Heartland Virus Disease-An Underreported Emerging Infection.

First recognized 15 years ago, Heartland virus disease (Heartland) is a tickborne infection contracted from the transmission of Heartland virus (HRTV) through tick bites from the lone star tick (Amblyomma americanum) and potentially other tick species. Heartland symptoms include a fever <100.4 °F, lethargy, fatigue, headaches, myalgia, a loss of appetite, nausea, diarrhea, weight loss, arthralgia, leukopenia and thrombocytopenia. We reviewed the existing peer-reviewed literature for HRTV and Heartland to more completely characterize this rarely reported, recently discovered illness. The absence of ongoing serosurveys and targeted clinical and tickborne virus investigations specific to HRTV presence and Heartland likely contributes to infection underestimation. While HRTV transmission occurs in southern and midwestern states, the true range of this infection is likely larger than now understood. The disease's proliferation benefits from an expanded tick range due to rising climate temperatures favoring habitat expansion. We recommend HRTV disease be considered in the differential diagnosis for patients with a reported exposure to ticks in areas where HRTV has been previously identified. HRTV testing should be considered early for those matching the Heartland disease profile and nonresponsive to initial broad-spectrum antimicrobial treatment. Despite aggressive supportive therapy, patients deteriorating to sepsis early in the course of the disease have a very grim prognosis.

Psittacosis: An Underappreciated and Often Undiagnosed Disease.

The bacterial agent Chlamydia psittaci, and the resulting disease of psittacosis, is a little-known and underappreciated infectious disease by healthcare practitioners and in public health in general. C. psittaci infections can cause significant psittacosis outbreaks, with person-to-person transmission documented in the last decade. In this publication, we review the pathogen and its disease, as well as examine the potential for genetic manipulation in this organism to create a more deadly pathogen. Recent disease surveys indicate that currently, the highest incidences of human disease exist in Australia, Germany and the UK. We recommend the universal public health reporting of C. psittaci and psittacosis disease and increasing the promotion of public health awareness.

Informing COVID-19 Response and Health Equity Agenda: Collection of Public Health Reports Articles on Emerging Viral Epidemics in the United States, 1878-2021.

OBJECTIVE: Public Health Reports (PHR) is the oldest public health journal in the United States and has reported on viral epidemics since the 19th century. We describe the creation and analysis of a collection of historic PHR articles on emerging viral epidemics in the United States to inform public health response to COVID-19 and future epidemics. METHODS: We searched databases from 1878 through 2021 using custom search strings and conducted a manual search for articles published under previously used names for PHR. We evaluated all articles based on inclusion/exclusion criteria and coded the final list for virus/disease, article type, public health emergency preparedness and response capabilities from the Centers for Disease Control and Prevention (CDC), and PubMed citation count. RESULTS: We identified 349 relevant articles including 130 commentaries/reviews/editorials, 79 epidemiologic reports, 75 research articles, and 65 case study/practice articles. The collection focused on influenza (n = 244), COVID-19 (n = 75), dengue (n = 14), and other emerging viruses, such as Zika and Ebola (n = 25). The collection included 48 articles on health disparities/health of various disadvantaged populations, highlighting such disparities as race and ethnicity (n = 22), socioeconomic status (n = 17), and age (n = 15). When we categorized articles by CDC public health emergency preparedness and response capabilities, we found that 207 addressed surveillance and epidemiologic investigation, 36 addressed community preparedness, and 28 addressed medical countermeasure dispensing and administration. The articles addressing surveillance and epidemiologic investigation, nonpharmaceutical interventions, and community preparedness had the most PubMed citations (799, 334, and 308, respectively). CONCLUSIONS: PHR's historic articles on US emerging viral epidemics covered a range of virus/disease types, emergency preparedness and response capabilities, and contribution types and were widely cited in the scholarly literature. This publicly available and continuously updated collection is a valuable resource for pandemic planning and response.

A Universal Travel Risk Assessment Questionnaire: Travel Assessment During COVID-19 Pandemic and Endemicity.

INTRODUCTION: Throughout the Coronavirus Disease 2019 (COVID-19) pandemic, military commanders have been challenged with providing appropriate travel guidance for their military and civilian personnel and dependents. This guidance, where promulgated, lacks uniformity. Travel aids and computer applications similarly differ and are not updated as often as jurisdictional travel health guidance is changed. Given the ever-evolving Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants with differing degrees of infectivity, COVID-19 travel guidance will remain relevant for military travelers during the transition from pandemic to endemic phases and for the foreseeable future. MATERIALS AND METHODS: We reviewed all germane travel guidance promulgated by the U.S, Department of Defense; the U.S. Centers for Disease Control and Prevention; and other federal, state, and international agencies. From these materials, we identified and delineated applicable universal components for COVID-19 travel risk and created a universal Travel Risk Assessment Questionnaire (TRAQ). RESULTS: We present a universal TRAQ that identifies and allows for a graded most-appropriate response to known travel risk assessment factors including travel restrictions, travel mode, travel time, travel party size, trip duration, COVID-19 incidence rate at travel destination, lodging, planned activities, personal interaction level, vaccination coverage at destination, travel location, traveler's vaccination status, previous COVID-19 infection, mask wear compliance, mask type, and work environment, along with additional considerations and post-travel COVID-19 questions. We provide examples of the use of this questionnaire that describe low, medium, and high risk to the traveler for contracting COVID-19. CONCLUSION: Our TRAQ provides an easy-to-use format that can enable military, business, or personal travelers to more completely assess their likelihood of COVID-19 exposure and help them to reduce their potential for contracting COVID-19 during travel and subsequently transmitting it to others upon return. It should help commanders and traveling personnel to better assess COVID-19 travel risks through application of known travel risk factors.

Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury.

Traumatic peripheral nerve injuries tend to be more common in younger, working age populations and can lead to long-lasting disability. Peripheral nerves have an impressive capacity to regenerate; however, successful recovery after injury depends on a number of factors including the mechanism and severity of the trauma, the distance from injury to the reinnervation target, connective tissue sheath integrity, and delay between injury and treatment. Even though modern surgical procedures have greatly improved the success rate, many peripheral nerve injuries still culminate in persistent neuropathic pain and incomplete functional recovery. Recent studies in animals suggest that botulinum neurotoxin A (BoNT/A) can accelerate nerve regeneration and improve functional recovery after injury to peripheral nerves. Possible mechanisms of BoNT/A action include activation or proliferation of support cells (Schwann cells, mast cells, and macrophages), increased angiogenesis, and improvement of blood flow to regenerating nerves.

Influence of Perfluoroalkyl Substances on Occurrence of Coronavirus Disease 2019.

Epidemiologic evidence indicates exposure to polyfluoroalkyl substances (PFAS) influences immunosuppression, with diminished vaccination response. The relationship between PFAS blood levels and coronavirus disease 2019 (COVID-19) occurrence by age warrants further examination. This assessment identified blood PFAS exposure levels in discrete populations. Recent PFAS population studies summarizing age and gender results were identified and included. Geographically corresponding COVID-19 incidence data were determined for selected counties in North Carolina (NC) and Ohio (OH), and the state of New Jersey (NJ). Centers for Disease Control and Prevention COVID-19 databases were accessed for national incidence data by age groupings. We assessed associations between blood PFAS concentrations, COVID-19 incidence rates, and key demographic characteristics, within subpopulations. COVID-19 incidence counts and blood PFAS concentration were obtained for each age group, along with estimated U.S. Census total population. A general trend observed is higher PFAS levels in older age groups. Younger age groups contained fewer COVID-19 cases. Global COVID-19 mortality is highest in elderly populations with hospitalization and death greatly increasing from age 50. PFAS exposures occurring early in life may cause deleterious health effects later in life, including decreased antibody response and reduced disease resistance. Highest levels of both PFAS exposure and COVID-19 were found in the oldest populations. While this does not determine causality, such associations should help promote further study.

Coronavirus Disease 2019 on the Heels of Ebola Virus Disease in West Africa.

This study utilized modeling and simulation to examine the effectiveness of current and potential future COVID-19 response interventions in the West African countries of Guinea, Liberia, and Sierra Leone. A comparison between simulations can highlight which interventions could have an effect on the pandemic in these countries. An extended compartmental model was used to run simulations incorporating multiple vaccination strategies and non-pharmaceutical interventions (NPIs). In addition to the customary categories of susceptible, exposed, infected, and recovered (SEIR) compartments, this COVID-19 model incorporated early and late disease states, isolation, treatment, and death. Lessons learned from the 2014-2016 Ebola virus disease outbreak-especially the optimization of each country's resource allocation-were incorporated in the presented models. For each country, models were calibrated to an estimated number of infections based on actual reported cases and deaths. Simulations were run to test the potential future effects of vaccination and NPIs. Multiple levels of vaccination were considered, based on announced vaccine allocation plans and notional scenarios. Increased vaccination combined with NPI mitigation strategies resulted in thousands of fewer COVID-19 infections in each country. This study demonstrates the importance of increased vaccinations. The levels of vaccination in this study would require substantial increases in vaccination supplies obtained through national purchases or international aid. While this study does not aim to develop a model that predicts the future, it can provide useful information for decision-makers in low- and middle-income nations. Such information can be used to prioritize and optimize limited available resources for targeted interventions that will have the greatest impact on COVID-19 pandemic response.

A Systems Perspective of DoD Global Health Engagement.

INTRODUCTION: A systems perspective was used to describe U.S. Department of Defense (DoD) Global Health Engagement (GHE). This description was based on DoD instructions and higher-level documents related to DoD GHE. A complex system of systems such as health care can benefit from using modeling approaches to help understand the interactions among major components. Models (conceptual, computer-based programs, realistic simulations, or training exercises) can be used to help stakeholders prioritize options and to identify important components and gaps for making performance improvements. Based on the cited documents, we identified major DoD GHE components to create a conceptual model. MATERIALS AND METHODS: Components were selected from DoDI 2000.30 for DoD GHE. Definitions of these interacting components are given and assigned to our network model that consists of three levels: strategic, operational, and tactical. These levels are linked by critical nodes (decision points) that allow feedback to previous levels for modifying appropriate components. A network that is reminiscent of this structure is Boyd's observe-orient-decision-act diagram. Acceptable strategic and operational plans are linked to the tactical level. Acceptable tactical components lead to the desired outcome of accomplishing the DoD GHE goals. Complex systems also have feedback loops to allow for component evaluations and modifications. Accomplishing DoD GHE goals need to have adaptable components in dynamic permissive environments. RESULTS: The network that we considered is multicomponent and interdisciplinary. The network uses DoD GHE goals as the input (observing in the observe-orient-decide-act loop) to provide relevant information. It consists of three levels of adaptable, interacting (orienting) components that are linked by critical nodes (decision points) involving the evaluation of plans and desired outcomes. Strategic components (eg, sharing, personal interactions, agreements, planning, readiness, etc.) are required to develop strategic plans, the first critical node. If these plans are acceptable, the information is passed on (feed forward, action) to the operational components (define problems, understand strategic direction and guidance, understand the operational environment, etc.). At the second critical node, the decision is made about moving the operational plans to the tactical components (eg, evaluation, data, training, etc.). Tactical components are essential to provide further information to the third critical node, desired outcomes, in accomplishing DoD GHE goals. Feedback from all critical nodes is essential to allow modifications of various components and to attain health-related interoperability in supporting security policies and military strategies. CONCLUSIONS: Examining the composition of DoD GHE and creating a defined model can help identify interacting features of this complex system. All of the identified components have been associated with gaps, such as the need for monitoring and measuring tools, and standards. The current state of this system is dynamic and is evolving when confronting gaps. DoD GHE represents an intersection of global health and security in supporting U.S. national security objectives by establishing access and influence with partner nations and among health care-related government and non-government organizations, and as a result, improves the readiness, health, and safety of our military personnel.

The Opioid Epidemic: Challenge to Military Medicine and National Security.

INTRODUCTION: We examine the current status of the military relevance of opioids, their use and misuse in military and veteran populations, the national security consequences of opioid use in our military age population, public health implications, and military, veteran, and government solutions for opioid addiction. MATERIALS AND METHODS: A literature search of recent published research, federal government, and related open source materials was conducted using PubMed, Google, and Google Scholar, and all materials retrieved were manually identified, screened, and evaluated for inclusion. A modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach was used for the selection of relevant articles. Heath policy literature and relevant demographic information published within the last 5 years was also included to provide current information and search for solutions to address the escalating national opioid crisis. RESULTS: Synthetic opioids are used for pain and trauma management, not readily substituted, and have exceptionally high addiction potential. Combat wounded veterans have greater potential for opioid misuse than civilian populations. Assessment, management, and treatment of opioid use in this population are essential. Veterans receiving synthetic opioids have been noted to have multiple overdose risk factors. Opioids are readily available nationally as "street drugs" and also in the form of fentanyl-contaminated heroin. The opioid crisis affects the military age population and the top states for military enlistments. Younger age males with lower education and income are at significant risk for opioid use disorder. Recently increased drug overdose deaths contribute to an increased U.S. mortality rate with a commensurate decline in life expectancy at birth. Opioid abuse contributes to increased incidence of infectious disease. Behavioral health programs directed at military and veterans to identify risk factors for opioid misuse have been introduced. Prescription drug monitoring initiatives continue for these populations with increased information exchanged between military and civilian healthcare. Lifesaving interventions for opioid addiction include methadone maintenance and fentanyl test strip accessibility. Newly implemented federal funding healthcare initiatives to the states are now directed at opioid use prevention and enhanced surveillance. CONCLUSIONS: Given increasing rates of opioid addiction and death, viable solutions are universally needed. Successful intervention measures should be widely shared between military, veteran, and civilian healthcare and public health communities. Increased collaboration between these groups could inculcate successful programs to prevent and decrease opioid use. Results received from recent military and veterans' programs for prescription and electronic medical record (EMR) monitoring and data sharing may also prove useful for civilian healthcare providers and hospital systems. Future evaluations from ongoing federally funded programs to the states for addiction surveillance and intervention may help create measures to address the proliferation of opioid addiction with increased death rates. Anticipated results from these federal efforts should help inform opioid programs in military and veterans' health systems.

Yesterday and Today: The Impact of Research Conducted at Camp Detrick on Botulinum Toxin.

Introduction: This review summarizes the research conducted on botulinum toxin (BoTx) from 1943 to 1956 by a small group of Camp Detrick investigators and their staff. A systematic, cross-disciplinary approach was used to develop effective vaccines against this biological warfare threat agent. In response to the potential need for medical countermeasures against BoTx during World War II, the refinement of isolation and purification techniques for BoTx successfully led to the large-scale production of botulinum toxoid vaccines. In addition, the work at Camp Detrick provided the foundation for the subsequent use of BoTx as a tool for studying the trophic regulation of skeletal muscle within motor neuron terminals and, more recently, for elucidation of the intricate details of neurotransmitter release at the molecular level. Indirectly, Camp Detrick investigators also played a significant role in studies that culminated in the use of BoTx as a pharmaceutical product that has been approved by the U.S. Food and Drug Administration for treating movement disorders, autonomic dysfunctions, and other conditions. Methods: Online literature searches were performed with Google, Google Scholar, PubMed, the bibliography from the Camp Detrick technical library, and at the Defense Technical Information Center. Reference lists in some of the primary research publications and reviews also provided source material. Search terms included botulinum, botulinus, and Camp Detrick. References related to the subsequent impacts of the Camp Detrick results were selected and cited from reviews and primary references in the more recent literature. Notes on toxin nomenclature and potential sources of error in this study are presented. Results: The literature searches returned 27 citations of Camp Detrick authors, 24 of which were articles in peer-reviewed journals. The publications by these investigators included several disciplines such as biochemistry, immunology, pharmacology, physiology, and toxicology. A fundamental finding was the identification of critical nutritional components for improved growth of Clostridium botulinum and the increased production of BoTx serotype A. The purification processes that were developed at Camp Detrick allowed for the production of crystalline material to be scaled up for the manufacture of toxoid vaccine. Based on the research by Camp Detrick scientists, a toxoid supply of over 1 million units was available to vaccinate ~300,000 troops before the large-scale operations of D-Day. Conclusions: BoTx research during the period 1943 to 1956 resulted in refinements in the techniques for isolating and purifying the crystalline BoTx type A. These results led to the development and manufacture of a toxoid vaccine that was available in a sufficient quantity to protect ~300,000 warfighters in a large-scale military operation. One of the most important long-term consequences derived from the knowledge gained by the efforts at Camp Detrick was the development in the 1980s of safe and effective therapeutic uses for BoTx type A, the most lethal biological substance known.

Operational Perspective of Lessons Learned From the Ebola Crisis.

Given its potential to quickly spread internationally and initially uncontrollable nature, the 2014 to 2015 Ebola outbreak has implications for global biosecurity. The Defense Threat Reduction Agency's Technical Reachback provided near real-time analysis and recommendations as outbreak-relevant events unfolded. Our review of often-conflicting or incomplete information was required to answer policy decision makers about the expanding Ebola epidemic, and enable the formulation of best-possible U.S. Department of Defense and Government response. Challenging questions often did not have obvious information available from which to provide a definitive answer. Nevertheless, through use of best-practice science and medicine, we provided timely and scientifically accurate weekly review for decision makers. Our comprehensive analyses included the nature of the outbreak, its global and national impact, contributing factors to this and future Ebola outbreaks, the U.S. Government and international response, and continuing interventions. We also provided guidance for Ebola transmission outside of West Africa, medical countermeasures, challenges with the international response, lessons learned, major constraints, and considerations for future preparedness. We believe an assessment of these events may help an improved response for future infectious disease outbreaks with global and national security implications.

Kinetic and reaction pathway analysis in the application of botulinum toxin a for wound healing.

A relatively new approach in the treatment of specific wounds in animal models and in patients with type A botulinum toxin is the focus of this paper. The indications or conditions include traumatic wounds (experimental and clinical), surgical (incision) wounds, and wounds such as fissures and ulcers that are signs/symptoms of disease or other processes. An objective was to conduct systematic literature searches and take note of the reactions involved in the healing process and identify corresponding pharmacokinetic data. From several case reports, we developed a qualitative model of how botulinum toxin disrupts the vicious cycle of muscle spasm, pain, inflammation, decreased blood flow, and ischemia. We transformed this model into a minimal kinetic scheme for healing chronic wounds. The model helped us to estimate the rate of decline of this toxin's therapeutic effect by calculating the rate of recurrence of clinical symptoms after a wound-healing treatment with this neurotoxin.

Botulism: cause, effects, diagnosis, clinical and laboratory identification, and treatment modalities.

Botulism is a neuroparalytic disease caused by neurotoxins produced by the bacteria Clostridium botulinum. Botulinum neurotoxins (BoNTs) are among the most potent naturally occurring toxins and are a category A biological threat agent. The 7 toxin serotypes of BoNTs (serotypes A-G) have different toxicities, act through 3 different intracellular protein targets, and exhibit different durations of effect. Botulism may follow ingestion of food contaminated with BoNT, from toxin production of C botulinum present in the intestine or wounds, or from inhalation of aerosolized toxin. Intoxication classically presents as an acute, symmetrical, descending flaccid paralysis. Early diagnosis is important because antitoxin therapy is most effective when administered early. Confirmatory testing of botulism with BoNT assays or C botulinum cultures is time-consuming, and may be insensitive in the diagnosis of inhalational botulism and in as many as 32% of food-borne botulism cases. Therefore, the decision to initiate botulinum antitoxin therapy is primarily based on symptoms and physical examination findings that are consistent with botulism, with support of epidemiological history and electrophysiological testing. Modern clinical practice and antitoxin treatment has reduced botulism mortality rates from approximately 60% to < or =10%. The pentavalent botulinum toxoid is an investigational product and has been used for more than 45 years in at-risk laboratory workers to protect against toxin serotypes A to E. Due to declining immunogenicity and potency of the pentavalent botulinum toxoid, novel vaccine candidates are being developed.

Guidelines for constructing a statewide hospital syndromic surveillance network.

INTRODUCTION: The process to initiate a comprehensive and inexpensive statewide hospital emergency department-based syndromic surveillance system (HEDSS) in Connecticut can serve as a template for others. OBJECTIVES: With limited financial resources, the Connecticut Department of Public Health (CDPH) determined the requirements necessary to establish and routinely conduct hospital emergency department (HED)-based syndromic surveillance. METHODS: A statewide survey assessed ability and willingness of Connecticut hospitals to participate in HED syndromic surveillance. The New York City HED-based system protocol and analysis programs, available without financial charge, were modified for use in Connecticut. This system is based on hospitals sending daily standardized files of chief complaint data through encrypted e-mail or an FTP protocol to CDPH with subsequent categorization into syndromes using a SAS program. Anticipating regional surveillance needs during the Republican National Convention in New York City (RNC), CDPH initiated HEDSS in August 2004. RESULTS: Most Connecticut HEDs were willing and able to participate on a voluntary basis. Beginning in July 2004, hospital recruitment began. By the time of the RNC, 11 of 32 Connecticut hospitals participated in HEDSS. Since then, an additional six HEDs have joined. CONCLUSION: Establishing a voluntary statewide HEDSS was possible using an existing, readily available protocol with minimum financial resources and consensus from a statewide workgroup over a several-month time period.

Hospital admissions syndromic surveillance--Connecticut, September 200-November 2003.

On September 11, 2001, the Connecticut Department of Public Health (CDPH) initiated daily, statewide syndromic surveillance based on unscheduled hospital admissions (HASS). The system's objectives were to monitor for outbreaks caused by Category A biologic agents and evaluate limits in space and time of identified outbreaks. Thirty-two acute-care hospitals were required to report their previous day's unscheduled admissions for 11 syndromes (pneumonia, hemoptysis, respiratory distress, acute neurologic illness, nontraumatic paralysis, sepsis and nontraumatic shock, fever with rash, fever of unknown cause, acute gastrointestinal illness, and possible cutaneous anthrax, and suspected illness clusters). Admissions for pneumonia, gastrointestinal illness, and sepsis were reported most frequently; admissions for fever with rash, possible cutaneous anthrax, and hemoptysis were rare. A method for determining the difference between random and systemic variation was used to identify differences of >/=3 standard deviations for each syndrome from a 6-month moving average. HASS was adapted to meet changing surveillance needs (e.g., surveillance for anthrax, smallpox, and severe acute respiratory syndrome). HASS was sensitive enough to reflect annual increases in hospital-admission rates for pneumonia during the influenza season and to confirm an outbreak of gastrointestinal illness. Follow-up of HASS neurologic-admissions reports has led to diagnosis of West Nile virus encephalitis cases. Report validation, syndrome-criteria standardization among hospitals, and expanded use of outbreak-detection algorithms will enhance the system's usefulness.

Missed sentinel case of naturally occurring pneumonic tularemia outbreak: lessons for detection of bioterrorism.

BACKGROUND: Family physicians are likely to care for patients that have been exposed to diseases associated with bioterrorism. Persons with seemingly nondescript initial disease symptoms could be harbingers of a larger outbreak, whether naturally occurring or purposefully created. METHODS: We report a missed sentinel case of pneumonic tularemia associated with a naturally occurring outbreak. The patient's initial clinical symptoms and signs were nondescript, and the diagnosis was recognized by subsequent blood tests. The medical literature was searched using the key words "tularemia," "bioterrorism," "index of suspicion," and "sentinel case." RESULTS AND CONCLUSIONS: Being alert to possible unexpected causes of a pneumonic summer illness in a patient with associated weight loss might have led to an earlier diagnosis of this sentinel case tularemia and its association with the subsequent outbreak. Individual patients are likely to visit a physician's office after a purposeful bioterrorism event. Greater efforts must be made to increase awareness in all primary care physicians who might see patients exposed to a bioterrorism illness.