The Potential for Combined Treponemal/Nontreponemal Rapid Point-of-Care Test and Treponema pallidum Polymerase Chain Reaction in the Diagnosis of Gestational and Congenital Syphilis in a Low-Resource, High-Prevalence Setting: Pilot Data From Malawi.

BACKGROUND

Congenital syphilis (CS) remains a major cause of stillbirth and neonatal morbidity, with an estimated 700,000 cases and 390,000 adverse birth outcomes annually. We evaluated the diagnostic utility of combined treponemal (TT) and nontreponemal (NTT) rapid point-of-care test and Treponema pallidum polymerase chain reaction (PCR) for detecting active maternal syphilis, CS, and treatment response in a high-prevalence, low-resource setting.

METHODS

Secondary analyses were conducted from a prospective case-control study at Queen Elizabeth Central Hospital, Malawi. Women were recruited ≤48 h postpartum. Maternal and infant sera underwent testing with the DPP® Syphilis Screen and Confirm (Dual rapid diagnostic test [RDT]) and T. pallidum PCR (maternal vaginal swabs and infant nasopharyngeal swabs), with predefined clinical-serological reference standards based on qualitative rapid plasma reagin (RPR).

RESULTS

Among 504 of 510 women with complete data, Dual RDT identified 110 seropositive cases at delivery, including 86 new maternal syphilis diagnoses. The NTT band showed good performance in mothers versus RPR (sensitivity: 84.8% [95% confidence interval: 77.4%-92.1%]; specificity 92.7% [95% confidence interval: 90.3%-95.1%]) but reduced sensitivity in infants, increasing from 51.9% to 80.0% with RPR titer. Laboratory visual and microreader interpretation showed high concordance (99.5%), while bedside visual accuracy was lower (77.4%). Any Dual RDT positivity identified 19 high-risk infants, of whom 7 of 19 (36.8%) were NTT positive. PCR detected maternal infection in 11 of 504 (2.2%), including 3 serology-negative cases.

CONCLUSIONS

Dual RDT improves detection over TT alone. The NTT band without quantitation is insufficient for treatment monitoring or infant diagnosis. Combining Dual RDT with PCR may enhance detection of active maternal infection and CS in high-burden settings.