The Food and Drug Administration (FDA) issued new guidance on February 29, 2020, for laboratories to be able to develop novel coronavirus (COVID-19) molecular diagnostics tests and begin use prior to obtaining Emergency Use Authorization (EUA). This permits laboratories that are CLIA certified and meet requirements to perform high complexity testing to start offering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular diagnostic testing after validation is completed as outlined in the guidance. Laboratories should submit an EUA request to the FDA within fifteen business days after validation. FDA will be hosting a webinar to provide more information on March 2, 2020, at 3 pm ET.
Clinical laboratories should contact their state health departments for guidance if they have a suspected COVID-19 case specimen. Clinical laboratories should NOT attempt viral isolation from specimens collected from COVID-19 persons under investigation (PUIs). For interim guidelines for collecting, handling, and testing clinical specimens from PUIs for COVID-19, please see the CDC Coronavirus Disease 2019 (COVID-19) website.
No, I’m not talking about Netflix or HRH Queen Elizabeth II, nor am I making references to tiaras, bars, beer brands, or imminently deliverable babies…I am, of course, talking about Coronavirus as it would certainly have caught most of our collective attention in the media by now.
I really enjoyed writing last month’s list of what I think are important things on the horizon for pathology and laboratory medicine this new year, but this month let’s take a more topical turn. So put your surgical masks on, wash your hands, quarantine the next 10 minutes of your time and get ready as I take a shot at the novel 2019 coronavirus outbreak!
***Let’s talk about you and me, Let’s talk about COVID-19…***
A long time ago, in a galaxy far, far away (aka: last year, about 20 minutes north of my apartment in Manhattan) I was in medical school, on rotations on the floors of a hospital in the Bronx. I experienced the surges of two flu-seasons and had a fantastic little mnemonic to remember the viruses that caused colds in most patients. Depending on age and immune system status, you had to think about the principal three viruses we see all the time—I remembered them as: “c-A-r,” note the capital “A.” Let me explain; the letters correspond to coronavirus, adenovirus, and rhinovirus. The are in a general order of when they appear during the months of the year (as coronavirus and rhinovirus kind of switch off in the spring, while adenovirus is around always thus is capital designation). There are a few hundred viruses which contribute to cold/flu-like symptoms in patients and, unless a patient is compromised in some way, we really worry most about one of them. Hint: it’s the one we give shots for annually, more on that in a minute.
As far as this coronavirus outbreak is concerned, this is a “novel” (i.e. new) variant (read: mutation) of a respiratory viral pathogen that is affecting a disproportionate number of patients in higher severity than expected. Its official entity name has now been filed by the World Health Organization (WHO) as COVID-19—corona virus disease of 2019. The actual virus is a relative of the infamous SARS virus from the early 2000s. That was SARS, this is SARS 2.0—literally. This virus is designated SARS-CoV-2. SARS stands for Severe Acute Respiratory Syndrome and is caused by strains of coronavirus found in the remnants of infected individuals’ coughs and sneezes—please wash your hands—and causes a spectrum of symptoms from mild to severe including pneumonia, respiratory disease, and even renal failure.
How Does this Even Happen?
Okay, who took a sabbatical to Wuhan, China, and ate a wild fruit-bat salad? No one, that’s not how this works. But, if you’re looking for quick grocery store recommendations at the present moment I’d probably tell you to check out ALDI or a farmer’s market a few spots higher on the list than the Huanan Seafood Wholesale Market in Wuhan which harbored a majority of outbreak case-cause tracings. The bottom line is that COVID-19 and the SARS-CoV-2 have appeared in the world the same way the previous similar outbreaks have—through zoonotic mutations which then spread to humans. This zoonotic transmission is so effective to presenting humans with super infectious entities because it sends us pathogenic material we would have never seen before and our “naïve” immune systems are caught off guard. Now don’t get all panicky; yes, I’ve seen Contagion, Outbreak, and read The Andromeda Strain—in fact, I absolutely love when epidemiological medicine has the media spotlight. It’s a very exciting way to showcase public health, medicine, and—our favorite—laboratory professional work!
Basically, this process of mutation and transmission is the modus operendi of a viral particle. You can’t quite kill them, they’re not quite alive by biological definitions, they’re just packaged proteins on autopilot. They’re kind of like natural robots that want to propagate their species by adapting over time—they’re The Borg or Cybermen, depending on your sci-fi preferences. But both offending automaton predators have a mutual enemy in public health—a doctor (get it? TARDIS pilot and/or Beverly Crusher both work wonders in a pinch…) Anyway, it’s never just physicians, but a whole hard-working team of health advocates that conduct surveillance, field research, epidemiologic studies, and first-hand treatment.
***Side note: if you’re bored, in a hurry, or just don’t like my articles—don’t fret! Go watch that Osmosis video on COVID-19 and you’ll be up to snuff on the current outbreak in no time. Or in 12ish minutes.***
***Hey, you made it this far. Great! Interested to know more about the COVID-19 virus from our very own American Journal of Clinical Pathology? Visit here to learn more about the story of how this pesky coronavirus mutated its way into headlines. Fresh off the AJCP presses this month!***
You Should Update Your Antivirus Software
No doubt in my mind you’ve probably seen plenty of coverage about SARS-CoV-2 in the media. I’d also be willing to bet a lot of it is either dilute, sensational, or possibly even misleading. Regardless, there are always going to be people that don’t “buy in” to the public health message. If you remember Contagion¸ Jude Law’s character pushes the efficacy of “forsythia,” a homeopathic herb supplement that supposedly mitigates the horrible disease spread from southeastern Asia from improper food handling—if I recall correctly, it was a paramyxovirus that time. In this SARS-CoV-2 epidemic we have no current effective treatments, so prevention is key.
In an effort to address this type of health misinformation the WHO and CDC are actively disseminating as much educational information and graphics as they can write. Trying to dispense advice for the public including proper mask wearing, education videos, and myth-busting (i.e. hand dryers do NOT kill the COVID-19 virus, UV lamps do NOT kill the virus, thermal readers are effective in screening populations for symptoms within limitations, alcohol and chlorine do NOT kill the virus, receiving packages from China is still safe, pets don’t harbor the virus at this time, other vaccines do not affect this virus, saline nose sprays do not affect this virus, garlic/oils/other supplements have no effect on this virus, and all age groups are affected)—good stuff there. The most trusted sources of information regarding epidemics should be the representatives of functional medicine and health outcomes, doing work every day to make people healthier. Often times, politics, misinformation, or complex situations make information delivery harder than you’d think and the risks are increasingly high.
A Crown of Thorns: Don’t Forget About the FLU!
Flu vaccine deniers: turn away now or be healed! —or at least exposed to another point of view rooted in evidence-only concepts in medicine and population health. Consider the following: as of this month, COVID-19 has infected 43,000 people and killed 1,000 (approximately 2-3%). Remember SARS? That infected 8,000 and killed 700 (approximately 10%). MERS? 2,500 infected, 860 deaths (approximately 34%). And what about Ebola? 29,000 infectious cases with 11,000 deaths (approximately 40%). That was sourced from the Osmosis video with data from the WHO. Pretty impressive right? Well, not if you look at this: according to the CDC, the 2019-2020 influenza burden statistics include 36,000,000 infectious cases, with 17,000,000 clinical visits, 440,000 hospitalizations, and 36,000 deaths. One might say “hey, Dr. Kanakis, slow down there you’re spitting out all these numbers and the facts won’t lie. Looks like influenza only killed 0.1% of cases.” And you know what, you’re right. 0.1% is lower than the other viral epidemics. But check this out, because of the sheer number of cases, that means more people died of influenza than COVID-19, SARS, MERS, and Ebola COMBINED and those happened in other years. That‘s just this year’s flu season alone. I’ve talked before about recognizing and detecting the common cold vs. influenza before, check it out if you’d like a refresher!
We have influenza every single year, and it kills so many more people than we realize. If you want to talk about a terrifying, global viral epidemic, we’ve already got one. And it’s closer than you think. So wash your hands, reduce exposures if you’re sick or immunocompromised, get proper rest, eat well, exercise, read my articles every month, but most importantly—and I cannot stress this enough—get your FLU SHOT!
Thank you so much, see you next time!
–Constantine E. Kanakis MD, MSc, MLS (ASCP)CM completed his BS at Loyola University Chicago and his MS at Rush University. He writes about experiences through medical school through the lens of a medical lab scientist with interests in hematopathology, molecular, bioethics, transfusion medicine, and graphic medicine. He is currently a 2020 AP/CP Residency Applicant and actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Follow him on Twitter @CEKanakisMD
The University Teaching Hospital of Kigali (CHUK) is the largest hospital in its District of Nyarugenge and the biggest national referral hospital in the country of Rwanda, with a 565 hospital bed capacity and 6 operating theaters. It is located in the heart of the capital of the country, Kigali, contributing to its easy accessibility by patients. Rwanda is a country of over 12.5 million people, with an estimated 70.2% of the population living in a rural setting. Per the World Bank, there is an estimated 1 physician per 10,000 people in-country. The government of Rwanda is focused on elevating the country from a low-income developing nation to a middle-income country with a robust health sector capable of ensuring a healthy people with adequate healthcare access. It provides universal healthcare, at a small cost, to all Rwandan citizens who aren’t provided health insurance through employment. In Rwanda there are a total of 14 practicing pathologists, which equates to approximately 1.1 pathologists per million people in the country. In contrast, within the United States there are an estimated 60 pathologists per million people. CHUK offers an array of outpatient, inpatient, surgical, and diagnostic medical services. Inpatient and outpatient services include surgery, accident & emergency, internal medicine, mental health, anesthesiology & critical care, gynecology, pediatrics, maternal & neonatology, ear/nose/throat, ophthalmology, neurosurgery, pediatric surgery, urology, nephrology, dialysis, oncology, and dermatology. Surgical services include general surgery, general pediatric surgery, neurosurgery, orthopaedics, ophthalmology, ear/nose/throat, and obstetrics/gynecology. Diagnostic services include ultrasound, digital x-ray, CT scan, and anatomic and clinical pathology services. In its current state, the hospital has a total of 18 divisions.
There are two facets to the pathology laboratory at CHUK: the Anatomic Pathology (AP) and the Clinical Pathology (CP) laboratories. Within the AP laboratory, also known as the histopathology laboratory, all surgical specimens are grossly examined by a pathology resident and/or pathologist, prepared by a pathology resident for processing, and processed by laboratory technicians into formalin-fixed paraffin-embedded tissue placed onto glass slides. These glass slides are then reviewed by both the pathology residents and the pathologists in order to render a diagnosis, which is communicated to the clinician in order to help direct appropriate patient management. Specimens reviewed at CHUK are predominantly “in-house” specimens generated by the surgeons and clinicians functioning within the walls of the institution. “Referral” specimens are a rarity and generally consist of small biopsies. Cytopathology specimens are also processed within the AP laboratory and include a mixture of fine needle aspiration (FNA) specimens, obtained by pathology residents via superficial FNA, as well as exfoliative cytology specimens such as effusions and urines collected by “in-house” clinicians. Cervical screening conventional pap smears are a rarity. Within the AP laboratory, Diff-Quik, Papanicolaou, and hematoxylin & eosin (H&E) staining was available for slides, as well as a limited panel of special stains: PAS-D, auramine, and a modified acid-fast stain. No immunohistochemistry was available on-site, though cases could be sent for free to nearby Butaro Hospital for IHC or consultation via digital slide scanning.
Regarding my experience at CHUK, I departed the United States on a Saturday evening and reached Kigali, Rwanda by 1AM the following Monday morning. On my first day at CHUK, I was introduced to the 5 anatomic pathology staff, 9 anatomic pathology residents, and the single visiting pathologist serving as a laboratory inspector conducting a mock inspection/assessment. I was given a tour of the pathology facilities as well as the entire hospital system.
There were two aspects to my primary job at CHUK: teaching the residents cytopathology and microscopic review of all live cytopathology cases received in the laboratory. Regarding resident education, there were four ways in which I interacted with the residents during my time to facilitate cytopathology education: lectures, multi-headed microscope unknown slide sessions (unknown case conference where I provided the residents with cases they had never seen before), multi-headed microscope “stump the chump” unknown slide sessions (where the residents presented me with unknown cases I had never seen before), and interactive practicals where we performed various hands-on aspects of cytopathology and general pathology practice.
In respect to lectures, I delivered a total of eight 1.5 hour powerpoint-based lectures covering the following topics: breast cytology, thyroid cytology, lymph node cytology, salivary gland cytology, urine cytology, effusion cytology, peritoneal washing cytology, and frozen section pathology (frozen section lecture presented as a combined effort with Dr. Raina Flores). For unknown slide sessions in which I presented cases to the residents, we had 6 sessions covering the following topics: breast, thyroid, salivary gland, urine, conventional pap, and cerebrospinal fluid. We completed a total of 5 “stump the chump” sessions, where residents gave me slides that I had never seen before and we discussed each case and its work-up as well as its associated differential diagnosis or final pathologic diagnosis at the multi-headed microscope. Topics covered included: breast, thyroid, salivary gland, lymph node, and effusions. Finally, with the assistance of “in-house” pathologists, I helped conduct 2 hands-on practicals with the residents: the first regarding fine needle aspiration technique and slide smearing technique (with Dr. Claire Nadyisaba) and the second regarding performance of frozen section intraoperative consultations using Leica CM1850 cryostats and cow liver (with Dr. Raina Flores).
The second of my duties, live cytopathology case review, was also performed at the multi-headed microscope with the residents each afternoon. On a given day, we would typically receive somewhere between 1 and 4 FNA consultations for which the residents would go to FNA clinic and perform the procedure. The laboratory also received various aspirated and exfoliative cytology specimens, such as pleural effusion and ascites fluids, from clinicians within the hospital system. In total, we reviewed 51 cytopathology cases together at the microscope. 27.5% were neoplastic, with 7.8% being malignant and 2% being lymphoma. 56.8% of cases were negative for malignancy, with 21.5% being inflammatory/infectious. In total, 9.8% of cases were interpreted as “atypical” and 5.9% of cases were non-diagnostic. Of the 51 cases, 21 (41.2%) were FNA consultations that I attended and the resident performed.
On my final day of work, I provided the residents with a 41-page cytology knowledge assessment (in PDF format) to complete at their leisure. This test covered the following topics: cervical and vaginal cytology (19 questions), urine and bladder cytology (11 questions), effusion cytology and peritoneal washings (13 questions), cerebrospinal fluid cytology (12 questions), breast cytology (8 questions), thyroid cytology (17 questions), salivary gland cytology (13 questions), and lymph node cytology (11 questions). Within the document, an answer key with associated detailed explanations was provided so it could serve as a learning aid/study guide for the trainees. On my last workday, the residents were asked to evaluate their experience with the Cytopathology Module/Course. A total of 7 of 9 residents completed the evaluation. Regarding preparation and organization of different topics, all residents found the quality of the powerpoints to be “very good” or “excellent”. The quality of the practical sessions was rated as “good,” “very good” or “excellent by all residents and the entire module was given an overall rating of “very good” or “excellent” by all of the residents. The majority of residents felt their time was used effectively during this module and that the venues for theoretical and practical learning were appropriate. In the free-text areas for additional comments, suggestions for improvement included a longer duration (at least 4 weeks) of the module, more hands-on practical time, the opportunity for residents to present information, and more microscopy sessions. For additional topics to be covered, respiratory cytology was suggested. In overarching comments regarding their module experience, the residents felt the module was well-prepared, the teaching sessions were well-organized, and that the course was interesting and helpful.
Finally, though not within the confines of my assigned “duties”, I also spent a portion of each day acting as “consultant” to the on-site pathologists for challenging surgical pathology cases, offering opinions as able for various lesions that were challenging to classify on H&E morphology alone. I also served as a “second reviewer” for new malignant diagnoses being rendered in the laboratory, offering my name to be included in the report as a board certified pathologist who has laid eyes on the case and agrees with the interpretation. Examples of some interesting surgical pathology cases I saw in “consultation” included Wilms tumor (nephroblastoma), cystic partially differentiated nephroblastoma (CPDN), pleomorphic xanthoastrocytoma (PXA), sinonasal undifferentiated carcinoma, basaloid moderately-differentiated carcinoma of the uterine cervix, high-grade large cell lymphoma of the cervical lymph node, high-grade squamous intraepithelial lesion of the vulva arising within a condyloma acuminatum, and low-grade papillary urothelial carcinoma of the bladder. I also attend a single Tumor Board Multidisciplinary Conference with two residents and 1 staff pathologist in which a resident presented a case of mucinous moderately-differentiated adenocarcinoma of the colon transmurally invading adjacent ileum. It was interesting to hear the clinicians, pathologists, and radiologists interact in addressing quality of care, efficiency of care, and clinical decision-making. The time of initial presentation to the time of surgery was greater than 1 year for this patient.
My time spent at CHUK in Kigali, Rwanda was an invaluable experience. The work setting granted me the opportunity to expand my role as an academic educator. I was offered the opportunity to present as many lectures as possible to the resident trainees, participate as the leader of multi-headed microscope slide sessions, serve as a spearheading physician in laboratory services expansion efforts, and work as an ‘attending’ physician overseeing trainees’ performance of FNAs. It was an experience that demanded personal growth, via the assumption of roles that I am not privy to as a post-graduate medical education trainee in the United States. Additionally, I was exposed to a cytopathology and surgical pathology workload for a patient population quite dissimilar from the community I am used to serving. With limited ancillary testing capabilities, I returned to a more “pure” form of rendering pathologic diagnoses, based on H&E morphology alone rather than on the synthesis of cyto- and/or histomorphologic appearance coupled with various ancillary diagnostic testing data points. In conclusion, this was an experience that expanded my understanding of the ways in which I can be useful as a board certified anatomic and clinical pathologist interested in incorporating medical mission work into my clinical practice. Beyond arriving in countries without expansive pathology laboratory systems and simply doing the work, I can also pursue opportunities where I can help educate and shape burgeoning in-country pathologists who will then go on to have productive, hopefully decades-long careers in their country, serving their countrymen. This trip certainly expanded my understanding of the role of a “visiting” pathologist. This experience was made possible by the ASCP Trainee Global Health Fellowship Award. Thank you so much to the ASCP, Dr. Dan Milner, Alpa Pandya, and the CHUK pathology department for helping to facilitate this opportunity!
-Kelsey McHugh, MD is a board certified anatomic and clinical pathologist, with cytopathology subspecialty certification, who is currently completing gastrointestinal, hepatic, and pancreatobiliary pathology subspecialty training. She anticipates graduating from the Cleveland Clinic Gastrointestinal, Hepatic, and Pancreatobiliary Pathology Fellowship in June 2020, after which she will remain at the Cleveland Clinic as a staff pathologist beginning July 2020.
2019 marked a very special year for me as I had the incredible opportunity to interview some of the most remarkable laboratory medicine specialists in the field of Pathology about their involvement in global health. Although their roles ranged from everything between medical technician, to PA, to medical student, to practicing pathologist, to the CEO of a major pathology organization, they all had one thing in common – they actively take the time to better their global community and contribute to improving pathology services in resource limited settings.
Now that the year is winding to a close, I’d like to take the opportunity to highlight all of these wonderful efforts and hopefully inspire you to take similar initiatives where applicable to your abilities and interest. Read on for a summary of each interview.
Dr. Kumarasen Cooper not only volunteers bi-annually in Botswana’s only academic pathology department as a way to give back to his native Africa, he has also worked to create an opportunity for residents at UPenn pathology to be involved too. Because of his efforts, the UPenn residents can accompany him and work together on the departments’ shared initiatives using official institutional elective time. This is a rare opportunity in pathology training, and is a model of how academic institutions can engage their trainees in global health initiatives.
Julie Papango, a medical technologist, has worked with Doctors without Borders/ Médecins Sans Frontières (MSF) to bring laboratory medicine to the world’s most remote places. She was one of MSF’s very few volunteers with laboratory experience and therefore has played a crucial role in projects ranging from addressing the infectious disease outbreaks in a Sudanese refugee camp, to helping the Cambodian Ministry of Health to improve their national tuberculosis detection program.
Dr. Ann Nelson is an expert in infectious disease pathology and has worked in many parts of Africa for more than 30 years. The focus of her work has been in HIV/AIDS pathology in the US and in sub-Saharan Africa. Currently she works on educational projects and capacity building in anatomic pathology, and linking anatomic pathology to ongoing clinical and epidemiologic research. She finds ways to be helpful in any new setting by just showing an open and willing attitude. “I went and built partnerships with everyone I could. You have to just go and talk to people, and ask them “What can we do?” With this approach, she’s been able to find countless ways to contribute her expertise to the world. She’s also spent innumerable hours in studying and publishing the issues affecting pathology services in Africa. Notably, she worked to conduct a landmark survey of African pathologists to determine the status of pathology resources in Sub-Saharan Africa.
Dr. Blair Holladay and Dr. Dan Milner have worked in global health most of their professional careers and now lead the American Society for Clinical Pathology’s efforts in improving laboratories worldwide. They are working with governments and local agencies to make sustainable changes in the neglected pathology and laboratory medicine landscape in low and middle income countries (LMICs). They are responding to the urgent need to improve pathology services to address the rapid increase in global non-communicable disease (NCD) incidence. As Dr. Holladay points out “Compared to the scale of the HIV crisis, NCDs are the health threat that gone unchecked, will go far beyond in affecting huge proportions of the global population.” In response to addressing this problem, Dr. Milner points out that the lab is the cornerstone to the solution: “In the field of cancer, which is a major problem in LMICs, you cannot treat the patient without a diagnosis – and the diagnosis must come from the laboratory.”
Dr. Constantine Kanakis is a medical student who decided to be an active part of the community of Sint Maarten while living there attending medical school. The community was facing multiple mosquito-borne infectious disease epidemics that includes Zika virus. In response, Dr. Kanakis took a service-learning elective course in medical school that focused on community outreach. He led the way to create an outreach program that has now been incorporated into the nation’s Ministry of Health Collective Prevention Services program. Dr. Kanakis encourages everyone to “Start by looking around at your immediate surroundings and take an assessment of the issues affecting the community. Anyone can do this, whether you are a physician, scientist, or a community member.”
Dr. Adebowale Adeniran, a cytopathologist, frequently works with the USCAP group “Friends of Africa” in which he speaks at the annual meetings, is involved in the group planning activities, and participates in educational initiatives and conferences in Africa. He encourages all academic institutions to engage in global health, stating “Academic institutions in the US can offer ways of enhancing training opportunities for African pathologists and trainees by offering short- or long-term exchange programs. This helps to bridge the gap between practiced based learning in resource limited vs. US institutions.”
Nichole Baker is a pathologist’s assistant that heard of a lab in Uganda that needed outside pathology help due to being severely understaffed. So Nichole decided to go visit the lab and see where she could help. One of the main issues was that the lab lacked an electronic medical record (EMR) system and keeping track of cases and patient reports was a real challenge. With no background in computer science, Nichole resourcefully reached out to her personal network to find someone that could help her build a free EMR and now the laboratory can track specimens, issue electronic reports, and has reduced their turnaround time as a result.
Dr. Drucilla Roberts is one of the world experts in perinatal pathology and has been working in Africa for over ten years with a focus on capacity building. Besides offering her surgical subspecialty expertise, she is also partnering with local pathologists to participate in ground breaking research on topics specific to low resource settings. She’s written widely on the need for pathology services in Africa. She says that one of the biggest problems in improving pathology services in Africa is that “there are not enough pathologists. You can help improve things in individual labs to a point, but for long term there has to be more pathologists working in Africa.” Dr. Roberts actively engages in solving this problem by helping train African pathology residents and by recruiting other pathologists to do the same.
Dr. Von Samedi, a cytopathologist, has worked with ASCP’s Center for Global Health at their partner sites all around the world. Dr. Samedi started working with ASCP as a resident, using his unique ability to speak French and Creole to assist ASCP in Haiti following the devastating 2010 earthquake. He has since worked on improving laboratory services in a vast array of ways, with everything from mentoring and local laboratorian training to running workshops on HIV related testing services. Volunteering gives Dr. Samedi a sense of purpose and he states that he “also benefits from interacting with my global colleagues and learning from them.”
There are so many more laboratory medicine specialists working in global health that I would have loved to feature on Lablogatory – but there are so many that I cannot capture all of their stories to share here. I hope that you have gained a snapshot of the potential ways that you can get involved, the possibilities are truly endless!
If you’ve been following this series, know that I am extremely grateful for your time and attention to this important matter. This will be my last post with Lablogatory for the time being, as I will be taking a break from writing to welcome my first child into the world! Wish me luck! J
Please also take a moment to fill out this survey (https://www.surveymonkey.com/r/K7YK8LW) so that we can learn more about your interest and experience in global health and you can enter to win a global pathology prize pack!
-Dana Razzano, MD is a former Chief Resident in her fourth year in anatomic and clinical pathology at New York Medical College at Westchester Medical Center and will be starting her fellowship in Cytopathology at Yale University in 2020. She is passionate about global health and bringing pathology and laboratory medicine services to low and middle income countries. She was a top 5 honoree in ASCP’s Forty Under 40 in 2018 and was named to The Pathologist’s Power List of 2018 and 2019. Follow Dr. Razzano on twitter @Dr_DR_Cells.
One of the challenges of providing healthcare to patients of any type is “staying current” or “keeping up with the literature.” This can be especially challenging in the diagnostics laboratory where novel or unique approaches to a given test or test method or disease may show early promise but have no clinical utility, be too expensive, or not actually significantly change work-flow and/or patient value to justify implementation. On the other hand, sometimes a technology or test which is in development or approval can be so anticipated that clinicians and laboratorians are frustrated that it is not yet available.
In global health, there is a different problem that is encountered every day. There are technologies and tests that are approved, have documented clinical utility, and add great value to patients but they are simply not available because of supply chain, cost, administration, or geography. In such situations, the practitioners in these settings face extreme frustration—especially with stock-outs—and can become jaded and non-dependent on laboratory testing as part of care. This latter issue is a major challenge in cancer care where cancer diagnoses are required before treatment can begin; yet, in a large number of countries, access to cancer diagnostics routinely is not available. It is to that end that ASCP along with a whole host of NGO, industry, academic, and government partners are making great efforts to improve cancer care in each part of the continuum.
In this environment, however, disruptive innovations are, in fact, much easier to recognize as forthcoming. In the early 2000’s when I was working and traveling in Malawi, our project had a landline in the hospital to call the landline at the doctor’s house for issues overnight with patients. This required 24-hour nurses to be physically in the ward, tied to the phone and the patients. Landlines were expensive to install, had a very long waiting list to be installed, and, for the most part, the majority of the population in the country had never had a phone line in their dwelling. By the mid-2000’s, our project had one or more cellphones (as did the nurses) and communications through texting were nearly constant (especially since it was less expensive than making a phone call). By 2010, cell phones were ubiquitous in Malawi (and almost everywhere else in Africa) and there was no demand for landlines. Although this is a commonly used example, consider the adoption of cellular telephones and now smartphones in the US compared with Africa. There was push back, denial, avoidance, and even refusal to use them because there was an existing, well established system of landline communication. If you want to install cable television and internet in your home as late as 2016, you were often required to bundle with a landline. The point is that the adoption pattern was significantly different because there was a pre-existing competitor with the new technology although—clearly—the new technology was superior.
Now consider a woman of 35 years who has a breast mass on mammogram in downtown Boston today. She will likely have an imaging study with immediate ultrasound and fine needle aspiration and/or core biopsy subsequent. A pathological diagnosis will be issued within 3 to 4 business days (or sooner) which includes a histological diagnosis along with hormone receptor status and Her2 staining. She will see a clinician likely within a week for a positive cancer diagnosis and a treatment plan will be decided upon and executed. If we consider a similar woman in downtown Nairobi, Kampala, or Lagos, they may, in fact, have a similar experience because of the recent efforts globally to improve cancer awareness, diagnosis, and treatment. There may be some delays (reports may take several weeks), potential stock-outs, etc. but, in these major cities, the services might exist. They are likely, however, provided in private clinics, will cost a premium, and may or may not have any guarantees about quality.
The reality, however, is that the vast majority of women in the US or Europe who present with breast cancer do so at a very early stage because of active screening programs which include mammography. The vast majority of women in low- and middle-income countries (LMICs) present with later staged disease because of lack of screening. The latter group of women, however, often live in rural conditions and/or poverty conditions such that seeking care for a breast mass (of any size) will require them to spend time and money to travel to one of the major cities and attempt to access services. With this situation, many of these cancers are detected by the health system at a late stage where curative therapy windows have been missed.
Onto these observations let’s now overlay access to a test for a breast mass that can be performed on a fine needle aspiration biopsy and resulted in ~4 hours which will provide a diagnosis of cancer (or benign) along with prognostic features directing treatment. If we consider the woman in Boston, we may see such a test providing an incremental improvement in care because billing systems, litigation fears, compliance requirements, or accreditation standards still include routine histology and immunohistochemistry to be performed on a tissue biopsy. To some degree, the test may be rejected because it is adding a cost over the standard costs without adding value (other than speed) to the results. However, for the woman in the rural village who likely has access to a community health worker, access to such a test could mean that she starts oral therapy the same day she has the health visit without ever having to leave her village. We have now removed the journey to a clinic that can performed a biopsy, the costs associated with that travel, the time lost while traveling and waiting for a result, and removed the risk that this is not breast cancer—which would mean all the time and money were wasted. For this woman, enormous value is created for her with a test that is performed same day with immediate results.
This concept of point-of-care (POC) cancer diagnostics would arguable meet resistance in the US or European system because of competition with existing systems and other issues as mentioned previously. In an LMIC setting, as there may be no competition, such an innovation would sweep the system and become standard of care—almost regardless of cost. This last bit is very important because traditional systems for performing histology and IHC are complex, costly, and require multiple highly trained individuals to get a quality result. If that process costs $75 to $100 US dollars (to the health system) to provide and, for the individual patient, $10s to $100s of dollar for the travel, lodging, and lost wages, the cost of such a test could, in a stable, high-income country (HIC) market, fetch a hefty price. However, if such a test is priced at $25 to $50 USD (half the cost of the current system excluding the travel), the immediate replacement of the old system with this new system for the given indication must and will occur. This uptake is amplified in an LMIC when the POC test moves to the patient in a geographically distributed process. Breast cancer is an obvious target for such an approach because the tumors are easily accessible, the disease is quite common globally, and the primary therapies are very inexpensive. Could such a test have an impact in an LMICs for bone marrow-based, lung, bladder, colon, prostate, liver, kidney, or soft tissue tumors? The answer to that question lies in the availability of therapy, incidence of disease, and access to radiological equipment rather than availability of the actual POC device. That is, once you have a POC test for one cancer, creating a subsequent POC test for another cancer is a surmountable technical hurdle. But will such a test be able to have an impact because of the alignment of the other factors? It is likely that as you are reading this sentence, you have thought of a few yourself but there are certain cancers where you are likely thinking, “not possible”.
For breast cancer, two such POC approaches are coming down the pipeline. The first is the Cepheid GeneXpert Breast STRAT4 assay which measures quantitative RNA (qRNA) for ESR1, PGR, ERBB2, and MKi67. These four assays are surrogates for standard immunohistochemical staining for ER, PR, Her2, and Ki-67, respectively. In a series of published and in press feasibility and validation studies, the qRNA assay is essentially equivalent to IHC. There are nearly a dozen studies of this new testing cartridge using formalin-fixed, paraffin embedded (FFPE) tissue throughout Africa where the test is being compared to standard IHC. However, in at least one site, the test is being performed directly on FNA material. The second test is from the laboratory of Dr. Sara Sukumar at Johns Hopkins which uses a set of DNA methylation markers that can separate benign from malignant disease on FNA using only 10 markers. By combining these two approaches (benign vs. malignant followed by STRAT4 for positive tumors), a diagnosis of malignant breast disease with prognostic factors for treatment could be obtained in less than 4 hours.
Let’s jump forward to the point in time when both of these POCs are available (or, in fact, any POC for cancer is available). How would they change the approach to breast or other cancer in an LMIC? Because both tests require only an FNA of a mass and because tumors of the breast and other organs today are often late staged, community health workers could be trained to evaluate patients with masses, perform the sampling, and run the test in a remote village. Regardless of stage, starting a breast cancer patient on estrogen receptor antagonists can provide palliative relief or pre-surgical treatment. As a population down stages—which occurs as community health workers begin routine screening—the testing can triage benign and malignant disease at a fraction of the cost for both the system and the patient. Based on population epidemiology, nearly exact costs for these services can be predicted for a population and stock outs can be avoided. Corollary note: Only for those cancers for which you HAVE a POC.
How would these tests change the approach to breast cancer in an HIC? There would likely be resistance at many levels but, eventually, the relatively low cost and the increased patient value would allow the tests to replace or displace standard diagnostics. Without complete replacement, there could, at a minimum, be multimodality redundancy which increases quality. However, the tests would find purchase within the system because in some settings their cost and added value would make any other choice impossible.
For both settings, we can now add other market entrants, other tests for other cancers, and a generalize increased in cancer awareness in the community, all of which would increase demand, improve morbidity and mortality, but decrease costs. Such a situation would be highly valued by the patients and, therefore, is the most important eventuality as this disruption ensues. Recognizing forthcoming change is sometimes hard and sometimes easy; however, accepting and embracing forthcoming change in healthcare can lead to best outcomes for our patients—the central mission of ASCP.
Dr. Milner has no financial disclosures regarding this blog post and has received no fiscal or in-kind support from any entity, named or otherwise, that involves this blog post.
Wu NC, Wong W, Ho KE, Chu VC, Rizo A, Davenport S, Kelly D, Makar R, Jassem J, Duchnowska R, Biernat W, Radecka B, Fujita T, Klein JL, Stonecypher M, Ohta S, Juhl H, Weidler JM, Bates M, Press MF. Comparison of central laboratory assessments of ER, PR, HER2, and Ki67 by IHC/FISH and the corresponding mRNAs (ESR1, PGR, ERBB2, and MKi67) by RT-qPCR on an automated, broadly deployed diagnostic platform. Breast Cancer Res Treat. 2018 Nov;172(2):327-338.
Wasserman BE, Carvajal-Hausdorf DE, Ho K, Wong W, Wu N, Chu VC, Lai EW, Weidler JM, Bates M, Neumeister V, Rimm DL. High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence. Lab Invest. 2017 Dec;97(12):1521-1526.
Downs BM, Mercado-Rodriguez C, Cimino-Mathews A, Chen C, Yuan JP, Van Den Berg E, Cope LM, Schmitt F, Tse GM, Ali SZ, Meir-Levi D, Sood R, Li J, Richardson AL, Mosunjac MB, Rizzo M, Tulac S, Kocmond KJ, de Guzman T, Lai EW, Rhees B, Bates M, Wolff AC, Gabrielson E, Harvey SC, Umbricht CB, Visvanathan K, Fackler MJ, Sukumar S. DNA Methylation Markers for Breast Cancer Detection in the Developing World. Clin Cancer Res. 2019 Nov 1;25(21):6357-6367.
-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.
Von G. Samedi, MD, PhD, is a cytopathologist at the
University of Colorado in Denver, CO. I had the pleasure of meeting Dr. Samedi
as a result of the thoughtful introduction facilitated by Dr. Melissa Upton,
who thought we should talk given our shared interest in global pathology.
I learned that Dr. Samedi is originally from Haiti and
completed his MD, PhD, and pathology training in the US. He has always been
interested in global health as part of his personal and professional passion
and has spent the last decade dedicating his expertise to improving pathology
services in low resource settings. It was readily apparent to me that Dr.
Samedi’s approach to the world’s healthcare issues is based in the fact that he
views these as shared problems – ones that he can and does help solve. This
mindset is reflected in the way he lives his life – admirably contributing to
society in any way that he possibly can. I was eager to hear of the
opportunities he’s found in order to contribute, so that I might learn and
share with all of you the ways that we can all get involved. Read on to
discover the inspiring story of someone who has persisted in finding ways to
give to the world through service!
Q: When did you first get started working in global
health through pathology?
A: I started working with ASCP when I was a 4th
year pathology resident in 2010 when they called me to assist their project in
Haiti, which was in response to the tremendous damage caused from the
earthquake. I had signed up as a potential volunteer on their website prior to
this and they reached out to me seeing that I had language proficiency in both
French and Creole. I spent 21 days working with them and my residency program
allowed me to count this time as an outside elective. Their main goal was to work
with the Haiti’s national public health laboratory (Laboratoire National de
Santé Publique) and its various national and international partners to set up
and run a laboratory in this acute disaster situation, and the hands-on
experience I gained in doing this was well worth my program elective time.
After this, ASCP requested that I continue to volunteer with
them and since then, I have been working on pathology and laboratory medicine
improvement projects at their partner sites all over the world.
Q: Can you tell me about your experiences volunteering
with ASCP’s global health initiatives?
A: Working with ASCP at their global partner sites
has allowed me to volunteer in a variety of ways which is unique to the needs
of each situation. Every trip has been different. In Botswana, I helped process
and read the cervical biopsy specimens that had accumulated as a result of a
government program to address the high incidence of cervical cancer. The biopsy
program was successful except that there weren’t enough pathologists to give
results from the tissue samples – so the government reached out to ASCP to help
fill the gap in care. In Ukraine, I worked with laboratorians and clinicians in
which I helped conduct a workshop on HIV related testing services. In the Ivory
Coast, I worked as a part of a mentorship program to assist a newly formed
pathology organization gain functional independence. In Rwanda, the project was
focused on bringing telepathology services into the laboratory. In Kenya, I
worked with ASCP to offer support to the local pathology association. I’ve also
returned to Haiti since 2010 and now we’ve shifted away from disaster
management and focused on local laboratorian training with the goal of
Q: Why do you volunteer to improve global pathology
A: Historically, pathology and global health are not
thought of as connected, yet without pathology, there is no practice of modern
medicine. It is the same anywhere in the world as it is in the US, you must
have a functioning pathology laboratory in order to effectively deliver health
care. Once you understand this, you understand the need that exists in low- and
middle-income countries where there is ample opportunity to serve and give
back. Doing so gives me a sense of purpose and it is not just a one-way relationship,
as I also benefit from interacting with my global colleagues and learning from
them. What I have seen my colleagues do with so few resources is impressive and
Q: How do you fit volunteering into your schedule?
A: My volunteering experiences have ranged anywhere
between 3 to 21 days. I prioritize this work and have been fortunate to work
for departments that support it, often allowing me to use professional time and
vacation time to work on these projects.
Q: What advice would you give someone new to engaging in
A: The key is to focus on building relationships for
the long term. Be patient, flexible, and realize that what you want to
accomplish may not happen in the first or even the second visit. Sometimes
things just don’t go as planned and you have to keep working and go with the
flow. If anyone in laboratory medicine is looking for volunteering opportunities,
reach out to ASCP and volunteer to get involved – you can travel to their
partner sites, volunteer to read cases through their telepathology program, or
serve on ASCP’s global health committees. There’s a way for everyone and anyone
working in laboratory medicine to get involved, no matter what your specialty
and capacity to serve is.
-Dana Razzano, MD is a former Chief Resident in her fourth year
in anatomic and clinical pathology at New York Medical College at
Westchester Medical Center and will be starting her fellowship in
Cytopathology at Yale University in 2020. She is passionate about global
health and bringing pathology and laboratory medicine services to low
and middle income countries. She was a top 5 honoree in ASCP’s Forty
Under 40 in 2018 and was named to The Pathologist’s Power List of 2018
and 2019. Follow Dr. Razzano on twitter @Dr_DR_Cells.
Constantine E. Kanakis, MSc, LS(ASCP)CM is a board certified Medical Laboratory Scientist and is a newly minted MD. Any pathology program director reading this should pay close attention, since he is currently completing the Pathology Match for July 2020 and you would be lucky to have him in your program. Constantine has done incredible work in the field of pathology already, and was recognized in the prestigious ASCP 40 Under Forty award program in 2017 and he was recognized as a Top Ten medical student with the ASCP Academic Achievement Award in the same year.It was his passion for working to better his community that earned him these, and I can only imagine what else he will do in his career. I came across his work through reading his ASCP Lablogatory blog contributions, to which he has contributed insightful and quality material for years. His work in global health particularly stands out as what he has been able to accomplish in such a short time and while in medical school is really spectacular. If you want to know how to get engaged in your community and make a tremendous impact in the world, read on, you will surely be inspired to do so after reading this!
Q: Can you tell me
about your background and what led you into Pathology for your career choice?
A: I received my undergraduate
and masters in Chicago studying molecular biology, political science, bioethics,
and medical laboratory science. I’ve worked in various laboratory roles for the
last ten years, mostly in blood bank and hematology. After some time, I decided
to return to pursuing a more advanced career in medicine and go to medical
school and was naturally drawn to pathology from having worked extensively in
Public health was always something I was interested in, but
didn’t know how to get involved. This changed when I had an opportunity to take
a service-learning elective course in medical school focused on community outreach.
We were prompted to choose a project to focus on, and since Zika virus was such
a heightened threat to the community of Sint Maarten in 2015-2016, as well as
the region at-large, I decided to focus my efforts there. I organized an effort
to reach out to the community and help educate them on Zika
prevention/infection through speaking at town hall meetings, health drives, and
by creating vector control projects in the field. Together with a team, we
developed school-based task forces to educate children so they would bring the
information home to their parents and siblings. This arm of the project was
mirrored after the recycling initiative in the 90’s that was targeted at US
school children to bring recycling programs into the home. Recycling started in
schools and it was effective in changing the home culture. Our Zika education
based program was so successful that the Sint Maarten Ministry of Health
adopted it as an official outreach program as part of their Collective
Prevention Services. And was even touted as a success by representatives at the
2016 Global Health Security Agenda session in Miami.
I also married this community outreach project to the Zika
virus research that I was involved in with my medical school. We used
commercially available antibody kits and I both wrote the SOPs and ran testing alongside
other team members in the laboratory.
With my background in public health, research, and working
in the laboratory as a technologist, Pathology is a career that will allow me
to engage in all of these things. Pathology is a perfect career for focusing on
global health due to its ability to intervene on behalf of the population in a
data driven way. Rather than helping one person at a time, I can help entire
demographics through epidemiologic based interventions.
Q: Why do you think
medical students should get involved in global or public health?
involved in solving the problems in your community enriches your education in a
way that solely reading about issues cannot. When you are actively engaged in
the solution, the problem becomes more than just something you are reading and
learning about in the text. Not only does this enhance your education and understanding,
but it also gives you the benefit of being part of your community in a
meaningful way. There are so many preventable issues to focus on – in the US
Q: How can someone
get started in serving their community?
A: Start by looking around at your immediate surroundings and take an assessment of the issues affecting the community. Anyone can do this, whether you are a physician, scientist, or a community member. The first step is to collect data to define the issue and narrow your target. Next is to plan an intervention; start small and organize or join a group working on the issue and just get involved. You will be surprised at how quickly things can develop. And don’t be afraid of failure—taking setbacks are critical in a continuing process of reevaluating and readjusting your project!
Q: Now that you have
finished with medical school, what is next for you and where do you see for your
A: In between
residency program interviews this month, I will be flying to Sint Maarten to
deliver a TEDx talk about the rapid evolution of medicine and how we can
prepare for the changing landscape. [You can view the talk here: https://vimeo.com/365844585 (skip ahead
to 5:00 to jump straight to Constantine’s presentation)].
Next I’m planning to present an abstract in the next Caribbean
Center for Disaster Medicine conference. With hurricanes threatening the
Caribbean islands and in particular Sint Maarten which was hit in 2016, there’s
been a lot of energy centered around disaster preparedness. My focus is on
making sure the planning efforts including blood bank and other lab services
are ready in the case of a major disaster.
In the future, as a pathology resident and beyond, I want to
continue to work in both my local US setting and abroad. In the US, there are
many public health issues that need to be focused on. For example, there’s been
a record resurgence in preventable infectious diseases due to the
anti-vaccination movement. There are also people suffering from Hepatitis C
related cirrhosis who aren’t aware that Hepatitis C is curable. There are many
educational campaigns for issues like this that can change lives, and
pathologists are the ones that can fulfill that role as health educators.
My wife is a RN, has a master’s of nursing science (MSN), is
a certified nurse leader (CNL), and is finishing her Doctorate of nursing
practice (DNP) in advanced public health with a focus on vulnerable populations
and disaster planning, has been an excellent partner and resource for community
outreach all along and we hope to focus on these issues throughout our careers.
It’s exciting to think of all the possible ways we can help make our community
-Dana Razzano, MD is a former Chief Resident in her fourth year
in anatomic and clinical pathology at New York Medical College at
Westchester Medical Center and will be starting her fellowship in
Cytopathology at Yale University in 2020. She is passionate about global
health and bringing pathology and laboratory medicine services to low
and middle income countries. She was a top 5 honoree in ASCP’s Forty
Under 40 in 2018 and was named to The Pathologist’s Power List of 2018
and 2019. Follow Dr. Razzano on twitter @Dr_DR_Cells.