Aim:

This project will optimise and validate an innovative and sensitive point-of-care (POC) test, which will rapidly and accurately diagnose active syphilis and allow for immediate treatment at the point of care.

Congenital syphilis affects more newborns than any other infection (including HIV or tetanus) with many infants dying within the first year of life. Every year maternal syphilis infection contributes to over 650,000 perinatal deaths, and an estimated quarter of all stillbirths.

In 2008, an estimated 1.4 million pregnant women were infected with syphilis, with adverse pregnancy outcomes including stillbirth, neonatal death, premature birth, low birth weight babies, and neonatal syphilis infection occurring in over 50 percent of untreated pregnancies.

Treatment of syphilis is simple and inexpensive, but diagnosis of active syphilis is challenging, requiring venous blood collection, laboratory equipment and trained staff, which hampers implementation and thus delivery of these potentially life-saving treatments.

Rapid point-of-care diagnostic tests can increase uptake by facilitating same-day treatment of pregnant women to treat maternal disease and prevent stillbirth and congenital syphilis. However, existing point-of-care tests cannot differentiate between active syphilis and past or treated syphilis, limiting their impact particularly in high-prevalence settings.

Objectives:

This project will optimise and validate an innovative, specific and sensitive point-of-care (POC) test, which, for the first time, will rapidly and accurately diagnose active syphilis and allow for immediate treatment at the point of care. This diagnostic test will result in significant improvements in the health of women and children through prevention of stillbirths and severe neonatal morbidity and mortality associated with congenital syphilis.

A test that could rapidly and accurately diagnose active syphilis at the point-of-care would lead to timely diagnosis and immediate treatment of pregnant women, thereby substantially impacting on maternal health, stillbirths and neonatal morbidity and mortality.

This new POC test will be simple to use, will be instrument free and will only need a finger-prick sample of blood. It will produce accurate results within 30 minutes. It will be a disposable, low-cost lateral flow test with proven manufacturing processes and being similar to other point-of-care tests already familiar to health care workers, requiring minimal training and readily applicable to primary health care facilities.

We aim to develop the first POC test to allow specific diagnosis of active syphilis infection at the point-of-care, which will minimise loss to follow-up and maximise effective treatment.

Activities:

This project involves developing a new optimised POC test that detects a novel biomarker present during active syphilis infection and IgG (present for life after syphilis infection) separately in a single device, and will therefore be able to differentiate active from past or treated infections.

The test will be developed at the Burnet laboratories by harmonising the proprietary methods incorporated in the current Omega VISITECT® syphilis total antibody test and an assay for the novel biomarker, and incorporating them in a single test device.

The new test will be optimised and validated in the laboratory against standard syphilis serology – RPR and TPHA – as well as a commercial laboratory assay (ELISA). The specificity and sensitivity will be assessed using a panel of approximately 60 plasma samples representing active syphilis (n=20), past syphilis (n=20) and healthy controls (n=20) obtained from the National Serology Reference Laboratory in Melbourne, Australia. Following the laboratory-based test optimisation, initial performance will be evaluated in a “blinded” study using an independent panel of stored plasma samples (n=450, NCSTDs, China; n=300, OPHID, Zimbabwe).

The new syphilis test will be compared with standard syphilis serology, an ELISA and three of the currently available syphilis POC tests. Positive and negative predictive values will be calculated for populations with different prevalence levels, demonstrating the potential of this new POC test to prevent congenital syphilis.

Timeline

October 2014 - December 2018

Results

The primary outcome of this study is the successful development of a point-of-care syphilis test with comparable sensitivity and specificity to available rapid syphilis diagnostic tests, and the ability to accurately distinguish between active and past treated infections. This test could result in immediate access to diagnosis and significantly increased syphilis treatment uptake, thereby improving maternal and neonatal health outcomes and reducing stillbirths.