Background: The immunogenicity and safety of an adjuvanted herpes zoster subunit vaccine (HZ/su) when co-administered with a quadrivalent seasonal inactivated influenza vaccine (IIV4) was investigated in a phase 3, open-label, randomized clinical trial in adults aged ≥50 years.
Methods: Subjects were randomized 1:1 to receive either HZ/su (VZV glycoprotein E [gE]; AS01B Adjuvant System) and IIV4 at day 0 followed by a second HZ/su dose at month 2 (Co-ad group), or IIV4 at month 0 and HZ/su at months 2 and 4 (Control group). Co-primary objectives were the HZ/su vaccine response rate (VRR) in the Co-ad group and the non-inferiority of the antibody responses to HZ/su and IIV4 in the Co-ad group compared to the Control group. Safety information was collected throughout the duration of the study.
Results: 413 subjects were vaccinated in the Co-ad group and 415 in the control group. The HZ/su VRR in the Co-ad group was 95.8% (95% CI 93.3-97.6) and the anti-gE GMCCo-ad/Control ratio was 1.08 (95% CI 0.97-1.20). Co-primary non-inferiority objectives were met. No safety concerns were observed.
Conclusions: No interference in the immune responses to either vaccine was observed when co-administered and no safety concerns were identified.
Clinical Trials Registration: Clinicaltrials.gov NCT01954251.
Vaccines (7), Infectious Diseases (3) Herpes Zoster (3), Human Influenza (3), more mentions
Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of adult respiratory illness. We evaluated routine viral testing and discharge diagnoses for identifying RSV and influenza burden. Polymerase chain reaction results performed in adults during emergency room visits or hospitalizations were reviewed. Peak RSV activity preceded influenza activity by 8 weeks. The ratio of total number of viral tests performed divided by total number of respiratory visits was higher during influenza than RSV peaks (1.31 vs 0.72; P = .0001). Influenza and RSV were listed primary diagnoses in 56 (30%) vs 7 (6%), respectively (P < .0001). Routine viral testing to estimate adult RSV disease burden has limitations.
The Global Certification Commission (GCC), Regional Certification Commissions (RCCs), and National Certification Committees (NCCs) provide a framework of independent bodies to assist the Global Polio Eradication Initiative (GPEI) in certifying and maintaining polio eradication in a standardized, ongoing, and credible manner. Their members meet regularly to comprehensively review population immunity, surveillance, laboratory, and other data to assess polio status in the country (NCC), World Health Organization (WHO) region (RCC), or globally (GCC). These highly visible bodies provide a framework to be replicated to independently verify measles and rubella elimination in the regions and globally.
Laboratory networks were established to provide accurate and timely laboratory confirmation of infections, an essential component of disease surveillance systems. The World Health Organization (WHO) coordinates global laboratory surveillance of vaccine-preventable diseases (VPDs), including polio, measles and rubella, yellow fever, Japanese encephalitis, rotavirus, and invasive bacterial diseases. In addition to providing high-quality laboratory surveillance data to help guide disease control, elimination, and eradication programs, these global networks provide capacity-building and an infrastructure for public health laboratories. There are major challenges with sustaining and expanding the global laboratory surveillance capacity: limited resources and the need for expansion to meet programmatic goals. Here, we describe the WHO-coordinated laboratory networks supporting VPD surveillance and present a plan for the further development of these networks.
Vaccines (3) Measles (4), Rubella (4), Poliomyelitis (4), more mentions
The growth of digital communication technologies for public health is offering an unconventional means to engage the general public in monitoring community health. Here we present Influenzanet, a participatory system for the syndromic surveillance of influenza-like illness (ILI) in Europe. Through standardized online surveys, the system collects detailed profile information and self-reported symptoms volunteered by participants resident in the Influenzanet countries. Established in 2009, it now includes 10 countries representing more than half of the 28 member states of the European Union population. The experience of 7 influenza seasons illustrates how Influenzanet has become an adjunct to existing ILI surveillance networks, offering coherence across countries, inclusion of nonmedically attended ILI, flexibility in case definition, and facilitating individual-level epidemiological analyses generally not possible in standard systems. Having the sensitivity to timely detect substantial changes in population health, Influenzanet has the potential to become a viable instrument for a wide variety of applications in public health preparedness and control.
We report rabies virus transmission among solid organ transplantation recipients in Changsha, China, in 2016. Two recipients were confirmed to have rabies and died. Our findings suggest that more attention should be paid to the possibility of rabies virus transmission through organ transplantation for clinical and public health reasons.
Viral respiratory infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of virus species and subtypes have been associated with these conditions, with influenza viruses (IFV), respiratory syncytial virus (RSV) and the rhinoviruses (RV) being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission or even just the symptoms. Strategies targeting all these aspects are concurrently developing and several novel and promising approaches are emerging. In this perspective, we overview the entire range of options and highlight some of the most promising approaches, including new antivirals, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, as well as vaccines and public health policies towards prevention. Wide scale prevention through immunisation appears to be within reach for RSV and promising for IFV, while additional effort is needed in regard to RV, as well as other respiratory viruses.
Vaccines (1) Respiratory Tract Infections (2), Human Influenza (1), more mentions
Background: In response to a mumps outbreak at the University of Iowa and surrounding community, university, state, and local health officials implemented a vaccination campaign targeting students <25 years of age with an additional dose of measles-mumps-rubella (MMR) vaccine. Over 4,700 vaccine campaign doses were administered; 97% were documented third doses. We describe the epidemiology of the outbreak before and after the campaign, focusing on cases in university students.
Methods: Mumps cases were identified from reportable disease databases and university health system records. Detailed information on student cases was obtained from interviews, medical chart abstractions, university and state vaccination records, and state public health laboratory results. Pre- and post-campaign incidence among students, university faculty/staff, and community members <25 vs. ≥25 years old were compared using Fisher's exact test. Multivariable regression modeling was performed to identify variables associated with a positive mumps polymerase chain reaction test.
Results: Of 453 cases in the county, 301 (66%) occurred in university students. Student cases were primarily undergraduates (90%) and highly vaccinated (86% had 2 MMR doses, and 12% had 3 MMR doses). Fewer cases occurred in students after the campaign (75; 25%) than before (226; 75%). Cases in the target group (students <25 years of age) declined 9% post-campaign (p = 0.01). A positive mumps PCR test was associated with the presence of parotitis and early sample collection, and inversely associated with recent receipt of MMR vaccine.
Conclusions: Following a large additional dose MMR vaccination campaign, fewer mumps cases occurred overall and in the target population.
Vaccines (4) Measles (3), Rubella (3), Parotitis (2), more mentions
SSc is clinically and pathogenetically heterogeneous. Consensus standards for trial design and outcome measures are needed. International experts experienced in SSc clinical trial design and a researcher experienced in systematic literature review screened the PubMed and Cochrane Central Register of Controlled Trials in order to develop points to consider when planning a clinical trial for muscle involvement in SSc. The experts conclude that SSc-associated muscle involvement is heterogeneous and lacks a universally accepted gold-standard for measuring therapeutic response. Although outcome studies are currently limited by the inability to clearly distinguish active, reversible muscle inflammation from irreversible muscle damage and extramuscular organ involvement, strong consideration should be given to enrolling patients with a myopathy that features several elements of likely reversibility such as muscle weakness, biopsy-proven active inflammation, an MRI indicating muscle inflammation and a baseline serum creatinine kinase above three times the upper limit of normal to prevent floor effect. Randomized controlled trials are preferred, with a duration of at least 24 weeks. Outcome measures should include a combination of elements that are likely to be reversible, such as muscle weakness, biopsy-proven active inflammation, creatinine kinase/aldolase and a quality of life questionnaire. The individual measurements might require a short pre-study for further validation. A biological sample repository is recommended.
Muscular and Skeletal Diseases (1) Muscle Weakness (2), Systemic Scleroderma (1), Muscular Diseases (1), more mentions
Influenza vaccination is estimated to only be effective in 17-53% of older adults. Multiple patient behaviors and psychological factors have been shown to act as 'immune modulators' sufficient to influence vaccination outcomes. However, the relative importance of such factors is unknown as they have typically been examined in isolation. The objective of the present study was to explore the effects of multiple behavioral (physical activity, nutrition, sleep) and psychological influences (stress, positive mood, negative mood) on the effectiveness of the immune response to influenza vaccination in the elderly. A prospective, diary-based longitudinal observational cohort study was conducted. One hundred and thirty-eight community-dwelling older adults (65-85years) who received the 2014/15 influenza vaccination completed repeated psycho-behavioral measures over the two weeks prior, and four weeks following influenza vaccination. IgG responses to vaccination were measured via antigen microarray and seroprotection via hemagglutination inhibition assays at 4 and 16weeks post-vaccination. High pre-vaccination seroprotection levels were observed for H3N2 and B viral strains. Positive mood on the day of vaccination was a significant predictor of H1N1 seroprotection at 16weeks post-vaccination and IgG responses to vaccination at 4 and 16weeks post-vaccination, controlling for age and gender. Positive mood across the 6-week observation period was also significantly associated with post-vaccination H1N1 seroprotection and IgG responses to vaccination at 16weeks post-vaccination, but in regression models the proportion of variance explained was lower than for positive mood on the day of vaccination alone. No other factors were found to significantly predict antibody responses to vaccination. Greater positive mood in older adults, particularly on the day of vaccination, is associated with enhanced responses to vaccination.
Vaccines (1) Human Influenza (6), H1N1 Influenza (2), more mentions
Public health messaging about antimicrobial resistance (AMR) sometimes conveys the problem as an epidemic. We outline why AMR is a serious endemic problem manifested in hospital and community-acquired infections. AMR is not an epidemic condition, but may complicate epidemics, which are characterised by sudden societal impact due to rapid rise in cases over a short timescale. Influenza, which causes direct viral effects, or secondary bacterial complications is the most likely cause of an epidemic or pandemic where AMR may be a problem. We discuss other possible causes of a pandemic with AMR, and present a risk assessment formula to estimate the impact of AMR during a pandemic. Finally, we flag the potential impact of genetic engineering of pathogens on global risk and how this could radically change the epidemiology of AMR as we know it. Understanding the epidemiology of AMR is key to successfully addressing the problem. AMR is an endemic condition but can play a role in epidemics or pandemics, and we present a risk analysis method for assessing the impact of AMR in a pandemic.
Infectious Diseases (1) Human Influenza (2), Bacterial Infection (1), Community-Acquired Infections (1), more mentions
INTRODUCTION: Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).
METHODS: We conducted a case-control study over two influenza seasons (2010-11, 2011-12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1-28days before the SAB.
RESULTS: The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1-3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1-28days was 3.7 (95% CI 1.4-9.4) in 2010-11 and 1.4 (95% CI 0.6-3.3) in 2011-12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1-28days was 7.7 (95% CI 2.2-27.3); the aOR was 1.3 (95% CI 0.7-2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.
CONCLUSION: SAB was associated with influenza vaccination in the preceding 28days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.
Vaccines (10) Human Influenza (11), Spontaneous Abortion (3), more mentions
Abstract: Virus-induced oxidative stress plays an important role in the regulation of the host immune system. In this review, we provide backgrounds of the pathogenic mechanism of oxidative stress induced by influenza virus and the specific oxidant-sensitive pathways, and highlight that antioxidant is one of the effective strategies against influenza virusinfection Keyword: Antioxidants. Keyword: Influenza virus.
Hepatitis A virus (HAV) infection is an ancient disease and likely to have afflicted mankind since humans first began to live in groups large enough to sustain transmission of the causative agent, HAV. In reviewing what was known as 'catarrhal jaundice' in 1912, Cockayne noted descriptions of epidemic jaundice extending back to antiquity1. The infectious nature of the disease was proven several decades later in deliberate human transmission studies2. Such experiments led to a clear distinction between hepatitis A ('infectious hepatitis') and hepatitis B ('homologous serum jaundice') and recognition of the lack of cross immunity between these two forms of transmissible hepatitis as early as 19453. However, the responsible virus was not identified until almost 30 years later, when small, round viral particles were discovered by immune electron microscopy in the feces of an experimentally-infected human subject by Feinstone et al. in 19734. This review provides an up-to-date in in-depth overview of HAV and the acute inflammatory hepatic infection it causes in humans, including recently recognized aspects of its molecular virology, evolution, natural history, pathogenesis, epidemiology and prevention.
Infectious Diseases (7), Vaccines (1) Hepatitis A (4), Jaundice (3), Hepatitis (2), more mentions
AIMS: The pathogenesis, viral localization and histopathological features of Middle East Respiratory Syndrome - Coronavirus (MERS-CoV) in human are not sufficiently described. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology.
METHODS AND RESULTS: We analyzed the postmortem histopathological findings and investigated viral particles localization in the pulmonary and extra-pulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T-cell lymphoma, who acquired MERS-CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 minutes from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotizing pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localized in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles.
CONCLUSION: The results highlight the pulmonary and extra-pulmonary pathological changes of MERS-CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue tropism for MERS-CoV in kidney. This article is protected by copyright. All rights reserved.
Affinity-matured, functional anti-pathogen antibodies are present at low frequencies in natural human repertoires. These antibodies are often excellent candidates for therapeutic monoclonal antibodies. However, mining natural human antibody repertoires is a challenge. In this study, we demonstrate a new method that uses microfluidics, yeast display, and deep sequencing to identify 247 natively paired anti-pathogen single-chain variable fragments (scFvs), which were initially as rare as 1 in 100,000 in the human repertoires. Influenza A vaccination increased the frequency of influenza A antigen-binding scFv within the peripheral B cell repertoire from <0.1% in non-vaccinated donors to 0.3-0.4% in vaccinated donors, whereas pneumococcus vaccination did not increase the frequency of antigen-binding scFv. However, the pneumococcus scFv binders from the vaccinated library had higher heavy and light chain Replacement/Silent mutation (R/S) ratios, a measure of affinity maturation, than the pneumococcus binders from the corresponding non-vaccinated library. Thus, pneumococcus vaccination may increase the frequency of affinity-matured antibodies in human repertoires. We synthesized 10 anti-influenza A and nine anti-pneumococcus full-length antibodies that were highly abundant among antigen-binding scFv. All 10 anti-influenza A antibodies bound the appropriate antigen at KD<10 nM and neutralized virus in cellular assays. All nine anti-pneumococcus full-length antibodies bound at least one polysaccharide serotype, and 71% of the anti-pneumococcus antibodies that we tested were functional in cell killing assays. Our approach has future application in a variety of fields, including the development of therapeutic antibodies for emerging viral diseases, autoimmune disorders, and cancer.
Oncology (1), Immune System Diseases (1) Human Influenza (5), Viral Diseases (1), Neoplasms (1), more mentions
BACKGROUND: Conflicting results regarding the impact of repeated vaccination on influenza vaccine effectiveness (VE) may cause confusion regarding the benefits of receiving the current season's vaccine.
METHODS: We systematically searched MEDLINE, Embase, PubMed, and Cumulative Index to Nursing and Allied Health Literature from database inception to August 17, 2016, for observational studies published in English that reported VE against laboratory-confirmed influenza for four vaccination groups, namely current season only, prior season only, both seasons, and neither season. We pooled differences in VE (∆VE) between vaccination groups by influenza season and type/subtype using a random effects model. The study protocol is registered with PROSPERO (registration number: CRD42016037241).
RESULTS: We identified 3435 unique articles, reviewed the full text of 634, and included 20 for meta-analysis. Compared to prior season vaccination only, vaccination in both seasons was associated with greater protection against influenza H1N1 (∆VE = 26%; 95% CI, 15% to 36%) and B (∆VE = 24%; 95% CI, 7% to 42%), but not H3N2 (∆VE = 10%; 95% CI, -6% to 25%). Compared to no vaccination for either season, individuals who received the current season's vaccine had greater protection against H1N1 (∆VE = 61%; 95% CI, 50% to 70%), H3N2 (∆VE = 41%; 95% CI, 33% to 48%), and B (∆VE = 62%; 95% CI, 54% to 68%). We observed no differences in VE between vaccination in both seasons and the current season only for H1N1 (∆VE = 4%; 95% CI, -7% to 15%), H3N2 (∆VE = -12%; 95% CI, -27% to 4%), or B (∆VE = -8%; 95% CI, -17% to 1%).
CONCLUSIONS: From the patient perspective, our results support current season vaccination regardless of prior season vaccination. We found no overall evidence that prior season vaccination negatively impacts current season VE. It is important that future VE studies include vaccination history over multiple seasons in order to evaluate repeated vaccination in more detail.
Vaccines (5) Human Influenza (6), H1N1 Influenza (3), more mentions
We evaluated serologic response of 42 Middle East respiratory syndrome coronavirus (MERS-CoV)-infected patients according to 4 severity groups: asymptomatic infection (Group 0), symptomatic infection without pneumonia (Group 1), pneumonia without respiratory failure (Group 2), and pneumonia progressing to respiratory failure (Group 3). None of the Group 0 patients showed seroconversion, while the seroconversion rate gradually increased with increasing disease severity (0.0%, 60.0%, 93.8%, and 100% in Group 0, 1, 2, 3, respectively; P = 0.001). Group 3 patients showed delayed increment of antibody titers during the fourth week, while Group 2 patients showed robust increment of antibody titer during the third week. Among patients having pneumonia, 75% of deceased patients did not show seroconversion by the third week, while 100% of the survived patients were seroconverted (P = 0.003).
Pneumonia (4), Respiratory Failure (2), Infections (2), more mentions