Author Interviews, CDC, NEJM, Pediatrics, Respiratory / 27.02.2015

Seema Jain, MD Medical Epidemiologist Epidemiology and Prevention Branch, Influenza Division Centers for Disease Control and Prevention Atlanta, GA 30329MedicalResearch.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…)
Author Interviews, C. difficile, CDC, Hand Washing, Outcomes & Safety / 26.02.2015

Fernanda C. Lessa, M.D., M.P.H. Centers for Disease Control and Prevention Atlanta, GAMedicalResearch.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. (more…)
Annals Internal Medicine, Author Interviews, Infections / 17.02.2015

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 35294-3407MedicalResearch.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…)
Author Interviews, MRSA, University of Pennsylvania / 17.02.2015

MedicalResearch.com Interview with: Valerie Cluzet, MD Hospital of the University of Pennsylvania Division of Infectious Diseases Philadelphia, PA 19104 MedicalResearch: What is the background for this study? What are the main findings? Dr. Cluzet: MRSA is a major cause of skin and soft tissue infection (SSTI) in the community and we know that colonization is an important risk factor for subsequent infection. Past studies have calculated duration of colonization based on colonization at hospital admission or focused on populations not representative of the typical community-dwelling patient. We wanted to identify the factors associated with duration of colonization in a typical patient that clinicians would see (i.e. adults and children presenting to ambulatory setting with a MRSA SSTI), so that the findings would be generalizable and relevant to their practice. In addition, there has been an increasing focus on the role of the household in transmission of MRSA, so wanted to specifically examine that in a longitudinal, systematic way. There are a few major points that emerged from our study. 1) The first is that the duration of colonization after treatment for a methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) is relatively short, but there is a significant subset of patients (approximately 20%) who will have persistent colonization. 2) We also found that treatment of the MRSA SSTI with clindamycin was associated with shorter duration of colonization, an association we did not see with other MRSA-active agents. 3) Finally, this study highlights the potential role of MRSA colonization among household members as a contributing factor in duration of colonization in patients. (more…)
Author Interviews, CDC, HIV, Sexual Health / 14.02.2015

MedicalResearch.com Interview with: Kristen Hess  ORISE Fellow Division of HIV/AIDS Prevention, National Center for HIV, Viral Hepatitis, STD and TB Prevention Centers for Disease Control and Prevention Atlanta, GA MedicalResearch: What is the background for this study? Response: Men who have sex with men (MSM) of all races continue to be the risk group most severely affected by HIV in the United States. CDC’s most recent HIV incidence data show that the number of new infections among MSM increased 12 percent between 2008 and 2010, with an even steeper increase among the youngest MSM. These data clearly show the urgent need to better understand the factors that affect their risk and to develop effective prevention interventions. One specific factor is excessive alcohol use, which is responsible for 88,000 deaths in this nation each year, and cost the U.S. about $224 billion in 2006. Binge drinking (consuming ≥5 drinks for men on an occasion; ≥4 drinks for women) is the most common form of excessive alcohol consumption. The association between excessive alcohol consumption, including binge drinking, and risky sexual behaviors among MSM has had mixed results in the literature with some studies finding an association and others not. One limitation of previous work is that the definition of excessive alcohol consumption varies between studies, so results are not easily compared between studies and populations. Our study examines the relationship between binge drinking and sexual risk behaviors among MSM who are current drinkers and who were either HIV-negative or unaware of their HIV status. MedicalResearch: What are the main findings? Response: We assessed the prevalence of binge drinking, using a standard definition, among a sample of MSM recruited from 20 cities across the U.S. We also examined the association between binge drinking and several risky sexual behaviors. The findings show that 6 in 10 MSM reported binge drinking. Those who binge drank, in comparison to non-binge drinkers, were more likely to engage in risky sexual behaviors such as sex with an HIV-positive or unknown status partner and exchange sex for money or drugs at last sex, as well as more likely to have concurrent partners and more condomless sex partners in the past year. We also found that the likelihood of risky sexual behaviors went up with increased frequency of binge drinking. In fact, MSM who reported 10 or more binge-drinking episodes in the past month were more likely to report risky behaviors. This is a critical point, especially given that, among those who binged, 22 percent reported 10 or more binge drinking episodes in the past month. (more…)
Author Interviews, Cancer Research, Critical Care - Intensive Care - ICUs, Infections / 12.02.2015

Dr. Cornejo-Juárez Department of Infectious Disease, Instituto Nacional de Cancerología Tlalpan MexicoMedicalResearch.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. (more…)
HIV, Kidney Disease, NEJM, Transplantation / 11.02.2015

Elmi Muller, M.B., Ch.B., M.Med. University of Cape Town–Surgery Groote Schuur Hospital Observatory Cape Town Cape Town, South Africa 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. (more…)
Author Interviews, Infections, Technology / 09.02.2015

MedicalResearch.com Interview with: Tassaneewan Laksanasopin PhD Candidate Molecular and Microscale Bioengineering Lab Columbia University Medical Research: What is the background for this study? What are the main findings? Response: We miniaturized and integrated all components needed for blood test (similar to ELISA) to be run on a smartphone accessory for point-of-care testing of infectious diseases.  The device simultaneously detects three infectious disease markers for HIV, treponemal syphilis and nontreponemal syphilis from a finger prick of blood in just 15 minutes.  In a blinded experiment in three health clinics in Rwanda, local health care workers obtained diagnostic results from 96 patients enrolled in prevention of mother-to-child transmission and voluntary counseling programs.  The test performance from our triplexed test was 92-100% sensitivity and 79-92% specificity compared to the gold standard of lab-based HIV ELISA, Treponema pallidum haemagglutination and rapid plasma reagin.  Importantly, patient preference for the dongle was 97% compared to lab-based tests, with most pointing to the convenience of obtaining quick results with a single finger prick.  This work suggests coupling microfluidics with recent advances in consumer electronics can make certain lab-based diagnostics accessible to almost any population with access to smartphones. (more…)
Author Interviews, CDC, HIV, Race/Ethnic Diversity / 06.02.2015

MedicalResearch.com Interview with: Azfar-e-Alam Siddiqi, MD, PhD Associate Chief of Science (Acting) HIV Incidence and Case Surveillance Branch Division of HIV/AIDS Prevention National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Centers for Disease Control and Prevention Medical Research: What is the background for this study? What are the main findings? Dr. Sidiqqi: African Americans remain the population most affected by HIV in the United States -- accounting for almost half (44 percent) of all new infections and more than a third (41 percent) of people living with HIV, despite representing just 12 percent of the U.S. population. We also know that far too many African Americans living with HIV do not get the medical care and treatment they need to stay healthy and protect themselves and others. In fact, less than half (40 percent) of African Americans living with HIV are engaged in care and only one-quarter (28 percent) have the virus under control through treatment. To better understand mortality among African Americans with HIV, our team analyzed data from the National HIV Surveillance System for 2008 through 2012. Because immune suppression caused by HIV infection can result in fatal co-illnesses, our analysis estimated deaths due to all causes, rather than limiting their analysis to deaths resulting directly from HIV infection. This method allowed us to capture the fullest picture of mortality among African Americans with HIV. According to our new analysis, from 2008-2012, the death rate per 1,000 blacks living with HIV decreased 28 percent, more than the overall decline (22 percent) observed among all persons living with HIV and more than declines observed among other races/ethnicities (13 percent for whites and 25 percent for Hispanics). Despite substantial declines in mortality, the death rate per 1,000 blacks living with HIV in 2012 was 13 percent higher than the rate for whites and 47 percent higher than the rate for Hispanics. (more…)
Asthma, Author Interviews, Infections / 06.02.2015

Meghan F. Davis, DVM MPH PhD Assistant Professor Department of Environmental Health Sciences Johns Hopkins Bloomberg School of Public HealthMedicalResearch.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. (more…)
Author Interviews, CDC, Cost of Health Care, HIV / 05.02.2015

MedicalResearch.com Interview with: Ya-lin (Aileen) Huang, PhD. Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention Atlanta, GA, 30329 Medical Research: What is the background for this study? What are the main findings? Dr. Huang: With an estimated 50,000 new HIV infections each year in this country, and no vaccine or cure available yet, prevention is critical. Maximizing the impact of all available prevention strategies could significantly reduce new infections in this country. The purpose of this study is to provide evidence for the cost effectiveness of the interventions recommended under the funding announcement and to highlight where more cost-effectiveness studies may be needed. We limited our scope to the four interventions required under the health department funding announcement, including HIV testing, prevention with HIV-positives and their partners, condom distribution and efforts to align policies with optimal HIV prevention, care and treatment. Our review provides an updated summary of the published evidence of cost-effectiveness of four key HIV prevention interventions recommended by CDC: HIV testing, prevention with HIV-positives and their partners, condom distribution and policy initiatives. Models suggest that more than 350,000 HIV infections have been avoided because of the nation’s HIV prevention efforts. In addition to lives saved, HIV prevention has also generated substantial economic benefits. For every HIV infection that is prevented, an estimated $402,000 (http://www.ncbi.nlm.nih.gov/pubmed/23615000) is saved in the cost of providing lifetime HIV treatment. It is estimated that HIV prevention efforts have averted more than $125 billion in medical costs since the beginning of the epidemic. (more…)
Author Interviews, Hepatitis - Liver Disease, HIV, Lancet / 05.02.2015

MedicalResearch.com Interview with: Prof Jean-Michel Molina Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, Paris France 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. (more…)
Author Interviews, CDC, Infections, Lancet, Vaccine Studies / 04.02.2015

MedicalResearch.com Interview with: Dr Matthew R Moore, MD National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USADr 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…)
Author Interviews, CDC, Gastrointestinal Disease, Infections, Pediatrics, Vaccine Studies / 04.02.2015

MedicalResearch.com Interview with: Margaret M. Cortese MD Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Dr. Cortese: The introduction of rotavirus vaccine in the United States resulted in a dramatic reduction in hospitalizations and emergency department care for rotavirus disease among young children, as well as provided indirect protection to unvaccinated peers. However, what our study looked at was whether or not older children and adults may experience indirect protection from having children in the house who are vaccinated for rotavirus. We used 2008-2012 Marketscan claims data to compare gastroenteritis rates among households whose child had received rotavirus vaccine with households whose child did not receive vaccine. We found statistically significantly lower rates of hospitalization from rotavirus gastroenteritis or unspecified-gastroenteritis in vaccinated households among all persons 20-29 years and females 20-29 years during the 2008-2009 rotavirus season as well as males 30-39 years in the 2009-2010 season. Lower emergency department gastroenteritis rates occurred in vaccinated households among females 20-29 years during the 2009-2010 season and individuals 5-19 years during the 2010-2011 season. (more…)
Author Interviews, Dengue, Technology / 31.01.2015

MedicalResearch.com Interview with: Professor Jackie Ying Institute of Bioengineering and Nanotechnology The Nanos, Singapore Medical Research: What is the background for this study? What are the main findings? Response: The Institute of Bioengineering and Nanotechnology (IBN) has developed a paper-based disposable device that will allow dengue-specific antibodies to be detected easily from saliva within 20 minutes. Currently, dengue infection is diagnosed in the laboratory by testing the patient’s blood sample for the presence of dengue antigens or antibodies. IBN’s device, on the other hand, is capable of detecting IgG, a dengue-specific antibody found at the onset of secondary infections, directly from saliva in one step. Unlike blood samples, saliva can be collected easily and painlessly for rapid point-of-care diagnostics. However, unlike other body fluids, it cannot be applied directly to commercially available test kits as it would cause the sensor nanoparticles to stick haphazardly to the test strip. In addition, conventional paper-based tests are not designed to handle the larger sample volume of saliva required. As described in the journal Lab on a Chip, the IBN researchers used an innovative stacking flow design to overcome key challenges faced by existing lateral flow devices, which are not designed to handle large volume of saliva samples. In IBN’s device, different flow paths are created for samples and reagents through a multiple stacked system. This allows the saliva sample to flow separately through a fiber glass matrix, which removes the substances that would interfere with the nanoparticle-based sensing system before it mixes with the sensor nanoparticles. IBN’s device configuration also helps to regulate the flow in the test strip, generating uniform test lines for more accurate results. (more…)
Author Interviews, Lancet, Neurological Disorders, Pediatrics, Respiratory / 31.01.2015

Samuel Dominguez MD Departments of Pediatric Infectious Diseases Children's Hospital Colorado and University of Colorado School of Medicine Aurora, COMedicalResearch.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. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, HIV, NEJM / 30.01.2015

Douglas B. Jacobs B.S., MD/MPH Candidate Harvard T.H. Chan School of Public HealthMedicalResearch.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. (more…)
Author Interviews, Brigham & Women's - Harvard, Infections, PNAS / 28.01.2015

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 02114MedicalResearch.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. (more…)
Author Interviews, Infections, PNAS, University Texas / 28.01.2015

Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin anMedicalResearch.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, 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. (more…)
Author Interviews, Cognitive Issues, HIV / 27.01.2015

Sophie Cohen MD, PhD Student Department of Pediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands Cairns Base Hospital Australia MedicalResearch.com Interview with: Sophie Cohen MD, PhD Student Department of Pediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands Cairns Base Hospital Australia Medical Research: What is the background for this study? What are the main findings? Response: Since combination antiretroviral therapy (cART) has become widely available for HIV-infected children, the incidence of severe neurological complications has decreased drastically from 30-50% to less than 2%. Unfortunately, even in cART-treated HIV-infected children a range of cognitive problems have been found, such as a lower intelligence quotient (IQ) and poorer visual-motor integration. Importantly, while most HIV-infected children in industrialized countries are immigrants with a relatively low socioeconomic status (SES), cognitive studies comparing HIV-infected children to SES-matched controls are very scarce.  Understanding the prevalence and etiology of cognitive deficits in HIV-infected children is essential because they may result in more pronounced problems, and influence future intellectual performance, job opportunities and community participation. Also, early detection of cognitive impairment might trigger the development of early intervention strategies. In this study we aimed to compare the neuropsychological profile of HIV-infected children to that of healthy controls, matched for age, gender, ethnicity and SES. Also, we aimed to determine the prevalence of cognitive impairment in the HIV-infected group and detect associations between HIV/cART parameters and cognitive performance. We found that the HIV-infected group had a poorer cognitive performance compared with the healthy children on all tested domains (including intelligence, information processing speed, attention, memory, executive- and visual-motor functioning). Using a novel statistical method called Multivariate normative comparison (MNC), we detected a prevalence of 17% with cognitive impairment in the HIV-infected group. Lastly, we found that the center for disease control (CDC) clinical category at HIV diagnosis was inversely associated with verbal IQ (CDC C: coefficient -22.98, P=0.010). (more…)
Antibiotic Resistance, Author Interviews, Infections / 26.01.2015

Anu Kantele, MD PhD Associate Professor, Department of Medicine, University of Helsinki Specialist of Infectious Diseases, Helsinki University Hospital Head of Travel Clinic, Aava Medical Centre "Photo taken by Leena Mattila/YLE/science"MedicalResearch.com Interview with: Anu Kantele, MD PhD Associate Professor, Department of Medicine, University of Helsinki Specialist of Infectious Diseases, Helsinki University Hospital Head of Travel Clinic, Aava Medical Centre Medical Research: What is the background for this study? What are the main findings? Dr. Kantele: Increasing antimicrobial resistance is considered a serious global threat for modern medicine. Resistance is rapidly surging in regions with poor hygiene and uncontrolled use of antibiotics. Resistant bacteria are gradually spreading from there to countries in which the prevalence has thus far been low. Our study was conducted among 430 healthy Finnish travelers visiting warm countries (tropical /subtropical regions). The volunteers provided stool samples before and after travel and filled in questionnaires. The stools were analyzed for multidrugresistant bacteria (not only so called ESBL bacteria but also CPE bacteria which are even more resistant). None of the travelers had CPE strains in their stools before or after their journey. 1% carried ESBL before travel, and 21% acquired a strain while overseas. The risk was greatest in the Indian subcontinent and almost similar in Southeast Asia. In Africa, it proved to be increased but did not reach such a high level. Two factors amplified the risk significantly: travellers’ diarrhea and use of antibiotics. Among the entire study population, ESBL was found in 11% of those staying healthy, 22% of those with diarrhea, and 37% of those who took antibiotics for their diarrhea. In the Indian subcontinent, the respective figures were 23%, 47%, and 80%, and in Southeast Asia 14%, 32%, and 69%. Medical Research: Why do antibiotics predispose to contracting resistant bacteria from the surroundings? Dr. Kantele: The effects of antibiotics cannot be restricted to killing merely the bugs we wish them to kill. When doing their job they also wipe out a huge number of our own intestinal bacteria, thereby opening the door for newcomers’ invasion. If antibiotics are taken in an environment exposing people to a multitude of resistant bacteria, part of these newcomers are likely to be resistant ones. Antibiotics may, in fact, kill the sensitive newcomers and favor the resistant ones. (more…)
Antibiotic Resistance, Author Interviews, Infections / 26.01.2015

Dr. Thiago César Nascimento Assistant Professor, Department of Basic Nursing Laboratory of Bacterial Physiology and Molecular Genetics Institute of Biological Sciences Federal University of Juiz de Fora, BrazilMedicalResearch.com Interview with: Dr. Thiago César Nascimento Assistant Professor, Department of Basic Nursing Laboratory of Bacterial Physiology and Molecular Genetics Institute of Biological Sciences Federal University of Juiz de Fora, Brazil Medical Research: What is the background for this study? What are the main findings? Response: Preliminarily, we observed a high incidence of coagulase-negative  Staphylococcus  strains (CoNS) recovered from the leachate of the health care waste in an untreated sanitary landfill. As Staphylococcus sp. especially oxacillin or methicillin-resistant CoNS remains as important putative pathogenic bacteria regarding human and other animals, in this study we investigated the antimicrobial susceptibility patterns and the occurrence of the  mecA  gene. In conclusion, our results raise issues related to the viability of putative pathogenic bacteria resistant to important antimicrobial drugs carrying important resistance markers in untreated healthcare waste in sanitary landfills.These risks regarding the potential spread of leachate from sanitary landfills due to human and animal activities, or even due to weather phenomena, such as torrential rains and floods, should be considered. Our results address a phenomenon related to the incorrect healthcare waste management in Brazil and in other geographical regions. Taking into account environmental health, more conscientious  policies should be considered by authorities to avoid the disposal of healthcare waste without any further treatment. (more…)
Author Interviews, Dermatology, HIV / 22.01.2015

MedicalResearch.com Interview with: Dr Sophie Grabar, MD, PhD Unité de Biostatistique et Epidémiologie (Aile B2-5ieme étage) Groupe Hospitalier Cochin Broca Hôtel-Dieu PARIS Medical Research: What is the background for this study? Dr. Grabar: We took advantage of a large cohort, the French Hospital on HIV-ANRS CO4 cohort, of more than 100 000 HIV-infected patients to study the incidence trends and risk factors of Herpes Zoster since the advent of cART (combination antiretroviral medications)that have been discrepantly reported in the literature. Also, because Herpes Zoster has been associated with Immune Reconstitution Inflammatory Syndrome, we studied the early impact of cART initiation on the risk of Herpes Zoster and finally evaluated the risk with regards to the risk in the general population that has never been reevaluated in recent years. Medical Research: What are the main findings? Dr. Grabar: We found that the incidence of Herpes Zoster has significantly declined with the arrival of cART and continue to decline probably owing to the immune recovery induced by cART. The risk in HIV-infected patients is globally 3-times higher to that of the general population, and 6-times higher between 15-45 years. Among cART naive patients, we found that the risk of Herpes Zoster increases in the first months of cART initiation but only moderately while it sharply decreases after 6 months of cART. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Hospital Acquired, Vanderbilt / 21.01.2015

Michael Noto, MD, PhD Pulmonary and Critical Care Medicine Vanderbilt University Medical CenterMedicalResearch.com Interview with: Michael Noto, MD, PhD Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Noto: Health care-associated infections are the most common complication for hospitalized patients and several studies have suggested that bathing critically ill patients with the antimicrobial chlorhexidine reduces health care-associated infections.  In the largest study of chlorhexidine bathing to date, however, we were unable to demonstrate a reduction in infections. (more…)
Author Interviews, Infections, Multiple Sclerosis / 20.01.2015

Allan G Kermode MBBS MD FRACP FRCP Clinical Professor of Neuroimmunology, Murdoch University Clinical Professor of Neurology, University of Western Australia Head, Department of Neurology and Clinical Neurophysiology SCGH Centre for Neuromuscular and Neurological Disorders Australian Neuromuscular Research Institute Sir Charles Gairdner Hospital Perth WA Australia Institute of Immunology and Infectious Diseases Murdoch University, Western AustraliaMedicalResearch.com Interview with: Allan G Kermode MBBS MD FRACP FRCP Clinical Professor of Neuroimmunology, Murdoch University Clinical Professor of Neurology, University of Western Australia Head, Department of Neurology and Clinical Neurophysiology SCGH Centre for Neuromuscular and Neurological Disorders Australian Neuromuscular Research Institute  Sir Charles Gairdner Hospital Perth WA Australia Institute of Immunology and Infectious Diseases Murdoch University, Western Australia MedicalResearch: You found that H. pylori sero-positivity was significantly lower in female patients with MS than in female healthy controls, but you didn’t find such a trend in men with Multiple Sclerosis… Briefly, what might explain this association between H. pylori and Multiple Sclerosis in women? (i.e the hygiene hypothesis I suppose?). Prof. Kemode: There are a number of possible explanations, but we believe that the most likely is that helicobacter colonisation is a surrogate marker for the baseline levels of exposure to environmental pathogens and organisms during childhood. We have argued this point of view in our manuscript. It should be emphasised that perhaps not all exposure to infectious agents need necessarily be pathogenic, and the concept of the protobiome is an important one. Every healthy (and unhealthy) individual is host to very many organisms, with the gut having the widest diversity. Other explanations for the association might include that there is some specific antigenic interaction occurring promoting specific immune tolerance to CNS antigens, but I believe that this conclusion would be drawing a very long bow with our current stage of knowledge regarding Multiple Sclerosis. MedicalResearch: Why does this relationship exist in women but not in men? (presumably, they are exposed to the same sanitation, hygiene etc.) Prof. Kemode: This is arguably one of the most fascinating observations of our study. Historically the sex ratio in Multiple Sclerosis was equal, yet in the last 100 years the prevalence of Multiple Sclerosis has increased markedly and the majority of this increase has occurred in women such that in Australia the sex ratio F:M approximates 3:1. The fact that over the same period prevalence of helicobacter in Western countries has declined markedly is a tantalising observation. At this stage scientific knowledge has not explained the changing sex ratios in Multiple Sclerosis nor can we yet explain the strong helicobacter association in females but not males in our study, but our study provides useful navigation to direct further research. (more…)
Author Interviews, Dengue, Infections, PLoS / 16.01.2015

MedicalResearch.com Interview with: Jose R. Loaiza Smithsonian Tropical Research Institute, Panama City, Panama, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología,  Universidad de Panamá, Ciudad de Panamá, Panamá   Medical Research: What is the background for this study? Response: The mosquito Aedes albopictus is a worldwide vector of both Dengue and Chikungunya viruses. This species invaded Panama in 2002, and it expanded across much of the country since that time. Our main goal was to determine the factors (e.g., ecological and non-ecological) associated with its expansion, and to comment on the implications for vector and disease control programs elsewhere in the American tropics. Medical Research: What are the main findings? Response: We found that road networks alone best predicted the distribution of Ae. albopictus in Panama over other variables such as population density and climate. Our data explain the invasion mode of this mosquito species on a local level and demonstrate a remarkable population expansion velocity across the country. Ae. albopictus is likely moving across the landscape as immature stages (i.e., larvae and pupae) in open water, such as used tires. (more…)
Author Interviews, CDC, Infections, JAMA, Pediatrics / 16.01.2015

MedicalResearch.com Interview with: Dr. Stefan Goldberg MD Medical Officer in CDC’s Division of Tuberculosis Elimination Clinical Research Branch Medical Research: What is the background for this study? What are the main findings? Dr. Goldberg: A shorter, simpler treatment regimen for children with latent TB infection can help prevent TB disease and reduce future transmission. The results from our study, a multinational, clinical trial, found that a once-weekly regimen of the anti-TB drugs rifapentine and isoniazid taken as directly observed therapy over a period of three months was safe and as effective for children (age 2-17) in preventing TB disease as the standard self-administered nine-month daily regimen of isoniazid alone. The study also showed that children are more likely to complete the shorter course of treatment, which is important given that treatment completion can be difficult. Specifically, we found that 88 percent of the trial participants on the combination regimen completed therapy while 81 percent completed the standard regimen. The CDC’s Tuberculosis Trials Consortium (TBTC), which conducted this study, works to include children in research when their inclusion is scientifically supportable and when children also might benefit from important new tools, such as alternative treatment regimens. This study is an extension of a large, international trial among persons age 12 and older, published by TBTC in 2011, which showed the shorter, simpler regimen to be as safe and effective as standard treatment. (more…)
Author Interviews, Ebola, PLoS / 16.01.2015

John M. Drake, Ph.D. Associate Professor, Odum School of Ecology, University of Georgia Director, Population Biology of Infectious Diseases REU SiteMedicalResearch.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…)