Pathology and Histology Services Being Developed at the Biamba Marie Mutombo Hospital (HBMM), Kinshasa, Democratic Republic of the Congo (DRC)

Dikembe Mutombo Foundation

The Dikembe Mutombo Foundation (DMF) was created by NBA Legend Dikembe Mutombo in in 1997 with a mission to improve the health, education, and quality of life for the people in his homeland, the Democratic Republic of the Congo (formerly Zaire).

It took 10 years of intense work and many challenges but in December 2007, the Biamba Marie Mutombo Hospital named in memory of Dikembe’s mother opened its doors to patients in the capital city of Kinshasa, DRC. Dikembe personally contributed more than $23 million to build and equip the hospital. The total cost of the new hospital was $29 million.

The hospital currently has close to 170 beds with an ultimate future capacity of 300 beds. It is a modern facility with state-of-the-art equipment including a new donated CT scanner (the first in the DRC.) This general hospital has the following traditional services: primary care, internal medicine, pediatrics, surgery, OB-GYN, surgical subspecialties such as neurosurgery, orthopedics, urology, and ENT. The goal for the hospital is to provide quality care and to train a cadre of health professionals who in turn will continue to build capacity in the health institutions of the country. Hospital management espouses the following values: respect for the dignity of the patients, professionalism, continuous quality improvement, transparency, and accountability. Currently, the hospital is the most modern, if not the best in the country and to date it has treated close to 500,000 patients.

In 2017, Dikembe Mutombo was honored by the Harvard University Medical School for his ongoing humanitarian efforts and dedication to health care during the Global Health Catalyst Cancer Summit in Boston. The three-day summit, hosted by Dana-Farber Cancer Institute, Brigham and Women’s Hospital (BWH) and Harvard Medical School, brought together African ambassadors, ministers of health, celebrity cancer advocates and global health stakeholders to discuss cancer and examine its global effects on society.

Background

In 2016, the Dikembe Mutombo Foundation successfully implemented a Women’s Oncology Institute at the Biamba Marie Mutombo Hospital (BMMH) in the capital city of Kinshasa. Using classic bedside and surgical teaching methodology, aided by low-cost telecommunications technology, and wise infrastructure investments, the Friends of Africa, Inc. (led by Dr. Groesbeck Parham) has been able to successfully build effective, Congolese-led programs for the early detection and treatment of female cancers at BMMH, thereby providing public access to these critical life-saving services for the first time ever in the DRC. Widespread access to such services is known to result in significant alterations in cancer death rates.

Several months ago, the hospital purchased a new ultrasound machine from GE Healthcare to aid in evaluating breast and abdomino-pelvic abnormalities for the female cancer patients.

Cervical Cancer Early Detection and Treatment Clinic

·     A new Cervical Cancer Early Detection and Treatment Clinic was opened at BMMH in July 2016, under the leadership of the Congolese healthcare providers that were trained in Zambia by Dr Groesbeck Parham.

·     During opening week 8,800 women requested cervical cancer screening services and 3,000 were accommodated

·     To date (July 2016-November 2017), the clinic has screened over 15,000 women for cervical cancer, the largest number ever reported in the DRC.

·     Almost 1,000 women (1 out of every 14 screened) were found to have cervical pre-cancer, all of whom were treated on the same day (the largest number ever reported in the DRC), using modern outpatient techniques.

Through intensive, quarterly, hands-on training demonstrations held at BMMH, a team of board-certified U.S. gynecologic oncologists from the University of North Carolina, Chapel Hill, successfully trained a local cadre of Congolese gynecologists to safely and effectively treat women diagnosed with invasive cervical cancer using oncologic surgical procedures. This novel form of competency-based surgical training was developed in Zambia and is specifically designed to rapidly build surgical proficiency in resource-constrained settings, based on the principles of “Deliberate Practice”, intense replication, and mental narration of a limited repertoire of surgical procedures. 

Using an approach tailored specifically for training surgeons in resource-constrained environments, a team of U.S., board-certified breast surgical oncologists from the University of Arkansas (led by Dr. Ronda Henry-Tillman) successfully trained local Congolese general surgeons to safely and effectively perform surgical procedures that are fundamental to the modern treatment of breast cancer. The training approach was identical to the one used to train gynecologists to perform cervical cancer surgery. To date 81 patients with breast cancer have been treated with surgery by the newly trained team of Congolese general surgeons, under the tutelage of U.S. breast surgical oncologists. All surgeries have taken place in the newly formed Breast Cancer Surgical Unit at BMMH.

In summary, the following has been accomplished:

  1. Developed a local Congolese workforce that has the capacity to provide modern, high quality cervical and breast cancer early detection, diagnostic and treatment services, and to train others
  2. Established two new female cancer (cervix and breast) specialty clinics at BMMH
  3. Established two new female cancer (cervix and breast) surgical units at BMMH
  4.  Leveraged web-based videoconferencing (Skype, Zoom) technology to facilitate continued education and develop an international women’s oncology community of practice, made up of Congolese, Zambians and Americans.
  5. Implemented a women’s oncology data collection system
  6. Designed culturally appropriate health promotion messages
  7. Initiated a cervical cancer prevention outreach program

 Women’s Oncology Care for Africa, known as WOCA. They are the visiting breast and cervical cancer team from the U.S.

Dr. Michael Hicks (L), gynecologic oncologist consultant from Detroit, Michigan, and Dr. Alex Mutombo Baleka (R) from Kinshasa, DRC, performing the first radical hysterectomy ever at BMMH in Kinshasa on a woman recently diagnosed with invasive cervical cancer during a cervical cancer screening program sponsored by the Dikembe Mutombo Foundation and supported by UNFPA.

Pathology and Histology

Histology is the next step that the HBMM hospital is working on establishing. This will provide a needed tool for a more complete diagnostic picture for better patient care. Presently, the hospital is working with 2 different Pathologists to help establish the diagnostic part of the Pathology lab. This is where I have come in to help the Pathologist develop their histology lab needs at BHMM. On my first trip over the hospital selected a team of medical techs to be the core of the histology lab. July 2019, I spent 3 weeks giving formal histology lab classes, organized our equipment and lab area, and started some initial hands-on training on basic histology procedures. On Feb 27th, 2020, I return to the DRC for my second trip to the HBMM hospital. The trip started on the 27th of Feb. in San Jose, Costa Rica. I spent parts of 2 days in Atlanta at the Mutombo Foundation picking up 2 donated microtomes and a double headed microscope to take over for the lab. My first task was to review my previous classroom teachings and spent more time on performing laboratory techniques. With the equipment we now have in the lab we were able to do some valuable training. We worked on tissue embedding, microtome sectioning, floatation bath pickup of the thin cut specimen tissues, and general good laboratory practices with the Pathology Lab. (photos)  Additionally, I was able to spend time visiting and training other histology groups in Kinshasa. I spend one day giving classes at the University of Kinshasa, in the Pathology Dept., to a hand full of Histologists from 4 different labs within the city of Kinshasa. My focus of visiting and presenting classes to those outside of the HBMM hospital was to educate the local labs more about basic histology, to help them to start networking to help each other, and for me to find out the available histological resources within the community. All this will not only help our present histology setup at the HBMM, but it will help the others develop better lab uniformity and quality to help each lab’s patients. We are still short a few things at the HBMM to get histology up and running. We would like to have the lab operational on our next trip to Kinshasa. We had projected the opening of Histology for July – Aug. 2020.  However, due to the COVID-19 pandemic and travel restrictions this timeline may not be met. We are still hoping for the histology\pathology lab opening at HBMM in 2020.

I would like to thank Dr. Dan Milner and Ms. Alpa Pandya from ASCP for their instrumental help in making this lab project possible. This is not the first time they have assisted me overseas and I hope it is not our last program to jointly help.  Additionally, I would like to thank Susan Johnson, Executive Director at DMF in Atlanta, GA, for her tireless support. She made sure everything came together for me. This included the obtaining (twice) a visa for me for the DRC.  This visa was not an easy task, especially for someone living in Costa Rica without a DRC Embassy in all Central America. Last, but of course not the least by any means, I would like to thank the Mutombos for their generosity and compassion for helping the medically underserved people of the Congo.

Each trip I have done overseas that I have provided teaching, basic or IHC lab setups, or fine-tuning of histology labs have all been different, but always rewarding. Just to note, many any of these trips I have done with the support of ASCP. I hope this article stimulates others to go out and help others. We all have something to offer. Please share your knowledge with others who many do not have the opportunities that you have been given. Do not let borders or languages be a deterrent. Remember, everything is possible if approached correctly.

The grounds at Biamba Marie Mutombo Hospital, Kinshasa, DRC.
A portion of one histology class.
Teaching in the lab at HBBM.

-David J. Davis BS, HT(ASCP)QIHC is a certified Histologist and has his qualification in immunohistochemistry with ASCP.  He has been a histologist for the past 38+ years. He has worked in various capacities in 26 countries around the world. Since 1992 he’s been teaching and assisting the international community in histology. He’s retired, but definitely not finished working.

The Social Medium is the Message

Hello again everyone and welcome back to Lablogatory!

If you read my post last time, I talked about preserving integrity and delivery of our professional duty as laboratorians in the face of both overwhelming pandemic demands as well as working to  advocate for our field as more people realize each day what goes into every single lab result around the world. A run on sentence and a heavy discussion—and it was just in time to celebrate Lab Week 2020!

This time let’s expand on the second topic a bit. Advocacy in our profession and spotlighting our critical roles as pathologists and medical laboratory scientists. As much as you or I might agree that this is proof positive, just from looking at the regular old news media this year, it’s not so easy. But something that’s been quietly creeping higher and higher on the Lab-Med radar this past year or so is now growing faster than it ever has before: Social Media.

The medium you disseminate information on also translates a message about the author/speaker. For me, I was not only staying the course about data-driven testing science regarding COVID, but I took every ad-lib and opportunity to praise the medical laboratory profession. I praised laboratorians for their hard work, and took a minute to say clearly and plainly, that they are indisputably healthcare heroes in this season of notability. In doing so, I found myself addressing a more pressing pandemic: The Path and MLS pipeline problem. We have a serious issue with finding new medical laboratory scientists and medical students to go into our field. The main cause and culprit? Our essential clinical invisibility. As we are much less patient facing than our other colleagues, it’s difficult to expose younger students considering various careers in healthcare to our specialty. Cue Twitter, Facebook, Instagram, LinkedIn, and even TikTok.

Image 1. Throwback to the 2019 ASCP Annual Meeting in Phoenix, AZ. Dr. Kamran Mirza (left), myself, and Dr. Adam Booth (right) are all part of the growing community of pathologists/trainees plugged into the social network to advocate, collaborate, and spotlight our profession. Follow them both on twitter at: @KMirza and @ALBoothMD, they are champions of using social media as an educational connection.

I’ve talked about this before. And, of course, I’m biased: I’m on the official ASCP Social Media Communications Committee and was highly active in previous iterations including the #SoMeTeam as well as ASCP Social Media Ambassadors programs. Anyone who reads my pieces here knows I’m not social media shy—heck, I weaponized my online presence for residency interview season, networking around the clock to get my name and my work out there for programs to notice. Spoilers: it worked really, really well.

(If you’re one of those senior medical students who is preparing to practice the age-old tradition of wiping the internet clean of your presence, consider a 180 turnaround from that plan—at least if you’re applying to pathology…)

So what worked so well for me? Well, first some background. You know I’m on two ASCP committees, CCPD and Social Media. I’ve already told you I’ve been working the social media angles for a while now, at ASCP meetings, sharing content, etc. And I had a super busy, and super rewarding, residency interview season. With rotations and interviews at some amazing places, I was able to both learn a lot about what it is I really want to do and meet folks to talk about it with. All that being said, sometimes things just fall into place. Specifically, a global pandemic happened. …too soon?

I’m not going to rehash the early days of the pandemic for you, or talk about how I became involved on the ground floor of a lot of outreach and education efforts: that was sooo last month, I did that already (read it all here). But what I will talk about is the butterfly effect that each media engagement set into place for me.

Image 2. When everyone’s talking, the loudest microphone gets the audience. When no one’s making sense, the best content wins. Many of the talks and interviews since the very first ones with my friend and colleague Dr. Ajufo set up a cascade of content to answer some serious concerns during these strange times.

In effect, the order of events for me these last few months looked like this:

  • Writing pieces for Lablogatory¸ some based in scientific analysis of testing, some to address public health concerns and education.
  • Making small viral online tid-bits aimed at educating lay people about overall health, avoiding exposure, and what testing means.
  • Social media connection to join the #PathCast lecture series, of which my video has garnered approximately 20,000 individual views and was seen in almost 50 countries.
  • Invitations from CDC-funded training agencies to explain testing considerations, virology details in translational science, and discuss how those most vulnerable to social determinants of health are most inequitably affected by pandemic conditions.
  • Informal features where I was invited to discuss those intersectional tenets of medicine, public health, and socioeconomics with lay persons in a virtual group setting.
  • An interview with Lifehacker magazine’s Vitals section, to answer reddit-style ask-me-anything questions regarding COVID testing online live with open to the public availability.
  • Inclusion in Lifehacker magazine’s online podcast, where I was featured alongside other experts to discuss the effect of the pandemic on many aspects of life from health to finances.
  • An interview with The Endless Files Podcast¸ where I was invited as a content expert to discuss the connections between laboratory data, public health, public policy, and discuss the political climate surrounding coronavirus concerns all over the sociopolitical spectrum.
  • An interview with People of Pathology Podcast which gave me the chance to talk about my individual career path and transition from education about testing to advocacy and representation for our amazing profession.
  • The nomination and selection by my medical school faculty and peers to deliver the student charge at my formal, virtual, medical graduation.
  • …more are on the way!

Why am I listing these things? Is it my misplaced Greek hubris? Maybe. But before I fly too close to the sun, I’m trying to prove a point. That what started out as creating content on social media for health and wellness during a pandemic essentially became a snowball by summer. I was addressing pressingly relevant information during the obvious opportunity to step up and educate. But something else was happening; something I didn’t realize until recently. And whatever it was, I wasn’t getting there alone.

**All of this was made possible by social media recommendations and connections from friends and colleagues!**

PathCast? I was recommended by a pathologist friend on ASCP’s CCPD committee with me. The CDC-funded training? A former grad student friend of mine when I studied at Rush. Lifehacker? Made possible in a public call for content by our favorite medical lab scientist and Lablogatory editor, Kelly Swails. The Endless Files? Reached out to an old political science professor and friend at Loyola. People of Pathology? Social media connections with friends and CLS colleagues in Canada—you want to make things happen? Don’t go at it alone!

Don’t know how to get started in all this social media frenzy? Don’t fret. Basically, here’s a four-step process: make accounts on one or all of your favorite platforms, follow everyone you want to learn more from, share other’s content or your own frequently, and (most importantly) promote others before yourself! There are countless webinars and talks on how to use social media to leverage advocacy and education, just look at some of the greatest pathology teachers on Twitter: @KMirza, @CArnold_GI, @MArnold_PedPath, @RodneyRhode, @HermelinMD, @KreuterMD, @JMGardnerMD, and many, many more. But there’s more than just twitter! Many super talented folks team up to produce lectures, webinars, and even podcasts (check out the brand-spankin’-new PathPod here!)

Just dive in!

Image 3. Virtual graduation, social media outreach. 2-for-1 sale. In my on-screen graduation quote during the conferment of degrees, part of it read “don’t let me be the last pathologist you were friends with…” and during my student address, I implored my classmates and anyone else watching to consider creative, new ways to solve clinical problems. Maybe with new tools, new skills, and a new understanding of interdisciplinary collaboration. I also reminded people that our digital presence can indicate our professional message, as champions of truth in science.

In conclusion, social media is the new (old) heavy hitter in the medical world. Younger med students are getting access to more specialty information than they ever have before, informing and guiding their career choices. Specialists of all kinds share and reshare excellent diamonds of content that galvanize medical discourse everywhere from Twitter to TikTok. What does this do? It closes the gap between professionals across disciplines, shines new spotlights on fields that traditionally got stamped with basement autopsy stereotypes, and creates digestible and understandable bridges for lay people to access our jargon-filled discourse. It only goes up from here.

Post-script: if you haven’t noticed the racially charged, horrible situations adding to the tumultuousness of 2020, there’s another lesson in this. Social media again proves a most-valuable and all-powerful tool to mobilize, demonstrate, collaborate, and unify thoughts, ideas, and causes. I doubt we will ever be free of tragic moments in history, but when we come together as one collective we can use our various platforms to honor heroes, shame wrong doers, celebrate positive change, and highlight systemic failings that might hold us back from true progress, justice, and peace. That includes the medical world, as all things cross at the intersections of human life and human rights.

Thank you for reading! Stay safe, stay well, and continue to practice safe, compassion-informed social distancing. The pandemic isn’t over, and neither is our work.

Until next time!


-Constantine E. Kanakis MD, MSc, MLS (ASCP)CM is a new first year resident physician in the Pathology and Laboratory Medicine Department at Loyola University Medical Center in Chicago with interests in hematopathology, transfusion medicine, bioethics, public health, and graphic medicine. His posts focus on the broader issues important to the practice of clinical laboratory medicine and their applications to global/public health, outreach/education, and advancing medical science. He is actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Watch his TEDx talk entitled “Unrecognizable Medicine” and follow him on Twitter @CEKanakisMD.

COVID-19 Testing Explained

By this point I believe we are all tired of reading and talking about COVID. However based on reading comments on social media, it’s quite clear that there are a lot of misconceptions about COVID testing. For starters COVID-19 is the disease caused by the SARS-CoV-2 virus. So all of the tests we are using to assist in the diagnosis of COVID-19 are really looking for signs that the person was infected with SARS-CoV-2. There are also 3 main categories of tests for SARS-CoV-2 based on the target of the assay: RNA, antigen, and antibody.

Diagnosis of COVID-19 should be based on clinical symptoms, risk of exposure, test results and timeline. The diagnostic tests based on detection of SARS-CoV-2 RNA are the most commonly used and reliable for diagnosis of COVID-19.1 All of these assays are based on amplifying the viral RNA to detect the presence of the RNA. Most assays use some form of PCR to amplify the virus, however because the virus is RNA-based it has to be converted to cDNA with reverse transcriptase PCR before amplification and detection. TMA or transcription-mediated amplification is another chemistry that can be used to amplify the RNA to a detectable level. Both PCR and TMA based assays are very sensitive at detecting the virus especially within the first week after symptoms develop.1,2 Due to the RNA-based nature of the SARS-CoV-2 genome, the mutation rate is anticipated to be high. Most of the RNA-based assays have adopted a strategy to target 2 different areas of the viral genome to prevent missing the presence of the virus due to a mutation in the primer binding site.

A SARS-CoV-2 antigen test received EUA in early May. The test is designed with immunofluorescence-based lateral flow. This type of test is designed to detect SARS-CoV-2 proteins present on the outside of the virus. In general, this class of test is cheaper and faster than RNA-based testing however it is less sensitive (80% clinical sensitivity).3 The clinical specificity of antigen assays is shown to be 100%,3 therefore a positive result is reliable. These tests can be used for screening; however patients with negative results may still need to proceed to testing by an RNA-based method. Antigen based tests is typically more sensitive during the same timeframe when PCR testing is more sensitive, ie earlier in the course of disease.

SARS-CoV-2 antibody tests are the last class of tests. Seroconversion appears to occur within 7-14 days of symptom onset2 or 15-20 days post exposure to the virus.4 There are many different tests to choose from to determine if the patient has previously been exposed to SARS-CoV-2. The assays range from lateral flow cassettes to high throughput chemiluminescent based assays. Some of the SARS-CoV-2 antibody assays detect IgG, IgM, IgA or some combination of the 3 including total antibody without differentiating between the three. The latest studies have shown that some patients develop IgM first, some with IgG, and others had both IgG and IgM develop at the same time.5 Therefore differentiating IgG from IgM is not providing a timeline for acute infection as we have seen in response to other viruses. Although sensitivity and specificity vary widely between manufacturers total antibody detection appears to be more sensitive than IgG or IgM detection alone.4 The FDA recently pulled numerous assays off of the market due to poor performance.

It is important to note that even with the most sensitive and specific antibody test, these tests cannot determine if a patient has protective immunity. Unfortunately we don’t know enough about immunity with regards to COVID yet. Early studies are promising, showing that some level of antibody will likely provide protection from future exposure. We don’t know if there is a threshold of antibody that needs to be present before a patient is immune, will the immunity only decrease the severity and not prevent reinfection, and how long the antibodies are maintained after exposure. These will be important questions to answer before the clinical utility of antibody testing can be realized. Right now the test is useful to determine is a patient was previously exposed to SARS-CoV-2 and is helpful to address epidemiological questions with regards to prevalence of COVID-19 in the community. The antibody test should not be used for diagnosis of current infection due to the delay to seroconvert after exposure.

References

  1. Sethuraman, N., Jeremiah, S. S., & Ryo, A. (2020). Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. doi:10.1001/jama.2020.8259
  2. Wolfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Muller, M. A., . . . Wendtner, C. (2020). Virological assessment of hospitalized patients with COVID-2019. Nature, 581(7809), 465-469. doi:10.1038/s41586-020-2196-x
  3. Quidel Sofia®2 SARS Antigen FIA. https://www.quidel.com/sites/default/files/product/documents/EF1438900EN00_0.pdf 5/29/2020.
  4. Lou, B., Li, T. D., Zheng, S. F., Su, Y. Y., Li, Z. Y., Liu, W., . . . Chen, Y. (2020). Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset. Eur Respir J. doi:10.1183/13993003.00763-2020
  5. Long, Q. X., Liu, B. Z., Deng, H. J., Wu, G. C., Deng, K., Chen, Y. K., . . . Huang, A. L. (2020). Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. doi:10.1038/s41591-020-0897-1

-Tabetha Sundin, PhD, HCLD (ABB), MB (ASCP)CM,  has over 10 years of laboratory experience in clinical molecular diagnostics including oncology, genetics, and infectious diseases. She is the Scientific Director of Molecular Diagnostics and Serology at Sentara Healthcare. Dr. Sundin holds appointments as Adjunct Associate Professor at Old Dominion University and Assistant Professor at Eastern Virginia Medical School and is involved with numerous efforts to support the molecular diagnostics field. 

Clinical Laboratory Scientists are Imperative to Patient Education

Medical Laboratory Professionals work behind the screens of the medical industry. The contributions produced by this diligent, dynamic, accuracy-driven teams, provide approximately 70% of diagnostic information. This information is imperative for proper diagnosis and treatment. Due to the nature of laboratory work, laboratory personnels are not visible at the forefront of delivering patient care. Therefore, much of society is unaware of the efforts conducted within other parts of the medical industry.

In November of 2018, I had an experience with an elderly couple that will always remain at the forefront of my mind. I was an evening shift Blood Bank Technical Supervisor at a Trauma Level I hospital housing with more than 1000 beds. The Blood Bank served in/out transfusion-dependent patients, as well as being a transplant institution conducting cardiac, liver, and lung transplants. To say we were busy is an understatement.

We had an outpatient order for an older woman who was accompanied by her husband. Her husband, being her advocate, was known to express his concern regarding an issue concerning his wife. The patient’s two units of blood were delayed and the patient’s husband proceeded to call the blood bank to inquire about the delay. The medical laboratory assistant informing him the order was being worked on was not enough, so he proceeded to hound the nurse. The nurse then proceeded to ask to speak to the supervisor.

Before speaking to the nurse, I got the status of the order and asked the technologist approximately how much longer the wait would be. She explained intital testing had revealed an antibody, and so she followed protocol and informed the nurse there would be a delay in blood products.Completing the workup and finding appropriate blood for the patient is what caused the delay. She was at the last portion of crossmatching the blood, and after my review of the workup, it should be 15 minutes.

I informed the nurse it would be 15 minutes, and she pleaded with me to explain the delay to the patient and her husband. After receiving confirmation from my manager to proceed, I hand-delivered the blood to the outpatient room.

“Perception is reality,” so it is imperative to be aware of all verbal and nonverbal communication when interacting with patients. Therefore, accompanied by the nurse, I entered the room and introduced myself and my position. I explained in layman’s term an ABO Type, antibody screen, and finding suitable blood when an antibody has developed. When I was through, they had an exceptional understanding of concept and turnaround time. The patient and husband were appreciative of my explanation and grateful for my staff. The patient’s husband then asked me about my education and what it entailed for me to hold my position. He was highly impressed and never knew all the science and math courses required to become a medical laboratory scientist. He said it was an opportunity he was going to pass along to his granddaughter, who was interested in science.

The following day, the patient’s husband called and apologized to the staff member he initially spoke with and praised the work we do for all patients. This experience highlighted the importance of training laboratory management when interacting with patients. It is more common for the pathologist or medical director to reach out to patients but there are times, especially on the off-shifts, where a laboratory supervisor or manager may be the best option available.

Being an advocate for the medical laboratory science profession is a means of educating the society of a vital career which impacts all lives. Medical laboratory lrofessionals may be behind the scenes, but to administer treatment, essential laboratory results are required; without the laboratory – you’re guessing.

-Tiffany Channer, MPH, MLS(ASCP)CM honed her skill and knowledge of Blood Banking at Memorial Sloan Kettering Cancer Center in New York, NY, where she completed her 9 year tenure at Memorial Sloan as Blood Bank Educational Lead Medical Technologist III/ Safety Officer. She’s currently working as a Quality Assurance Specialist / Educational Supervisor at Memorial Sloan Kettering Cancer Center. Tiffany was a Top Five 40 under Forty Honoree in 2015 for her dedication and advocacy to education and laboratory medicine.

Overview of Laboratory Tests for Cytomegalovirus

Introduction

Cytomegalovirus (CMV) is considered the most important pathogen in transplant recipient patients as it can cause significant morbidity and mortality. Anti-CMV treatments have proven to be effective but are not without adverse side effects. Thus, there is a strong need for sensitive and reliable tests to diagnose and monitor active CMV infection. Several testing methodologies are available in today’s clinical laboratories to evaluate a patient’s CMV status: viral culture, serology, histopathology, pp65 antigenemia, and quantitative PCR. In this post, we will review the advantages and limitations of these tests.

Viral culture

Viral culture is performed most commonly by the shell vial assay (also known as rapid culture), in which a cell line (usually human fibroblast cells) is inoculated with patient sample by centrifugation. The virus is then detected by either direct or indirect fluorescent monoclonal antibody, providing results within 1-3 days. The centrifugation step greatly improves turnaround time when compared to traditional tube cell culture technique, which may take 2-3 weeks before a result can be reported as negative.

Culturing CMV has been largely replaced by newer methodologies like quantitative PCR and CMV antigenemia. This is due to relatively weaker sensitivity for diagnosing CMV infection compared to newer tests, as well as slower turnaround time. Viral cultures of urine, oral secretions, and stool are not recommended due to poor specificity; however, for diagnosis of congenital CMV, viral culture of urine or saliva samples is an acceptable alternative if PCR is not available.

Serology

CMV serostatus is an important metric to evaluate prior to patients receiving a hematopoietic or solid organ transplant. Serologic testing is done primarily via enzyme immunoassays and indirect immunofluorescence assays. These tests check for presence of anti-CMV immunoglobulin (Ig)M and IgG to provide evidence of recent or past infection. Outside of establishing serostatus (primarily in organ donors and recipients), serologic testing for CMV is not recommended in diagnosing or monitoring active CMV infection.

CMV IgM antibodies can be detected within the first two weeks of symptom development and can be present for another 4-6 months. IgG antibodies can be detected 2-3 weeks after symptoms develop, and remain present lifelong. These antibody measurements are particularly useful in determining risk of CMV acquisition in seronegative patients (negative for IgM and IgG) at time of transplantation. IgG titers can also be measured every 2-4 weeks to assess for CMV reactivation in seropositive patients. Since CMV IgG persistently remains in circulation, testing for it has a higher specificity compared to IgM, and thus is the preferred immunoglobulin to test for in establishing serostatus. Serologic tests can be falsely positive if patients have recently received IVIG or blood products, so testing on pretransfusion samples are preferred if possible.

Histopathology

Under the microscope, cells infected with CMV can express certain viral cytopathic effects. These infected cells classically show cytoplasmic and nuclear inclusions (owl eye nuclei) with cytoplasmic and nuclear enlargement. Additionally, immunohistochemistry (IHC) can stain antibodies specifically for CMV proteins to highlight infected cells, making histologic examination quicker and improving diagnostic sensitivity.

Histopathology can be useful in identifying tissue-invasive disease, such as CMV colitis or pneumonitis. Cases in which PCR testing is negative does not necessarily exclude tissue-invasive disease; thus, the diagnosis of tissue-invasive disease relies on histologic examination (with or without IHC) or possibly viral culture. On the other hand, a negative histologic result does not exclude tissue-invasive disease, possibly due to inadequate sampling, and shows the potential for weak diagnostic sensitivity.

pp65 antigenemia

CMV antigenemia testing uses indirect immunofluorescence to identify pp65 antigen, a CMV-specific matrix protein, in peripheral blood polymorphonuclear leukocytes. Whole blood specimens are lysed and then the leukocytes are cytocentrifuged onto a glass slide. Monoclonal antibodies to pp65 are applied, followed by a secondary FITC-labeled antibody. The slide is then read using a fluorescence microscope for homogenous yellow-green polylobate nuclear staining, indicating presence of CMV antigen-positive leukocytes. Studies have suggested that a higher number of positive cells correlates with an increased risk of developing active disease. The sensitivity of antigenemia testing is higher than that of viral culture and offers a turnaround time within several hours.

This test has been utilized since the 1980s, but has seen less use recently due to the increasing popularity of quantitative PCR. Antigenemia testing is labor intensive, and requires experienced and trained personnel to interpret the results (which can be somewhat subjective). This test also must be performed on whole blood specimens within 6-8 hours of collection due to decreasing sensitivity over time, which limits transportability of specimens. Additionally, It is not recommended to be run on patients with absolute neutrophil counts below 1000/mm3, due to decreased sensitivity. Despite these limitations, CMV antigenemia testing is still considered a viable choice for diagnosing and monitoring CMV infection, especially when viral load testing is not available.

Quantitative PCR

Quantitative real-team polymerase chain reaction (PCR) is the most commonly used method to monitor patients at risk for CMV disease and response to therapy, as well as for diagnosing active CMV infection. The advantages of using a quantitative PCR assay include increased sensitivity over antigenemia testing, quick turnaround time, flexibility of using whole blood or plasma specimens for up to 3-4 days at room temperature, and the availability of an international reference standard published by the World Health Organization (WHO).

Several assays from Roche, Abbott, and Qiagen are available and FDA-approved. The targets of these assays vary, with some targeting polymerase and other targeting CMV major immediate early gene. These assays are all calibrated with the WHO international standard, which was developed in 2010 to help standardize viral load values among different labs when results are reported in international units/mL. The goal of this international standard is to decrease the interlaboratory variability of viral load, and determine the appropriate cut-offs for determining clinical CMV disease. There is still improvement to be made in this area, as variability still exists between labs.

Conclusion

There are several tests to determine the CMV status of patients. Some of these tests are suited for particular goals, such as serology for determining serostatus prior to organ transplantation, or histology and IHC to diagnose tissue-specific CMV disease. For diagnosis and monitoring of general CMV disease, the test of choice in most laboratories is quantitative PCR, which offers automated, quick and sensitive results. Antigenemia, while dated and labor intensive, is still an acceptable alternative when PCR is neither available nor cost-effective for smaller labs. Both of these testing methods are preferred over viral culture, which has poorer diagnostic sensitivity and relatively longer turnaround time.

Despite the numerous advantages quantitative PCR has, there is still variability in viral load counts among laboratories. This is due to varying DNA extraction techniques, gene targets used by PCR, and specimen types used. There is still a lot of work to be done in standardizing testing in regards to not just CMV, but also other viral pathogens like Epstein-Barr virus, BK virus, adenovirus and HHV6. Updated standards and increased use of standardized assays will hopefully decrease this variability between labs to improve testing results and in turn, improve patient care.

References

  1. https://www.uptodate.com/contents/overview-of-diagnostic-tests-for-cytomegalovirus-infection#H104411749
  2. https://www.uptodate.com/contents/congenital-cytomegalovirus-infection-clinical-features-and-diagnosis?topicRef=8305&source=related_link#H9542666
  3. Kotton CN, Kumar D, Caliendo AM, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2013;96(4):333-60.
  4. Hayden RT, Sun Y, Tang L, et al. Progress in Quantitative Viral Load Testing: Variability and Impact of the WHO Quantitative International Standards. J Clin Microbiol. 2017;55(2):423-430.
  5. Kotton CN, Kumar D, Caliendo AM, et al. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018;102(6):900-931.

-David Joseph, MD is a 2nd year anatomic and clinical pathology resident at Houston Methodist Hospital in Houston, TX. He is planning on pursuing a fellowship in forensic pathology after completing residency. His interests outside of work include photography, playing bass guitar and video games, making (and eating) homemade ice cream, and biking.

Laboratory Safety and COVID-19: References You Need to Know

Three months ago, life in the laboratories in these United States carried on as usual, and no one could probably have predicted where we stand today. The COVID-19 pandemic has changed the way laboratorians work everywhere. Some staff have had hours cut because of decreased workloads, other labs worked around the clock to bring new testing on board, and others dealt with staffing shortages due to illness. It has been a wild ride, and through it all, a great many safety issues have arisen. Common lab practices are now viewed through a new lens- is it acceptable to bring hematology slides for review into a clean pathologist’s office? Can we wear surgical masks worn in the lab into the break room? There are many good questions, but some of the answers can be found using references offered from reliable sources. Not everything you read online can be believed, but here are some references that may be necessary and that provide important information.

The pandemic has created a world-wide shortage of PPE, and some have wondered what can be done as resources diminish. The CDC has some good information about calculating how long PPE can be used and how long it can last. There are good guidelines about re-use and extended use of PPE.

PPE Burn Rate Calculator:

https://www.cdc.gov/coronavirus/2019-ncov/hcp/ppe-strategy/burn-calculator.html

Strategies to Optimize the Supply of PPE and Equipment:

https://www.cdc.gov/coronavirus/2019-ncov/hcp/ppe-strategy/index.html

There are specific references regarding respirators and how they should be used.

Respiratory Protection During Outbreaks: Respirators versus Surgical Masks

Understanding the Use of Imported Non-NIOSH-Approved Respirators

Proper N95 Respirator Use for Respiratory Protection Preparedness

Some laboratory disinfectants have become more difficult to purchase. The gold standard for disinfection remains a 10% bleach solution, but there are many other options that can be used as well.

Disinfectants for Use Against SARS-CoV-2 (EPA List N):

https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2

EPA’s Registered Antimicrobial Products Effective Against Human HIV-1 and Hepatitis B Virus:

https://www.epa.gov/pesticide-registration/list-d-epas-registered-antimicrobial-products-effective-against-human-hiv-1

The CDC also offers laboratories a set of COVID-19 guidelines for performing testing, biosafety issues, waste management, and protection against aerosols. These guidelines are thorough, and they can be very helpful should safety challenges arise.

Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19):

https://www.cdc.gov/coronavirus/2019-nCoV/lab/lab-biosafety-guidelines.html

Many of these references are updated regularly, so be sure you go to go to the source when making safety policy about COVID-19 tasks.

Laboratorians are now literally on the front lines during this novel coronavirus pandemic. While many public and commercial services have been scaled back, restaurants are closing, and many people are staying or working at home, lab staff are doing their level best to keep coming to work despite the extremely unusual circumstances and hardships.

I am here to serve as well. If you have questions about how to safely navigate this national (and global) emergency while working in the lab, ask me (info@danthelabsafetyman.com). I will do my best to provide any lab safety resources you may need. Make sure the decisions you make during these days are safe, sound, and based on the most recent resources available to you.

Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years experience as a certified medical technologist. Today he is the Laboratory Safety Officer for Sentara Healthcare, a system of seven hospitals and over 20 laboratories and draw sites in the Tidewater area of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.

Microbiology Case Study: Elderly woman with Ear Pain

An elderly woman with a past medical history significant for end-stage renal disease status post deceased donor kidney transplant in 2018 (on immunosuppression), type 2 diabetes mellitus, and recurrent urinary tract infections presented to nephrology clinic with right ear pain and rash of three weeks. She was otherwise in her usual state of health. On physical exam, there were exophytic itchy papules with hemorrhagic crust and ulcerations on the ear (Image 1) and arm. A few of these papules showed central umbilication (Image 2). Erosions were also present on the upper back, face, neck, and forearms. Patient was referred to dermatology with concern for disseminated infection versus neoplasia. Complete blood count showed mildly elevated white cells. Serologies, cultures, imaging, lumbar puncture, and biopsy were performed.

Blood studies revealed a Cryptococcus antigen titer of 1:4096 along with a CSF antigen titer of 1:2048. Additionally, the CSF gram stain demonstrated yeast and cultures grew Cryptococcus neoformans. Opening pressure was normal and protein was slightly elevated to 53 mg/mL with 36 nucleated cells with a differential including 64% lymphocytes. Biopsy culture of the left cheek was positive for C. neoformans and a left forearm biopsy showed nodular aggregates of encapsulated yeasts, surrounded by relatively sparse lymphohistiocytic inflammation (Images 3-4). A CT of the chest showed innumerable pulmonary nodules concerning for infection.

Image 1. Erythematous and crusted pink plaque with ulceration on the pinna of the ear.
Image 2. Pink, domed papule on the arm with central umbilication and crust.
Image 3. Hematoxylin and eosin stain of the arm biopsy with Cryptococcus, low magnification. Note the loss of epidermis (left-hand side) and underlying foamy stroma with numerous yeasts within the dermis.
Image 4. Hematoxylin and eosin stain of Cryptococcus, high magnification. The yeasts show variable size and some demonstrate a halo of pale staining capsule. There is no significant inflammation in the background parenchyma.

Discussion

Cryptococcus is an encapsulated basidiomycetous fungus typically found in soil and pigeon droppings.1 Two species comprise the majority of Cryptococcus infections: C. neoformans and C. gatti. C. neoformans is most commonly seen in immunosuppressed patients, particularly in the setting of AIDS.2 C. gatti infections may be seen in more immunocompetent patients and appears to be more geographically restricted to the tropics and Pacific Northwest.3 C. neoformans infections can present as lung disease associated with symptoms of fever, shortness of breath, or cough and characteristically may spread to the central nervous system to cause meningitis.4 Lumbar puncture may show significantly elevated opening pressures.5 Other features of disseminated Cryptococcus infections include rash, endocarditis, ocular lesions, or multiorgan failure.6

This case is a somewhat unusual presentation of disseminated Cryptococcus infection characterized only by skin findings without clinical features of pulmonary or CNS infection. Approximately 15% of patients with disseminated infection may show cutaneous findings but primary cutaneous cryptococcosis is rare.7 Cryptococcal skin findings are quite varied, but may present similar to molluscum contagiosum, as dome shaped papules with central umbilication.7,8 On microscopy, small variably sized round yeasts without hyphae are characteristic. These yeasts may show a clear or pale staining halo representing the capsule and are highlighted well on Grocott’s Methenamine Silver or Periodic Acid-Schiff stains. Histology may demonstrate innumerable extracellular yeasts accompanied by foamy stroma and minimal inflammation or more granulomatous tissue reaction with necrosis, ulceration, and mixed inflammation. In conclusion, disseminated Cryptococcus must be considered in the context of new skin findings in an immunocompromised patient even if typical pulmonary or CNS findings are not identified.

References

  1. Sorrell TC, Ellis DH. Ecology of Cryptococcus neoformans. Rev Iberoam Micol. 1997 Jun;14(2):42-3.
  2. Bratton EW, El Husseini N, Chastain CA, Lee MS, Poole C, Sturmer T, et al. Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative/non-transplant. PloS One. 2012;7(8):e43582
  3. MacDougall L, Fyfe M, Romney M, Starr M, Galanis E. Risk factors for Cryptococcus gattii infection, British Columbia, Canada. Emerg Infect Dis. 2011 Feb;17(2):193-9.
  4. Sabiiti W, May RC. Mechanisms of infection by the human fungal pathogen Cryptococcus neoformans. Future microbiol. 2012 Nov;7(11):1297-313.
  5. Abassi M, Boulware DR, Rhein J. Cryptococcal Meningitis: Diagnosis and Management Update. Curr Trop Med Rep. 2015;2(2):90–99. doi:10.1007/s40475-015-0046-y
  6. Clark RA, Greer D, Atkinson W, Valainis GT, Hyslop N. Spectrum of Cryptococcus neoformans infection in 68 patients infected with human immunodeficiency virus. Rev Infect Dis. 1990 Sep-Oct;12(5):768-77.
  7. Srivastava GN, Tilak R, Yadav J, Bansal M. Cutaneous Cryptococcus: marker for disseminated infection. BMJ Case Rep. 2015;2015:bcr2015210898. Published 2015 Jul 21. doi:10.1136/bcr-2015-210898
  8. Akram SM, Koirala J. Cutaneous Cryptococcus (Cryptococcosis) [Updated 2019 Aug 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448148/

-Dr. Stanton Miller is a second year AP/CP resident at UT Southwestern Medical Center who is interested in Dermatopathology.

-Dr. IJ Frame is a board-certified Clinical Pathologist who is completing his Medical Microbiology fellowship at UT Southwestern Medical Center.

-Dr. Dominick Cavuoti is a professor of AP and CP at UT Southwestern, specializing in infectious disease pathology, cytology and medical microbiology.

-Clare McCormick-Baw, MD, PhD is an Assistant Professor of Clinical Microbiology at UT Southwestern in Dallas, Texas. She has a passion for teaching about laboratory medicine in general and the best uses of the microbiology lab in particular.

COVID19 and the Lessons We Learned from Prior Pandemics

With recent criticisms in the media, both foreign and domestic, on the United States’ response to COVID19 as well as accusations and summary conclusions that the United States is not a global health power house nor is it as prepared to handle COVID19 as nations around the world that are plagued by infectious challenges daily, it is important to revisit history of recent pandemics and the prior US responses to them to put the current interpretations of “failing” into perspective.

In 2003, the SARS epidemic began in China with the first possible case documented in November 2002. At the time, US relations with China were such that CDC field offices and CDC field officers, including permanent deploys and temporary lead deploys from central CDC in Atlanta, GA, were available to assist the Chinese healthcare system and government with the response to SARS. Through this effort, statements from CDC field directors such as, “This town is going to have a spike and we need 300 more beds,” was answered by the Chinese with a new hospital being built with 300 beds in less than 3 days. Such transparency, collaboration, and communication were possible at the time but relationships have diminished in recent years. During the SARS outbreak, there were 8,098 patients infected (known by positive testing) and 774 deaths (9.5%) which affected 26 countries including the US; however, the US only had 8 to 27 cases (depending on source) and no deaths. Although the first cases traced back to late 2002, the disease was not sequenced and declared until April 2003, but testing was available shortly thereafter. Control measures locally and globally with some help from testing stifled the pandemic in a matter of weeks and the threat was near zero by the end of 2003. No resurgence has occurred. From this outbreak, the US and the world learned how to deal with novel coronaviruses and how to coordinate and collaborate for future potential outbreaks. Such lessons include the need for transparent communication and direct in country collaboration, rapid move to testing distribution, and high-level knowledge of pandemics and who nations should respond.

In 2009, the H1N1 pandemic began. The CDC activated its emergency system within 7 days of the first case, the US and the WHO declared the pandemic within 9 days of the first case, and testing was available within 14 days of the first case. The US had 60.8 million cases (confirmed positive tests) with 274,000 hospitalizations (0.5%) and 12,469 deaths (4.5% of hospitalizations, 0.02% of cases). The incidence from the disease was due to the rapid respiratory spread very similar to routine influenza but on top of a system (including hospital processes and national approaches to testing with integrated public health laboratory systems) that was prepared and able to nimbly adapt. In this case the rapid advent of testing was crucial to controlling case, getting patients on treatment, and tracking the disease. H1N1 was then subsequently included in the annual influenza vaccines.

From 2012-2014, the MERS-CoV virus, originating from and primarily endemic in the Arabian Peninsula, was a challenge for global heatlh because of the high mortality rate (30 to 40%) and the very efficient spread of the virus. All cases arising outside of the Arabian Peninsula were traced to travelers from that region. The first known cases were in April 2012 with the first recognition of the virus causing the disease in September 2012. The CDC developed a test for MERS in 2012 and subsequently an EUA from FDA was granted on June 5, 2013. The first positive cases of MERS in the US occurred in May 2014, almost 1 year after testing had been available. To date, only 2 confirmed cases of MERS have been diagnosed in the US which were traveling healthcare workers who had treated patients in Saudi Arabia.

The Ebola epidemic in West Africa from 2014-2016 had a total global case count of 27,000+ with 11,000+ deaths (46% mortality). However, in the US only 4 patients were ever diagnosed with EBOLA and 11 patients were treated for EBOLA with only 2 total deaths (18% mortality). Why was the case count so low for the US and why was the mortality nearly a 1/3rd of the overall epidemic? Immediate response from the US government to control incoming patients (the only transmission inside the US was from patients who were travelers to healthcare workers) and availability of testing prior to the outbreak (with the CDC). Nigeria was able to diagnose the first case in Lagos (a traveler from Liberia) because a scientist in Nigeria had developed a rapid EBOLA PCR six months before the outbreak occurred. Nigeria only had 8 deaths from 20 confirmed infections (40% mortality). Why did Nigeria get ahead of the game? Immediate response from government and availability of testing. The unfortunate results in Liberia, Sierra Leone, and Guinea were less about lack of response and lack of testing and mostly due to poor infrastructure for health.

The current pandemic of COVID19 started on November 17th (earliest confirmed case in China) and was a reported disease cluster from China to WHO by December 31st, 2019. The first case in the US was documented to have occurred on January 19, 2020. The FDA, in response to information from central administration and pressure from multiple entities, allowed testing for COVID19 through Emergency Use Authorization (EUA) on February 28, 2020 (more than one month after the first US case). As of April 28, 2020, the US has had 1,026,771 confirmed cases (positive testing) and 58,269 deaths (5.7% mortality) affecting all 50 states in the setting of an unprepared system (i.e., insufficient testing, insufficient pandemic planning at the national level, insufficient in country data from source countries). Data has shown in the laboratory that the SARS-CoV-2 virus shares 74 to 90% genetic homology with the original SARS virus but has a 10-fold increased affinity for binding which suggests that its natural biological virulence could be 10x that of SARS. If proper systems, testing, and planning had been in place, we can conservatively estimate that there would currently be 102,667 confirmed cases in the US and 5,827 deaths. These excess cases and excess death are, therefore, a direct result of the lack of systems, testing, and planning (52,442 excess deaths of US citizens).

There are conspiracy theorists that argue SARS-CoV-2 was created or modified from a different virus by human manipulation with a most recent endorsement of HIV Nobel Prize Laureate Luc Montagnier—statements that were almost immediately refuted by other prominent scientists. If there was a credible threat from SARS-CoV-2 when the sequence was released, that would have been an even more convincing argument that preparation was needed. But the threat of SARS-CoV-2 from just the observed medical cases and initial reports should have warranted a brisk and complete response from leadership. That such responses were delayed because of a multitude of failed responses (pandemic planning, testing, situational awareness, field deployments, etc.) can be argued from now until the next pandemic occurs. But our collective prior experience with pandemics (4 of them in 2 decades) provided plenty of evidence and case-studies for how we should have responded.

ASCP along with other organizations reached out to our membership and the community for support of a call for a National Testing Strategy resulting in tens of thousands of letters to elected representatives and a subsequent plan for a National Testing Strategy released by the US government. The CARES Act released this week includes billions for testing.

These efforts are for our membership who are the medical laboratory professionals working 12 hours shifts to provide the testing needed by their patient populations.

These efforts are for our pathologist members who are informing and controlling hospital and government responses around testing through their rapid decisions and their expertise.

These efforts are for our pathologist’s assistance at all levels who keep anatomic pathology running with our pathology trainees despite massive volume challenges.

These efforts are for our PhD members whose expertise in science, design, and evidence acquisition is rapidly leading to new testing and eventually new vaccines.

These efforts are, most importantly, for our patients, the center of all that we do, to ensure that they have access to testing and the peace of mind they need to move forward from this pandemic.

References

  1. https://www.webmd.com/lung/news/20030411/sars-timeline-of-outbreak#1
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904415/
  3. https://en.wikipedia.org/wiki/2002%E2%80%932004_SARS_outbreak
  4. https://www.fda.gov/media/72313/download
  5. https://www.who.int/csr/sars/testing2003_04_18/en/
  6. https://www.cdc.gov/about/history/sars/timeline.htm
  7. https://www.cdc.gov/flu/pandemic-resources/2009-pandemic-timeline.html
  8. https://www.cdc.gov/flu/pandemic-resources/2009-h1n1-pandemic.html
  9. https://www.cdc.gov/coronavirus/mers/about/index.html
  10. https://www.cdc.gov/about/ebola/timeline.html
  11. https://en.wikipedia.org/wiki/Western_African_Ebola_virus_epidemic
  12. https://www.scmp.com/news/china/society/article/3074991/coronavirus-chinas-first-confirmed-covid-19-case-traced-back
  13. https://www.who.int/news-room/detail/27-04-2020-who-timeline—covid-19 https://www.nature.com/articles/s41467-020-15562-9
  14. https://www.worldometers.info/coronavirus/country/us/
  15. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191
  16. https://en.wikipedia.org/wiki/COVID-19_testing
  17. http://www.xinhuanet.com/english/2020-04/21/c_138995464.htm
milner-small

-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.

Love in the Time of COVID-19

Hi everybody—welcome back!

Although you better not have gone too far since last time, self-isolation and social distancing are still critical for us to get through this. Wash those hands, and dust off books and board games. #StrongerTogether (apart), am I right?

Yes, it’s going to be another piece on the current pandemic. It probably will continue to be so until conditions change. So, as your contributor to virology and testing these last two months, I’d like to take a minute to “zoom out” a bit and look at this pandemic in a different way.

It’s highlighting lots of things in healthcare from supply chain, to political regulatory red tape, to the mechanism of deliverables in the United States. And despite the title, I have no romantic epilogues about anything happening in Columbia at the turn of the 20th century. However, very much like the original book’s protagonist, I’d say there are a lot of us in Pathology and Laboratory Medicine alike who are champions of the scientific cause for advancement, education, and positive outcomes. And what better, more fitting of a time to celebrate this cause, than Laboratory Professionals Week 2020!

*** Never forget how vital you all are at every level. Technicians, technologists, medical laboratory scientists, administrators, directors, managers, residents, fellows, faculty, and staff all fit together in a magnificent (but often too unseen) tapestry that makes every patients’ tests results mean something so much more than numbers on a printed report. You’re all lab heroes, we’re all lab heroes. Go make sure you thank some of them this week (or anytime) and a heartfelt thank you to all of you from me as well! ***

In the mere month since I last wrote a piece for Lablogatory, so much has changed with the pandemic as well as my role in local and academic public health efforts. To name a few, I trained with the New York City Medical Reserve Corps as a public health educator early during the pandemic, I was invited to give a lecture on SARS-CoV-2 and COVID-19 testing considerations for lab professionals by the excellent pathologists who run the PathCast series, and I just recently finished a two-day series with an organization called Proceed who are sponsored by the National Center for Training, Support, and Technical Assistance (NCTSTA)—a CDC grant-funded education web series. I’ll mention a little bit about all these things (and of course link you to the material) and talk about how it all fits into what has quickly become a complicated social pandemic response.

NYC-MRC

Almost as soon as I set up shop to start my medical school clerkships and clinical training in New York City, I joined the New York City Medical Reserve Corps—a collection of volunteer healthcare first responders in the event that the city at large ever needed to mobilize every available healthcare personnel during a disaster or health emergency. *Spoilers: turn on the news* At the same time I was prepping some pre-clinical research in infectious disease healthcare and contributing to ASCP’s Choosing Wisely initiatives addressing Hepatitis C testing in vulnerable communities with some of the nation’s highest rates of infection (read the flashback primers I wrote here and here), I was attending NYC-MRC seminars and becoming a nationally certified disaster responder. There have been drills, seminars, and lectures since joining in 2018 but nothing to really contribute to while I moved through clinicals. Welp, clinicals ended, I had a few weeks off for residency interviews, then Kung Pow! Enter the defining viral pandemic of 2020! Smooth sailing lectures became phone network scrambles to see if I obtained my medical license yet since New York’s hospitals were slammed! The last meeting I remember going to was a training on disseminating appropriate information to various levels of practice/professions. I didn’t know it yet, but this became paramount knowledge for me.

Image 1. Throw back from my Instagram (@CEKanakisMD) and one of my first sessions on training to become a disaster responder for the NYC-MRC.
Image 2. The last meeting I attended, and probably the last meeting I’ll have attended while living in Manhattan. Learning some tools, tips, and tricks on effective communication during uncertain times proved invaluable for what was to come. (also from my Instagram @CEKanakisMD)

What Information Matters Most?

So what exactly did I learn? Essentially, it’s nothing groundbreaking or new, but the way you address certain topics matters more than you might realize. I once found myself in a room of mixed level healthcare providers, homeless shelter staff, local public health officials, hospital nurses, and lay people—that’s a broad range of knowledge and practice exposure. If you talk about upregulated ACE-2 receptor expression in intra-viral inflammatory response before full blown ARDS and DAD visible in lung biopsies you’ve lost half the crowd; and if you talk about epidemiology basics like reproductive number (R0), first cases found (FFX), and trace tracking, your provider audience is suddenly looking at their phones. But almost none of them know enough about laboratory testing, regulations, or quality assurance measures—so that became my target, and my bridge to connect everyone. I began collaborating with a friend and colleague Dr. Emeka Ajufo, who matched into his top-choice pain management and rehabilitation (PM&R) residency, and started creating content that connected topics like wellness, one health, and prevention while at the same time understanding deliverables and quality behind lab testing.

Image 3. We’re still in editing and sound production, but we’ve worked together before on podcasts and other content I’ve featured in previous blog posts, like this one! Check out more of Dr. Ajufo’s PM&R work here. (We may or may not be discussing the finer points of adequate nasopharyngeal swab technique here…)

PathCast

So this partnership content got noticed on Twitter (@CEKanakisMD) by the folks that run the PathCast simulcast series on Facebook and YouTube. Dr. Rifat Mannan (@mannanrifat03 on Twitter) from the University of Pennsylvania Hospital and Dr. Emilio Madrigal (@EMadrigalDO on Twitter) from Massachusetts General Hospital have been hosting and promoting a mountain of impressive faculty lectures for all kinds of topics in pathology since 2016. They host them live for viewing across an international audience, take questions, and save each video for future viewers. Their wide and comprehensive hour-a-piece lecture series is enjoyed my many and offers a free, no-hassle viewing experience. I was honored enough to be considered to give a talk on their channel, and after discussing more details with them, it appeared that there was a unique opportunity for some high-value topical information on laboratory and quality testing during this COVID-19 pandemic. If you haven’t heard of this series, you’re missing out. Please go like and subscribe to both their Facebook and YouTube platforms ASAP—you won’t be disappointed!

Image 4. Here’s the title card for my lecture on SARS-CoV-2 and COVID-19 testing considerations for laboratorians. It aired on Friday, April 10th at 8:00 ET and I’m proud to say that it received almost 20,000 individual views from just under 100 countries around the globe. Talk about global pandemic attention and response timing! Got an hour? Check it out here.

What’s a Good Test in a Pandemic?

Excellent question! You’ve probably already heard me talk about this before… This specific question came from discussions on social media with friend, colleague, and fellow ASCP Social Media Committee member Dr. Rodney Rhode (@RodneyRohde on Twitter). If I make it sound like I’ve been busy these last months, Dr. Rhode operates at another level: he’s publishing articles on the pandemic, running laboratory operations, is a research dean and department chair at Texas State, and is disseminating clinical information faster than I could even process it—he’s one of many pathology rockstars in our field! When we spoke before the PathCast series, we talked a bit about the problems in FDA fast-track clearance of all these new tests that would barely make the cut during non-pandemic “peace time.” The Emergency Use Authorization program allows the FDA to push forth tests available for commercial distribution with around 30 or so specimen validations that often don’t break the 60-70% sensitivity/specificity ceiling—yeah, I know. But it’s the best we’ve got and hospitals all over the country are working as hard as they can to bolster their validation studies with more specimens, better controls, modified protocols, and enhanced LDTs (laboratory developed tests) just to meet demand.

Image 5a. Here’s an updated slide from the PathCast talk. The current situation report: 43 commercially available kits, pumped out daily like an overworked approval factory, some are better than others. We’re focused more on molecular/PCR/NAAT for now for its clinical and diagnostic utility. Antibodies will become useful when we discuss “post peak curve” solutions like tracking, vaccines, and therapies like convalescent plasma. What makes a good test in a pandemic? Good laboratory practices.
Image 5b. This is the rapid serology kit that is commercially available but not FDA reviewed, at all. Courtesy of Kelly Swails. I’m not here to name or shame, but this is just one of hundreds of these tests out there. And it’s a definite challenge when those of us in Laboratory Medicine are not part of the process. So caveat emptor/buyer beware—don’t let your lab’s precious time or resources go into snake oils.

There are not enough tests, but there are also too many tests. Just before that PathCast lecture went live, I got an email from our awesome Lablogatory manager and editor, Kelly Swails (@kellyswails on Twitter) about some generic antibody testing kit that people were going nuts over. The problem was on page 6 of the manufacturers’ insert: “this test has not been reviewed or cleared by the FDA.” Well, there’s a problem—and they’re a dime a dozen. Since then, friends, colleagues, and all kinds of inquiries have come my way to ask, “is this a good test?” as people find kits available for purchase… it’s been a mess to say the least. But we laboratorians know: one of our core principles isn’t to let quantity overrule quality, especially when it comes to patient testing. That’s a non-starter.

NCTSTA

Shortly after the PathCast buzz started to settle, one of my MLS grad school classmates who now works with a local public health education and training organization in New Jersey, reached out to see if I could expand the discussion on testing to include problems with access and issues with vulnerable populations. Check and check. Go back and look at some of my posts on Zika and arbovirus work in the Caribbean and you just know I was excited to help! Proceed, Inc. has been a supportive community leader in addressing health and accessibility concerns in their local region and reaching out to form partnerships under the banner of the National Center for Training, Support, and Technical Assistance program (supported by the Centers for Disease Control and Prevention (CDC), Office of Minority Health (OMH), Administration for Children & Families (ACF), and other local entities.)

Image 6. Title card and promotional material for the Proceed/NCTSTA webinar on April 21st, at 2:00p ET with question and answer session and a following day’s meeting called “coffee house chat” where informal discussion and questions were directed at me regarding the topics discussed. It was a fantastic dual session, something I would promote and do again in the future. Unlike the previous hour lecture aimed exclusively at a pathology audience, these attendees came from mixed roles from frontline healthcare workers to government officials in public health and were located all over the US! Here’s the link to the recorded webinar, check it out here.

Who’s Vulnerable?

If you watch the news it’s individuals over 65 years of age and/or anyone with a significant related underlying condition: asthma, COPD, hypertension, etc. And, while that’s true, that’s just the tip of the vulnerability iceberg. Let’s remind ourselves for a minute about the inward and outward concepts of “social determinants of health.” When we want to label a population as vulnerable, or better put, increasingly susceptible to the negative effects of their living conditions in the setting of health care access, we have to think about all the things that contribute to a person’s health: their relationships, their stable/unstable living conditions, level of education, their income/expense ratio, possible language barriers, race/creed/color, disability, addiction, those experiencing homelessness, and concerns for their individual safety to name just a few! Inwardly, should we choose to engage these vulnerable communities we must do so with proper inclusion and a foundation of trust, communication, clarity of purpose, partnership, support, and—arguably most importantly—cultural humility. I also offered the attendees two resources as handouts which are available to you if you attend the recorded webinar as well: one COVID-19 safety factsheet directly from the CDC, and an adaptation of social determinants inventory I designed when my arbovirus team worked on Zika education in Sint Maarten. In truth, we’re all vulnerable in different ways, but when we work together to address gaps in delivery and access we end up #StrongerTogether—and that’s something our laboratory community knows a thing or two about!

Image 7a. Some selected slides from the Proceed/NCTSTA webinar on testing and vulnerability. (51) addresses that “tip of the vulnerability iceberg” that goes beyond physical susceptibility to viral infection, (52) clearly demonstrates that the number of confirmed cases in the 5 boroughs of New York City—the hardest hit location in the United States right now—correlates not only to income/expense ratios, but also people of color, and especially those individuals who can’t leave their work because of the “essential” nature of the service industry. (53) This tense situation between paycheck-to-paycheck workers and depending on employment for insurance is point proven if you look at unemployment claims going back to the 60’s! Notice the dramatic spike of 3.3 million claims this year because of the pandemic! That’s more than any oil embargo, dot-com burst, housing bubble, or recession we’ve ever seen! Finally, in (54) I introduce what I think is a “new” type of vulnerable population: individuals who don’t “buy-in” to the science and medical literacy of the current situation. That’s a whole other blog post folks…
Image 7b. Here it is, my COVID-19 Assessment and Preparedness Inventory Toolkit which incorporates data from FEMA, the CDC, the WHO, previous literature on inciting behavioral changes, and evidence-based best practices for addressing the most vulnerable populations.

The Tipping Point

The $64,000 two-part question: are things getting better or worse, and when will things go back to normal? My 64¢ answer: we don’t really know yet because there’s not enough active current data. The best estimates have case-peaks in places like Manhattan reaching a sort-of plateau as non-emergent hospitalizations, intubations, and COVID-19 cases slow down—but don’t mistake that for a full-on stop. Social distancing and quarantine initiatives in places like New York, Chicago, and other cities are the most effective NPI (non-pharmaceutical intervention) we’ve got. And that’s saying a lot. We have data that suggests previous pandemics had second waves as soldiers came back from war during the 1918 Flu pandemic in the states, so we’ve got to be careful and mindful of what we’re up against. But it’s getting easier and easier to become listless and bored of Netflix and stress-baking. People are getting legitimate cabin fever, although I’d rather we all had that than another, more topical viral illness these days. We’ve got a ways to go with all our frontline work, our NPI distancing, and stratified testing/tracking measures and we have to keep at it, otherwise we’ll undo all the progress we’ve made. And, that “new” vulnerable population, with motivations most certainly rooted in fear and stress, demanding to “reopen” the country since COVID is, after all, a hoax: don’t underestimate their power to tip the scales and send us back. The marriage of policy and politics is a patchy one at best, but efforts from professional advocacy societies like the ASCP are making strides, pushing both at the local and federal levels to demand active and appropriate responses to address proper COVID testing. But things don’t have to be so contentious.

Image 8. “Operation Gridlock”: re-open protestors in Denver, CO come face-to-face with frontline workers like this nurse in the middle of this tenuous mass protest and battle between politics and science. Scenes like this are happening all over the country like in Ohio, Michigan, and more. (Image: NBC news)
Image 9. ASCP has been the definitive forefront in leading the national charge to address our federal response to proper testing guidelines, strategy, and support. Read more about it here.

Fear and Loathing vs. Love in the Time of COVID?

So where does this leave us now? You’ve listened to my litany of testing complexities and considerations for preserving quality of healthcare delivery to all types of patients and you know where I stand on having a passion for preserving the importance and integrity of our professional role as leaders in this field. Do we give in to frustration or keep fighting this pandemic in more, creative ways? The answer, to me, is obvious. We move forward, as always. But most especially, this lab week should be something different because it not only highlights our work as traditionally “behind the scene,” but underscores our critical importance to the delicate house of cards balanced between clinical healthcare, decision making, public health, and public opinion. It’s not only our job to make sure the tests are good (even during pandemics) but that we represent a consistent and reliable message of evidence-based truth for patients and clinicians to rely on—like we always do.

Happy Lab Week 2020. Stay safe, wash your hands, and remember social distancing doesn’t just mean staying at home. It also means integrating compassion into a new routine, and caring for neighbors, colleagues, and friends in new profound ways.

See you all next time!

Image 10. Lab week 2020, ASCP’s Fellowship of the Lab, One Team to Diagnose Them All


-Constantine E. Kanakis MD, MSc, MLS (ASCP)CM is a new first year resident physician in the Pathology and Laboratory Medicine Department at Loyola University Medical Center in Chicago with interests in hematopathology, transfusion medicine, bioethics, public health, and graphic medicine. His posts focus on the broader issues important to the practice of clinical laboratory medicine and their applications to global/public health, outreach/education, and advancing medical science. He is actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Watch his TEDx talk entitled “Unrecognizable Medicine” and follow him on Twitter @CEKanakisMD.

COVID-19 Laboratory Safety: The Wrong Conclusion?

In the classic Barry Manilow song, Copa Cabana, the singer admonishes his audience at the end not to fall in love. We are told to avoid love because some guy named Rico might exterminate our loved one and we will end up a drunken barfly like Lola in did in the song. It’s a pretty funny conclusion when you think about it. If you were the victim in the story though, you might draw the same conclusion, however flawed. As the COVID-19 pandemic continues, laboratorians are seeing people draw incorrect conclusions as well, and some of those assumptions are leading to some potentially unsafe practices in some laboratories.

It’s easy to understand and even to forgive any misconceptions. The COVID-19 pandemic is unprecedented in our lifetime. The virus is new, it has spread very quickly, and there are unknowns about its make-up and mode of transmission. The situation has changed rapidly, and agencies like the CDC have had to change safety recommendations almost daily at times. Couple that with a media that by its nature uses fear and drama to ensure continued viewership, and people everywhere are going to make some fast decisions, and not all of them will be good.

One example of a change in guidance came from the CDC. At first, they were very careful not to give out any more information for lab safety than what was posted on their COVID-19 web page. When asked if typical lab specimens (blood and urine) from COVID-19 patients could be transported via a pneumatic tube system, they said that all specimens should be hand-carried to the lab. Since many patients were asymptomatic and many more could not be tested because of kit shortages, that would basically mean that all specimens in all hospitals would be carried to the lab. Before hospitals could react or even find the information, the CDC changed its recommendations. Only respiratory specimens from these patients should be carried directly to the lab (https://www.cdc.gov/csels/dls/locs/2020/transport_recommendations_for_covid-19_specimens.html), blood and urine can safely be transported. Given what is known about viruses and other pathogens in blood, walking all specimens to the lab doesn’t sound like a necessary guideline, does it? But this judgement in guidance simply illustrates what can happen when a situation changes rapidly.

With the push for the need for COVID-19 testing, news has come out about specimen collection kits and new and faster testing platforms. Not everything that has been reported has been factual. Every night we see numbers of cases and mortality rates reported in the media. Mathematically, one cannot determine a mortality rate without knowing the total number of patients’ cases. If there aren’t enough test swabs and reagents, and if we don’t test those who are asymptomatic (estimated to be about 25% of cases), how can we calculate any kind of accurate rate? Some laboratories have been pushed to bring on testing, and with little experience with brand new instruments, there has been work performed in some locations without adequate PPE or other safety measures. Look at your testing platform. Review the steps to see if there are any potential aerosol-creating steps. Are the correct PPE or engineering controls in place? Now more than ever it is vital to adhere to lab safety regulations while paying attention to the latest COVID-19 safety guidance. If you feel there is work being performed without adequate safety protection, escalate the situation as soon as possible. There will be no one to run teste if all of the laboratory staff becomes sick.

In many locations, hospitals have responded to the shortage of N95 respirators and surgical masks by developing methods to decontaminate and reuse them. While that is an innovative idea, make sure the system in place has physical and biological checks in place to ensure the reprocessing is effective. Spot test disinfected N95 respirators by performing fit-testing with them as batches are reprocessed. Use a biological indicator to ensure the COVID-19 virus particles have been eradicated. Do not reprocess N95 respirators used for protection against tuberculosis unless it is certain the disinfection process is known to effectively destroy TB bacteria.

Sometimes we come to the wrong conclusion, and sometimes mistakes are made, even in the world of science. But we are human, and we have to come to terms with that or we might end up alone in a disco like the aforementioned Lola. That’s why it’s important that we stop for a moment and pause, especially when an event occurs rapidly and transforms the very environment where we work. Take the time to ensure safety measures are in place for everyone involved. If something doesn’t make sense, question it. Examine it, and work with your staff as a team to make sure we can do what we are called to do- to safely perform lab work in order to provide quality results for the patients we serve.

Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years experience as a certified medical technologist. Today he is the Laboratory Safety Officer for Sentara Healthcare, a system of seven hospitals and over 20 laboratories and draw sites in the Tidewater area of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.