Background A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome exposure. Recently,... Show moreBackground A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome exposure. Recently, we established CHI-S model using single-sex male-only Schistosoma mansoni (Sm) cercariae in Schistosoma-naive individuals. Given important differences in antigenic profile and human immune responses to schistosomes of different sex, we pioneered a single-sex female-only CHI-S model for future use in vaccine development.Methods We exposed 13 healthy, Schistosoma-naive adult participants to 10 (n = 3) or 20 (n = 10) female cercariae and followed for 20 weeks, receiving treatment with praziquantel (PZQ) 60 mg/kg at week 8 and 12 after exposure.Findings The majority (11/13) participants reported rash and/or itch at the site of exposure, 5/13 had transient symptoms of acute schistosomiasis. Exposure to 20 cercariae led to detectable infection, defined as serum circulating anodic antigen levels >1.0 pg/mL, in 6/10 participants. Despite two rounds of PZQ treatment, 4/13 participants showed signs of persistent infection. Additional one-or three-day PZQ treatment (1 x 60 mg/kg and 3 x 60 mg/kg) or artemether did not result in cure, but over time three participants self-cured. Antibody, cellular, and cytokine responses peaked at week 4 post infection, with a mixed Th1, Th2, and regulatory profile. Cellular responses were (most) discriminative for symptoms.Interpretation Female-only infections exhibit similar clinical and immunological profiles as male-only infections but are more resistant to PZQ treatment. This limits future use of this model and may have important implications for disease control programs. Show less
Availability of accurate tests to diagnose schistosomiasis, a neglected tropical disease caused by parasitic worms, is crucial for successful reduction of the burden of disease and eventually... Show moreAvailability of accurate tests to diagnose schistosomiasis, a neglected tropical disease caused by parasitic worms, is crucial for successful reduction of the burden of disease and eventually moving towards elimination. This thesis provides further evidence on the suitability of CAA detection for diagnosing Schistosoma infections and monitoring treatment efficacy by evaluating the UCP-LF CAA test in the context of various endemic and non-endemic settings. The UCP-LF CAA test is a lateral flow (LF) test for sensitive quantitative detection – using luminescent up-converting reporter particles (UCP) – of circulating anodic antigen (CAA). This antigen is regurgitated by live schistosome worms into the human circulation. The presence of CAA in blood or urine thus reflects an active Schistosoma infection. CAA-levels decrease rapidly after treatment of infected patients with anti-schistosomal drugs. In non-endemic settings (i.e. the absence of reinfection), CAA-levels became undetectable after treatment, indicating clearance of infection. This is in contrast to endemic settings of continuous exposure and ongoing transmission. Here, CAA-levels significantly decreased post-treatment but often remained detectable. Although alternative procedures such as antibody and DNA detection methods remain crucial for certain context-specific purposes, this thesis shows that CAA is the most favorable diagnostic marker currently available for diagnosis of active Schistosoma infections. Show less
Background:The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circu... Show moreBackground:The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment.Methods:Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels.Results:CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods.Conclusions:S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment. Show less
