LIVING THE LAB LIFE
A BLOG FOR ASCLS REGION V
Periodically, ASCLS shines a Spotlight on one of its members to highlight their contributions to the profession and to ASCLS. This month, the #IamASCLS post featured the University of Minnesota - Twin Cities Medical Laboratory Science Program Director and ASCLS-MN member Janice Conway-Klaassen.
Check out the full post on the ASCLS website at: http://connect.ascls.org/blogs/andrea-hickey/2017/01/18/iamascls-janice-conway-klaasen
I came across an interesting news article the other day. Global health correspondent for BBC News, Tulip Mazumdar, discussed three viruses that have been labelled as the next potential agent for global healthcare crisis. We are all aware of the destruction caused by Ebola and Zika, for which no vaccine was developed. Having vaccines developed at the onset of outbreaks can keep the illness from spreading and evolving into full-fledged epidemics. Right now, a coalition of charities and governments has committed $460 million to developing these vaccines, while researchers are seeking another $500 million from the funders and the World Economic Forum Davos. This money will be used to develop two vaccines for each of the three viruses, to be made available within five years.
The three viruses Mazumdar discussed in “Vaccines for three deadly viruses fast-tracked” where the MERS virus, Lassa virus, and Nipah virus. In the following review, I will discuss what we already know about these viruses.
Middle eastern respiratory syndrome (MERS) virus comes from the Coronavirus family, the same family as the severe acute respiratory syndrome (SARS) virus. Coronaviruses are plus-strand RNA viruses that cause upper respiratory tract infections in humans. Most of these infections are harmless colds (Coronaviruses are second only to Rhinoviruses in causing common colds). Both MERS and SARS cause a much more severe respiratory infection. Before SARS, only two coronavirus strains had been isolated in humans, but the family has been a subject of much research since SARS first appeared in 2003.
Since September of 2012 (when the MERS virus was first identified in Saudi Arabia), the World Health Organization has been notified of 1,879 laboratory-confirmed cases of MERS in twenty-seven countries, with 666 deaths (mortality rate of 35%). Camels have been indicated as a natural reservoir host for MERS virus, with both camel to human and direct human to human modes of transmission contributing to human infections.
Lassa virus belongs to the family Arenaviruses, which are enveloped single-stranded RNA viruses. This is a hemorrhagic fever virus, like it more famous friend the Filovirus Ebola. Lassa virus made quite an entrance back in 1969. The virus’ first victims where two nurses who worked at a mission in Lassa, Nigeria. A third nurse was saved when she was airlifted to Yale University Medical School in New Haven, CT. Researchers at Yale successfully isolated the new virus from their patient, but at a cost: one virologist became ill and survived, and one laboratory technician died after being infected. The virologist’s survival was attributed to transfusion with plasma from the Lassa-infected nurse that had survived.
Even though Lassa virus first came on the scene in 1969, little is known about how the virus works because its area of activity includes the countries of Sierra Leone, Liberia, and Guinea, which have seen years of civil war and unrest, to the deterrence of research activities. Cultural factors have also inhibited research: in certain African cultures, the manipulation of a body after death is taboo, therefore autopsies are off-limits. The natural reservoir for Lassa is the West African mouse Mastomys natalensis, which then can spread the virus by entering human homes and sheading the virus through their urine. Human to human transmission is possible, but is far less common. Most infections occur after contact with infected mouse urine.
Lassa is believed to be endemic in many West African countries, with only 20% of those infected showing any clinical presentation. Estimates put the annual death toll for Lassa at about 5,000.
Nipah virus belongs to the family of Paramyxoviruses, which also includes several famous viruses: the measles virus, the mumps virus, parainfluenza virus, respiratory syncytial virus, and human metapneumovirus. Paramyxoviruses are non-segmented minus-strand RNA viruses. Nipah virus was first discovered in Malaysia in 1998 after an outbreak of severe encephalitis that killed over one-hundred people (108 deceased out of 269 known cases, approximately 40% mortality rate). This virus first infected pigs, and then spread on to the human host. After the initial outbreak, one million pigs were slaughtered to prevent the spread of the disease; this mass-slaughtering did succeed in curtailing the outbreak. The pteropid bat appears to be the natural host for this virus as well as other members of the Paramyxovirus family, the Hendra and Menangle viruses. Bats spread the virus to the pigs (that show few clinical symptoms), the pigs then spread the virus both to each other and to humans who worked with them. There were no identified cases of human to human transmission in this outbreak. In later outbreaks occurring in Bangladesh in 2004, pigs did not serve as the intermediate hosts, so it is not clear if the virus spread from bat to human or if some human to human transmission occurred. Additionally, it is worth noting that the outbreaks in Bangladesh saw a mortality rate of 74%--yikes!
It is important to note that human activity is likely responsible for the initial outbreak of this virus. A large area of rainforest was cleared to make room for a new airport at Kuala Lumpur. The bats that had been living in this rainforest then re-habituated to areas surrounding local pig farms. This same destruction of habitats of host animals contributed to the spread of the Ebola virus through West Africa.
In the outbreaks where they have been indicated, these viruses have caused substantial morbidity and mortality. We cannot afford to wait until an epidemic starts to start developing a vaccine that would have prevented infection in the first place. If any good can come from serious epidemics like Ebola and Zika, let it be that more time and money is invested into vaccine development before epidemics occur.
Mazumdar, T. (2017, January 18). Vaccines for three deadly viruses fast-tracked. BBC News. Retrieved January 20, 2017, from http://www.bbc.com/news
Norkin, L. C. (2010). Virology: Molecular Biology and Pathogenesis. Washington, DC: ASM Press.
World Health Organization. (2016, December 5). Middle East respiratory syndrome coronavirus (MERS-CoV). Retrieved January 22, 2017, from http://www.who.int/
Now is the time to get involved. Anyone looking to get further involved in ASCLS, we want you! Deadline for applications for numerous volunteer positions is Feb. 6th, 2017.
Read the full request from ASCLS President-Elect (an ASCLS-MN member) Deb Rodahl below:
Even though we are just half way through the society year, we are already looking forward to our next year that begins at the Annual Meeting in San Diego this summer.
Applications are now open for a number of volunteer opportunities that begin this spring as well as the national committee appointments for terms beginning in August.
The lifeblood of ASCLS is its volunteers whose talent, passion, insight, experience, effort and wisdom of is what powers the Society’s good work, amplifying the single voice of the laboratory science profession.
National volunteers on committees are critical to the achievement of the ASCLS mission, and grass roots members like you, who serve on them, are the people that GET THINGS DONE and help keep our organization moving forward.
ASCLS Representatives serve as the face of the Society to other organizations, such as the Board of Certification, the American Hospital Association and NAACLS. Serving ASCLS in one of these capacities allows you to have an influence within your professional organization which, in turn, sets the direction for the medical laboratory profession.
Diversity within the volunteer ranks makes ASCLS stronger. A mix of new and experienced professionals on all of the committees rejuvenate the organization with fresh ideas while those who have served ASCLS in various capacities over the years bring a wealth of institutional knowledge.
ASCLS utilizes an online system that matches volunteers with positions. Adding yourself to the volunteer pool is as easy as 1-2-3.
Debra Rodahl, MBA, MLSCM(ASCP)
Some of the Volunteer Opportunities Open Now
American Society for Clinical Laboratory Science
1861 International Drive, Suite 200
McLean, Virginia USA 22102
Last Saturday, those of us who braved the cold to attend the continuing education event held at the Allina Commons in Minneapolis had the pleasure of hearing a lecture by Joshua Soldo of Roche Diagnostics entitled “The Measurement of Natriuretic Peptides in the Era of Neprilysin Inhibition.” In this lecture, information regarding a newly-approved drug for treating systolic heart failure and its impact in the clinical and laboratory setting was presented.
Heart failure (HF) is a leading cause of death in the United States, across all demographics. It occurs when the heart muscle is weakened due to damage and is no longer able to pump enough blood around the body to maintain proper oxygenation. This results in tell-tale symptoms such as shortness of breath, orthopnea, fatigue, and swelling at the lower extremities and stomach. 50% of patients diagnosed with HF will die within five years; 5.7 million adults are currently living with HF. This disease costs approximately $30.7 billion each year in the United States.
The treatment of HF has traditionally involved therapy with Angiotensin-converting-enzyme (ACE) inhibitors, Angiotensin receptor blockers (ARB), beta blockers, or Mineralocorticoid receptor antagonist (MRA). ACE inhibitors and ARBs prevent symptoms by inhibiting the Renin-Aldosterone (RAS) system, while beta blockers and MRA keep the heart rate low and the oxygen capacity high. Digoxin, diuretics, and various blood pressure medications are also indicated for many HF patients.
The B-type natriuretic peptide (BNP) hormone functions to counteract the RAS system, causing vasodilation, hypotension, and sodium/water loss. BNP (along with biologic metabolite NT-proBNP) are released into the body as a response to stretching of the cardiac wall, as seen in HF. Therefore, providers use BNP or NT-proBNP levels to assess ventricular dysfunction in HF patients. Levels of these cardiac biomarkers are also increased in situations of myocardial damage, such as in heart attacks. BNP assays do not correlate well between various platforms, NT-proBNP assays do. Therefore, the NT-proBNP assay has the advantage in long-term monitoring of HF patients, since results should correlate between laboratories. Additionally, NT-proBNP is more stable in vitro than BNP (over 72 hours compared to 4 hours), which is a valuable time difference in outpatient testing. As laboratorians, it is important that we understand the differences in these assays so that we can properly educate health care providers.
In 2015, Novartis received FDA approval for Entresto, a drug that takes a new approach to treating systolic HF. Entresto is the first drug to enter the market in a new class of drugs to treat HF: Angiotension receptor-neprilysin inhibitors (ARNi). This drug is a 1:1 molecular ratio of an ARB (Valsartan) and a neprilysin inhibitor (Sacubitril). Neprilysin functions by inactivating BNP. So, by inhibiting Neprilysin, BNP concentration in the body increases, which further amplifies the anti-RAS system activity in the body. This combination effect of Entresto therapy has produced powerful results in clinical trials. In test populations, Entresto therapy reduced cardiovascular death as well as hospitalization for HF by 20%, when compared to ACE inhibitor therapy. Overall mortality for these patients was reduced by 16%; those are the kind of results that can add years to patient’s lives. Improved physical function and reduced symptoms were also reported, increasing the quality of life for those living with HF.
Entresto is by no means perfect. It has side effects such as hyperkalemia, hypotension, renal impairment, and angioedema. Also, if a patient has been on an ACE inhibitor, they must discontinue therapy for three days before starting Entresto (which could make for a nerve-racking three days for patients and their cardiologists). The drug is also considerably more expensive that other HF treatments, limiting its accessibility to the uninsured and those with limited income.
Due to the anti-neprilysin function of Entresto, BNP and NT-proBNP levels will be elevated (at least initially) in patients on this drug. Therefore, these tests are no longer as useful in assessing if the patient’s HF is worsening (or if any other myocardial damage is occurring). It is imperative that providers, particularly in acute care or emergency medicine settings, are aware of this reality so patients can still be diagnosed and treated appropriately. In research studies involving patients on Entresto, a long-term NT-proBNP level of <1,000 pg/?? was established as a potential therapeutic target level, as patients who attained that level had reduced morbidity and mortality.
Thank you to Joshua Soldo for presenting this information. Additional thanks go out to the ASCLS members who help put this event together, and to Allina Health for hosting the event.
Clarke, W. (Ed.). (2011). Contemporary Practice in Clinical Chemistry (2nd ed.). Washington DC: AACC Press.
Department of Health and Human Services, Centers for Disease Control and Prevention. (2016). Heart Failure Fact Sheet. USA. Retrieved January 14, 2017, from http://www.cdc.gov/dhdsp/data_statistics/factsheets/docs/fs_heart_failure.pdf
Joshua Soldo. (2017). The Measurement of Natriuretic Peptides in the Era of Neprilysin Inhibition. Medical Scientific Affairs. Roche Diagnostics. Retrieved January 7, 2017
U.S. Food and Drug Administration. (2015, July 15). FDA Approves New Drug to Treat Heart Failure. Retrieved January 14, 2017, from http://www.fda.gov/NewsEvents/NewsAnnouncements?ucm453845.htm