More than 75% of the global burden of sickle cell disease (SCD) is carried by the low-income developing countries of sub-Saharan Africa, where incidence at birth can be as high as 4.2% for SCD and 23.7% for sickle trait. SCD is particularly lethal to young children, accounting for up to 15% of under-5 mortality in countries with the highest prevalence of the disease. Data from pilot programs in Africa demonstrate that most of these deaths can be prevented with inexpensive treatments (e.g. penicillin prophylaxis, pneumococcal immunizations, malaria bed nets, and education about the importance of seeking medical attention for fever) ? provided SCD could be diagnosed early in life. In our Phase I work, we have successfully developed a simple and inexpensive paper-based test for the diagnosis of SCD in infants and young children >6 months old. Our test enables the diagnosis via visual interpretation of the stain pattern produced on chromatography paper by a droplet of blood mixed with hemoglobin (Hb) solubility buffer. The current version of the paper-based SCD test kit is completely equipment- and electricity-free, requires only a 10L blood sample, costs <$0.15 per test, can be completed in 35 min, and is unaffected by severe anemia, high HbF, elevated ambient temperature or humidity. It has a limit of detection of <20% HbS, and was able to detect the presence of any HbS (sickle cell trait or disease) in patient samples with 94% sensitivity and 97% specificity in a pre-clinical study in a resource- limited setting (n = 226, Cabinda, Angola). In our laboratory, the test was able to diagnose SCD with 93% sensitivity and 94% specificity (n = 55). In Phase II, we propose to develop a complete, self-contained diagnostic kit, and to demonstrate its diagnostic accuracy in a pivotal clinical trial across multiple sites in several countries in sub-Saharan Africa. We will first evaluate the feasibility of using a prototype kit for diagnosing SCD in the target patient population of children presenting with acute illness to Hospital Provincial de Cabinda. We will also collect input on design and usability of the test?s components and instructions from the site personnel, to inform parallel development of the finished, marketable diagnostic kit. We will then work with our contract manufacturing partners to develop a version of the diagnostic kit that is optimized for mass production, regulatory trials, and subsequent marketing. This iterative process will be continually informed by research and development in our laboratory, the usability data from the Cabinda site, and advice from our marketing and distribution partners. Finally, we will demonstrate the diagnostic accuracy of the finished, marketable SCD test kit in a pivotal clinical trial in sub-Saharan Africa. We have, to date, identified 5 well- qualified clinical sites ? Morogoro (Tanzania), Bamako (Mali), Lusaka (Zambia), Ibadan (Nigeria), and Cabinda (Angola) ? each highly-interested in participating in our trial. We will work closely with our Steering Committee and the FDA to finalize the design of the proposed trial.
Most children born with sickle cell disease in sub-Saharan Africa die in early childhood from causes that could be easily prevented through simple and inexpensive prophylaxis if their disease was diagnosed soon after birth. Universal screening of newborns is impractical in low-income countries due to a large number of out-of- hospital births and the prohibitive cost of conventional testing methods. This highly-innovative project plans to develop and commercialize an ultra-low-cost, paper-based diagnostic test for sickle cell disease to enable screening infants and young children during their first visit to a local clinic.
