Alexander J. Millman

Hepatitis C: Review of the Epidemiology, Clinical Care, and Continued Challenges in the Direct-Acting Antiviral Era

Purpose of ReviewThis review highlights key studies and recently published data, policies, and recommendations related to hepatitis C virus (HCV) epidemiology, transmission, and treatment.Recent FindingsHCV is a leading cause of liver-related deaths, cirrhosis, and hepatocellular carcinoma. Since 2011 and accelerating since 2013, new, safe, tolerable, and curative therapies have considerably altered clinical and public health frameworks related to the prevention, control, and clinical management of HCV. Nevertheless, there are several populations in the USA that are important to consider because of disparities in HCV prevalence and transmission risk. Adults born during 1945–1965 have an estimated anti-HCV antibody prevalence of ∼3%, which is six times higher than among other adults, are often unaware of their infections, and are at increased risk of having HCV-associated morbidity and mortality from decades of chronic infection. Since the early 2000s, increasing incidence of acute HCV infections among young, white, non-urban people who inject drugs has been reported. Despite promising therapeutic advances, significant challenges remain for reducing HCV-associated morbidity and mortality.SummaryThe high burden of HCV and significant health consequences associated with chronic infection make HCV a critical public health priority. Advances in HCV treatment have created new opportunities for reducing HCV-associated morbidity and mortality. These treatments are safe, well tolerated, and highly effective; however, benefits cannot be realized without a significant increase in the number of persons tested for HCV so that all chronically infected individuals can be aware of their diagnosis and linked to appropriate clinical care.

Detecting Spread of Avian Influenza A(H7N9) Virus Beyond China

This virus is unlikely to have spread substantially among humans in Vietnam, Thailand, Cambodia, and Laos.

Improving Accuracy of Influenza-Associated Hospitalization Rate Estimates

Adjusting for diagnostic test sensitivity enables more accurate and timely comparisons over time.

Chikungunya and Dengue Virus Infections Among United States Community Service Volunteers Returning from the Dominican Republic, 2014.

Chikungunya spread throughout the Dominican Republic (DR) after the first identified laboratory-confirmed cases were reported in April 2014. In June 2014, a U.S.-based service organization operating in the DR reported chikungunya-like illnesses among several staff. We assessed the incidence of chikungunya virus (CHIKV) and dengue virus (DENV) infection and illnesses and evaluated adherence to mosquito avoidance measures among volunteers/staff deployed in the DR who returned to the United States during July-August 2014. Investigation participants completed a questionnaire that collected information on demographics, medical history, self-reported illnesses, and mosquito exposures and avoidance behaviors and provided serum for CHIKV and DENV diagnostic testing by reverse transcription polymerase chain reaction and IgM enzyme-linked immunosorbent assay. Of 102 participants, 42 (41%) had evidence of recent CHIKV infection and two (2%) had evidence of recent DENV infection. Of the 41 participants with evidence of recent CHIKV infection only, 39 (95%) reported fever, 37 (90%) reported rash, and 37 (90%) reported joint pain during their assignment. All attended the organizations health trainings, and 89 (87%) sought a pretravel health consultation. Most (∼95%) used insect repellent; however, only 30% applied it multiple times daily and < 5% stayed in housing with window/door screens. In sum, CHIKV infections were common among these volunteers during the 2014 chikungunya epidemic in the DR. Despite high levels of preparation, reported adherence to mosquito avoidance measures were inconsistent. Clinicians should discuss chikungunya with travelers visiting areas with ongoing CHIKV outbreaks and should consider chikungunya when diagnosing febrile illnesses in travelers returning from affected areas.

Non-mumps Viral Parotitis During the 2014–2015 Influenza Season in the United States

Background During the 2014-2015 US influenza season, 320 cases of non-mumps parotitis (NMP) among residents of 21 states were reported to the Centers for Disease Control and Prevention (CDC). We conducted an epidemiologic and laboratory investigation to determine viral etiologies and clinical features of NMP during this unusually large occurrence. Methods NMP was defined as acute parotitis or other salivary gland swelling of >2 days duration in a person with a mumps- negative laboratory result. Using a standardized questionnaire, we collected demographic and clinical information. Buccal samples were tested at the CDC for selected viruses, including mumps, influenza, human parainfluenza viruses (HPIVs) 1-4, adenoviruses, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses (HSVs) 1 and 2, and human herpes viruses (HHVs) 6A and 6B. Results Among the 320 patients, 65% were male, median age was 14.5 years (range, 0-90), and 67% reported unilateral parotitis. Commonly reported symptoms included sore throat (55%) and fever (48%). Viruses were detected in 210 (71%) of 294 NMP patients with adequate samples for testing, ≥2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2. Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses. Conclusions Our findings suggest that, in addition to mumps, clinicians should consider respiratory viral (influenza) and herpes viral etiologies for parotitis, particularly among patients without epidemiologic links to mumps cases or outbreaks.

Hospitalizations within 14 days of vaccination among pediatric recipients of the live attenuated influenza vaccine, United States 2010–2012

BACKGROUND Live attenuated influenza vaccine (LAIV) is safe in healthy children ⩾2years. The original clinical trials excluded individuals with underlying conditions; however, post-marketing data suggest LAIV may be safe for these populations. METHODS We analyzed MarketScan Commercial Claims Databases from 2010 to 2012 to describe hospitalizations within 14days of vaccination among LAIV recipients. We evaluated LAIV recipients aged 2-18years and defined underlying conditions by presence of inpatient or outpatient ICD-9 code during the previous calendar year. We excluded asthma and immunocompromising conditions. We defined risk windows as 1-7days and 8-14days after vaccination; the control period was 12-4days prior to and 15-23days after vaccination. We conducted a self-controlled case series analysis using a conditional Poisson regression model to estimate incidence-rate ratios (IRR). RESULTS 1,216,123 children aged 2-18years received LAIV from 2010 to 2012. 634 children met our inclusion criteria and were hospitalized during the observation period (12days prior to vaccination to 23days after vaccination). Of those hospitalized, 72 (11.4%) had non-asthma, non-immunocompromising underlying conditions. Children with non-asthma, non-immunocompromising underlying conditions had an all-cause hospitalization IRR of 1.1 (95% CI 0.6-2.0, p=0.83) in the 1-7day risk period and 0.9 (95% CI 0.4-1.7, p=0.67) in the 8-14day risk period. Children with no underlying conditions had an all-cause hospitalization IRR of 0.9 (0.8-1.2, p=0.60) in the 1-7day risk period and 1.1 (95% CI 0.9-1.3, p=0.53) in the 8-14day risk period. There were no differences in all-cause hospitalization risk in individuals with non-asthma, non-immunocompromising underlying conditions compared to those without underlying conditions in the 1-7day (p=0.88) or 8-14day (p=0.24) risk period. CONCLUSIONS We found no evidence of differences in post-LAIV hospitalization risk among children with non-asthma, non-immunocompromising underlying conditions compared to healthy children.

Comparison of hepatitis C virus testing recommendations in high-income countries

AIM To investigate hepatitis C virus (HCV) testing recommendations from the United States and other high-income countries. METHODS A comprehensive search for current HCV testing recommendations from the top quartile of United Nations Human Development Index (HDI) countries (very high HDI) was performed using Google and reviewed from May 1 - October 30, 2014 and re-reviewed April 1 - October 2, 2017. RESULTS Of the 51 countries identified, 16 had HCV testing recommendations from a government body or recommendations issued collaboratively between a government and a medical organization. Of these 16 countries, 15 had HCV testing recommendations that were primarily risk-based and highlight behaviors, exposures, and conditions that are associated with HCV transmission in that region. In addition to risk-based testing, the HCV Guidance Panel (United States) incorporates recommendations for a one-time test for individuals born during 1945-1965 (the birth cohort) without prior ascertainment of risk into their guidance. In addition to the United States, six other countries either have an age-based testing recommendation or recommend one-time testing for all adults independent of risk factors typical of the region. CONCLUSION This review affirmed the similarities of the HCV Guidance Panel’s guidance with those of recommendations from very high HDI countries.

Influenza-Associated Parotitis During the 2014–2015 Influenza Season in the United States

Background During the 2014-2015 influenza season in the United States, 256 cases of influenza-associated parotitis were reported from 27 states. We conducted a case-control study and laboratory investigation to further describe this rare clinical manifestation of influenza. Methods During February 2015-April 2015, we interviewed 50 cases (with parotitis) and 124 ill controls (without parotitis) with laboratory-confirmed influenza; participants resided in 11 states and were matched by age, state, hospital admission status, and specimen collection date. Influenza viruses were characterized using real-time polymerase chain reaction and next-generation sequencing. We compared cases and controls using conditional logistic regression. Specimens from additional reported cases were also analyzed. Results Cases, 73% of whom were aged <20 years, experienced painful (86%), unilateral (68%) parotitis a median of 4 (range, 0-16) days after onset of systemic or respiratory symptoms. Cases were more likely than controls to be male (76% vs 51%; P = .005). We detected influenza A(H3N2) viruses, genetic group 3C.2a, in 100% (32/32) of case and 92% (105/108) of control specimens sequenced (P = .22). Influenza B and A(H3N2) 3C.3 and 3C.3b genetic group virus infections were detected in specimens from additional cases. Conclusions Influenza-associated parotitis, as reported here and in prior sporadic case reports, seems to occur primarily with influenza A(H3N2) virus infection. Because of the different clinical and infection control considerations for mumps and influenza virus infections, we recommend clinicians consider influenza in the differential diagnoses among patients with acute parotitis during the influenza season.

Interagency and Commercial Collaboration During an Investigation of Chikungunya and Dengue Among Returning Travelers to the United States.

Public health investigations can require intensive collaboration between numerous governmental and nongovernmental organizations. We describe an investigation involving several governmental and nongovernmental partners that was successfully planned and performed in an organized, comprehensive, and timely manner with several governmental and nongovernmental partners.

780Clinical Characteristics And Outcomes among Children with Neurological Disorders Hospitalized with Community-acquired Pneumonia (CAP) in the Etiology of Pneumonia in the Community (EPIC) Study

Neurological Disorders Hospitalized with Community-acquired Pneumonia (CAP) in the Etiology of Pneumonia in the Community (EPIC) Study Alexander J. Millman, MD; Lyn Finelli, Dr PH, MS; Anna M. Bramley, MPH; Georgina Peacock, MD, MPH; Derek J. Williams, MD, MPH; Sandra R. Arnold, MD; Carlos G. Grijalva, MD, MPH; Evan J. Anderson, MD; Jonathan A. Mccullers, MD; Krow Ampofo, MD; Andrew Pavia, MD, FIDSA, FSHEA; Kathryn Edwards, MD, FIDSA; Seema Jain, MD, MPH; Centers for Disease Control and Prevention, Atlanta, GA; Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA; National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA; Vanderbilt University School of Medicine, Nashville, TN; Le Bonheur Children’s Hospital, Memphis, TN; Preventative Medicine, Vanderbilt University School of Medicine, Nashville, TN; Pediatrics and Medicine, Emory University School of Medicine, Atlanta, GA; St. Jude Children’s Research Hospital, Memphis, TN; Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Utah School of Medicine, Salt Lake City, UT; Division of Pediatric Infectious Disease, Vanderbilt University Medical Center, Nashville, TN