection of Wolbachia wAlbB into Culex quinquefasciatus mosquitoes does not alter vector competence for Hawaiian avian malaria (Plasmodium relictum GRW4).

Avian malaria is expanding upslope with warmer temperatures and driving multiple species of Hawaiian birds towards extinction. Methods to reduce malaria transmission are urgently needed to prevent further declines. Releasing Wolbachia-infected incompatible male mosquitoes could suppress mosquito populations and releasing Wolbachia-infected female mosquitoes (or both sexes) could reduce pathogen transmission if the Wolbachia strain reduced vector competence. We cleared Culex quinquefasciatus of their natural Wolbachia pipientis wPip infection and transinfected them with Wolbachia wAlbB isolated from Aedes albopictus. We show that wAlbB infection was transmitted transovarially, and demonstrate cytoplasmic incompatibility with wild-type mosquitoes infected with wPip from Oahu and Maui, Hawaii. We measured vector competence for avian malaria, Plasmodium relictum, lineage GRW4, of seven mosquito lines (two with wAlbB; three with natural wPip infection, and two cleared of Wolbachia infection) by allowing them to feed on canaries infected with recently collected field isolates of Hawaiian P. relictum. We tested 73 groups (Ntotal = 1176) of mosquitoes for P. relictum infection in abdomens and thoraxes 6-14 days after feeding on a range of parasitemias from 0.028% to 2.49%, as well as a smaller subset of salivary glands. We found no measurable effect of Wolbachia on any endpoint, but strong effects of parasitemia, days post feeding, and mosquito strain on both abdomen and thorax infection prevalence. These results suggest that releasing male wAlbB-infected C. quinquefasciatus mosquitoes could suppress wPip-infected mosquito populations, but would have little positive or negative impact on mosquito vector competence for P. relictum if wAlbB became established in local mosquito populations. More broadly, the lack of Wolbachia effects on vector competence we observed highlights the variable impacts of both native and transinfected Wolbachia infections in mosquitoes.

Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.

Releasing incompatible males drives strong suppression across populations of wild and Wolbachia-carrying Aedes aegypti in Australia.

Releasing sterile or incompatible male insects is a proven method of population management in agricultural systems with the potential to revolutionize mosquito control. Through a collaborative venture with the "Debug" Verily Life Sciences team, we assessed the incompatible insect technique (IIT) with the mosquito vector Aedes aegypti in northern Australia in a replicated treatment control field trial. Backcrossing a US strain of Ae. aegypti carrying Wolbachia wAlbB from Aedes albopictus with a local strain, we generated a wAlbB2-F4 strain incompatible with both the wild-type (no Wolbachia) and wMel-Wolbachia Ae. aegypti now extant in North Queensland. The wAlbB2-F4 strain was manually mass reared with males separated from females using Verily sex-sorting technologies to obtain no detectable female contamination in the field. With community consent, we delivered a total of three million IIT males into three isolated landscapes of over 200 houses each, releasing ∼50 males per house three times a week over 20 wk. Detecting initial overflooding ratios of between 5:1 and 10:1, strong population declines well beyond 80% were detected across all treatment landscapes when compared to controls. Monitoring through the following season to observe the ongoing effect saw one treatment landscape devoid of adult Ae. aegypti early in the season. A second landscape showed reduced adults, and the third recovered fully. These encouraging results in suppressing both wild-type and wMel-Ae. aegypti confirms the utility of bidirectional incompatibility in the field setting, show the IIT to be robust, and indicate that the removal of this arbovirus vector from human-occupied landscapes may be achievable.

Trends of Enterovirus D68 Concentrations in Wastewater, California, USA, February 2021-April 2023.

In this retrospective study, we measured enterovirus D68 (EV-D68) genomic RNA in wastewater solids longitudinally at 2 California, USA, wastewater treatment plants twice per week for 26 months. EV-D68 RNA was undetectable except when concentrations increased from mid-July to mid-December 2022, which coincided with a peak in confirmed EV-D68 cases.

Perspectives of Young Men Who Have Sex with Men on PrEP Adherence and Peer Navigation: A Qualitative Study.

HIV incidence is disproportionately high among young cisgender men who have sex with men (YMSM), but YMSM are less likely than adults to use HIV pre-exposure prophylaxis (PrEP). Among YMSM living with HIV, peer navigation programs have been effective in linkage to care and increasing medication adherence; such programs may aid HIV-uninfected YMSM in overcoming barriers to engagement in PrEP care. We conducted 32 semi-structured qualitative interviews at a community health center in Massachusetts, USA, specializing in sexual and gender minority health with four sub-groups of YMSM who: (1) had never discussed PrEP with a medical provider, (2) had discussed PrEP with a medical provider but declined a prescription, (3) were prescribed PrEP and have sub-optimal adherence (taking fewer than 4 pills per week), and (4) were prescribed PrEP and were optimally adherent. Domains addressed in the interviews included knowledge of PrEP and HIV prevention, barriers and facilitators to PrEP adherence, and attitudes toward peer navigation for PrEP. Interviews were transcribed and coded using thematic analysis methodology. Multiple themes emerged from the interviews, including finding that perceived costs, anticipated stigma, sexual activity, and relationship status influence PrEP uptake and adherence; establishing pill-taking routines is an important adherence facilitator; and peer navigators could offer benefits for PrEP adherence.

An Africa-wide genomic evolution of insecticide resistance in the malaria vector Anopheles funestus involves selective sweeps, copy number variations, gene conversion and transposons.

Insecticide resistance in malaria vectors threatens to reverse recent gains in malaria control. Deciphering patterns of gene flow and resistance evolution in malaria vectors is crucial to improving control strategies and preventing malaria resurgence. A genome-wide survey of Anopheles funestus genetic diversity Africa-wide revealed evidences of a major division between southern Africa and elsewhere, associated with different population histories. Three genomic regions exhibited strong signatures of selective sweeps, each spanning major resistance loci (CYP6P9a/b, GSTe2 and CYP9K1). However, a sharp regional contrast was observed between populations correlating with gene flow barriers. Signatures of complex molecular evolution of resistance were detected with evidence of copy number variation, transposon insertion and a gene conversion between CYP6P9a/b paralog genes. Temporal analyses of samples before and after bed net scale up suggest that these genomic changes are driven by this control intervention. Multiple independent selective sweeps at the same locus in different parts of Africa suggests that local evolution of resistance in malaria vectors may be a greater threat than trans-regional spread of resistance haplotypes.

Social problems in young children: the interplay of ADHD symptoms and facial emotion recognition.

Facial emotion recognition (FER) deficits interfere with interpretation of social situations and selection of appropriate responses. Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms are independently associated with social difficulties and might exacerbate the influence of deficient FER, because children with ADHD symptoms have fewer compensatory resources in social situations when they misinterpret emotions. Very few studies have tested this hypothesis in a community context, where child ADHD symptoms vary on a continuum. The current study extended this work by utilising a community sample (N = 87) of boys and girls in middle childhood (M = 7.83 years) and testing for moderation of FER effects separately by ADHD symptom type (ADHD-I = inattentive, H = hyperactive/impulsive, C = combined) using linear regression. While lower FER was associated with more social problems, this relationship was qualified by the presence of ADHD symptoms. Specifically, only children with relatively high ADHD symptoms in our community sample showed this inverse relationship, which was clearest among children with elevated ADHD-C or ADHD-I symptoms. No gender differences were observed. These results support our primary hypothesis, extend prior findings to boys and girls in the community, and have implications for understanding how ADHD symptoms and FER influence youth social deficits.

Exploring Relationships Between State-Level LGBTQ Inclusivity and BRFSS Indicators of Mental Health and Risk Behaviors: A Secondary Analysis.

OBJECTIVES: Minority Stress Theory suggests that repeated exposure to enacted stigma adversely affects mental health. States have wide authority to enact policies affecting the level of inclusivity experienced by lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) residents. The purpose of this study was to explore relationships between states' level of LGBTQ inclusivity and indicators of mental health/risk behaviors among an LGBTQ sample. METHODS: The 2018 Human Rights Campaign State Equality Index (SEI) and the 2018 Behavioral Risk Factor Surveillance Survey (BRFSS) were used to examine relationships between states' levels of LGBTQ inclusivity (predictor variable) and indicators of mental health/risk behaviors (outcome variables). Relationships were explored using descriptive statistics and survey-weighted logistic regression. RESULTS: Lower state inclusivity increased odds of fair/poor general health (adjusted odds ratio [AOR]: 1.22, 95% confidence interval [CI]: 1.01-1.48), increased odds of poor mental health days (AOR: 1.34, 95% CI: 1.11-1.62), increased odds of smoking (AOR: 1.62, 95% CI: 1.27-2.07), and increased odds of heavy drinking (AOR: 1.54, 95% CI: 1.26-1.86) and binge drinking (AOR: 1.23, 95% CI: 1.01-1.49). State inclusivity did not influence odds of a depressive disorder diagnosis or driving under the influence of alcohol. CONCLUSIONS: LGBTQ persons in restrictive states had increased odds of experiencing several indicators of mental health and risk behaviors. More research is needed to determine whether state policies affect other domains of LGBTQ persons' health. Health care providers should be mindful of LGBTQ persons' mental health/risk behaviors and the state policy environment, and should seek to implement mitigating health care strategies such as the use of validated assessment.

Estimating Relative Abundance of 2 SARS-CoV-2 Variants through Wastewater Surveillance at 2 Large Metropolitan Sites, United States.

Monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) is critical for public health management of coronavirus disease. Sequencing is resource-intensive and incompletely representative, and not all isolates can be sequenced. Because wastewater SARS-CoV-2 RNA concentrations correlate with coronavirus disease incidence in sewersheds, tracking VOCs through wastewater is appealing. We developed digital reverse transcription PCRs to monitor abundance of select mutations in Alpha and Delta VOCs in wastewater settled solids, applied these to July 2020-August 2021 samples from 2 large US metropolitan sewersheds, and compared results to estimates of VOC abundance from case isolate sequencing. Wastewater measurements tracked closely with case isolate estimates (Alpha, rp 0.82-0.88; Delta, rp 0.97). Mutations were detected in wastewater even at levels <5% of total SARS-CoV-2 RNA and in samples available 1-3 weeks before case isolate results. Wastewater variant monitoring should be strategically deployed to complement case isolate sequencing.

Detection of SARS-CoV-2 Variants Mu, Beta, Gamma, Lambda, Delta, Alpha, and Omicron in Wastewater Settled Solids Using Mutation-Specific Assays Is Associated with Regional Detection of Variants in Clinical Samples.

Changes in the circulation of SARS-CoV-2 variants of concern (VOCs) may require changes in the public health response to the COVID-19 pandemic, as they have the potential to evade vaccines and pharmaceutical interventions and may be more transmissive than other SARS-CoV-2 variants. As such, it is essential to track and prevent their spread in susceptible communities. We developed digital reverse transcription (RT)-PCR assays for mutations characteristic of VOCs and used them to quantify those mutations in samples of wastewater settled solids collected from a publicly owned treatment works (POTW) during different phases of the COVID-19 pandemic. Wastewater concentrations of single mutations characteristic of each VOC, normalized by the concentration of a conserved SARS-CoV-2 N gene, correlate with regional estimates of the proportion of clinical infections caused by each VOC. These results suggest that targeted RT-PCR assays can be used to detect variants circulating in communities and inform the public health response to the pandemic. IMPORTANCE Wastewater represents a pooled biological sample of the contributing community and thus a resource for assessing community health. Here, we show that emergence, spread, and disappearance of SARS-CoV-2 infections caused by variants of concern are reflected in the presence of variant genomic RNA in wastewater settled solids. This work highlights an important public health use case for wastewater.

Urinary Symptoms and Bladder Voiding Dysfunction Are Common in Young Men with Defecatory Disorders: A Retrospective Evaluation.

BACKGROUND AND AIMS: Lower urinary tract symptoms (LUTS) are frequently reported by constipated patients. Prospective studies investigating the association between defecatory disorders (DDs) and voiding dysfunction, predominantly in women, have reported conflicting results. This study investigated (1) the prevalence of LUTS in young men with DDs and (2) the association between objectively documented DDs and voiding dysfunction in constipated young men with LUTS. METHODS: We reviewed the medical records, including validated questionnaires, of men aged 18-40 with confirmed DDs treated with pelvic floor physical therapy (PT) at our institution from May 2018 to November 2020. In a separate group of constipated young men with LUTS who underwent high-resolution anorectal manometry (HRM), rectal balloon expulsion test (BET), and uroflowmetry, we explored the relationship between DDs and voiding dysfunction. RESULTS: A total of 72 men were evaluated in the study. Among 43 men receiving PT for a proven DD, 82% reported ≥ 1 LUTS, most commonly frequent urination. Over half of these men experienced a reduction in LUTS severity after bowel-directed pelvic floor PT. Among 29 constipated men with LUTS who had undergone HRM/BET and uroflowmetry, 28% had concurrent defecatory and voiding dysfunction, 10% had DD alone, 14% had only voiding dysfunction, and 48% had neither. The presence of DD was associated with significantly increased odds of concurrent voiding dysfunction (odds ratio 9.3 [95% CI 1.7-52.7]). CONCLUSIONS: Most young men with DDs experience LUTS, which may respond to bowel-directed physical therapy. Patients with DD and urinary symptoms have increased odds of voiding dysfunction.

Facial Affect Sensitivity Training for Young Children with Emerging CU Traits: An Experimental Therapeutics Approach.

OBJECTIVE: This article delineates best practices in the application of the experimental therapeutics framework for evaluating interventions within the context of randomized controlled trials (RCTs), offering a methodological primer and guiding framework for this approach. We illustrate these practices using an ongoing clinical trial conducted within the framework of a National Institute of Mental Health exploratory phased-innovation award for the development of psychosocial therapeutic interventions for mental disorders (R61/R33), describing the implementation of a novel "Facial Affect Sensitivity Training" (FAST) intervention for children with callous-unemotional (CU) traits. CU traits (e.g., lack of guilt or remorse, low empathy, shallow affect) are an established risk factor for persistent and severe youth misconduct, which reflect impairment in identified neurocognitive mechanisms that interfere with child socialization, and predict poor treatment outcomes, even with well-established treatments for disruptive behavior. METHOD: We outline the stages, goals, and best practices for an experimental therapeutics framework. In the FAST trial, we assert that impaired sensitivity for emotional distress cues (fear and/or sadness) is mechanistically linked to CU traits in children, and that by targeting sensitivity to facial affect directly via a computerized automated feedback and incentive system, we can exert downstream effects on CU traits. RESULTS: In the context of an open pilot trial, we found preliminary support for feasibility and mechanism engagement using FAST. CONCLUSIONS: We summarize pilot study limitations and how they are being addressed in the R61/R33 RCTs, as well as challenges and future directions for psychosocial experimental therapeutics.

Health impacts of climate change on gender diverse populations: A scoping review.

PURPOSE: To determine what is known about climate change health effects for gender diverse (GD) populations, and identify gaps in research, practice, education, and policy. DESIGN/METHODS: A scoping review was conducted. FINDINGS: Twenty-seven information sources met inclusion criteria. Natural disasters and inadequate disaster relief responses were identified as an overarching health threat for GD populations. Within this theme, four sub-themes emerged. No other climate-related health impacts for GD populations were mentioned in the sources reviewed. CONCLUSIONS: There are major gaps in knowledge about health implications of climate change for GD populations. Gender-sensitive data must be collected in order to better understand these threats and detect disparities. Currently most practice and policy recommendations focus on disaster relief. More research on the broad effects of climate change on GD populations is urgently needed to inform practice and policy. CLINICAL RELEVANCE: Climate change amplifies existing risks of adverse health outcomes. Because of discrimination, stigma, and violence, gender diverse individuals are particularly vulnerable.

The cortical organization of listening effort: New insight from functional near-infrared spectroscopy.

Everyday challenges impact our ability to hear and comprehend spoken language with ease, such as accented speech (source factors), spectral degradation (transmission factors), complex or unfamiliar language use (message factors), and predictability (context factors). Auditory degradation and linguistic complexity in the brain and behavior have been well investigated, and several computational models have emerged. The work here provides a novel test of the hypotheses that listening effort is partially reliant on higher cognitive auditory attention and working memory mechanisms in the frontal lobe, and partially reliant on hierarchical linguistic computation in the brain's left hemisphere. We specifically hypothesize that these models are robust and can be applied in ecologically relevant and coarse-grain contexts that rigorously control for acoustic and linguistic listening challenges. Using functional near-infrared spectroscopy during an auditory plausibility judgment task, we show the hierarchical cortical organization for listening effort in the frontal and left temporal-parietal brain regions. In response to increasing levels of cognitive demand, we found (i) poorer comprehension, (ii) slower reaction times, (iii) increasing levels of perceived mental effort, (iv) increasing levels of brain activity in the prefrontal cortex, (v) hierarchical modulation of core language processing regions that reflect increasingly higher-order auditory-linguistic processing, and (vi) a correlation between participants' mental effort ratings and their performance on the task. Our results demonstrate that listening effort is partly reliant on higher cognitive auditory attention and working memory mechanisms in the frontal lobe and partly reliant on hierarchical linguistic computation in the brain's left hemisphere. Further, listening effort is driven by a voluntary, motivation-based attention system for which our results validate the use of a single-item post-task questionnaire for measuring perceived levels of mental effort and predicting listening performance. We anticipate our study to be a starting point for more sophisticated models of listening effort and even cognitive neuroplasticity in hearing aid and cochlear implant users.

Impact of Enhanced Recovery After Surgery on Postoperative Outcomes for Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been associated with significant morbidity and increased hospital length of stay (LOS). The authors report their experience after implementation of an enhanced recovery after surgery (ERAS) program for CRS-HIPEC. METHODS: Outcomes were analyzed before and after ERAS implementation. The components of ERAS included preoperative carbohydrate loading, goal-directed fluid management, multimodal pain management, minimization of narcotic use, avoidance of nasogastric tubes, and early mobilization and feeding. RESULTS: Of 168 procedures, 88 (52%) were in the pre-ERAS group and 80 (48%) were in the post-ERAS group. The two groups did not differ in terms of age, sex, comorbidities, peritoneal carcinomatosis index scores, completeness of cytoreduction, or operative time. The ERAS patients received fewer fluids intraoperatively (mean, 4.2 vs 6.4 L; p < 0.01). The mean LOS was 7.9 days post-ERAS compared with 10.0 days pre-ERAS (p = 0.015). Clavien-Dindo complications classified as grade ≥ 3 were lower after ERAS (23.7% vs 38.6%; p = 0.04). Moreover, the readmission rates remained the same (16.2% vs 13.6%; p = 0.635). CONCLUSIONS: Implementation of an ERAS program for patients undergoing CRS-HIPEC is feasible and not associated with an increase in overall major complications or readmissions. These data support incorporation of ERAS protocols for CRS-HIPEC procedures.

Germline Cas9 expression yields highly efficient genome engineering in a major worldwide disease vector, Aedes aegypti.

The development of CRISPR/Cas9 technologies has dramatically increased the accessibility and efficiency of genome editing in many organisms. In general, in vivo germline expression of Cas9 results in substantially higher activity than embryonic injection. However, no transgenic lines expressing Cas9 have been developed for the major mosquito disease vector Aedes aegypti Here, we describe the generation of multiple stable, transgenic Ae. aegypti strains expressing Cas9 in the germline, resulting in dramatic improvements in both the consistency and efficiency of genome modifications using CRISPR. Using these strains, we disrupted numerous genes important for normal morphological development, and even generated triple mutants from a single injection. We have also managed to increase the rates of homology-directed repair by more than an order of magnitude. Given the exceptional mutagenic efficiency and specificity of the Cas9 strains we engineered, they can be used for high-throughput reverse genetic screens to help functionally annotate the Ae. aegypti genome. Additionally, these strains represent a step toward the development of novel population control technologies targeting Ae. aegypti that rely on Cas9-based gene drives.

Mobile App Strategy to Facilitate Human Papillomavirus Vaccination Among Young Men Who Have Sex With Men: Pilot Intervention Study.

BACKGROUND: Mobile app-based interventions have been identified as potential facilitators for vaccination among young men who have sex with men (MSM). OBJECTIVE: This pilot study aimed to test the feasibility of a theoretically informed mobile health (mHealth) tool designed to reduce health disparities and facilitate human papillomavirus (HPV) vaccination among a sample of young MSM. METHODS: The development of the mHealth tool was guided by previous research, implementation intention theory, and design thinking. We recruited MSM aged 18-26 years through a popular online dating app and linked participants to our mHealth tool, which provided HPV vaccine information and fostered access to care. RESULTS: A total of 42 young MSM participated in this pilot study in Boston, Massachusetts. Participants reported variable HPV knowledge (ie, high knowledge of HPV risk factors and low knowledge of HPV-related cancer risks for men) and positive vaccine beliefs and attitudes. Of those who were either unvaccinated, not up to date, or did not report vaccine status, 23% (8/35) utilized the mHealth tool to obtain HPV vaccination. Participants primarily utilized the tool's (1) educational components and (2) capabilities facilitating concrete vaccine action plans. CONCLUSIONS: We recruited an underserved at-risk population of youth via an online dating app for our mHealth intervention that resulted in in-person health care delivery. This study was limited by enrollment challenges, including low willingness to download the mHealth tool to mobile devices.

Transgender and non-conforming persons' mental healthcare experiences: An integrative review.

INTRODUCTION: Transgender and gender non-conforming (TGNC) people in the United States face disproportionate rates of mental health disorders, including suicidality, depression, anxiety, and substance use disorders than the general population. Patients' experiences utilizing mental healthcare is a determinant in their care-seeking behaviors and treatment success. AIM/QUESTION: The purpose of this integrative review is to better understand the firsthand mental healthcare experiences of TGNC persons. METHOD: The authors sought to locate recent English-language articles that described the mental healthcare experiences of TGNC persons. To do so, only articles that conducted data collection with a TGNC sample were considered for review. RESULTS: Seven articles met criteria for review. Four themes emerged that depicted experiences of health promotion (welcoming environments, staff knowledge and response) and health prevention (enacted stigma, racial disparities and intersectional insensitivity). DISCUSSION: Themes indicated that TGNC persons have mixed experiences (excellent to harmful/damaging) when receiving mental healthcare. There is room for healthcare provider growth in skills to increase TGNC cultural competency. IMPLICATIONS FOR PRACTICE: Mental healthcare providers and nurses would benefit from interventions to promote TGNC culturally competent care, including in-service training or continuing education for the current work force as well as incorporating TGNC content into pre-licensure educational curricula.

Pollutants and Insecticides Drive Local Adaptation in African Malaria Mosquitoes.

The Anopheles gambiae complex contains a number of highly anthropophilic mosquito species that have acquired exceptional ability to thrive in complex human habitats. Thus, examining the evolutionary history of this Afrotropical mosquito may yield vital information on the selective processes that occurred during the adaptation to human-dominated environments. We performed reduced representation sequencing on 941 mosquitoes of the Anopheles gambiae complex collected across four ecogeographic zones in Cameroon. We find evidence for genetic and geographic subdivision within An. coluzzii and An. gambiae sensu stricto-the two most significant malaria vectors in the region. Importantly, in both species, rural and urban populations are genetically differentiated. Genome scans reveal pervasive signatures of selection centered on genes involved in xenobiotic resistance. Notably, a selective sweep containing detoxification enzymes is prominent in urban mosquitoes that exploit polluted breeding sites. Overall, our study suggests that recent anthropogenic environmental modifications and widespread use of insecticides are driving population differentiation and local adaptation in vectors with potentially significant consequences for malaria epidemiology.