A rapid test for congenital syphilis screening

PROJECT SUMMARY
Since 2014, Congenital Syphilis (CS) cases in the United States, caused by the transplacental transmission of
the bacterium Treponema pallidum from mother to child, have increased at an alarming rate. Targeted
surveillance studies indicate a rise andgt;185% from 2014 to 2018 alone. Women who acquire syphilis within 4
years of pregnancy will transmit the infection to 80% of their fetuses, and 4 in 10 pregnancies will end in
stillbirth or infant death. Infants contracting CS may be asymptomatic, but they can also suffer from serious
early- (andlt; 3 months) and late-stage (andgt;2 years) manifestations of multisystemic syphilis infection, including skin
lesions, bone deformities, liver abnormalities, and blindness. Treponema strains are extremely difficult to
culture, thus sensitive and specific diagnosis requires multi-step testing paradigms that are labor intensive,
subject to false-positives and false-negatives, and limited in scalability. No single test is currently commercially
available that enables accurate, rapid, inexpensive, and simple widespread testing for syphilis infection. Yet,
such a test could reduce syphilis-associated stillbirth and perinatal death by up to 75%. Here we propose to
extend the capabilities of “MeltSeq”, our novel pathogen identification platform that is specifically geared
towards neonatal infections and small-volume blood samples. Phase I builds upon our previous work in
broad-based pathogen identification at single-genome levels to develop a fast and actionable Treponema
detection and strain differentiating assay. In addition, we will reduce testing times from ~3 hours to andlt;1 hour, the
typical time of an office visit, by using our unique device to achieve rapid amplification and by optimizing our
novel blood sample preparation technology. These advances will enable syphilis screening during pregnancy.
Finally, we will advance microbial DNA extraction from dried blood spot (DBS), which are collected on virtually
all newborns in the United States, to enable universal newborn syphilis screening. Phase II involves both
retrospective and prospective clinical evaluation for 510(k) approval and commercialization of a point-of-care
device. Our multidisciplinary team approach combines expertise in clinical neonatology, bioengineering, and
commercial product development to create a simple and inexpensive syphilis test that can be utilized for
pregnant women and newborn screening programs.PROJECT NARRATIVE
Each year, nearly 1.4 million pregnant women are infected with syphilis worldwide, and transmission to fetuses
frequently results in infant mortality. Undiagnosed or mis-treated cases account for nearly 90% of these deaths,
yet, no commercially-available test provides the rapid, inexpensive, and differentiative identification of the
causative bacteria, Treponema pallidum. Our goal is to create a robust, cost-effective platform for syphilis
detection, which will be integrated into our novel, broad-based detection strategy encompassing a multitude of
infectious diseases afflicting pregnant women and neonates to significantly reduce morbidity and mortality.