Both anemia and sickle cell disease (SCD) are highly prevalent across sub-Saharan Africa, and limited resources exist to diagnose these conditions quickly and accurately. The development of simple, inexpensive, and accurate point-of-care (POC) assays represents an important advance for global hematology, one that could facilitate timely and life-saving medical interventions. In this prospective study, Robust Assays for Point-of-care Identification of Disease (RAPID), we simultaneously evaluated a POC immunoassay (Sickle SCAN™) to diagnose SCD and a first-generation POC color-based assay to detect anemia. Performed at Bugando Medical Center in Mwanza, Tanzania, RAPID tested 752 participants (age 1 day to 20 years) in four busy clinical locations. With minimally trained medical staff, the SCD POC assay diagnosed SCD with 98.1% sensitivity and 91.1% specificity. The hemoglobin POC assay had 83.2% sensitivity and 74.5% specificity for detection of severe anemia (Hb ≤ 7 g/dL). Interobserver agreement was excellent for both POC assays (r = 0.95-0.96). Results for the hemoglobin POC assay have informed the second-generation assay design to be more suitable for low-resource settings. RAPID provides practical feasibility data regarding two novel POC assays for the diagnosis of anemia and SCD in real-world field evaluations and documents the utility and potential impact of these POC assays for sub-Saharan Africa.

Introduction. Anemia is a common cause of global morbidity and mortality, disproportionately affecting women and children living in resource-limited settings. The etiology of anemia is multifactorial, but sickle cell disease (SCD) is one of the most important causes and is associated with significant morbidity and early mortality. Simple, inexpensive, point-of-care (POC) diagnostic assays for both anemia and SCD could allow for timely, life-saving medical interventions. Recently developed POC assays have been evaluated in controlled laboratory settings by experienced US investigators, but their feasibility and accuracy have yet to be evaluated in a busy low-resource setting by minimally trained local end-users. In the Robust Assays for Point-of-care Identification of Disease (RAPID) study, we simultaneously evaluated POC assays for both anemia and SCD in Mwanza, Tanzania. Methods. RAPID was a prospective study performed at Bugando Medical Centre, a busy referral hospital in northwest Tanzania. Patients <21 years old were recruited from the sickle cell clinic, the outpatient pediatric clinic, the emergency department, and the inpatient pediatric ward. SCD status was determined using Sickle SCANTM (Biomedomics, Research Triangle Park, North Carolina), a POC lateral flow assay able to qualitatively identify the presence of HbS, HbC, and HbA. The presence and severity of anemia was determined using a first generation novel POC color-based assay that quantifies the hemoglobin concentration by chemically altering the sample's color and comparing it to a pre-defined color scale. Both assays are performed using 5-10 μL of blood collected by finger prick, providing results within 5 minutes. Hemoglobin electrophoresis and a complete blood count (CBC) were also completed for each participant. Both POC assays were independently interpreted by 2 care providers at the bedside, one being an experienced primary member of the RAPID study team and the other a minimally trained medical staff member. Interobserver agreement was calculated, and the sensitivity and specificity of each POC assay was determined using the electrophoresis and CBC results as the gold standard. The sickle cell POC devices were provided free-of-charge by Biomedomics. They had no access to the data or results. Results. RAPID recruited 752 participants (age range 1 day to 20 years, average age 5.2 ± 4.2 years), and data were available for 745. Children were primarily recruited from the inpatient pediatric ward (58.2%) or the sickle cell clinic (38.5%). Two individuals served as Scorer 1, and they interpreted 99% of the assays. Scorer 2 included 136 different Tanzanian pediatricians, interns, students, and nurses. Sensitivity and specificity for the SCD POC assay were excellent for both Scorer 1 (sensitivity 99.4%; specificity 94%) and Scorer 2 (sensitivity 98.1%; specificity 91.1%), with excellent interobserver agreement (Kappa = 0.95). The absolute difference (mean ± SD) between the color-based anemia POC assay and the CBC result was 1.0 ± 0.9 g/dL for Scorer 1 and 1.1 ± 0.9 g/dL for Scorer 2. There was a moderately strong correlation between the anemia POC assay and the measured hemoglobin concentration (r=0.65), and the POC assay had 83.2% sensitivity and 74.5% specificity for detection of severe anemia (Hb ≤7 g/dL, n=171). Interobserver agreement was excellent in the POC anemia assay (r = 0.96). Conclusions. RAPID provides practical feasibility data regarding two novel POC assays for the diagnosis of anemia and SCD in a real-world field evaluation within sub-Saharan Africa. The POC SCD device was highly sensitive and specific compared to the laboratory result, even when interpreted by numerous minimally trained personnel with variable expertise in clinical medicine. The first generation POC anemia assay demonstrated good correlation with the laboratory result and showed excellent interobserver agreement. Pilot results for the POC anemia assay are being used to design a subsequent generation, better suited for low-resource settings. Overall, the pilot data for these POC assays represent important steps toward refining and implementing them in limited resource settings where they are needed the most. Disclosures Tyburski: Sanguina, LLC: Equity Ownership. Lam: Sanguina, LLC: Equity Ownership. Ware: Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.