Comparative evaluation of plasma biomarkers of Schistosoma haematobium infection in endemic populations from Burkina Faso

Infection with Schistosoma haematobium causes urogenital disease associated with organ disfunction, bleeding, pain, and higher susceptibility to infections and cancer. Timely and accurate diagnosis is crucial for prompt and appropriate treatment as well as surveillance efforts, and the use of plasma biomarkers offers important advantages over parasitological examination of urine, including increased sensitivity and the possibility to use the same specimen for multiple investigations. The present study aims to evaluate the diagnostic performance of different plasma biomarkers in endemic populations from Burkina Faso, West Africa. Schistosoma spp. Circulating Anodic Antigen (CAA), cell free S. haematobium DNA (cfDNA), class M and G antibodies against S. haematobium Soluble Worm Antigen Preparation (SWAP) and Soluble Egg Antigen (SEA) were measured in 406 plasma samples. Results of each biomarker test were compared to those of CAA, a Composite Reference Standard (CRS) and Latent Class Analysis (LCA). An identical proportion of positive samples (29%) was observed as a result of CAA and cfDNA testing, with a substantial agreement (84%, Cohen k=0.62) between the results of the two tests, and a comparable agreement with the results of CRS and LCA. A higher positivity was observed, as expected, as a result of specific antibody testing (47%-72%), with IgG showing a higher agreement than IgM with the three references. Also, higher IgG levels were observed in current vs past infection, and ROC analysis identified optimal cutoff values for improved testing accuracy. This study provides compelling evidence that can inform the choice of the most appropriate diagnostic plasma biomarker for urogenital schistosomiasis in endemic areas, depending on the purpose, context, and available resources for testing. Either CAA or cfDNA testing can be used for the diagnosis of patients and for epidemiological investigations, even in absence of urine filtration microscopy, whereas anti-SWAP or anti-SEA IgG can be employed for surveillance and integrated monitoring of control interventions against poverty-associated diseases. Author summaryUrogenital schistosomiasis is a chronic debilitating disease affecting populations living in Africa and the Middle East and showing a strong association with poverty. Accurate detection of infection is important both for disease treatment and surveillance. Several tests based on detection in plasma of parasite protein (CAA), parasite DNA or parasite-specific host antibodies (IgM and IgG against SWAP and SEA antigens) are available and this study aims at comparing them to evaluate their accuracy. The comparison showed that tests based on parasite CAA or DNA yield very similar results and therefore the test of choice for diagnosis or epidemiological investigations can be based on laboratory resources. Additionally, the comparison showed that IgG against SWAP and SEA outperform IgM, and that high accuracy can be achieved by identifying an optimal level to determine positivity (cut-off), making these antibody tests ideal for surveillance purposes.