Background: Female genital tract inflammation increases risk of adverse sexual and reproductive outcomes, including HIV acquisition and preterm birth. This inflammation is primarily caused by sexually transmitted infections (STIs) and bacterial vaginosis (BV), which are asymptomatic in most women. Although gold standard nucleic acid amplification diagnostic tests (NAATs) have been developed to detect these infections, their cost and required resources limit their use for routine screening. We have validated biomarkers of vaginal inflammation (IL-1α, IL-1β, IP-10) caused by STIs/BV in five African cohorts. We aim to develop and implement a low-cost rapid point-of-care test, called the Genital InFlammation Test (GIFT), to measure these biomarkers and increase STI/BV case-finding.
Methods: We developed two lateral flow immunochromatographic prototypes measuring both IL-1α and β in a multiplexed assay and IP-10. The devices were evaluated using recombinant cytokines and vaginal swabs collected from South African women and the results were compared to ELISA. Optimal vaginal swab type and equipment-free processing methods were determined. A two-round modified Delphi survey was administered globally to evaluate stakeholder recommendations for implementation.
Results: The prototype devices had analytical sensitivities <50pg/ml for IL-1α and β and <70pg/ml for IP-10. The test line intensities observed by the naked eye correlated with ELISA concentrations (r=0.78, p=0.02; r=0.90, p=0.001; r=0.97, p<0.0001 for IL-1α and β and IP-10, respectively). Flocked swabs were identified as the best swab type and swab compression by hand in phosphate buffered saline preloaded into soft nozzle-cap tubes increased cytokine recovery from vaginal swab secretions compared to vortexing. Sixty-four stakeholders, mainly healthcare professionals, responded to the Delphi survey. The majority (84%) would offer screening with GIFT to sexually active asymptomatic women in low and middle-income regions.
Conclusion: If offered to women attending healthcare clinics or used for self-testing, GIFT could increase STI/BV case-finding. The GIFT device, user experience and cost-effectiveness are currently being evaluated in three settings in Africa. The next step will be to identify use cases for GIFT in other world regions, including the Asia-Pacific.