Defective Viral Genomes May Indicate Greater Flu Virus Severity

MedicalResearch.com Interview with:
Ana Falcón
Department of Molecular and Cellular Biology
National Center for Biotechnology
Spanish National Research Council (CNB-CSIC)
Madrid, Spain

MedicalResearch.com: What is the background for this study?

Response: Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses.

IAV virulence and pathogenesis are dependent on complex, multigenic mechanisms involving the viral genetic characteristics, the host conditions, the virus-host interactions, and the host response to the infection. Influenza virus pathogenicity has been studied in depth for many years, and several amino acid changes have been identified as virulence determinants, however, a general pathogenicity determinant has not been characterized.

A proportion of influenza virus particles have defective genome RNAs (Defective Viral Genomes-DVGs) due to internal deletions of viral segments. The DVGs have the 3’ and 5’ ends of the parental RNA segments, and most have a single, large central deletion that generates viral RNAs of 180–1000 nucleotides. The presence of DVGs potentiates the host response in cultured cells and in animal models and leads to attenuated infection, possibly through recognition of double-stranded RNA by receptors that activate antiviral signaling cascades.

Continue reading

Pandemic Flu May Increase Risk of Type 1 Diabetes In Genetically Predisposed Patients

MedicalResearch.com Interview with:
Paz Lopez-Doriga Ruiz MD, PhD candidate Norwegian Institute of Public Health Department of Non Communicable Diseases OsloPaz Lopez-Doriga Ruiz MD, PhD candidate

Norwegian Institute of Public Health
Department of Non Communicable Diseases
Oslo 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Some case reports have linked pandemic influenza to the development of type 1 diabetes. Other studies have suggested that also respiratory infections may contribute to type 1 diabetes risk.

 Our findings supports a suggested role of respiratory infections in the etiology of type 1 diabetes and influenza virus could be a contributing factor to the development of clinical diabetes, due to stress and inflammation in predisposed individuals.

Continue reading

Nasal Spray Flu Vaccine Ineffective and Not Recommended

MedicalResearch.com Interview with:

Michael Jackson  PhD, MPH Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network

Dr. Jackson

Michael Jackson  PhD, MPH
Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network 

MedicalResearch.com: What is the background for this study?

  • Response: Each year, Kaiser Permanente Washington is one of five sites across the country that participate in the United States Influenza Vaccine Effectiveness Network. The Network reports its early interim results in the MMWRand presents additional interim results to the Advisory Committee on Immunization Practices (ACIP)This New England Journal of Medicine publication is an update of those interim results.
  • The findings in this New England Journal of Medicine are special because prior randomized controlled trials indicated that the nasal spray vaccine (FluMist)—also called live attenuated influenza vaccine (LAIV)—would work well to protect children and teens from the flu, whereas in actual practice we found that the flu shot worked much better, particularly against the predominant strain, A(H1N1)pdm09.
  • The nasal spray vaccine was first seen to be less effective for young children than the flu shot in 2013-2014 for the A(H1N1)pdm09 virus strain. In response, the A(H1N1)pdm09 virus strain used in the nasal spray vaccine was changed for the 2015-2016 influenza season. The 2016/17 season was the first since 2015-2016 to be dominated by the A(H1N1)pdm09 virus, making this our first opportunity to evaluate the updated nasal spray vaccine.
  • The Influenza Vaccine Effectiveness Network evaluated the impact of this change as part of our estimates of influenza vaccine effectiveness in 2015-2016. Preliminary findings from this study were presented to the ACIP in June 2016, which led to the nasal spray vaccine not being recommended in 2016-2017 in the US, although the nasal spray vaccine remains licensed in the US. In 2016-2017, the LAIV A(H1N1)pdm09 vaccine strain was unchanged from 2015-2016.

Continue reading

Dissolvable Microneedle Patches Can Be Vaccination Game Changer

MedicalResearch.com Interview with:
Dr Nadine G Rouphael MD
Associate Professor of Medicine, Emory University
Director of the VTEU and HIPC networks at the
Hope Clinic of the Emory Vaccine Center
Decatur GA 30030, USA

MedicalResearch.com: What is the background for this new technology and study? What are the main findings?

Response: Different groups including a group of researchers at Georgia Tech have been working on the microneedle technology for more than 20 years. The dissolvable microneedle patches are already used in several cosmetic products and drugs. However, vaccination with microneedle patches has been studied mostly in animals.

Our phase 1 trial published this week in The Lancet showed that vaccination with the microneedle patches was safe, with no related serious adverse events reported. Local skin reactions to the patches were mostly mild itching and faint redness that lasted two to three days. No new chronic medical illnesses or influenza-like illnesses were reported with either the patch or the injection groups. Antibody responses generated by the vaccine, as measured through analysis of blood samples, were similar in the groups vaccinated using patches and those receiving intramuscular injection, and these immune responses were still present after six months. When asked after immunization, more than 70 percent of patch recipients reported they would prefer patch vaccination over injection or intranasal vaccination for future vaccinations.

Continue reading

Efficacy of Recombinant Flu Vaccine in Adults 50 Years of Age or Older 

MedicalResearch.com Interview with:

Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT 

Dr. Dunkle

Lisa M. Dunkle, M.D.
Chief Medical Officer
Protein Sciences Corporation
1000 Research Parkway
Meriden, CT

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The first and only recombinant protein influenza vaccine (RIV, Flublok) was approved in 2013 as a trivalent formulation for use in adults 18 years of age and older. This approval was based on demonstration of clinical efficacy (full approval) in adults 18-49 years of age and accelerated approval was granted for adults 50 years of age and older. Two clinical trials were conducted in 2014-2015 with RIV4 (Flublok Quadrivalent), of which the trial reported in the current NEJM is one.

These studies supported full approval of Flublok in adults 50 years of age and older and approval of Flublok Quadrivalent in all adults 18 years of age and older. The second trial of immunogenicity of Flublok Quadrivalent in adults 18-49 years of age will be the subject of another publication in the near future.

The main findings of the current trial are well summarized in the Conclusion of the Abstract: “RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness in older adults.”

Additionally, the recombinant vaccine (RIV4, Flublok Quadrivalent) demonstrated significantly less injection site pain and tenderness following vaccination. Based on the characteristics of the study participants, one can conclude that RIV4 is safe and effective in most individuals with underlying chronic diseases

Continue reading

Study Finds No Link Between First Trimester Influenza Vaccination and Major Structural Birth Defects

MedicalResearch.com Interview with:

Dr. Elyse Olshen Kharbanda, MD MPH HealthPartners Institute Minneapolis, MN

Dr. Kharbanda

Dr. Elyse Olshen Kharbanda, MD MPH

HealthPartners Institute
Minneapolis, MN

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pregnant women who get the flu are at an increased risk for severe illness. To protect pregnant women, the Advisory Committee on Immunization Practices recommends women receive inactivated influenza vaccine (IIV) during any trimester of their pregnancy.

This study used data from the Vaccine Safety Datalink to evaluate if there was an increased risk for selected major structural birth defects for infants whose mothers received IIV in the first trimester of pregnancy versus infants who were unexposed to IIV. Among over 425,000 live births, including 52,856 whose mothers received IIV during first trimester, we evaluated risks for major structural birth defects.  In this large observational study, we did not observe increased risks for major structural birth defects in offspring following first trimester maternal inactivated influenza vaccine exposure.

Continue reading

Flu Treatment With Neuraminidase Inhibitors During Pregnancy Not Linked To Birth Defects

MedicalResearch.com Interview with:

Dr. Sophie Graner Department of Women's and Childrens Health Karolinska Institute, Stockholm, Sweden

Dr. Graner

Dr. Sophie Graner
Department of Women’s and Childrens Health
Karolinska Institute, Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pregnant women are at increased risks of severe disease and death due to influensa infection, as well as hospitalization. Also influenza and fever increase the risk of adverse pregnancy outcomes for their infants such as intrauterine death and preterm birth. Due to this, the regulatory agencies in Europe and the US recommended post exposure prophylaxis and treatment for pregnant women with neuraminidase inhibitors during the last influenza pandemic 2009-10. Despite the recommendations, the knowledge on the effect of neuraminidase inhibitors on the infant has been limited. Previously published studies have not shown any increased risk, but they have had limited power to assess specific neonatal outcomes such as stillbirth, neonatal mortality, preterm birth, low Agar score, neonatal morbidity and congenital malformations.
Continue reading

First Childhood Exposure Determines How Sick You Get From Flu As Adult

MedicalResearch.com Interview with:
Katelyn M. Gostic and
Monique Ambrose

Department of Ecology and Evolutionary Biology
University of California
Los Angeles

MedicalResearch.com: What is the background for this study? What are the main findings?

Monique Ambrose: Influenza pandemics pose a serious, recurrent threat to human public health. One of the most probable sources of future pandemic influenza viruses is the pool of influenza A virus (IAV) subtypes that currently circulate in non-human animals. It has traditionally been thought that the human population is immunologically naïve and unprotected against these unfamiliar subtypes. However, our work suggests that an individual ‘imprints’ to the influenza A virus (IAV) encountered in early childhood in such a way that they retain protection against severe disease if they later encounter a novel IAV subtype that belongs to the same genetic group as their first exposure.

Our research looked at human cases of H5N1 and H7N9, two avian IAV subtypes of global concern, to investigate what factors most strongly predicted risk of severe disease. The most striking explanatory factor was childhood IAV imprinting: our results suggest that individuals who had childhood imprinting on an IAV in the same genetic group as the avian IAV they encountered later in life experienced 75% protection against severe disease and 80% protection against death.

Continue reading

Many Children With Asthma Still Not Receiving Flu Vaccine

MedicalResearch.com Interview with:

Deepa Patadia, MD Wexner Medical Center The Ohio State University

Dr. Deepa Patadia

Deepa Patadia, MD
Wexner Medical Center
The Ohio State University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Influenza vaccination is recommended every autumn for all children 6 months of age and older. It is particularly important for children with asthma, who are at high risk of hospitalization or severe illness if they contract influenza infection. The rates of influenza vaccination in children with asthma have not previously been well studied, but Healthy People 2020 has set a target goal to vaccinate 70% of all children for influenza. We found that rates of vaccination in our large primary care population was much lower than the target rate, with less than 50% of all children receiving the vaccine each year over a 5 year period; however rates were higher in children with asthma, albeit still only at 55%.

Continue reading

Live Nasal and Injectable Flu Vaccines Had Similar Effectiveness in Pediatric Study

MedicalResearch.com Interview with:

Dr. Mark Loeb BSc (McGill), MD (McGill), MSc (McMaster), FRCPC Professor, Department of Pathology and Molecular Medicine Joint Member, Dept of Clinical Epidemiology & Biostatistics Division Director, Infectious Diseases, McMaster University

Dr. Mark Loeb

Dr. Mark Loeb
BSc (McGill), MD (McGill), MSc (McMaster), FRCPC
Professor, Department of Pathology and Molecular Medicine
Joint Member, Dept of Clinical Epidemiology & Biostatistics
Division Director, Infectious Diseases, McMaster University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The background for this study is that in the U.S, the Advisory Committee on Immunization Practices (ACIP), the committee that advises the CDC on vaccination policy, decided this June not to recommend LAIV (nasal live vaccine) for children. This is because of non-randomized studies conducted in the U.S suggesting that the vaccine was ineffective. This was an unprecedented decision in influenza vaccine policy making for children.

Our study, a randomized, blinded, controlled trial, which is the most rigorous type of study design, conducted over 3 years (2012-13, 2013-2014, 2014-2015 influenza seasons), showed in fact very similar protection for children and their communities for the live and inactivated vaccines. We conducted the study in the Hutterite community of Western Canada which allowed us to compare the effect of the vaccines in entire communities. That is, we were able to study the direct effect and the indirect effect of these vaccines.

Continue reading

Flu Vaccination During Pregnancy Protects Mother and Infant

MedicalResearch.com Interview with:

Marta C. Nunes, PhD DST/NRF:Vaccine Preventable Diseases Respiratory and Meningeal Pathogens Research Unit University of Witwatersrand Chris Hani Baragwanath Academic Hospital Soweto, South Africa

Dr. Marta Nunes

Marta C. Nunes, PhD
DST/NRF:Vaccine Preventable Diseases
Respiratory and Meningeal Pathogens Research Unit
University of Witwatersrand
Chris Hani Baragwanath Academic Hospital
Soweto, South Africa

MedicalResearch.com: What is the background for this study?

Response: Young infants are at increased risk for influenza infection and hospitalizations associated with influenza infection. While active annual influenza vaccination is the most efficient mode for the prevention of influenza infection, current vaccines are poorly immunogenic and not licensed for use in infants

Continue reading

Flu Vaccination During Pregnancy Protects Both Mother and Baby

MedicalResearch.com Interview with:

Julie H. Shakib, DO, MS, MPH Assistant Professor of Pediatrics | University of Utah Medical Director | Well Baby and Intermediate Nursery Salt Lake City

Dr. Julie Shakib

Julie H. Shakib, DO, MS, MPH
Assistant Professor of Pediatrics | University of Utah
Medical Director | Well Baby and Intermediate Nursery
Salt Lake City 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Shakib: Immunization against influenza in the first six months of life is ineffective  due to an immature immune response. Passive protection via maternal immunization offers an alternative but only a few studies have evaluated the efficacy of this immunization strategy. We found that in infants born to women immunized against influenza during pregnancy, the risk of laboratory-confirmed influenza and influenza-related hospitalization were reduced by 70% and 81% in their first 6 months of life, respectively.This large study provides more evidence that when women are immunized against influenza during pregnancy, their infants are much less likely to be diagnosed with influenza in their first 6 months.

Continue reading

Morning Flu Vaccinations May Be More Effective

MedicalResearch.com Interview with:

Dr Anna C. Phillips PhD CPsychol AFBPsS Reader in Behavioural Medicine School of Sport, Exercise & Rehabilitation Sciences University of Birmingham Edgbaston Birmingham

Dr. Anna Phillips

Dr Anna C. Phillips PhD CPsychol AFBPsS
Reader in Behavioural Medicine
School of Sport, Exercise & Rehabilitation Sciences
University of Birmingham
Edgbaston Birmingham

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Phillips: We know that various factors can affect the response to vaccination and that older adults have a poorer response than younger people, i.e. they produce fewer antibodies.  We also know that many immune messengers and important hormones have daily rhythms in their levels and wanted to test whether the antibody response to vaccination might also be affected by time of day.  We randomised surgeries to giving morning or afternoon vaccinations and tested before and one month after the vaccination for levels of antibodies.

Two of the three flu strains (viruses) contained in the vaccine showed a higher antibody response in the morning than in the afternoon, up to 4 x higher to one of the strains (A/California) and 1.5 x higher to the B strain. None of the potential mechanisms we measured (immune messengers, hormones) seemed to be driving this effect.

Continue reading

Hospital Stays Provide Opportunity to Vaccinate High Risk Patients

MedicalResearch.com Interview with:

Sara Y. Tartof, PhD, MPH Kaiser Permanente Southern California Department of Research & Evaluation

Dr. Sarah Tartoff

Sara Y. Tartof, PhD, MPH
Kaiser Permanente Southern California Department of Research & Evaluation

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Tartof: The flu is a highly contagious respiratory infection that can cause serious complications, hospitalizations and, in some cases, even death. Some people, such as older adults, young children and people with certain health conditions, are at high risk for serious complications. In addition to recommending annual flu vaccination for people 6 months of age and older, the Centers for Disease Control and Prevention recommends that hospitalized patients who are eligible receive the flu vaccine before discharge.

Historically, inpatient rates of vaccination have been low. There has been concern among surgeons that vaccinating patients while they are in the hospital can contribute to increased risk of vaccine-related fever or muscle pain, which might be incorrectly attributed to surgical complications. However, there have been no data to support that concern. The objective of this study was to provide clinical evidence that would either substantiate or refute concerns about the safety of perioperative vaccination.

Continue reading

Flu Infection Raises Risk of New Onset Atrial fibrillation

MedicalResearch.com Interview with:
Tze-Fan Chao MD PhD
Division of Cardiology, Department of Medicine
Taipei Veterans General Hospital
Institute of Clinical Medicine, and Cardiovascular Research Center
National Yang-Ming University, Taipei, Taiwan
Su-Jung Chen MD
Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital,
Institute of Public Health and School of Medicine, National Yang-Ming University
Taipei, Taiwan

MedicalResearch: What is the background for this study? What are the main findings?

Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, accounting for frequent hospitalizations, hemodynamic abnormalities, and thromboembolic events. Although the detailed mechanism of the occurrence of Atrial fibrillation remains unclear, systemic inflammation and sympathetic nervous system have been demonstrated to play an important role in the pathogenesis of AF. Flu (influenza infection) is a common disease which could happen to everyone in the daily life. It could cause significant morbidity and mortality, and is a serious human health concern worldwide. Previous studies have shown that influenza infection not only results in the productions of pro-inflammatory cytokines, but also activates the sympathetic nervous system, which are all related to the occurrence of  Atrial fibrillation. Therefore, we hypothesized that influenza infection could be a risk factor of new-onset AF. We also tested the hypothesis that influenza vaccination, a useful way to reduce the risk of influenza infection, could decrease the risk of AF.

In this large scale nationwide case-control study, a total of 11,374 patients with newly diagnosed  Atrial fibrillation were identified from the Taiwan National Health Insurance Research Database. On the same date of enrollment, 4 control patients (without AF) with matched age and sex were selected to be the control group for each study patient. The relationship between AF and influenza infection/vaccination 1 year before the enrollment was analyzed. The results showed that influenza infection was associated with an 18% increased risk of AF, and the risk could be easily reduced through influenza vaccination.

Continue reading

Pregnant Women With Flu At High Risk of Serious Illness and Complications

Ikwo Oboho, MD, ScMLCDR, United States Public Health Service Medical Epidemiologist, Centers for Disease Control and PreventionPriority Populations Treatment Team| HIV Care & Treatment Branch | Division of Global HIV/TB Atlanta, GA 30333

Dr. Ikwo Oboho

MedicalResearch.com Interview with:
Ikwo Oboho, MD, ScMLCDR

United States Public Health Service
Medical Epidemiologist, Centers for Disease Control and PreventionPriority Populations Treatment Team| HIV Care & Treatment Branch | Division of Global HIV/TB
Atlanta, GA 30333

MedicalResearch.com: What is the background for this study?

Dr. Oboho: ·Pregnant women with flu are at high risk of serious illness and complications, including death.

The study is based on data gathered from a nationwide flu surveillance network that includes 14 states. The analysis focused on pregnant women hospitalized with laboratory-confirmed flu over four recent flu seasons, from 2010 to 2014.

MedicalResearch.com: What are the main findings? 

Dr. Oboho: ·       During the study period, 865 pregnant women were hospitalized with flu. Sixty-three of these patients, or about 7 percent, had severe illness.

  • After adjusting for underlying medical conditions, vaccination status, and pregnancy trimester, we found that early treatment with the antiviral drug oseltamivir was associated with a shorter hospital stay.
  • Among pregnant women with severe flu illness who were treated early with oseltamivir — within two days of the start of symptoms — the median length of stay was about five days shorter compared to hospitalized pregnant women with severe flu illness who were treated later
  • Pregnant women who were hospitalized with severe cases of flu illness were half as likely to have been vaccinated as women with non-severe illness.

Continue reading

Genetic Links To Fatal Inflammatory Flu Reaction Discovered

Grant S Schubert MD, PhD Clinical Fellow, Division of Rheumatology Cincinnati Childrens Hospital

Dr. Schulert

MedicalResearch.com Interview
Grant S Schulert MD, PhD
Clinical Fellow, Division of Rheumatology
Cincinnati Childrens Hospital 

Medical Research: What is the background for this study? What are the main findings?

Dr. Schulert: Influenza infection causes millions of illnesses annually, but most of those are relatively mild.  In a subset of cases, patients can become critically ill, even if they are relatively young and healthy.  Several previous reports had observed in these critically ill patients features of a hyperinflammatory syndrome known as HLH (hemophagocytic lymphohistiocytosis) or MAS (macrophage activation syndrome).  This hyperinflammation can be triggered by other infections as well as in a subtype of juvenile arthritis, but there is also a familial form occurring in early childhood with known genetic causes.  Our questions with this study were

1) how often are features consistent with HLH/MAS seen in fatal H1N1 influenza infections and
2) do patients with fatal H1N1 infection have genetic mutations associated with HLH/MAS?

Our collaborator Paul Harms, MD, and his team at the Michigan Center for Translational Pathology, University of Michigan Medical School identified 16 cases of fatal H1N1 influenza infection.  Based on their clinical features, between 41-88% of these patients could be categorized as having a hyperinflammatory HLH/MAS.  We then used processed tissue samples from the patients for whole exome genetic sequencing, which reads the entire genetic code of every gene in a person. Five patients carried mutations in genes which cause HLH, and several others carried mutations in genes linked to MAS.  This suggests that there may be genetic risk factors for developing fatal hyperinflammatory syndromes in H1N1 infection.

Continue reading

Three Waves of MERS Infections Closely Followed Influenza Outbreaks

MedicalResearch.com Interview with:
Daihai He, PhD

Assistant Professor
Department of Applied Mathematics
Hong Kong Polytechnic University 

Medical Research: What is the background for this study? What are the main findings?

Response: We studied the patterns of MERS-CoV cases and influenza cases from May 1, 2012 to May 31, 2015 in the Middle East. Our key findings are that the three waves of MERS appear to follow the waves of influenza A in the Middle East during the period. The influenza A(H1N1)pdm wave which occurred in Egypt in early 2014 closely led to the first major MERS wave in May 2014, while the H3N2 wave in late 2014 in Egypt closely led to the third MERS wave in early 2015. The second MERS wave in late 2014 and third MERS wave in early 2015 appeared to be split off by a H3N2 and/or A(H1N1)pdm waves in the region.

Continue reading

All Health Care Workers Should Receive Flu Vaccination Every Year

MedicalResearch.com Interview with:
Carla L. Black PhD Immunization Services Division National Center for Immunization and Respiratory Diseases CDC
Carla L. Black PhD
Immunization Services Division
National Center for Immunization and Respiratory Diseases
CDC 

Medical Research: What is the background for this study? What are the main findings?

Dr. Black: The Advisory Committee on Immunization Practices (ACIP) recommends that all health-care personnel (HCP) be vaccinated annually against influenza. Vaccination of health-care personnel can reduce influenza-related morbidity and mortality among HCP and their patients. Overall, 77.3% of HCP reported receiving an influenza vaccination in the 2014-15 season, similar to the 75.2% coverage among HCP reported in the 2013-14 season. Coverage was highest among  health-care personnel working in hospitals (90.4%) and lowest among HCP working in long-term care (LTC) settings (63.9%).

Flu vaccination coverage was highest in settings with employer flu vaccination requirements and promotion of flu vaccination. Vaccination coverage was 96% among HCP with an employer requirement for vaccination. Among HCP without an employer requirement for vaccination, vaccination coverage was higher for HCP working in settings where vaccination was offered on-site at no cost for one day (73.6%) or multiple days (83.9%) compared with  health-care personnel  working in settings where vaccination was promoted but not offered on-site (59.5%) or not promoted in any manner (44.0%).

Continue reading

Commuter Patterns Can Help Predict Influenza Spread

MedicalResearch.com Interview with:
Brooke Bozick

Ph.D. Candidate
Population Biology, Ecology, & Evolution Program
Emory University

MedicalResearch: What is the background for this study?

Response: Previous research at the global scale has shown that air travel is important for the spread of disease. For example, much work has focused on the recent Ebola epidemic in Africa, identifying where this disease emerged and then using air travel networks to predict the path of spread from there.

At a more local scale, other modes of transportation may be more important to structuring pathogen populations. We were interested in investigating seasonal influenza in the United States. Previous research has shown that once the winter influenza epidemic starts, it spreads very rapidly across the continental states, suggesting that the US may act as one large, well-mixed population. Previous work using genetic data to look for spatial structure at this scale didn’t identify any patterns. However, these studies used geographic proximity to define the distance between states; we wanted to see whether similar patterns existed at this spatial scale if we instead used movement data as a proxy for the distance between locations. Commuter movements have previously been shown to correlate with influenza timing and spread based on influenza-like-illness and mortality data.

MedicalResearch: What are the main findings?

Response: We found that spatial structure is detectable within the US. We used data on the genetic distance between sequences collected from different states and compared that to different measures of ‘distance’ between states—geographic proximity, the daily number of people flying between states and the daily number of commuters traveling between states using ground transportation—to see whether any correlations were present. Further, we did this for two different subtypes of seasonal influenza: A/H3N2 and A/H1N1. These subtypes have different epidemiological properties, so there was reason to believe that the observed patterns might differ depending on subtype.

We found that some correlations were present for all the distance metrics studied, but that they were observed a greater proportion of the time when looking at commuter movements, and when looking at the A/H1N1 subtype. Since A/H1N1 is generally milder and spreads more slowly throughout the US compared to A/H3N2, we interpret this to mean that spatial structure is likely more easily detected in this subtype. If A/H3N2 spreads rapidly from coast to coast, any signature of spatial structure is likely obscured before we have a chance to observe it.

Continue reading

High-Dose Flu Vaccine Prevented More Influenza Infections In Elderly Than Standard Dose

Dr Richard Forshee PhD Food and Drug Administration, Silver Spring, MD MedicalResearch.com Interview with:
Dr Richard Forshee PhD

Associate Director for Research in the Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research
U.S. Food and Drug Administration

Silver Spring, MD
On behalf of the study authors

Medical Research: What is the background for this study? What are the main findings?

Dr. Forshee: Influenza continues to be a major public health concern causing illness, hospitalization, and death. The elderly are at highest risk for seasonal influenza complications, including hospitalization and death. As people grow older their ability to raise a strong protective immune response can weaken.  The availability of a vaccine that uses a higher dose to induce a stronger immune response could reduce the serious impact of influenza in this age group.  The purpose of this study was to determine whether a high-dose inactivated influenza vaccine was more effective for prevention of probable influenza infections and influenza-related hospital admissions, compared to standard-dose inactivated influenza recipients.

In December 2009, the U.S. Food and Drug Administration (FDA) licensed Fluzone High Dose, an injectable inactivated trivalent seasonal influenza vaccine for people ages 65 years and older. This high-dose vaccine contains four times more hemagglutinin—the active ingredient in influenza vaccines that cause the human body to produce antibodies against the influenza viruses—than the standard-dose vaccine. The FDA approved the high-dose vaccine using the accelerated approval regulatory pathway, which allows the agency to approve products for serious or life-threatening diseases based on reasonable evidence of a product’s effectiveness.  This pathway reduces the time it takes for needed medical products to become available to the public.  Studies conducted prior to licensure showed an enhanced immune response to the high-dose vaccine compared with the standard-dose vaccine in individuals 65 years of age and older indicating that the high-dose vaccine was reasonably likely to be more effective in preventing influenza disease.

As part of the accelerated approval process, the manufacturer, Sanofi Pasteur, was required to conduct a randomized clinical study post-licensure to confirm that the high-dose vaccine decreased seasonal influenza disease after vaccination relative to standard dose vaccine. This confirmatory study demonstrated that the high–dose vaccine prevented 24% more cases of laboratory-confirmed influenza illness compared to standard-dose vaccines in people 65 years of age and older. However, the study was not large enough to determine efficacy of the vaccine against severe disease.

A team of scientists from FDA, the Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and Acumen LLC ( an independent research organization) studied the relative effectiveness of the high-dose influenza vaccine in the U.S. population ages 65 years and older.  The observational study, which covered the 2012-2013 influenza season, found a significant reduction both in influenza-associated illness and in influenza-related hospitalizations among individuals who received the high-dose vaccine, compared to those receiving the standard dose.

Additional background about this study: “Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis” is available at:

http://dx.doi.org/10.1016/S1473-3099(14)71087-4

A commentary on the study titled “Novel observational study designs with new influenza vaccines” is available at:

http://dx.doi.org/10.1016/S1473-3099(15)70020-4 Continue reading

Text Message Improves Pediatric Flu Vaccination Rates

Melissa Stockwell, MD, MPH, FAAP Florence Irving Assistant Professor of Pediatrics and Population and Family Health Columbia University - College of Physicians & Surgeons and Mailman School of Public Health Medical Director, New York-Presbyterian Hospital Immunization Registry (EzVac) Co-Director, Primary Care Clinician Research Fellowship in Community Health New York, NY 10032MedicalResearch.com Interview with:
Melissa Stockwell, MD, MPH, FAAP

Florence Irving Assistant Professor of Pediatrics and Population and Family Health, Columbia University – College of Physicians & Surgeons and Mailman School of Public Health
Medical Director, New York-Presbyterian Hospital Immunization Registry (EzVac);
Co-Director, Primary Care Clinician Research Fellowship in Community Health

Medical Research: What is the background for this study? What are the main findings?

Response:  Influenza can be a very serious disease and is more than just a bad cold.  Some children who are 6 months through 8 years need two doses of the influenza vaccine in a season depending on if and when they received previous influenza vaccine doses. We know that only about half of these families who want to vaccinate their children against the flu and get the first dose, come back to get the second dose.
Continue reading

Flu Vaccination May Be Effective Even When Circulating Strain Different From Vaccine

MedicalResearch.com Interview with:
Maryam Darvishian MSc
Department of Epidemiology, University Medical Center Groningen,
Unit of PharmacoEpidemiology and PharmacoEconomics (PE2),
Department of Pharmacy, University of Groningen,
and 
Prof Edwin R van den Heuvel
Department of Epidemiology, University Medical Center Groningen,
University of Groningen, Groningen, Netherlands
Department of Mathematics and Computer Science,
Eindhoven University of Technology, Eindhoven, Netherlands

Medical Research: What is the background for this study?

Reply: In most developed countries, seasonal influenza vaccine is the standard care for elderly people, but there exists still discussions on whether vaccination is effective. Conducting RCT is not considered ethical and thus the main body of evidence comes from observational studies. Unfortunately, these studies (e.g. cohort studies) are susceptible to different sources of biases especially selection bias which makes it difficult to judge the effectiveness. In recent years test-negative design (TND) studies has been designed. It is a special type of case-control study which would limit the bias, due to similar health care-seeking behavior in cases and controls. The current study is a meta-analysis of TND case-control studies. It is the first meta-analysis of this type of studies and also the first meta-analysis that combined 35 studies for estimation of influenza vaccine effectiveness. More specifically, the meta-analysis assesses the influenza vaccine effectiveness against laboratory-confirmed influenza (LCI) among the elderly population. Continue reading

Flu Season Linked To Increase in Acute Aortic Dissection

MedicalResearch.com Interview with:
Harleen Sandhu, MD MPH
Senior Researcher
University of Texas Health Science Center at Houston

Medical Research: What is the background for this study? What are the main findings?

Dr. Sandhu: Previous studies have shown a correlation between seasonal variations and occurrence of acute aortic dissection, however, reasons for such associations are unknown. Seasonal flu activity has been associated with the occurrence of cardiovascular diseases such as acute myocardial infarction in the past. This led us to verify this seasonal correlation in our experience with acute aortic dissection patients and to further investigate if its incidence was associated with flu activity. Our results confirmed the seasonal variation in acute aortic dissection as well as demonstrated a positive correlation with seasonal flu activity.

Continue reading

Flu Mutations Led To More Disease Among Middle-Aged Adults

Scott E. Hensley, Ph.D. Assistant Professor, The Wistar Institute Philadelphia, PA 19104MedicalResearch.com Interview with
Scott E. Hensley, Ph.D.
Assistant Professor, The Wistar Institute
Philadelphia, PA 19104

 

Medical Research: What are the main findings of the study?

Dr. Hensley: We found that H1N1 viruses recently acquired a mutation that abrogates binding of influenza antibodies that are present in a large number of middle-aged adults.  We propose that this mutation lead to increased disease among middle-aged adults during the 2013-2014 influenza season.
Continue reading

Prior Bird Flu Vaccination Offers Some Protection Against Newer Strains

Robert B Belshe, MD  Division of Infectious Diseases, Allergy & Immunology Saint Louis University School of MedicineMedicalResearch.com Interview with:
Robert B Belshe, MD 
Division of Infectious Diseases, Allergy & Immunology
Saint Louis University School of Medicine

 

Medical Research: What are the main findings of the study?

Response: A vaccine that protects against an old strain of avian flu primes the immune system to mount a rapid response when a vaccine designed to protect against a related but different and new strain of avian flu is given a year later, according to Saint Louis University research findings reported in JAMA.

In addition, when combined with an adjuvant, which is a chemical that stimulates the immune system to produce more antibodies, a lower dose of the new avian flu vaccine worked better in triggering an immune response than a stronger dose without adjuvant. That means the amount of vaccine against a new strain of bird flu can be stretched to protect more people if an adjuvant is added.

Both findings represent important strategies researchers can continue to study to fight new strains of bird flu that people previously have not been exposed to, and consequently can rapidly turn into a pandemic outbreak and public health emergency, said Robert Belshe, M.D., professor of infectious diseases, allergy and immunology at Saint Louis University and the lead author of the article, which appeared in the Oct. 8, 2014 issue of JAMA.

Continue reading

Fluzone High-Dose Vaccine Found More Effective Than Standard-Dose Vaccine

David P. Greenberg, M.D. Vice President, Scientific & Medical Affairs, and Chief Medical Officer Sanofi Pasteur US.MedicalResearch.com Interview with:
David P. Greenberg, M.D.
Vice President, Scientific & Medical Affairs, and Chief Medical Officer
Sanofi Pasteur US.

 

Medical Research: What are the main findings of the study?

Dr. Greenberg: The New England Journal of Medicine published positive results from a randomized, double-blind, large-scale, multi-center efficacy trial, which found that Fluzone® High-Dose (Influenza Vaccine) was more efficacious in preventing influenza illness (“the flu”) in adults 65 years of age and older compared to standard-dose Fluzone vaccine. Fluzone High-Dose vaccine was found to be 24.2 percent (95% CI, 9.7 to 36.5) more effective in preventing influenza relative to standard-dose Fluzone vaccine for the primary endpoint (laboratory-confirmed influenza associated with typical clinical symptoms occurring at least 14 days post-vaccination caused by any viral type or subtype). In other words, investigators determined that participants in the Fluzone High-Dose vaccine group were less likely to get the flu than those in the standard-dose Fluzone vaccine group. The study safety data were consistent with previous Fluzone High-Dose vaccine studies.

Continue reading

Promising New Influenza Drug Reduces Flu Symptoms and Viral Shedding

MedicalResearch.com Interview with:
Prof. Jean-Francois Rossignol, FRSC, FRCPath
Romark Laboratories, LC

MedicalResearch: What are the main findings of the study?

Prof. Rossignol: Nitazoxanide, a new orally administered drug in development for treating influenza, reduced the duration of symptoms of uncomplicated influenza compared to a placebo. The drug also reduced viral shedding. Side effects were similar for the drug and placebo treatment arms. The study was designed and conducted in compliance with FDA guidelines for studying new drugs for influenza.
Continue reading

Flu Vaccination During Pregnancy and Infant Outcomes

MedicalResearch Interview:
Dr Nicoline van der Maas MD
Epidemiologist
National Institute for Public Health and the Environment
Centre for Infectious Disease Control
Epidemiology and Surveillance
The Netherlands

MedicalResearch: What are the main findings of the study?

Dr. van der Maas: The main finding, presented at the ESPID, is that we found no difference in growth, development and infection related contact rates with the general practitioner after the first year of life between infants of unvaccinated mothers and infants of mothers, vaccinated with an adjuvanted Influenza A (H1N1) vaccine during the second and third trimester of pregnancy.

The offer of a H1N1 vaccination to pregnant women in their second and third trimester did not have a negative impact on infants’ health during the first year of life.

Continue reading

Increased Risk of Flu-Like Illnesses After Well-Child Visits

Philip M. Polgreen, MD, MPH. Associate Professor of Internal Medicine - Infectious Diseases University of Iowa Carver College of MedicineMedicalResearch.com Interview with:
Philip M. Polgreen, MD, MPH.
Associate Professor of Internal Medicine – Infectious Diseases
University of Iowa Carver College of Medicine

MedicalResearch.com: What are the main findings of the study?

Dr. Polgreen: In this paper, to determine if well-child visits are associated with increased risk for subsequent influenza-like-illness visits, we used a large database that tracks healthcare expenditures of families over time. Controlling for other factors such as the presence of other children, insurance and demographics, we found that well-child visits were a risk factor for subsequent influenza-like-illness within the next two weeks for a patient or for a family member. The estimated probability of a subsequent influenza-like illness visit was increased by 3.2 percentage points for those with well-child visit. We estimated that this additional risk translates to over 700,000 cases of influenza-like-illness per year in the United States. Total costs (lost wages, medical costs, etc.) for these infections could amount to $500 million annually.
Continue reading

Severe Flu Associated with Younger Age, Lack of Vaccination

Dr Cameron Wolfe MBBS(Hons), MPH Assistant Professor of Medicine Clinical / Transplant Infectious Diseases Duke University Medical CenterMedicalResearch.com Interview with:
Dr Cameron Wolfe MBBS(Hons), MPH
Assistant Professor of Medicine
Clinical / Transplant Infectious Diseases
Duke University Medical Center


MedicalResearch.com: What are the main findings of the study?

Dr. Wolfe: The major findings of the study were that at least in our center, there was a significant burden of critical illness due to H1N1 influenza infection.  The average age of the patients admitted to the hospital was just 28yrs, consistent with the younger patient age in 2009 when H1N1 emerged.  Most critically, we also observed a significantly lower rate of influenza vaccine uptake in patients admitted to the Intensive Care Units at our center.
Continue reading

Flu: Vaccine For Prevention in Children

Ghassan Dbaibo, M.D., FAAP Professor and Vice-Chair for Research and Faculty Development Department of Pediatrics and Adolescent Medicine Head, Division of Pediatric Infectious Diseases Director, Center for Infectious Diseases Research Professor, Department of Biochemistry and Molecular Genetics American University of Beirut Beirut, LebanonMedicalResearch.com Interview with:
Ghassan Dbaibo, M.D., FAAP
Professor and Vice-Chair for Research and Faculty Development
Department of Pediatrics and Adolescent Medicine
Head, Division of Pediatric Infectious Diseases
Director, Center for Infectious Diseases Research
Professor, Department of Biochemistry and Molecular Genetics
American University of Beirut Beirut, Lebanon

MedicalResearch.com: What are the main findings of the study?

Dr. Dbaibo:

  • 55% efficacy (95% CI 39–67%) for prevention of all influenza
  • These results are comparable with other estimates of efficacy and effectiveness for trivalent inactivated flu vaccines in this age group
  •  73% efficacy (97.5% CI 47–86%) for prevention of moderate-to-severe influenza
  • By preventing moderate-to-severe influenza, vaccination prevented the most clinically consequential outcomes of infection, reducing hospitalisations by 75% and medical visits by 69%.
  • Seroprotection rates of more than 95% for each of the four influenza strains in the vaccine
  • An acceptable safety and reactogenicity profile
    Continue reading

Flu: Media Reporting and Competing Interests

MedicalResearch.com with:
Dr Kate Mandeville MD MPH Clinical Research Fellow, London School of Hygiene and Tropical MedicineDr Kate Mandeville MD MPH
Clinical Research Fellow, London School of Hygiene and Tropical Medicine

 


MedicalResearch.com: What is the background for your study?

Dr. Mandeville: The UK spent nearly one billion pounds on pharmaceutical drugs during the swine flu pandemic, including vaccine and antiviral drugs. After the swine flu pandemic, it was revealed that some scientists on the World Health Organization’s advisory committee had links with the pharmaceutical industry. Scientists often provide commentary for journalists on emerging health risks and we set out to see whether scientists commentating on swine flu were also more likely to have links to pharmaceutical companies. We analysed UK newspaper coverage of the swine flu pandemic between April and July 2009. This was the period in which the UK government was making decisions on how best to respond to the emerging pandemic, including providing the public with vaccine and antiviral drugs. We looked for how often scientists were quoted in articles on the pandemic from a wide range of newspapers. We then examined these comments in more detail to see if scientists made an assessment of the risk to the public from swine flu, and compared these against assessments made by official agencies like the Department of Health. We also judged whether the scientists promoted or rejected the use of vaccines or antiviral drugs. For each scientist, we then looked for links with the pharmaceutical industry – or what we formally call competing interests – from a variety of sources, including scientific papers and the internet.

Continue reading

Flu and Pediatric Deaths

MedicalResearch.com Interview with:
Karen K. Wong, MD MPH
Community Interventions for Infection Control Unit
Division of Global Migration & Quarantine
Centers for Disease Control and Prevention

MedicalResearch.com: What are the main findings of the study?

Dr. Wong: There were 830 pediatric influenza-associated deaths reported to CDC during the 2004–2005 through 2011–2012 seasons; deaths occurred in children of all ages, and 43% had no high-risk medical conditions. Of children 6 months of age or older whose vaccination status was known, only 16% had been fully vaccinated with seasonal influenza vaccine.
Continue reading

Influenza Virus Aerosols in Human Exhaled Breath: Particle Size, Culturability, and Effect of Surgical Masks

MedicalResearch.com Author Interview: Dr. Donald K. Milton, MD, Dr.P.H

dr_donalk_k_miltonDr. Donald K. Milton, MD, Dr.P.H
Professor and Director
Maryland Institute for Applied Environmental Health
University of Maryland

MedicalResearch.com: What are the main findings of the study?

Dr. Milton: We found that total viral copies detected by molecular methods were 8.8 times more numerous in fine (≤5 µm) than in coarse (>5 µm) aerosol particles and that the fine particles from cases with the highest total number of viral RNA copies contained infectious virus.

Surgical masks reduced the overall number of RNA copies by 3.4 fold.
Continue reading

Study showed Flu vaccines for nursing home workers effective in reducing outbreaks

Eurekalert Sept 12 2011

Higher flu vaccination rates for health care personnel can dramatically reduce the threat of flu outbreak among nursing home residents, according to a study published in the October issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

The study, which focused on nursing homes in New Mexico, found that when a facility had between 51 and 75 percent of its health care personnel with direct patient care vaccinated, the chances of a flu outbreak in that facility went down by 87 percent.

“The Centers for Disease Control and Prevention have long recommended that health care personnel in nursing homes get vaccinated against the flu, but we didn’t know just how much help these recommendations might be in reducing flu outbreaks among residents,” said Aaron Wendelboe of the University of Oklahoma, the lead author of the study. “We found strong evidence to support the CDC’s recommendation that to protect residents of nursing homes, health care personnel should be vaccinated annually.”

In association with the New Mexico Department of Health, Wendelboe and his team surveyed influenza rates at the state’s 75 long-term care facilities during the 2006-2007 and 2007-2008 flu seasons. They then looked for correlations between vaccination rates at each facility and whether there was an influenza outbreak.

While increased vaccination of direct care healthcare workers was associated with fewer flu outbreaks, the study found that vaccination rates among residents did not discourage outbreaks. In fact, higher resident vaccination was correlated with a higher probability of an outbreak. That result was unexpected and hard to explain, the researchers say. “While the explanation is likely multi-factorial, we suspect a large factor is that facilities with high resident vaccination rates may over-rely on the direct protection bestowed by vaccinating the residents and under-value the indirect protection bestowed by vaccinating employees,” Wendelboe and his team write.

Despite recommendations by the CDC and the Society for Healthcare Epidemiology of America, vaccination rates among U.S. healthcare workers still hover under 65 percent.

“That vaccinating health care personnel provided more protection to residents than vaccinating residents themselves underscores the importance of these recommendations,” Wendelboe said.