A rapid, point-of-care red blood cell agglutination assay detecting antibodies against SARS-CoV-2.

The COVID-19 pandemic has caused significant morbidity and mortality. There is an urgent need for serological tests to detect antibodies against SARS-CoV-2, which could be used to assess past infection, evaluate responses to vaccines in development, and determine individuals who may be protected from future infection. Current serological tests developed for SARS-CoV-2 rely on traditional technologies such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays, which have not scaled to meet the demand of hundreds of millions of antibody tests so far. Herein, we present an alternative method of antibody testing that depends on one protein reagent being added to patient serum/plasma or whole blood with direct, visual readout. Two novel fusion proteins, RBD-2E8 and B6-CH1-RBD, were designed to bind red blood cells (RBCs) via a single-chain variable fragment (scFv), thereby displaying the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on the surface of RBCs. Mixing mammalian-derived RBD-2E8 and B6-CH1-RBD with convalescent COVID-19 patient serum and RBCs led to visible hemagglutination, indicating the presence of antibodies against SARS-CoV-2 RBD. B6-CH1-RBD made in bacteria was not as effective in inducing agglutination, indicating better recognition of RBD epitopes from mammalian cells. Given that our hemagglutination test uses methods routinely used in hospital clinical labs across the world for blood typing, we anticipate the test can be rapidly deployed at minimal cost. We anticipate our hemagglutination assay may find extensive use in low-resource settings for detecting SARS-CoV-2 antibodies.

Essential Diagnostics for the Use of World Health Organization Essential Medicines.

BACKGROUND: There are numerous barriers to achieving high-quality laboratory diagnostic testing in resource-limited countries. These include inconsistent supply chains, variable quality of diagnostic devices, lack of human and financial resources, the ever-growing list of available tests, and a historical reliance on syndromic treatment algorithms. A list of essential diagnostics based on an accepted standard like the WHO Essential Medicines List (EML) could coordinate stakeholders in the strengthening of laboratory capacity globally. METHODS: To aid in the creation of an essential diagnostics list (EDL), we identified laboratory test indications from expert databases for the safe and effective use of WHO EML medicines. In all, 446 EML medicines were included in the study. We identified 279 conditions targeted by these medicines, spanning communicable and noncommunicable diseases (e.g., HIV, diabetes mellitus). RESULTS: We found 325 unique diagnostic tests, across 2717 indications, associated with the identified conditions or their associated medicines. The indications were divided into 10 categories: toxicity (865), diagnosis (591), monitoring (379), dosing/safety (325), complications (217), pathophysiology (154), differential diagnosis (97), comorbidities (53), drug-susceptibility testing (22), and companion diagnostic testing (14). We also created a sublist of 74 higher-priority tests to help define the core of the EDL. CONCLUSIONS: An EDL such as we describe here could align the global health community to solve the problems impeding equitable access to high-quality diagnostic testing in support of the global health agenda.

Drone transportation of blood products.

BACKGROUND: Small civilian unmanned aerial vehicles (drones) are a novel way to transport small goods. To the best of our knowledge there are no studies examining the impact of drone transport on blood products, describing approaches to maintaining temperature control, or component physical characteristics during drone transport. STUDY DESIGN AND METHODS: Six leukoreduced red blood cell (RBC) and six apheresis platelet (PLT) units were split using sterile techniques. The larger parent RBC and PLT units, as well as six unthawed plasma units frozen within 24 hours of collection (FP24), were placed in a cooler, attached to the drone, and flown for up to 26.5 minutes with temperature logging. Ambient temperatures during the experimental window ranged between -1 and 18°C across 2 days. The difference between the ambient and unit temperatures was approximately 20°C for PLT and FP24 units. After flight, the RBC parent units were centrifuged and visually checked for hemolysis; the PLTs were checked for changes in mean PLT volumes (MPVs), pH, and PLT count; and the frozen air bubbles on the back of the FP24 units were examined for any changes in size or shape, as evidence of thawing. RESULTS: There was no evidence of RBC hemolysis; no significant changes in PLT count, pH, or MPVs; and no changes in the FP24 bubbles. The temperature of all units was maintained during transport and flight. CONCLUSION: There was no adverse impact of drone transport on RBC, PLT, or FP24 units. These findings suggest that drone transportation systems are a viable option for the transportation of blood products.

Drone Transport of Microbes in Blood and Sputum Laboratory Specimens.

Unmanned aerial vehicles (UAVs) could potentially be used to transport microbiological specimens. To examine the impact of UAVs on microbiological specimens, blood and sputum culture specimens were seeded with usual pathogens and flown in a UAV for 30 ± 2 min. Times to recovery, colony counts, morphologies, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based identifications of the flown and stationary specimens were similar for all microbes studied.

Remote support of an external quality assessment program in 10 laboratories in Bhutan, Uganda, and Malawi: Pathologists Overseas experience between 2009 and 2017.

OBJECTIVES: This article describes Pathologists Overseas (PO) experience supporting external quality assessment (EQA) programs in 10 clinical laboratories across 3 countries between 2009 and 2017. METHODS: Laboratories were enrolled in the condensed chemical pathology EQA program provided by the Royal College of Pathologists of Australasia Quality Assurance Program. Participants were given an initial 2- to 4-day in-person training, followed by 1 year of active feedback on performance via emails or phone calls by a PO volunteer. RESULTS: There were 2 performance metrics: percentage of reported results as a measure of compliance and percentage of acceptable reported results as a measure of accuracy. Laboratories demonstrated high compliance with result reporting, with medians of 69.9%, 71.7%, and 81.3% before, during, and after feedback, respectively. Concomitant medians for the percentage of acceptable reported results were 41.2%, 57.3%, and 53.5%, respectively. Six laboratories had low performance in terms of accuracy at baseline (<60%). Active feedback improved the percentage of acceptable reported results for these lower-performing laboratories. CONCLUSIONS: External quality assessment programs can be successfully adopted long term by laboratories in low-resource settings. Active feedback requires significant time and effort but could be especially beneficial for laboratories with poor baseline performance.

Characterizing the role of informal payments in the delivery of pathology and clinical laboratory services.

OBJECTIVES: Informal payments (IPs) are unofficial cash or in-kind payments for goods or services that should be covered by the health care system. They are a common but regressive method of financing health care in low- and lower-middle-income countries (LMICs). This study aims to characterize the prevalence and impact of IPs on pathology and laboratory medicine (PALM) services. METHODS: From September 2021 to September 2022, PALM staff were surveyed about the frequency, determinants, and impacts of IPs in their respective workplaces. RESULTS: In total, 268 responses were received, and 46.6% (125/268) reported experience with IPs. These 125 participants were more likely to work in the public sector and in LMICs. Approximately 65% reported accepting IPs to perform tests or release results. Obtaining faster results was the most commonly perceived reason for patients offering IPs. Overall, participants reported that IPs had more negative than positive impacts on their workplace. CONCLUSIONS: This represents a first step in characterizing IPs within PALM and how this practice may affect access to these services in LMICs. Specifically, the fact that faster turnaround time was the most frequently perceived reason for offering IPs uncovers a potential barrier to improving PALM capacity in these regions.

Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub-study of the ODYSSEY randomized controlled trial.

INTRODUCTION: Dolutegravir-based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre-conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub-study to look at the effect of dolutegravir on levels of folate and vitamin B12 in children and adolescents within the randomized ODYSSEY trial, as folate and vitamin B12 are known to play a crucial role in neural tube development. METHODS: We conducted the sub-study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir-based ART (DTG) and non-dolutegravir-based standard-of-care treatment (SOC). Plasma folate was measured at enrolment and week 4 on stored samples; in addition, plasma and red blood cell (RBC) folate and vitamin B12 were assayed at week ≥96 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24-weekly in all ODYSSEY participants. Samples analysed in the sub-study were collected between September 2016 and October 2020. RESULTS: A total of 229 children aged ≥6 years were included in the sub-study with median age at trial enrolment of 12.3 (interquartile range [IQR] 9.0, 14.7) years, and CD4 count of 501 (IQR 228, 695); 112 (49%) children were male. Most participants (225/229, 98%) had plasma folate results at enrolment and 214 (93%) children had results available for RBC folate, vitamin B12 and plasma folate at week ≥96. MCV results were analysed on 679 children aged ≥6 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG-SOC] 1.6 ng/ml, 95% CI 0.8, 2.3; p<0.001), and this difference persisted to week ≥96 (2.7 ng/ml, 95% CI 1.7, 3.7; p<0.001). Mean RBC folate at ≥96 weeks was also higher in the DTG arm (difference 73 ng/ml, 95% CI 3, 143; p = 0.041). There was no difference in the treatment arms for vitamin B12 levels at ≥96 weeks or change in MCV through trial follow-up. CONCLUSIONS: Plasma and RBC folate levels were higher in children and adolescents receiving dolutegravir-based ART than on other ART regimens. Further studies are needed to clarify the mechanisms of these interactions and the clinical implications of increased blood folate levels.

Pathologists Overseas: A volunteer-based model for building sustainable, high-quality pathology and laboratory medicine services in low- and middle-income countries.

For thirty years Pathologists Overseas (PO) has worked in low- and middle-income countries (LMICs) to provide affordable, sustainable, and high-quality pathology and laboratory medicine (PALM) services through strategic partnerships and the efforts of our large volunteer network. We address low quality diagnostic services by targeting the 3 pillars of PALM quality: human resources, systems, and quality and accreditation. To improve human resource capacity, PO and our partnering organizations provide virtual continuing education to pathologists and laboratory professionals in these countries. To improve systems, we provide laboratory information system installation and implementation support. Lastly, to improve quality and help laboratories progress toward accreditation, we support an external quality assurance program for laboratories in LMICs. As a relatively small organization, PO demonstrates that a network of dedicated volunteers, in partnership with corporations and professional organizations, can initiate sustainable change in the quality of PALM services in LMICs by focusing efforts on the core components of laboratory quality.

African countries established COVID-19 testing in one month: Here's how they did it.

BACKGROUND: As a novel and deadly acute respiratory syndrome, which later became known as coronavirus disease 2019 (COVID-19), spread beyond China in late January 2020, there were no laboratories in Africa that could test for the disease. However, in early March, just over a month later, 42 African countries had developed the expertise and resources to perform COVID-19 testing. Our goal was to document this public health success story, learn from it, and use it to inform future public health action. INTERVENTION: Three groups were primarily responsible for establishing COVID-19 testing capacity in Africa. The first group comprised early test manufacturers who reacted with incredible speed and ingenuity early in the pandemic, such as the German company TIB MolBiol that developed a molecular test for COVID-19 before the SARS-CoV-2 genome sequence was available. The second group included private and public donors such as the Jack Ma Foundation, and the last were the coordinators of the rollout, such as the World Health Organization and the Africa Centres for Disease Control and Prevention (CDC). LESSONS LEARNT: The first lesson was that speed is critical, especially during a crisis. It was also demonstrated that being a predictable and transparent trusted institution opens doors and improves effectiveness. Africa CDC, which was only three years old, was able to secure significant resources from external partners and rapidly build substantial testing capacity within Africa because it is a trusted institution. RECOMMENDATIONS: Low- and middle-income countries must build local trusted institutions to better prepare for public health challenges.

Corruption: An Impediment to Delivering Pathology and Laboratory Services in Resource-Limited Settings.

OBJECTIVES: Corruption is a widely acknowledged problem in the health sector of low- and middle-income countries (LMICs). Yet, little is known about the types of corruption that affect the delivery of pathology and laboratory medicine (PALM) services. This review is a first step at examining corruption risks in PALM. METHODS: We performed a critical review of medical literature focused on health sector corruption in LMICs. To provide context, we categorized cases of laboratory-related fraud and abuse in the United States. RESULTS: Forms of corruption in LMICs that may affect the provision of PALM services include informal payments, absenteeism, theft and diversion, kickbacks, self-referral, and fraudulent billing. CONCLUSIONS: Corruption represents a functional reality in many LMICs and hinders the delivery of services and distribution of resources to which individuals and entities are legally entitled. Further study is needed to estimate the extent of corruption in PALM and develop appropriate anticorruption strategies.

Availability and Prices of WHO Essential Diagnostics in Laboratories in West Africa: A Landscape Survey of Diagnostic Testing in Northern Ghana.

BACKGROUND: We determined the availability and pricing of laboratory testing in the Northern Region of Ghana to identify current gaps with respect to the WHO's Essential Diagnostics List (EDL). METHODS: A representative sample of facilities offering diagnostic testing within the Northern Region was geographically mapped and evaluated, with random sampling stratified by population density. Data were collected on testing menus, volumes, turn-around times, and out-of-pocket test prices. A total of 27 health centers and 39 clinical laboratories were surveyed between June and August 2019. RESULTS: Health centers offered a median of 2 of 20 tests recommended by the WHO for facilities without laboratories. The most common tests offered included point-of-care tests for malaria, HIV, and pregnancy. Clinical laboratories offered a median of 11 of 72 tests on the EDL. These facilities most commonly provided testing for malaria, HIV, pregnancy, HBsAg, urinalysis, HCV Ab, syphilis, glucose, and CBC. Urban laboratories had a total of 36 EDL tests available while rural laboratories had 12. Test prices were higher in private compared to public laboratories. National Health Insurance reimbursements were lower than out-of-pocket prices (38%), and when controlling for test price, test availability was negatively associated with this gap in reimbursement. CONCLUSIONS: Availability of diagnostic testing in Ghana's Northern Region is severely limited compared to the WHO's EDL. The disparity is pronounced in rural facilities. Reimbursement rates should be reset to more closely match out-of-pocket test prices in order to achieve the Universal Health Coverage target of the Sustainable Development Goals.

Test Cost and Test Accuracy in Clinical Laboratories in Kampala, Uganda.

OBJECTIVES: To assess the accuracy and costs of laboratory tests in Kampala, Uganda. METHODS: A random selection of 78 laboratories tested external quality assurance samples at market rates. There were 40 moderate- to high-complexity and 38 low-complexity laboratories. Four percent (3/78) of these laboratories were accredited and 94% (73/78) were private. The 40 moderate- to high-complexity laboratories performed malaria blood smear, urine human chorionic gonadotropin (hCG), human immunodeficiency virus (HIV), syphilis, glucose, and three-panel tests: CBC, liver function tests, and kidney function tests. The 38 low-complexity laboratories performed malaria blood smear, urine hCG, and syphilis testing only. Hematology, HIV, syphilis, and malarial proficiency testing samples were prepared by accredited laboratories in Kampala. All other samples were provided by the Royal College of Pathologists of Australia. RESULTS: 77.1% of all results were accurate (met target values). It varied widely by laboratory (50%-100%), test identity (malaria blood smear, 96%; serum urea nitrogen, 38%), and test type (quantitative: 66% [31%-89%], qualitative: 91% [68%-97%]). Test prices varied by up to 3,600%, and there was no correlation between test cost and accuracy (r2 = 0.02). CONCLUSIONS: There were large differences in accuracy and price across laboratories in Kampala. Price was not associated with quality.

Voices from the Field: Interviews with Global Health Pathology Volunteers.

Volunteerism in pathology is an uncommon experience. This article attempts to shed light on this experience based on guided narrative interviews. The authors' interviews suggest that prototypical pathology volunteers participate in long-term missions, tend to be later in their careers, are motivated by personal reasons, get involved in volunteering through nongovernmental organizations, focuses on capacity building, and at least partially self-funds their efforts.

The Evolution of Earned, Transparent, and Quantifiable Faculty Salary Compensation: The Johns Hopkins Pathology Experience.

Faculty value equitable and transparent policies for determining salaries and expect their compensation to compare favorably to the marketplace. Academic institutions use compensation to recruit and retain talented faculty as well as to reward accomplishment. Institutions are therefore working to decrease salary disparities that appear arbitrary or reflect long-standing biases and to identify metrics for merit-based remuneration. Ours is a large academic pathology department with 97 tenure-track faculty. Faculty salaries are comprised of 3 parts (A + B + C). Part A is determined by the type of appointment and years at rank; part B recognizes defined administrative, educational, or clinical roles; and part C is a bonus to reward and incentivize activities that forward the missions of the department and medical school. A policy for part C allocations was first codified and approved by department faculty in 1993. It rewarded performance using a semiquantitative scale, based on subjective evaluations of the department director (chair) in consultation with deputy directors (vice chairs) and division directors. Faculty could not directly calculate their part C, and distributions data were not widely disclosed. Over the last 2 years (2015-2017), we have implemented a more objective formula for quantifying an earned part C, which is primarily designed to recognize scholarship in the form of research productivity, educational excellence, and clinical quality improvement. Here, we share our experience with this approach, reviewing part C calculations as made for individual faculty members, providing a global view of the resulting allocations, and considering how the process and outcomes reflect our values.

Creation and Evaluation of a Laboratory Administration Curriculum for Pathology Residents.

OBJECTIVES: A clinical laboratory management (CLM) curriculum that can objectively assess the Accreditation Council for Graduate Medical Education pathology systems-based practice milestones and can provide consistent resident training across institutions is needed. METHODS: Faculty at Emory University created a curriculum that consists of assay verification exercises and interactive, case-based online modules. Beta testing was done at Emory University and Johns Hopkins. Residents were required to obtain a score of more than 80% in the online modules to achieve levels 3 to 4 in the milestones. In addition, residents shadowed a laboratory director, performed an inspection of a laboratory section, and completed training in human subjects research and test utilization. RESULTS: Fourteen residents took and evaluated the laboratory administration curriculum. The printed certificates from the modules were used for objective faculty evaluation of mastery of concepts. Of all the activities the residents performed during the rotation, the online modules were ranked most helpful by all residents. A 25-question knowledge assessment was performed before and after the rotation and showed an average increase of 8 points (P = .0001). CONCLUSIONS: The multimodal CLM training described here is an easily adoptable, objective system for teaching CLM. It was well liked by residents and provided an objective measurement of mastery of concepts for faculty.