A Response to “Offline: Why has global health forgotten cancer?”

I read with great interest Richard Horton’s comment, “Offline: Why has global health forgotten cancer?” ASCP applauds his bringing light to this issue and his strong call to action for both the global health community and governments to take up the challenge of dealing with cancer. There is no doubt that the world needs a “Global Fund for Cancer” or the “President’s Emergency Plan for Cancer.” There is no question on what those funds could be spent—

prevention, screening, diagnosis, and treatment of cancer has been well worked out in high-income countries (HIC). There is definitely a question of how best to spend those funds, what is the most effective approach in a given population, and what special circumstances exist in a population that must be considered. We thank him for shouting about this and being so direct and for using the Lancet as a platform for this important message.

We would like to clarify, however, that Richard is certainly not the first person to shout this call (and hopefully he will not be the last!). Please review the 17 references below; one of the earliest was authored by pathologists and appeared in Lancet in 2012.  In addition, the three most recent were from a Lancet Series. When I was in Malawi working in a diagnostic laboratory in 2000, more than 75% of what I saw was cancer. Although, at the time, a lot of cases found their etiology in untreated HIV. My senior colleagues told me I was wasting my time because there was “no way to treat cancer in Africa.” As I continued to visit Malawi over the next 15 years, the percentage of cases that were cancers increased. The HIV-related cancers decreased. Lung cancer never crossed the scope because there were no resources to biopsy or resect patients; yet, lung cancer was a leading cause of death in cancer registries. Today, the limited oncologists in Blantyre are overwhelmed by breast cancer cases. A similar story is found in Butaro, Rwanda and Mirebalais, Haiti.

But in all three places, patients can access a diagnosis because pathology services have been installed, bolstered, or maintained through commitments of NGOs, academic institutions, and governments. More importantly, they have access to treatment because oncologists and oncology nurses have joined the fight against cancer in global health in these units. There are many organizations in the United States and around the world that focus on cancer in low- and middle-income (LMIC) countries including (but not limited to) ASCP, PIH, UICC, ACS, CHAI, BVGH, ICCP, ICCR, NIH, APECSA, ASLM, ASCO, and, yes, the WHO. Do all of these organizations need more resources to make their missions more effective? Absolutely! Do more organizations need to join the fight? Absolutely! But, even with limited resources, huge progress can be made for individuals and populations.

In his comment, Richard points out two arguments used to explain why global health has forgotten cancer. The first is that cancer is not a statistical priority in LMICs. This is actually untrue. Advances in treatment for communicable diseases, especially HIV, have “unmasked” cancer in every one of these nations with clear evidence that many are preventable, many are curable, and many require palliative care. Mortality in Africa from cancer reaches 80% compared with only 35% for all cancers in the US. We clearly have a goal to focus on in mortality reduction with measurable targets. The WHO has announced a cancer resolution at the World Health Assembly. National Cancer Control Plans have been written for most LMICs. The stage is set for any one or all LMICs to develop, build, and expand cancer centers of excellence with people in and out of those countries eager to help. What is missing is not desire or resolve. What is missing is funding. And in this challenge, we find an actual barrier for advancing cancer care. Many organizations are drunk with funding for infectious diseases. They have no experience with cancer and no capacity to tackle it. If funding were suddenly diverted from these communicable disease organizations (CDO) to NCD organizations that could deal with cancer, many CDOs would have to close their doors. And millions would suffer at the loss of infrastructure and capacity that these organizations have created. But THAT is the ultimate barrier—the assumption that we have to divert funding. We don’t need to move funding from one program to another. We must find creative ways to finance cancer for every patient everywhere around the world.

Richard second points out that global health people tout “building systems” rather than focusing on specific cancer types (e.g., breast or cervix) as an excuse to not start cancer care. However, this is not accurate because a) health systems ARE needed to treat cancer and b) it is impossible to treat a single entity cancer and maintain an ethical program. For example, focusing on breast cancer or cervical cancer “first” or “only” is highly unethical because all the tools for those cancers also allow one to partially move a non-breast/non-cervical cancer patient through the system (the main difference being the chemotherapy types used). I do not disagree with the concept of “you have to start somewhere” but, if we think back to HIV and malaria, there is a precedent for why this is a flawed approach. HIV was a single test that diagnosed a single disease but the pre-test probability was high (since very few things looked like HIV at the height of the epidemic). RDTs for malaria were a single test that diagnosed a single disease but the pre-test probability was medium (many things look like malaria that are not). But we focused on HIV diagnosis and treatment and we focused on malaria diagnosis and treatment. Now we have HIV patients who are doing great—and getting cancer. We have malaria patients that are doing great with RDTs and ACTs—but any child with a fever of another cause probably dies. If you ask anyone with an understanding of biology or epidemiology to look at the history of the HIV epidemic or malaria in the modern age, they would all predict these findings. It’s not an epiphany…it was deliberate ignorance. Building systems is hard but it IS the answer. So, I 100% disagree with Richard that treating a single cancer will have an impact beyond those few patients that benefit from that disease. Do those patients with a specific cancer deserve treatment? Of course! But so do patients with all cancers. So, the answer IS still systems.

In order to treat cancer, clinicians must have a pathological diagnosis. For example, if clinicians decided that they would by assumption treat all women with Stage 4 breast cancer in Peru (with positive lymph nodes on palpation), 20% of patients would actually have tuberculosis. But a % of the patients will also have metastasis from other tumor types (such as lymphoma, benign lesions, and soft tissue tumors). If we provide chemotherapy for invasive ductal carcinoma and a pathology service to biopsy the patients to prove the diagnosis, what do we do with those that don’t actually have invasive ductal cancer? How is that ethical? Once we expand our breast tumor regiment to cover all tumors that MAY occur in the breast, now we must treat patients that have those tumors in other locations, otherwise we are in an ethical nightmare.

At the heart of this issue is the pathological diagnosis. There is no treatment without a pathological diagnosis and, once you have the ability to make a pathological diagnosis, there is not justifiable excuse for not treating patients who present with any cancer. The curse of a tissue biopsy processed for histology is that it is one test with, literally, thousands of possible results. Remember HIV and Malaria? They are each one test with one actionable result. A histology slide can present thousands of actionable results! So, no, it is not possible within an ethical construct of healthcare or within a paradigm of equity to focus on one cancer. We can deploy thousands of oncologists and nurses across LMICs with truckloads of every chemotherapy known to humankind and there would be NO IMPACT—absolutely none—unless every patient was pathologically diagnosed before treatment was begun. Surgeons could enter a country and remove every breast with a lump in it—the number of women with inappropriate surgical treatment would result in criminal charges. Pathology is the central tool for diagnosing cancer and creating an appropriate treatment plan, but it is also a single tool that can diagnose EVERY cancer so we must be able to fulfill every appropriate treatment plan.

It is for this reason that PIH with assistance from Dana-Farber Cancer Institute and Brigham and Women’s Hospital began diagnosing and treating patients in Haiti, Lesotho, and Rwanda in 2005 with cancer. By 2011, the trickle of patients that would find their way to PIH clinics had become a flood. It was now necessary to not only build pathology laboratories in countries that could handle the volume and range of diagnoses but also import nurses and oncologists to formulate and run programs. Before the pathology laboratory was built in Butaro, Rwanda, patients may have waited for up to 6 months (if ever) to receive a result which may have been incomplete or inaccurate due to the limitation of staffing. In Butaro today, after the construction of a laboratory, training of staff, addition of immunohistochemistry, installation of telepathology, and residence of a permanent Rwandan pathologist, the turnaround time is < 72 hours. There are other success stories like this but these systems need to be replicated within country and in other countries at a rate of at least one cancer treatment center per 5 million people or less. And, as Richard rightly points out, these centers need to have resources to treat every patient.

ASCP has been in the global health arena working with PEPFAR since its inception. In 2015, ASCP launched Partners for Cancer Diagnosis and Treatment in Africa (including Haiti) which was built on the premise that telepathology would be a key tool to diagnose patients more rapidly and accurate in LMICs. Butaro, Rwanda was the first site to receive telepathology with ASCP but there were many examples of other labs with telepathology in place prior to that; however, the bulk of them were focused on single-entity or research-based programs. The ASCP program starts with the premise that the site where telepathology is placed plans to treat all cancers that are diagnosed. Thus, ASCP requires that a system for cancer care is at least planned or in process. So, the old adage, “you have to start somewhere” is great but, for cancer, that first start must be the provision of pathology services. The ethical framework that follows will require that all cancer move into the realm of treatment.

Again, ASCP thanks Richard Horton for bringing this issue up with the Lancet audience and ASCP hopes that we, all shouting together, can move the needle much further along towards funding for cancer across the systems spectrum.

References

  1. Horton S, Sullivan R, Flanigan J, Fleming KA, Kuti MA, Looi LM, Pai SA, Lawler M. Delivering modern, high-quality, affordable pathology and laboratory medicine to low-income and middle-income countries: a call to action. Lancet. 2018 May 12;391(10133):1953-1964. doi: 10.1016/S0140-6736(18)30460-4. Epub 2018 Mar 15. Review. PubMed PMID: 29550030.
  2. Sayed S, Cherniak W, Lawler M, Tan SY, El Sadr W, Wolf N, Silkensen S, Brand N, Looi LM, Pai SA, Wilson ML, Milner D, Flanigan J, Fleming KA. Improving pathology and laboratory medicine in low-income and middle-income countries: roadmap to solutions. Lancet. 2018 May 12;391(10133):1939-1952. doi: 10.1016/S0140-6736(18)30459-8. Epub 2018 Mar 15. Review. PubMed PMID: 29550027.
  3. Wilson ML, Fleming KA, Kuti MA, Looi LM, Lago N, Ru K. Access to pathology and laboratory medicine services: a crucial gap. Lancet. 2018 May 12;391(10133):1927-1938. doi: 10.1016/S0140-6736(18)30458-6. Epub 2018 Mar 15. Review. PubMed PMID: 29550029.
  4. Sayed S, Cherniak W, Lawler M, Tan SY, El Sadr W, Wolf N, Silkensen S, Brand N, Looi LM, Pai SA, Wilson ML, Milner D, Flanigan J, Fleming KA. Improving pathology and laboratory medicine in low-income and middle-income countries: roadmap to solutions. Lancet. 2018 May 12;391(10133):1939-1952. doi: 10.1016/S0140-6736(18)30459-8. Epub 2018 Mar 15. Review. PubMed PMID: 29550027.
  5. Milner DA Jr. Pathology: Central and Essential. Clin Lab Med. 2018 Mar;38(1):xv-xvi. doi: 10.1016/j.cll.2017.11.001. Epub 2017 Dec 12. PubMed PMID: 29412893.
  6. Milner DA Jr. Global Health and Pathology. Clin Lab Med. 2018 Mar;38(1):i. doi: 10.1016/S0272-2712(17)30139-7. Epub 2018 Feb 3. PubMed PMID: 29412888.
  7. Orozco JD, Greenberg LA, Desai IK, Anglade F, Ruhangaza D, Johnson M, Ivers LC, Milner DA Jr, Farmer PE. Building Laboratory Capacity to Strengthen Health Systems: The Partners In Health Experience. Clin Lab Med. 2018 Mar;38(1):101-117. doi: 10.1016/j.cll.2017.10.008. Epub 2017 Dec 28. Review. PubMed PMID: 29412874.
  8. Milner DA Jr, Holladay EB. Laboratories as the Core for Health Systems Building. Clin Lab Med. 2018 Mar;38(1):1-9. doi: 10.1016/j.cll.2017.10.001. Epub 2017 Dec 1. Review. PubMed PMID: 29412873.
  9. Dayton V, Nguyen CK, Van TT, Thanh NV, To TV, Hung NP, Dung NN, Milner DA Jr. Evaluation of Opportunities to Improve Hematopathology Diagnosis for Vietnam Pathologists. Am J Clin Pathol. 2017 Nov 20;148(6):529-537. doi: 10.1093/ajcp/aqx108. PubMed PMID: 29140404.
  10. Mpunga T, Hedt-Gauthier BL, Tapela N, Nshimiyimana I, Muvugabigwi G, Pritchett N, Greenberg L, Benewe O, Shulman DS, Pepoon JR, Shulman LN, Milner DA Jr. Implementation and Validation of Telepathology Triage at Cancer Referral Center in Rural Rwanda. J Glob Oncol. 2016 Jan 20;2(2):76-82. doi: 10.1200/JGO.2015.002162. eCollection 2016 Apr. PubMed PMID: 28717686; PubMed Central PMCID: PMC5495446.
  11. Sayed S, Lukande R, Fleming KA. Providing Pathology Support in Low-Income Countries. J Glob Oncol. 2015 Sep 23;1(1):3-6. doi: 10.1200/JGO.2015.000943. eCollection 2015 Oct. PubMed PMID: 28804765; PubMed Central PMCID: PMC5551652.
  12. Nelson AM, Milner DA, Rebbeck TR, Iliyasu Y. Oncologic Care and Pathology Resources in Africa: Survey and Recommendations. J Clin Oncol. 2016 Jan 1;34(1):20-6. doi: 10.1200/JCO.2015.61.9767. Epub 2015 Nov 17. Review. PubMed PMID: 26578619.
  13. Mpunga T, Tapela N, Hedt-Gauthier BL, Milner D, Nshimiyimana I, Muvugabigwi G, Moore M, Shulman DS, Pepoon JR, Shulman LN. Diagnosis of cancer in rural Rwanda: early outcomes of a phased approach to implement anatomic pathology services in resource-limited settings. Am J Clin Pathol. 2014 Oct;142(4):541-5. doi: 10.1309/AJCPYPDES6Z8ELEY. PubMed PMID: 25239422.
  14. Mtonga P, Masamba L, Milner D, Shulman LN, Nyirenda R, Mwafulirwa K. Biopsy case mix and diagnostic yield at a Malawian central hospital. Malawi Med J. 2013 Sep;25(3):62-4. PubMed PMID: 24358421; PubMed Central PMCID: PMC3859990.
  15. Berezowska S, Tomoka T, Kamiza S, Milner DA Jr, Langer R. Surgical pathology in sub-Saharan Africa–volunteering in Malawi. Virchows Arch. 2012 Apr;460(4):363-70. doi: 10.1007/s00428-012-1217-z. Epub 2012 Mar 10. PubMed PMID: 22407448.
  16. Roberts DJ, Wilson ML, Nelson AM, Adesina AM, Fleming KA, Milner D, Guarner J, Rebbeck TR, Castle P, Lucas S. The good news about cancer in developing countries–pathology answers the call. Lancet. 2012 Feb 25;379(9817):712. doi: 10.1016/S0140-6736(12)60306-7. PubMed PMID: 22364759.
  17. Carlson JW, Lyon E, Walton D, Foo WC, Sievers AC, Shulman LN, Farmer P, Nosé V, Milner DA Jr. Partners in pathology: a collaborative model to bring pathology to resource poor settings. Am J Surg Pathol. 2010 Jan;34(1):118-23. doi: 10.1097/PAS.0b013e3181c17fe6. PubMed PMID: 19898229.

 

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-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.

Essential Diagnostics List – Ready, Set, Go!

In a recent post I introduced the WHO’s draft of the Essential Diagnostics List (the EDL). The EDL is a catalog of in vitro diagnostics (IVD) designed to complement the Essential Medicines List. The EDL is not necessary meant to be a global list, but something to be adopted and adapted by each country, and tests added, subtracted, or prioritized based on each country’s disease burden. While the draft is still in development, at least one country is already on track to have adopted a country specific EDL by the end of the year!

India is working towards being the first country to have an EDL by the end of 2018. It so happens that the draft of the EDL was announced while India was in the process of rolling out a Free Diagnostics Initiative (FDI) in 29 of its states. The goal of the FDI is to “ensure the availability of a minimum set of diagnostics appropriate to the level of care to reduce out of pocket expenditure on diagnostics and to encourage appropriate treatment of based on accurate diagnosis”. Similar to the EDL, the FDI plans for different IVDs at different levels of laboratories, from community healthcare centers to reference laboratories. The development of an EDL seems like a natural product of India’s FDI. Talk about perfect timing!

The Indian Council on Medical Research (ICMR), comprised of clinicians, microbiologists, and medical device industry leaders, has convened to adapt the EDL to India’s infection patterns and diseases. They plan to have their national EDL ready to present by the beginning of 2019. The ICMR intends that an Indian EDL will optimize utilization of the Indian EML. “The objective is to test and treat rather than treat and test” states Dr. Kamina Walia of the ICMR. The ICMR also realizes that in order for diagnostics to be affordable, the country’s laboratory infrastructure will need to be strengthened, including building laboratory capacity where none currently exists.

It is so exciting to see the EDL already under consideration by a nation. It’s even more exciting to hear medical experts speak about how laboratory infrastructure should be strengthened, and to know that medical device industry leaders are coming to the table. It’s going to be fun to watch this develop over the next decade.

Do you want to be involved in the EDL project? There is time! The WHO is accepting applications for IVDs to be added to the second edition of the EDL, which will be released in 2019. The deadline for submissions is September 15, 2019. Instructions can be found here.

 

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Sarah Riley, PhD, DABCC, is an Assistant Professor of Pediatrics and Pathology and Immunology at Washington University in St. Louis School of Medicine. She is passionate about bringing the lab out of the basement and into the forefront of global health.  

Ebola 2018

Approximately two years after Liberia, the hardest hit and last of the 6 countries to be affected in the largest Ebola outbreak since discovery of the disease in 1976, was declared Ebola-free, the virus has again reared its head. This time, its in the Democratic Republic of the Congo (DRC).

Timeline of the Outbreak:

  • May 3, 2018: a district in the Province of Equateur, DRC, reported 21 cases of undiagnosed illness with 17 deaths. Samples from 5 of these cases were sent to the Institute National Recherche Biomedicale in Kinshasa.
  • May 7: Ebola virus was confirmed by RT-PCR.
  • May 8, 2018: Ebola outbreak declared.
  • May 21: 628 contacts of confirmed or suspected cases listed.
  • May 25: 58 cases and 27 deaths.
  • June 1: the outbreak is contained in the Province of Equateur. This Province covers an area of 130442 km2 and has a population of 2,543,936. Equateur as 16 health zones and 284 health centers – this works out as 1 health center for every 9,000 people! The WHO warns that this outbreak has the potential to expand, and while at the moment there is no international spread, the Congo’s neighbors have been placed on alert. The WHO has distributed personal protective equipment, infrared thermometers, and rapid diagnostic tests to health centers in Equateur as well as neighboring countries.

The WHO considers laboratory diagnostics on of the pillars of the Ebola response. They recommend “strengthening diagnostic capabilities” as part of a strategic approach to the prevention, detection, and control of Ebola. In fact, laboratory diagnostics might be a key to how this epidemic plays out, versus the previous outbreak in West Africa wherein six African countries were affected and over 11,000 patients died. This time, there are rapid tests tests available ranging from lateral flow to molecular.

As part of the DRC’s National Laboratory Strategy developed in response to the outbreak, the GeneXpert confirmatory Ebola PCR test is being used a key sites in mobile laboratories. As of June 1, the WHO has deployed four mobile labs through out Equateur including the epicenter of the outbreak. Government Health Centers are equipped with rapid lateral flow tests: the ReEBOV Antigen Rapid Test released under Emergency Use Approval in 2015. According to WHO documents, this test has a sensitivity of 91% and specificity of 84.6%. Both positives and negatives should be confirmed with RT-PCR. The following is the guidance for the use of rapid tests:

Special settings where rapid antigen for Ebola may be beneficial:

  1. In the investigation of suspected Ebola outbreaks in remote settings where PCR tests are not immediately available. While awaiting confirmatory testing, action can be taken to: a) isolate test-positive patients, b) repeat daily testing on patients who initially tested negative but remain symptomatic, c) mobilize transport of samples for confirmatory testing and initiate outbreak-management procedures.
  2. In settings where the number of cases and suspects arriving for triage and care cannot be managed with the existing health staff and laboratory facilities.

Example situations where rapid antigen detection tests should NOT be used:

  • Individual case management – including for establishing definitive diagnosis or making therapeutic decisisions
  • Certification of Ebola virus-free status prior to medical care for other illnesses
  • Release of Ebola patients from Ebola Treatment Centers
  • Pooled blood samples for community-based testing
  • Testing blood before transfusion
  • Active case finding without confirmatory PCR
  • Any setting where action (quarantine, referral, care) based on results is not possible
  • Airport screening

So to summarize, currently in the Province of Equateur, suspected cases are tested by rapid test for initial triage, then samples are sent to the nearest lab for confirmation (positive or negative) by PCR. A suspected case cannot be released until there is a negative test by PCR. Suspected cases that initially negative by the rapid test are isolated from cases that are initially positive.

What about outside Equateur? I talked to Dr. Tim Rice, a friend and colleague serving as a missionary physician in Vanga, Congo. Vanga is the in Province of Bandundu, the northern neighbor of Equateur. While this province has not had a reported case of Ebola, they are getting ready. I asked him about their readiness plan and any laboratory capabilities they had. They have a rapid test: Ebola rapid lateral flow test from STADA Diagnostik (Germany). This assay detects the Ebola virus antigen VP 40 with a sensitivity of 92% and specificity of 98% (according to the package insert). Serum and throat swabs are acceptable specimens, although it is not clear which matrix was used to determine the performance characteristics. The package insert states that the performance characteristics are still being evaluated. Dr. Rice said they use the rapid test with patients with potential exposure and severely ill with fever.  Someone arriving from the Equatorial province with a fever, even if not severely ill, would be tested and isolated. They are to call the local health department for help in obtaining the correct confirmatory samples, properly storing the sample, alerting the regional and national leaders, and transporting the sample properly protected the 10 hours overland to Kinshasa for confirmatory PCR testing at the Institute National Recherche Biomedicale.

The response to the 2018 Ebola outbreak has been impressive and I sincerely hope that with the benefits of laboratory diagnostics and a vaccine, the world will be spared the devastation experienced in the previous outbreak.

 

Sarah Brown Headshot_small

Sarah Riley, PhD, DABCC, is an Assistant Professor of Pediatrics and Pathology and Immunology at Washington University in St. Louis School of Medicine. She is passionate about bringing the lab out of the basement and into the forefront of global health.  

Essential Diagnostics List

A propos of Lab Week 2018, the WHO announced the development of an Essential Diagnostic List (EDL). The first Strategic Advisory Group of Experts on In Vitro Diagnostics (SAGE IVD) met in Geneva in April. The role of the SAGE-IVD is to act as an advisory body to matters of global policy and strategies related to in vitro diagnostics (IVDs) – to guide the development of the EDL.

The EDL is, as it sounds, a catalog of IVDs that are essential for diagnosis, treatment, and management of diseases. An EDL was called for in 2016 by Dr. Tim Amukele, a clinical pathologist at Johns Hopkins and President of the non-profit organization Pathologists Oveseas, and Dr. Lee Schroeder, a clinical pathologist at University of Michigan Ann Arbor (N Engl J Med 2016; 374:2511-4). Amukele and Schroeder suggested the EDL to complement the WHO’s Essential Medicines List (EML). They suggested 19 categories of IVDs that are essential for 10 of the medicines appearing on the EML. As it stands, the initial EDL focuses on 4 disease areas: HIV, TB, Malaria, and Hepatitis B & C. The following categories are provided for each disease area: analyte, intended use, level of facility that should have the IVD, assay format, specimen type, and links to WHO guidelines and any WHO prequalified or endorsed products.

For example, in the disease area “Malaria”, the analyte P. falciparum has the intended use of diagnosis of P. falciparum. The rapid diagnostic assay format is recommended for all level facilities. The specimen type is capillary whole blood, and the corresponding WHO guideline is “Good practices for selecting and procuring rapid diagnostic tests for malaria, 2011”.

The EDL will provide countries a way to focus attention on which tests are most appropriate, which can have a huge impact on the cost-effectiveness of the health care system, and also improve the quality of the laboratory results. Cost-effectiveness can be achieved by 1) focusing on evidence-based IVDs appropriate for a specific disease burden and 2) facilitating proper utilization of medicines and other clinical supplies necessary for treatment/management. In my experience, many laboratories in resource-limited areas are developed seemingly on a whim; testing might reflect a pet project of an absentee lab director, or donated equipment. Focusing on more appropriate testing, as Dr. Amukele told Clinical Laboratory News, give a lab more bang for their buck. Dr. Schroeder indicated that “lab testing develop ad hoc is more prone to quality issues”. The hope is that providing more direction for development of lab testing will encourage greater quality control programs. One way I can see that playing out is, if more labs in a specific area adopt the same testing, a shared sample program for cost-effective proficiency testing might be developed.

The WHO hopes that countries will use the EDL to develop country-specific EDLs, based on the disease burden specific to the country. National EMLs have been successful. Personally, I am very excited about the EDL! The WHO efforts to control HIV, Malaria, and TB have highlighted the need for laboratory diagnostics. I think it’s about time that labs got a chance to show their worth! The EDL is an important step in bringing the lab out of the basement and onto the global health stage.

 

Sarah Brown Headshot_small

Sarah Riley, PhD, DABCC, is an Assistant Professor of Pediatrics and Pathology and Immunology at Washington University in St. Louis School of Medicine. She is passionate about bringing the lab out of the basement and into the forefront of global health.  

Critical Care, Critical Labs

Sepsis is a medical emergency and a global public health concern. The Surviving Sepsis Campaign started in 2012 and has since issued International Guidelines for Management of Sepsis and Septic Shock. These Guidelines have been updated several times, and the 4th edition of the 2016 guideline have been issued. The Guidelines are written from the perspective of developed (“resource-rich”) countries, where critical care settings are equipped with tools for managing these patients. Yet, the developing world carries the greatest burden of sepsis-related mortality. Unfortunately, the developing world lacks access to many of the necessary tools for managing the critically ill patient – including basic laboratory testing.

Laboratory values are a significant part of the management of the septic patient. Take a look at the sepsis screening tool. Analytes and lab tests included in screening patients for sepsis include: lactate, creatinine, bilirubin, INR, and blood gases. The Surviving Sepsis bundles require a lactate concentration within 3 hours of presentation, and a subsequent lactate within 6 hours. The care bundle also requires a blood culture within 3 hours of presentation and prior to administration of antibiotics. Early-goal directed therapy for sepsis requires administration of crystalloid based on lactate concentrations. Basics of laboratories in the US, lactate and blood cultures are both difficult to obtain and far from routine in the resource-poor care settings.

Blood gases and lactate are particularly difficult to find and to maintain in the developing world. While there are a number of point-of-care or small benchtop devices – like the iStat (Abbott), the Piccolo (Abaxis), and the Stat Profile pHOx (Nova), it is often cost-prohibitive to maintain these devices.  The iStat and the Piccolo are examples of cartridge-based devices. All of the chemistry takes place in single-use cartridges and the device itself is basically a timer. In my experience, cartridge based devices hold up in environmental extremes better than open reagent systems. However, they are not cheap and this can be prohibitive. Cost of a single cartridge can range from $3-10 USD. In countries where patients and their families are expected to pay upfront or as they go for even inpatient medical care, and the income for a family is $2USD/day, routine monitoring of blood gases and lactate by cartridge is just not feasible. Reagent based devices like the Stat Profile use cartons of reagent for many uses. This is much cheaper – if all the reagent is used before it expires! Some healthcare settings can accommodate only 1-3 critical patients, and might not be able to use a whole carton before the expiry, even when adhering to Surviving Sepsis guidelines.

Blood cultures and subsequent treatment with appropriate antibiotics is a large part of the surviving sepsis campaign. Microbiology in the developing world is often limited to a few reference laboratories in country. Also, the number of potential infectious agents is larger in the developing world where diseases like malaria and dengue fever are common. Multiplexed nucleic acid tests might fill the gap here. Again, the cost is a major factor. Just reagents alone for a single multiplexed NAT can be over $250 USD.

In short, if the surviving sepsis guidelines really do help decrease sepsis mortality, the developing world doesn’t have a chance unless it has a greater laboratory capacity. Basic labs that we don’t think twice about can be very hard to come by in resource-poor environments. The tests already exist in forms that can be used in resource-poor settings – they just need to be cheaper, at least for those in limited resource settings. Are you listening, Abbott?

 

Sarah Brown Headshot_small

Sarah Riley, PhD, DABCC, is an Assistant Professor of Pediatrics and Pathology and Immunology at Washington University in St. Louis School of Medicine. She is passionate about bringing the lab out of the basement and into the forefront of global health.  

The Challenges of Clinical Laboratories in Developing Countries

Achieving and maintaining quality is arguably one of the most critical tasks in clinical laboratories. Without a proper quality, clinical laboratories are essentially unsafe for patients. Poor quality results can cause mistrust between laboratories and end users, and therefore, endangers the practice of evidence-based medicine and precludes viable engagements between clinicians and laboratorians. Furthermore, poor quality clinical laboratories can hinder global efforts to fight infectious diseases and outbreaks (1).

Ensuring quality is a journey without a destination. It demands constant attention and continuous active participation of all involved in the testing processes. For example, the majority of testing transactions are mediated by clinicians. Their direct involvement in the testing processes makes them inevitable partners in ensuring quality. Thus, close cooperation and constructive engagement with clinicians is critical for laboratorians to provide sustainable quality service. However, ensuring quality can be laborious as it includes coordination with multiple bodies that are not conventional members of clinical laboratories.

The quality of most clinical laboratories in most developing countries is poor.  For example, most clinical laboratories in Africa do not meet international standards (2, 3). Why? There are several factors that contribute to this occurrence but the answer distills into the following: Lack of adequate resources, proper regulations, and supportive health care system.

Lack of adequate resources

The contributions of laboratorians in the diagnosis and management of diseases are generally under-recognized. Laboratorians in developing countries are no exception, if not worse. The lack of recognition compounded by inadequate compensation often leads to job dissatisfaction, negligence, lack of interest, and as a result, departure from the profession. The worst consequence of this phenomenon is over time depletion of qualified personnel, seeking for better opportunities elsewhere. While it is indisputable that developing countries face acute resource limitations, it is not necessarily due to lack of funding but also due to resource misappropriation, improper governance, and rampant corruption.

Lack of proper regulations

The notion that no result is better than poor quality result underscores the critical importance of quality in clinical laboratories. However, it is usually difficult to maintain quality without imposing proper regulatory requirements and enforcing strict regulations. For example, a survey conducted in clinical laboratories in Kampala, Uganda, reveals that most clinical laboratories do not meet international standards (1). Most clinical laboratories in Africa are not accredited (2). Most of the laboratories are not enrolled in external assurance programs; those enrolled do not necessarily adhere to strict follow-ups. These kinds of problems can be averted, at least in part, by introducing stringent regulatory requirements and enforcing the regulations to the details.

Lack of adequate support

Clinical laboratories in developing countries suffer inadvertent neglect and are not well-supported to ensure accurate diagnosis. The healthcare system in developing countries perceives clinical laboratories as “tools” rather than “partners” in the disease diagnosis processes. This kind of unfortunate perception is inherently flawed because clinical laboratories are indeed critical in diagnosing diseases, curbing outbreaks, addressing growing global health concerns. In that sense, laboratories and laboratorians should be deemed and treated as partners.  This is an important distinction to make because partnership fosters collaboration, respect, and recognition, encourages horizontal communications between laboratorians and clinicians, and helps garner support from clinicians, the public, and policymakers.

In summary, the majority of treatment decisions in developing countries are based on clinical judgment and empiric diagnosis (4). Because access to reliable diagnostic testing is limited or undervalued, misdiagnosis commonly occurs, resulting in inadequate treatment, increased mortality, and an inability to determine the true prevalence of diseases. Furthermore, mistrust is rampant due to poor quality results and consequently, viable engagements between the clinical laboratories and clinicians are often impaired.

Laboratorians in developing countries should set up efficient professional societies, enhance communication and diplomacy with clinicians and policymakers, and foster collaborative environment towards achieving continuous quality improvement. Strong and viable societies should then advocate for the wellbeing of clinical laboratories and laboratorians in developing countries. Furthermore, any effort from the global health community should first be directed to identifying and targeting fundamental problems in partnership with local professionals and authorities.

References

  1. Berkelman R, Cassell G, Specter S, Hamburg M, Klugman K. The “Achilles heel” Of global efforts to combat infectious diseases. Clin infect dis, Vol. 42. United States, 2006:1503-4.
  2. Schroeder LF, Amukele T. Medical laboratories in sub-saharan africa that meet international quality standards. Am J Clin Pathol 2014;141:791-5.
  3. Elbireer AM, Jackson JB, Sendagire H, Opio A, Bagenda D, Amukele TK. The good, the bad, and the unknown: Quality of clinical laboratories in kampala, uganda. PLoS One 2013;8:e64661.
  4. Petti CA, Polage CR, Quinn TC, Ronald AR, Sande MA. Laboratory medicine in africa: A barrier to effective health care. Clin Infect Dis 2006;42:377-82.

 

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-Merih T Tesfazghi, PhD, is a Clinical Chemistry Fellow with the Department of Pathology and Immunology at Washington University School of Medicine in St. Louis, MO.

Logistics, Meetings, and Evacuations

Almost perfectly timed during my classroom-to-clinicals transition period from American University of the Caribbean School of Medicine (AUC), the 2017 ASCP Annual Meeting in Chicago was an excellent opportunity to get back to my lab roots. The Annual Meeting is always an excellent opportunity to expand lab-related knowledge, learn some new clinical skills, and easily network with colleagues. Professional societies like ours are highly dependent on the partnership and collaboration of our fellow scientists, sponsors, and clinicians. I have been fortunate enough to attend two of these meetings as an award recipient bookending my pre-clinical years in medical school. In 2015, I attended the ASCP Annual Meeting in Long Beach, California as a Regional Member of the Year. This year’s Annual Meeting was held in my hometown of Chicago, where I’m proud to say I attended as a 2017 ASCP Top 40 Under Forty honoree! But these meetings are more than just conferences with awards ceremonies—at every ASCP meeting I reconnected with old friends in workshops, shook hands with our great ASCP leadership, and collaborated with colleagues in roundtables or other sessions. There is a place for all of us in laboratory medicine. Our respective insights bring something valuable to the final outcomes of improved patient care. Nowhere is this more evident than the Annual Meeting.

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Image 1. ASCP Annual Meeting Chicago 2017, Top 40 Under Forty, and ASCP CEO Dr. Blair Holladay

Among the endless list of educational events and sessions, I especially enjoyed being a collaborator in round table discussions including “The Benefits of Data Integration in Clinical Decisions.” I truly enjoy these roundtables and wish I could have done more of them! Topics included effective feedback, utilization and evaluations, education, and global health initiatives—all of which I’m sure I’ve written about in one way or another this past year. Seeing some of the content in my online Lab Management University (LMU) modules applied in real-life situations was reaffirming. Attending sessions and meeting renowned experts from informatics to hematopathology was exciting. The keynote speakers were captivating. Dr. Birx’s discussion on PEPFAR and global health initiatives clearly piqued my interests, and Drs. Caliguiri and Pritchard’s lectures on analytics and resources spoke directly to my work in cancer research. And don’t forget: it’s all worth continuing education credit—can’t beat that.

I would just like to simply thank ASCP again for all the work that goes into these meetings. I know from experience that planning large events involves quite a bit of logistics. And in managing these events ASCP truly provides an excellent environment to collaborate and learn. What brought this appreciation for logistics to the forefront was a disaster that had unfolded in the week prior to the meeting. On the island of Sint Maarten, the location of my medical school and my home for two years, was absolutely decimated by hurricane Irma. The school managed to withstand for the most part intact and acted as a shelter for students, faculty, and family. While being sheltered from that storm, endless homes, apartments, and business were destroyed. Taking nothing but a suitcase or two to campus ended up the only possessions many people in the AUC community had left. The school and its administration did a spectacular job creating a stable, safe, and even comfortable environment for students and their families while evacuation efforts were organized. While AUC managed to get students off the island via military assistance and/or charter flights, evacuees were taken to the Chicago suburbs. Right after the ASCP Annual Meeting I began having conversations with contacts in the Chicago Department of Public Health and Emergency Preparedness to offer assistance. I provided contact data, relayed satellite telephone numbers to the right contact points, and provided relevant information regarding demographics, health, and needs. Both my wife (a trained nursing leader) and myself were happy to be involved with connecting critical points in this process. All the students and their families were accounted for and taken care of in the Chicago suburbs, and were later moved to the new school location relatively unscathed. Logistics from a distance can be difficult, especially when it’s behind-the-scenes. A lot of lab decisions are made that way, and ultimately we do our best for our patients.

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Image 2. Resort and villas halfway between my apartment and AUC campus on Sint Maarten before the hurricane.

 

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Image 3. Resort and villas halfway between my apartment and AUC campus on Sint Maarten after the hurricane.

The take home message: be flexible, be humble, and be helpful. If we want to improve patient outcomes, we need to work with evidence-based approaches matched with intelligent compassion. As laboratorians, we apply our scientific approach to critical life-saving algorithms. This was no exception. Lessons discussed at the Annual Meeting between networking colleagues and official sessions are accurate. Tap into your resources, keep an active and dynamic network, know what you can do and what you cannot, and always try to help. That’s what makes a good laboratorian, a good clinician, a good friend, and hopefully a good physician.

Thanks for reading! If you’re interested in donating to disaster relief for anyone affected by this year’s violent hurricane season in Sint Maarten, visit www.rotarysxm.org.

 

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Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student at the American University of the Caribbean and actively involved with local public health.