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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 [...]

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 [...]

Background: The WHO is exploring the value of adding RSV testing to existing influenza surveillance systems to inform RSV control programs. We evaluate the usefulness of four commonly used influenza surveillance case-definitions for influenza and RSV surveillance.Methods: SHIVERS, a multi-institutional collaboration, conducted surveillance for influenza and RSV in four New Zealand hospitals. Nurses reviewed admission logs, enrolled patients with suspected acute respiratory infections (ARI), and obtained nasopharyngeal swabs for RT-PCR. We compared the performance characteristics for identifying laboratory-confirmed influenza and RSV severe acute respiratory infection (SARI), defined as persons admitted with measured or reported fever and cough within 10 days of illness, to three other case definitions: 1. reported fever and cough or shortness of breath, 2. cough and shortness of breath, or 3. cough.Results: During April-September 2012-2016, SHIVERS identified 16,055 admissions with ARI; of 6374 cases consented and tested for influenza or RSV, 5437 (85%) had SARI and 937 (15%) did not. SARI had the highest specificity in detecting influenza (40.6%) and RSV (40.8%) but the lowest sensitivity (influenza 78.8%, RSV 60.3%) among patients of all ages. Cough or shortness of breath had the highest sensitivity (influenza 99.3%, RSV 99.9%) but the lowest specificity (influenza 1.6%, RSV 1.9%). SARI sensitivity among children aged <3 months was 60.8% for influenza and 43.6% for RSV-both lower than in other age groups.Conclusions: While SARI had the highest specificity, its sensitivity was limited, especially among children aged <3 months. Cough or shortness of breath was the most sensitive. [ABSTRACT FROM AUTHOR]

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]

PURPOSE: To investigate potential risk factors for desquamative inflammatory vaginitis (DIV), a rare but severe form of vaginitis. We are aware of no other controlled studies of DIV.METHODS: We conducted a case control study comparing DIV cases (n = 47), identified from the Wayne State University Vaginitis Clinic, to friend controls. For some variables, cases were also compared to 1432 women participating in a random digit dialing survey.RESULTS: Most cases reported that their last episode of DIV caused at least some pain (76.9%) and worry (73.1%). Cases were more likely than either friend or population controls to report (ORs from population controls) a history of vulvovaginal candidiasis (OR = 4.40, 95% CI 2.24, 8.65), bacterial vaginosis (OR = 25.58, 95% CI 15.91, 41.15), or pelvic inflammatory disease (OR = 16.90, 95% CI 8.26, 34.55); use of oral contraceptives (OR = 4.91, 95% CI 2.11, 11.43); use of hormone replacement therapy (OR = 4.74, 95% CI 2.69, 8.37); and laparoscopic procedures (OR = 22.24, 95% CI 11.46, 42.69).CONCLUSIONS: Future studies should be conducted to explain the association with fertility surgeries, hormone usage, and other urogenital conditions; to clarify the timing of these associations; and to identify other factors related to DIV. [Copyright &y& Elsevier]

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]

• Mathematical models of respiratory syncytial virus (RSV) transmission can help describe seasonal epidemics and assess the impact of potential vaccines and immunoprophylaxis with monoclonal antibodies (mAb). • Our models suggest that either a maternal RSV vaccine or mAb would effectively reduce RSV hospitalization disease burden in New Zealand. • A seasonal mAb resulted in a larger RSV disease prevention impact than a maternal vaccine. Mathematical models of respiratory syncytial virus (RSV) transmission can help describe seasonal epidemics and assess the impact of potential vaccines and immunoprophylaxis with monoclonal antibodies (mAb). We developed a deterministic, compartmental model for RSV transmission, which was fitted to population-based RSV hospital surveillance data from Auckland, New Zealand. The model simulated the introduction of either a maternal vaccine or a seasonal mAb among infants aged less than 6 months and estimated the reduction in RSV hospitalizations for a range of effectiveness and coverage values. The model accurately reproduced the annual seasonality of RSV epidemics in Auckland. We found that a maternal vaccine with effectiveness of 30–40% in the first 90 days and 15–20% for the next 90 days could reduce RSV hospitalizations by 18–24% in children younger than 3 months, by 11–14% in children aged 3–5 months, and by 2–3% in children aged 6–23 months. A seasonal infant mAb with 40–60% effectiveness for 150 days could reduce RSV hospitalizations by 30–43%, 34–48% and by 14–21% in children aged 0–2 months, 3–5 months and 6–23 months, respectively. Our results suggest that either a maternal RSV vaccine or mAb would effectively reduce RSV hospitalization disease burden in New Zealand. Overall, a seasonal mAb resulted in a larger disease prevention impact than a maternal vaccine. [ABSTRACT FROM AUTHOR]

Despite evidence that antibodies targeting the influenza virus neuraminidase (NA) protein can be protective and are broadly cross-reactive, the immune response to NA during infection is poorly understood compared to the response to hemagglutinin (HA) protein. As such, we compared the antibody profile to HA and NA in two naturally-infected human cohorts in Auckland, New Zealand; a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR- confirmed influenza cases (n=50), and an immunology cohort, consisting of paired sera collected after PCR-confirmation of infection (n=94). The induction of both HA and NA-antibodies in these cohorts was influenced by age and subtype. Seroconversion to HA was more frequent in those < 20 years old (yo) for influenza A (Serosurvey, p=0.01, Immunology, p=0.02), but not influenza B virus infection. Seroconversion to NA was not influenced by age or virus type. Adults ≥ 20 yo infected with influenza A viruses were more likely to show NA-only seroconversion compared to children (56% vs 14% [5 - 19 yo] and 0% [0 - 4 yo] respectively). Conversely, children infected with influenza B viruses were more likely than adults to show NA- only seroconversion (88% [0 - 4 yo] and 75% [5 - 19 yo] vs 40% [≥ 20 yo]). These data indicate a potential role for immunological memory in the dynamics of HA and NA-antibody responses. A better mechanistic understanding of this phenomenon will be critical for any future vaccines aimed at eliciting NA immunity. [ABSTRACT FROM AUTHOR]

Despite evidence that antibodies targeting the influenza virus neuraminidase (NA) protein can be protective and are broadly cross-reactive, the immune response to NA during infection is poorly understood compared to the response to hemagglutinin (HA) protein. As such, we compared the antibody profile to HA and NA in two naturally infected human cohorts in Auckland, New Zealand: (i) a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR-confirmed influenza cases ( n  = 50), and (ii) an immunology cohort, consisting of paired sera collected after PCR-confirmation of infection ( n  = 94). The induction of both HA and NA antibodies in these cohorts was influenced by age and subtype. Seroconversion to HA was more frequent in those <20 years old (yo) for influenza A (serosurvey, P  = 0.01; immunology, P  = 0.02) but not influenza B virus infection. Seroconversion to NA was not influenced by age or virus type. Adults ≥20 yo infected with influenza A viruses were more likely to show NA-only seroconversion compared to children (56% versus 14% [5 to 19 yo] and 0% [0 to 4 yo], respectively). Conversely, children infected with influenza B viruses were more likely than adults to show NA-only seroconversion (88% [0 to 4 yo] and 75% [5 to 19 yo] versus 40% [≥20 yo]). These data indicate a potential role for immunological memory in the dynamics of HA and NA antibody responses. A better mechanistic understanding of this phenomenon will be critical for any future vaccines aimed at eliciting NA immunity. IMPORTANCE Data on the immunologic responses to neuraminidase (NA) is lacking compared to what is available on hemagglutinin (HA) responses, despite growing evidence that NA immunity can be protective and broadly cross-reactive. Understanding these NA responses during natural infection is key to exploiting these properties for improving influenza vaccines. Using two community-acquired influenza cohorts, we showed that the induction of both HA and NA antibodies after infection is influenced by age and subtypes. Such response dynamics suggest the influence of immunological memory, and understanding how this process is regulated will be critical to any vaccine effort targeting NA immunity., (Copyright © 2020 Wong et al.)

Objectives: We estimated the risk of HIV associated with sexually transmitted infection (STI) history during adolescence., Methods: We retrospectively studied a cohort of adolescents (n = 75 273, born in 1985-1993) who participated in the Philadelphia High School STD Screening Program between 2003 and 2010. We matched the cohort to STI and HIV surveillance data sets and death certificates and performed Poisson regression to estimate the association between adolescent STI exposures and subsequent HIV diagnosis., Results: Compared with individuals reporting no STIs during adolescence, adolescents with STIs had an increased risk for subsequent HIV infection (incidence rate ratio [IRR] for adolescent girls = 2.6; 95% confidence interval [CI] = 1.5, 4.7; IRR for adolescent boys = 2.3; 95% CI = 1.7, 3.1). Risk increased with number of STIs. The risk of subsequent HIV infection was more than 3 times as high among those with multiple gonococcal infections during adolescence as among those with none., Conclusions: Effective interventions that reduce adolescent STIs are needed to avert future STI and HIV acquisition. Focusing on adolescents with gonococcal infections or multiple STIs might have the greatest impact on future HIV risk.