There is a global shortage of pathology and laboratory professionals, and this phenomenon is especially worse in developing countries.1 Central to combating public and global health emergencies is a functional healthcare system, and at the fulcrum of that is pathology and laboratory services. According to Dr. David Madziwa of the Zimbabwe Association of Pathologists, “the issue is in the tissue.” To effectively address global healthcare challenges like the one currently experienced with the COVID-19 pandemic, Pathologists and laboratory science professionals are needed to develop effective testing and reporting strategies for optimal patient care. One way to address this problem is the development of effective global partnerships across healthcare systems.
However, developing such partnerships requires effective communication and strategies. There are documented instances where attempted efforts by public health professionals from developed nations have been futile in developing countries, because of conflicting priorities and ambiguous goal setting.2 Many public health interventions do not usually involve pathology and laboratory professionals in their planning and execution. And in doing this, they fail to understand the critical role of the lab in any successful healthcare system.
Building successful global health partnerships through effective laboratory services begins with a clear understanding of the healthcare systems in the region of interest.3 Critical questions that need to be answered include, what kind of healthcare model thrives? Is the focus more on preventive or corrective medicine? How important are healthcare issues prioritized in terms of budgetary allocations and other resources?
The purpose of such partnerships should also be well articulated. Partnerships must be guided by a shared vision and purpose that builds trust and recognizes the value and contribution of all members.4 Each partner must understand and accept the importance of the agreed-upon goals. This leads to improved coordination of policies, programs, and service delivery. Shared and transparent decision-making processes are also essential as partners work towards their common purpose.
Successful partnerships depend on shared values, mutual understanding and acceptance of differences-cultural norms, knowledge and ways of thinking or doing things, between both parties.4 When partners respect each other’s contributions and regard each other as equals, then the likelihood for shared goals to be achieved significantly increases.
Functional laboratory services are fundamental to effective healthcare systems. Laboratory professionals can play a huge role in addressing the global burden of disease by partnering with local, national and international communities in addressing the challenges associated with ineffective and sub-standard diagnostic services.
For example, one major factor that has been a huge barrier to effectively addressing the rising scourge of cervical cancer for women in developing countries is ineffective screening programs and the dearth of trained laboratory personnel and pathologists.5 To address this problem, global partnerships can be established in regions with limited resources to provide personnel training in the evaluation and interpretation of cervical pap smears. Mortality from cervical carcinoma will continue to remain a huge public health crisis in these regions if the gap created by a shortage of trained laboratory personnel is not addressed. And as pathologists, we can close this gap by stepping up to the rising health challenges of the 21st Century by becoming more visible and vocal in the global communities that we serve through effective partnerships.
1. Fleming K. Pathology and cancer in Africa. Ecancermedicalscience. 2019;13:945. Published 2019 Jul 25. doi:10.3332/ecancer.2019.945
2. Brooks, A., Smith, T.A., de Savigny, D. et al. Implementing new health interventions in developing countries: why do we lose a decade or more?. BMC Public Health12, 683 (2012). https://doi.org/10.1186/1471-2458-12-683
3. Toth F. Classification of healthcare systems: Can we go further? Health Policy. 2016 May;120(5):535-43. doi: 10.1016/j.healthpol.2016.03.011. Epub 2016 Mar 28. PMID: 27041537.
4. John, C.C., Ayodo, G., Musoke, P. Successful Global Health Research Partnerships: What Makes Them Work? Am. J. Trop. Med. Hyg., 94(1), 2016, pp. 5–7 doi:10.4269/ajtmh.15-0611
5. Catarino R, Petignat P, Dongui G, Vassilakos P. Cervical cancer screening in developing countries at a crossroad: Emerging technologies and policy choices. World J Clin Oncol. 2015;6(6):281-290. doi:10.5306/wjco.v6.i6.281
-Evi Abada, MD, MS is a Resident Physician in anatomic and clinical pathology at the Wayne State University School of Medicine/Detroit Medical Center in Michigan. She earned her Masters of Science in International Health Policy and Management from Brandeis University in Massachusetts, and is a global health advocate. Dr. Abada has been appointed to serve on the ASCP’s Resident’s Council and was named one of ASCP’S 40 under Forty honorees for the year 2020. You can follow her on twitter @EviAbadaMD.
Recently, I interviewed for a subspecialty surgical pathology fellowship, and one of my interviewers posed a question to me: “What has pathology got to do with global health?” She asked me that question because my resume highlights some of my global health-related activities and interests.
Pathology1 is the foundation upon which other specialties in medicine are situated. However, pathology as a specialty is seldom talked about or even referenced by other colleagues in other clinical specialties. One possible reason for this is that pathologists are often out of the perceptions of other clinicians.
That’s unfortunate, because the roles of pathologists in patient care cannot be overemphasized. Pathologists have a solid understanding of the pathophysiology of various diseases. We can identify when tissues are diseased or free from disease, and can also differentiate between various disease processes. We are also versed in the molecular and genetic basis of diseases. We also develop biomarkers to identify different disease processes. Through the assessment of various histopathologic, immunohistochemical analyses and morphologic features, we can also prognosticate various disease processes, a process that has become more effective with advances in molecular pathology. In addition, through our expertise, we serve as consultants to clinical teams to guide patient management.
However, beyond playing the above critical roles, pathologists can exert their influences by getting involved in public health and global health discussions, to influence policies that ultimately impact the outcome of patients. During the COVID-19 pandemic, the role of pathologists and laboratory professionals has become more critical in healthcare delivery.2 We play a huge role in the development of rapid and effective diagnostic assays, as well as influence the interpretation and delivery of timely test results. In addition, through the conduct of autopsies on deceased patients, we have been able to describe some of the clinical and morphologic alterations associated with the SARS-CoV-2 (coronavirus).3
In spite of our important roles in the practice and delivery of medical services, it’s not common practice to have pathologists sit on major hospital boards, or participate in policy discussions that impact healthcare delivery. In addition, many low resource settings outside the United States still experience a shortage of effective laboratory services, with its attendant catastrophic effects on patient care.4 And even in the United States, the pathology workforce is gradually shrinking which could portend dire consequences for effective patient care delivery.5 In order to gain more traction to our specialty, it’s time for pathologists, to step out of our comfort zones and become more visible in the communities that we serve.
Pathology and laboratory services in many developing countries are currently suboptimal from a combination of scarcity of trained pathologists to sub-standard laboratory operations. Pathologists can step in to close this gap by developing collaborations that could foster partnerships in care delivery, training and research opportunities. I want to highly commend healthcare institutions that currently have dedicated pathology global health programs.6
This is a call to action for our specialty. If we really want to become more visible, relevant and attract some of the best talents to our specialty, then we should be ready to show that we bring so much more to the table than just peering into the microscope. The value of our pathology reports in the management of patients cannot be over emphasized. However, we must exert our relevance and expertise in healthcare discussions by stepping out into the communities that need us the most. A great place to start is getting involved with local public/global health-related work, including exploring opportunities, offered by the American Society for Clinical Pathology (ASCP) Center for Global Health.7
Calabrese F, Pezzuto F, Fortarezza F, et al. Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists. Virchows Arch. 2020;477(3):359-372. doi:10.1007/s00428-020-02886-6
Sayed S, Lukande R, Fleming KA. Providing Pathology Support in Low-Income Countries. J Glob Oncol. 2015;1(1):3-6. doi:10.1200/JGO.2015.000943
Lundberg GD. How Many Pathologists Does the United States Need? JAMA Netw Open. 2019;2(5):e194308. doi:10.1001/jamanetworkopen.2019.4308
-Evi Abada, MD, MSis a Resident Physician in anatomic and clinical pathology at the Wayne State University School of Medicine/Detroit Medical Center in Michigan. She earned her Masters of Science in International Health Policy and Management from Brandeis University in Massachusetts, and is a global health advocate. Dr. Abada has been appointed to serve on the ASCP’s Resident’s Council and was named one of ASCP’S 40 under Forty honorees for the year 2020. You can follow her on twitter @EviAbadaMD.
Hospitals and health authorities in affected cities and regions must recognize that AIDS, malaria and TB are surging again.
Researchers must continue to refine their models using more real-world data.
There is a need for public-information campaigns
These campaigns cannot on their own keep surgeries and wards open, or equipment functioning. The resurgence of infectious diseases has created a greater demand for tests, treatments and research. All of these need more funding.
Do those strike you as odd? The entire economy of nations along with the focus of their healthcare has been derailed and distracted by COVID-19 and the solution for these diseases is to recognize them, improve models, inform the public and seek more funding. You are either completely in tuned with the author in seeing that more funding is needed or you are a bit miffed that, in the wake of all that is happening, THESE guys want more money?
The US is a major contributor to the Global Fund for HIV, TB, and Malaria (the largest funder of these activities) and the total pledges to date for the GF approach $69 billion dollars with the US providing $54 billion (92%). From 2008 to 2016, the US contribution increased almost every year from $840 million to $1.65 billion annually until 2015 when it was frozen at $1.35 billion until 2019. In 2020, prior to the COVID-19 pandemic (i.e., during calendar year 2019 when the fiscal year 2020 budget was being planned), the amount from the US dropped to $958 million (2010 levels), representing a 30% drop in funding. So, to recap: The Global Fund started the year down by nearly 30% of what had been available, COVID-19 derailed all activities and drained the fiscal resources of patients and nations, and now, the progress that has been made on these diseases has been set back bay possibly a decade. The situation couldn’t be more desperate and, YES, the program needs a massive increase in funding. But, to be very clear, that massive increase pre-dated COVID-19 and represents something more distressing underneath.
I was fortunate to give the Michelle Rablais lecture at the ASCP Annual Meeting in Phoenix in 2019 where I carefully laid out the costs of controlling JUST malaria (not to mention TB and HIV) and demonstrated for the audience that as the number of cases get smaller and smaller (because your measures are so successful), the cost of finding the remaining cases goes up. As we successfully approach elimination or eradication of a disease, the final push requires at least the same but often more funding to make it across the finish line. This is not an opinion but is based on an enormous amount of data from other diseases as well as from the world’s experience with the first malaria eradication campaign. For HIV, we can’t eliminate it or eradicate it but we have converted it to a chronic disease and, therefore, infrastructure and funding to support patients ongoing is needed and by any form of math has to increase as the population lives longer and more people are added to the disease pool (although those numbers had been greatly reducing). Tuberculosis in its simplest form is a disease of poverty related to lack of access to drugs and healthcare, cramped living conditions, etc. When a pandemic derails the economy and causes the poor to become even more poor, tuberculosis is going to surge.
To the authors of this editorial I offer a gracious thank you and note with a heavy heart that the estimate of $28.5 billion additional dollars being needed to make up the ground lost by COVID-19 does also include the ground they had already lost by defunding principles trending over the last 4 years for global health.
But at least the countries that struggle with these diseases only have HIV, TB, and malaria to worry about, right? Wrong. In almost every low- to middle-income country where HIV, TB, and malaria are or have been major health challenges, hypertension, diabetes, cancer, cardiovascular disease, stroke, and mental health are equivalent or worse health problems than compared with high income countries. Do not be dissuaded by sheer numbers and always consider the outcomes, pre-COVID-19. For cancer, mortality in the US averages around 35% while in Africa it is closer to 80%. In full COVID-19 response mode, cancer programs—fledgling, underfunded, and disorganized—became non-existent and are only now (nearly 6 months after closing) starting to re-open and find their way back to where they were—fledgling, underfunded, and disorganized! Diabetics cannot go 6 months without insulin, hypertensive patients cannot have unregulated blood pressure, etc. While in the safety of a high-income country, makeshift systems, telehealth, contactless visits, etc. were brought on board to keep some semblance of a healthcare system in place, cancer patients were delayed in receiving diagnoses and treatment due to rationing of time and elimination of “elective” procedures.
As the data continues to be tallied and as models continue to be developed to understand just how much we have lost from our failed response to COVID-19 as a world and certainly as a nation, please do not slough off the staggering “additional” deaths that are going to be reported because of patients who didn’t have access to their regular health system. Every person from November 2019 until the end of this pandemic whose death occurred because their regular supply lines were disrupted, their planned treatments were cancelled, their medical supplies were not available, or their access to life-saving interventions were delayed is just as much a casualty from COVID-19 as a directly infected patient who succumbs to the disease. Our recent experience as a nation with the disasters in Puerto Rico around both the confusing death tolls from the hurricanes as well as the total death toll from the fiscal challenges of their medical system (prior to COVID-19) should serve as valuable lessons. Let us not come out of the other side of this pandemic with a similar disregard for the value of every human life or without an understanding of how our individual and collective mistakes as a nation have lead directly to these effects.
-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.
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.
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:
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
Established two new female cancer (cervix and breast) specialty clinics at BMMH
Established two new female cancer (cervix and breast) surgical units at BMMH
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.
Implemented a women’s oncology data collection system
Designed culturally appropriate health promotion messages
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.
-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.
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.
-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.
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.