Pacific Coast tick fever is a recently described zoonotic disease in California caused by a spotted fever group rickettsia, Rickettsia rickettsii subsp. californica (formerly Rickettsia 364D) and transmitted by the Pacific Coast tick, Dermacentor occidentalis. Like many emerging vector-borne diseases, knowledge regarding the transmission cycle, contribution from potential amplifying hosts, and geographic distribution of R. rickettsii californica is limited. We paired molecular analysis with comparative spatial niche modeling to identify vertebrate hosts potentially involved in the transmission cycle of this pathogen. We identified R. rickettsii californica DNA in three mammal species (Otospermophilus beecheyi, Lepus californicus, and Sylvilagus audubonii). This is the first record of R. rickettsii californica detected in mammals and may indicate potential amplifying hosts for this human pathogen. Species niche modeling of uninfected and infected D. occidentalis identified areas of high suitability along the coast and Sierra Nevada foothills of California. These findings support the hypothesis that amplifying host(s) may support higher infection prevalence in the infected tick regions compared to other parts of the tick's range. Potential host species distribution models (SDMs) were constructed from museum records and niche overlap statistics were used to compare habitat suitability with R. rickettsii californica-infected tick SDMs. We found higher than null overlap of infected ticks with California ground squirrels (O. beecheyii) and trending, but nonsignificant, overlap with two lagomorph species. Pairing molecular and niche modeling may be a useful approach to identify species that are involved in the maintenance of emerging tick-borne zoonoses.

Gulf War Illness (GWI) is a disorder experienced by many veterans of the 1991 Gulf War, with symptoms including fatigue, chronic pain, respiratory and memory problems. Exposure to toxic chemicals during the war, such as oil well fire smoke, pesticides, physiological stress, and nerve agents, is thought to have triggered abnormal neuroinflammatory responses that contribute to GWI. Previous studies have examined the acute effects of combined physiological stress and chemical exposures using GWI rodent models and presented findings related to neuroinflammation and changes in diffusion magnetic resonance imaging (MRI) measures, suggesting a neuroimmune basis for GWI. In the current study, using ex vivo MRI, cytokine mRNA expression, and immunohistological analyses of brain tissues, we examined the brain structure and immune function of a chronic rat model of GWI. Our data showed that a combination of long-term corticosterone treatment (to mimic high physiological stress) and diisopropyl fluorophosphate exposure (to mimic sarin exposure) primed the response to subsequent systemic immune challenge with lipopolysaccharide resulting in elevations of multiple cytokine mRNAs, an increased activated glial population, and disrupted brain microstructure in the cingulate cortex and hippocampus compared to control groups. Our findings support the critical role of neuroinflammation, dysregulated glial activation, and their relationship to disrupted brain microstructural integrity in the pathophysiology of GWI and highlight the unique consequences of long-term combined exposures on brain biochemistry and structural connectivity. © 2024

BACKGROUND: Differences in acute COVID-19 associated morbidity based on race, ethnicity, and gender have been well described; however, less is known about differences in subsequent longer term health-related quality of life and well-being. METHODS: This prospective cohort study included symptomatic adults tested for SARS-CoV-2 who completed baseline and 3-month follow-up surveys. Using the PROMIS-29 tool, a validated measure of health and well-being, we compared outcomes at 3 months and change in outcomes from baseline to 3 months among groups with different races, ethnicities, and/or sexes. RESULTS: Among 6044 participants, 4113 (3202 COVID +) were included. Among COVID + participants, compared to non-Hispanic White participants, Black participants had better PROMIS T-scores for cognitive function (3.6 [1.1, 6.2]) and fatigue (- 4.3 [- 6.6, - 2.0]) at 3 months and experienced more improvement in fatigue over 3 months (- 2.7 [- 4.7, - 0.8]). At 3 months, compared with males, females had worse PROMIS T-scores for cognitive function (- 4.1 [- 5.6, - 2.6]), physical function (- 2.1 [- 3.1, - 1.0]), social participation (- 2.8 [- 4.2, - 1.5]), anxiety (2.8 [1.5, 4.1]), fatigue (5.1 [3.7, 6.4]), and pain interference (2.0 [0.9, 3.2]). Females experienced less improvement in fatigue over 3 months (3.1 [2.0, 4.3]). Transgender/non-binary/other gender participants had worse 3-month scores in all domains except for sleep disturbance and pain interference. CONCLUSIONS: Three months after the initial COVID-19 infection, Black participants reported better cognitive function and fatigue, while females and other gender minoritized groups experienced lower well-being. Future studies are necessary to better understand how and why social constructs, specifically race, ethnicity, and gender, influence differences in COVID-19-related health outcomes. Trials Registration ClinicalTrials.gov Identifier: NCT04610515.

INTRODUCTION: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. METHODS: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. RESULTS: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). DISCUSSION: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes.

BACKGROUND: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection. METHODS: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms. RESULTS: Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months. CONCLUSIONS: We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.

BACKGROUND: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. METHODS: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. RESULTS: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28). CONCLUSIONS: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. TRIAL REGISTRATION: NCT04610515.

Considering the hazardous effects of particulate matter (PM) exposure on students and teachers and the high PM concentration issue in South Korea, air purifiers have recently been installed in most classrooms to improve air quality. However, some on-site challenges, such as operational costs and noise, have been issues with the continuous operation of air purifiers. Therefore, a guideline is needed to dynamically predict the indoor PM concentration based on the changes in outdoor PM concentration and activate the air purifiers only when necessary. This study develops a grey-box model that uses measured data and physical differential equations to perform the given objective and verifies its accuracy using ASTM D5157. Modeling and analysis results have obtained information that can form the basis for developing guidelines to address PM issues in schools: The air purifier should be operated during periods where the predicted values exceed the limit in closed windows and the air purifier is not operating. It was also confirmed that the need for the operation of the air purifier varies between schools and classrooms under the same outdoor PM concentration. Indoor PM concentration increased significantly after students' simultaneous mass movement, necessitating air purifiers' operation before and after the events. The pre-filter of the heater also aided in the removal of coarse PM. Additionally, the limitations and future development directions of the model were discussed.

BACKGROUND: Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron). METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic characteristics, baseline health, and vaccine status. RESULTS: The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status. CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms.

BACKGROUND: Long-term symptoms following SARS-CoV-2 infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (COVID+) with adults who tested negative (COVID-), enrolled within 28 days of an FDA-approved SARS-CoV2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the CDC Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (i.e., fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1,000 participants, 722 were COVID + and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID + group than the COVID - group. At 3-months, SARS-CoV-2 symptoms declined in both groups although were more prevalent in the COVID + group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID + and COVID - groups at 3 months. CONCLUSIONS: Approximately half of COVID + participants, as compared with one-quarter of COVID - participants, had at least one SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish Long COVID.

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged 18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. EXPOSURES: SARS-CoV-2 status (positive or negative test result) at enrollment. MAIN OUTCOMES AND MEASURES: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. RESULTS: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (=3.32; 95% CI, 1.84-4.80; P<.001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: =3.90; 95% CI, 1.75-6.05; P<.001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: =4.16; 95% CI, 2.12-6.20; P<.001). CONCLUSIONS AND RELEVANCE: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

The complex etiology behind Gulf War Illness (GWI) has been attributed to the combined exposure to neurotoxicant chemicals, brain injuries, and some combat experiences. Chronic GWI symptoms have been shown to be associated with intensified neuroinflammatory responses in animal and human studies. To investigate the neuroinflammatory responses and potential causes in Gulf War (GW) veterans, we focused on the effects of chemical/biological weapons (CBW) exposure and mild traumatic brain injury (mTBI) during the war. We applied a novel MRI diffusion processing method, Neurite density imaging (NDI), on high-order diffusion imaging to estimate microstructural alterations of brain imaging in Gulf War veterans with and without GWI, and collected plasma proinflammatory cytokine samples as well as self-reported health symptom scores. Our study identified microstructural changes specific to GWI in the frontal and limbic regions due to CBW and mTBI, and further showed distinctive microstructural patterns such that widespread changes were associated with CBW and more focal changes on diffusion imaging were observed in GW veterans with an mTBI during the war. In addition, microstructural alterations on brain imaging correlated with upregulated blood proinflammatory cytokine markers TNFRI and TNFRII and with worse outcomes on self-reported symptom measures for fatigue and sleep functioning. Taken together, these results suggest TNF signaling mediated inflammation affects frontal and limbic regions of the brain, which may contribute to the fatigue and sleep symptoms of the disease and suggest a strong neuroinflammatory component to GWI. These results also suggest exposures to chemical weapons and mTBI during the war are associated with different patterns of peripheral and central inflammation and highlight the brain regions vulnerable to further subtle microscale morphological changes and chronic signaling to nearby glia.

Importance: Powassan virus is a rare but increasingly recognized cause of severe neurological disease. Objective: To highlight the diagnostic challenges and neuropathological findings in a fatal case of Powassan encephalitis caused by deer tick virus (lineage II) in a patient with follicular lymphoma receiving rituximab, with nonspecific anti-GAD65 antibodies, who was initially seen with fever and orchiepididymitis. Design, Setting, and Participants: Comparison of clinical, radiological, histological, and laboratory findings, including immunohistochemistry, real-time polymerase chain reaction, antibody detection, and unbiased sequencing assays, in a single case report (first seen in December 2016) at an academic medical center. Exposure: Infection with Powassan virus. Main Outcomes and Measures: Results of individual assays compared retrospectively. Results: In a 63-year-old man with fatal Powassan encephalitis, serum and cerebrospinal fluid IgM antibodies were not detected via standard methods, likely because of rituximab exposure. Neuropathological findings were extensive, including diffuse leptomeningeal and parenchymal lymphohistiocytic infiltration, microglial proliferation, marked neuronal loss, and white matter microinfarctions most severely involving the cerebellum, thalamus, and basal ganglia. Diagnosis was made after death by 3 independent methods, including demonstration of Powassan virus antigen in brain biopsy and autopsy tissue, detection of viral RNA in serum and cerebrospinal fluid by targeted real-time polymerase chain reaction, and detection of viral RNA in cerebrospinal fluid by unbiased sequencing. Extensive testing for other etiologies yielded negative results, including mumps virus owing to prodromal orchiepididymitis. Low-titer anti-GAD65 antibodies identified in serum, suggestive of limbic encephalitis, were not detected in cerebrospinal fluid. Conclusions and Relevance: Owing to the rarity of Powassan encephalitis, a high degree of suspicion is required to make the diagnosis, particularly in an immunocompromised patient, in whom antibody-based assays may be falsely negative. Unbiased sequencing assays have the potential to detect uncommon infectious agents and may prove useful in similar scenarios.

Veterans of the 1991 Gulf War were potentially exposed to a variety of toxic chemicals, including sarin nerve agent and pesticides, which have been suspected to be involved in the development of Gulf War Illness (GWI). Several of these exposures cause a neuroinflammatory response in mice, which may serve as a basis for the sickness behavior-like symptoms seen in veterans with GWI. Furthermore, conditions mimicking the physiological stress experienced during the war can exacerbate this effect. While neuroinflammation has been observed post-exposure using animal models, it remains a challenge to evaluate neuroinflammation and its associated cellular and molecular changes in vivo in veterans with GWI. Here, we evaluated neuroimmune-associated alterations in intact brains, applying our existing GWI mouse model to rats, by exposing them to 4 days of corticosterone (CORT; 200 mg/L in the drinking water), to mimic high physiological stress, followed by a single injection of the sarin nerve agent surrogate, diisopropyl fluorophosphate (DFP; 1.5 mg/kg, i.p.). Then, we evaluated the neuroinflammatory responses using qPCR of cytokine mRNA and also examined brain structure with a novel high-order diffusion MRI. We found a CORT-enhancement of DFP-induced neuroinflammation, extending our mouse GWI model to the rat. High order diffusion MRI revealed different patterns among the different treatment groups. Particularly, while the CORT+DFP rats had more restricted spatial patterns in the hippocampus and the hypothalamus, the highest and most wide-spread differences were shown in DFP-treated rats compared to the controls in the thalamus, the amygdala, the piriform cortex and the ventral tegmental area. The association of these diffusion changes with neuroinflammatory cytokine expression indicates the potential for GW-relevant exposures to result in connectivity changes in the brain. By transferring this high order diffusion MRI into in vivo imaging in veterans with GWI, we can achieve further insights on the trajectories of the neuroimmune response over time and its impacts on behavior and potential neurological damage.

In April 2014, a kidney transplant recipient in the United States experienced headache, diplopia, and confusion, followed by neurologic decline and death. An investigation to evaluate the possibility of donor-derived infection determined that 3 patients had received 4 organs (kidney, liver, heart/kidney) from the same donor. The liver recipient experienced tremor and gait instability; the heart/kidney and contralateral kidney recipients were hospitalized with encephalitis. None experienced gastrointestinal symptoms. Encephalitozoon cuniculi was detected by tissue PCR in the central nervous system of the deceased kidney recipient and in renal allograft tissue from both kidney recipients. Urine PCR was positive for E. cuniculi in the 2 surviving recipients. Donor serum was positive for E. cuniculi antibodies. E. cuniculi was transmitted to 3 recipients from 1 donor. This rare presentation of disseminated disease resulted in diagnostic delays. Clinicians should consider donor-derived microsporidial infection in organ recipients with unexplained encephalitis, even when gastrointestinal manifestations are absent.

With the passage of the Patient Protection and Affordable Care Act, the requirements for hospitals to achieve tax-exempt status include performing a triennial community health needs assessment and developing a plan to address identified needs. To address community health needs, multisector collaborative efforts to improve both health care and non-health care determinants of health outcomes have been the most effective and sustainable. In 2015, CDC released the Community Health Improvement Navigator to facilitate the development of these efforts. This report describes the development of the database of interventions included in the Community Health Improvement Navigator. The database of interventions allows the user to easily search for multisector, collaborative, evidence-based interventions to address the underlying causes of the greatest morbidity and mortality in the United States: tobacco use and exposure, physical inactivity, unhealthy diet, high cholesterol, high blood pressure, diabetes, and obesity.

The foundational importance of social, environmental, and economic factors as determinants of health has long been recognized (1–5). Until recently, this recognition had resulted in few sustained, organized efforts to positively influence these determinants to foster health at the community level. In recent years, however, numerous efforts have arisen across the United States that explicitly seek to improve the public’s health by catalyzing collaboration across multiple societal sectors, with the goal of leveraging policy, systems, and environmental changes to drive sustained improvements in the public’s health. Many are using concepts such as “Health in All Policies” (6,7) and collective impact (8) to structure their efforts. These initiatives vary in scope and scale, and they address the challenge of multisector approaches to the social determinants in a variety of ways, often innovating as they evolve. | These pioneering efforts face several challenges. First, they are generally not guided by any national strategy or coherent plan to promote such cross-sector partnerships or to leverage resources across these initiatives. Second, many community efforts are developing in relative isolation, with little opportunity to learn from the successes and failures of similar undertakings in other communities. Third, the accelerated pace at which broad, health-oriented community collaboratives are being launched makes it difficult to maintain awareness of the many opportunities, toolkits, and frameworks that already exist. | These efforts are laudable and offer much to adapt and apply in communities across the country. To begin to systematize such cross-sector, expansive approaches to community health, in this article we identify, categorize, and describe an array of multisector initiatives and collaborations currently under way across the United States that explicitly include attention to social, economic, and environmental factors to foster community health and well-being.

It is time to boldly expand the scope and reach of public health to address all factors that promote health and well-being, including those related to economic development, education, transportation, food, environment, and housing. Despite nearly $3.0 trillion in annual health care spending, the United States ranks 27th in the world in life expectancy, and relatively low in many other measures of health and well-being. Worse yet, for the poor in this country, life expectancy is actually decreasing. Given these trends, and persistent gaps in health status, it’s time for a major upgrade to Public Health 3.0.

PURPOSE: To identify macro-level trends that are changing the needs of epidemiologic research and practice and to develop and disseminate a set of competencies and recommendations for epidemiologic training that will be responsive to these changing needs. METHODS: There were three stages to the project: (1) assembling of a working group of senior epidemiologists from multiple sectors, (2) identifying relevant literature, and (3) conducting key informant interviews with 15 experienced epidemiologists. RESULTS: Twelve macro trends were identified along with associated actions for the field and educational competencies. The macro trends include the following: (1) "Big Data" or informatics, (2) the changing health communication environment, (3) the Affordable Care Act or health care system reform, (4) shifting demographics, (5) globalization, (6) emerging high-throughput technologies (omics), (7) a greater focus on accountability, (8) privacy changes, (9) a greater focus on "upstream" causes of disease, (10) the emergence of translational sciences, (11) the growing centrality of team and transdisciplinary science, and (12) the evolving funding environment. CONCLUSIONS: Addressing these issues through curricular change is needed to allow the field of epidemiology to more fully reach and sustain its full potential to benefit population health and remain a scientific discipline that makes critical contributions toward ensuring clinical, social, and population health.

In 1994, the Core Public Health Functions Steering Committee, which was convened by the Assistant Secretary for Health and included representatives from U.S. Public Health Service agencies and other major public health organizations, was organized to clarify the public health functions of assessment, policy development, and assurance identified by the IOM Committee on Public Health. Among its other activities, the Steering Committee was charged with developing the framework for the Essential Public Health Services to categorize all public health activities.1 It also commissioned a subcommittee on public health workforce, training, and education to provide a profile of the public health workforce and make projections regarding the workforce of the 21st century. | Twenty years later, the Essential Public Health Services continue to serve as a framework for public health initiatives across public health organizations; additionally, substantial advances have been made in establishing strong national, state, and local leadership with emphasis in collaborative partnerships among practice and academic entities to deliver the Essential Public Health Services across the nation. Efforts to better understand the workforce composition also followed these seminal efforts. Gebbie et al.2 estimated the size and composition of the public health workforce in 2000, and others3–5 followed more recently with comprehensive assessments of the epidemiologist, public health nurse, and other public health workforce capacity. Despite continuing challenges with defining position classifications and the organizational level and location of departments of health, workforce information is now routinely collected by the National Association of County and City Health Officials and the Association of State and Territorial Health Officials in their regular profile surveys of local and state public health agencies, respectively. The Council of State and Territorial Epidemiologists and Association of Public Health Laboratories also have contributed similar efforts for their respective constituents. Improvements have also occurred in training and educating the public health workforce. Within the last 10 years, schools of public health and health professions schools have made substantial changes in their curricula, including improved practice-based education and stronger applied research agendas. Both schools of public health and liberal arts colleges have introduced public health education at the undergraduate level, where it has become one of the fastest-growing majors. Enhancements in the continuing education curricula to support training of public health workers, including use of integrated distance learning systems built on existing public networks, make information on best public health practices readily available.6,7 Additionally, as information systems and technologies improve, the introduction of the evolving field of public health informatics is fundamentally transforming certain aspects of public health practice, research, and learning.8

CDC designed its Health Systems Integration Program to prepare leaders to function-at the interface of public health and health care. Specific Health Systems Integration Program competencies in the areas of communication, analysis and assessment, and health systems were developed to nurture evidence-based decision-making and leadership skills crucial for future public health leaders. The program therefore designed an innovative journal club as part of its competency-based curriculum not only to meet the standard goals for a journal club critical reading, interpretation, and acquiring content knowledge but also to foster leadership development. This report describes the Health Systems Integration Program journal club format, its implementation, challenges, and key elements of success. Other programs using a journal club model as a learning format might consider using the Health Systems Integration Program's innovative approach that focuses on leadership development.

The public health workforce is vital to protecting the health and safety of the public, yet for years, state and local governmental public health agencies have reported substantial workforce losses and other challenges to the workforce that threaten the public's health. These challenges are complex, often involve multiple influencing or related causal factors, and demand comprehensive solutions. However, proposed solutions often focus on selected factors and might be fragmented rather than comprehensive. This paper describes approaches to characterizing the situation more comprehensively and includes two visual tools: (1) a fishbone, or Ishikawa, diagram that depicts multiple factors affecting the public health workforce; and (2) a roadmap that displays key elements-goals and strategies-to strengthen the public health workforce, thus moving from the problems depicted in the fishbone toward solutions. The visual tools aid thinking about ways to strengthen the public health workforce through collective solutions and to help leverage resources and build on each other's work. The strategic roadmap is intended to serve as a dynamic tool for partnership, prioritization, and gap assessment. These tools reflect and support CDC's commitment to working with partners on the highest priorities for strengthening the workforce to improve the public's health.

CONTEXT: Health professionals who can bridge the gap between public health and clinical medicine are needed. The Centers for Disease Control and Prevention Epidemiology Elective Program (EEP) offers a rotation in public health for medical and veterinary students that provides an introduction to public health, preventive medicine, and the principles of applied epidemiology through real-world, hands-on experiential learning. OBJECTIVE: To describe EEP, including its role in the integration of medicine and public health, and career paths for those who subsequently have enrolled in the Epidemic Intelligence Service (EIS). DESIGN: A review of files of EEP students participating June 1975 to May 2012 and EIS files to determine which EEP participants subsequently enrolled in EIS and their current employment. RESULTS: During January 1975 to May 2012, a total of 1548 students participated in EEP. Six hundred thirty-eight (41.2%) EEP students participated in field-based epidemic-assistance investigations. Among 187 students completing an exit survey implemented during 2007, a total of 175 (93.6%) indicated an increased understanding or competence in applied epidemiology and public health, and 98 (52.4%) indicated that they would apply to EIS. Among the 165 (10.7%) who enrolled in and completed EIS by July 2012, 106 (64.2%) are currently employed in public health and 65 (39.4%) are board-certified in preventive medicine, board eligible, or currently enrolled in the Centers for Disease Control and Prevention Preventive Medicine Residency or Fellowship. CONCLUSIONS: The CDC Epidemiology Elective Program offers opportunities for medical and veterinary students to participate in real-world public health learning activities. The Epidemiology Elective Program provides increased understanding and competence in applied epidemiology, provides students with opportunities to learn about population health and health care problems and the tools to help them bridge the gap between clinical medicine and public health, and serves as a source for EIS and other public health-related training and careers.

CONTEXT: Studies characterizing the public health workforce are needed for providing the evidence on which to base planning and policy decision making both for workforce staffing and for addressing uncertainties regarding organizing, financing, and delivering effective public health strategies. The Centers for Disease Control and Prevention (CDC) is leading the enumeration of the US public health workforce with an initial focus on CDC as the leading federal public health agency. OBJECTIVE: To characterize CDC's workforce, assess retirement eligibility and potential staff losses, and contribute these data as the federal component of national enumeration efforts. METHODS: Two sources containing data related to CDC employees were analyzed. CDC's workforce was characterized by using data elements recommended for public health workforce enumeration and categorized the occupations of CDC staff into 15 standard occupational classifications by using position titles. Retirement eligibility and potential staffing losses were analyzed by using 1-, 3-, and 5-year increments and compared these data across occupational classifications to determine the future impact of potential loss of workforce. RESULTS: As of the first quarter of calendar year 2012, a total 11 223 persons were working at CDC; 10 316 were civil servants, and 907 were Commissioned Corps officers. Women accounted for 61%. Public health managers, laboratory workers, and administrative-clerical staff comprised the top 3 most common occupational classifications among CDC staff. Sixteen percent of the workforce was eligible to retire by December 2012, and more than 30% will be eligible to retire by December 2017. CONCLUSIONS: This study represents the first characterization of CDC's workforce and provides an evidence base upon which to develop policies for ensuring an ongoing ability to fulfill the CDC mission of maintaining and strengthening the public's health. Establishing a system for continually monitoring the public health workforce will support future efforts in understanding workforce shortages, capacity, and effectiveness; projecting trends; and initiating policies.

Adenovirus infections frequently complicate allogeneic stem cell transplants but nervous system involvement, usually presenting as encephalitis, is atypical. Progression from encephalitis to myeloradiculitis has not been described previously.(1) We present a unique case of fatal adenoviral encephalomyeloradiculitis with imaging and pathologic correlates.

A 2012 Institute of Medicine report is the latest in the growing number of calls to incorporate a population health approach in health professionals' training. Over the last decade, Duke University, particularly its Department of Community and Family Medicine, has been heavily involved with community partners in Durham, North Carolina, to improve the local community's health. On the basis of these initiatives, a group of interprofessional faculty began tackling the need to fill the curriculum gap to train future health professionals in public health practice, community engagement, critical thinking, and team skills to improve population health effectively in Durham and elsewhere. The Department of Community and Family Medicine has spent years in care delivery redesign and curriculum experimentation, design, and evaluation to distinguish the skills trainees and faculty need for population health improvement and to integrate them into educational programs. These clinical and educational experiences have led to a set of competencies that form an organizational framework for curricular planning and training. This framework delineates which learning objectives are appropriate and necessary for each learning level, from novice through expert, across multiple disciplines and domains. The resulting competency map has guided Duke's efforts to develop, implement, and assess training in population health for learners and faculty. In this article, the authors describe the competency map development process as well as examples of its application and evaluation at Duke and limitations to its use with the hope that other institutions will apply it in different settings.

Although electronic data systems that monitor for health threats are becoming increasingly automated, human expertise is, and always will be, critical to recognizing potential cases of disease, diagnosing disease, reporting diseases or conditions, analyzing and interpreting data, and communicating results to all stakeholders. For this reason, the nation's health professionals from all disciplines and at all levels are fundamental to sustaining and enhancing public health surveillance capacity.

The fields of primary care and public health in the U.S. have for the last century generally functioned independently of each other. This is not optimal; our current health challenges require improved efforts to work together in an integrated fashion to address the root causes of illness and prevent additional cases of disease, and to make the default choice a healthy one.1 Effective support of healthy behaviors will require coordination of the work of clinicians, particularly primary care clinicians, with public health agencies, schools, businesses, and community groups to better utilize community resources. In such an integrated system, primary care and public health work together to support individuals, families, patients and their caregivers, and to improve the health of individuals and populations (i.e., a true health system).2 | How will health care in the U.S. evolve to become part of such a health system? On March 28, 2012, the IOM released the report “Primary Care and Public Health: Exploring Integration to Improve Population Health”3 in which the Committee on Integrating Primary Care and Public Health reviewed promising models of primary care and public health integration, often with shared accountability for improved community and population health outcomes. From their review of numerous examples, the IOM committee developed a set of principles that they deem essential for successful integration of primary care and public health: | 1 | a shared goal of population health improvement; | 2 | community engagement in defining and addressing population health needs; | 3 | aligned leadership; | 4 | sustainability, including shared infrastructure; and | 5 | sharing and collaborative use of data and analysis.

Twelve years ago, the Association of American Medical Colleges (AAMC) and the CDC established a formal relationship through a cooperative agreement “to strengthen collaborations between academic medicine and public health.” A consistent focus of cooperative agreement activities has been improving the public health, population health, and prevention aspects of medical education. Historically, these subjects were often omitted from the training of physicians. Contemporary medical educators continue to struggle to secure the time and resources to effectively integrate this content into the curricula, despite the urgent need for physicians with a better appreciation for these issues to help address complex public health challenges that include rising chronic disease burdens, persistent health disparities, and healthcare financing that encourages treatment over prevention. | The cooperative agreement has supported the Regional Medicine–Public Health Education Centers (RMPHECs)1 initiative, an effort to integrate public/population and prevention education into medical school and residency curricula through partnerships with local and state public health agencies and other public health partners, as well as reports focusing on public health topics that have not traditionally been included in medical school curricula.2, 3 To help disseminate the lessons learned by the RMPHEC grantees and to identify other promising efforts, the AAMC and the CDC convened the “Patients and Populations: Public Health in Medical Education” conference in Cleveland, Ohio, on September 14 and 15, 2010. More than 190 medical and public health educators and public health practitioners from the U.S. and Canada gathered to share innovative curricular models and strategies to integrate public health into the continuum of medical education. The papers in this supplement to the American Journal of Preventive Medicine4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 are based on many of the presentations and discussions that occurred during the conference.

The term shoe-leather epidemiology is often synonymous with field epidemiology or intervention epidemiology. All 3 terms imply investigations initiated in response to urgent public health problems and for which the investigative team does much of its work in the field (i.e., outside the office or laboratory). Alexander D. Langmuir is credited with articulating the concept of disease surveillance as it is applied to populations rather than individuals. He also founded the Epidemic Intelligence Service (EIS) Program in 1951, a 2-year training experience in applied epidemiology that places professionals in the field, domestically and internationally, in real-life situations. Today, 70-90 EIS officers are assigned each year to Centers for Disease Control and Prevention programs and to state and local health departments to meet the broad spectrum of challenges in chronic disease, injury prevention, violence, environmental health, occupational safety and health, and maternal and child health, as well as infectious diseases. Throughout their assignments, EIS officers are encouraged to strive for analytic rigor as well as public health consequence, which requires technical competence blended with good judgment and awareness of context. Effective applied epidemiologists must have skills beyond just epidemiology to improve a population's health; the field of applied epidemiology requires multiple team members, all having different but complementary skills, to be effective.