Noelle Cocoros

H1N1 2009 influenza virus infection during pregnancy in the USA

BACKGROUND Pandemic H1N1 2009 influenza virus has been identified as the cause of a widespread outbreak of febrile respiratory infection in the USA and worldwide. We summarised cases of infection with pandemic H1N1 virus in pregnant women identified in the USA during the first month of the present outbreak, and deaths associated with this virus during the first 2 months of the outbreak. METHODS After initial reports of infection in pregnant women, the US Centers for Disease Control and Prevention (CDC) began systematically collecting additional information about cases and deaths in pregnant women in the USA with pandemic H1N1 virus infection as part of enhanced surveillance. A confirmed case was defined as an acute respiratory illness with laboratory-confirmed pandemic H1N1 virus infection by real-time reverse-transcriptase PCR or viral culture; a probable case was defined as a person with an acute febrile respiratory illness who was positive for influenza A, but negative for H1 and H3. We used population estimates derived from the 2007 census data to calculate rates of admission to hospital and illness. FINDINGS From April 15 to May 18, 2009, 34 confirmed or probable cases of pandemic H1N1 in pregnant women were reported to CDC from 13 states. 11 (32%) women were admitted to hospital. The estimated rate of admission for pandemic H1N1 influenza virus infection in pregnant women during the first month of the outbreak was higher than it was in the general population (0.32 per 100 000 pregnant women, 95% CI 0.13-0.52 vs 0.076 per 100 000 population at risk, 95% CI 0.07-0.09). Between April 15 and June 16, 2009, six deaths in pregnant women were reported to the CDC; all were in women who had developed pneumonia and subsequent acute respiratory distress syndrome requiring mechanical ventilation. INTERPRETATION Pregnant women might be at increased risk for complications from pandemic H1N1 virus infection. These data lend support to the present recommendation to promptly treat pregnant women with H1N1 influenza virus infection with anti-influenza drugs. FUNDING US CDC.

Epidemiology of 2009 Pandemic Influenza A (H1N1) Deaths in the United States, April–July 2009

During the spring of 2009, pandemic influenza A (H1N1) virus (pH1N1) was recognized and rapidly spread worldwide. To describe the geographic distribution and patient characteristics of pH1N1-associated deaths in the United States, the Centers for Disease Control and Prevention requested information from health departments on all laboratory-confirmed pH1N1 deaths reported from 17 April through 23 July 2009. Data were collected using medical charts, medical examiner reports, and death certificates. A total of 377 pH1N1-associated deaths were identified, for a mortality rate of .12 deaths per 100,000 population. Activity was geographically localized, with the highest mortality rates in Hawaii, New York, and Utah. Seventy-six percent of deaths occurred in persons aged 18-65 years, and 9% occurred in persons aged ≥ 65 years. Underlying medical conditions were reported for 78% of deaths: chronic lung disease among adults (39%) and neurologic disease among children (54%). Overall mortality associated with pH1N1 was low; however, the majority of deaths occurred in persons aged <65 years with underlying medical conditions.

Sources of Infant Pertussis Infection in the United States

BACKGROUND: Pertussis is poorly controlled, with the highest rates of morbidity and mortality among infants. Although the source of infant pertussis is often unknown, when identified, mothers have historically been the most common reservoir of transmission. Despite high vaccination coverage, disease incidence has been increasing. We examined whether infant source of infection (SOI) has changed in the United States in light of the changing epidemiology. METHODS: Cases <1 year old were identified at Enhanced Pertussis Surveillance sites between January 1, 2006 to December 31, 2013. SOI was collected during patient interview and was defined as a suspected pertussis case in contact with the infant case 7 to 20 days before infant cough onset. RESULTS: A total of 1306 infant cases were identified; 24.2% were <2 months old. An SOI was identified for 569 cases. Infants 0 to 1 months old were more likely to have an SOI identified than 2- to 11-month-olds (54.1% vs 40.2%, respectively; P < .0001). More than 66% of SOIs were immediate family members, most commonly siblings (35.5%), mothers (20.6%), and fathers (10.0%); mothers predominated until the transition to siblings beginning in 2008. Overall, the SOI median age was 14 years (range: 0–74 years); median age for sibling SOIs was 8 years. CONCLUSIONS: In contrast to previous studies, our data suggest that the most common source of transmission to infants is now siblings. While continued monitoring of SOIs will optimize pertussis prevention strategies, recommendations for vaccination during pregnancy should directly increase protection of infants, regardless of SOI.

Enzyme-Linked Immunospot Assay Detection of Mumps-Specific Antibody-Secreting B Cells as an Alternative Method of Laboratory Diagnosis

ABSTRACT Although high measles, mumps, and rubella (MMR) vaccination coverage has been successful in dramatically reducing mumps disease in the United States, mumps (re)infections occasionally occur in individuals who have been either previously vaccinated or naturally infected. Standard diagnostics that detect virus or virus-specific antibody are dependable for confirming primary mumps infection in immunologically naïve persons, but these methods perform inconsistently for individuals with prior immune exposure. We hypothesized that detection of activated mumps-specific antibody-secreting B cells (ASCs) by enzyme-linked immunospot (ELISPOT) assay could be used as a more reliable diagnostic. To test this, a time course of virus-specific ASC responses was measured by ELISPOT assay following MMR vaccination of 16 previously vaccinated or naturally exposed adult volunteers. Mumps-specific ASCs were detectable in 68% of these individuals at some point during the first 3 weeks following revaccination. In addition, mumps-specific ASCs were detected in 7/7 previously vaccinated individuals who recently had been infected as part of a confirmed mumps outbreak. These data suggest that ELISPOT detection of mumps-specific ASCs has the potential for use as an alternative method of diagnosis when suspect cases cannot be confirmed by detection of IgM or virus. In addition, it was determined that mumps-specific memory B cells are detected at a much lower frequency than measles- or rubella-specific cells, suggesting that mumps infection may not generate robust B-cell memory.

Obesity as a risk factor for severe influenza-like illness

Obesity was recognized as in independent risk factor for influenza during the 2009 H1N1 influenza pandemic.

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

Ventilator-Associated Events in Neonates and Children--A New Paradigm.

Objectives:To identify a pediatric ventilator-associated condition definition for use in neonates and children by exploring whether potential ventilator-associated condition definitions identify patients with worse outcomes. Design:Retrospective cohort study and a matched cohort analysis. Setting:Pediatric, cardiac, and neonatal ICUs in five U.S. hospitals. Patients:Children 18 years old or younger ventilated for at least 1 day. Interventions:None. Measurements and Main Results:We evaluated the evidence of worsening oxygenation via a range of thresholds for increases in daily minimum fraction of inspired oxygen (by 0.20, 0.25, and 0.30) and daily minimum mean airway pressure (by 4, 5, 6, and 7 cm H2O). We required worsening oxygenation be sustained for at least 2 days after at least 2 days of stability. We matched patients with a ventilator-associated condition to those without and used Cox proportional hazard models with frailties to examine associations with hospital mortality, hospital and ICU length of stay, and duration of ventilation. The cohort included 8,862 children with 10,209 hospitalizations and 77,751 ventilator days. For the fraction of inspired oxygen 0.25/mean airway pressure 4 definition (i.e., increase in minimum daily fraction of inspired oxygen by 0.25 or mean airway pressure by 4), rates ranged from 2.9 to 3.2 per 1,000 ventilator days depending on ICU type; the fraction of inspired oxygen 0.30/mean airway pressure 7 definition yielded ventilator-associated condition rates of 1.1–1.3 per 1,000 ventilator days. All definitions were significantly associated with greater risk of hospital death, with hazard ratios ranging from 1.6 (95% CI, 0.7–3.4) to 6.8 (2.9–16.0), depending on thresholds and ICU type. Each definition was associated with prolonged hospitalization, time in ICU, and duration of ventilation, among survivors. The advisory board of the study proposed using the fraction of inspired oxygen 0.25/mean airway pressure 4 thresholds to identify pediatric ventilator-associated conditions in ICUs. Conclusions:Pediatric patients with ventilator-associated conditions are at substantially higher risk for mortality and morbidity across ICUs, regardless of thresholds used. Next steps include identification of risk factors, etiologies, and preventative measures for pediatric ventilator-associated conditions.

Screening for Hepatitis C as a Prevention Enhancement (SHAPE) for HIV: An Integration Pilot Initiative in a Massachusetts County Correctional Facility

Objectives. The Massachusetts Department of Public Health (MDPH) and the Barnstable County Sheriffs Department (BCSD) in Massachusetts initiated a pilot program in July 2009 offering education and hepatitis C virus (HCV) antibody testing to inmates and detainees, concurrent with routine HIV testing. The initiative was implemented to assess the feasibility of integrating HCV screening into an HIV screening program in a correctional setting and the efficacy of linking HCV antibody-positive inmates to clinical care upon release. Methods. Through the Screening for Hepatitis C as a Prevention Enhancement initiative, HCV and HIV testing were offered to inmates and detainees shortly after admission, and by request at any time during incarceration. In preparation for release, referrals were made to community-based medical providers for HCV follow-up care. Data from BCSD were compared with routine surveillance data received by MDPH. Confirmatory HCV test results received by April 15, 2012, were considered indicators of appropriate post-release clinical care. Results. From July 2009 through December 2011, 22% (n=596) and 25% (n=667) of 2,716 inmates/detainees accepted HCV and HIV testing, respectively. Of those tested for HCV antibody, 20.5% (n=122) were positive. Of those tested for HIV antibody, 0.8% (n=5) were positive. Of the inmates who tested HCV positive at BCSD and had been released, 37.8% were identified as receiving post-release medical care. Conclusions. We determined that integration of HCV education and screening into correctional facilities is feasible and reveals high rates of HCV infection. Although this model presupposes programmatic infrastructure, elements of the service design and integration could inform a range of correctional programs. Effective linkage to care, while substantial, was not routine based on our analysis, and may require additional resources given its cost and complexity.

Infectious Disease Surveillance in the 21st Century: An Integrated Web-Based Surveillance and Case Management System

The Massachusetts Virtual Epidemiologic Network (MAVEN) was deployed in 2006 by the Massachusetts Department of Public Health, Bureau of Infectious Disease to serve as an integrated, Web-based disease surveillance and case management system. MAVEN replaced program-specific, siloed databases, which were inaccessible to local public health and unable to integrate electronic reporting. Disease events are automatically created without human intervention when a case or laboratory report is received and triaged in real time to state and local public health personnel. Events move through workflows for initial notification, case investigation, and case management. Initial development was completed within 12 months and recent state regulations mandate the use of MAVEN by all 351 jurisdictions. More than 300 local boards of health are using MAVEN, there are approximately one million events, and 70 laboratories report electronically. MAVEN has demonstrated responsiveness and flexibility to emerging diseases while also streamlining routine surveillance processes and improving timeliness of notifications and data completeness, although the long-term resource requirements are significant.

Automated influenza-like illness reporting--an efficient adjunct to traditional sentinel surveillance.

Objectives. We compared an electronic health record-based influenza-like illness (ILI) surveillance system with manual sentinel surveillance and virologic data to evaluate the utility of the automated system for routine ILI surveillance. Methods. We obtained weekly aggregate ILI reports from the Electronic medical record Support for Public Health (ESP) disease-detection and reporting system, which used an automated algorithm to identify ILI visits among a patient population of about 700,000 in Eastern Massachusetts. The percentage of total visits for ILI (“percent ILI”) in ESP, percent ILI in the Massachusetts Department of Public Healths sentinel surveillance system, and percentage of laboratory specimens submitted to participating Massachusetts laboratories that tested positive for influenza were compared for the period October 2007–September 2011. We calculated Spearmans correlation coefficients and compared ESP and sentinel surveillance systems qualitatively, in terms of simplicity, flexibility, data quality, acceptability, timeliness, and usefulness. Results. ESP and sentinel surveillance percent ILI always peaked within one week of each other. There was 80% correlation between the two and 71%–73% correlation with laboratory data. Sentinel surveillance percent ILI was higher than ESP percent ILI during influenza seasons. The amplitude of variation in ESP percent ILI was greatest for 5- to 49-year-olds and typically peaked for the 5- to 24-year-old age group before the others. Conclusions. The ESP system produces percent ILI data of similar quality to sentinel surveillance and offers the advantages of shifting disease reporting burden from clinicians to information systems, allowing tracking of disease by age group, facilitating efficient surveillance for very large populations, and producing consistent and timely reports.