Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay.

Objective: To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods: We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings: We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion: Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in sub-Saharan African laboratories, leading to improved treatment selection and better clinical outcomes.

Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay

Objective To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in subSaharan African laboratories, leading to improved treatment selection and better clinical outcomes.

Pathology Training for Cancer Diagnosis in Africa.

OBJECTIVES: In response to requests for training in cancer pathology, two virtual training courses were organized: one in English for participants in Nigeria and another in French for participants in Francophone Africa. Each course had weekly 90-minute sessions covering essential topics in cancer pathology led by global experts. METHODS: Two research questions were investigated for both courses: (1) did the participants improve their knowledge of the topics covered during the course, and (2) did the course participants appreciate the virtual training format? RESULTS: The Nigeria course enrolled 85 participants from 26 Nigerian states; the Francophone Africa course enrolled 425 participants from 18 African countries. In the pre-post technical assessment, participants increased their scores on average by 3.4% (P > .05) in the Nigeria course and by 13.1% (P < .001) in the Francophone Africa course. On the postcourse survey, 95.8% of Nigerian respondents and 96.1% of Francophone African respondents reported being satisfied or very satisfied with the virtual format. CONCLUSIONS: Virtual training is a promising tool to improve cancer diagnosis in Africa, as the experience of the courses illustrates that participants appreciate the virtual format. Continued training is required to reinforce skills and enable participants to appropriately apply new knowledge to their daily practice.

Multisector Collaborations and Global Oncology: The Only Way Forward.

PURPOSE: At the 12th meeting of AORTIC (African Organization for Research and Training in Cancer) in Maputo, Mozambique, held between November 5 and November 8, 2019, a special workshop was organized to focus on the need for collaboration and coordination between governments and health systems in Africa with academic, industry, association, and other nongovernmental organizations to effect sustainable positive change for the care of patients with cancer. METHODS: Representatives from seven different projects in Africa presented implementation science and demonstration projects of their to date efforts in cancer system improvement including patient access, South-South partnerships, in-country specialized training, palliative care consortium, treatment outcomes, and focused pathology and diagnostic capacity building. Key partners of the various projects served as moderators and commentators during the session. RESULTS: From across all the presentations, lessons learned and exemplary evidence of the value of partnerships were gathered and summarized. CONCLUSION: The concluding synthesis of the presentations determined that with the broad needs across cancer requiring in-depth expertise at each point on a patient's journey, no single organization can effect change alone. Multipartner collaborations not only should be the norm but should also be coordinated so that efforts are not duplicated and maximum patient access to cancer diagnosis and care is achieved.

Providing Laboratory Medicine Training in a Low-Resource Setting.

OBJECTIVES: We developed and participated in a 1-week laboratory medicine training presented from June 3, 2019, to June 7, 2019. METHODS: The training was a combination of daily morning lectures and case presentations as well as afternoon practical sessions in the clinical laboratory. The content was selected over months by local organizers and the visiting faculty and further modified on site to reflect local needs. RESULTS: Participants identified practice changes that could be realized in the short term but most faced significant barriers to implementation in the absence of structured and long-term follow-up. CONCLUSIONS: In this report, we review insights learned from our experience and reflect on strategies for realistic, meaningful, and relevant contributions in the setting of laboratory medicine-oriented short-term programs.

Survey of Global Health Education and Training in Pathology Residency Programs in the United States.

OBJECTIVES: This study assessed the prevalence, general interest, and barriers to implementing global health curricula in pathology residency programs. METHODS: We conducted a survey of 166 US pathology residency programs. RESULTS: Thirty-two (195) of 166 programs responded. Of these, 13% have a formalized global health program (n = 4), and the majority indicated at least some general interest in global health among trainees (88%, n = 28) and faculty (94%, n = 30), albeit at a low to moderate level. Funding limitations, regulatory constraints, and insufficient knowledge of global health were frequently cited barriers to developing a global health program. CONCLUSIONS: Few US pathology departments incorporate global health education into postgraduate training. The importance of pathology in global health has been underappreciated, despite its critical role in the delivery of health care in resource-limited settings. One solution is for pathology departments to expand global health educational opportunities for trainees.

Cerebral melioidosis for the first time in the western hemisphere.

This report is the first published case of cerebral melioidosis in the western hemisphere. In this paper the authors review the literature on neurological melioidosis and its presentation and treatment in endemic areas, describe the clinical course of this unique case of a presentation of the disease with cranial abscess in the US, review the pathological and radiological findings associated with this seminal case, and put forth recommendations for recognizing and treating possible future instances of the disease within the western hemisphere.

Infectious granulomatous dermatitis associated with Rothia mucilaginosa bacteremia: A case report.

Infections with rare pathogens are being recognized with increasing frequency in severely immunocompromised patients. As a result of these patients' underlying compromised defenses and susceptibility to atypical organisms, tissue biopsies from patients within this population may demonstrate nonclassical histopathological findings. Here, we describe an unusual granulomatous reaction to gram-positive cocci in the skin of a 52-year-old man undergoing salvage chemotherapy for acute myeloid leukemia. The patient presented with a papular eruption on the arms, trunk, and face and fever; concomitant blood cultures were positive for Rothia mucilaginosa and Streptococcus salivarius. Histologic evaluation revealed a granulomatous dermatitis associated with numerous small, round, predominantly intracellular bacteria. Classically, cutaneous infiltrates associated with coccoid bacterial infections are suppurative and not granulomatous. The intracellular organisms stained positive for Gram, periodic acid-Schiff, and Grocott methenamine silver stains, suggestive of R. mucilaginosa. Rothia mucilaginosa, a component of the oral flora, was first reported as a human pathogen in 1978. Although the majority of cases in the literature have described R. mucilaginosa bacteremia, other reported manifestations include meningitis, endocarditis, pneumonia, osteomyelitis, and peritonitis. To our knowledge, however, only 1 prior report has described a cutaneous manifestation of R. mucilaginosa septicemia, which occurred in a patient with neutropenia. This is the second reported case of an infectious granulomatous dermatitis associated with R. mucilaginosa bacteremia and raises awareness of this unusual histopathological presentation in the setting of a bacterial infection affecting the skin.

Suppurative inflammation with microabscess and pseudocyst formation is a characteristic histologic manifestation of cutaneous infections with rapid-growing Mycobacterium species.

Mycobacterial infections of the skin classically cause a granulomatous tissue reaction. We have observed a suppurative pattern of inflammation associated with infections by rapid-growing Mycobacterium species in immunocompromised patients. We report 6 cases in skin and soft tissue with an unusual but consistent lack of a predominance of granulomatous inflammation. Of the 6 cases, 4 had predominantly (approximately 75%) suppurative inflammation, 1 case predominantly demonstrated (approximately 75%) a mix of acute and chronic inflammation, and 1 case showed an approximately equal contribution of suppurative and granulomatous inflammation. All 6 cases showed abscess formation and numerous acid-fast bacilli (AFB) on AFB stain and were confirmed by tissue culture. Of these 6 cases, 2 had microabscesses with central pseudocysts harboring microorganisms. Five patients were taking oral prednisone, and 1 had an uncharacterized immunodeficiency. These cases highlight the need for awareness of this unusual manifestation of infection with rapid-growing Mycobacterium species, particularly in immunocompromised patients.

Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease.

Malaria is an ancient disease that continues to cause enormous human morbidity and mortality. The life cycle of the causative parasite involves multiple tissues in two distinct host organisms, mosquitoes and humans. However, all the clinical symptoms of malaria are a consequence of infection of human erythrocytes. An understanding of the basic mechanisms that govern parasite invasion, remodeling, growth, and reinvasion of erythrocytes and the complex events leading to tissue pathology may yield new diagnostics and treatments for malaria. This approach is revealing a more complete picture of the most serious syndrome associated with this infection-cerebral malaria. We focus on the most recent understanding of the molecular basis of infection, summarize our finding from an ongoing pediatric cerebral malaria autopsy study in Malawi, and integrate these insights to malarial pathology.