Evaluation of a Density-Based Rapid Diagnostic Test for Sickle Cell Disease in a Clinical Setting in Zambia

Abstract

Although simple and low-cost interventions for sickle cell disease (SCD) exist in many developing countries, child mortality associated with SCD remains high, in part, because of the lack of access to diagnostic tests for SCD. A density-based test using aqueous multiphase systems (SCD-AMPS) is a candidate for a low-cost, point-of-care diagnostic for SCD. In this paper, the field evaluation of SCD-AMPS in a large (n = 505) case-control study in Zambia is described. Of the two variations of the SCD-AMPS used, the best system (SCD-AMPS-2) demonstrated a sensitivity of 86% (82–90%) and a specificity of 60% (53–67%). Subsequent analysis identified potential sources of false positives that include clotting, variation between batches of SCD-AMPS, and shipping conditions. Importantly, SCD-AMPS-2 was 84% (62–94%) sensitive in detecting SCD in children between 6 months and 1 year old. In addition to an evaluation of performance, an assessment of end-user operability was done with health workers in rural clinics in Zambia. These health workers rated the SCD-AMPS tests to be as simple to use as lateral flow tests for malaria and HIV.

From the Bench to the Field in Low‐Cost Diagnostics: Two Case Studies

“…This extra shipping time, and the much elevated temperatures encountered by the tests as they awaited shipment through the damaged airport, could have compromised the tests, but unfortunately, the conditions during shipment were unknown. Indeed, the performance of the delayed batch was significantly worse than the other batches, [12] but without additional information, we could not justify exclusion from the data analysis. This experience demonstrates the importance of setting clear parameters for valid results, including shipping and storage conditions, along with the use of temperature and humidity loggers to capture the relevant data.…”

“…[44,45,47,48] We developed aqueous multiphase systems (AMPS)-mixtures of polymers in water that spontaneously separate into immiscible liquid phases-to separate and visually identify the presence of dense cells characteristic of SCD. [10,12] The densities of the phases of AMPS provide a step-gradient in density. We designed a two-phase system (ρ top = 1.078 g/cm 3 ; ρ bot = 1.129 g/cm 3 ) and a three-phase system (ρ top = 1.077 g/cm 3 ; ρ mid = 1.108 g/cm 3 ; ρ bot =1.120 g/cm 3 ) such that only dense cells characteristic of SCD would be able to sink through the bottom phase (most dense) and form a visible red layer at the interface between the bottom phase and the seal at the bottom of the container.…”

“…[12] Briefly, of the two prototypes tested, the best system had a diagnostic accuracy of 77%. In general, false positives were more frequent than false negatives (more so than was found in the initial validation studies).…”

“…In the last seven years, we have taken two technologies from the bench [7][8][9][10] to the field. [11,12] Each technology, has required a different approach. In one case, development and field testing were done through a strong partnership with a non-profit company.…”

Time to Invest in Sickle Cell Anemia as a Global Health Priority

“…There are a number of prototypes that are currently being developed and validated, and it appears that POC testing for SCA will soon become widely available. [11][12][13][14][15][16] Once simple and inexpensive POC tests become available, they will be highly useful for both NBS and public awareness campaigns to empower adolescents and young adults with both the knowledge and implications of their "sickle status" to make informed reproductive decisions. Although it is somewhat controversial in many geographic regions, genetic counseling should also be a priority, as neonatal screening programs may be able to reduce morbidity and mortality associated with SCA, but it cannot reduce the actual number of SCA births.…”