A basophil-neuronal axis promotes itch.

Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations. Recent discoveries have unearthed the neuroimmune circuitry of itch, leading to the development of anti-itch treatments. However, mechanisms underlying acute itch exacerbations remain overlooked. Herein, we identify that a large proportion of patients with AD harbor allergen-specific immunoglobulin E (IgE) and exhibit a propensity for acute itch flares. In mice, while allergen-provoked acute itch is mediated by the mast cell-histamine axis in steady state, AD-associated inflammation renders this pathway dispensable. Instead, a previously unrecognized basophil-leukotriene (LT) axis emerges as critical for acute itch flares. By probing fundamental itch mechanisms, our study highlights a basophil-neuronal circuit that may underlie a variety of neuroimmune processes.

Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

A dominant negative variant of RAB5B disrupts maturation of surfactant protein B and surfactant protein C.

Pathogenic variants in surfactant proteins SP-B and SP-C cause surfactant deficiency and interstitial lung disease. Surfactant proteins are synthesized as precursors (proSP-B, proSP-C), trafficked, and processed via a vesicular-regulated secretion pathway; however, control of vesicular trafficking events is not fully understood. Through the Undiagnosed Diseases Network, we evaluated a child with interstitial lung disease suggestive of surfactant deficiency. Variants in known surfactant dysfunction disorder genes were not found in trio exome sequencing. Instead, a de novo heterozygous variant in RAB5B was identified in the Ras/Rab GTPases family nucleotide binding domain, p.Asp136His. Functional studies were performed in Caenorhabditis elegans by knocking the proband variant into the conserved position (Asp135) of the ortholog, rab-5 Genetic analysis demonstrated that rab-5[Asp135His] is damaging, producing a strong dominant negative gene product. rab-5[Asp135His] heterozygotes were also defective in endocytosis and early endosome (EE) fusion. Immunostaining studies of the proband's lung biopsy revealed that RAB5B and EE marker EEA1 were significantly reduced in alveolar type II cells and that mature SP-B and SP-C were significantly reduced, while proSP-B and proSP-C were normal. Furthermore, staining normal lung showed colocalization of RAB5B and EEA1 with proSP-B and proSP-C. These findings indicate that dominant negative-acting RAB5B Asp136His and EE dysfunction cause a defect in processing/trafficking to produce mature SP-B and SP-C, resulting in interstitial lung disease, and that RAB5B and EEs normally function in the surfactant secretion pathway. Together, the data suggest a noncanonical function for RAB5B and identify RAB5B p.Asp136His as a genetic mechanism for a surfactant dysfunction disorder.

Cruise Ship Travel in the Era of Coronavirus Disease 2019 (COVID-19): A Summary of Outbreaks and a Model of Public Health Interventions.

BACKGROUND: Cruise travel contributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission when there were relatively few cases in the United States. By 14 March 2020, the Centers for Disease Control and Prevention (CDC) issued a No Sail Order suspending US cruise operations; the last US passenger ship docked on 16 April. METHODS: We analyzed SARS-CoV-2 outbreaks on cruises in US waters or carrying US citizens and used regression models to compare voyage characteristics. We used compartmental models to simulate the potential impact of 4 interventions (screening for coronavirus disease 2019 (COVID-19) symptoms; viral testing on 2 days and isolation of positive persons; reduction of passengers by 40%, crew by 20%, and reducing port visits to 1) for 7-day and 14-day voyages. RESULTS: During 19 January to 16 April 2020, 89 voyages on 70 ships had known SARS-CoV-2 outbreaks; 16 ships had recurrent outbreaks. There were 1669 reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and 29 confirmed deaths. Longer voyages were associated with more cases (adjusted incidence rate ratio, 1.10, 95% confidence interval [CI]: 1.03-1.17, P < .003). Mathematical models showed that 7-day voyages had about 70% fewer cases than 14-day voyages. On 7-day voyages, the most effective interventions were reducing the number of individuals onboard (43.3% reduction in total infections) and testing passengers and crew (42% reduction in total infections). All four interventions reduced transmission by 80.1%, but no single intervention or combination eliminated transmission. Results were similar for 14-day voyages. CONCLUSIONS: SARS-CoV-2 outbreaks on cruises were common during January-April 2020. Despite all interventions modeled, cruise travel still poses a significant SARS-CoV-2 transmission risk.

Use of Individualized Learning Plans to Facilitate Feedback Among Medical Students.

THEORY: Self-regulated learning theory suggests that individualized learning plans can benefit medical trainees by providing a structured means of goal setting, self-monitoring, and self-evaluation. External feedback also plays an important role in affecting learner motivations, perceptions, and self-evaluations. Accordingly, having learners share individualized learning plans with preceptors might promote self-regulated learning by helping align the feedback they receive with their learning goals. Hypothesis: We hypothesized having medical students share individualized learning plans with attendings and residents would improve the quality of the feedback they received, increase the likelihood that feedback correlated to their learning goals, and improve their perceptions of feedback received. Method: In this multisite study, third-year medical students on their pediatric clerkship created individualized learning plans and shared them with residents and attendings by writing a learning goal on at least one of their required faculty feedback forms. The quality of feedback on forms with versus without a learning goal written on top was scored using a validated scoring tool and compared using a Wilcoxon signed-ranks test, and the frequency with which feedback directly correlated to a student learning goal on forms with versus without a learning goal written on top was compared using a chi-square test. Students completed a post-clerkship survey rating the quality of feedback and teaching they received, perceptions of the individualized learning plans, progress toward achieving learning goals, and whether or not they received teaching and/or feedback related to learning goals. Results: Thirty-six students completed a total of 108 learning goals and 181 feedback forms, of which 42 forms (23.2%) had a learning goal written on top. The mean (SD) feedback score between forms with [3.9 (0.9)] versus without [3.6 (0.6)] a learning goal written on top was not different (p = .113). Feedback on forms with a learning goal written on top was more likely to correlate to a student learning goal than feedback on forms without a learning goal (92.9% vs 23.0% respectively, p < .001). Student perceptions of the usefulness of learning goals did not differ between students who reported receiving teaching or feedback related to a learning goal and those who did not. Conclusions: Sharing individualized learning plans with preceptors helped align feedback with learning goals but did not affect the quality of feedback. Further research should examine the bidirectional relationship between individualized learning plans and feedback in light of other contextual and interpersonal factors.

Long-term single-center comparison of ICD lead survival: Evidence for premature Linox lead failure.

INTRODUCTION: ICD lead failure is a potential source of significant morbidity and mortality. This study investigates the survival rates of Sprint Quattro, Endotak Reliance, and Linox ICD leads. METHODS AND RESULTS: A retrospective cohort study of all patients with an ICD implanted between January 2007 and December 2012 from the Wellington Hospital region, New Zealand, a tertiary referral center. Lead and patient details were established by review of clinical notes and the PaceArt Optima database. We analyzed a total of 287 implants using Sprint Quattro (n  =  92), Endotak Reliance (n  =  37), Linox (n  =  151), Riata (n  =  4), and Sprint Fidelis (n  =  2) leads. Median follow-up was 61.6 (26.0-81.6) months for Sprint Quattro leads, 66.7 (53.3-88.8) months for Linox leads, and 82.9 (45.9-107.4) months for Endotak Reliance leads. There were 20 cases of lead failure of which 19 were in Linox leads. The 4-, 6-, and 8-year survival for Linox leads was 97% (92.6-99.1), 93% (85.5-96.5), and 76% (62.3-85.5), respectively. The predominant abnormality was detection of nonphysiological electrical signals. Linox lead failure was associated with a younger age of patient (49.2 vs. 57.7 years, P  =  0.007). CONCLUSIONS: The 7-year survival of Linox leads was significantly worse than shown in Biotronik surveillance reports, but in line with other single-center studies from around the world.

Projected Zika Virus Importation and Subsequent Ongoing Transmission after Travel to the 2016 Olympic and Paralympic Games - Country-Specific Assessment, July 2016.

Zika virus belongs to the genus Flavivirus of the family Flaviviridae; it is transmitted to humans primarily through the bite of an infected Aedes species mosquito (e.g., Ae. aegypti and Ae. albopictus) (1). Zika virus has been identified as a cause of congenital microcephaly and other serious brain defects (2). As of June 30, 2016, CDC had issued travel notices for 49 countries and U.S. territories across much of the Western hemisphere (3), including Brazil, where the 2016 Olympic and Paralympic Games (Games of the XXXI Olympiad, also known as Rio 2016; Games) will be hosted in Rio de Janeiro in August and September 2016. During the Games, mosquito-borne Zika virus transmission is expected to be low because August and September are winter months in Brazil, when cooler and drier weather typically reduces mosquito populations (4). CDC conducted a risk assessment to predict those countries susceptible to ongoing Zika virus transmission resulting from introduction by a single traveler to the Games. Whereas all countries are at risk for travel-associated importation of Zika virus, CDC estimated that 19 countries currently not reporting Zika outbreaks have the environmental conditions and population susceptibility to sustain mosquito-borne transmission of Zika virus if a case were imported from infection at the Games. For 15 of these 19 countries, travel to Rio de Janeiro during the Games is not estimated to increase substantially the level of risk above that incurred by the usual aviation travel baseline for these countries. The remaining four countries, Chad, Djibouti, Eritrea, and Yemen, are unique in that they do not have a substantial number of travelers to any country with local Zika virus transmission, except for anticipated travel to the Games. These four countries will be represented by a projected, combined total of 19 athletes (plus a projected delegation of about 60 persons), a tiny fraction of the 350,000-500,000 visitors expected at the Games.* Overall travel volume to the Games represents a very small fraction (<0.25%) of the total estimated 2015 travel volume to Zika-affected countries,(†) highlighting the unlikely scenario that Zika importation would be solely attributable to travel to the Games. To prevent Zika virus infection and its complications among athletes and visitors to the Games and importation of Zika virus into countries that could sustain local transmission, pregnant women should not travel to the Games, mosquito bites should be avoided while traveling and for 3 weeks after returning home, and measures should be taken to prevent sexual transmission (Box).

Lived Experiences of Fatherhood After Infertility.

OBJECTIVE: To explore the lived experiences of fathers in the perinatal period after infertility. DESIGN: A descriptive, phenomenological study. SETTING: Researcher's private office and participants' homes in an Eastern Canadian province. PARTICIPANTS: Eight fathers who met the eligibility criteria. METHODS: We recruited a purposive sample of eight participants and held one-on-one interviews in person, by telephone, and via virtual platforms. We analyzed the verbatim transcripts of the audiotaped interviews using Colaizzi's phenomenological data analysis method. RESULTS: We uncovered seven themes that described the lived experiences of participants: The Journey: A Long Winding Road, Roles and Responsibilities: Supporter and Protector, Support: The Often-Forgotten Parent, Challenges and Hurdles: Bumps on the Road, So Many Feelings: The Rollercoaster, Coping: Living on the Road, and Reflection: An Unforgotten Journey. Participants shared their experiences of the perinatal period after infertility as long journeys and described how bumps along the road marked these journeys. The journeys were essential parts of their lives that they continued to remember years later. CONCLUSION: The perinatal experience after infertility is an important and remembered time for fathers. It is essential to involve and support them in the perinatal process to facilitate positive experiences and overall family health, especially after infertility. There is an ongoing need to conduct research with fathers and to develop evidence-based programming and resources to assist them in the perinatal period after infertility.

National Institute on Aging's 50th anniversary: Advancing aging research and the health and well-being of older adults.

The National Institute on Aging (NIA), part of the National Institutes of Health (NIH), was founded in 1974 to support and conduct research on aging and the health and well-being of older adults. Fifty years ago, the concept of studying aging generated much skepticism. Early NIA-funded research findings helped establish the great value of aging research and provided the foundation for significant science advances that have improved our understanding of the aging process, diseases and conditions associated with aging, and the effects of health inequities, as well as the need to promote healthy aging lifestyles. Today, we celebrate the many important contributions to aging research made possible by NIA, as well as opportunities to continue to make meaningful progress. NIA emphasizes that the broad aging research community must continue to increase and expand our collective efforts to recruit and train a diverse next generation of aging researchers.

On alert for Ebola: public health risk assessment of travellers from Uganda to the USA during the 2022 outbreak.

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

Isolation and proteomic characterization of the Arabidopsis Golgi defines functional and novel components involved in plant cell wall biosynthesis.

The plant Golgi plays a pivotal role in the biosynthesis of cell wall matrix polysaccharides, protein glycosylation, and vesicle trafficking. Golgi-localized proteins have become prospective targets for reengineering cell wall biosynthetic pathways for the efficient production of biofuels from plant cell walls. However, proteomic characterization of the Golgi has so far been limited, owing to the technical challenges inherent in Golgi purification. In this study, a combination of density centrifugation and surface charge separation techniques have allowed the reproducible isolation of Golgi membranes from Arabidopsis (Arabidopsis thaliana) at sufficiently high purity levels for in-depth proteomic analysis. Quantitative proteomic analysis, immunoblotting, enzyme activity assays, and electron microscopy all confirm high purity levels. A composition analysis indicated that approximately 19% of proteins were likely derived from contaminating compartments and ribosomes. The localization of 13 newly assigned proteins to the Golgi using transient fluorescent markers further validated the proteome. A collection of 371 proteins consistently identified in all replicates has been proposed to represent the Golgi proteome, marking an appreciable advancement in numbers of Golgi-localized proteins. A significant proportion of proteins likely involved in matrix polysaccharide biosynthesis were identified. The potential within this proteome for advances in understanding Golgi processes has been demonstrated by the identification and functional characterization of the first plant Golgi-resident nucleoside diphosphatase, using a yeast complementation assay. Overall, these data show key proteins involved in primary cell wall synthesis and include a mixture of well-characterized and unknown proteins whose biological roles and importance as targets for future research can now be realized.

When Fear Surrounding Childbirth Leads Women to Request a Planned Cesarean Birth.

Fear surrounding childbirth requires a more in-depth understanding from women's perspectives, especially those who request a planned cesarean due to that fear. Therefore, we explored primiparous and multiparous women's lived experiences of fear surrounding childbirth in relation to their decision to request a planned cesarean birth. We used Colaizzi's (1978) phenomenological method to interview 16 women from 4 provinces and to analyze the data. Women expressed numerous fears and most experienced more than one fear. Most feared their baby/babies being injured or dying during childbirth or developing complications themselves. Others feared experiencing a traumatic birth. Women described numerous emotional and physical manifestations of fear, and all believed that a planned cesarean birth would provide more control over the birth process. For some, the birth of their healthy baby/babies began a healing process, whereas others noted that their fear subsided or resolved upon confirmation that they would have a planned cesarean.

Risk factors for injuries in the U.S. Army Ordnance School.

OBJECTIVE: To investigate risk factors for time-loss injuries among soldiers attending U.S. Army Ordnance School Advanced Individual Training. METHODS: Injuries were obtained from an injury surveillance system. A health questionnaire provided data on age, race, rank, current self-reported injury and illness, and tobacco use. Fitness data was obtained from operations office. RESULTS: Cumulative time-loss injury incidence was 31% for men and 54% for women. For men, higher risk of injury was associated with race, a current self-reported injury, smoking before entering the Army, lower sit-up performance, and slower 2-mile run times. For women, higher risk of injury was associated with race, a current self-reported injury, and slower 2-mile run times. CONCLUSION: Smoking cessation and fitness training before entry are potential strategies to reduce injuries among soldiers in the Ordnance School.

Modelling airport catchment areas to anticipate the spread of infectious diseases across land and air travel.

Air travel is an increasingly important conduit for the worldwide spread of infectious diseases. However, methods to identify which airports an individual may use to initiate travel, or where an individual may travel to upon arrival at an airport is not well studied. This knowledge gap can be addressed by estimating airport catchment areas: the geographic extent from which the airport derives most of its patronage. While airport catchment areas can provide a simple decision-support tool to help delineate the spatial extent of infectious disease spread at a local scale, observed data for airport catchment areas are rarely made publicly available. Therefore, we evaluated a probabilistic choice behavior model, the Huff model, as a potential methodology to estimate airport catchment areas in the United States in data-limited scenarios. We explored the impact of varying input parameters to the Huff model on estimated airport catchment areas: distance decay exponent, distance cut-off, and measures of airport attractiveness. We compared Huff model catchment area patterns for Miami International Airport (MIA) and Harrisburg International Airport (MDT). We specifically compared our model output to observed data sampled for MDT to align model parameters with an established, observed catchment area. Airport catchment areas derived using the Huff model were highly sensitive to changes in model parameters. We observed that a distance decay exponent of 2 and a distance cut-off of 500 km represented the most realistic spatial extent and heterogeneity of the MIA catchment area. When these parameters were applied to MDT, the Huff model produced similar spatial patterns to the observed MDT catchment area. Finally, our evaluation of airport attractiveness showed that travel volume to the specific international destinations of interest for infectious disease importation risks (i.e., Brazil) had little impact on the predicted choice of airport when compared to all international travel. Our work is a proof of concept for use of the Huff model to estimate airport catchment areas as a generalizable decision-support tool in data-limited scenarios. While our work represents an initial examination of the Huff model as a method to approximate airport catchment areas, an essential next step is to conduct a quantitative calibration and validation of the model based on multiple airports, possibly leveraging local human mobility data such as call detail records or online social network data collected from mobile devices. Ultimately, we demonstrate how the Huff model could be potentially helpful to improve the precision of early warning systems that anticipate infectious disease spread, or to incorporate when local public health decision makers need to identify where to mobilize screening infrastructure or containment strategies at a local level.

Early introductions and community transmission of SARS-CoV-2 variant B.1.1.7 in the United States.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2500 COVID-19 cases associated with this variant have been detected in the US since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

Risk of yellow fever virus importation into the United States from Brazil, outbreak years 2016-2017 and 2017-2018.

Southeast Brazil has experienced two large yellow fever (YF) outbreaks since 2016. While the 2016-2017 outbreak mainly affected the states of Espírito Santo and Minas Gerais, the 2017-2018 YF outbreak primarily involved the states of Minas Gerais, São Paulo, and Rio de Janeiro, the latter two of which are highly populated and popular destinations for international travelers. This analysis quantifies the risk of YF virus (YFV) infected travelers arriving in the United States via air travel from Brazil, including both incoming Brazilian travelers and returning US travelers. We assumed that US travelers were subject to the same daily risk of YF infection as Brazilian residents. During both YF outbreaks in Southeast Brazil, three international airports-Miami, New York-John F. Kennedy, and Orlando-had the highest risk of receiving a traveler infected with YFV. Most of the risk was observed among incoming Brazilian travelers. Overall, we found low risk of YFV introduction into the United States during the 2016-2017 and 2017-2018 outbreaks. Decision makers can use these results to employ the most efficient and least restrictive actions and interventions.

Quinolone nonsusceptibility among enteric pathogens isolated from international travelers - Foodborne Diseases Active Surveillance Network (FoodNet) and National Antimicrobial Monitoring System (NARMS), 10 United States sites, 2004 - 2014.

Gastrointestinal illnesses are the most frequently diagnosed conditions among returning U.S. travelers. Although most episodes of travelers' diarrhea do not require antibiotic therapy, fluoroquinolones (a type of quinolone antibiotic) are recommended for treatment of moderate and severe travelers' diarrhea as well as many other types of severe infection. To assess associations between quinolone susceptibility and international travel, we linked data about isolate susceptibility in NARMS to cases of enteric infections reported to FoodNet. We categorized isolates as quinolone-nonsusceptible (QNS) if they were resistant or had intermediate susceptibility to ≥1 quinolone. Among 1,726 travel-associated infections reported to FoodNet with antimicrobial susceptibility data in NARMS during 2004-2014, 56% of isolates were quinolone-nonsusceptible, of which most (904/960) were Campylobacter. International travel was associated with >10-fold increased odds of infection with quinolone-nonsusceptible bacteria. Most QNS infections were associated with travel to Latin America and the Caribbean (390/743; 52%); however, the greatest risk of QNS infection was associated with travel to Africa (120 per 1,000,000 passenger journeys). Preventing acquisition and onward transmission of antimicrobial-resistant enteric infections among travelers is critical.

Germline translocations in mice: unique tools for analyzing gene function and long-distance regulatory mechanisms.

Translocations have provided invaluable tools for identifying both cancer-linked genes and loci associated with heritable human diseases, but heritable human translocations are rare and few mouse models exist. Here we report progress on analysis of a collection of heritable translocations generated by treatment of mice with specific chemicals or radiation during late spermatogenic stages. The translocation mutants exhibit a range of visible phenotypes reflecting the disruption of coding sequences or the separation of genes from essential regulatory elements. The breakpoints of both radiation-induced and chemically induced mutations in these mice are remarkably clean, with very short deletions, duplications, or inversions in some cases, and ligation mediated by microhomology, suggesting nonhomologous end joining as the major path of repair. These mutations provide new tools for the discovery of novel genes and regulatory elements linked to human developmental disorders and new clues to the molecular basis of human genetic disease.

Mining the literature for genes associated with placenta-mediated maternal diseases.

Automated literature analysis could significantly speed up understanding of the role of the placenta and the impact of its development and functions on the health of the mother and the child. To facilitate automatic extraction of information about placenta-mediated disorders from the literature, we manually annotated genes and proteins, the associated diseases, and the functions and processes involved in the development and function of placenta in a collection of PubMed/MEDLINE abstracts. We developed three baseline approaches to finding sentences containing this information: one based on supervised machine learning (ML) and two based on distant supervision: 1) using automated detection of named entities and 2) using MeSH. We compare the performance of several well-known supervised ML algorithms and identify two approaches, Support Vector Machines (SVM) and Generalized Linear Models (GLM), which yield up to 98% recall precision and F1 score. We demonstrate that distant supervision approaches could be used at the expense of missing up to 15% of relevant documents.

Elevation as a proxy for mosquito-borne Zika virus transmission in the Americas.

INTRODUCTION: When Zika virus (ZIKV) first began its spread from Brazil to other parts of the Americas, national-level travel notices were issued, carrying with them significant economic consequences to affected countries. Although regions of some affected countries were likely unsuitable for mosquito-borne transmission of ZIKV, the absence of high quality, timely surveillance data made it difficult to confidently demarcate infection risk at a sub-national level. In the absence of reliable data on ZIKV activity, a pragmatic approach was needed to identify subnational geographic areas where the risk of ZIKV infection via mosquitoes was expected to be negligible. To address this urgent need, we evaluated elevation as a proxy for mosquito-borne ZIKV transmission. METHODS: For sixteen countries with local ZIKV transmission in the Americas, we analyzed (i) modelled occurrence of the primary vector for ZIKV, Aedes aegypti, (ii) human population counts, and (iii) reported historical dengue cases, specifically across 100-meter elevation levels between 1,500m and 2,500m. Specifically, we quantified land area, population size, and the number of observed dengue cases above each elevation level to identify a threshold where the predicted risks of encountering Ae. aegypti become negligible. RESULTS: Above 1,600m, less than 1% of each country's total land area was predicted to have Ae. aegypti occurrence. Above 1,900m, less than 1% of each country's resident population lived in areas where Ae. aegypti was predicted to occur. Across all 16 countries, 1.1% of historical dengue cases were reported above 2,000m. DISCUSSION: These results suggest low potential for mosquito-borne ZIKV transmission above 2,000m in the Americas. Although elevation is a crude predictor of environmental suitability for ZIKV transmission, its constancy made it a pragmatic input for policy decision-making during this public health emergency.