Author Interviews, Duke, Genetic Research, Infections / 24.01.2016 Interview with: Ephraim L. Tsalik, MD MHS PhD Assistant Professor of Medicine Division of Infectious Diseases Center for Applied Genomics & Precision Medicine Duke University Medical Center Emergency Department Service Line Durham VA Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Tsalik: This study was motivated by the convergence of two research interests. The first was spearheaded by Dr. Sack, leading our collaboration at Johns Hopkins. Dr. Sack and his colleagues have a long history and expertise in studying enteric infections such as E. coli. The second is our group here at Duke’s Center for Applied Genomics & Precision Medicine as well as the Durham VA Medical Center. Specifically, we have an interest in studying the host response to infectious disease. One of the ways we’ve done that historically is through challenge studies where healthy volunteers are exposed to a pathogen in a controlled setting. Despite everyone getting the same exposure, not everyone gets sick. That observation gives us a unique opportunity to study the host biology of symptomatic individuals, asymptomatic individuals, and what distinguishes the two from each other. That is precisely what we did here. Volunteers ingested Enterotoxigenic E. coli (ETEC), which is a common cause of traveler’s diarrhea. Some subjects became ill with diarrhea while others remained well. In this study, we focused on gene expression patterns, which is a snapshot of how genes in the body are being used in response to this infection. Some genes are more active, some are less. The pattern of those changes that occur in response to infection is what we call a “signature”. This approach allowed us to generate some key findings. First of all, we were able to define the genes involved in the body’s response to this type of E. coli infection. Second, we discovered genes that were differentially expressed at baseline that could distinguish people who would go on to become ill from those that would remain healthy. Although this study was not designed to identify the mechanism for that resilience to infection, it does focus our attention on where to look. We suspect the genes we identified are likely to play a role in infectious disease resilience and susceptibility based on their known immune function roles. We also have data, which wasn’t published in this study, that implicates some of these genes in the resilience to other infections such as influenza. The last major finding was something called Drug Repositioning Analysis. This is a tool that allowed us to identify drugs and drug classes that could be used to mitigate infections caused by ETEC. That analysis highlighted some compounds already known to be effective such as Zinc. But it also identified several other drug classes that have not previously been investigated and could be important tools to combat such infections especially as antibiotic resistance looms. (more…)
Author Interviews, HPV, JAMA / 22.01.2016

More on HPV on Interview with: Ilir Agalliu, M.D., Sc.D. Assistant Professor, Department of Epidemiology & Population Health and Department of Urology Albert Einstein College of Medicine Jack and Pearl Resnick Campus Bronx, NY Medical Research: What is the background for this study? Dr. Burk: We performed this study since we had previously detected an unusually high prevalence of HPV types found on the skin and skin cancers in the oral cavity in addition to HPV16 and other high-risk (HR) types (as defined by their association with cervix cancer) (see Journal of Infectious Diseases 204:787, 2011). We wished to determine if these types were associated with risk of head and neck cancers (HNSCCs). In addition, we wished to determine if HPV detection preceded the diagnosis of HNSCCs and might serve as a biomarker. Currently there are no good screening tests for HNSCC. Dr. Agalliu: To-date, there have been no prospective studies examining the temporal relationship between oral HPV detection and risk of head and neck squamous cell carcinoma (HNSCC). In this manuscript we examined prospectively associations between detection of a wide spectrum of oral HPVs (alpha, beta and gamma) with incident HNSCC in a nested case-control study among ~100,000 participants who provided mouthwash samples in the American Cancer Society-CPS II cohort and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Dr. Agalliu: Oral HPV16 detection, which preceded cancer development on average for 4 years, was associated with a 22-fold increased risk for incident oropharyngeal cancer. Detection of other oral HPVs (beta1 HPV5, and gamma11 and 12 species) were associated with a 3.3 to 5.5-fold higher risk of head and neck squamous cell carcinoma after adjustment for smoking, alcohol and HPV16. Associations of beta and gamma HPVs, which have been identified in the skin, with risk of HNSCC suggest a broader role for HPVs in HNSCC etiology. (more…)
Author Interviews, Dermatology, Infections / 22.01.2016

More on Dermatology on Interview with: Gregory R. Delost, DO University Hospitals Regional Hospitals Richmond Heights, OH What is the background for this study? Dr. Delost: Acne vulgaris is a common dermatological disorder with an incidence of approximately 85% in adolescents and young adults. Treatment options include topical antibiotics, topical retinoids, benzoyl peroxide, oral antibiotics and isotretinoin. Antibiotics are generally prescribed for cases of moderate to severe acne. However, long-term antibiotic use may affect the normal flora bacteria and perhaps promote the development of antibiotic resistant bacteria. There is little prospective research in outpatient settings to determine if these concerns are valid. In our study, we used a prospective, cross-sectional, quasi-experimental design, which compared colonization of Staphylococcus aureus in 263 patients undergoing treatment for clinically diagnosed acne in two northeastern Ohio dermatology practices. (more…)
Author Interviews, CDC, Lyme / 21.01.2016

More on Lyme Disease on Interview with: Rebecca Eisen PhD research biologist and Ben Beard, Ph.D. Chief, Bacterial Diseases Branch Division of Vector-Borne Diseases Centers for Disease Control and Prevention Medical Research: What is the background for this study? Dr. Eisen: Since the late 1990s, the number of reported cases of Lyme disease in the United States has tripled and the number of counties in the northeastern United States that are considered high-risk for Lyme disease has increased by more than >320%. In 1998, a comprehensive review was published that described the geographic distributions of the blacklegged tick (Ixodes scapularis) and the Western blacklegged tick (Ixodes pacificus). These ticks are responsible for infecting humans with the pathogens that cause Lyme disease, anaplasmosis, and babesiosis. Medical Research: Would you tell us about the methodology? Response: CDC researchers recently published an update to the 1998 tick distribution map. The authors reviewed the scientific literature and individual state health department websites for data. Additionally, they contacted public health officials, entomologists, and Lyme disease investigators throughout the United States to assess county-level tick collection data. Researchers characterized counties with Ixodes scapularis and Ixodes pacificus ticks as “established” if at least 6 individual ticks or at least 2 of the 3 tick life stages had been identified during a collection period. Counties were characterized as “reported” if at least one tick of any life stage had been identified at any time in that county, or if county records did not specify the number of ticks or life stages collected. (more…)
Author Interviews, Heart Disease, Infections, JACC / 20.01.2016 Interview with: François Delahaye, MD, PhD Department of Cardiology Hôpital Louis Pradel, Hospices Civils de Lyon Université Claude Bernard Lyon, France Medical Research: What is the background for this study? Response: Infective endocarditis (IE) is a severe disease, with an in-hospital mortality rate of about 20%. Five percent to 10% of patients will have additional episodes of IE. Thus, looking for and treating the portal of entry (POE) of IE is particularly important. The POE of the present episode must be identified in order to treat it. The potential POE of a new episode must be searched for in order to eradicate it and thus lower the risk for a new IE episode. Yet published research on this topic is nonexistent. The search for and treatment of the POE are not even mentioned in the guidelines on IE. We thus undertook a study of the performance of a systematic search for the portal of entry of the present episode of IE and of a potential new episode of Infective endocarditis. Patients were systematically seen by a stomatologist, an ear, nose, and throat specialist, and a urologist; women were systematically seen by a gynecologist; patients were seen by a dermatologist when there were cutaneous and/or mucous lesions. Colonoscopy and gastroscopy were performed if the microorganism came from the gastrointestinal tract in patients ≥ 50 years of age and in those with familial histories of colonic polyposis. Treatment of the portal of entry was systematically considered. Medical Research: What are the main findings? Response: The POEs of the present Infective endocarditis episodes were identified in 74% of the 318 included patients. The most frequent portal of entry was cutaneous (40% of identified POEs). It was mainly (62% of cutaneous POEs) associated with health care and with intravenous drug use. The second most frequent POE was oral or dental (29%). A dental infectious focus was more often involved (59% of oral or dental POEs) than a dental procedure (12%). POEs were gastrointestinal in 23% of patients. Colonic polyps were found in one-half of the patients and colorectal adenocarcinomas in 14%. Performance was good regarding the search for an oral or dental or a colonic potential POE, which were found in 53% and 40% of patients, respectively. (more…)
Author Interviews, C. difficile, Hospital Acquired, Infections, Microbiome / 07.01.2016 Interview with: Casey M. Theriot, Ph.D. Assistant Professor Infectious Disease College of Veterinary Medicine Department of Population Health and Pathobiology North Carolina State University Raleigh, NC 27607 Medical Research: What is the background for this study? What are the main findings? Dr. Theriot: This study is an extension of the work we did in 2014 in our Nature Communications paper (Theriot et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection, 2014). We really wanted to know how different antibiotics that varied in their mechanism of action altered the gut microbiota in different ways and also in turn how this altered the bile acids present in the small and large intestine of mice. Primary bile acids are made by the host and are further converted to secondary bile acids by members of the microbiota in the large intestine. We know from previous work that secondary bile acids can inhibit the growth of C. difficile, but no one has looked in depth at the bile acid makeup in the actual gut before in the context of C. difficile. In this study we show that specific antibiotics that significantly alter the large intestinal gut microbiota and deplete all secondary bile acids allow for C. difficile to grow without any inhibition. We also showed that C. difficile spores are always germinating in the small intestine, which means in order to prevent this pathogen from colonizing the gut, we will have to target the growth of the pathogen. Moving forward the focus will be on trying to repopulate the gut with bacteria that are capable of restoring the secondary bile acid pools in order to inhibit C. difficile. (more…)
Author Interviews, HIV / 05.01.2016 Interview with: Dr. Christina Polyak MD MPH Acting Instructor with the University of Washington Clinical research physician at the U.S. Military HIV Research Program Walter Reed Army Institute of Research at WRAIR Bethesda, MD 20817 Medical Research: What is the background for this study? What are the main findings? Dr. Polyak: Today, 35 million people are infected with HIV, the virus that causes AIDS. (CTX) is low-cost and widely utilized broad spectrum antibiotic used to prevent opportunistic infections in patients with HIV. CTX prophylaxis is recommended by the World Health Organization (WHO) for HIV infected adults in settings with high infectious disease prevalence. In these settings, the threshold for CTX discontinuation is undefined. We designed a study to determine whether CTX discontinuation was non-inferior to continued CTX-prophylaxis in decreasing morbidity in adults with evidence of immune reconstitution (CD4 >350 and 18 months on ART). Our findings show that combined morbidity/mortality was significantly higher in the CTX discontinuation arm (RR=2.27, 95% CI 1.52-3.38;p<0.001), driven by malaria morbidity. This suggests that CTX discontinuation among ART-treated, immune-reconstituted adults in malaria-endemic regions resulted in increased incidence of malaria but not pneumonia or diarrhea. These data helped inform and support the 2014 WHO CTX guidelines. (more…)
Author Interviews, BMJ, Urinary Tract Infections / 02.01.2016 Interview with: Ildikó Gágyor MD Senior researcher in primary care Department of General Practice University Medical Center Göttingen Göttingen, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Gágyor: Uncomplicated urinary tract infection is a common problem for women. Affected patients are usually treated with antibiotics to combat both unpleasant symptoms and to combat infection. However, prescription of antibiotics for a self-limiting condition, contributes to increased resistance rates posing a serious long-term threat to public health. In a double blind randomised controlled trial we examined whether symptomatic treatment of uncomplicated urinary tract infection with ibuprofen reduces the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications. In all, 494 women were randomly assigned to receive: either ibuprofen for three days and antibiotics only if symptoms are persistent; or antibiotic treatment with fosfomycin. Results showed that antibiotic use could be reduced significantly: of the 248 women in the ibuprofen group two thirds recovered without antibiotics and one third received antibiotics subsequently. Women in the ibuprofen group had a higher symptom burden but in both groups, symptoms decreased within the first week (Figure 1). Six cases of pyelonephritis occurred, one in the fosfomycin group, five in the ibuprofen group. (more…)
Author Interviews, Education, Flu - Influenza, Vaccine Studies / 30.12.2015 Interview with: Mubdiul Ali Imtiaz, MD Department of Internal Medicine Rutgers University, New Jersey Medical School Newark, NJ 07103 Medical Research: What is the background for this study? Response: Resident physicians (RPs) were defined to be all individuals enrolled in a graduate medical education training program in a healthcare setting. There were 611 resident physicians enrolled in 47 post-graduate residency and fellowship programs at RU-NJMS during the 2013-2014 academic year. Influenza immunization was strongly recommended, but not mandatory for Resident physicians during 2013-2014. A link to the online survey using a standardized, anonymous, self-administered questionnaire was emailed by the program-chiefs to their respective RPs to collect demographic characteristics, influenza immunization status during the 2013-2014 and the previous season, and reasons for non-vaccination. Medical Research: What are the main findings? Response: The overall self-reported immunization rate of Resident physicians in 2013-2014 was 76.7%. The immunization rate did not differ by the location of medical school attended (P= 0.55) or sex (P= 0.69). Among the respondents, 95.8% had influenza vaccination in the past and 83.1% received influenza vaccine during 2012-2013 flu season. History of influenza vaccination ever and in 2012-2013 were both significantly associated with receiving the vaccine during the 2013-2014 season (P<0.01 for both). The most common reason for not being vaccinated (38.6%) was “lack of time to get immunized” (see Figure 1). The most common cited motivating factors to be vaccinated during the next influenza season among the NVRPs were “making vaccinations in the workplace at convenient locations and times” (43.2%), “availability of mobile flu vaccination carts in hospital floors” (40.9%), and “establishing mandatory flu vaccination for employment” (36.4%). (more…)
Author Interviews, Hospital Acquired, Infections, OBGYNE, Outcomes & Safety / 30.12.2015 Interview with: Muhammad A. Halwani, MSc, PhD Faculty of Medicine, Al Baha University Al Baha, Saudi Arabia. Medical Research: What is the background for this study? What are the main findings? Response: The study idea was based on examining the current rate of post cesarean section infections that were detected in the hospital at the time. It was hypothesized that the detected infections were actually less than the real number identified. Therefore, we challenged the traditional surveillance method that was applied in the hospital with a new enhanced methodology which is telephone follow-ups for patients who under go C-section operations. Our main finding proved that this new applied method was able to detect more cases than the traditional one. Using phone calls as a gold standard, the sensitivity of the standard methodology to capture SSI after cesarean increased to 73.3% with the new methodology identifying an extra five cases. These patients represented 26.3% (5 of 19) of all the patients who developed SSI. In other words, for every 100 C-section procedures there were 2.6% missed cases which the new method was able to detect. The duration of the calls ranged from 1 to 5 minutes and were well received by the patients. (more…)
Author Interviews, Infections, JAMA, Microbiome / 24.12.2015 Interview with: Tara F Carr, MD Assistant Professor, Medicine and Otolaryngology Allergy and Immunology Fellowship Training Program Director Director, Adult Allergy Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Arizona Tucson, AZ 85724 Medical Research: What is the background for this study? What are the main findings? Dr. Carr: Some patients with chronic rhinosinusitis continue to suffer from symptoms despite aggressive medical and surgical treatments. For these individuals, therapy is generally chosen based on bacterial culture results, and often includes the use of topical antibacterial rinses with a medication called mupirocin. We found that if patients are still having problems after this treatment, the bacteria identified from repeated sinus cultures are very different than those usually expected, and in general more difficult to treat. (more…)
Author Interviews, HPV, Infections, Pediatrics, Sexual Health / 23.12.2015 Interview with: Seo Yoon Lee, RN Department of Health Policy and Management Graduate School of Public Health Eun-Cheol Park MD, PhD Institute of Health Services Research Department of Preventive Medicine Yonsei University, Seoul, South Korea Medical Research: What is the background for this study? What are the main findings? Response: Sexually Transmitted Infections (STIs) are a major public health issue which causes acute illness, infertility, long-term disability or other serious medical and psychological consequences, around the world. Adolescence is a key developmental period with rapid cognitive growth. In recent decades, substantial change in the sexual behaviors and attitudes of adolescents has occurred and this would lead them greater risk of STIs than other. Our study looked at the relationship between adolescents’ first sexual intercourse age and their STI experience, as well as to identify vulnerable time table of their sexual activity by considering the time gap between their secondary sex characteristic occurrence age and first sexual intercourse age. The findings from our study show that earlier initiation of sexual intercourse increases the odds of experiencing STIs. Also as the age gap gets shorter, the odds of experiencing STIs increase. Approximately 7.4% of boys and 7.5% of girls reported had STI. For both boys and girls, the chance of experiencing STIs increased as the age of first sexual intercourse decreased [boys: before elementary school (age 7 or under) OR=10.81, first grade (age 7or 8) OR=4.44, second grade (age 8 or 9) OR=8.90, fourth grade (age 10 or 11) OR=7.20, ninth grade (age 15 or 16) OR=2.31; girls: before elementary school OR=18.09, first grade OR=7.26, second grade OR=7.12, fourth grade OR=8.93, ninth grade OR=2.74]. The association between the absolute age gap (AAG: defined as absolute value of “Age gap” = [Age at first sexual intercourse] - [age of secondary sexual manifest]) and STI experience was examined additionally which the result showed, students who had sexual intercourse after their secondary sexual manifestation, as the AAG increases, the odds of STI experience were decreased (boys OR=0.93, girls OR=0.87). (more…)
Author Interviews, PLoS, Urinary Tract Infections / 18.12.2015 Interview with: Dr Sandra A. Wilks PhD Senior Research Fellow IfLS Knowledge Mobilisation Fellow in Healthcare Technologies Faculty of Natural and Environmental Science & Faculty of Health Sciences Centre for Biological Sciences, University of Southampton, Southampton, UK Medical Research: What is the background for this study? What are the main findings? Dr. Wilks: The use of indwelling Foley urinary catheters for extended periods of time results in high risks of urinary tract infections (UTI) and catheter blockages. Blockages are often caused by the presence of Proteus mirabilis, a urease-producing bacterium which results in an increase of the urine pH and the development of crystalline biofilms. Biofilms develop when bacteria attach to a surface, forming a community structure, held together by extracellular polymeric substances (EPS). Once in a biofilm, bacteria exhibit high resistance to the action of antibiotics and are protected by other stress factors. The crystalline biofilms resulting from the presence of Proteus are highly complex environments and cause complete blockage of the catheter within days. Such blockages cause pain and trauma for patients, and result in high demands on healthcare resources. In this study, we have used an advanced microscopy technique (episcopic differential interference contrast, EDIC microscopy developed by Best Scientific) to track the development of these crystalline encrustations on two commonly used catheter materials; silicone and hydrogel latex. We have identified four distinct stages to crystalline biofilm formation;
  • (1) an initial foundation layer (conditioning film) formed by individual 'colonising' P. mirabilis cells, which occurred in less than 1 hour;
  • (2) this was rapidly followed by a sheet-like microcrystalline material (after 24 hours) that covers this conditioning film;
  • (3) after 4 days exposure, large amounts of crystalline material was seen to extend out from the surface with;
  • (4) defined struvite crystals embedded within the structure and P. mirabilis visible throughout. This pattern was the same on both materials.
Author Interviews, Cost of Health Care, Emory, Infections, Pharmacology / 17.12.2015 Interview Questions Carlos del Rio, MD Chair, HIV Medicine Association Department of Medicine Hubert Professor and Chair of the Department of Global Health at the Rollins School of Public Health Professor of Medicine in the Division of Infectious Diseases Emory University School of Medicine Editor's note: Dr. Carlos del Rio discusses the statement from the Infectious Diseases Society of America (IDSA), HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS) regarding the news that Express Scripts is taking steps to improve access to obtaining pyrimethamine for patients with toxoplasmosis. Medical Research: What is the background for this Express Scripts announcement? Dr. del Rio: The HIV Medicine Association (HIVMA) and the Infectious Diseases Society of America initially heard from our members (ID and HIV clinicians) in August about the 5000% price increase in Daraprim® (from $13.50 to $750 per tablet) following Turing Pharmaceuticals’ acquisition of the rights to distribute Daraprim® from Impax Laboratories, Inc.[1] ID and HIV clinicians told us they had been having difficulties obtaining pyrimethamine since earlier in the summer when Impax implemented a controlled distribution system making the drug available only through Walgreen’s Specialty Pharmacy. Despite HIVMA, IDSA and others urging Turing to reverse the price hike, no action was taken and providers continued to report the scarcity of the drug due to the cost and issues with the distribution system. [2] Due to these ongoing challenges, HIVMA and IDSA thought it was important to provide information to our members and other providers regarding the new lower cost option so they could evaluate this option in consultation with their patients. Initially Turing agreed to reconsider the price increase and to lower it; however, on Nov. 24th Turing announced that they would not lower the list price of Daraprim but instead planned to offer discounts of up to 50% to some hospitals. [3] The announcement reinforced the urgent need for affordable treatment options and failed to address that a majority of the eight to twelve month treatment course occurs on an outpatient basis. (more…)
Author Interviews, Biomarkers, Infections, PLoS, Technology / 10.12.2015 Interview with: Leo McHugh, Ph.D. Director, Bioinformatics Immunexpress Seattle, Washington Medical Research: What is the background for this study? What are the main findings? Dr. McHugh: Sepsis is the leading cause of child mortality in the world, and in developing countries kills more adults than breast cancer, prostate cancer and HIV combined. Approximately 30% of people admitted to ICU have sepsis, and up to 50% of these patients die. It’s a major cost burden also, costing the US health system $17 billion per year. The best way to reduce costs and improve patient outcomes is to detect sepsis early and with confidence, so that appropriate treatments can be applied. Each hour delay in the detection of sepsis has been reported to correspond to an 8% increase in mortality. So the need for a rapid and accurate diagnostic is recognized. Traditional methods rely on detection of the specific pathogen causing the infection, and these methods often take more than 24 hours, and find a pathogen in only 30% of clinically confirmed cases because they’re trying to detect a minuscule amount of pathogen or pathogenic product in the blood. Our approach was to use the host’s own immune system, which is highly tuned to respond to the presence of pathogens. Around 30% of all genes are dysregulated in sepsis, so there is a huge signal base to draw from. The trick with using multi marker host response is to pick out the specific combination of gene expression patterns that cover the broad range of patients that present with sepsis and who may present either early or late in the episode, thus with different gene activation patterns. This paper describes a simple combination of such genes that can be used to detect sepsis and performs over the full range of patients irrespective of stage of infection or severity of infection. In it’s current format, the test is manual and takes 4-6 hours, and is a great advance on the current tools, however the methods we’ve used are specifically designed to meet requirements to port this assay onto a fully automated Point of Care platform that could deliver a result in under 90 minutes. (more…)
Author Interviews, Flu - Influenza, Pharmacology, Pulmonary Disease / 09.12.2015 Interview with: Dr. Irene Braithwaite Deputy Director Medical Research Institute of New Zealand Wellington NZ Medical Research: What is the background for this study? What are the main findings? Dr. Braithwaite: We know from animal models that the reduction of fever is associated with an increased risk of dying from influenza. We also know that some influenza viruses cannot replicate well in the human febrile range (38 to 40 Celsius). Yet, guidelines on the management of community acquired influenza infection in humans is to rest, maintain hydration and to take antipyretics such as paracetamol on the basis that this may help and is unlikely to cause harm. We undertook this study to see whether using regular paracetamol during influenza infection might be harmful, as it may allow the influenza virus to replicate more readily, and increase and/or prolong symptoms. To the best of our knowledge, this is the first randomised controlled trial comparing the effects of regular paracetamol (1gram four times daily for five days) versus placebo in human adults infected with influenza. We found that there was no difference in influenza viral loads, temperature or influenza symptoms between the regular paracetamol group and placebo group. (more…)
Author Interviews, HIV, Immunotherapy, PLoS / 04.12.2015 Interview with: Andreas Meyerhans, PhD ICREA Research Professor at the University Pompeu Fabra Infection Biology Group Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain Medical Research: What is the background for this study? What are the main findings? Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion. We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds. (more…)
Author Interviews, CDC, Gender Differences, HIV / 03.12.2015 Interview with: Dr. Andrew Auld MD, MSc Medical Epidemiologist Division of Global HIV & TB CDC MedicalResearch: What is the background for this study? Dr. Auld: Equitable access to antiretroviral therapy for men and women living with HIV is a principle endorsed by most countries and funding bodies, including the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). This analysis, including more than 765,000 adult patients starting antiretroviral therapy in 12 countries (10 African countries, Haiti, and Vietnam), is the most up-to-date and comprehensive assessment of differences in HIV treatment access among men and women with HIV in developing countries. MedicalResearch: What are the main findings? Dr. Auld: Investigators showed that in all 10 African countries and Haiti, women with HIV were far more likely to be on treatment than men. In these 11 countries, women were 23%–83% more likely to access antiretroviral therapy than men with HIV. In addition, in six African countries and Haiti, gender imbalance in HIV treatment access appears to be getting worse over time. (more…)
Author Interviews, Infections, Nature / 02.12.2015 Interview with: Professor Søren Riis Paludan DMSc, PhD Department of Biomedicine Aarhus University Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Paluden: We were interested in understanding the first immune reactions that occur when an organism meets an infectious agent (virus or bacteria). The main finding is that we have identified an immune reaction that is activated as the microbe disturbed the mucus layer at mucosal surfaces. This is an immune reaction occuring earlier than what has been thought previously, and may represent a mechanism that enables the organism to fight most microbes that we meet without mounting strong immune responses. This is important, since strong immune reactions - in addition to contributing to elimination of microbes - also have negative effects such as fever, etc. (more…)
Author Interviews, HIV, NEJM, Sexual Health / 02.12.2015 Interview with: Dr Jean-Michel Molina Department of Infectious Diseases Saint-Louis Hospital and University of Paris Diderot Paris France MedicalResearch: What is the background for this study? What are the main findings? Dr. Molina: Men who have sex with men (MSM) are disproportionately affected by HIV worldwide and represent the today in Europe the largest group in which new HIV infections are diagnosed with no decrease over the last 8 years. The first study assessing preexposure prophylaxis (PrEP) efficacy among MSM was published in 2010 (the Iprex study) which reported for the first time a 44% reduced incidence of HIV in those randomized to receive daily tenofovir/emtricitabine TDF/FTC (one pill per day) as compared to placebo. Adherence to a daily pill regimen was found to be challenging however since only half of the participants (according to drug detection in blood) were taking their daily regimen. Post-hoc analyses suggested that among those with drugs detectable in plasma, PrEP efficacy could be as high as 92%. However, long term adherence to a daily regimen represents the Achille’s heel of daily PrEP, as shown later in other large PrEP trials among women in Africa (VOICE and Fem-PrEP). Based on data from animal models we wished to assess whether PrEP with TDF/FTC taken on demand, at the time of sexual activity, could improve adherence, thereby efficacy and also improve safety and cost. In this randomized double blind placebo controlled trial, on demand PrEP with TDF/FTC reduced the incidence of HIV by 86% in the intent to treat analysis as compared to placebo, and the only 2 participants who became infected in the TDF/FTC arm after more than a year of follow-up, had discontinued the use of PrEP months before infection. The ANRS Ipergay study reports therefore a very high efficacy of PrEP, similar to that also reported in another PrEP study carried out in the UK among MSM with daily TDF/FTC (PROUD), which results were disclosed at the same time. Both studies have increased awareness about the real potential of PrEP and have had a strong impact on WHO and European guidelines. (more…)
Author Interviews, Hospital Acquired, Infections / 27.11.2015 Interview with: Prof. Jean-Yves Maillard Professor of Pharmaceutical Microbiology College of Biomedical and Life Sciences Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University Cardiff United Kingdom Medical Research: What is the background for this study? What are the main findings? Prof. Maillard: Environmental surfaces in healthcare and other settings become contaminated with a variety of infectious agents which may survive long enough to infect susceptible hosts, either directly or through secondary vehicles such as hands. Therefore, routine decontamination of environmental surfaces, in particular those that are frequently touched, is crucial to reduce the risk of infections. Such decontamination is often performed by wiping the target surface with disinfectant-soaked or pre-wetted wipes. However, the label claims of wipes marketed for this purpose are often based upon testing that does not reflect their field use, where contact times are frequently no more than a few seconds with wide variations in the pressure applied during wiping. In addition, wipes impregnated with a disinfectant or detergent can potentially transfer microbial contaminants to a wider area, when the same wipe is used on multiple surfaces. A device called the ‘Wiperator’ was invented to address these issues. It can be used to test wipes with predetermined pressures, wiping times and number of wiping strokes, using a standardized rotary action. It can not only assess the decontaminating efficiency of the test wipe, but also its ability to transfer the acquired contamination to clean surfaces. The test procedure developed using the device is now a standard (E2967) of ASTM International, a highly-respected standards-setting organization. The Wiperator was used in a multi-laboratory collaborative to test commercially-available wipes for their ability to decontaminate metal disks that had been experimentally-contaminated with vegetative bacteria representing healthcare-associated pathogens. The used wipes were subsequently tested for their potential to transfer viable bacteria to clean surfaces. The contact time for wiping and transfer was 10 seconds. Only one of the wipes tested reduced the contamination to an undetectable level while not transferring any viable bacteria to a clean surface. All others left behind detectable levels of contamination on the wiped disks and transferred the contamination to clean surfaces. (more…)
Author Interviews, Clots - Coagulation, Infections / 19.11.2015 Interview with: Professor Adam Cunningham PhD Institute of Immunology and Immunotherapy MRC Centre for Immune Regulation University of Birmingham Medical Research: What is the background for this study? Dr. Cunningham: Our original question was “Why do people die from Salmonella infections that spread beyond the gut”. Some reasons are known but these do not account for all. In particular infants in sub-Saharan Africa seem particularly prone to Salmonella infections that in the West do no more than cause a self-limiting gastroenteritis. A puzzling feature of many of infections in such infants is that they do not have many bacteria in the blood, probably <10 / ml of blood, yet this low density is a strong predictor of death. Therefore, we thought that it may be the host response to the infection that complicates its control and contributes. (more…)
Author Interviews, JAMA, Outcomes & Safety, Urinary Tract Infections, Urology / 19.11.2015 Interview with: Jerome A. Leis, MD MSc FRCPC Staff physician, General Internal Medicine and Infectious Diseases Physician Lead, Antimicrobial Stewardship Team Staff member, Centre for Quality Improvement and Patient Safety Sunnybrook Health Sciences Centre Assistant Professor, Department of Medicine, University of Toronto Medical Research: What is the background for this study? What are the main findings? Dr. Leis: Overuse of urinary catheters leads to significant morbidity among hospitalized patients. In most hospitals, discontinuation of urinary catheters relies on individual providers remembering to re-assess whether patients have an ongoing reason for a urinary catheter. We engaged all of the attending physicians to agree on the appropriate reasons for leaving a urinary catheter in place and developed a medical directive for nurses to remove all urinary catheters lacking these indications. This nurse-led intervention resulted in a significant reduction in urinary catheter use and catheter-associated urinary tract infections, compared with wards that continued to rely on usual practice. (more…)
Author Interviews, STD / 18.11.2015 Interview with: Dr Pam Sonnenberg Reader in Infectious Disease Epidemiology Research Department of Infection & Population Health University College London London MedicalResearch: What is the background for this study? What are the main findings? Dr. Sonnenberg: This study strengthens growing evidence that Mycoplasma genitalium (MG) is a sexually transmitted infection (STI). Analyses of over 4500 of urine samples from Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) showed that MG was prevalent in up to 1% of the general population aged 16-44, who had reported at least one sexual partner. Prevalence was much higher in those who had reported more than four sexual partners in the past year – 5.2% in men and 3.1% in women. Absence of the infection in over 200 16-17 year olds who had not had vaginal, anal, or oral sex provided further evidence that MG is transmitted sexually. The study also analysed risk factors for Mycoplasma genitalium, such as ethnicity, number of partners, and areas of deprivation. There were strong associations with risky sexual behaviours, with similar behavioural risk factors to other known STIs. The authors found that men of Black ethnicity and those living in the most deprived areas were more likely to test positive for MG. Over 90% of Mycoplasma genitalium in men and over two-thirds of MG cases in women were in those aged 25–44 years; an age group who would not be included in STI prevention measures currently aimed at young people in Britain. Interestingly, the majority of participants who tested positive for MG did not report any STI symptoms in the last month. Over half of women did not report any symptoms, but among those who did, bleeding after sex was most common. Over 90% of MG positive men did not report any symptoms. (more…)
Author Interviews, JAMA, Pediatrics, Respiratory / 17.11.2015 Interview with: Leonard B. Bacharier, MD Professor of pediatrics Clinical Director, Division of Allergy, Immunology and Pulmonary Medicine St Louis School of Medicine Washington University St Louis, Missouri Medical Research: What is the background for this study? What are the main findings? Dr. Bacharier: Oral corticosteroids such as prednisone have become the standard of care for children whose colds tend to progress and lead to severe wheezing and difficulty breathing. “But there are some studies that suggest these treatments don’t consistently work for young children. That’s why we want to find ways to prevent upper respiratory infections from progressing to lower respiratory tract illnesses. Once the episode gets going, standard interventions are less effective than would be desired”​​​​​​​​​​​​​​​​, reported Dr. Bacharier. (more…)
Author Interviews, CDC, Infections, OBGYNE, STD / 13.11.2015 Interview with: Dr. Virginia Bowen PhD Epidemic Intelligence Service Division of STD 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. Bowen: Congenital syphilis (CS) occurs when a mother infected with syphilis transmits the infection to her child during the course of pregnancy. Our study looked at recent trends in CS between 2008 and 2014. After four years of decline, Congenital syphilis rates increased by 38% from 2012 to 2014. The findings from this report show we are missing opportunities to screen and treat pregnant women for STDs. Syphilis in pregnant women can cause miscarriages, premature births, stillbirths, or death of newborn babies. We have effective tests and treatment for syphilis – there’s no excuse for allowing it to resurge. Every case of CS is one too many. (more…)
Author Interviews, Biomarkers, Lyme, Rheumatology / 10.11.2015 Interview with: Robert B. Lochhead PhD Clinical Fellow in Medicine Division of Rheumatology, Allergy & Immunology Massachusetts General Hospital Harvard Medical School, Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Lochhead: Lyme arthritis (LA), caused by the tick-borne spirochete Borrelia burgdorferi, usually resolves appropriately with antibiotic treatment, called antibiotic-responsive Lyme arthritis. However, in some patients, arthritis persists for months or years after spirochetal killing with oral and IV antibiotic therapy, called antibiotic-refractory Lyme arthritis. Synovial lesions in these patients show marked synovial proliferation, inflammation, and vascularization, accompanied by autoimmune T and B cell responses. MicroRNAs (miRNAs) regulate many biological processes including inflammation, immune responses, and cell proliferation, and are effective biomarkers that may reveal molecular mechanisms of disease. Our objective here was to identify extracellular miRNAs (ex-miRNAs) in synovial fluid (SF) that distinguish regulated (responsive) from dysregulated (refractory) immune responses in Lyme arthritis, thereby providing insights into underlying biological processes and potential diagnostic biomarkers to distinguish between these disease courses. (more…)
Author Interviews, Infections, Pediatrics, Respiratory / 06.11.2015 Interview with: Dominik Mertz, MD, MSc, FMH (CH) Assistant Professor, McMaster University Department of Medicine, Division of Infectious Diseases Associate Membership Department of Clinical Epidemiology and Biostatistics / Pathology and Molecular Medicine Medical Director Infection Prevention & Control, Hamilton Health Sciences Juravinski Hospital and Cancer Center Hamilton, ON, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Mertz: There was a perception that there was an increase in ICU admissions and deaths, initially in Kansas City and Chicago, which was found to be related to the enterovirus strain EV-D68, which had previously not resulted in any major outbreaks in North America. We have one of the first laboratories that was able to provide a specific EV-D68 PCR routine testing allowing us identify EV-D68 cases and to compare the outcomes in patients infected with this strain to children infected by other rhino/enteroviruses. We found a substantial overlap in how the patients presented between patients with EV-D68 and non-EV-D68 infection. It seems that children infected with EV-D68 were in deed at higher risk for having respiratory distress and needing hospital admission, with children with allergies being at a higher risk. We did not find an increase in more severe outcomes, though, i.e. no higher risk for ICU admission (23 vs 15%) and 0 deaths in the EV-D68 group. We also did not find any evidence of in-hospital transmission of EV-D68. (more…)
Author Interviews, CDC, Infections / 05.11.2015 Interview with: Sam Crowe, PhD, MPH Epidemic Intelligence Service Officer Enteric Diseases Epidemiology Branch Division of Foodborne, Waterborne, and Environmental Diseases Centers for Disease Control and Prevention Medical Research: What were the leading causes of multistate foodborne outbreaks and the most common contaminated foods during the study period? Dr. Crowe: Salmonella, Shiga toxin-producing Escherichia coli, and Listeria monocytogenes were the leading pathogens causing multistate foodborne outbreaks. In order of frequency, fruits, vegetable row crops, beef, sprouts, and seeded vegetables were the leading contaminated foods. Medical Research: How severe are multistate foodborne outbreaks? Dr. Crowe: From 2010 through 2014, multistate foodborne outbreaks accounted for only 3% of all U.S. foodborne outbreaks detected, but caused over one third of the hospitalizations and more than half of the deaths. Medical Research: Are these outbreaks occurring more frequently? Dr. Crowe: Multistate foodborne outbreaks are being identified more often in the United States because of better surveillance. Greater centralization of food processing and distribution practices also could be increasing the frequency and size of multistate foodborne outbreaks. This is why your business should Look for Ruggedised Industrial Pointing Devices Today, to ensure your business is staying up with the industry standards. (more…)
Author Interviews, Columbia, Compliance, HIV, JAMA, Pediatrics / 04.11.2015 Interview with: Dr. Louise Kuhn PhD Professor, Epidemiology Sergievsky Center Columbia University Medical Research: What is the background for this study? What are the main findings? Dr. Kuhn: Ritonavir-boosted lopinavir-based antiretroviral therapy is recommended as first-line treatment for HIV-infected infants and young children while efavirenz is recommended for adults and older children. There are several advantages of transitioning HIV-infected children to efavirenz-based treatment as they get older. These advantages include the possibility of once-daily dosing, simplification of co-treatment for tuberculosis, avoidance of some metabolic toxicities, preservation of ritonavir-boosted lopinavir for second-line treatment, and alignment of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz-based treatment in children exposed to nevirapine for prevention of mother-to-child transmission. This is because efavirenz and nevirapine are in the same drug class and the majority of children who become infected despite exposure to nevirapine used for prevention have mutations in their virus that usually predict resistance to this drug class. In this study, we randomized HIV-infected children to two different treatment strategies: In the control strategy they remained on their initial ritonavir-boosted lopinavir regimen; in the alternative strategy they transitioned to an efavirenz-based regimen. All children had been exposed to nevirapine used (unsuccessfully) to prevent mother to child HIV transmission and were virologically-suppressed (HIV in blood < 50 copies/ml) at the time of enrollment into the study. We observed excellent virological control in both groups with fewer than 3% of children having levels of HIV in their blood greater than 1000 copies/ml. Sustained suppression of virus in blood below 50 copies/ml throughout follow-up was achieved in 82% of the children transitioned to efavirenz-based treatment compared to 72% of children remaining on the control treatment. (more…)