CDC Guidelines for the Prevention and Treatment of Anthrax, 2023.

This report updates previous CDC guidelines and recommendations on preferred prevention and treatment regimens regarding naturally occurring anthrax. Also provided are a wide range of alternative regimens to first-line antimicrobial drugs for use if patients have contraindications or intolerances or after a wide-area aerosol release of: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. Changes from previous CDC guidelines and recommendations include an expanded list of alternative antimicrobial drugs to use when first-line antimicrobial drugs are contraindicated or not tolerated or after a bioterrorism event when first-line antimicrobial drugs are depleted or ineffective against a genetically engineered resistant: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.

Systematic Review of Hospital Treatment Outcomes for Naturally Acquired and Bioterrorism-Related Anthrax, 1880-2018.

BACKGROUND: Bacillus anthracis can cause anthrax and is a potential bioterrorism agent. The 2014 Centers for Disease Control and Prevention recommendations for medical countermeasures against anthrax were based on in vitro data and expert opinion. However, a century of previously uncompiled observational human data that often includes treatment and outcomes is available in the literature for analysis. METHODS: We reviewed treatment outcomes for patients hospitalized with anthrax. We stratified patients by meningitis status, route of infection, and systemic criteria, then analyzed survival by treatment type, including antimicrobials, antitoxin/antiserum, and steroids. Using logistic regression, we calculated odds ratios and 95% confidence intervals to compare survival between treatments. We also calculated hospital length of stay. Finally, we evaluated antimicrobial postexposure prophylaxis (PEPAbx) using data from a 1970 Russian-language article. RESULTS: We identified 965 anthrax patients reported from 1880 through 2018. After exclusions, 605 remained: 430 adults, 145 children, and 30 missing age. Survival was low for untreated patients and meningitis patients, regardless of treatment. Most patients with localized cutaneous or nonmeningitis systemic anthrax survived with 1 or more antimicrobials; patients with inhalation anthrax without meningitis fared better with at least 2. Bactericidal antimicrobials were effective for systemic anthrax; addition of a protein synthesis inhibitor(s) (PSI) to a bactericidal antimicrobial(s) did not improve survival. Likewise, addition of antitoxin/antiserum to antimicrobials did not improve survival. Mannitol improved survival for meningitis patients, but steroids did not. PEPAbx reduced risk of anthrax following exposure to B. anthracis. CONCLUSIONS: Combination therapy appeared to be superior to monotherapy for inhalation anthrax without meningitis. For anthrax meningitis, neither monotherapy nor combination therapy were particularly effective; however, numbers were small. For localized cutaneous anthrax, monotherapy was sufficient. For B. anthracis exposures, PEPAbx was effective.

Algorithms for the Identification of Anthrax Meningitis During a Mass Casualty Event Based on a Systematic Review of Systemic Anthrax From 1880 Through 2018.

BACKGROUND: During an anthrax mass casualty event, prompt identification of patients with anthrax meningitis is important. Previous research has suggested use of a screening tool based on neurological symptoms and signs. METHODS: Using historical anthrax patient data from 1880 through 2018, we analyzed risk factors for meningitis. We developed lists of symptoms and signs (ie, algorithms) for predicting meningitis with high sensitivity and specificity. We evaluated both single and paired algorithms as screening tools. RESULTS: A single algorithm with 1 or more neurological symptoms or signs identifying patients with likely meningitis achieved high sensitivity (86%; 95% confidence interval [CI], 71%-100%) and specificity (90%; 95% CI, 82%-98%). Pairing algorithms with the same symptoms and signs (severe headache, altered mental status, meningeal signs, and "other neurological deficits") improved specificity (99%; 95% CI, 97%-100%) but left 17.3% of patients in a middle "indeterminate" meningitis category and in need of additional diagnostic testing to determine likely meningitis status. Pairing algorithms with differing symptoms and signs also improved specificity over the single algorithm (92%; 95% CI, 85%-99%) but categorized just 2.5% of patients as indeterminate. CONCLUSIONS: Our study confirms prior research suggesting quick and reliable assessment of patients for anthrax meningitis is possible based on the presence or absence of certain symptoms and signs. A single algorithm was adequate; however, if we assumed low-resource diagnostic testing was feasible for some patients, pairing algorithms improved specificity. Pairing algorithms with differing symptoms and signs minimized the proportion of patients requiring additional diagnostics.

Risk Factors for Death or Meningitis in Adults Hospitalized for Cutaneous Anthrax, 1950-2018: A Systematic Review.

BACKGROUND: Cutaneous anthrax accounts for approximately 95% of anthrax cases worldwide. About 24% of untreated patients die, and many cases are complicated by meningitis. Here, we explore clinical features of cutaneous disease associated with poor outcomes. METHODS: A systematic review identified 303 full-text articles published from 1950 through 2018 that met predefined inclusion criteria. Cases were abstracted, and descriptive analyses and univariate logistic regression were conducted to identify prognostic indicators for cutaneous anthrax. RESULTS: Of 182 included patients, 47 (25.8%) died. Previously reported independent predictors for death or meningitis that we confirmed included fever or chills; nausea or vomiting; headache; severe headache; nonheadache, nonmeningeal signs; leukocytosis; and bacteremia. Newly identified predictors included anxiety, abdominal pain, diastolic hypotension, skin trauma, thoracic edema, malignant pustule edema, lymphadenopathy, and evidence of coagulopathy (all with P < .05). CONCLUSIONS: We identified patient presentations not previously associated with poor outcomes.

Clinical Features of Patients Hospitalized for All Routes of Anthrax, 1880-2018: A Systematic Review.

BACKGROUND: Anthrax is a toxin-mediated zoonotic disease caused by Bacillus anthracis, with a worldwide distribution recognized for millennia. Bacillus anthracis is considered a potential biowarfare agent. METHODS: We completed a systematic review for clinical and demographic characteristics of adults and children hospitalized with anthrax (cutaneous, inhalation, ingestion, injection [from contaminated heroin], primary meningitis) abstracted from published case reports, case series, and line lists in English from 1880 through 2018, assessing treatment impact by type and severity of disease. We analyzed geographic distribution, route of infection, exposure to anthrax, and incubation period. RESULTS: Data on 764 adults and 167 children were reviewed. Most cases reported for 1880 through 1915 were from Europe; those for 1916 through 1950 were from North America; and from 1951 on, cases were from Asia. Cutaneous was the most common form of anthrax for all populations. Since 1960, adult anthrax mortality has ranged from 31% for cutaneous to 90% for primary meningitis. Median incubation periods ranged from 1 day (interquartile range [IQR], 0-4) for injection to 7 days (IQR, 4-9) for inhalation anthrax. Most patients with inhalation anthrax developed pleural effusions and more than half with ingestion anthrax developed ascites. Treatment and critical care advances have improved survival for those with systemic symptoms, from approximately 30% in those untreated to approximately 70% in those receiving antimicrobials or antiserum/antitoxin. CONCLUSIONS: This review provides an improved evidence base for both clinical care of individual anthrax patients and public health planning for wide-area aerosol releases of B. anthracis spores.

Postexposure Prophylaxis and Treatment of Bacillus anthracis Infections: A Systematic Review and Meta-analyses of Animal Models, 1947-2019.

BACKGROUND: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. METHODS: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. RESULTS: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, ß-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. CONCLUSIONS: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.

Risk Factors for Severe Cutaneous Anthrax in a Retrospective Case Series and Use of a Clinical Algorithm to Identify Likely Meningitis and Evaluate Treatment Outcomes, Kyrgyz Republic, 2005-2012.

BACKGROUND: US Centers for Disease Control and Prevention guidelines currently recommend triple-therapy antimicrobial treatment for anthrax meningitis. In the Kyrgyz Republic, a country with endemic anthrax, cutaneous anthrax patients are routinely hospitalized and treated successfully with only monotherapy or dual therapy. Clinical algorithms have been developed to identify patients with likely anthrax meningitis based on signs and symptoms alone. We sought to retrospectively identify likely meningitis patients in the Kyrgyz Republic using a clinical algorithm and evaluate risk factors and their outcomes by type of treatment. METHODS: We conducted a retrospective chart review of cutaneous anthrax patients in the Kyrgyz Republic from 2005 through 2012. Using previous methods, we developed a highly specific algorithm to categorize patients by meningitis status. We then evaluated patient risk factors, treatments, and outcomes by disease severity and meningitis status. RESULTS: We categorized 37 of 230 cutaneous anthrax patients as likely having meningitis. All 37 likely meningitis patients survived, receiving only mono- or dual-therapy antimicrobials. We identified underlying medical conditions, such as obesity, hypertension, and chronic obstructive pulmonary disease, and tobacco and alcohol use, as potential risk factors for severe anthrax and anthrax meningitis. CONCLUSIONS: Based on our analyses, treatment of anthrax meningitis may not require 3 antimicrobials, which could impact future anthrax treatment recommendations. In addition, chronic comorbidities may increase risk for severe anthrax and anthrax meningitis. Future research should further investigate potential risk factors for severe anthrax and their impact on laboratory-confirmed meningitis and evaluate mono- and dual-therapy antimicrobial regimens for anthrax meningitis.

Use of Ebola Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020.

This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the rVSVΔG-ZEBOV-GP Ebola vaccine (Ervebo) in the United States. The vaccine contains rice-derived recombinant human serum albumin and live attenuated recombinant vesicular stomatitis virus (VSV) in which the gene encoding the glycoprotein of VSV was replaced with the gene encoding the glycoprotein of Ebola virus species Zaire ebolavirus. Persons with a history of severe allergic reaction (e.g., anaphylaxis) to rice protein should not receive Ervebo. This is the first and only vaccine currently licensed by the Food and Drug Administration for the prevention of Ebola virus disease (EVD). These guidelines will be updated based on availability of new data or as new vaccines are licensed to protect against EVD.ACIP recommends preexposure vaccination with Ervebo for adults aged ≥18 years in the U.S. population who are at highest risk for potential occupational exposure to Ebola virus species Zaire ebolavirus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff at biosafety level 4 facilities in the United States. Recommendations for use of Ervebo in additional populations at risk for exposure and other settings will be considered and discussed by ACIP in the future.

Bat and Lyssavirus Exposure among Humans in Area that Celebrates Bat Festival, Nigeria, 2010 and 2013.

Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.

Development and Performance of a Checklist for Initial Triage After an Anthrax Mass Exposure Event.

Background: Population exposure to Bacillus anthracis spores could cause mass casualties requiring complex medical care. Rapid identification of patients needing anthrax-specific therapies will improve patient outcomes and resource use. Objective: To develop a checklist that rapidly distinguishes most anthrax from nonanthrax illnesses on the basis of clinical presentation and identifies patients requiring diagnostic testing after a population exposure. Design: Comparison of published anthrax case reports from 1880 through 2013 that included patients seeking anthrax-related care at 2 epicenters of the 2001 U.S. anthrax attacks. Setting: Outpatient and inpatient. Patients: 408 case patients with inhalation, ingestion, and cutaneous anthrax and primary anthrax meningitis, and 657 control patients. Measurements: Diagnostic test characteristics, including positive and negative likelihood ratios (LRs) and patient triage assignation. Results: Checklist-directed triage without diagnostic testing correctly classified 95% (95% CI, 93% to 97%) of 353 adult anthrax case patients and 76% (CI, 73% to 79%) of 647 control patients (positive LR, 3.96 [CI, 3.45 to 4.55]; negative LR, 0.07 [CI, 0.04 to 0.11]; false-negative rate, 5%; false-positive rate, 24%). Diagnostic testing was needed for triage in up to 5% of case patients and 15% of control patients and improved overall test characteristics (positive LR, 8.90 [CI, 7.05 to 11.24]; negative LR, 0.06 [CI, 0.04 to 0.09]; false-negative rate, 5%; false-positive rate, 11%). Checklist sensitivity and specificity were minimally affected by inclusion of pediatric patients. Sensitivity increased to 97% (CI, 94% to 100%) and 98% (CI, 96% to 100%), respectively, when only inhalation anthrax cases or higher-quality case reports were investigated. Limitations: Data on case patients were limited to nonstandardized, published observational reports, many of which lacked complete data on symptoms and signs of interest. Reporting bias favoring more severe cases and lack of intercurrent outbreaks (such as influenza) in the control populations may have improved test characteristics. Conclusion: A brief checklist covering symptoms and signs can distinguish anthrax from other conditions with minimal need for diagnostic testing after known or suspected population exposure. Primary Funding Source: U.S. Department of Health and Human Services.

Trends in Pelvic Inflammatory Disease Among American Indian and Alaska Native Women, Indian Health Service, 2001-2015.

OBJECTIVES: To describe trends in rates of pelvic inflammatory disease (PID) encounters among American Indian/Alaska Native (AI/AN) women aged 15 to 44 years in the United States receiving care within the Indian Health Service (IHS). METHODS: We analyzed IHS discharge data sets for PID encounters during 2001 to 2015 with International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes. We calculated rates of PID encounters per 100 000 women overall and stratified by age group, region, and health care setting. We used regression to identify trends in the total, annual, and average annual percent changes in the rate of PID encounters. RESULTS: There were 44 042 PID encounters during 2001 to 2015 (rate = 825 per 100 000). The highest rates were among women aged 20 to 24 years (1104) and from the Alaska region (1556). Rates significantly decreased overall (2001: 1084; 2015: 512; P < .001) and within all age groups and health care settings. There was variability in Alaska, with large increases during 2001 to 2010 followed by large decreases during 2010 to 2015. CONCLUSIONS: We observed decreasing trends in PID encounters among AI/AN women aged 15 to 44 years during 2001 to 2015, with the exception of increases in the Alaska region.

Assessing Disparities in the Rates of HCV Diagnoses Within American Indian or Alaska Native Populations Served by the U.S. Indian Health Service, 2005-2015.

Hepatitis C virus (HCV) disproportionately affects American Indians/Alaska Natives (AI/AN). The Indian Health Service (IHS), via federal and tribal health facilities provides medical services to an estimated 2.2 million AI/AN people in the United States. HCV diagnoses, defined by International Classification of Diseases 9th Revision, Clinical Modification (ICD-9-CM) codes, were analyzed from 2005 to 2015. Results showed 29,803 patients with an HCV diagnosis; 53.4% were among persons born 1945-1965 and overall HCV burden was higher among males than females. These data will help inform local, regional, and national efforts to address, plan for and carry out a national strategy to provide treatment for HCV infected patients and programs to prevent new HCV infections.

Identifying Meningitis During an Anthrax Mass Casualty Incident: Systematic Review of Systemic Anthrax Since 1880.

BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is a potential bioterrorism agent. Anthrax meningitis is a common manifestation of B. anthracis infection, has high mortality, and requires more aggressive treatment than anthrax without meningitis. Its rapid identification and treatment are essential for successful management of an anthrax mass casualty incident. METHODS: Three hundred six published reports from 1880 through 2013 met predefined inclusion criteria. We calculated descriptive statistics for abstracted cases and conducted multivariable regression on separate derivation and validation cohorts to identify clinical diagnostic and prognostic factors for anthrax meningitis. RESULTS: One hundred thirty-two of 363 (36%) cases with systemic anthrax met anthrax meningitis criteria. Severe headache, altered mental status, meningeal signs, and other neurological signs at presentation independently predicted meningitis in the derivation cohort and were tested as a 4-item assessment tool for use during anthrax mass casualty incidents. Presence of any 1 factor on admission had a sensitivity for finding anthrax meningitis of 89% (83%) in the adult (pediatric) validation cohorts. Anthrax meningitis was unlikely in the absence of any of these signs or symptoms (likelihood ratio [LR]- = 0.12 [0.19] for adult [pediatric] cohorts), while presence of 2 or more made meningitis very likely (LR+ = 26.5 [30.0]). Survival of anthrax meningitis was predicted by treatment with a bactericidal agent (P = .005) and use of multiple antimicrobials (P = .01). CONCLUSIONS: We developed an evidence-based assessment tool for screening patients for meningitis during an anthrax mass casualty incident. Its use could improve both patient outcomes and resource allocation in such an event.

Alzheimer's disease and related dementia diagnoses among American Indian and Alaska Native adults aged ≥45 years, Indian Health Service System, 2016-2020.

BACKGROUND: Alzheimer's disease is the most common type of dementia and is responsible for up to 80% of dementia diagnoses and is the sixth leading cause of death in the United States. An estimated 38,000 American Indian/Alaska Native (AI/AN) people aged ≥65 years were living with Alzheimer's disease and related dementias (ADRD) in 2020, a number expected to double by 2030 and quadruple by 2050. Administrative healthcare data from the Indian Health Service (IHS) were used to estimate ADRD among AI/AN populations. METHODS: Administrative IHS healthcare data from federal fiscal years 2016 to 2020 from the IHS National Data Warehouse were used to calculate the count and rate per 100,000 AI/AN adults aged ≥45 years with at least one ADRD diagnosis code on their medical record. RESULTS: This study identified 12,877 AI/AN adults aged ≥45 years with an ADRD diagnosis code, with an overall rate of 514 per 100,000. Of those, 1856 people were aged 45-64. Females were 1.2 times (95% confidence interval: 1.1-1.2) more likely than males to have a medical visit with an ADRD diagnosis code. CONCLUSIONS: Many AI/AN people with ADRD rely on IHS, tribal, and urban Indian health programs. The high burden of ADRD in AI/AN populations aged 45-64 utilizing IHS health services highlights the need for implementation of ADRD risk reduction strategies and assessment and diagnosis of ADRD in younger AI/AN populations. This study provides a baseline to assess future progress for efforts addressing ADRD in AI/AN communities.

Mental Illness in Adults With HIV and HCV Infection: Indian Health Service, 2001-2020.

INTRODUCTION: Mental health disorders (MHDs) and substance use disorders (SUDs) in people living with HIV, hepatitis C virus (HCV) infection, and HIV/HCV coinfection are common and result in significant morbidity. However, there are no national prevalence estimates of these comorbidities in American Indian and Alaska Native (AI/AN) adults with HIV, HCV infection, or HIV/HCV coinfection. This study estimates the prevalence of MHD and SUD diagnoses in AI/AN adults diagnosed with HIV, HCV infection, or HIV/HCV coinfection within the Indian Health Service (IHS). METHODS: In 2021, a cross-sectional study using data from the National Patient Information Reporting System was completed to identify MHD or SUD diagnoses in AI/AN adults with HIV, HCV infection, or HIV/HCV coinfection within the IHS during fiscal years 2001‒2020. Logistic regression was used to compare the odds of MHD or SUD diagnoses, adjusting for age and sex. RESULTS: Of AI/AN adults diagnosed with HIV, hepatitis C virus infection, or HIV/HCV coinfection, the period prevalence of MHD or SUD diagnoses ranged from 57.2% to 81.1%. Adjusting for age and sex, individuals with HCV infection had higher odds of receiving a MHD diagnosis (AOR=1.57; 95% CI=1.47, 1.68) or SUD diagnosis (AOR=3.40; 95% CI=3.18, 3.65) than those with HIV, and individuals with HIV/HCV coinfection had higher odds of receiving a MHD diagnosis (AOR=1.60; 95% CI=1.35, 1.89) or SUD diagnosis (AOR=2.81; 95% CI=2.32, 3.41) than those with HIV. CONCLUSIONS: MHD and SUD diagnoses were common in AI/AN adults diagnosed with HIV, HCV infection, or HIV/HCV coinfection, highlighting the need for culturally appropriate screening and treatment programs sensitive to the diverse strengths of AI/AN populations and structural challenges they endure.

Evaluating Surveillance for and Estimating Administration of Rabies Postexposure Prophylaxis in the United States, 2012-2018.

BACKGROUND: An evaluation of postexposure prophylaxis (PEP) surveillance has not been conducted in over 10 years in the United States. An accurate assessment would be important to understand current rabies trends and inform public health preparedness and response to human rabies. METHODOLOGY/PRINCIPLE FINDINGS: To understand PEP surveillance, we sent a survey to public health leads for rabies in 50 U.S. states, Puerto Rico, Washington DC, Philadelphia, and New York City. Of leads from 54 jurisdictions, 39 (72%) responded to the survey; 12 reported having PEP-specific surveillance, five had animal bite surveillance that included data about PEP, four had animal bite surveillance without data about PEP, and 18 (46%) had neither. Although 12 jurisdictions provided data about PEP use, poor data quality and lack of national representativeness prevented use of this data to derive a national-level PEP estimate. We used national-level and state specific data from the Healthcare Cost & Utilization Project (HCUP) to estimate the number of people who received PEP based on emergency department (ED) visits. The estimated annual average of initial ED visits for PEP administration during 2012-2017 in the United States was 46,814 (SE: 1,697), costing upwards of 165 million USD. State-level ED data for initial visits for administration of PEP for rabies exposure using HCUP data was compared to state-level surveillance data from Maryland, Vermont, and Georgia between 2012-2017. In all states, state-level surveillance data was consistently lower than estimates of initial ED visits, suggesting even states with robust PEP surveillance may not adequately capture individuals who receive PEP. CONCLUSIONS: Our findings suggest that making PEP a nationally reportable condition may not be feasible. Other methods of tracking administration of PEP such as syndromic surveillance or identification of sentinel states should be considered to obtain an accurate assessment.

Kawasaki Disease and Kawasaki Disease Shock Syndrome Hospitalization Rates in the United States, 2006-2018.

BACKGROUND: Kawasaki disease (KD) is a febrile illness of unknown etiology. Patients with Kawasaki disease shock syndrome (KDSS) may present with clinical signs of poor perfusion and systolic hypotension in addition to typical KD features. The United States Centers for Disease Control and Prevention analyzes and interprets large hospitalization databases as a mechanism for conducting national KD surveillance. METHODS: The Kids' Inpatient Database (KID), the National (Nationwide) Inpatient Sample (NIS), and the IBM MarketScan Commercial (MSC) and MarketScan Medicaid (MSM) databases were analyzed to determine KD-associated hospitalization rates and trends from 2006 to the most recent year of available data. KD and potential KDSS hospitalizations were defined using International Classification of Disease-Clinical Modification codes. RESULTS: For the most recent year, the KD-associated hospitalization rates for children <5 years of age were 19.8 (95% CI: 17.2-22.3, KID: 2016), 19.6 (95% CI: 16.8-22.4, NIS: 2017), 19.3 (MSC: 2018), and 18.4 (MSM: 2018) per 100,000. There was no indication of an increase in KD rates over the time period. Rates of potential KDSS among children <18 years of age, ranging from 0.0 to 0.7 per 100,000, increased; coding indicated potential KDSS for approximately 2.8%-5.3% of KD hospitalizations. CONCLUSIONS: Analyses of these large, national databases produced consistent KD-associated hospitalization rates, with no increase over time detected; however, the percentage of KD hospitalizations with potential KDSS increased. Given reports of increasing incidence elsewhere and the recent identification of a novel virus-associated syndrome with possible Kawasaki-like features, continued national surveillance is important to detect changes in disease epidemiology.

Prion disease incidence in the United States: 2003-2015.

OBJECTIVE: To report the incidence of prion disease in the United States. METHODS: Prion disease decedents were retrospectively identified from the US national multiple cause-of-death data for 2003-2015 and matched with decedents in the National Prion Disease Pathology Surveillance Center (NPDPSC) database through comparison of demographic variables. NPDPSC decedents with neuropathologic or genetic test results positive for prion disease for whom no match was found in the multiple cause-of-death data were added as cases for incidence calculations; those with cause-of-death data indicating prion disease but with negative neuropathology results were removed. Age-specific and age-adjusted average annual incidence rates were then calculated. RESULTS: A total of 5,212 decedents were identified as having prion disease, for an age-adjusted average annual incidence of 1.2 cases per million population (range 1.0 per million [2004 and 2006] to 1.4 per million [2013]). The median age at death was 67 years. Ten decedents were <30 years of age (average annual incidence of 6.2 per billion); only 2 of these very young cases were sporadic forms of prion disease. Average annual incidence among those ≥65 years of age was 5.9 per million. CONCLUSIONS: Prion disease incidence can be estimated by augmenting mortality data with the results of neuropathologic and genetic testing. Cases <30 years of age were extremely rare, and most could be attributed to exogenous factors or the presence of a genetic mutation. Continued vigilance for prion diseases in all age groups remains prudent.

Rat-Bite Fever in the United States: An Analysis Using Multiple National Data Sources, 2001-2015.

BACKGROUND: Rat-bite fever is a rare disease associated with rat bites or direct/indirect rodent contact. METHODS: We examined rat-bite fever and rat-bite injury diagnoses in the United States during 2001-2015. We analyzed national, state, and Indian Health Service healthcare encounter datasets for rat-bite fever and rat-bite injury diagnoses. We calculated average-annual encounter rates per 1 000 000 persons. RESULTS: Nationally, the rat-bite fever Emergency Department visit rate was 0.33 (95% confidence interval [CI], 0.19-0.47) and the hospitalization rate was 0.20 (95% CI, 0.17-0.24). The rat-bite injury Emergency Department visit rate was 10.51 (95% CI, 10.13-10.88) and the hospitalization rate was 0.27 (95% CI, 0.23-0.30). The Indian Health Service Emergency Department/outpatient visit rate was 3.00 for rat-bite fever and 18.89 for rat-bite injury. The majority of rat-bite fever encounters were among individuals 0-19 years of age. CONCLUSIONS: Our results support the literature that rat-bite fever is rare and affects children and young adults. Targeted education could benefit specific risk groups.