MedicalResearch.com Interview with: Lorena Espinoza Center for Disease Control MedicalResearch: What is the background for this study? What are the main findings? Response: Men...
MedicalResearch.com Interview with:
Marc Brisson
Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease
Associate Professor, Université Laval
Medical Research: What is the background for this study? What are the main findings?
Response: Since 2007, 52 countries have implemented human papillomavirus vaccination (HPV) programmes. Two HPV vaccines are currently available worldwide: the bivalent vaccine, which targets HPV types 16 and 18, causing 70-80% of cervical cancer, and the quadrivalent vaccine, which also targets HPV types 6 and 11, associated with 85-95% of anogenital wart cases. Large international randomised controlled clinical trials have shown both vaccines to be safe, well tolerated and highly efficacious against vaccine-type persistent infections and precancerous cervical lesions. Furthermore, both vaccines have shown some level of cross-protection against 3 HPV types (HPV 31, 33 and 45) not included in the vaccine and associated with a supplementary 10-15% of cervical cancers worldwide. Now that 7 years have elapsed since the implementation of the first HPV vaccination program, we verified whether the promising results from clinical trials are materialising at the population level. We conducted a meta-analysis to examine the population-level impact in countries that have introduced HPV vaccination programs.
In countries with high female vaccination coverage (<50%), our main findings indicate:
MedicalResearch.com Interview with:
Dr. Michael Farzan PhD
Vice Chairman
Department of Immunology and Microbial Science
Florida Campus
The Scripps Research Institute
Medical Research: What is the background for this study?
Dr. Farzan: The key points are that HIV-1 needs two receptors – CD4 and CCR5 – to infect cells. CD4’s primary job is to initially bind the viral entry protein, which upon CD4 binding, uncloaks its CCR5 binding site. A number of years ago we observed that CCR5 had an unusual modification that was really important to HIV-1. We later showed that antibodies – protein your body makes to protect from pathogens – mimics CCR5 by incorporating this modification. We develop a peptide from one of these antibodies that mimics CCR5.
Medical Research: What are the main findings?
Dr. Farzan: By combined a soluble form of CD4 with this CCR5-mimicking peptide, we created a protein that neutralizes all HIV-1 isolates tested, including the hardest-to-stop viruses, as well as distantly related viruses found in monkeys. It does so better than the best HIV-1 antibodies. We expressed this protein using a commonly used gene-therapy vector, and showed that after a one-time inoculation we could protect from doses much higher than most humans are likely to see, and we did so 34 weeks after the inoculation.
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MedicalResearch.com Interview with:
Shyamasundaran Kottilil MBBS, PhD
Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
Medical Research: What is the background for this study? What are the main findings?
Dr. Kottilil: Due to shared routes of transmission, almost half of all HIV-infected patients also have HCV infection. Traditionally, interferon based therapies have resulted in lower cure rates of HCV in HIV-infected subjects. Treatment for HCV is rapidly changing from an injection (interferon) based therapy to oral well tolerated pill based therapy for a shorter duration.Our intention was to test whether a treatment regimen without the use of interferon and ribavirin can be effective in HIV/HCV infected patients.
Our study demonstrated that HIV/HCV connected patients without cirrhosis can be effectively treated with ledipasvir and sofosbuvir in 12 weeks. Overall 98% of patients were cured.
(more…)MedicalResearch.com Interview With Jacek Skarbinski, MD Medical officer Centers for Disease Control and Prevention MedicalResearch: What is the background for this study? What are...
MedicalResearch.com Interview with:
Elmar A. Joura, M.D
Gynecologist
University of Vienna
MedicalResearch: What are the main findings of this study?
Dr. Joura: This study demonstrates that the new ninevalent HPV vaccine induces a good immunogenicity against HPV 6/11/16/18 and gives a 97% protection against disease caused by HPV 31/33/45/52/58. This has a potential of a 90% reduction of cervical cancer and other HPV related cancers and a similar protection against genital warts. The full benefit is seen in persons without current HPV infection, this reinforces early vaccination against HPV. The safety profile was favourable.
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MedicalResearch.com Interview with:
Dr. Masae Kawamura MD
Senior Director, QuantiFERON Medical and Scientific Affairs QIAGEN
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Kawamura: The report in The Lancet presents the baseline phase of China’s first large-scale, multi-center prospective study of the epidemiology of latent tuberculosis infection. The comparison study of more than 21,000 patients allowed detailed analysis of demographics and risk factors, along with robust comparisons within subgroups. The study’s follow-up phase is now underway, and patients with Latent Tuberculosis Infection (LTBI) will be evaluated for rates of disease and associated risks. Generally, up to 10% of people with Latent Tuberculosis Infection will develop active, contagious Tuberculosis (TB) disease at some point.
The overall TB infection rate was 18.8% measured by QuantiFERON-TB Gold compared to 28% by the traditional tuberculin skin test (TST), a difference of over 125 million people (based on 2014 population estimates from China). Unlike the tuberculin skin test, positive rates of QuantiFERON-TB Gold were not related to prior Bacille Calmette-Guérin (BCG) vaccination, but correlated with background active TB and suspect rates, as well as known risks for TB. BCG vaccination is recommended to newborns by the World Health Organization (WHO) as a matter of TB control policy in many countries, including China. (more…)
MedicalResearch.com Interview with:
Seema Jain, MD
Medical Epidemiologist
Epidemiology and Prevention Branch, Influenza Division
Centers for Disease Control and Prevention
Atlanta, GA 30329
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Jain: Pneumonia is the leading cause of hospitalization among children in the United States with medical costs estimated at almost $1 billion in 2009. The Centers for Disease Control and Prevention’s Etiology of Pneumonia in the Community (EPIC) study was a multi-center, active population-based surveillance study that aimed to estimate the incidence and etiology of community-acquired pneumonia requiring hospitalization in U.S. children. Children in the study were enrolled from January 2010 to June 2012 in three U.S. children’s hospitals in Memphis, Nashville, and Salt Lake City. Study staff tested children using a range of laboratory tests for viral and bacterial respiratory pathogen detection.
During the study period, the EPIC study team enrolled 2,638 children, of which 2,358 (89 percent) had radiographically-confirmed pneumonia. The median age of children in the study was 2 years old. Intensive care was required for 497 (21 percent) of the children, and three children died. Among 2,222 children with radiographic pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 1802 (81%). One or more viruses were detected in 1,472 (66%) of these children. Bacteria were detected in 175 (8%), and bacterial and viral co-detection occurred in 155 (7%). The study estimated that annual pneumonia incidence was 15.7/10,000 children during the study period. The highest incidence was among children younger than 2 years old (62.2/10,000). Respiratory syncytial virus (RSV) was the most common pathogen detected (28%), and it was associated with the highest incidence among children younger than 2 years old with pneumonia. Human rhinovirus was detected in 22 percent of cases, but it was also identified in 17 percent of asymptomatic controls who were enrolled, by convenience sample, at the same site during the same time period; thus, making it challenging to interpret the meaning of human rhinovirus detection in children hospitalized with pneumonia. Other detected pathogens were human metapneumovirus (13%), adenovirus (11%), Mycoplasma pneumoniae (8%), parainfluenza viruses (7%), influenza (7%), coronaviruses (5%), Streptococcus pneumoniae (4%), Staphylococcus aureus (1%), and Streptococcus pyogenes (<1%). The low prevalence of bacterial detections likely reflects both the effectiveness of bacterial conjugate vaccines and suboptimal sensitivity of bacterial diagnostic tests. (more…)
MedicalResearch.com Interview with:
Fernanda C. Lessa, M.D., M.P.H.
Centers for Disease Control and Prevention
Atlanta, GA
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Lessa: The epidemiology of Clostridium difficile has gone through dramatic changes over the last decade. C. difficile has become the most common cause of healthcare-associated infections in US hospitals and it has been also increasingly reported outside of healthcare settings. As the epidemiology of this pathogen changes, it is important to understand the magnitude and scope of this infection in the United States to help guide priorities for prevention.
Main findings:
1) C. difficile was responsible for almost half million infections and associated with 29,000 deaths in 2011 in the United States
2) Among the patients who developed C. difficile, 83,000 had recurrent infections
3) C. difficile incidence was higher among females, whites, and persons 65 years of age or older
4) Approximately 345,400 infections occurred outside of the hospital indicating that C. difficile prevention should go beyond hospital settings.
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MedicalResearch.com Interview with:
Robert M Centor, MD, MACP
Chair ACP Board of Regents
Regional Dean, UAB Huntsville Regional Medical Campus
Huntsville, AL 35801
Professor, General Internal Medicine
UAB Birmingham, AL 35294-3407
Medical Research: What is the background for this study? What are the main findings?
Dr. Centor: European researchers have shown that Fusobacterium necrophorum, an obligate gram-negative anaerobe, likely causes approximately 10% of young adult pharyngitis. This same organism is the major cause of peritonsillar abscess in the age group (and this age group has the highest rate of peritonsillar abscess). The organism also causes around 80% of the Lemierre Syndrome. We knew of no US data evaluating the role of this bacteria as a cause of pharyngitis. The European studies also did not report the signs and symptoms of Fusobacterium pharyngitis. (more…)
MedicalResearch.com Interview with:
Dr. Cornejo-Juárez
Department of Infectious Disease,
Instituto Nacional de Cancerología
Tlalpan Mexico
MedicalResearch: What is the background for this study?
Dr. Cornejo: Critically ill patients in the intensive care unit are at major risk of hospital-acquired infections. Immunosuppressed patients have a higher risk related with continuous exposure to the hospital setting, mucositis and disruption of skin integrity, presence of indwelling catheters and abnormal immune system because of primary malignancy or chemotherapy. Our aimed was to investigate prevalence and outcome of hospital-acquired infections in an oncology ICU.
MedicalResearch: What are the main findings?
Dr. Cornejo: We found that hospital-acquired infections are a major problem in the ICU. Hospital-acquired infections are related with higher mortality. Multidrug resistant bacteria are frequently involved in these infections, and are associated with increased mortality.
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MedicalResearch.com Interview with:
Elmi Muller, M.B., Ch.B., M.Med.
University of Cape Town–Surgery
Groote Schuur Hospital Observatory Cape Town
Cape Town, South Africa
Medical Research: What is the background for this study?
Dr. Muller: South Africa currently offers dialysis and transplantation as a treatment option for patients with End Stage Renal Disease (ESRD). However, dialysis is not freely available to everyone, but severely limited and only available to a selected group of patients. This means that patients get assessed when they present with ESRD and they only get accepted onto a dialysis programme if they fulfill certain criteria. These criteria are criteria to assess the patient’s medical fitness in general as well as social criteria to assess whether the patient will be compliant with follow-up. In most state hospitals, patients will only be accepted onto a dialysis program if they are also fit to receive a transplant in the long run. The idea is that dialysis programs should naturally feed into transplant programs. Therefore a patient who is not a suitable transplant candidate will normally be turned down for dialysis.
In 2008, when the HIV positive-to-positive program started, patients with ESRD and HIV would be turned down for dialysis. The reason was that they were seen as unfit for transplantation and therefore not suitable dialysis patients. This meant that anybody with HIV and ESRD was doomed to die. This situation remained unchallenged for a number of years, especially as the rollout of antiretroviral therapy was quite slow in the state sector.
Because of very high HIV rates in the country, more and more HIV positive brain-dead donors presented to the Groote Schuur Hospital Transplant team. These donors were mostly braindead people who were worked up for organ donation (after consent was obtained from the family) and who then turned out to be HIV positive. In 2008 it made sense to try and marry this supply of donors with the group of HIV positive patients without any treatment options in the country.
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MedicalResearch.com Interview with:
Meghan F. Davis, DVM MPH PhD
Assistant Professor
Department of Environmental Health Sciences
Johns Hopkins Bloomberg School of Public Health
Medical Research: What is the background for this study? What are the main findings?
Dr. Davis: Asthma rates have been on the rise, particularly in children. Interventions targeted at allergens and other environmental factors known to exacerbate asthma are only partially successful, suggesting a role for novel drivers of morbidity among existing patients with asthma. In this study, we evaluated associations between nasal colonization with the bacterium Staphylococcus aureus and symptoms related to wheeze and asthma using data from the nationally-representative NHANES database. We found that S. aureus nasal colonization was associated with asthma symptoms in children and young adults, but not in older adults.
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MedicalResearch.com Interview with:
Prof Jean-Michel Molina
Maladies Infectieuses et Tropicales, Hôpital
Saint-Louis, Paris France
Medical Research: What is the background for this study? What are the main findings?
Prof. Molina: Treatment of co-infected patients is complicated by drug drug interactions with HIV drugs, and the news DAAs are not very potent on HCV G2 and 3 infections.
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Dr Matthew R Moore, MD
National Center for Immunization and Respiratory Diseases,
Centers for Disease Control and Prevention, Atlanta, GA, USA
MedicalResearch: What is the background for this study?
Dr. Moore: Since introduction, pneumococcal conjugate vaccines have resulted in dramatic decreases in the number of cases of invasive pneumococcal disease in both children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine infant immunization program in the United States in 2000. It was recommended for infants using a 4-dose schedule: 2, 4, 6, and 12 through 15 months of age. Studies showed that PCV7 was highly effective in preventing invasive pneumococcal disease. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 using the same 4-dose schedule. PCV13 is similar to PCV7, but includes protection against six additional serotypes of Streptococcus pneumoniae. There are more than 90 serotypes of pneumococcal bacteria.
Streptococcus pneumoniae, or pneumococcus, is a major cause of illness and death globally. Pneumococcus can cause many types of illness that ranging from mild to life-threatening, including pneumonia, ear and sinus infections, meningitis, and bacteremia. Some of these infections are considered invasive because they invade parts of the body that are normally free from bacteria. Invasive pneumococcal disease, including meningitis and bacteremia, is often severe and can be deadly.
MedicalResearch: What are the main findings?
Dr. Moore: Invasive pneumococcal disease decreased substantially in the first 3 years after PCV13 was introduced into the U.S. infant immunization schedule. By June 2013, more than 30,000 cases of invasive pneumococcal disease and 3,000 deaths are estimated to have been prevented in the United States due to PCV13. Children under the age of five, which is the age group that actually received the vaccine, experienced the greatest and quickest benefit from PCV13. For example, the overall number of cases of invasive pneumococcal disease decreased by 64% in this age group between 2010 and 2013. Significant decreases were seen as early as six months after the immunization recommendation was made.
Adults, who were not targeted for vaccination, also experienced health benefits from PCV13 introduction. For example, the overall number of cases of invasive pneumococcal disease decreased by 32% for adults aged 18 to 49 years, while adults 65 and older experienced a more modest 12% decrease. These reductions are further evidence that both PCV7 and PCV13 reduce the spread of pneumococcus, which is why vaccinating children leads to disease reductions in adults.
For both children and adults, the greatest reductions were seen in the number of cases of invasive pneumococcal disease that were caused by serotypes that are covered by PCV13 but not PCV7 (serotypes 19A and 7F specifically).
(more…)MedicalResearch.com Interview with: Byron Caughey, PhD Senior Investigator Rocky Mountain Laboratories National Institute for Allergy and Infectious Diseases National Institutes of Health Hamilton, Montana 59840 MedicalResearch: What...
MedicalResearch.com Interview with:
Samuel Dominguez MD
Departments of Pediatric Infectious Diseases
Children's Hospital Colorado and University of Colorado School of Medicine Aurora, CO
Medical Research: What is the background for this study? What are the main findings?
Dr. Dominguez: Due to global poliovirus eradication efforts, clusters of acute flaccid paralysis (AFP) and/or cranial nerve dysfunction in children are rare and associated with few pathogens, primarily enteroviruses and flaviviruses. Our study reports the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of EV-D68 respiratory illness, strengthening the potential link between EV-D68 and neurologic disease in children.
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MedicalResearch.com Interview with:
Douglas B. Jacobs B.S., MD/MPH Candidate
Harvard T.H. Chan School of Public Health
Medical Research: What is the background for this study?
Response: In May 2014, a formal complaint submitted to the Department of Health and Human Services contended that four Florida insurers were structuring their formularies in a way that discouraged enrollment from HIV positive beneficiaries. These insurers placed all HIV drugs, including generics, on the highest cost-sharing tiers.
This formal complaint served as the impetus for this research. We wanted to discover if this was a phenomenon that was isolated to Florida, or if it was national in scope, and what the implications would be for HIV positive beneficiaries. As such, we analyzed what we called “adverse tiering”—in which all drugs for certain conditions are placed in the highest cost sharing tiers—in 12 states in the federal marketplace. We compared cost-sharing for a commonly prescribed class of HIV medication, called Nucleoside Reverse Transcriptase Inhibitors, or NRTIs.
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MedicalResearch.com Interview with:
Rakesh K. Jain, Ph.D.
A.W.Cook Professor of Tumor Biology
Director, E.L. Steele Laboratory
Department of Radiation Oncology
Harvard Medical School and
Massachusetts General Hospital Boston, MA 02114
Medical Research: What are the primary findings of this study and why are they important?
Dr. Jain: Pulmonary granulomas are the hallmark of the Tuberculosis (TB) infection, yet it is not fully understood how these structures contribute to disease progression and treatment resistance. In this study, we applied our insight in tumor biology – gained over three decades – to explore and exploit the similarities between vasculature (blood vessel network) in solid cancerous tumors and TB pulmonary granulomas. We demonstrate for the first time that TB granulomas have abnormal vasculature. This abnormality provides a mechanism for the observation that TB granulomas are often hypoxic (have low oxygen conditions) and have differential distribution of anti-TB drugs. We showed that bevacizumab, a widely prescribed anti-VEGF antibody for cancer and eye diseases, is able to create more structurally and functionally normal granuloma vasculature and improve small molecule delivery. This study suggests that vasculature normalization in combination with anti-TB drugs has the potential to enhance treatment in patients with TB.
Tuberculosis (TB) is a global scourge that is responsible for nearly 2 million deaths annually. Due to the inability of currently available treatment regimens to eradicate this devastating disease, it is clear that new treatment strategies are urgently needed. Unlike many researchers in the TB field, we do not seek to discover new therapeutics that target bacterial resistance; instead, we strive to overcome physiological resistance to treatment resulting from abnormalities in the granuloma vasculature that impair drug delivery and create hypoxia that impairs efficacy of drugs and immune system. By using an FDA-approved drug, our study has the potential to be rapidly translated into the clinic.
Medical Research: Has any association previously been made between the vascular structure of TB granulomas and the challenges of treating TB – both the fact that treatment takes so long and the development of multidrug resistance?
Dr. Jain: Our study is the first to implicate a specific facet of the granuloma – the abnormal vasculature – as a potential contributor to disease progression and treatment resistance. Granuloma hypoxia is known to negatively affect the local immune system while conferring resistance to some of the TB drugs. Our collaborators have shown that different anti-TB drugs have differential abilities to penetrate the granuloma structure, especially to the interior granuloma regions where the TB bacteria are found in greatest numbers. Our study is the first to provide evidence that by modulating the granuloma vasculature, hypoxia can be alleviated and drug delivery can be improved.
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MedicalResearch.com Interview with:
Christopher S. Sullivan, Ph.D.
Associate Professor
Dept. Molecular Biosciences
The University of Texas at Austin and
Jennifer Cox, lead author
Graduate student in Dr. Sullivan’s laboratory.
Jennifer Cox's Replies:
MedicalResearch: What is the background for this study? What are the main findings?
Jennifer Cox: In the last decade, researchers have identified that many viruses encode small regulatory molecules known as microRNAs. Some viral microRNAs are able to manipulate host processes including stress responses, proliferation, and cell death. However, there are many viral microRNAs with unknown functions. Many of the viruses that encode microRNAs are associated with severe pathologies including various cancers so understanding the role of viral microRNAs can shed light on virus biology.
For this study, we focused on identifying viral microRNAs that can regulate innate immune signaling for several reasons. First, all viruses have proteins to combat interferon signaling. Second, we have identified microRNAs from two diverse viruses (retro and annello) that can inhibit interferon signaling so we hypothesized that additional viral microRNAs will perform this same function. We screened ~70 viral microRNAs for the ability to regulate innate immune signaling and identified three herpesviruses, Epstein-Barr Virus, Kaposi’s Sarcoma Associated Virus, and Human Cytomegalovirus, that inhibit the interferon response.
Epstein-Barr Virus, causes an estimated 200,000 cancers every year, including lymphomas, nasopharyngeal cancers and some stomach cancers. Interestingly, most of these cancers harbor latent EBV – a state of limited gene expression that produces no virus. microRNAs are one of the few viral gene product expressed during latency.
Our further work identified that Epstein-Barr Virus, KSHV, and Human Cytomegalovirus have converged to inhibit interferon signaling in the same manner – through decreasing expression of a central hub of innate immune signaling, CREB binding protein (CBP). We show that this regulation conveys partial resistance to the negative effects of interferon treatment on an EBV+ lymphoma cell line. Additionally, removing the microRNA from a similar cell line increases the sensitivity to interferon.
Interferon can be used in combination with other chemotherapies to treat lymphomas but varies in success. Our results may partially explain the variability seen in patients with EBV-associated cancers.
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