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Background In contrast with respiratory disease caused by influenza, information on the risk of respiratory syncytial virus (RSV) disease among adults with chronic medical conditions (CMCs) is limited. Methods We linked population-based surveillance of acute respiratory illness hospitalizations to national administrative data to estimate seasonal RSV hospitalization rates among adults aged 18–80 years with the following preexisting CMCs: chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), diabetes mellitus (DM), and end-stage renal disease (ESRD). Age- and ethnicity-adjusted rates stratified by age group were estimated. Results Among 883 999 adult residents aged 18–80 years, 281 RSV-positive hospitalizations were detected during 2012–2015 winter seasons. Across all ages, RSV hospitalization rates were significantly higher among adults with COPD, asthma, CHF, and CAD compared with those without each corresponding condition. RSV hospitalization rates were significantly higher among adults with ESRD aged 50–64 years and adults with DM aged 18–49 years and 65–80 years compared with adults in each age group without these conditions. No increased risk was seen for adults with CVA. The CMC with the highest risk of RSV hospitalization was CHF (incidence rate ratio [IRR] range, 4.6–36.5 across age strata) and COPD (IRR range, 9.6–9.7). Among RSV-positive adults, CHF and COPD were independently associated with increased length of hospital stay. Conclusions Adults with specific CMCs are at increased risk of RSV hospitalizations. Age affects this relationship for some CMCs. Such populations maybe relevant for future RSV prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of illness in adults; however, data on RSV disease and economic burden in this age group remain limited. We aimed to provide comprehensive estimates of RSV disease burden among adults aged ≥18 years. Methods: During 2012–2015, population-based, active surveillance of acute respiratory infection (ARI) hospitalizations enabled estimation of the seasonal incidence of RSV hospitalizations and direct health costs in adults aged ≥18 years in Auckland, New Zealand. Results: Of 4,600 ARI hospitalizations tested for RSV, 348 (7.6%) were RSV positive. The median (interquartile range) length of hospital stay for RSV positive patients was 4 (2–6) days. The seasonal incidence rate (IR) of RSV hospitalizations, corrected for non-testing, was 23.6 (95% confidence intervals [CI] 21.0–26.1) per 100,000 adults aged ≥18 years. Hospitalization risk increased with age with the highest incidence among adults aged ≥80 years (IR 190.8 per 100,000, 95% CI 137.6–244.0). Being of Māori or Pacific ethnicity or living in a neighborhood with low socioeconomic status (SES) were independently associated with increased RSV hospitalization rates. We estimate RSV-associated hospitalizations among adults aged ≥18 years to cost on average NZD $4,758 per event. Conclusions: RSV infection is associated with considerable disease and economic cost in adults. RSV disproportionally affects adult sub-groups defined by age, ethnicity, and neighborhood SES. An effective RSV vaccine or RSV treatment may offer benefits for older adults. [ABSTRACT FROM AUTHOR]

Background: Severe influenza illness is presumed more common in adults with chronic medical conditions (CMCs), but evidence is sparse and often combined into broad CMC categories.Methods: Residents (aged 18-80 years) of Central and South Auckland hospitalized for World Health Organization-defined severe acute respiratory illness (SARI) (2012-2015) underwent influenza virus polymerase chain reaction testing. The CMC statuses for Auckland residents were modeled using hospitalization International Classification of Diseases, Tenth Revision codes, pharmaceutical claims, and laboratory results. Population-level influenza rates in adults with congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus (DM), and end-stage renal disease (ESRD) were calculated by Poisson regression stratified by age and adjusted for ethnicity.Results: Among 891 276 adults, 2435 influenza-associated SARI hospitalizations occurred. Rates were significantly higher in those with CMCs compared with those without the respective CMC, except for older adults with DM or those aged <65 years with CVA. The largest effects occurred with CHF (incidence rate ratio [IRR] range, 4.84-13.4 across age strata), ESRD (IRR range, 3.30-9.02), CAD (IRR range, 2.77-10.7), and COPD (IRR range, 5.89-8.78) and tapered with age.Conclusions: Our findings support the increased risk of severe, laboratory-confirmed influenza disease among adults with specific CMCs compared with those without these conditions. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are prioritized for seasonal influenza vaccination, but the evidence on the risk of influenza during pregnancy that is used to inform these policies is limited.Methods: Individual-level administrative data sets and active surveillance data were joined to estimate influenza-associated hospitalization and outpatient visit rates by pregnancy, postpartum, and trimester status.Results: During 2012-2015, 46 of 260 (17.7%) influenza-confirmed hospitalizations for acute respiratory infection and 13 of 294 (4.4%) influenza-confirmed outpatient visits were among pregnant and postpartum women. Pregnant and postpartum women experienced higher rates of influenza-associated hospitalization than nonpregnant women overall (rate ratio [RR], 3.4; 95% confidence interval [CI], 2.5-4.7) and by trimester (first, 2.5 [95% CI, 1.2-5.4]; second, 3.9 [95% CI, 2.4-6.3]; and third, 4.8 [95% CI, 3.0-7.7]); the RR for the postpartum period was 0.7 (95% CI, 3.0-7.7). Influenza A viruses were associated with an increased risk (RR for 2009 pandemic influenza A[H1N1] virus, 5.3 [95% CI, 3.2-8.7]; RR for influenza A(H3N2) virus, 3.0 [95% CI, 1.8-5.0]), but influenza B virus was not (RR, 1.8; 95% CI, .7-4.6). Influenza-associated hospitalization rates in pregnancy were significantly higher for Māori women (RR, 3.2; 95% CI, 1.3-8.4), compared with women of European or other ethnicity. Similar risks for influenza-confirmed outpatient visits were not observed.Conclusion: Seasonal influenza poses higher risks of hospitalization among pregnant women in all trimesters, compared with nonpregnant women. Hospitalization rates vary by influenza virus type and ethnicity among pregnant women. [ABSTRACT FROM AUTHOR]

Background: Understanding the attack rate of influenza infection and the proportion who become ill by risk group is key to implementing prevention measures. While population-based studies of antihemagglutinin antibody responses have been described previously, studies examining both antihemagglutinin and antineuraminidase antibodies are lacking.Methods: In 2015, we conducted a seroepidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) titers for seroconversion. We followed participants weekly and performed influenza polymerase chain reaction (PCR) for those reporting influenza-like illness (ILI).Results: Influenza infection (either HAI or NAI seroconversion) was found in 321 (35% [95% confidence interval, 32%-38%]) of 911 unvaccinated participants, of whom 100 (31%) seroconverted to NAI alone. Young children and Pacific peoples experienced the highest influenza infection attack rates, but overall only a quarter of all infected reported influenza PCR-confirmed ILI, and one-quarter of these sought medical attention. Seroconversion to NAI alone was higher among children aged <5 years vs those aged ≥5 years (14% vs 4%; P < .001) and among those with influenza B vs A(H3N2) virus infections (7% vs 0.3%; P < .001).Conclusions: Measurement of antineuraminidase antibodies in addition to antihemagglutinin antibodies may be important in capturing the true influenza infection rates. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to describe the capture-recapture method used by the Philadelphia Department of Public Health to enhance surveillance of perinatal hepatitis B virus (HBV), report on results and limitations of the process, and determine why some HBV-positive mother-infant pairs were not initially identified by Philadelphia's Perinatal Hepatitis B Prevention Program (PHBPP). Methods: We performed capture-recapture retrospectively for births in 2008 and 2009 in Philadelphia and prospectively for births from 2010 to 2014 by independently matching annual birth certificate data to PHBPP and HBV surveillance data. We compared the number of HBV-positive mother-infant pairs identified each year to the point estimates and lower-limit estimates calculated by the Centers for Disease Control and Prevention for the Philadelphia PHBPP. Results: Of 156 605 pregnancy outcomes identified between 2008 and 2014, we found 1549 HBV-positive mother-infant pairs. Of 705 pairs that were initially determined, 358 (50.7%) were confirmed to be previously unidentified HBV-positive pairs. Reasons for failing to identify these mother-infant pairs prior to capture-recapture included internal administrative issues (n = 191, 53.4%), HBV testing and reporting issues (n = 92, 25.7%), and being lost to follow-up (n = 75, 20.9%). Each year that capture-recapture was used, the number of pairs identified by the Philadelphia PHBPP exceeded the Centers for Disease Control and Prevention's lower-limit estimates for HBV-positive mother-infant pairs. Conclusions: Capture-recapture was useful for identifying HBV-positive pregnant women for Philadelphia's PHBPP and for highlighting inadequacies in health department protocols and HBV testing during pregnancy. Other health departments with access to similar data sources and staff members with the necessary technical skills can adapt this method. [ABSTRACT FROM AUTHOR]

Diagnosis of pertussis remains a challenge, and consequently research on the risk of disease might be biased because of misclassification. We quantified this misclassification and corrected for it in a case-control study of children in Philadelphia, Pennsylvania, who were 3 months to 6 years of age and diagnosed with pertussis between 2011 and 2013. Vaccine effectiveness (VE; calculated as (1 - odds ratio) x 100) was used to describe the average reduction in reported pertussis incidence resulting from persons being up to date on pertussis-antigen containing vaccines. Bayesian techniques were used to correct for purported nondifferential misclassification by reclassifying the cases per the 2014 Council of State and Territorial Epidemiologists pertussis case definition. Naïve VE was 50% (95% confidence interval: 16%, 69%). After correcting for misclassification, VE ranged from 57% (95% credible interval: 30, 73) to 82% (95% credible interval: 43, 95), depending on the amount of underreporting of pertussis that was assumed to have occurred in the study period. Meaningful misclassification was observed in terms of false negatives detected after the incorporation of infant apnea to the 2014 case definition. Although specificity was nearly perfect, sensitivity of the case definition varied from 90% to 20%, depending on the assumption about missed cases. Knowing the degree of the underreporting is essential to the accurate evaluation of VE. [ABSTRACT FROM AUTHOR]

Background. Vertical transmission of hepatitis C virus (HCV) is the most common route of pediatric HCV infection. Approximately 5% of children born to HCV-infected mothers develop chronic infection. Recommendations employ risk-based HCV testing of pregnant women, and screening children at a young age. This study assesses testing rates of children born to mothers tested HCVpositive in a major US city with a high burden of HCV infection. Methods. HCV surveillance data reported to the Philadelphia Department of Public Health are housed in the Hepatitis Registry. Additional tests, including negative results, were retrospectively collected. HCV data were matched with 2011-2013 birth certificates of children aged ≥20 months to identify mothers tested HCV-positive and screened children. The observed perinatal HCV seropositivity rate was compared to the expected rate (5%). Results. A total of 8119 females aged 12-54 years tested HCV-positive and in the Hepatitis Registry. Of these, 500 (5%) had delivered ≥1 child, accounting for 537 (1%) of the 55 623 children born in Philadelphia during the study period. Eighty-four (16%) of these children had HCV testing; 4 (1% of the total) were confirmed cases. Twenty-three additional children are expected to have chronic HCV infection, but were not identified by 20 months of age. Conclusions. These findings illustrate that a significant number of women giving birth in Philadelphia test positive for HCV and that most of their at-risk children remain untested. To successfully identify all HCV-infected children and integrate them into HCVspecific care, practices for HCV screening of pregnant women and their children should be improved. [ABSTRACT FROM AUTHOR]

Objectives. We assessed provider knowledge, attitudes, and practices for the management of breakthrough varicella and identified barriers to implementation of laboratory testing and reporting. Methods. We surveyed 145 health-care providers (HCPs) from 30 pediatric practices in Philadelphia who did not have a history of laboratory testing for breakthrough varicella. The self-administered survey instrument collected information on clinicians' practices for management of children presenting with rash, infection-control strategies, reporting to public health agencies, and laboratory testing. Results. Among the 144 HCPs who completed the survey, 73 (51%) had practiced for more than 10 years. While 115 HCPs (80%) would elect to evaluate a child with rash in the office, only 19 (13%) would submit diagnostics. When patients had a known recent exposure to varicella, 84 HCPs (58%) would use laboratory tests: 40% would use direct fluorescent antibody staining on a specimen from a cutaneous lesion, 24% would use polymerase chain reaction on a lesion specimen, 21% would use acute and convalescent serology, and 10% would use other tests. While waiting for test results, 82 HCPs (57%) would advise that the child be kept at home, 39 (27%) would notify the local health department, and 33 (23%) would inform the school nurse. Conclusion. As varicella becomes increasingly uncommon, laboratory confirmation becomes more critical for appropriate diagnosis, similar to poliomyelitis and measles. Our findings suggest that HCPs need further education regarding laboratory confirmation, containment, and reporting of breakthrough varicella. [ABSTRACT FROM AUTHOR]

Objectives. We assessed provider knowledge, attitudes, and practices for the management of breakthrough varicella and identified barriers to implementation of laboratory testing and reporting. Methods. We surveyed 145 health-care providers (HCPs) from 30 pediatric practices in Philadelphia who did not have a history of laboratory testing for breakthrough varicella. The self-administered survey instrument collected information on clinicians' practices for management of children presenting with rash, infection-control strategies, reporting to public health agencies, and laboratory testing. Results. Among the 144 HCPs who completed the survey, 73 (51%) had practiced for more than 10 years. While 115 HCPs (80%) would elect to evaluate a child with rash in the office, only 19 (13%) would submit diagnostics. When patients had a known recent exposure to varicella, 84 HCPs (58%) would use laboratory tests: 40% would use direct fluorescent antibody staining on a specimen from a cutaneous lesion, 24% would use polymerase chain reaction on a lesion specimen, 21% would use acute and convalescent serology, and 10% would use other tests. While waiting for test results, 82 HCPs (57%) would advise that the child be kept at home, 39 (27%) would notify the local health department, and 33 (23%) would inform the school nurse. Conclusion. As varicella becomes increasingly uncommon, laboratory confirmation becomes more critical for appropriate diagnosis, similar to poliomyelitis and measles. Our findings suggest that HCPs need further education regarding laboratory confirmation, containment, and reporting of breakthrough varicella. [ABSTRACT FROM AUTHOR]

Rotavirus (RV) infections progressively confer natural immunity against subsequent infection. Similarly to natural infection, vaccination with a live attenuated vaccine potentially reduces RV transmission and induces herd protection. A mathematical transmission model was developed to project the impact of a vaccination programme on the incidence of RV infection and disease for five countries in the European Union. With vaccination coverage rates of 70%, 90% and 95% the model predicted that, in addition to the direct effect of vaccination, herd protection induced a reduction in RV-related gastroenteritis (GE) incidence of 25%, 22% and 20%, respectively, for RV-GE of any severity, and of 19%, 15%, and 13%, respectively, for moderate-to-severe RV-GE, 5 years after implementation of a vaccination programme. [ABSTRACT FROM AUTHOR]

Background. Listeriosis, a life-threatening foodborne illness caused by Listeria monocytogenes, affects ∼2500 Americans annually. Between July and October 2002, an uncommon strain of L. monocytogenes caused an outbreak of listeriosis in 9 states. Methods. We conducted case finding, a case-control study, and traceback and microbiological investigations to determine the extent and source of the outbreak and to propose control measures. Case patients were infected with the outbreak strain of L. monocytogenes between July and November 2002 in 9 states, and control patients were infected with different L. monocytogenes strains. Outcome measures included food exposure associated with outbreak strain infection and source of the implicated food. Results. Fifty-four case patients were identified; 8 died, and 3 pregnant women had fetal deaths. The casecontrol study included 38 case patients and 53 control patients. Case patients consumed turkey deli meat much more frequently than did control patients (P=.008, by Wilcoxon rank-sum test). In the 4 weeks before illness, 55% of case patients had eaten deli turkey breast more than 1-2 times, compared with 28% of control patients (odds ratio, 4.5; 95% confidence interval, 1.3-17.1). Investigation of turkey deli meat eaten by case patients led to several turkey processing plants. The outbreak strain was found in the environment of 1 processing plant and in turkey products from a second. Together, the processing plants recalled >30 million pounds of products. Following the outbreak, the US Department of Agriculture's Food Safety and Inspection Service issued new regulations outlining a L. monocytogenes control and testing program for ready-to-eat meat and poultry processing plants. Conclusions. Turkey deli meat was the source of a large multistate outbreak of listeriosis. Investigation of this outbreak helped guide policy changes designed to prevent future L. monocytogenes contamination of ready-to-eat meat and poultry products. [ABSTRACT FROM AUTHOR]

We report a case of ocular vaccinia infection in an unvaccinated laboratory worker. The patient was infected by a unique strain used in an experiment performed partly outside a biosafety cabinet. Vaccination should continue to be recommended, but laboratories with unvaccinated workers should also implement more stringent biosafety practices. [ABSTRACT FROM AUTHOR]

In early April 2003, severe acute respiratory syndrome (SARS) was diagnosed in a Pennsylvania resident after his exposure to persons with SARS in Toronto, Canada. To identify contacts of the case-patient and evaluate the risk for SARS transmission, a detailed epidemiologic investigation was performed. On the basis of this investigation, 26 persons (17 healthcare workers, 4 household contacts, and 5 others) were identified as having had close contact with this case-patient before infection-control practices were implemented. Laboratory evaluation of clinical specimens showed no evidence of transmission of SARS-associated coronavirus (SARS-CoV) infection to any close contact of this patient. This investigation documents that, under certain circumstances, SARS-CoV is not readily transmitted to close contacts, despite ample unprotected exposures. Improving the understanding of risk factors for transmission will help focus public health control measures. [ABSTRACT FROM AUTHOR]

Many structural, signaling, and adhesion molecules contain tandemly repeated amino acid motifs. The α-actinin/ spectrin/dystrophin superfamily of F-actin-crosslinking proteins contains an array of triple α-helical motifs (spectrin repeats). We present here the complete sequence of the novel β-spectrin isoform βHeavy-spectrin (βH). The sequence of βH supports the origin of (α- and β-spectrins from a common ancestor, and we present a novel model for the origin of the spectrins from a homodimeric actin-crosslinking precursor. The pattern of similarity between the spectrin repeat units indicates that they have evolved by a series of nested, nonuniform duplications. Furthermore, the spectrins and dystrophins clearly have common ancestry, yet the repeat unit is of a different length in each family. Together, these observations suggest a dynamic period of increase in repeat number accompanied by homogenization within each array by concerted evolution. However, today, there is greater similarity of homologous repeats between species than there is across repeats within species, suggesting that concerted evolution ceased some time before the arthropod/vertebrate split. We propose a two-phase model for the evolution of the spectrin repeat arrays in which an initial phase of concerted evolution is subsequently retarded as each new protein becomes constrained to a specific length and the repeats diverge at the DNA level. This evolutionary model has general applicability to the origins of the many other proteins that have tandemly repeated motifs. [ABSTRACT FROM AUTHOR]

We aimed to provide comprehensive estimates of laboratory-confirmed respiratory syncytial virus (RSV)-associated hospitalisations. Between 2012 and 2015, active surveillance of acute respiratory infection (ARI) hospitalisations during winter seasons was used to estimate the seasonal incidence of laboratory-confirmed RSV hospitalisations in children aged <5 years in Auckland, New Zealand (NZ). Incidence rates were estimated by fine age group, ethnicity and socio-economic status (SES) strata. Additionally, RSV disease estimates determined through active surveillance were compared to rates estimated from hospital discharge codes. There were 5309 ARI hospitalisations among children during the study period, of which 3923 (73.9%) were tested for RSV and 1597 (40.7%) were RSV-positive. The seasonal incidence of RSV-associated ARI hospitalisations, once corrected for non-testing, was 6.1 (95% confidence intervals 5.8-6.4) per 1000 children <5 years old. The highest incidence was among children aged <3 months. Being of indigenous Māori or Pacific ethnicity or living in a neighbourhood with low SES independently increased the risk of an RSV-associated hospitalisation. RSV hospital discharge codes had a sensitivity of 71% for identifying laboratory-confirmed RSV cases. RSV infection is a leading cause of hospitalisation among children in NZ, with significant disparities by ethnicity and SES. Our findings highlight the need for effective RSV vaccines and therapies. [ABSTRACT FROM AUTHOR]