New Sickle Cell Disease Screening Test Is Highly Accurate – and Inexpensive

Editor’s note: On March 11, 2019, the editors of Blood retracted this abstract, after a co-author stated it was submitted without his consent.

In a population of young children in Uganda, a new screening test for sickle cell disease (SCD) that delivers point-of-care results and costs $2 or less to perform was more than 99 percent accurate in detecting the disease, according to results presented as a late-breaking abstract at the 2018 ASH Annual Meeting.1

Standard diagnostic tools for SCD are not suitable for most parts of Africa, as they require expensive machinery and large volumes of blood. This new “uncomplicated and rapid procedure” is ideal for limited-resource regions; it takes just 10 minutes, six drops of water, and one drop of blood to complete, study author Erik Serrao, PhD, from Silver Lake Research Corporation in Azusa, California, noted.

“Diagnostic screening for SCD in newborns and young children – followed by treatment, prophylaxis, and counseling – has been shown to dramatically reduce the mortality of this disease in higher-resource regions,” Dr. Serrao explained. “However, sickle cell screening has not been widely implemented in Africa, so individuals with the disease are commonly identified only after they die or when they present at the hospital with life-threatening symptoms.”

In this study, investigators established an SCD screening program at a major hospital in southeastern Uganda, an area where SCD accounts for approximately 20 percent of childhood deaths each year.

Blood samples from 1,000 recruited children younger than 5 years old were run through HemoTypeSC and a reference test, capillary zone electrophoresis (CZE), which costs $12 to perform.

HemoTypeSC is a lateral flow assay that relies on highly specific monoclonal antibodies for hemoglobin (Hb) A, HbS, and HbC to diagnose SCD. The testing kit instructs clinicians to place a drop of blood onto a paper strip, then dip it into a vial with a few drops of blood. A test strip containing the antibodies is then added to the test tube, where it encounters the blood. In ten minutes, the paper strip shows a specific test line if the patient has markers for SCD.

HemoTypeSC diagnostic results matched the results of the reference test for 998 of the 1,000 specimens analyzed, for an accuracy rate of 99.8 percent. Of these specimens, 720 were found to have HbAA by both HemoTypeSC and CZE. Of the remaining 280 specimens, two yielded discordant results, in which specimens identified as HbSS (meaning both of the child’s parents had HbS gene, denoting SCD) by CZE were identified as HbAS (meaning one parent had HbS, denoting sickle cell trait) by HemoTypeSC.

As part of the study protocol, investigators ran a secondary analysis on tests with discordant results. When parents were contacted to obtain another blood sample, researchers learned that the two patients who had discordant results had been diagnosed with HbSS and were recently transfused with HbAA, which led to trace levels of HbA in their blood. “Therefore, their true phenotype at the time of testing was HbAS for both samples – as detected by HemoTypeSC,” Dr. Serrao explained. When researchers adjusted for these results, the accuracy improved to 100 percent.

Anecdotally, he said that clinicians in the program have not reported any difficulty either in performing or reading results from the test.

Although the results show that the HemoTypeSC test is a promising screening tool, Dr. Serrao acknowledged that “one limitation is that the youngest age screened is 1 month, so we didn’t include any newborns in this study.” However, he cited an earlier study that evaluated HemoTypeSC in 57 newborns, in which the test had sensitivity and specificity above 99 percent.2

“SCD screening programs have been projected to be cost-effective in Africa and could actually save significant amounts of money for governments as [more of their] budgets are allocated to screening and less to identifying the disease after patients present with life-threatening symptoms,” he concluded.

The authors report financial relationships with Silver Lake Research Corporation, which developed HemoTypeSC and supported this study.


References

  1. Nankanja R, Kiyaga C, Geisberg M, et al. Implementation of a Sickle Cell Disease Screening Initiative in Uganda with HemoTypeSCTM. Abstract #LBA-3. Presented at the 2018 ASH Annual Meeting, December 4, 2018; San Diego, CA.
  2. Steele C, Sinski A, Asibey J, et al. Point-of-care screening for sickle cell disease in low-resource settings: a multi-center evaluation of HemoTypeSC, a novel rapid test. Am J Hematol. 2018 October 5. [Epub ahead of print]

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