Local-scale phylodynamics reveal differential community impact of SARS-CoV-2 in a metropolitan US county.

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.

Sentinel Surveillance System Implementation and Evaluation for SARS-CoV-2 Genomic Data, Washington, USA, 2020-2021.

Genomic data provides useful information for public health practice, particularly when combined with epidemiologic data. However, sampling bias is a concern because inferences from nonrandom data can be misleading. In March 2021, the Washington State Department of Health, USA, partnered with submitting and sequencing laboratories to establish sentinel surveillance for SARS-CoV-2 genomic data. We analyzed available genomic and epidemiologic data during presentinel and sentinel periods to assess representativeness and timeliness of availability. Genomic data during the presentinel period was largely unrepresentative of all COVID-19 cases. Data available during the sentinel period improved representativeness for age, death from COVID-19, outbreak association, long-term care facility-affiliated status, and geographic coverage; timeliness of data availability and captured viral diversity also improved. Hospitalized cases were underrepresented, indicating a need to increase inpatient sampling. Our analysis emphasizes the need to understand and quantify sampling bias in phylogenetic studies and continue evaluation and improvement of public health surveillance systems.

Associations Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants and Risk of Coronavirus Disease 2019 (COVID-19) Hospitalization Among Confirmed Cases in Washington State: A Retrospective Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. RESULTS: In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40-4.26), Beta (HR 2.85, 95% CI 1.56-5.23), Delta (HR 2.28 95% CI 1.56-3.34), or Alpha (HR 1.64, 95% CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSIONS: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Household Transmission of SARS-CoV-2 from Humans to Pets, Washington and Idaho, USA.

SARS-CoV-2 likely emerged from an animal reservoir. However, the frequency of and risk factors for interspecies transmission remain unclear. We conducted a community-based study in Idaho, USA, of pets in households that had >1 confirmed SARS-CoV-2 infections in humans. Among 119 dogs and 57 cats, clinical signs consistent with SARS-CoV-2 were reported for 20 dogs (21%) and 19 cats (39%). Of 81 dogs and 32 cats sampled, 40% of dogs and 43% of cats were seropositive, and 5% of dogs and 8% of cats were PCR positive. This discordance might be caused by delays in sampling. Respondents commonly reported close human‒animal contact and willingness to take measures to prevent transmission to their pets. Reported preventive measures showed a slightly protective but nonsignificant trend for both illness and seropositivity in pets. Sharing of beds and bowls had slight harmful effects, reaching statistical significance for sharing bowls and seropositivity.

Antimicrobial Resistance Patterns of Urinary Escherichia coli Among Outpatients in Washington State, 2013-2017: Associations With Age and Sex.

BACKGROUND: Management of acute, uncomplicated cystitis in outpatients benefits from knowledge of drug resistance patterns in the population. However, antibiograms are often not available for the outpatient setting, and the role of host factors such as sex and age in assessing the likelihood of resistance are not well understood. We investigated whether antibiotic resistance patterns of outpatient urinary Escherichia coli isolates vary by age group and sex in a large database of antibiotic susceptibility test (AST) results from Washington State. METHODS: We retrospectively analyzed AST data for outpatient urinary E. coli isolates in Washington State tested at a clinical reference laboratory from 2013 to 2017. In logistic regression models stratified by sex, we tested the associations of antibiotic resistance with patient age. RESULTS: We found females >50 years had greater odds than females younger than 19 for resistance to amoxicillin-clavulanate (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.22-1.69), ciprofloxacin (OR, 3.04; 95% CI, 2.48-3.74), ceftriaxone (OR, 2.58; 95% CI, 1.77-3.92), and gentamicin (OR, 1.62; 95% CI, 1.27-2.08) (all P < .001). Compared to males younger than 19, males >50 years had greater odds of resistance to ciprofloxacin (OR, 2.59; 95% CI, 1.18-5.69) and lower odds of resistance to amoxicillin-clavulanate (OR, 0.56; 95% CI, .34-.96) (all P < .05). CONCLUSIONS: These findings demonstrate that age and sex are associated with variability in antibiotic resistance patterns in the outpatient setting. Availability of outpatient antibiotic resistance data based on sex and age may be useful to inform empiric prescribing for outpatient UTIs and to support antibiotic stewardship efforts.

A Model for Genome-First Care: Returning Secondary Genomic Findings to Participants and Their Healthcare Providers in a Large Research Cohort.

There is growing interest in communicating clinically relevant DNA sequence findings to research participants who join projects with a primary research goal other than the clinical return of such results. Since Geisinger's MyCode Community Health Initiative (MyCode) was launched in 2007, more than 200,000 participants have been broadly consented for discovery research. In 2013 the MyCode consent was amended to include a secondary analysis of research genomic sequences that allows for delivery of clinical results. Since May 2015, pathogenic and likely pathogenic variants from a set list of genes associated with monogenic conditions have prompted "genome-first" clinical encounters. The encounters are described as genome-first because they are identified independent of any clinical parameters. This article (1) details our process for generating clinical results from research data, delivering results to participants and providers, facilitating condition-specific clinical evaluations, and promoting cascade testing of relatives, and (2) summarizes early results and participant uptake. We report on 542 participants who had results uploaded to the electronic health record as of February 1, 2018 and 291 unique clinical providers notified with one or more participant results. Of these 542 participants, 515 (95.0%) were reached to disclose their results and 27 (5.0%) were lost to follow-up. We describe an exportable model for delivery of clinical care through secondary use of research data. In addition, subject and provider participation data from the initial phase of these efforts can inform other institutions planning similar programs.

A novel approach to modeling epidemic vulnerability, applied to Aedes aegypti-vectored diseases in Perú.

BACKGROUND: A proactive approach to preventing and responding to emerging infectious diseases is critical to global health security. We present a three-stage approach to modeling the spatial distribution of outbreak vulnerability to Aedes aegypti-vectored diseases in Perú. METHODS: Extending a framework developed for modeling hemorrhagic fever vulnerability in Africa, we modeled outbreak vulnerability in three stages: index case potential (stage 1), outbreak receptivity (stage 2), and epidemic potential (stage 3), stratifying scores on season and El Niño events. Subsequently, we evaluated the validity of these scores using dengue surveillance data and spatial models. RESULTS: We found high validity for stage 1 and 2 scores, but not stage 3 scores. Vulnerability was highest in Selva Baja and Costa, and in summer and during El Niño events, with index case potential (stage 1) being high in both regions but outbreak receptivity (stage 2) being generally high in Selva Baja only. CONCLUSIONS: Stage 1 and 2 scores are well-suited to predicting outbreaks of Ae. aegypti-vectored diseases in this setting, however stage 3 scores appear better suited to diseases with direct human-to-human transmission. To prevent outbreaks, measures to detect index cases should be targeted to both Selva Baja and Costa, while Selva Baja should be prioritized for healthcare system strengthening. Successful extension of this framework from hemorrhagic fevers in Africa to an arbovirus in Latin America indicates its broad utility for outbreak and pandemic preparedness and response activities.

Clinical outcomes of a genomic screening program for actionable genetic conditions.

PURPOSE: Three genetic conditions-hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia-have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population. METHODS: Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger's MyCode project. EHR of all eligible participants was evaluated for a prior genetic diagnosis and, among participants without such a diagnosis, relevant personal/family history, postdisclosure clinical diagnoses, and postdisclosure risk management. RESULTS: Eighty-seven percent of participants (305/351) did not have a prior genetic diagnosis of their tier 1 result. Of these, 65% had EHR evidence of relevant personal and/or family history of disease. Of 255 individuals eligible to have risk management, 70% (n = 179) had a recommended risk management procedure after results disclosure. Thirteen percent of participants (41/305) received a relevant clinical diagnosis after results disclosure. CONCLUSION: Genomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.

Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution.

Knockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution.

Fine-scale spatial and social patterns of SARS-CoV-2 transmission from identical pathogen sequences.

Pathogen genomics can provide insights into disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets. Genetically proximal viruses indicate epidemiological linkage and are informative about transmission events. Here, we leverage pairs of identical sequences using 114,298 SARS-CoV-2 genomes collected via sentinel surveillance from March 2021 to December 2022 in Washington State, USA, with linked age and residence information to characterize fine-scale transmission. The location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postal codes with male prisons, consistent with transmission between prison facilities. Transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. This work improves our ability to characterize transmission from large pathogen genome datasets.

A Cross Sectional Study of Respiratory and Allergy Status in Dairy Workers.

INTRODUCTION: Workers on dairy farms face exposures to organic dusts and endotoxin. At the same time, a number of studies of farmers have reported a lower prevalence of asthma in farmworkers compared to persons without farm contact. The "hygiene hypothesis" suggests that early life exposures on farms could be protective against allergic disease and asthma. Such protective relationships are less well studied in adult farm workers. METHODS: A cross-sectional analysis of respiratory function and allergy status was performed in a sample of dairy farm workers (n = 42) and community controls (n = 40). Measures of respiratory status (spirometry, exhaled nitric oxide FeNO, self-reported symptoms) and levels of total and bovine-specific IgE were compared between the groups. RESULTS: Prevalence of self-reported asthma and most respiratory symptoms was similar in the two groups, with the exception of increased report of dyspnea among dairy workers. In the dairy workers, level of lung function was not reduced and FeNO was not increased. In unadjusted and adjusted models, dairy work was not associated with reduced lung function or increased airway inflammation. Mean IgE levels did not differ significantly between workers and controls, but elevated bovine-specific IgE was detected only among dairy workers, with an apparent association between elevated bovine IgE and increased FeNO. CONCLUSION: While dairy workers did not demonstrate increased asthma prevalence compared to controls, sensitization to bovine antigen in several workers appeared to be associated with airway inflammation. Occupational health programs for dairy workers should consider the risk of animal allergy as part of respiratory health protection efforts.

Outpatient Antibiotic Resistance Patterns of Escherichia coli Urinary Isolates Differ by Specialty Type.

Antibiotic-resistant E. coli infections represent a major cause of morbidity and mortality and pose a challenge to antibiotic stewardship. We analyzed a large outpatient data set of E. coli urinary isolates to determine whether resistance patterns vary between types of outpatient practices. Using deidentified data from a clinical reference laboratory over 5 years and logistic regression, we examined the association of antibiotic resistance with outpatient practice type, controlling for testing year, patient sex, and patient age. The odds of antibiotic resistance were significantly higher in urology/nephrology practices for ampicillin (odds ratio [OR] 1.36; 95% CI, 1.10 to 1.69), ciprofloxacin (OR 2.29; 95% CI, 1.77 to 2.94), trimethoprim-sulfamethoxazole (OR 1.52; 95% CI, 1.18 to 1.94), and gentamicin (OR 1.72; 95% CI, 1.16 to 2.46). Odds of resistance were also higher for ciprofloxacin in oncology practices (OR 1.54; 95% CI, 1.08 to 2.15) and "all other specialties" (OR 1.33; 95% CI, 1.13 to 1.56). In contrast, specimens from obstetrics and gynecology practices had lower odds of having resistance to ampicillin (OR 0.90; 95% CI, 0.82 to 0.99) and trimethoprim-sulfa (OR 0.83; 95% CI, 0.73 to 0.93) but higher odds of having resistance to nitrofurantoin (OR 1.33; 95% CI, 1.03 to 1.70). Other findings included lower odds of having resistance to trimethoprim-sulfa in pediatric practices (OR 0.78; 95% CI, 0.64 to 0.94) and lower odds of having resistance to gentamicin in isolates from internal medicine practices (OR 0.66; 95% CI, 0.51 to 0.84) (all P < 0.05). IMPORTANCE Patterns of antibiotic resistance in E. coli urinary isolates can vary between outpatient specialties. The use of clinical data to create practice and specialty-specific antibiograms in outpatient settings may improve antibiotic stewardship.

The effect of weather and climate on dengue outbreak risk in Peru, 2000-2018: A time-series analysis.

BACKGROUND: Dengue fever is the most common arboviral disease in humans, with an estimated 50-100 million annual infections worldwide. Dengue fever cases have increased substantially in the past four decades, driven largely by anthropogenic factors including climate change. More than half the population of Peru is at risk of dengue infection and due to its geography, Peru is also particularly sensitive to the effects of El Niño Southern Oscillation (ENSO). Determining the effect of ENSO on the risk for dengue outbreaks is of particular public health relevance and may also be applicable to other Aedes-vectored viruses. METHODS: We conducted a time-series analysis at the level of the district-month, using surveillance data collected from January 2000 to September 2018 from all districts with a mean elevation suitable to survival of the mosquito vector (<2,500m), and ENSO and weather data from publicly-available datasets maintained by national and international agencies. We took a Bayesian hierarchical modeling approach to address correlation in space, and B-splines with four knots per year to address correlation in time. We furthermore conducted subgroup analyses by season and natural region. RESULTS: We detected a positive and significant effect of temperature (°C, RR 1.14, 95% CI 1.13, 1.15, adjusted for precipitation) and ENSO (ICEN index: RR 1.17, 95% CI 1.15, 1.20; ONI index: RR 1.04, 95% CI 1.02, 1.07) on outbreak risk, but no evidence of a strong effect for precipitation after adjustment for temperature. Both natural region and season were found to be significant effect modifiers of the ENSO-dengue effect, with the effect of ENSO being stronger in the summer and the Selva Alta and Costa regions, compared with winter and Selva Baja and Sierra regions. CONCLUSIONS: Our results provide strong evidence that temperature and ENSO have significant effects on dengue outbreaks in Peru, however these results interact with region and season, and are stronger for local ENSO impacts than remote ENSO impacts. These findings support optimization of a dengue early warning system based on local weather and climate monitoring, including where and when to deploy such a system and parameterization of ENSO events, and provide high-precision effect estimates for future climate and dengue modeling efforts.

Household transmission of SARS-CoV-2 from humans to pets in Washington and Idaho: burden and risk factors.

SARS-CoV-2 is believed to have emerged from an animal reservoir; however, the frequency of and risk factors for inter-species transmission remain unclear. We carried out a community-based study of pets in households with one or more confirmed SARS-CoV-2 infection in humans. Among 119 dogs and 57 cats with completed surveys, clinical signs consistent with SARS-CoV-2 were reported in 20 dogs (21%) and 19 cats (39%). Out of 81 dogs and 32 cats sampled for testing, 40% of dogs and 43% of cats were seropositive, and 5% of dogs and 8% of cats were PCR positive; this discordance may be due to delays in sampling. Respondents commonly reported close human-animal contact and willingness to take measures to prevent transmission to their pets. Reported preventative measures showed a slightly protective trend for both illness and seropositivity in pets, while sharing of beds and bowls had slight harmful effects.

Local-Scale phylodynamics reveal differential community impact of SARS-CoV-2 in metropolitan US county.

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.

Associations between SARS-CoV-2 variants and risk of COVID-19 hospitalization among confirmed cases in Washington State: a retrospective cohort study.

BACKGROUND: The COVID-19 pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with seven SARS-CoV-2 variants. METHODS: Our study includes individuals with positive SARS-CoV-2 RT-PCR in the Washington Disease Reporting System with available viral genome data, from December 1, 2020 to January 14, 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. FINDINGS: 58,848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95%CI 2.40-4.26), Beta (HR 2.85, 95%CI 1.56-5.23), Delta (HR 2.28 95%CI 1.56-3.34) or Alpha (HR 1.64, 95%CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95%CI 0.56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSION: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance. SUMMARY: Hospitalization risk following infection with SARS-CoV-2 variant remains unclear. We find a higher hospitalization risk in cases infected with Alpha, Beta, Gamma, and Delta, but not Omicron, with vaccination lowering risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Exome Sequencing-Based Screening for BRCA1/2 Expected Pathogenic Variants Among Adult Biobank Participants.

Importance: Detection of disease-associated variants in the BRCA1 and BRCA2 (BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals. Objectives: To identify pathogenic and likely pathogenic (P/LP) BRCA1/2 variants in an unselected research cohort, and to characterize the features associated with P/LP variants. Design, Setting, and Participants: This is a cross-sectional study of adult volunteers (n = 50 726) who underwent exome sequencing at a single health care system (Geisinger Health System, Danville, Pennsylvania) from January 1, 2014, to March 1, 2016. Participants are part of the DiscovEHR cohort and were identified through the Geisinger MyCode Community Health Initiative. They consented to a research protocol that included sequencing and return of actionable test results. Clinical data from electronic health records and clinical visits were correlated with variants. Comparisons were made between those with (cases) and those without (controls) P/LP variants in BRCA1/2. Main Outcomes: Prevalence of P/LP BRCA1/2 variants in cohort, proportion of variant carriers not previously ascertained through clinical testing, and personal and family history of relevant cancers among BRCA1/2 variant carriers and noncarriers. Results: Of the 50 726 health system patients who underwent exome sequencing, 50 459 (99.5%) had no expected pathogenic BRCA1/2 variants and 267 (0.5%) were BRCA1/2 carriers. Of the 267 cases (148 [55.4%] were women and 119 [44.6%] were men with a mean [range] age of 58.9 [23-90] years), 183 (68.5%) received clinically confirmed results in their electronic health record. Among the 267 participants with P/LP BRCA1/2 variants, 219 (82.0%) had no prior clinical testing, 95 (35.6%) had BRCA1 variants, and 172 (64.4%) had BRCA2 variants. Syndromic cancer diagnoses were present in 11 (47.8%) of the 23 deceased BRCA1/2 carriers and in 56 (20.9%) of all 267 BRCA1/2 carriers. Among women, 31 (20.9%) of 148 variant carriers had a personal history of breast cancer, compared with 1554 (5.2%) of 29 880 noncarriers (odds ratio [OR], 5.95; 95% CI, 3.88-9.13; P < .001). Ovarian cancer history was present in 15 (10.1%) of 148 variant carriers and in 195 (0.6%) of 29 880 variant noncarriers (OR, 18.30; 95% CI, 10.48-31.4; P < .001). Among 89 BRCA1/2 carriers without prior testing but with comprehensive personal and family history data, 44 (49.4%) did not meet published guidelines for clinical testing. Conclusions and Relevance: This study found that compared with previous clinical care, exome sequencing-based screening identified 5 times as many individuals with P/LP BRCA1/2 variants. These findings suggest that genomic screening may identify BRCA1/2-associated cancer risk that might otherwise remain undetected within health care systems and may provide opportunities to reduce morbidity and mortality in patients.

Asymmetric effects of native and exotic invasive shrubs on ecology of the West Nile virus vector Culex pipiens (Diptera: Culicidae).

BACKGROUND: Exotic invasive plants alter the structure and function of native ecosystems and may influence the distribution and abundance of arthropod disease vectors by modifying habitat quality. This study investigated how invasive plants alter the ecology of Culex pipiens, an important vector of West Nile virus (WNV) in northeastern and midwestern regions of the United States. METHODS: Field and laboratory experiments were conducted to test the hypothesis that three native leaf species (Rubus allegheniensis, blackberry; Sambucus canadensis, elderberry; and Amelanchier laevis, serviceberry), and three exotic invasive leaf species (Lonicera maackii, Amur honeysuckle; Elaeagnus umbellata, autumn olive; and Rosa multiflora, multiflora rose) alter Cx. pipiens oviposition site selection, emergence rates, development time, and adult body size. The relative abundance of seven bacterial phyla in infusions of the six leaf species also was determined using quantitative real-time polymerase chain reaction to test the hypothesis that variation in emergence, development, and oviposition site selection is correlated to differences in the diversity and abundance of bacteria associated with different leaf species, important determinants of nutrient quality and availability for mosquito larvae. RESULTS: Leaf detritus from invasive honeysuckle and autumn olive yielded significantly higher adult emergence rates compared to detritus from the remaining leaf species and honeysuckle alleviated the negative effects of intraspecific competition on adult emergence. Conversely, leaves of native blackberry acted as an ecological trap, generating high oviposition but low emergence rates. Variation in bacterial flora associated with different leaf species may explain this asymmetrical production of mosquitoes: emergence rates and oviposition rates were positively correlated to bacterial abundance and diversity, respectively. CONCLUSIONS: We conclude that the displacement of native understory plant species by certain invasive shrubs may increase production of Cx. pipiens with potential negative repercussions for human and wildlife health. These findings may be relevant to mosquito control and invasive plant management practices in the geographic range of Cx. pipiens. Further, our discovery of a previously unknown ecological trap for an important vector of WNV has the potential to lead to novel alternatives to conventional insecticides in mosquito control by exploiting the apparent "attract-kill" properties of this native plant species.