Prospective, observational study to assess the performance of CAA measurement as a diagnostic tool for the detection of Schistosoma haematobium infections in pregnant women and their child in Lambaréné, Gabon: study protocol of the freeBILy clinical trial in Gabon
Authors: Honkpehedji Yabo Josiane , Adegnika Ayôla Akim , Dejon-Agobe Jean Claude , Zinsou Jeannot Fréjus , Mba Romuald Beh , Gerstenberg Jacob , Rakotozandrindrainy Raphaël , Rakotoarivelo Rivo Andry , Rasamoelina Tahinamandranto , Sicuri Elisa , Schwarz Norbert G. , Corstjens Paul L. A. M. , Hoekstra Pytsje T. , van Dam Govert J. , Kreidenweiss Andrea ,   on behalf of the freeBILy Consortium, van Dam G. J. , Corstjens P. L. A. M. , Amoah A. S. , de Dood C. J. , Keshinro M. I. , Hoekstra P. T. , Kreidenweiss A. , Schwarz N. G. , Fusco D. , Klein P. , Jaeger A. , Lorenz E. , Adegnika A. A. , Honkpehedji Y. J. , Dejon-Agobe J. C. , Mba R. Beh , Ngwese M. Mbong , Maloum M. Nzamba , Moure A. Nguema , Meulah B. T. , Rakotozandrindrainy R. , Rakotozandrindrainy N. , Solonirina M. J. , Randriamaniara J. , Rakotoarivelo R. A. , Ralaizandry A. , Radomanana M. , Andrianarivelo M. Rakoto , Rasamoelina T. , Razafindrakoto R. , Siciru E. , Aerts C. 
Published: September 2020

Abstract
Background
Schistosoma antigen detection in urine is a valuable diagnostic approach for schistosomiasis control programmes because of the higher sensitivity compared to parasitological methods and preferred sampling of urine over stool. Highly accurate diagnostics are important in low Schistosoma transmission areas. Pregnant women and young children could particularly benefit from antigen testing as praziquantel (PZQ) can be given to only confirmed Schistosoma cases. This prevents the unborn baby from unnecessary exposure to PZQ. We present here the protocol of a diagnostic study that forms part of the freeBILy project. The aim is to evaluate the accuracy of circulating anodic antigen (CAA) detection for diagnosis of Schistosoma haematobium infections in pregnant women and to validate CAA as an endpoint measure for anti-Schistosoma drug efficacy. The study will also investigate Schistosoma infections in infants.

Methods
A set of three interlinked prospective, observational studies is conducted in Gabon. The upconverting phosphor lateral flow (UCP-LF) CAA test is the index diagnostic test that will be evaluated. The core trial, sub-study A, comprehensively evaluates the accuracy of the UCP-LF CAA urine test against a set of other Schistosoma diagnostics in a cross-sectional trial design. Women positive for S. haematobium will proceed with sub-study B and will be randomised to receive PZQ treatment immediately or after delivery followed by weekly sample collection. This approach includes comparative monitoring of CAA levels following PZQ intake and will also contribute further data for safety of PZQ administration during pregnancy. Sub-study C is a longitudinal study to determine the incidence of S. haematobium infection as well as the age for first infection in life-time.

Discussion
The freeBILy trial in Gabon will generate a comprehensive set of data on the accuracy of the UCP-LF CAA test for the detection of S. haematobium infection in pregnant women and newborn babies and for the use of CAA as a marker to determine PZQ efficacy. Furthermore, incidence of Schistosoma infection in infants will be reported. Using the ultrasensitive diagnostics, this information will be highly relevant for Schistosoma prevalence monitoring by national control programs as well as for the development of medicaments and vaccines.

Trial registration
The registration number of this study is NCT03779347 (clinicaltrials.gov, date of registration: 19 December 2018).