Congenital and Maternal Point of Care Rapid Testing for Syphilis Study, Uganda

Maternal syphilis is a major cause of poor birth outcomes including congenital syphilis (CS), which may cause miscarriage, stillbirth, or birth defects. In 2016, the global maternal syphilis prevalence was an estimated 0.69% resulting in a global CS rate of 473 per 100,000 live births and 661,000 total CS cases, including 355,000 adverse birth outcomes and 306,000 non-clinical CS cases (infants without clinical signs born to untreated mothers). The prevalence of syphilis and CS in Uganda is high. In a study of 570 antenatal women with HIV in Kampala, 5.1% had syphilis. Other Ugandan studies have demonstrated >3% prevalence of antenatal syphilis and CS prevalence of 3.8% among newborns.

Testing for syphilis in pregnancy accompanied by effective treatment with benzyl penicillin G (benzathine penicillin) can significantly reduce the risk of CS. This should ideally occur as early in pregnancy as possible, with each additional week of delay in diagnosis and treatment increasing the risk of CS. Syphilis testing in Uganda, as in many other low- and middle-income countries, primarily relies on rapid diagnostic tests that detect IgG antibodies against Treponema pallidum, the bacterium responsible for syphilis. These treponemal tests (TT) are highly sensitive and therefore valuable for initial diagnosis but cannot differentiate between untreated and previously treated syphilis due to their lifelong positive result.

To confirm infection, a lipoidal, non-treponemal test (NTT) like the rapid plasma reagin (RPR) test is also required. NTTs are relatively inexpensive but require a reliable electricity supply, reagents, laboratory infrastructure and trained laboratory personnel. The performance of tests like the RPR may be suboptimal with wide inter-laboratory variation, especially in low-income settings with high humidity levels. This prevents diagnosis and treatment from occurring during the same antenatal visit, leading to treatment delays or treatment being missed entirely. Following treatment, NTT antibody titres are ideally followed up to 12 or 24 months (depending on syphilis stage and HIV status), which is also complicated by the above issues.

In babies born to mothers with syphilis, serological diagnosis of CS is made by demonstrating a ≥4- fold higher NTT titre in infant compared to maternal blood (e.g., maternal NTT titre 1:2, infant NTT titre 1:8). The higher titre in the infant suggests that NTT antibodies were being made in the fetus representing infant infection. TTs are not useful in the serological diagnosis of CS because they likely represent transplacental transfer of maternal treponemal IgG. The infrastructure required and delays to provision of results for traditional RPR testing creates similar challenges in diagnosing and treating infants born at risk of CS or with clinical features consistent with CS as it does in pregnant persons.

Lateral flow assays are simple, quick, and potentially low-cost tests that can be conducted at the point- of-care, enabling clinicians to make timely diagnoses and allowing testing and treatment to be provided during the same encounter. This has clear benefits for patients in reducing number of clinic visits required, and in the context of the Ugandan healthcare system where only 37% of women receive antenatal care in the first trimester and 68% have 4 or more antenatal visits, reducing any delays to treatment and risk of loss to follow up are essential.