Congenital syphilis (CS), caused by mother-to-child transmission of spirochete bacterium Treponema Pallidum (TP), is a major global health problem associated with substantial morbidity and mortality in children. Without adequate treatment CS causes significant developmental, neurological and musculoskeletal disability in children, and many infected infants will die within the first year of life.

In 2016, estimated global incidence for CS was 473 (385-561) cases per 100,000 live births with a total of 661,000 (538,000-784,000) cases, including 355,000 (290,000-419,000) adverse birth outcomes (143,000 stillbirths; 61,000 neonatal deaths; 41,000 preterm/low-birth weight births; and 109,000 infants with clinical CS). These estimates represent a marginal decrease compared to that of 2012.

Treatment of syphilis is simple, effective and inexpensive; however, definitive diagnosis of active syphilis requires confirmatory testing which is often not available in many LRS in low and middle-income countries.

In 81 countries which account for more than 95 per cent maternal deaths and more than 90 per cent of deaths in children under five years old, 74 per cent of pregnant women who had at least four antenatal care visits did not receive syphilis testing.

A combination of treponemal and non-treponemal tests is required for diagnosis of active syphilis but there is no POCT that can effectively distinguish between past/treated and active syphilis. There is no POCT for diagnosis of CS available on the market.

Burnet Institute has developed a novel point-of-care test for confirmation of active syphilis (TP-IgA POCT), which shows excellent diagnostic performance in early evaluations in China and South Africa.

The TP-IgA POCT has the further potential to assist early diagnosis of CS in infants (less than 30 days of age).

We will conduct a prospective clinical validation study to assess clinical utility of the TP-IgA in diagnosis of active syphilis in pregnant women and examining the test capacity in diagnosis of CS in infants born to infected mothers.

A total of 2,433 pregnant women attending ANC clinics at the Colonial War Memorial Hospital in Suva, Fiji will be recruited into the study.

The sample size was calculated based on a disease prevalence of 3%, an expected sensitivity of the TP-IgA of 95% with maximum marginal error of estimate ≤5% at 95% confidence level. At least 70 infants will be tested for CS (i.e. infants born to mothers with positive result in the TP screening and/or confirmatory test).

Data from this study will be used for regulatory approvals (CE mark, WHO prequalification) and guide implementation trials of the TP-IgA in a variety of low-resource settings.

Timeline

August 2021 – July 2024

Outcomes

Following a successful development and early evaluation of a prototype POCT (TP-IgA) for confirmatory testing of active syphilis, this project will, for the first time, assess the clinical utility of the GMP manufactured test among pregnant women and infants in real-world settings.