A value-based approach to optimize red blood cell transfusion in patients receiving extracorporeal membrane oxygenation.

INTRODUCTION: The risk, cost, and adverse outcomes associated with packed red blood cell (RBC) transfusions in patients with cardiopulmonary failure requiring extracorporeal membrane oxygenation (ECMO) have raised concerns regarding the overutilization of RBC products. It is, therefore, necessary to establish optimal transfusion criteria and protocols for patients supported with ECMO. The goal of this study was to establish specific criteria for RBC transfusions in patients undergoing ECMO. METHODS: This was a retrospective cohort study conducted at Stanford University Hospital. Data on RBC utilization during the entire hospital stay were obtained, which included patients aged ≥18 years who received ECMO support between 1 January 2017, and 30 June 2020 (n = 281). The primary outcome was in-hospital mortality. RESULTS: Hemoglobin (HGB) levels >10 g/dL before transfusion did not improve in-hospital survival. Therefore, we revised the HGB threshold to ≤10 g/dL to guide transfusion in patients undergoing ECMO. To validate this intervention, we prospectively compared the pre- and post-intervention cohorts for in-hospital mortality. Post-intervention analyses found 100% compliance for all eligible records and a decrease in the requirement for RBC transfusion by 1.2 units per patient without affecting the mortality. CONCLUSIONS: As an institution-driven value-based approach to guide transfusion in patients undergoing ECMO, we lowered the threshold HGB level. Validation of this revised intervention demonstrated excellent compliance and reduced the need for RBC transfusion while maintaining the clinical outcome. Our findings can help reform value-based healthcare in this cohort while maintaining the outcome.

Cross-talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossification.

BACKGROUND: Progressive maturation of growth plate chondrocytes drives long bone growth during endochondral ossification. Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein-2 (BMP2), are required for normal chondrocyte maturation. Here, we investigated cross-talk between EGFR and BMP2 signals in developing and adult growth plates. RESULTS: Using in vivo mouse models of conditional cartilage-targeted EGFR or BMP2 loss, we show that canonical BMP signal activation is increased in the hypertrophic chondrocytes of EGFR-deficient growth plates; whereas EGFR signal activation is increased in the reserve, prehypertrophic and hypertrophic chondrocytes of BMP2-deficient growth plates. EGFR-deficient chondrocytes displayed increased BMP signal activation in vitro, accompanied by increased expression of IHH, COL10A1, and RUNX2. Hypertrophic differentiation and BMP signal activation were suppressed in normal chondrocyte cultures treated with the EGFR ligand betacellulin, effects that were partially blocked by simultaneous treatment with BMP2 or a chemical EGFR antagonist. CONCLUSIONS: Cross-talk between EGFR and BMP2 signals occurs during chondrocyte maturation. In the reserve and prehypertrophic zones, BMP2 signals unilaterally suppress EGFR activity; in the hypertrophic zone, EGFR and BMP2 signals repress each other. This cross-talk may play a role in regulating chondrocyte maturation in developing and adult growth plates.

Post-Vaccination Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections and Incidence of the Presumptive B.1.427/B.1.429 Variant Among Healthcare Personnel at a Northern California Academic Medical Center.

BACKGROUND: Although mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines report >90% efficacy, breakthrough infections occur. Little is known about their effectiveness against SARS-CoV-2 variants, including the highly prevalent B.1.427/B.1.429 variant. METHODS: In this quality improvement project, we collected demographic and clinical information from post-vaccine SARS-CoV-2 cases (PVSCs), defined as healthcare personnel (HCP) with positive SARS-CoV-2 nucleic acid amplification test after receiving ≥1 vaccine dose. Available specimens were tested for L452R, N501Y, and E484K mutations using reverse-transcription polymerase chain reaction. Mutation prevalence was compared among unvaccinated, early post-vaccinated (≤14 days after dose 1), partially vaccinated (positive test >14 days after dose 1 and <14 days after dose 2), and fully vaccinated (>14 days after dose 2) PVSCs. RESULTS: From December 2020 to April 2021, ≥23 090 HCP received ≥1 dose of an mRNA-based SARS-CoV-2 vaccine, and 660 HCP cases of SARS-CoV-2 occurred, of which 189 were PVSCs. Among the PVSCs, 114 (60.3%), 49 (25.9%), and 26 (13.8%) were early post-vaccination, partially vaccinated, and fully vaccinated, respectively. Of 261 available samples from vaccinated and unvaccinated HCP, 103 (39.5%), including 42 PVSCs (36.5%), had the L452R mutation presumptive of B.1.427/B.1.429. When adjusted for community prevalence of B.1.427/B.1.429, PVSCs did not have significantly elevated risk of B.1.427/B.1.429 compared with unvaccinated HCP. CONCLUSIONS: Most PVSCs occurred prior to expected onset of full, vaccine-derived immunity. Presumptive B.1.427/B.1.429 was not more prevalent in post-vaccine cases than in unvaccinated SARS-CoV-2 HCP. Continued infection control measures, particularly <14 days post-vaccination, and continued variant surveillance in PVSCs are imperative to control future SARS-CoV-2 surges.

Adenoma and Sessile Serrated Lesion Detection Rates at Screening Colonoscopy for Ages 45-49 Years vs Older Ages Since the Introduction of New Colorectal Cancer Screening Guidelines.

BACKGROUND AND AIMS: All major U.S. guidelines now endorse average-risk colorectal cancer (CRC) screening at 45-49 years of age. Concerns exist that endoscopic capacity may be strained, that low-risk persons may self-select for screening, and that calculations of the adenoma detection rate may be diluted. We analyzed age-specific screening colonoscopy volumes and lesion detection rates before vs after the endorsement of CRC screening at 45-49 years of age. METHODS: We compared colonoscopy volumes and lesion detection rates in our healthcare system during period 1 (October 2017 to December 2018), before the first change in guidelines, vs period 2 (January 2019 to August 2021), the era of new guidelines. RESULTS: The proportion of first-time screening colonoscopies performed in 45- to 49-year-olds increased from 3.5% to 11.6% (relative risk, 3.36; 95% CI, 2.45-4.61). The period 2 detection rates for adenoma, advanced adenoma, sessile serrated lesion, advanced sessile serrated lesion, adenomas per colonoscopy, and lesions per colonoscopy were very similar for 45- to 49-year-olds (34.3%, 6.3%, 8.6%, 2.9%, 0.58, and 0.69, respectively) and 50- to 54-year-olds (38.2%, 5.8%, 9.4%, 3.0%, 0.63, and 0.76, respectively) at first-time screening, and for 60- to 64-year-olds at rescreening (33.4%, 6.1%, 7.2%, 2.3%, 0.61, and 0.70, respectively). All detection rates, adenomas per colonoscopy, and lesions per colonoscopy increased from period 1 to period 2 (eg, overall adenoma detection rate 35.1% vs 42.6%; P < .0001), without any decreases among 45- to 49-year-olds. CONCLUSIONS: In our healthcare system, a lower CRC screening initiation age has modestly affected colonoscopy volume by age without compromising screening yield. Lesion detection rates, including for advanced adenomas, in average-risk 45- to 49-year-olds approximate those in 50- to 54-year-olds at first-time screening and 60- to 64-year-olds at rescreening. National monitoring is needed to assess fully the impact of lowering the CRC screening initiation age.

Adenoma and Serrated Lesion Detection by Colonoscopy Indication: The ADR-ESS (ADR Extended to all Screening/Surveillance) Score.

BACKGROUND: The adenoma detection rate at screening (ADR) predicts interval colorectal cancer. Monitoring other lesion detection rates and colonoscopy indications has been proposed. We developed a comprehensive, automated colonoscopy audit program based on standardized clinical documentation, explored detection rates across indications, and developed the Adenoma Detection Rate - Extended to all Screening / Surveillance (ADR-ESS) score. METHODS: In a prospective cohort study, we calculated overall and advanced adenoma and sessile serrated lesion (SSL) detection rates among 15,253 colonoscopies by 35 endoscopists from 4 endoscopy units across all colonoscopy indications. We explored correlations between detection rates, and the precision and stability of ADR-ESS versus ADR. RESULTS: The overall "screening, first" ADR was 36.3% (95% confidence interval [CI], 34.5%-38.1%). The adenoma detection rate was lower for "screening, not first" (relative rate [RR], 0.80; 95% CI, 0.74-0.87) and "family history" (RR, 0.84; 95% CI, 0.74-0.96), and higher for "surveillance" (RR, 1.22; 95% CI, 1.15-1.31) and "follow-up, FIT" (RR, 1.21; 95% CI, 1.07-1.37). For "screening, first," the detection rates for advanced adenoma, SSL, and advanced SSL were 6.7% (95% CI, 5.7%-7.7%), 7.2% (95% CI, 6.2%-8.2%), and 2.6% (95% CI, 2.0%-3.2%), respectively. Adenoma and SSL detection were correlated (r = 0.44; P = .008). ADR-ESS had substantially narrower confidence intervals and less period-to-period variability than ADR, and was not improved by weighting for indication volume and correction for detection by indication. CONCLUSIONS: Comprehensive, automated colonoscopy audit based on standardized clinical documentation is feasible. Adenoma detection is a fair but imperfect proxy for SSL detection. ADR-ESS increases the precision of adenoma detection assessments and emphasizes quality across colonoscopy indications.

Amblyospora khaliulini (Microsporidia: Amblyosporidae): Investigations on its life cycle and ecology in Aedes communis (Diptera: Culicidae) and Acanthocyclops vernalis (Copepoda: Cyclopidae) with redescription of the species.

A multi-year study was conducted to examine the natural ecology of the microsporidium Amblyospora khaliulini and more fully characterize parasite development and histopathology in all stages of its primary mosquito host, Aedes communis and intermediate copepod host, Acanthocyclops vernalis with redescription of the species. A. khaliulini exhibits polymorphic development, produces three morphologically and functionally distinct spores, and is both horizontally and vertically transmitted. Development in A. vernalis is restricted to females, occurs within the ovaries and results in death of the host. Development is haplophasic with division by binary and multiple fission producing rosette-shaped sporogonial plasmodia and conical uninucleate spores that are orally infectious to Ae. communis larvae. Both sexes are equally susceptible and infections are confined to testes in males and ovaries in females. Initial stages of development include uninucleate schizonts that undergo karyokinesis forming diplokaryotic meronts that divide repeatedly by binary fission. Sporogony occurs in both host sexes, but sporogenesis does not progress normally in adult males and elliptical, thin walled binucleate spores that function in vertical transmission of the microsporidium via infection of the ovaries and eggs are formed in adult females only. Development of vertically acquired infections in larval Ae. communis hosts occurs within fat body tissue, leads to the production of meiospores in male hosts only and results in death during the 4th larval stadium. Initial development is characterized by merogonial multiplication of diplokarya by synchronous binary division producing additional diplokarya. The cessation of merogony and the onset of sporogony are characterized by the simultaneous secretion of a sporophorous vesicle and meiotic division of diplokarya resulting in the formation of octonucleate sporonts that undergo cytokinesis and sporogenesis to form eight uninucleate, broadly ovoid meiospores enclosed within a sporophorous vesicle. The natural prevalence of patent vertically acquired fat body infections in field populations of Ae. communis ranged from 1.6% to 3.6%. Yearly infection rates in A. vernalis copepods ranged from 57.1% to 15.0%. Prevalence rates of horizontally acquired infections in emerging adult Ae. communis ranged from 69.0% to 11.9% in males and 50.0% to 16.4% in females.

Real-Time Electronic Tracking of Diarrheal Episodes and Laxative Therapy Enables Verification of Clostridium difficile Clinical Testing Criteria and Reduction of Clostridium difficile Infection Rates.

Health care-onset health care facility-associated Clostridium difficile infection (HO-CDI) is overdiagnosed for several reasons, including the high prevalence of C. difficile colonization and the inability of hospitals to limit testing to patients with clinically significant diarrhea. We conducted a quasiexperimental study from 22 June 2015 to 30 June 2016 on consecutive inpatients with C. difficile test orders at an academic hospital. Real-time electronic patient data tracking was used by the laboratory to enforce testing criteria (defined as the presence of diarrhea [≥3 unformed stools in 24 h] and absence of laxative intake in the prior 48 h). Outcome measures included C. difficile test utilization, HO-CDI incidence, oral vancomycin utilization, and clinical complications. During the intervention, 7.1% (164) and 9.1% (211) of 2,321 C. difficile test orders were canceled due to absence of diarrhea and receipt of laxative therapy, respectively. C. difficile test utilization decreased upon implementation from an average of 208.8 tests to 143.0 tests per 10,000 patient-days (P < 0.001). HO-CDI incidence rate decreased from an average of 13.0 cases to 9.7 cases per 10,000 patient-days (P = 0.008). Oral vancomycin days of therapy decreased from an average of 13.8 days to 9.4 days per 1,000 patient-days (P = 0.009). Clinical complication rates were not significantly different in patients with 375 canceled orders compared with 869 episodes with diarrhea but negative C. difficile results. Real-time electronic clinical data tracking is an effective tool for verification of C. difficile clinical testing criteria and safe reduction of inflated HO-CDI rates.

Assessment of salivary cadmium levels and breast density in the Marin Women's Study.

BACKGROUND: We aimed to determine if salivary cadmium (Cd) levels had any association with breast density, hoping to establish a less invasive cost-effective method of stratifying Cd burden as an environmental breast cancer risk factor. METHODS: Salivary Cd levels were quantified from the Marin Women's Study, a Marin County, California population composite. Volumetric compositional breast density (BDsxa ) data were measured by single x-ray absorptiometry techniques. Digital screening mammography was performed by the San Francisco Mammography Registry. Radiologists reviewed mammograms and assigned a Breast Imaging-Reporting and Data System score. Early morning salivary Cd samples were assayed. Association analyses were then performed. RESULTS: Cd was quantifiable in over 90% of saliva samples (mean = 55.7 pg/L, SD = 29). Women with higher saliva Cd levels had a non-significant odds ratio of 1.34 with BI-RAD scores (3 or 4) (95% CI 0.75-2.39, p = 0.329). Cd levels were higher in current smokers (mean = 61.4 pg/L, SD = 34.8) than former smokers or non-smokers. These results were non-significant. Pilot data revealed that higher age and higher BMI were associated with higher BI-RAD scores (p < 0.001). CONCLUSION: Salivary Cd is a viable quantification source in large epidemiologic studies. Association analyses between Cd levels and breast density may provide additional information for breast cancer risk assessment, risk reduction plans, and future research directions. Further work is needed to demonstrate a more robust testing protocol before the extent of its usefulness can be established.

Low infectivity among asymptomatic patients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) admission test at a tertiary care center, 2020-2022.

We used a strand-specific RT-qPCR to evaluate viral replication as a surrogate for infectiousness among 242 asymptomatic inpatients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) admission test. Only 21 patients (9%) had detectable SARS-CoV-2 minus-strand RNA. Because most patients were found to be noninfectious, our findings support the suspension of asymptomatic admission testing.

How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by episodic yet cumulative heterotopic ossification (HO) of skeletal muscles, tendons, ligaments, and fascia. FOP arises from missense mutations in Activin Receptor type I (ACVR1), a type I bone morphogenetic protein (BMP) receptor. Although initial findings implicated constitutive activity of FOP-variant ACVR1 (ACVR1FOP) and/or hyperactivation by BMPs, it was later shown that HO in FOP requires activation of ACVR1FOP by Activin A. Inhibition of Activin A completely prevents HO in FOP mice, indicating that Activin A is an obligate driver of HO in FOP, and excluding a key role for BMPs in this process. This discovery led to the clinical development of garetosmab, an investigational antibody that blocks Activin A. In a phase 2 trial, garetosmab inhibited new heterotopic bone lesion formation in FOP patients. In contrast, antibodies to ACVR1 activate ACVR1FOP and promote HO in FOP mice. Beyond their potential clinical relevance, these findings have enhanced our understanding of FOP's pathophysiology, leading to the identification of fibroadipogenic progenitors as the cells that form HO, and the discovery of non-signaling complexes between Activin A and wild type ACVR1 and their role in tempering HO, and are also starting to inform biological processes beyond FOP.

An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms.

BACKGROUND: Admission to a room previously occupied by a patient with certain multidrug-resistant organisms (MDROs) increases the risk of acquisition. Traditional cleaning strategies do not remove all environmental MDROs. We evaluated the environmental and clinical impact of hydrogen peroxide vapor (HPV) room disinfection. METHODS: We performed a 30-month prospective cohort intervention study on 6 high-risk units in a 994-bed tertiary care hospital. Following a 12-month preintervention phase, HPV was implemented on 3 units to decontaminate the rooms of patients known to be infected or colonized with epidemiologically important MDROs, following their discharge. Monthly environmental samples for MDROs were collected on all study units for 3 preintervention and 6 intervention months. The risk of MDRO acquisition in patients admitted to rooms decontaminated using HPV was compared with rooms disinfected using standard methods. RESULTS: The prior room occupant was known to be infected or colonized with an MDRO in 22% of 6350 admissions. Patients admitted to rooms decontaminated using HPV were 64% less likely to acquire any MDRO (incidence rate ratio [IRR], 0.36; 95% confidence interval [CI], .19-.70; P < .001) and 80% less likely to acquire VRE (IRR, 0.20; 95% CI, .08-.52; P < .001) after adjusting for other factors. The risk of acquiring Clostridium difficile, methicillin-resistant Staphylococcus aureus, and multidrug-resistant gram-negative rods individually was reduced, but not significantly. The proportion of rooms environmentally contaminated with MDROs was reduced significantly on the HPV units (relative risk, 0.65, P = .03), but not on non-HPV units. CONCLUSIONS: HPV decontamination reduced environmental contamination and the risk of acquiring MDROs compared with standard cleaning protocols.

Jamestown Canyon virus comes into view: understanding the threat from an underrecognized arbovirus.

This review examines the epidemiology, ecology, and evolution of Jamestown Canyon virus (JCV) and highlights new findings from the literature to better understand the virus, the vectors driving its transmission, and its emergence as an agent of arboviral disease. We also reanalyze data from the Connecticut Arbovirus Surveillance Program which represents the largest dataset on JCV infection in mosquitoes. JCV is a member of the California serogroup of the genus Orthobunyavirus, family Peribunyaviridae, and is found throughout much of temperate North America. This segmented, negative-sense RNA virus evolves predominately by genetic drift punctuated by infrequent episodes of genetic reassortment among novel strains. It frequently infects humans within affected communities and occasionally causes febrile illness and neuroinvasive disease in people. Reported human cases are relatively rare but are on the rise during the last 20 yr, particularly within the northcentral and northeastern United States. JCV appears to overwinter and reemerge each season by transovarial or vertical transmission involving univoltine Aedes (Diptera: Culicidae) species, specifically members of the Aedes communis (de Geer) and Ae. stimulans (Walker) Groups. The virus is further amplified in a mosquito-deer transmission cycle involving a diversity of mammalophilic mosquito species. Despite progress in our understanding of this virus, many aspects of the vector biology, virology, and human disease remain poorly understood. Remaining questions and future directions of research are discussed.

Establishing Colonies from Field-Collected Mosquitoes: Special Accommodations for Wild Strains.

A researcher may have many reasons for wanting to establish new laboratory colonies from field-collected mosquitoes. In particular, the ability to study the diversity found within and among natural populations in a controlled laboratory environment opens up a wide range of possibilities for understanding how and why burdens of vector-borne disease vary over space and time. However, field-collected mosquitoes are often more difficult to work with than established laboratory strains, and considerable logistical challenges are involved in safely transporting field-collected mosquitoes into the laboratory. Here, we provide advice for researchers working with Aedes aegypti, Anopheles gambiae, and Culex pipiens, as well as notes on other closely related species. We provide guidance on each stage of the life cycle and highlight the life stages for which it is easiest to initiate new laboratory colonies for each species. In accompanying protocols, we provide methods detailing Ae. aegypti egg collection and hatching as well as how to transport larvae and pupae from the field.

Collecting, Storing, and Hatching Aedes aegypti Eggs.

Laboratory study of natural populations of mosquitoes can play a key role in determining the underlying causes of variation in burdens of mosquito-borne disease. Aedes aegypti is the main vector of the viruses that cause dengue, chikungunya, Zika, and yellow fever, making it a high priority for laboratory study. Ae. aegypti eggs provide an ideal starting point for new laboratory colonies. Eggs can be collected using ovicups, which are small plastic cups lined with seed-germination paper and partially filled with leaf-infused H2O. Once collected, dry eggs will remain viable for months and can be safely transported long distances back to the laboratory as long as they are properly stored. This protocol provides step-by-step instructions for preparing for collecting, storing, and hatching Ae. aegypti eggs and has successfully yielded laboratory colonies from locations across both the native and invasive range of this species.

Mosquito Larvae and Pupae Transport from the Field.

Laboratory study of field-collected mosquitoes can allow researchers to better understand the ways variation within and among mosquito populations shapes burdens of mosquito-borne disease. The Anopheles gambiae complex comprises the most important vectors of malaria, but it can be challenging to keep in the laboratory. For some species of mosquitoes, especially An. gambiae, it is very difficult to bring viable eggs into the laboratory. Instead, it is preferable to collect larvae or pupae and then transport them as carefully as possible back to the laboratory. This simple protocol allows a researcher to start new laboratory colonies from larvae or pupae collected from natural breeding sites or proceed directly to their planned experiments. The use of natural breeding sites provides additional reassurance that the resulting colonies are representative of natural populations.

Evidence of Uranotaenia sapphirina (Diptera: Culicidae) feeding on annelid worms in the Northeastern United States.

Mosquito host-feeding behavior is an important parameter for determining the vector potential of mosquito species in a given locale. Despite the recent discovery of Uranotaenia sapphirina Osten Sacken feeding on annelid hosts in Florida, host association studies for this mosquito species in the United States remain limited. To investigate the blood-feeding pattern of Ur. sapphirina in the northeastern United States, mosquitoes were collected from Massachusetts, Connecticut, and New Jersey using CDC miniature light traps, peat fiber resting boxes, gravid traps, and backpack aspirators. Vertebrate and invertebrate hosts of this mosquito species were identified through PCR amplification and nucleotide sequencing of portions of the mitochondrial cytochrome b gene and the 28S ribosomal RNA gene, respectively. Of 21 (24.7%) specimens successfully identified to host species, 47.6% contained solely annelid blood, 14.3% mammalian blood, 14.3% avian blood, and 23.8% with mixed blood of annelid and avian origin. The mud earthworm, Sparganophilus tennesseensis Reynolds (Haplotaxida: Sparganophilidae), was identified as the most common host (n = 14, including mixed bloods), followed by American robin, Turdus migratorius (n = 7, including mixed bloods). Testing of these blood engorged mosquitoes for West Nile virus and eastern equine encephalitis virus did not result in any positive specimens. This is the first report of Ur. sapphirina feeding on annelids and on both vertebrate and invertebrate hosts in mixed bloodmeals in the northeastern United States. Our findings support the recent report of Ur. sapphirina feeding on invertebrates and further emphasizes the inclination of some mosquito species to feed on a wider range of hosts spanning nontraditional taxonomic groups.

Use of a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) strand-specific assay to evaluate for prolonged viral replication >20 days from illness onset.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) real-time reverse-transcription polymerase chain reaction (rRT-PCR) strand-specific assay can be used to identify active SARS-CoV-2 viral replication. We describe the characteristics of 337 hospitalized patients with at least 1 minus-strand SARS-CoV-2 assay performed >20 days after illness onset. This test is a novel tool to identify high-risk hospitalized patients with prolonged SARS-CoV-2 replication.

Dynamics of eastern equine encephalitis virus during the 2019 outbreak in the Northeast United States.

Eastern equine encephalitis virus (EEEV) causes a rare but severe disease in horses and humans and is maintained in an enzootic transmission cycle between songbirds and Culiseta melanura mosquitoes. In 2019, the largest EEEV outbreak in the United States for more than 50 years occurred, centered in the Northeast. To explore the dynamics of the outbreak, we sequenced 80 isolates of EEEV and combined them with existing genomic data. We found that, similar to previous years, cases were driven by multiple independent but short-lived virus introductions into the Northeast from Florida. Once in the Northeast, we found that Massachusetts was important for regional spread. We found no evidence of any changes in viral, human, or bird factors which would explain the increase in cases in 2019, although the ecology of EEEV is complex and further data is required to explore these in more detail. By using detailed mosquito surveillance data collected by Massachusetts and Connecticut, however, we found that the abundance of Cs. melanura was exceptionally high in 2019, as was the EEEV infection rate. We employed these mosquito data to build a negative binomial regression model and applied it to estimate early season risks of human or horse cases. We found that the month of first detection of EEEV in mosquito surveillance data and vector index (abundance multiplied by infection rate) were predictive of cases later in the season. We therefore highlight the importance of mosquito surveillance programs as an integral part of public health and disease control.