MedicalResearch.com Interview with:
John M. Drake, Ph.D.
Associate Professor, Odum School of Ecology
University of Georgia
Director, Population Biology of Infectious Diseases REU Site
Medical Research: What is the background for this study? What are the main findings?
Dr. Drake: Ebola virus disease is a deadly illness caused by infection with the zoonotic Ebola virus. The world's largest epidemic of Ebola virus disease is currently ongoing in West Africa, concentrated in the countries of Liberia, Sierra Leone, and Guinea. Ebola emerges in a human population after contact with an infected animal host and persists through human-to-human transmission. Persons with late stage illness are especially infectious. Ebola outbreaks are typically contained by outbreak investigation and patient isolation. But, as the current epidemic shows, containment may be very difficult to achieve in areas of high population density or where there is little health infrastructure.
During the second half of 2014, the West African nation of Liberia suffered the greatest rates of Ebola transmission. Slowing the spread of Ebola was found to be especially difficult after the virus reached the urban areas around Monrovia, particularly the township of West Point. The United States, other nations, and non-governmental organizations promised aid and developed a plan to improve Liberia's health infrastructure, but many aspects of urban Ebola transmission were then unknown, including the relative importance of hospital- and community-acquired infection, how much hospital capacity must be increased to provide care for the anticipated patient burden, and what level patient of isolation would be required to contain the outbreak. To address these issues, we developed a model for Ebola transmission that accounted for the separate sites at which infection could occur, for instance in the home, in public places (particularly at funerals), or in health facilities. Based on information available by mid-October, it was not clear whether enough was being done to contain the epidemic in Liberia. But, through public vigilance and community participation, particularly the willingness of infected persons to be treated in health facilities and to allow safe handling of the bodies of the deceased, transmission dropped dramatically in the last quarter of the year. An updated version of our model developed in early December suggests that if these gains can be maintained then the epidemic may be over by the middle of 2015. (more…)
MedicalResearch.com Interview with:
Gustavo Dayan, MD
Director, Clinical Development
Sanofi Pasteur Discovery Drive
Swiftwater, PA 18370
Medical Research: What is the background for this study? What are the main findings?
Dr. Dayan: This is the first dengue vaccine efficacy trial conducted in Latin America. The trial met its primary objective showing an efficacy of 60.8% against symptomatic VCD (virologically confirmed dengue) after a 3-dose vaccination schedule. Serotype-specific efficacy was also demonstrated against all four serotypes. Furthermore, the dengue vaccine candidate effectively reduced hospitalization due to dengue by 80.3% and severe dengue disease by 95.5% over the 25-month study period. (more…)
MedicalResearch.com Interview with:
Teresa Waters PhD
Professor and Chair, Preventive Medicine
University of Tennessee Health Science Center
Memphis TN
Medical Research: What is the background for this study? What are the main findings?
Dr. Waters: On October 1, 2008, Medicare implemented the Hospital-Acquired Conditions (HACs) Initiative, a policy penalizing hospitals for eight complications of hospital care, also known as never events. Under the HACs Initiative, hospitals could no longer justify a higher level Medicare MS-DRG when caring for a patient who developed 1 of the 8 never events. This Initiative was one in a series of CMS payment reforms intended to increase emphasis on value-based purchasing.
We found that Medicare's nonpayment policy was associated with significant improvements in the time trends for central line associated blood stream infections (CLABSIs) and catheter associated urinary tract infections(CAUTIs). For these outcomes, our data from the National Database of Nursing Quality Indicators showed that introduction of the Medicare policy was associated with an 11% reduction in the rate of change in central line associated blood stream infections and a 10% reduction in the rate of change in CAUTIs. We did not find any relationship between introduction of the policy and significant changes in injurious falls or hospital acquired pressure ulcers (two other important never events covered by the policy). We hypothesized that the Hospital-Acquired Conditions Initiative may have a great effect for conditions where there is strong evidence that better hospital processes yield better outcomes or where processes are more conducive to standardization.
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MedicalResearch.com Interview with:
Alison G Abraham PhD
Associate Scientist
Department of Epidemiology
Johns Hopkins Bloomberg School of Public Health
Medical Research: What was the motivation for this study?Dr. Abraham: HIV-infected individuals are at higher risk for kidney dysfunction compared to the general population. Prior to effective antiretroviral therapy, very aggressive forms of kidney disease were described primarily among black HIV-infected individuals. While effective therapy and increasing viral suppression rates have made HIV-associated nephropathy rare, some of these same drugs have nephrotoxic effects. In addition, the reduction in AIDS and mortality has led to HIV-infected individuals living long enough to experience age-related chronic diseases, which are also risk factors for kidney disease and end-stage renal disease. Thus we wanted to know how these competing forces were affecting end-stage renal disease risk in the well-treated HIV-infected North American population over time. Are we seeing more ESRD as a result of nephrotoxic drugs and chronic disease, or less ESRD as a result of better viral suppression and large reductions in HIV-associated nephropathy?
Medical Research: What are the main findings?Dr. Abraham: We found that end stage renal disease rates have been steadily falling over the past 10 years coincident with notable improvements in viral suppression prevalence. However a large racial discrepancy in ESRD risk has persisted even though HIV-associated nephropathy cases are now rare. While ESRD cases among blacks in our study tended to have higher viral loads and lower CD4 counts compared to non-black ESRD cases, suggesting less effective HIV treatment, we found that the racial discrepancy in ESRD risk persisted even among the well-suppressed subset, i.e. those who had undetectable viral loads for 90% of their follow-up time.
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MedicalResearch.com Interview with:
Jonathan Olsen
Institute of Primary Care and Public Health
Cardiff University Heath Park Cardiff
MedicalResearch: What is the background for this study? What are the main findings?Response: Molluscum Contagiosum is a common skin condition in children which has a prevalence of between 5.1% to 8% in children aged 14 years and under. Strikingly however, there is little epidemiological evidence describing the natural history, transmission between family members and impact upon quality of life of molluscum contagiosum. Our research aimed to address this gap in evidence by conducting a prospective cohort study of UK children recruited by clinical and self-referral using the validated Molluscum Contagiosum Diagnostic Tool for Parents (MCDTP).
We recruited 306 children during 2013 and showed that on average lesions will last for 12 months, however 30% still had lesions at 18 months and 13% still had lesions at 24 months. Most children experienced only a small effect on their quality of life from the condition, however 1 in 10 experienced a large or very large impact on their quality of life. The condition was shown to be highly contagious with further transmission between children living in the same household as an index case shown in 40%.
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MedicalResearch.com Interview with:
Anders Hviid, M.Sc., Dr.Med.Sci.
Senior Investigator, Statens Serum Institut
Medical Research: What is the background for this study?
Response: After the widespread introduction of HPV vaccination of adolescent girls, a number of safety concerns have emerged. In this case, demyelinating diseases, including multiple sclerosis, occurring after HPV vaccination has been reported in social media, news media and medical journals.
Medical Research: What are the main findings?Response: In a study of almost 4 million Danish and Swedish women, we found no support for an increased risk of multiple sclerosis or other demyelinating diseases following HPV vaccination. (more…)
MedicalResearch.com Interview with:
Melanie Blokesch PhD
Assistant Professor (tenure-track)
Laboratory of Molecular Microbiology
Global Health Institute, School of Life Sciences
Swiss Federal Institute of Technology Lausanne (EPFL)
Lausanne Switzerland
Medical Research: What is the background for this study? What are the main findings?Dr. Blokesch: We have been studying the cholera-causing bacterium Vibrio cholerae for many years in my laboratory. Our main focus has always been on elucidating how this pathogen acquires new genetic material that allows it to evolve. This is often accomplished through a mechanism known as horizontal gene transfer (HGT). There are three main modes of horizontal gene transfer in bacteria and the one we are primarily interested in is called natural competence for transformation. When the bacterium enters the state of natural competence it can take up free genetic material from its surrounding and in case it recombines this new material into its own genome the bacterium is considered to be naturally transformed. Notably, natural competence/transformation was first described in 1928 by Fred Griffith, who showed that transformation can render harmless bacteria pathogenic. These early experiments can be considered a milestone in molecular biology as it later led to the discovery of DNA as the carrier of genetic information.
Medical Research: What are the main findings?
Dr. Blokesch: The main finding of our study is that the pathogen V. cholerae does not solely rely on free DNA floating around but that it actively kills neighbouring bacteria followed by the uptake of their DNA. Indeed, we were able to show that the two processes - killing of other bacteria and DNA uptake - are co-regulated by the same proteins within the bacterial cell. We also used imaging techniques to visualize the killing of other bacteria by V. cholerae, followed by the release of their genetic material, which the predator then pulled into its own cell. We further quantified these HGT events by following the transfer of an antibiotic resistance gene from the killed bacterium to the predatory V. cholerae cell. Notably, the spread of antibiotic resistances is a major health concern and HGT is a major driver of it.
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MedicalResearch.com Interview with:
Michael G. Rossmann PhD
Hanley Professor of Biological Sciences
Hockmeyer Hall of Structural Biology
Purdue University, West Lafayette IN
Medical Research: What is the background for this study? What are the main findings?
Dr. Rossmann: My laboratory has long been interested in the structure of viruses and especially of Picornaviruses (e.g. EV-D68). We published the first 3D, near atomic resolution map of any animal virus in 1985. That was of Human Rhino (common cold) virus serotype 14. We then went on to show where and how the virus would bind to cellular receptors and also how certain small capsid binding compounds inhibited the viral infectivity. The latter was a collaboration first with the Sterling Winthrop company and later with ViroPharma. Thus our work on EV-D68 is a direct continuation of my interest in picornaviruses.
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MedicalResearch.com Interview with:
Shashank Gupta, Ph.D.
Center for Tuberculosis Research
Department of Medicine, JHU, Baltimore, Maryland, USA
Medical Research: What is the background for this study? What are the main findings?
Dr. Gupta: Verapamil is an efflux pump inhibitor drug that has been used to treat hypertension and other cardiac conditions in patients. Adding verapamil to standard tuberculosis (TB) treatment accelerates both the killing activity of the regimen in mouse model. We have recently shown in vitro that supplementing bedaquiline with verapamil profoundly decreases the MIC of bedaquiline in the wild type strain M. tuberculosis H37Rv, and also in drug-susceptible and drug-resistant clinical isolates. The MIC of another anti-mycobacterial drug clofazimine against M. tuberculosis H37Rv also decreased significantly in the presence of verapamil.
Bedaquiline is the first drug to be approved by the USFDA in last forty years for the treatment of multidrug-resistant tuberculosis (MDR-TB). Bedaquiline usage in patients presents several safety concerns including increased mortality and hepatic-related adverse drug reactions. Bedaquiline also prolongs the QT interval in patients, which is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In a phase 2 trial involving patients with advanced MDR-TB, a significantly higher number of participants receiving bedaquiline died than those receiving placebo although the causes of mortality were not directly attributable to the drug. Thus strategies to reduce the human dose of bedaquiline while retaining antibacterial activity may be valuable. We hypothesized verapamil may potentiate the killing of M. tuberculosis by bedaquiline and accelerate clearance of mycobacteria that in an in vivo infection model. Shortening treatment regimens and reducing the required doses may be a promising strategy to reduce the incidence of bedaquiline-related adverse effects and thereby improve MDR-TB treatment outcomes.
In this study, we investigated the effect of verapamil on the activity of bedaquiline against M. tuberculosis in a mouse model of TB infection. In addition to investigating the effects of verapamil on the full human bioequivalent dose of bedaquiline (25 mg/kg), we also used a sub-optimal dose of bedaquiline (12.5 mg/kg) daily, with or without verapamil to test if verapamil may potentiate the activity of bedaquiline. We have also determined if verapamil can protect bedaquiline monotherapy from the development of resistance.
Using mouse model of tuberculosis, we have shown lower doses of bedaquiline together with verapamil have the same antibacterial effect as the higher toxic doses. A lower dose of bedaquiline will cause no or less severe side effects. Verapamil also protected bedaquiline against the development of resistant mutants of the bacteria in the animals. (more…)
MedicalResearch.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.
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MedicalResearch.com Interview with:
Huachun Zou PhD on behalf of all authors.
Melbourne Sexual Health Centre, Alfred Health, Carlton, VIC,
Melbourne School of Population and Global Health
University of Melbourne, Melbourne, VIC, AustraliaMedical Research: What is the background for this study? What are the main findings?
Response: Anogenital human papillomavirus (HPV) infection and anal cancer are common among men who have sex with men (MSM) and preventable with the HPV vaccine. However, the optimal strategy for vaccinating MSM against HPV requires an accurate understanding of the age specific incidence of early HPV infection. In addition to understanding the optimal age at which to vaccinate young MSM, policy makers also need to know the vaccine coverage required in MSM. In this paper we aimed to provide estimates for the site specific incidence of HPV and to use this to estimate the probability of transmission per partner in a cohort of very young MSM aged 16 to 20 years. These data will assist governments in deciding what HPV vaccination strategy is likely to be the most effective in MSM.
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MedicalResearch.com Interview with: Dr. Peter Torre III PhDAssociate Professor, AudiologyDirector, Recreational Noise Exposure and Hearing Lab
San Diego State University
Medical Research: What is the background for this study? What are the main findings?
Dr. Torre: The primary purpose of our study was to evaluate hearing sensitivity in HIV+ and HIV- adults. And subsequently, in HIV+ adults only, to examine whether HIV disease variables or treatment was associated with hearing sensitivity.
The main findings were that HIV+ adult had poorer hearing for both the lower and higher frequencies compared with HIV- adults, although we did not find any significant associations between HIV variables and treatment variables with hearing loss.
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MedicalResearch.com Interview with:
Jared Baeten, MD PhD
Professor, Departments of Global Health and Medicine
Adjunct Professor, Department of Epidemiology
University of Washington Seattle, WA 98104
Medical Research: What is the background for this study? What are the main findings?
Dr. Baeten: The medication tenofovir disoproxil fumarate is used widely for the treatment of HIV-1 infection and, more recently, as pre-exposure prophylaxis (PrEP) to protect against HIV-1 infection for at-risk HIV-1 uninfected persons. Its use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by HIV-1 infected persons, but limited data are available for risk when used as PrEP for HIV-1 prevention.
Using data from the largest randomized, placebo-controlled trial of PrEP, among heterosexual women and men in Africa, eGFR changes were assessed during prospective follow-up in those receiving pre-exposure prophylaxis and compared to those receiving placebo. PrEP use resulted in a small (-1.59 mL/min/1.73m2, 95% CI -2.44, -0.74) but statistically significant decline in eGFR that was non-progressive over a median of 18 months and a maximum of 36 months of follow-up. PrEP use was not accompanied by a substantial increase in the risk of clinically relevant (≥25%) eGFR decline.
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MedicalResearch.com Interview with:
Femi Oshin
Consultant in Communicable Disease Control
Devon, Cornwall & Somerset PHE Centre and
Dan Murphy
Cornwall & Isles of Scilly Health Protection Team,
Cornwall, UK
Medical Research: What is the background for this study? What are the main findings?
Response: Salmonella disease are significant infections, particularly so in children. Ownership of reptiles kept as pets has risen sharply in recent years, as has Salmonella infections in children. Our study found children living in homes with a reptile as a pet are more likely to require hospitalisation from Salmonella infection, and the risk appears to increase with decreasing age of the child.
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MedicalResearch.com Interview with:
Professors Lynda A. Morrison, Ph.D. and John E. Tavis, Ph.D.
Dept. of Molecular Microbiology and Immunology
Saint Louis University School of Medicine
St. Louis, MO 63104
Medical Research: What is the background for this study? What are the main findings?
Response: A number of viruses use enzymes in the nucleotidyl transferase superfamily (NTS) to carry out their genome replication. These enzymes include the RNaseH and integrase of HIV and the RNaseH of hepatitis B virus (HBV). Herpesviruses also encode proteins with functions that are consistent with NTS enzymes. We therefore tested compounds known or suspected to inhibit the HBV RNaseH for their capacity to reduce herpes simplex virus (HSV)-1 and HSV-2 in cell culture assays. We found that certain compounds from several different chemical families could inhibit HSV replication up to 1 million-fold, and were effective down to concentrations that are already in the same range as existing anti-herpesvirus drugs. Many of the same compounds that inhibited HSV-1 and HSV-2 also inhibited another human herpesvirus, cytomegalovirus. Importantly, we showed that these new inhibitory compounds have a different mechanism of action than acyclovir, a nucleoside analog that is the standard of care. In addition, the new compounds we identified could inhibit the replication of acyclovir-resistant HSV-1 and HSV-2.
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MedicalResearch.com Interview with:
Pedro Moro MD MPH
Immunization Safety Office, Division of Healthcare Quality Promotion
National Center for Emerging and Zoonotic Infectious Diseases
Centers for Disease Control and Prevention
Medical Research: What is the background for this study? What are the main findings?
Dr. Moro: Gardasil® is a human papillomavirus (HPV) vaccine recommended for all girls and boys at age 11 or 12, and teens and young adults who did not get the vaccine when they were younger. Because there is limited safety data available on use of the vaccine during pregnancy, it is not currently recommended for pregnant women. However, some pregnant women will inadvertently receive Gardasil® because they do not yet know that they are pregnant at the time of vaccination.
The study reviewed non-manufacturer reports to the Vaccine Adverse Event Reporting System (VAERS) about pregnant women who received Gardasil®. VAERS is a national vaccine safety surveillance program co-administered by the Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA). VAERS accepts reports of health problems that occur after any US-licensed vaccine (these are called adverse events). VAERS may also accept reports not describing any health problem but vaccination errors (for example, administration of a vaccine not recommended to a particular group of people like pregnant women). VAERS is an early-warning system and cannot generally assess if a vaccine caused an adverse event.
After reviewing all non-manufacturer reports of Gardasil vaccination during pregnancy, this study found no unexpected patterns of safety issues for pregnant woman who received Gardasil®, or for their babies. This finding is reassuring and reconfirms the safety of this vaccine for pregnant women, as was previously reported by the pregnancy registry maintained by Gardasil®’s manufacturer.
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MedicalResearch.com Interview with:
David Gerberry PhD
Assistant Professor
Department of Mathematics and Computer Science
Xavier University, Cincinnati, Ohio
Medical Research: What is the background for this study? What are the main findings?Response: In an attempt to control the spread of HIV, governments in sub-Saharan Africa are considering providing antiretroviral drugs to people who do not have the virus but are at risk for becoming infected. Such drugs are known as pre-exposure prophylaxis, or PrEP. Given the cost of PrEP, an important question is how to maximize the impact of interventions given a fixed level of prevention resources.
A common strategy is to target resources to the individuals that are at the highest risk for infection. This group of people is often referred to as the "core group" and can be thought of as sex workers, clients of sex workers and other individuals that are at very high risk for infection. While targeting this core group is ideal and would result in the most cost-effectiveness interventions, being able to identify these individuals is difficult in practice and they are often unwilling to participate in the intervention; take pre-exposure prophylaxis or change their behavior for example. From a mathematical perspective it is also very difficult to quantify their increased level of risk. For example, is a sex worker at 5 times, 25 times, 100 times or 1000 times the risk for HIV infection? Without this quantification, it is impossible to estimate the cost-effectiveness of a targeted strategy.
In our work, we build an intervention strategy based on geographical targeting. This takes advantage of the fact that HIV incidence is much higher in certain geographical locations than others. Therefore, individuals in these areas are at increased risk for HIV infection. Most importantly, such an intervention is feasible because reliable data exists across much of sub-Saharan Africa for the severity of the HIV epidemic in different regions. To illustrate our ideas we used mathematical modeling to consider resource allocation in South Africa and found that targeting the provinces with highest HIV incidence would prevent 40% more infections than a plan that ignored geographic variation while using the same amount of resources.
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MedicalResearch.com Interview with:
Leonard A. Mermel DO FACP, FIDSA, FSHEA
Professor of Medicine,
Warren Alpert Medical School of Brown University and Division of Infectious Diseases,
Rhode Island Hospital Providence, Rhode Island
Medical Research: What is the background for this study? What are the main findings?Dr. Mermel: While talking to infectious diseases physicians some years ago in Israel, Greece, and Thailand, I learned that unlike my experiene here in the US, most of the bloodstream infections they see are far and away due to Gram-negative bacteria. So, a hypothesis was generated, namely that the likelihood of Gram-negative bacteremia compared to Gram-positive bacteremia was greater the closer to the equator. A writing group was formed, colleagues around the world graciously shared their data. The main finding is that in fact, we unequivocally found that the likelihood of Gram-negative, compared to Gram-positive bacteremia is more common closer to the equator. This difference was greatest during the warmer months of the year. We also found that the % GDP spent on healthcare in a given country is also associated with more Gram-negative than Gram-positive bacteremia. These findings may reflect differences in the human microbiome as one gets closer or farther from the equator as has been recently demonstrated, differences in survival of Gram-negative compared to Gram-positive bacteria under certain environmental conditions, and likely reflects differences in public health and other factors.
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MedicalResearch.com Interview with:
Thomas Wisniewski MD
Lulu P. and David J. Levidow Professor of Neurology
Professor; Director Aging and Dementia
New York University School of Medicine
Dept. of Neurology, Psychiatry and Pathology
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Wisniewski: Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. This is a relatively new prion disease that has many similarities to bovine spongiform encephalopathy which spread to humans to produce new variant Creutzfeldt-Jakob disease. Chronic wasting disease is the most infectious prion disease to date; having the potential to spread by aerosol. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. In the current study, white-tailed deer were orally inoculated with attenuated Salmonella expressing PrP, while control deer were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals were boosted orally and locally by application of polymerized recombinant PrP onto the tonsils and rectal mucosa. The vaccinated and control animals were then challenged orally with CWD-infected brain homogenate. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a significant prolongation of the incubation period (median survival 909 days; p=0.012 by Weibull regression analysis) and one deer has remained CWD free both clinically and by RAMALT and tonsil biopsies. This negative vaccinate has the highest titers of IgA in saliva and systemic IgG against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrPCWD. We document the first partially successful vaccination for a prion disease in a species naturally at risk.
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MedicalResearch.com Interview with:
Ann J. Melvin MD, MPH
Division of Pediatric Infectious Disease
Department of Pediatrics
Seattle Children's Hospital, Seattle, WA 98105.
Medical Research: What is the background for this study? What are the main findings?
Dr. Melvin: While relatively uncommon, neonatal Herpes Simplex Virus is a potentially devastating infection with significant morbidity and mortality. We reviewed all of the neonatal HSV cases treated at our institution between 1993 and 2012 who had HSV DNA PCR results available from the plasma and/or CSF. Most of the infants had quantitative PCR results available. The objective of the study was to determine the clinical correlation of HSV PCR levels in the plasma and CSF. We found a clear association between the plasma HSV level, clinical presentation and mortality. All of the infants who died had HSV plasma DNA levels of greater than 7 log10 copies/ml. However, neither plasma nor CSF HSV levels predicted neurologic outcome. Clinical evidence of CNS disease was more predictive of neurologic outcome than was the CSF PCR level. We also showed the most sensitive test for diagnosis of neonatal HSV to be HSV PCR on the plasma. However, no single test diagnostic test (plasma PCR, CSF PCR, surface cultures) was positive across all infants, so it is important to obtain samples from plasma, CSF and surface swabs in infants with symptoms consistent with HSV infection.
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MedicalResearch.com Interview with: Adrian Egli, MD PhD Research Group leader
Infection Biology Laboratory
Department of Biomedicine
University of Basel and University Hospital Basel
Basel, Switzerland
Medical Research: What is the background for this study? What are the main findings?
Dr. Egli: Infections with influenza viruses are associated with a high morbidity and mortality. In particular, people with a weak immune system are at danger for more severe complications. This includes elderly people, pregnant women, patients after transplantation, patients with HIV infection, chronic diseases such as diabetes and many more. In these high-risk groups, annual vaccination is clearly recommended.
However, due to the immunsuppressive condition the immune response to the influenza vaccine is often reduced. The seroconversion rate - a 4-fold antibody titer increase upon vaccination - is one of the key markers for a successful vaccination. In young adults the seroconversion rate is normally >85%; however, in patients with immunosuppression, this can be lower than 40%. Improving vaccine efficacy is one of the key focuses of my research group. We try to understand, how to improve vaccines and better protect the people at the highest risks for influenza-associated complications.
In this study, we could show that an important cytokine, called Interferon lambda, is clearly associated with the vaccine induced antibody response upon influenza vaccination. We could show that genetic polymorphisms, in one of the Interferon lambda gene family (IFNL3), are modulating the expression of this gene. This strongly affects the cross talk between the innate and adaptive immune response in the context of vaccination. We observed that, the more Interferon lambda is present, the lower the antibody response is. People with a lower expression of Interferon lambda had a significant higher response to the vaccine. Therefore, we developed substances to block the effect of Interferon lambda. We could show in vitro, that due to the Interferon lambda blockade, the antibody production was improved.
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MedicalResearch.com Interview with:
Leah M. Smith PhD
Department of Epidemiology, Biostatistics, and Occupational Health (Smith, Kaufman, Strumpf)
McGill University, Montréal, Quebec
Medical Research: What is the background for this study? What are the main findings?
Dr. Smith: The human papillomavirus (HPV) vaccine protects against types of HPV that cause cervical cancer and anogenital warts. The vaccine first became available in 2006. Since then, it has faced a great deal of controversy surrounding, in part, some of the unanswered questions about the real-world effects of the vaccine, especially on the young girls targeted for immunization. One issue that has received a great deal of public attention has been the concern that HPV vaccination might give girls a false sense of protection against all sexually transmitted infections that might lead them to be more sexually active than they would otherwise. As a result, some parents have been reluctant to have their daughters vaccinated. It is also reason why some religious groups have spoken out against the vaccine. This question is further important from a public health perspective because increases in risky sexual behaviour would inevitably also lead to increases in teen pregnancy and sexually transmitted infections (excluding anogenital warts), which would of course undermine the potential health benefits of the vaccine.
In this study, we directly addressed the question of whether HPV vaccination has led to increases in pregnancy and non-HPV-related sexually transmitted infections (both of which are proxies for risky sexual behaviour) among adolescent girls.
In our study of over 260,000 girls, we did not find any evidence that the HPV vaccine had a negative impact on these outcomes.
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MedicalResearch.com Interview with:
Dr. Michael Yeaman Ph.D.
Professor of Medicine, Infectious Disease Specialist
Chief, Division of Molecular Medicine
David Geffen School of Medicine at UCLA
Los Angeles Biomedical Research Institute
Harbor-UCLA Medical CenterMedical Research: What is the background for this study? What are the main findings?Dr. Yeaman: In the U.S. and around the globe, skin and soft tissue infections caused by
methicillin-resistant Staphylococcus aureus (MRSA) continue to endanger the
health and lives of patients and otherwise healthy individuals. Treatment is
difficult because MRSA is resistant to many antibiotics, and the infections
can recur, placing family members and other close contacts at risk of
infection.
Infectious disease specialists at the Los Angeles Biomedical Research
Institute at Harbor-UCLA Medical Center (LA BioMed) tested a new
investigational vaccine, NDV-3, and found it holds new hope for preventing
or reducing the severity of infections caused by the "superbug" MRSA.
In the study, which was published Dec. 8 in the Proceedings of the National
Academy of Sciences USA, the researchers reported that NDV-3, employing the
recombinant protein Als3, can mobilize the immune system to fight off MRSA
skin infections in an experimental model. The researchers found the vaccine
works by enhancing molecular and cellular immune defenses of the skin in
response to MRSA and other S. aureus bacteria in disease models.
This is the first published study to demonstrate the effectiveness of a
cross-kingdom recombinant vaccine against MRSA skin infections. NDV-3 is
unique as it is the first vaccine to demonstrate it can be effective in
protecting against infections caused by both S. aureus and the fungus
Candida albicans. NDV-3 represents a novel approach to vaccine design that
pioneers an approach termed convergent immunity.
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MedicalResearch.com Interview with:
Jack A Gilbert PhD
Department of Ecology & Evolution
Graduate Program in Biophysical Sciences
University of Chicago, Chicago, IL 60637
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Gilbert: We have performed extensive analysis of the microbial distribution between humans and home surfaces in peoples houses. And are still exploring how bacteria are distributed around hospitals. Here we wanted to explore how bacteria from humans were distributed into a space in real time. By taking samples every hour post sterilization and seeing how the community stabilized, who remained active and whether they were pathogenic. We found that communities stabilized on a skin-associated microbiome within 5 hours, that staphylococcus remained active and yet none of these were particularly pathogenic. Yet we were able to identify pathogenic MRSA on surfaces around the bathroom, but they were extremely rare.
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MedicalResearch.com Interview with:
Victoria Vaughan
Medical College of Georgia, Augusta, Georgia
Medical Research: What is the background for this study? What are the main findings?Response: The Global Mortality of Skin Disease study compares age adjusted mortality of disease with skin manifestations between developing and developed countries for the years 1990 and 2010. The main findings were that mortality from infectious conditions was greater in the developing world while melanoma contributed to mortality in the developed world. Ebola Virus Disease has cutaneous manifestations and affects the developing world preferentially. As of November 27, 2014, the mortality in West Africa totals 5444 according to the CDC. However, the United States has had only two deaths from Ebola Virus Disease.
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MedicalResearch.com Interview with: Heather Bradley, PhD
Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
Medical Research: What is the background for this study? What are the main findings?Dr. Bradley:The key to controlling the HIV epidemic is controlling the virus. When used consistently, antiretroviral medication can keep HIV controlled at very low levels in the body (known as viral suppression), allowing people with HIV to live longer, healthier lives and reducing the likelihood they will transmit HIV to others. Yet, only one-third of the 1.2 million people with HIV in the U.S. have the virus under control. Among those who did not have the virus under control, approximately two-thirds had been diagnosed but were not in medical care.
Young people were least likely to have the virus under control. Only 13 percent of 18 – 24 year olds were virally suppressed, primarily because half don’t know they are infected. To close this gap among young people, increased HIV testing is critical.
The study did not find statistically significant differences in viral suppression by race or ethnicity, sex, or risk group.
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MedicalResearch.com Interview with:
Dr. John K. DiBaise MD
Gastroenterology and Hepatology
Mayo Clinic, Scottsdale Arizona
Medical Research:What is the background for this study? What are the main findings?Dr. DiBaise: Despite nearly 25 years of safe and effective use of proton pump inhibitors (PPI), in recent years there have been an increasing number of reports suggesting potentially harmful effects and harmful associations with their use. One such association with PPI use has been Clostridium difficile infection (CDI) which can cause severe and recurrent episodes of diarrhea. Previous reports evaluating the microbes present within the gastrointestinal tract (ie, gut microbiome) of individuals with CDI have shown a reduction in overall microbial community diversity. We studied the gut microbiome in healthy individuals both before and after using a proton pump inhibitors for one month and found a similar reduction in microbial diversity while taking the PPI that did not entirely revert back to the ‘normal’ baseline after being off the medication for a month. While this does not demonstrate a causal association between proton pump inhibitors use and CDI, it demonstrates that PPI use creates a situation in the gut microbial environment that may increase the individual’s susceptibility to CDI.
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MedicalResearch.com Interview with:
Christina Nelson, MD, MPH, FAAP
Medical Epidemiologist
Centers for Disease Control and Prevention
Division of Vector-Borne Diseases | Bacterial Diseases Branch
Fort Collins, CO
Medical Research: What is the background for this study? Dr. Nelson: Evidence-based guidelines for the diagnosis and treatment of Lyme disease have been provided by the Infectious Diseases Society of America for many years. These comprehensive guidelines have been vetted by external review panels as the best option for patient care. In endemic areas, patients with the typical rash (erythema migrans) can be diagnosed with Lyme disease clinically. Otherwise, the guidelines recommend that diagnosis be based on a history of possible exposure, compatible clinical features, and positive two-tier serologic testing.
Some patients who have been treated for Lyme disease may develop post-treatment Lyme disease syndrome (PTLDS) – fatigue, arthralgias, or other symptoms that persist after completing antibiotic treatment. Although the exact cause of post-treatment Lyme disease syndrome is unknown, it is thought to be due to an altered immune response or residual damage to tissues during the acute infection. A diagnosis of exclusion, PTLDS should only be diagnosed after the patient has been thoroughly evaluated and other potential causes of symptoms ruled out.
On the other hand, “chronic Lyme disease” is a loosely defined diagnosis that has been used to describe a variety of ailments. A small cadre of providers use unconventional methods to diagnose patients with chronic Lyme disease, and sometimes there is no objective evidence that the patient ever had Lyme disease. Multiple factors contribute to this phenomenon, including misconceptions about serologic testing, use of unvalidated diagnostic tests, and clinical diagnosis of Lyme disease based on nonspecific symptoms alone.
We know that patients have been – and continue to be – harmed by treatments for chronic Lyme disease. Patients have suffered from emboli, severe allergic reactions to antibiotics, neutropenia, and infections such as Clostridium difficile. This is terrible and should never happen. However, there is another important danger related to these alternative practices. Some patients who have been diagnosed and treated for chronic Lyme disease later discover that another condition is the root of their physical problem. We wanted to highlight some of these cases in order to help educate providers and patients about this issue.
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MedicalResearch.com Interview with:
Dr. Martin Thornhill PhD
Department of Cardiology, Taunton and Somerset NHS Trust
Taunton, Somerset, UK
Medical Research:What is the background for this study? What are the main findings?Dr. Thornhill: In 2008 NICE introduced controversial new guidance recommending that antibiotic prophylaxis to prevent infective endocarditis should no longer be used. It was a rational decision, given the evidence for the effectiveness of antibiotic prophylaxis and potential concerns about costs, the development of antibiotic resistance and possible side effects from antibiotics, but it went against other guidelines from around the world that existed at the time.
The main findings are that in England:
There has been a large and significant decline in the use of antibiotic prophylaxis.
There has been a significant increase in the number of cases of infective endocarditis, above the baseline trend, using hospital coding data, corrected for changes in the size of the English population.
MedicalResearch.com Interview with:Dr. Raquel Qualls-Hampton MD, MS
Assistant Professor
University of North Texas Health Science Center
Medical Research: What is the background for this study? What are the main findings?Dr. Qualls-Hampton: There are currently two vaccines approved by the Food and Drug Administration (FDA)—Gardasil for males and Gardasil and Cervix for females – that protect against the human papilloma virus (HPV). These vaccines are recommended by the ACIP for females ages 9 to 26 years and males ages 9 to 21 years. Both vaccines protect males and females against some of the most common types of HPV. HPV vaccines are administered in three doses over six months and are considered safe and effective. However, the promise of these vaccines is going unfulfilled as initiation and completion rates for the three doses are suboptimal among females and males.
Nationally, although HPV vaccination initiation coverage is increasing, overall vaccine completion rates are at suboptimal levels and below the U.S. Department of Health and Human Services’ Healthy People 2020 initiative target of 80%. Thus, many states are turning to legislative interventions in efforts to increase initiation and completion rates. This study examines HPV vaccination legislative initiatives and their impact, specifically in estimating state legislation’s effects on HPV vaccine initiation, completion and patient care provider recommendations by gender.
(more…)
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MedicalResearch.com Interview with:
John M. Drake, Ph.D.
Associate Professor, Odum School of Ecology
University of Georgia
Director, Population Biology of Infectious Diseases REU Site
Medical Research: What is the background for this study? What are the main findings?
Dr. Drake: Ebola virus disease is a deadly illness caused by infection with the zoonotic Ebola virus. The world's largest epidemic of Ebola virus disease is currently ongoing in West Africa, concentrated in the countries of Liberia, Sierra Leone, and Guinea. Ebola emerges in a human population after contact with an infected animal host and persists through human-to-human transmission. Persons with late stage illness are especially infectious. Ebola outbreaks are typically contained by outbreak investigation and patient isolation. But, as the current epidemic shows, containment may be very difficult to achieve in areas of high population density or where there is little health infrastructure.
During the second half of 2014, the West African nation of Liberia suffered the greatest rates of Ebola transmission. Slowing the spread of Ebola was found to be especially difficult after the virus reached the urban areas around Monrovia, particularly the township of West Point. The United States, other nations, and non-governmental organizations promised aid and developed a plan to improve Liberia's health infrastructure, but many aspects of urban Ebola transmission were then unknown, including the relative importance of hospital- and community-acquired infection, how much hospital capacity must be increased to provide care for the anticipated patient burden, and what level patient of isolation would be required to contain the outbreak. To address these issues, we developed a model for Ebola transmission that accounted for the separate sites at which infection could occur, for instance in the home, in public places (particularly at funerals), or in health facilities. Based on information available by mid-October, it was not clear whether enough was being done to contain the epidemic in Liberia. But, through public vigilance and community participation, particularly the willingness of infected persons to be treated in health facilities and to allow safe handling of the bodies of the deceased, transmission dropped dramatically in the last quarter of the year. An updated version of our model developed in early December suggests that if these gains can be maintained then the epidemic may be over by the middle of 2015. (more…)
