Infectious Disease
On June 1, the World Health Organization (WHO) declared the end of Ebola virus transmission in the Republic of Guinea. At the time, forty-two days had passed since the last person confirmed to have Ebola virus disease had tested negative for the second time. Guinea then entered a 90-day period of heightened surveillance to ensure that any new cases are identified quickly before they can spread to other people.
In the latest outbreak, seven confirmed and three probable cases of Ebola virus disease were reported between March 17 and April 6 in Guinea. In addition, three confirmed cases were reported during the first five days of April in a woman and her two children who had travelled from Macenta, Guinea, to Monrovia, Liberia.
The source of infection in this latest outbreak was probably exposure to infected body fluid from an Ebola survivor. The risk of additional outbreaks from exposure to infected body fluids of survivors remains.
WHO and partners are working with the governments of Liberia, Sierra Leone, and Guinea to help ensure that survivors have access to medical and psychosocial care, screening for persistent virus, and counselling and education to help them reintegrate into family and community life, reduce stigma, and minimize the risk of Ebola virus transmission.
WHO is supporting the three most-affected countries to strengthen key public health programs, especially maternal and child health, while continuing to maintain the capacity to detect, prevent, and respond to any further flare-up of Ebola.
Researchers work to distinguish deadly staph bacteria from harmless strains. Staphylococcus aureus bacteria are the leading cause of skin, soft tissue, and several other types of infections. Staph is also a global public threat due to the rapid rise of antibiotic-resistant strains, including methicillin-resistant Staphylococcus aureus (MRSA). Yet staph also commonly colonize our nasal passages and other body sites without harm. To better understand these bacteria and develop more effective treatments, University of California San Diego researchers examined not just a single representative staph genome, but the “pan-genome”—the genomes of 64 different strains that differ in where they live, the types of hosts they infect, and their antibiotic resistance profiles. This effort, published in Proceedings of the National Academy of Sciences, places all staph genes into one of two categories: the core genome or the dispensable genome.
“The most exciting thing about this study is the computational ability to analyze so many strains simultaneously—an unlimited number, really—to better understand the interrelationships between fundamental metabolism of the organisms and their virulence, or ability to cause human disease,” says study co-author Victor Nizet, MD. The researchers used genome-scale models—computer simulations—of staph metabolism to systematically analyze the ability of 64 staph strains to thrive in more than 300 different environments.
On average, a single staph genome encodes 2,800 genes. But here the researchers found a total of 7,457 genes across 64 strains of the bacterium—the staph pan-genome. Nineteen percent of the pan-genome made up what the team calls the core genome, referring to the genes essential for life and encoded by all strains. In contrast, the vast majority of the staph pan-genome was dispensable, and more variable across strains; 39 percent were deemed “accessory,” meaning they were present in some but not all strains, and 42 percent “unique,” meaning they were found in only one strain.
Dispensable genes give the strains that possess them advantages under particular environmental conditions, such as adaptation to distinct living spaces, the ability to colonize new human or animal hosts, and antibiotic resistance.
Zika Virus
Scientists offer first look at how our cells can “swallow up and quarantine” Zika. Scientists at UMass Medical School have shown that a very small protein we all have in our bodies—interferon-induced protein 3 (IFITM3)—can dramatically reduce the ability of Zika virus to infect human and mouse cells. In some cases, IFITM3 can also prevent Zika virus from killing cells. The findings, by senior study author Abraham Brass, MD, PhD, suggest that boosting the actions of IFITM3 may be useful for inhibiting Zika virus and other emerging viral infections. The study appears in the journal Cell Reports.
“This work represents the first look at how our cells defend themselves against Zika virus’ attack,” says Brass. “Our results show that Zika virus has a weakness that we could potentially exploit to prevent or stop infection.”
Previous studies have shown that people who have a genetic variant, or allele, of the IFITM3 gene are more susceptible to the development of severe influenza. The current study suggests that it will be important to test whether this allele might contribute to the risk of more severe Zika virus infections and birth defects, according to Brass, who has developed a suite of genomic tools to probe how human cells respond to pathogens and how these invaders exploit host cell factors and proteins to replicate.
“Having these tools allowed us to respond quickly when the Zika virus threat emerged,” says Brass. “We simply adapted the technology we’d developed working with dengue, influenza, and other viruses to begin work on Zika virus.”
Brass and his group had a hunch that IFITM3 might reduce or block viral infection. Using the IFITM3 tools and assays they’d developed for studying dengue and influenza viruses, the researchers were able to rapidly test IFITM3’s effect on Zika virus. “We just plugged Zika virus into our system and immediately began testing it,” says Brass.
Found in nearly all human cells, IFITM3 works to alter the cell membrane, making it more difficult for viruses to penetrate this outer defense. The researchers found that when IFITM3 levels are low, Zika virus can more readily infiltrate into the cell interior and cause infection. Conversely, they discovered that when IFITM3 is abundant and on guard, it strongly prevents Zika virus from reaching the interior of the cell and so blocks its infection.
New Assay
FDA approves first blood test to detect gene mutation associated with NSCLC. The U.S. Food and Drug Administration (FDA) has approved the cobas EGFR Mutation Test v2, a blood-based companion diagnostic for the cancer drug Tarceva (erlotinib). This is the first FDA-approved, blood-based genetic test that can detect epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC). Such mutations are present in approximately 10 to 20 percent of NSCLC patients.
With the cobas EGFR Mutation Test v2, the presence of specific NSCLC mutations (exon 19 deletion or exon 21 [L858R] substitution mutations) detected in patients’ blood samples aids in selecting those patients who may benefit from treatment with Tarceva. However, if such mutations are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present. Insofar as the test provides positive results, it may benefit patients who may be too ill to provide a tumor specimen for EGFR testing or are otherwise unable to do so.
The efficacy of the cobas EGFR Mutation Test v2 using blood samples was determined by using the test to identify the EGFR mutation status in patients enrolled into a clinical trial whose tumor biopsies were previously confirmed positive for the EGFR exon 19 deletion or L858R mutations as determined by the cobas EGFR Mutation Test v1.
The assay is manufactured by Roche Molecular Systems in Pleasanton, CA. Tarceva is manufactured by Astellas Pharma Technologies, Inc., of Norman, OK, and distributed by Genentech Inc., of South San Francisco, CA.
Specimen Collection
Silk stabilizes blood samples for months at high temperatures. Researchers at Tufts University have stabilized blood samples for long periods of time without refrigeration and at high temperatures by encapsulating them in air-dried silk protein. The technique, which was published online in the Proceedings of the National Academy of Sciences, has broad applications for clinical care and research that rely on accurate analysis of blood and other biofluids.
Blood contains proteins, enzymes, lipids, metabolites, and peptides that serve as biomarkers for health screening, monitoring, and diagnostics. Both research and clinical care often require blood to be collected outside a laboratory. However, unless the blood is stored at controlled temperatures, these biomarkers rapidly deteriorate, jeopardizing the accuracy of subsequent laboratory analysis. Existing alternative collection and storage solutions, such as drying blood on paper cards, still fail to effectively protect biomarkers from heat and humidity.
The Tufts scientists successfully mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture. The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, encapsulated blood samples were recovered by dissolving the films in water and analyzed.
“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities. For example, this could support large-scale epidemiologic studies or remote pharmacological trials,” says senior and corresponding author David L. Kaplan, PhD.
“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F. Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures which a shipment might encounter during overseas or summer transport,” says the paper’s co-first author Jonathan A. Kluge, PhD.
The paper notes that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.
Industry News
COLA offers recommendations in response to Johns Hopkins study that finds medical errors are third-leading cause of death in United States. COLA, a national laboratory accreditor and advocate for quality in laboratory medicine, has drawn attention to the findings of a Johns Hopkins study that concludes that if medical errors were tabulated similarly to diseases, they would rank as the third- leading cause of death in the U.S. (with more than 250,000 deaths each year), behind only heart disease and cancer. The accreditor has called on the medical community to begin addressing the concerns raised by the study, while issuing a series of recommendations to help laboratories reduce the potential for medical errors.
The study, which was recently published in BMJ (formerly the British Medical Journal), indicates that most medical errors represent systemic problems that include the absence of safety nets and standard protocols, poorly coordinated care, and human error. The researchers conclude that shortcomings in the International Classification of Disease (ICD) coding system for cause of death have concealed the severity of the problem, and hinder the ability to both cultivate and fund system-wide solutions.
In 2015, the National Academies of Sciences, Engineering, and Medicine (formerly the Institute of Medicine) issued a similar report entitled “Improving Diagnosis in Health Care,” which asserted that most people will experience at least one diagnostic error in their lifetime.
“While these medical errors are a result of inefficiencies throughout the entire system, the laboratory can play a significant role in preventing many of these errors,” says Doug Beigel, CEO of COLA. “It is estimated that laboratory testing influences approximately 70 percent of all medical decisions. Ensuring quality and excellence in the practice of laboratory medicine can go a long way in reducing overall adverse patient outcomes.”
In alignment with both the research from Johns Hopkins and the 2015 IOM report, COLA has issued recommendations in four areas to help laboratories reduce the potential for medical errors, and help build a systemic solution that focuses on ensuring the best quality care for patients: Inter-professional Teamwork and Communication; Laboratory Training and Education; Transparency in Reporting; and Increased Research.
ASCP’s 40 Under Forty program recognizes future lab leaders. Forty high-achieving pathologists, pathology residents, and medical laboratory professionals under age 40 have been named to the prestigious 2016 ASCP (American Society for Clinical Pathology) 40 Under Forty list. This year’s pool of applicants was the largest ever, making the selection process highly competitive within this remarkable group of pathology and laboratory medicine professionals.
ASCP’s 40 Under Forty program shines the spotlight on the forty individuals, all of whom have made significant contributions to the profession and collectively stand out as the future of laboratory leadership. The recognition has made a powerful impact on all of its honorees, ranging from well-deserved recognition within their organization to exciting media attention.
The honorees will each have the opportunity to share their knowledge about topics pertinent to pathology and laboratory medicine with a blog platform on ASCP’s ONELab website. ASCP will select the top five individuals from the 40 honorees, who will each receive free registration to attend the ASCP 2016 Annual Meeting to be held in Las Vegas, NV, in September, along with a $1,000 stipend toward airfare and lodging. In addition, the winners will receive free enrollment in Lab Management University, a collaborative educational initiative of ASCP and the American Pathology Foundation.
The applicants were asked to submit a resume and write an essay addressing the most rewarding aspect of lab medicine, how they see themselves as future innovators in healthcare, or bringing the clinical care team together to work towards a common goal.
