Schistosomiasis Diagnosis Using a CAA Antigen Test

Study design

The freeBILy-GAB study is a set of interlinked prospective, observational studies conducted in Gabon to comprehensively assess the performance of CAA measurement for the detection of S. haematobium infections in pregnant women and infants. The study is composed of 3 sub-studies each targeted to assess a specific objective (see figure 1 for a schematic trial design, procedures and stages). The study activities will also contribute to safety reporting of PZQ use in pregnant women.

Sub-study A: At baseline, a diagnostic study will be conducted that will also allow to select sub-study B study participants. The approach is a prospective, cross-sectional, observational study conducted in pregnant women to determine the sensitivity and specificity of the UCP-LF CAA test for the detection of S. haematobium infections using urine samples. In the absence of a sensitive reference standard test, the index test (UCP-LF CAA) will be compared against a composite diagnostic reference test based on extensive egg microscopy, serology, qPCR on egg DNA, and POC-CCA. Sampling will include standardized urine collection of 3 consecutive days for S. haematobium diagnosis by egg microscopy, UCP-LF CAA testing, qPCR, and POC-CCA, one (1) stool sample (within the 3 days of urine sampling) to control for S. intercalatum and soil-transmitted helminths infections, and 1 blood sample (within the 3 days of urine sampling) to measure anti-Schistosoma antibodies and to detect any other parasitic infections endemic in the region including filarial and Plasmodia spps. and to provide blood cell counts and hemoglobin to assess pregnant women health status. The laboratory staff involved in performing the laboratory assays using the new techniques will be trained prior to the start of the study. Volunteers positive for any parasitic infection except filaria will be treated for the respective parasitic infection (S. haematobium, STH and malaria parasites) following national treatment guidelines. Women positive for S. haematobium by egg microscopy or UCP-LF CAA at baseline will receive either PZQ treatment (1x 40 mg/kg) within 7 days after the third urine sample (early PZQ treatment) or after delivery (late PZQ treatment) following an allocation ratio of 3:1. The late PZQ treatment group serves as a safety control group of PZQ administration to pregnant women and exposure of their offspring (s). Maternal and perinatal safety and efficacy outcomes will be assessed. For efficacy in offspring, birthweight (with low birthweight defined as weight at birth \<2.5 kg) and small gestational age (used as an indicator for possible intrauterine growth restriction) will be investigated. In addition, the exposure to PZQ during pregnancy will be evaluated in infants at the age of 12 and 24 months. For efficacy in mothers, maternal anemia (defined as Hb \< 11 g/dl) at inclusion and at delivery will be investigated.

Sub-study B is an observational, follow-up study of pregnant women infected with S. haematobium by egg microscopy and/or UCP-LF CAA test and treated with PZQ or intended for late PZQ treatment (see sub-study A). The aim of this sub-study is to assess if the UCP-LF CAA test can be used to evaluate treatment efficacy of PZQ during pregnancy. Women positive for S. haematobium by egg microscopy and/or UCP-LF CAA test and treated with PZQ (see sub-study A) will be actively followed-up. Urine will be collected on day 2, day 4 and day 6 after PZQ treatment to determine the kinetics of CAA decay and then once a week until both egg microscopy as well UCP-LF CAA assay become negative but no longer than 6 weeks after PZQ treatment.

Sub-study C is an observational, longitudinal study on mothers and their newborn babies. This sub-study aims to determine the incidence of S. haematobium infections and age to first S. haematobium infection in life time in infants born from mothers included in the study. Therefore, between 6 and 24 months post-delivery, mother and her infant will be asked to provide urine every three month until UCP-LF CAA test becomes positive for S. haematobium detection. In addition a questionnaire addressing water contact of mother and infant will be applied. If UCP-LF CAA test becomes positive, mothers will be treated with 1x 40 mg/kg PZQ.

Furthermore, outcome of PZQ treatment during pregnancy on infant development will be assessed at the age of 12 and 24 months after delivery in the two groups (early and late PZQ treatment groups). This allows for a comparison to the freeBILy-MAD study in Madagascar.