Fast and reliable easy-to-use diagnostics for eliminating bilharzia in young children and mothers: An introduction to the freeBILy project

Hoekstra, Pytsje T.; Schwarz, Norbert; Adegnika, Ayôla Akim; Andrianarivelo, Mala Rakoto; Corstjens, Paul L. A. M.; Rakotoarivelo, R.; Rakotozandrindrainy, Raphäel; Kreidenweiss, Andrea; Dam, Govert J. van

doi:10.1016/j.actatropica.2020.105631

Cited by 11 publications

(10 citation statements)

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“…Although praziquantel therapy of schistosomiasis during pregnancy is recommended by the World Health Organization (WHO) [46], nationwide screening and screening-based therapy for pregnant women is so far not established in resource-poor Madagascar. At present, investigations on the suitability of test-and-treat strategies for the reduction of the burden of schistosomiasis in pregnant Madagascan women are underway [47].…”

Section: Discussionmentioning

confidence: 99%

“…PCRs were run on RotorGene Q (Qiagen, Hilden, Germany) or MIC (Bio Molecular Systems, Upper Coomera, Australia) cyclers as previously described [31,33,34,48]. The Sm1-7 assay and the Dra1 assay were run in a one-tube duplex approach as detailed elsewhere [47]. Internal control was based upon the amplification of Phocid herpes virus DNA [51].…”

Section: Pcr Protocolsmentioning

confidence: 99%

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Serology- and Blood-PCR-Based Screening for Schistosomiasis in Pregnant Women in Madagascar—A Cross-Sectional Study and Test Comparison Approach

et al. 2021

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This work was conducted as a cross sectional study to define the disease burden of schistosomiasis in pregnant Madagascan women and to evaluate serological and molecular diagnostic assays. A total of 1154 residual EDTA blood samples from pregnant Madagascan women were assessed. The nucleic acid extractions were subjected to in-house real-time PCRs specifically targeting S. mansoni complex, S. haematobium complex, and African Schistosoma spp. on genus level, while the EDTA plasma samples were analyzed using Schistosoma-specific IgG and IgM commercial ELISA and immunofluorescence assays. The analyses indicated an overall prevalence of schistosomiasis in Madagascan pregnant women of 40.4%, with only minor regional differences and differences between serology- and blood PCR-based surveillance. The S. mansoni specific real-time PCR showed superior sensitivity of 74% (specificity 80%) compared with the genus-specific real-time PCR (sensitivity 13%, specificity 100%) in blood. The laborious immunofluorescence (sensitivity IgM 49%, IgG 87%, specificity IgM 85%, IgG 96%) scored only slightly better than the automatable ELISA (sensitivity IgM 38%, IgG 88%, specificity IgM 78%, IgG 91%). Infections with S. mansoni were detected only. The high prevalence of schistosomiasis recorded here among pregnant women in Madagascar calls for actions in order to reduce the disease burden.

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Section: Discussionmentioning

confidence: 99%

Section: Pcr Protocolsmentioning

confidence: 99%

Serology- and Blood-PCR-Based Screening for Schistosomiasis in Pregnant Women in Madagascar—A Cross-Sectional Study and Test Comparison Approach

et al. 2021

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“…freeBILy was established as an international consortium in 2018 to focus on diagnostic alternatives to inform public health strategies to improve the management of schistosomiasis in high endemic countries (16). The Madagascar freeBILy study is being conducted under the direction of a Trial Steering Committee (TSC), which provides overall supervision for the trial on behalf of the sponsor, BNITM.…”

Section: Trial Governancementioning

confidence: 99%

“…In order to improve the diagnostic strategies for the management of schistosomiasis in vulnerable groups, the international consortium freeBILy (Fast and reliable easy-to-use-diagnostics for eliminating Bilharzia in young children and mothers) was initiated (16). The freeBILy consortium carries out two conceptually different trials, one in Madagascar (Universities of Antananarivo and Fianarantsoa and Centre d'Infectiologie Charles Mérieux) and the other one in Gabon (Centre de Recherches Médicales de Lambaréné) in collaboration with the Bernhard Nocht Institute for Tropical Medicine (BNITM), the Barcelona Institute for Global Health (ISGlobal), the Eberhard Karls Universität of Tübingen and the Leiden University Medical Center.…”

Section: Introductionmentioning

confidence: 99%

A Cluster Randomised Controlled Trial for Assessing POC-CCA Test Based Praziquantel Treatment for Schistosomiasis Control in Pregnant Women and Their Young Children: Study Protocol of the Freebily Clinical Trial in Madagascar

Fusco

Rakotozandrindrainy

Rakotoarivelo

et al. 2021

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Background: Mass drug administration (MDA) of praziquantel is one of the main control measures against human schistosomiasis. Although there are claims for including pregnant women, infants and children under the age of 5 years in high endemic regions in MDA campaigns, they are usually not treated without diagnosis. Diagnostic tools identifying infections at primary health care centre (PHCC) level could therefore help to integrate these vulnerable groups into control programmes. freeBILy (Fast and reliable easy-to-use-diagnostics for eliminating Bilharzia in young children and mothers) is an international consortium focused on implementing and evaluating new schistosomiasis diagnostic strategies. In Madagascar, the study aims to determine the effectiveness of a Test-Based-Schistosomiasis-Treatment (TBST) strategy for pregnant women and their infants and children up until the age of 2 years. Methods : A two-armed, cluster-randomised, controlled phase III trial including 5200 women and their offspring assesses the impact of TBST on child growth and maternal haemoglobin in areas of medium to high endemicity of Schistosoma mansoni . The participants are being tested with the Point of Care-Circulating Cathodic Antigen (POC-CCA) test, a commercially available urine-based non-invasive rapid diagnostic test for schistosomiasis. In the intervention arm, a POC-CCA-TBST strategy is offered to women during pregnancy and 9 months after delivery, for their infants at 9 months of age. In the control arm, study visit procedures are the same, but without the POC-CCA-TBST procedure. All participants are being offered the POC-CCA-TBST at 24 months after delivery. This trial is being integrated into the routine maternal and child primary health care programmes at 40 different PHCC in Madagascar’s highlands. The purpose of the trial is to assess the effectiveness of the POC-CCA-TBST for controlling schistosomiasis in young children and mothers. Discussion : This trial assesses a strategy to integrate pregnant women and their children under the age of 2 years into schistosomiasis control programmes using rapid diagnostic tests. It includes local capacity building for clinical trials and large-scale intervention research. Trial registration : Retrospectively registered with the Pan-African Clinical Trial Register PACTR201905784271304 (15/05/2019)

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“…The overall aim of this study is to evaluate the accuracy of the UCP-LF CAA urine test for the detection of S. haematobium infections in pregnant women and to validate CAA as an endpoint measure for PZQ efficacy. This study is part of the Fast and Reliable Easy-to-Use Diagnostics for Eliminating Bilharzia in Young Children and Mothers (freeBILy) project which aims to thoroughly evaluate the use of CCA and CAA antigen tests for the diagnosis of Schistosoma infections in pregnant women and their newborns [42]. The freeBILy project is complemented by an additional trial performed in Madagascar that investigates a CCA-based test-and-treat strategy integrated into routine maternal and child primary health care programmes.…”

Section: Rationale For the Studymentioning

confidence: 99%

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

et al. 2020

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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).

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Fast and reliable easy-to-use diagnostics for eliminating bilharzia in young children and mothers: An introduction to the freeBILy project

Cited by 11 publications

References 65 publications

Serology- and Blood-PCR-Based Screening for Schistosomiasis in Pregnant Women in Madagascar—A Cross-Sectional Study and Test Comparison Approach

Serology- and Blood-PCR-Based Screening for Schistosomiasis in Pregnant Women in Madagascar—A Cross-Sectional Study and Test Comparison Approach

A Cluster Randomised Controlled Trial for Assessing POC-CCA Test Based Praziquantel Treatment for Schistosomiasis Control in Pregnant Women and Their Young Children: Study Protocol of the Freebily Clinical Trial in Madagascar

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

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