Kerri Barton

Emerging Epidemic of Hepatitis C Virus Infections Among Young Nonurban Persons Who Inject Drugs in the United States, 2006–2012

BACKGROUND Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged ≤30 years). METHODS We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV-infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions. RESULTS From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons-13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin. CONCLUSIONS These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention.

Notes from the Field: Ongoing Transmission of Candida auris in Health Care Facilities — United States, June 2016–May 2017

Ongoing Transmission of Candida auris in Health Care Facilities — United States, June 2016–May 2017 Sharon Tsay, MD1,2; Rory M. Welsh, PhD1; Eleanor H. Adams, MD3; Nancy A. Chow, PhD1; Lalitha Gade, MPharm1; Elizabeth L. Berkow, PhD1; Eugenie Poirot, PhD2,4; Emily Lutterloh, MD3,5; Monica Quinn, MS3; Sudha Chaturvedi, PhD3,5; Janna Kerins, VMD2,6; Stephanie R. Black, MD6; Sarah K. Kemble, MD6; Patricia M. Barrett, MSD7; Kerri Barton, MPH8; D.J. Shannon, MPH9; Kristy Bradley, DVM10; Shawn R. Lockhart, PhD1; Anastasia P. Litvintseva, PhD1; Heather MoultonMeissner, PhD11; Alicia Shugart, MA11; Alex Kallen, MD11; Snigdha Vallabhaneni, MD1; Tom M. Chiller, MD1; Brendan R. Jackson, MD1

Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance System: A Case Series and Chart Review

At least 185 million persons worldwide are infected with hepatitis C virus (HCV), with an estimated 3 to 4 million new infections occurring each year (1, 2). In developed countries, persons who inject drugs are primarily at risk for HCV infection from bloodborne exposure by means of contaminated drug paraphernalia (3). After a sharp decrease in the incidence of HCV infection in the United States in the 1990s, estimates suggest a more moderate but steady decline over the past decade, with rates calculated at 0.3 to 0.7 cases per 100 000 persons (4, 5). Accurate and current estimates of the incidence of HCV infection at the local, state, and national levels are critical for quantifying disease burden, guiding public health agency initiatives, and tracking the outcomes of preventive interventions. Unlike acute hepatitis A and hepatitis B infections, which are diagnosed with immunoglobulin M (IgM) antibody testing, there is no single diagnostic test for acute HCV infection. Without a definitive test, surveillance by local public health officials hinges on a complex composite of risk factors; symptom reporting; laboratory assessments, including antibodies to HCV (anti-HCVs), nucleic acid testing, and aminotransferase levels; and exclusion of alternative causes of hepatitis. During acute HCV infection, aminotransferase and HCV RNA levels can fluctuate and seroconversion from negative to positive anti-HCV status can occur over time. Most patients are asymptomatic and specific symptoms, such as jaundice, are uncommon in acute infections, which further complicates detection. Patients whose acute infections clear spontaneously may have low or normal aminotransferase levels at presentation and thereby escape detection. Acute HCV infections are reportable in most jurisdictions in the United States, which subsequently report cases to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Disease Surveillance System. In 2010, 850 acute cases of HCV infection were reported to the CDC, which applied a multiplier of 20 to arrive at an estimate of 17 000 new HCV infections per year in the United States (4, 6). This calculation assumes that for each reported acute infection there are 20 unreported cases because most patients are asymptomatic and persons who inject drugs—the group with highest incidence of infection—often do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to its department of public health. Heroin use has increased markedly in Massachusetts and has been accompanied by a sharp increase in cases of HCV infection in patients younger than 30 years, with more than 2000 new reports of prevalent cases in this age group in 2012 (7, 8). To assess the contribution of acute cases of HCV infection in Massachusetts to national incidence estimates, we retrospectively reviewed 183 diagnoses of acute HCV infection in a local cohort. We aimed to determine the proportion of clinical cases of acute HCV infection classified as confirmed for surveillance purposes and to determine why clinical cases were not counted in national statistics.Context Estimates of the incidence of acute hepatitis C virus (HCV) infection are complicated by the absence of a specific laboratory test and its generally asymptomatic presentation. Contribution Among patients with clinically diagnosed acute HCV infection participating in a research study, virtually none fit the national case definition of acute infection used for reporting to the Centers for Disease Control and Prevention. Limitations to accurate case ascertainment included incomplete reporting, problematic case definitions, requirements for negative laboratory results for hepatitis A and B, and incomplete data capture. Caution Patients were from 2 hospitals in 1 state. Implication Current national estimates of the incidence of acute HCV infection may not be reliable. At least 185 million persons worldwide are infected with hepatitis C virus (HCV), with an estimated 3 to 4 million new infections occurring each year (1, 2). In developed countries, persons who inject drugs are primarily at risk for HCV infection from bloodborne exposure by means of contaminated drug paraphernalia (3). After a sharp decrease in the incidence of HCV infection in the United States in the 1990s, estimates suggest a more moderate but steady decline over the past decade, with rates calculated at 0.3 to 0.7 cases per 100000 persons (4, 5). Accurate and current estimates of the incidence of HCV infection at the local, state, and national levels are critical for quantifying disease burden, guiding public health agency initiatives, and tracking the outcomes of preventive interventions. Unlike acute hepatitis A and B infections, which are diagnosed with IgM antibody testing, there is no single diagnostic test for acute HCV infection. Without a definitive test, surveillance by local public health officials hinges on a complex composite of risk factors; symptom reporting; laboratory assessments, including antibodies to HCV (anti-HCV), nucleic acid testing, and aminotransferase levels; and exclusion of alternative causes of hepatitis. During acute HCV infection, aminotransferase and HCV RNA levels can fluctuate and seroconversion from negative to positive anti-HCV status can occur over time. Most patients are asymptomatic and specific symptoms, such as jaundice, are uncommon in acute infections, which further complicates detection. Patients whose acute infections clear spontaneously may have low or normal aminotransferase levels at presentation and thereby escape detection. Acute HCV infections are reportable in most jurisdictions in the United States, which subsequently report cases to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Disease Surveillance System. In 2010, 850 acute cases of HCV infection were reported to the CDC, which applied a multiplier of 20 to arrive at an estimate of 17000 new HCV infections per year in the United States (4, 6). This calculation assumes that for each reported acute infection there are 20 unreported cases because most patients are asymptomatic and persons who inject drugsthe group with highest incidence of infectionoften do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to the Massachusetts Department of Public Health (MDPH). Heroin use has increased markedly in Massachusetts and has been accompanied by a sharp increase in cases of HCV infection in patients younger than 30 years, with more than 2000 new reports of prevalent cases in this age group in 2012 (7, 8). To assess the contribution of acute cases of HCV infection in Massachusetts to national incidence estimates, we retrospectively reviewed 183 diagnoses of acute HCV infection in a local cohort. We aimed to determine the proportion of clinical cases of acute HCV infection classified as confirmed for surveillance purposes and to determine why clinical cases were not counted in national statistics. Methods Participants BAHSTION (Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network) is a longitudinal study that recruited patients with acute HCV infection (9). Recruitment began in 1998, and patients from 2 hospitals in Boston (Massachusetts General Hospital, a tertiary care hospital that also provides primary care services in several communities, and Lemuel Shattuck Hospital, a facility that serves prisoners and patients referred by public agencies) were enrolled through referrals to specialists in infectious disease and gastroenterology. The cohort also included inmates who entered Massachusetts correctional facilities and were enrolled through referrals from health care providers (10) and through a systematic screening program that asked incoming inmates about specific injection practices. This resulted in a tripling of the rate of identification of acute HCV infection from that previously reported in those facilities (11). For study purposes, a clinical case of acute HCV infection was defined by both of the following criteria and classified as definite, probable, or possible (Figure 1): risk factor for HCV infection within the past year and consistent or supportive clinical or laboratory criteria, including compatible illness (especially jaundice), alanine aminotransferase (ALT) level greater than 7 times the upper limit of normal, seroconversion (defined as a newly positive anti-HCV test result in the context of a previous negative result), and HCV RNA characteristics (low-level viremia or fluctuations), as described in previous reports (11, 12). Figure 1. Definitions of acute HCV in BAHSTION. ALT = alanine aminotransferase; BAHSTION = Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network; HCV = hepatitis C virus; ULN = upper limit of normal. Surveillance Definitions of Past or Present HCV Infection and Acute HCV Infection Since 2003, a confirmed case of past or present HCV infection for CDC surveillance purposes has been defined as having 1 or more of the following criteria: anti-HCV with a signalcutoff ratio predictive of a true positive result, positive results for HCV on a recombinant immunoblot assay, or positive results for HCV RNA on a nucleic acid test (including qualitative, quantitative, or genotype testing) (13). Details of specific requirements are found in the Appendix. Before 2012, the CDC defined a confirmed case of acute HCV infection for surveillance purposes as first meeting the previously mentioned definition of past or present HCV infection, plus meeting clinical criteria, including an acute illness with discrete onset of any sign or symptom consistent with acute viral hepatitis (that is, anorexia, abdominal discomfort, nausea, or vomiting) and either 1) jaundice or dark urine or 2) serum ALT levels greater than 400 IU/L. To meet the case definition, the test results must be negative for both IgM antibodies to hepatitis A virus and hepatitis B core antigen. The BAHSTION clinical case definition differs from the pre-2012 CDC surveillance definition of acute HCV infection by including the following criteria: detailed risk factor history, HCV RNA criteria that help to differentiate acute from chronic infection (low-level viremia or HCV RNA level fluctuations and spontaneous clearance of detectable viremia), use of a different threshold of ALT elevation (that is, 7 times the upper limit of normal [385 U/L vs. 400 U/L]), and inclusion of seroconversion (Appendix Table 1). In 2012, the CDC adopted changes in the case definition of acute HCV infection developed by the Council of State and Territorial Epidemiologists. These changes included seroconversion within 6 months as sufficient for diagnosis and removal of the requirement of documentation of the status of IgM antibodies to hepatitis A virus or hepatitis B core antigen (13). Appendix Table 1. Case Definition Comparison Surveillance in Massachusetts for Acute HCV Infection Hepatitis C virus infection in Massachusetts residents has been reportable to the MDPH since 1992. In 2005, because of the high burden of new reports of HCV infection, the MDPH switched from case investigations done by local health departments to clinician-based reporting, in which the ordering provider completes a short, single-page HCV case report form (CRF) with patient demographic characteristics, clinical history, confirmatory laboratory results, and basic risk factors (Supplement 1). Before 2007, if the submitted form indicated a case potentially meeting the surveillance definition for acute HCV infection (acute illness with jaundice or ALT levels >400 IU/L), follow-up was assigned to the local public health official who interviewed the patient using a more detailed acute HCV CRF (Supplement 2). After recognition of an increase in cases of acute HCV infection identified in young patients in 2007 (7, 8), the MDPH also began sending the longer form directly to clinicians for patients aged 15 to 25 years. Epidemiologists from the MDPH review all completed acute HCV CRFs and reported laboratory results and assign case status based on the current standard surveillance case definitions. Case classification may be modified and updated based on additional information. Those classified according to the national surveillance case definition are submitted to the CDC on a weekly basis. Reporting is the providers responsibility, and enrollment in BAHSTION does not result in reporting to the MDPH. Supplement 1. Case Report Form for Past or Present Hepatitis C Virus Infection Supplement 2. Enhanced Case Report Form for Acute Hepatitis C Virus Infection Much of the data capture and management process of acute HCV infection by the MDPH has been automated through the Massachusetts Virtual Epidemiologic Network (MAVEN), an integrated surveillance and case management system that enables state and local public health professionals to share data efficiently and securely over the Internet (14). MAVEN was instituted in 2006 and houses historical surveillance data dating back to 1988. Automated electronic labora

Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: a molecular epidemiological survey

BACKGROUND Transmission of multidrug-resistant Candida auris infection has been reported in the USA. To better understand its emergence and transmission dynamics and to guide clinical and public health responses, we did a molecular epidemiological investigation of C auris cases in the USA. METHODS In this molecular epidemiological survey, we used whole-genome sequencing to assess the genetic similarity between isolates collected from patients in ten US states (California, Connecticut, Florida, Illinois, Indiana, Maryland, Massachusetts, New Jersey, New York, and Oklahoma) and those identified in several other countries (Colombia, India, Japan, Pakistan, South Africa, South Korea, and Venezuela). We worked with state health departments, who provided us with isolates for sequencing. These isolates of C auris were collected during the normal course of clinical care (clinical cases) or as part of contact investigations or point prevalence surveys (screening cases). We integrated data from standardised case report forms and contact investigations, including travel history and epidemiological links (ie, patients that had shared a room or ward with a patient with C auris). Genetic diversity of C auris within a patient, a facility, and a state were evaluated by pairwise differences in single-nucleotide polymorphisms (SNPs). FINDINGS From May 11, 2013, to Aug 31, 2017, isolates that corresponded to 133 cases (73 clinical cases and 60 screening cases) were collected. Of 73 clinical cases, 66 (90%) cases involved isolates related to south Asian isolates, five (7%) cases were related to South American isolates, one (1%) case to African isolates, and one (1%) case to east Asian isolates. Most (60 [82%]) clinical cases were identified in New York and New Jersey; these isolates, although related to south Asian isolates, were genetically distinct. Genomic data corroborated five (7%) clinical cases in which patients probably acquired C auris through health-care exposures abroad. Among clinical and screening cases, the genetic diversity of C auris isolates within a person was similar to that within a facility during an outbreak (median SNP difference three SNPs, range 0-12). INTERPRETATION Isolates of C auris in the USA were genetically related to those from four global regions, suggesting that C auris was introduced into the USA several times. The five travel-related cases are examples of how introductions can occur. Genetic diversity among isolates from the same patients, health-care facilities, and states indicates that there is local and ongoing transmission. FUNDING US Centers for Disease Control and Prevention.

Predicting Future Antibiotic Susceptibility using Regression-based Methods on Longitudinal Massachusetts Antibiogram Data.

Antibiotic resistance evolves alarmingly quickly, requiring constant reevaluation of resistance patterns to guide empiric treatment of bacterial infections. Aggregate antimicrobial susceptibility reports, called antibiograms, are critical for evaluating the likelihood of effectiveness of antibiotics prior to the availability of patient specific laboratory data. Our objective is to analyze the ability of the methods to predict antimicrobial susceptibility. This research utilizes Massachusetts statewide antibiogram data, a rich dataset composed of average percent susceptibilities of 10 species of bacteria to a variety of antibiotics collected by the Massachusetts Department of Public Health from over 50 acute-care hospitals from 2002 to 2015. First, we improved data quality by implementing data filtering strategies. We then predicted up to three future years of antibiotic susceptibilities using regression-based strategies on nine previous years of data. We discovered the same prediction methodology should not be utilized uniformly for all 239 antibiotic-bacteria pairs. Thus, we propose model selection strategies that automatically select a suitable model for each antibiotic-bacteria pair based on minimizing those models’ mean squared error and previous year’s prediction error. By comparing the predictions against the actual mean susceptibility, our experimental analysis revealed that the model selectors based on the predictions of the previous performed best.

Transmission of Mobile Colistin Resistance (mcr-1) by Duodenoscope

BACKGROUND Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1-harboring bacteria in the United States. METHODS A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. RESULTS Two patients had highly related mcr-1-positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. Klebsiella pneumoniae and Escherichia coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. CONCLUSIONS We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of a US Food and Drug Administration-cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings.

Using public health surveillance data to measure Clostridium difficile infection population burden in Massachusetts

ABSTRACT Clostridium difficile occurs both inside and outside of health care facilities, but surveillance has been traditionally limited to the hospital setting. To measure the population‐based burden of C difficile infection (CDI), we used multiple routine sources of data. We found an overall rate of CDI in Massachusetts in 2016 of 132.5 per 100,000 population, with mortality in 2014 of 6.4 per 100,000 population. Population‐based measurement of CDI burden appears feasible without conducting a special study.

Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance SystemA Case Series and Chart ReviewUnderascertainment of Acute HCV Infections

At least 185 million persons worldwide are infected with hepatitis C virus (HCV), with an estimated 3 to 4 million new infections occurring each year (1, 2). In developed countries, persons who inject drugs are primarily at risk for HCV infection from bloodborne exposure by means of contaminated drug paraphernalia (3). After a sharp decrease in the incidence of HCV infection in the United States in the 1990s, estimates suggest a more moderate but steady decline over the past decade, with rates calculated at 0.3 to 0.7 cases per 100 000 persons (4, 5). Accurate and current estimates of the incidence of HCV infection at the local, state, and national levels are critical for quantifying disease burden, guiding public health agency initiatives, and tracking the outcomes of preventive interventions. Unlike acute hepatitis A and hepatitis B infections, which are diagnosed with immunoglobulin M (IgM) antibody testing, there is no single diagnostic test for acute HCV infection. Without a definitive test, surveillance by local public health officials hinges on a complex composite of risk factors; symptom reporting; laboratory assessments, including antibodies to HCV (anti-HCVs), nucleic acid testing, and aminotransferase levels; and exclusion of alternative causes of hepatitis. During acute HCV infection, aminotransferase and HCV RNA levels can fluctuate and seroconversion from negative to positive anti-HCV status can occur over time. Most patients are asymptomatic and specific symptoms, such as jaundice, are uncommon in acute infections, which further complicates detection. Patients whose acute infections clear spontaneously may have low or normal aminotransferase levels at presentation and thereby escape detection. Acute HCV infections are reportable in most jurisdictions in the United States, which subsequently report cases to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Disease Surveillance System. In 2010, 850 acute cases of HCV infection were reported to the CDC, which applied a multiplier of 20 to arrive at an estimate of 17 000 new HCV infections per year in the United States (4, 6). This calculation assumes that for each reported acute infection there are 20 unreported cases because most patients are asymptomatic and persons who inject drugs—the group with highest incidence of infection—often do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to its department of public health. Heroin use has increased markedly in Massachusetts and has been accompanied by a sharp increase in cases of HCV infection in patients younger than 30 years, with more than 2000 new reports of prevalent cases in this age group in 2012 (7, 8). To assess the contribution of acute cases of HCV infection in Massachusetts to national incidence estimates, we retrospectively reviewed 183 diagnoses of acute HCV infection in a local cohort. We aimed to determine the proportion of clinical cases of acute HCV infection classified as confirmed for surveillance purposes and to determine why clinical cases were not counted in national statistics.Context Estimates of the incidence of acute hepatitis C virus (HCV) infection are complicated by the absence of a specific laboratory test and its generally asymptomatic presentation. Contribution Among patients with clinically diagnosed acute HCV infection participating in a research study, virtually none fit the national case definition of acute infection used for reporting to the Centers for Disease Control and Prevention. Limitations to accurate case ascertainment included incomplete reporting, problematic case definitions, requirements for negative laboratory results for hepatitis A and B, and incomplete data capture. Caution Patients were from 2 hospitals in 1 state. Implication Current national estimates of the incidence of acute HCV infection may not be reliable. At least 185 million persons worldwide are infected with hepatitis C virus (HCV), with an estimated 3 to 4 million new infections occurring each year (1, 2). In developed countries, persons who inject drugs are primarily at risk for HCV infection from bloodborne exposure by means of contaminated drug paraphernalia (3). After a sharp decrease in the incidence of HCV infection in the United States in the 1990s, estimates suggest a more moderate but steady decline over the past decade, with rates calculated at 0.3 to 0.7 cases per 100000 persons (4, 5). Accurate and current estimates of the incidence of HCV infection at the local, state, and national levels are critical for quantifying disease burden, guiding public health agency initiatives, and tracking the outcomes of preventive interventions. Unlike acute hepatitis A and B infections, which are diagnosed with IgM antibody testing, there is no single diagnostic test for acute HCV infection. Without a definitive test, surveillance by local public health officials hinges on a complex composite of risk factors; symptom reporting; laboratory assessments, including antibodies to HCV (anti-HCV), nucleic acid testing, and aminotransferase levels; and exclusion of alternative causes of hepatitis. During acute HCV infection, aminotransferase and HCV RNA levels can fluctuate and seroconversion from negative to positive anti-HCV status can occur over time. Most patients are asymptomatic and specific symptoms, such as jaundice, are uncommon in acute infections, which further complicates detection. Patients whose acute infections clear spontaneously may have low or normal aminotransferase levels at presentation and thereby escape detection. Acute HCV infections are reportable in most jurisdictions in the United States, which subsequently report cases to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Disease Surveillance System. In 2010, 850 acute cases of HCV infection were reported to the CDC, which applied a multiplier of 20 to arrive at an estimate of 17000 new HCV infections per year in the United States (4, 6). This calculation assumes that for each reported acute infection there are 20 unreported cases because most patients are asymptomatic and persons who inject drugsthe group with highest incidence of infectionoften do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to the Massachusetts Department of Public Health (MDPH). Heroin use has increased markedly in Massachusetts and has been accompanied by a sharp increase in cases of HCV infection in patients younger than 30 years, with more than 2000 new reports of prevalent cases in this age group in 2012 (7, 8). To assess the contribution of acute cases of HCV infection in Massachusetts to national incidence estimates, we retrospectively reviewed 183 diagnoses of acute HCV infection in a local cohort. We aimed to determine the proportion of clinical cases of acute HCV infection classified as confirmed for surveillance purposes and to determine why clinical cases were not counted in national statistics. Methods Participants BAHSTION (Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network) is a longitudinal study that recruited patients with acute HCV infection (9). Recruitment began in 1998, and patients from 2 hospitals in Boston (Massachusetts General Hospital, a tertiary care hospital that also provides primary care services in several communities, and Lemuel Shattuck Hospital, a facility that serves prisoners and patients referred by public agencies) were enrolled through referrals to specialists in infectious disease and gastroenterology. The cohort also included inmates who entered Massachusetts correctional facilities and were enrolled through referrals from health care providers (10) and through a systematic screening program that asked incoming inmates about specific injection practices. This resulted in a tripling of the rate of identification of acute HCV infection from that previously reported in those facilities (11). For study purposes, a clinical case of acute HCV infection was defined by both of the following criteria and classified as definite, probable, or possible (Figure 1): risk factor for HCV infection within the past year and consistent or supportive clinical or laboratory criteria, including compatible illness (especially jaundice), alanine aminotransferase (ALT) level greater than 7 times the upper limit of normal, seroconversion (defined as a newly positive anti-HCV test result in the context of a previous negative result), and HCV RNA characteristics (low-level viremia or fluctuations), as described in previous reports (11, 12). Figure 1. Definitions of acute HCV in BAHSTION. ALT = alanine aminotransferase; BAHSTION = Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network; HCV = hepatitis C virus; ULN = upper limit of normal. Surveillance Definitions of Past or Present HCV Infection and Acute HCV Infection Since 2003, a confirmed case of past or present HCV infection for CDC surveillance purposes has been defined as having 1 or more of the following criteria: anti-HCV with a signalcutoff ratio predictive of a true positive result, positive results for HCV on a recombinant immunoblot assay, or positive results for HCV RNA on a nucleic acid test (including qualitative, quantitative, or genotype testing) (13). Details of specific requirements are found in the Appendix. Before 2012, the CDC defined a confirmed case of acute HCV infection for surveillance purposes as first meeting the previously mentioned definition of past or present HCV infection, plus meeting clinical criteria, including an acute illness with discrete onset of any sign or symptom consistent with acute viral hepatitis (that is, anorexia, abdominal discomfort, nausea, or vomiting) and either 1) jaundice or dark urine or 2) serum ALT levels greater than 400 IU/L. To meet the case definition, the test results must be negative for both IgM antibodies to hepatitis A virus and hepatitis B core antigen. The BAHSTION clinical case definition differs from the pre-2012 CDC surveillance definition of acute HCV infection by including the following criteria: detailed risk factor history, HCV RNA criteria that help to differentiate acute from chronic infection (low-level viremia or HCV RNA level fluctuations and spontaneous clearance of detectable viremia), use of a different threshold of ALT elevation (that is, 7 times the upper limit of normal [385 U/L vs. 400 U/L]), and inclusion of seroconversion (Appendix Table 1). In 2012, the CDC adopted changes in the case definition of acute HCV infection developed by the Council of State and Territorial Epidemiologists. These changes included seroconversion within 6 months as sufficient for diagnosis and removal of the requirement of documentation of the status of IgM antibodies to hepatitis A virus or hepatitis B core antigen (13). Appendix Table 1. Case Definition Comparison Surveillance in Massachusetts for Acute HCV Infection Hepatitis C virus infection in Massachusetts residents has been reportable to the MDPH since 1992. In 2005, because of the high burden of new reports of HCV infection, the MDPH switched from case investigations done by local health departments to clinician-based reporting, in which the ordering provider completes a short, single-page HCV case report form (CRF) with patient demographic characteristics, clinical history, confirmatory laboratory results, and basic risk factors (Supplement 1). Before 2007, if the submitted form indicated a case potentially meeting the surveillance definition for acute HCV infection (acute illness with jaundice or ALT levels >400 IU/L), follow-up was assigned to the local public health official who interviewed the patient using a more detailed acute HCV CRF (Supplement 2). After recognition of an increase in cases of acute HCV infection identified in young patients in 2007 (7, 8), the MDPH also began sending the longer form directly to clinicians for patients aged 15 to 25 years. Epidemiologists from the MDPH review all completed acute HCV CRFs and reported laboratory results and assign case status based on the current standard surveillance case definitions. Case classification may be modified and updated based on additional information. Those classified according to the national surveillance case definition are submitted to the CDC on a weekly basis. Reporting is the providers responsibility, and enrollment in BAHSTION does not result in reporting to the MDPH. Supplement 1. Case Report Form for Past or Present Hepatitis C Virus Infection Supplement 2. Enhanced Case Report Form for Acute Hepatitis C Virus Infection Much of the data capture and management process of acute HCV infection by the MDPH has been automated through the Massachusetts Virtual Epidemiologic Network (MAVEN), an integrated surveillance and case management system that enables state and local public health professionals to share data efficiently and securely over the Internet (14). MAVEN was instituted in 2006 and houses historical surveillance data dating back to 1988. Automated electronic labora

Underascertainment of Acute HCV Infections Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance System A Case Series and Chart Review

At least 185 million persons worldwide are infected with hepatitis C virus (HCV), with an estimated 3 to 4 million new infections occurring each year (1, 2). In developed countries, persons who inject drugs are primarily at risk for HCV infection from bloodborne exposure by means of contaminated drug paraphernalia (3). After a sharp decrease in the incidence of HCV infection in the United States in the 1990s, estimates suggest a more moderate but steady decline over the past decade, with rates calculated at 0.3 to 0.7 cases per 100 000 persons (4, 5). Accurate and current estimates of the incidence of HCV infection at the local, state, and national levels are critical for quantifying disease burden, guiding public health agency initiatives, and tracking the outcomes of preventive interventions. Unlike acute hepatitis A and hepatitis B infections, which are diagnosed with immunoglobulin M (IgM) antibody testing, there is no single diagnostic test for acute HCV infection. Without a definitive test, surveillance by local public health officials hinges on a complex composite of risk factors; symptom reporting; laboratory assessments, including antibodies to HCV (anti-HCVs), nucleic acid testing, and aminotransferase levels; and exclusion of alternative causes of hepatitis. During acute HCV infection, aminotransferase and HCV RNA levels can fluctuate and seroconversion from negative to positive anti-HCV status can occur over time. Most patients are asymptomatic and specific symptoms, such as jaundice, are uncommon in acute infections, which further complicates detection. Patients whose acute infections clear spontaneously may have low or normal aminotransferase levels at presentation and thereby escape detection. Acute HCV infections are reportable in most jurisdictions in the United States, which subsequently report cases to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Disease Surveillance System. In 2010, 850 acute cases of HCV infection were reported to the CDC, which applied a multiplier of 20 to arrive at an estimate of 17 000 new HCV infections per year in the United States (4, 6). This calculation assumes that for each reported acute infection there are 20 unreported cases because most patients are asymptomatic and persons who inject drugs—the group with highest incidence of infection—often do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to its department of public health. Heroin use has increased markedly in Massachusetts and has been accompanied by a sharp increase in cases of HCV infection in patients younger than 30 years, with more than 2000 new reports of prevalent cases in this age group in 2012 (7, 8). To assess the contribution of acute cases of HCV infection in Massachusetts to national incidence estimates, we retrospectively reviewed 183 diagnoses of acute HCV infection in a local cohort. We aimed to determine the proportion of clinical cases of acute HCV infection classified as confirmed for surveillance purposes and to determine why clinical cases were not counted in national statistics.Context Estimates of the incidence of acute hepatitis C virus (HCV) infection are complicated by the absence of a specific laboratory test and its generally asymptomatic presentation. Contribution Among patients with clinically diagnosed acute HCV infection participating in a research study, virtually none fit the national case definition of acute infection used for reporting to the Centers for Disease Control and Prevention. Limitations to accurate case ascertainment included incomplete reporting, problematic case definitions, requirements for negative laboratory results for hepatitis A and B, and incomplete data capture. Caution Patients were from 2 hospitals in 1 state. Implication Current national estimates of the incidence of acute HCV infection may not be reliable. At least 185 million persons worldwide are infected with hepatitis C virus (HCV), with an estimated 3 to 4 million new infections occurring each year (1, 2). In developed countries, persons who inject drugs are primarily at risk for HCV infection from bloodborne exposure by means of contaminated drug paraphernalia (3). After a sharp decrease in the incidence of HCV infection in the United States in the 1990s, estimates suggest a more moderate but steady decline over the past decade, with rates calculated at 0.3 to 0.7 cases per 100000 persons (4, 5). Accurate and current estimates of the incidence of HCV infection at the local, state, and national levels are critical for quantifying disease burden, guiding public health agency initiatives, and tracking the outcomes of preventive interventions. Unlike acute hepatitis A and B infections, which are diagnosed with IgM antibody testing, there is no single diagnostic test for acute HCV infection. Without a definitive test, surveillance by local public health officials hinges on a complex composite of risk factors; symptom reporting; laboratory assessments, including antibodies to HCV (anti-HCV), nucleic acid testing, and aminotransferase levels; and exclusion of alternative causes of hepatitis. During acute HCV infection, aminotransferase and HCV RNA levels can fluctuate and seroconversion from negative to positive anti-HCV status can occur over time. Most patients are asymptomatic and specific symptoms, such as jaundice, are uncommon in acute infections, which further complicates detection. Patients whose acute infections clear spontaneously may have low or normal aminotransferase levels at presentation and thereby escape detection. Acute HCV infections are reportable in most jurisdictions in the United States, which subsequently report cases to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Disease Surveillance System. In 2010, 850 acute cases of HCV infection were reported to the CDC, which applied a multiplier of 20 to arrive at an estimate of 17000 new HCV infections per year in the United States (4, 6). This calculation assumes that for each reported acute infection there are 20 unreported cases because most patients are asymptomatic and persons who inject drugsthe group with highest incidence of infectionoften do not seek medical care. In Massachusetts, all laboratory evidence of HCV infection is reportable to the Massachusetts Department of Public Health (MDPH). Heroin use has increased markedly in Massachusetts and has been accompanied by a sharp increase in cases of HCV infection in patients younger than 30 years, with more than 2000 new reports of prevalent cases in this age group in 2012 (7, 8). To assess the contribution of acute cases of HCV infection in Massachusetts to national incidence estimates, we retrospectively reviewed 183 diagnoses of acute HCV infection in a local cohort. We aimed to determine the proportion of clinical cases of acute HCV infection classified as confirmed for surveillance purposes and to determine why clinical cases were not counted in national statistics. Methods Participants BAHSTION (Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network) is a longitudinal study that recruited patients with acute HCV infection (9). Recruitment began in 1998, and patients from 2 hospitals in Boston (Massachusetts General Hospital, a tertiary care hospital that also provides primary care services in several communities, and Lemuel Shattuck Hospital, a facility that serves prisoners and patients referred by public agencies) were enrolled through referrals to specialists in infectious disease and gastroenterology. The cohort also included inmates who entered Massachusetts correctional facilities and were enrolled through referrals from health care providers (10) and through a systematic screening program that asked incoming inmates about specific injection practices. This resulted in a tripling of the rate of identification of acute HCV infection from that previously reported in those facilities (11). For study purposes, a clinical case of acute HCV infection was defined by both of the following criteria and classified as definite, probable, or possible (Figure 1): risk factor for HCV infection within the past year and consistent or supportive clinical or laboratory criteria, including compatible illness (especially jaundice), alanine aminotransferase (ALT) level greater than 7 times the upper limit of normal, seroconversion (defined as a newly positive anti-HCV test result in the context of a previous negative result), and HCV RNA characteristics (low-level viremia or fluctuations), as described in previous reports (11, 12). Figure 1. Definitions of acute HCV in BAHSTION. ALT = alanine aminotransferase; BAHSTION = Boston Acute HCV Study: Transmission, Immunity, and Outcomes Network; HCV = hepatitis C virus; ULN = upper limit of normal. Surveillance Definitions of Past or Present HCV Infection and Acute HCV Infection Since 2003, a confirmed case of past or present HCV infection for CDC surveillance purposes has been defined as having 1 or more of the following criteria: anti-HCV with a signalcutoff ratio predictive of a true positive result, positive results for HCV on a recombinant immunoblot assay, or positive results for HCV RNA on a nucleic acid test (including qualitative, quantitative, or genotype testing) (13). Details of specific requirements are found in the Appendix. Before 2012, the CDC defined a confirmed case of acute HCV infection for surveillance purposes as first meeting the previously mentioned definition of past or present HCV infection, plus meeting clinical criteria, including an acute illness with discrete onset of any sign or symptom consistent with acute viral hepatitis (that is, anorexia, abdominal discomfort, nausea, or vomiting) and either 1) jaundice or dark urine or 2) serum ALT levels greater than 400 IU/L. To meet the case definition, the test results must be negative for both IgM antibodies to hepatitis A virus and hepatitis B core antigen. The BAHSTION clinical case definition differs from the pre-2012 CDC surveillance definition of acute HCV infection by including the following criteria: detailed risk factor history, HCV RNA criteria that help to differentiate acute from chronic infection (low-level viremia or HCV RNA level fluctuations and spontaneous clearance of detectable viremia), use of a different threshold of ALT elevation (that is, 7 times the upper limit of normal [385 U/L vs. 400 U/L]), and inclusion of seroconversion (Appendix Table 1). In 2012, the CDC adopted changes in the case definition of acute HCV infection developed by the Council of State and Territorial Epidemiologists. These changes included seroconversion within 6 months as sufficient for diagnosis and removal of the requirement of documentation of the status of IgM antibodies to hepatitis A virus or hepatitis B core antigen (13). Appendix Table 1. Case Definition Comparison Surveillance in Massachusetts for Acute HCV Infection Hepatitis C virus infection in Massachusetts residents has been reportable to the MDPH since 1992. In 2005, because of the high burden of new reports of HCV infection, the MDPH switched from case investigations done by local health departments to clinician-based reporting, in which the ordering provider completes a short, single-page HCV case report form (CRF) with patient demographic characteristics, clinical history, confirmatory laboratory results, and basic risk factors (Supplement 1). Before 2007, if the submitted form indicated a case potentially meeting the surveillance definition for acute HCV infection (acute illness with jaundice or ALT levels >400 IU/L), follow-up was assigned to the local public health official who interviewed the patient using a more detailed acute HCV CRF (Supplement 2). After recognition of an increase in cases of acute HCV infection identified in young patients in 2007 (7, 8), the MDPH also began sending the longer form directly to clinicians for patients aged 15 to 25 years. Epidemiologists from the MDPH review all completed acute HCV CRFs and reported laboratory results and assign case status based on the current standard surveillance case definitions. Case classification may be modified and updated based on additional information. Those classified according to the national surveillance case definition are submitted to the CDC on a weekly basis. Reporting is the providers responsibility, and enrollment in BAHSTION does not result in reporting to the MDPH. Supplement 1. Case Report Form for Past or Present Hepatitis C Virus Infection Supplement 2. Enhanced Case Report Form for Acute Hepatitis C Virus Infection Much of the data capture and management process of acute HCV infection by the MDPH has been automated through the Massachusetts Virtual Epidemiologic Network (MAVEN), an integrated surveillance and case management system that enables state and local public health professionals to share data efficiently and securely over the Internet (14). MAVEN was instituted in 2006 and houses historical surveillance data dating back to 1988. Automated electronic labora

Follow-up testing for hepatitis C virus infection: an analysis of Massachusetts surveillance data, 2007-2010.

The Massachusetts Department of Public Health (MDPH) identified cases of hepatitis C virus (HCV) infection reported from 2007 through 2010 to assess evidence of appropriate follow-up testing for the diagnosis of active HCV infection. Surveillance data were used to assess the number of people with reported HCV who had an antibody test and nucleic acid test (NAT) for HCV, to determine the time between tests, and to identify demographic characteristics. Out of the 34,005 cases of HCV reported with laboratory results during the study period, 45% (n=15,279) had only an antibody test reported and 55% (n=18,726) had a NAT reported, with differences by age, gender, and region of residence. Nearly half of those with reported cases of HCV infection in Massachusetts did not have a NAT reported to MDPH, indicating that these individuals may not have received appropriate diagnostic testing. Analysis of demographics suggests differences by age, gender, and region.