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
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
Background: An accurate test for the diagnosis and post-treatment follow-up of patients with schistosomiasis is needed. We assessed the performance of different laboratory parameters, including the... Show moreBackground: An accurate test for the diagnosis and post-treatment follow-up of patients with schistosomiasis is needed. We assessed the performance of different laboratory parameters, including the up-converting reporter particle technology lateral flow assay to detect circulating anodic antigen (UCP-LF CAA), for the post-treatment follow-up of schistosomiasis in migrants attending a dedicated outpatient clinic in a non-endemic country.Methods: Routine anti-Schistosoma serology results and eosinophil counts were obtained of patients with positive urine/stool microscopy and/or PCR (confirmed cases) or only positive serology (possible cases), and at least one follow-up visit at 6 (T6) or 12 (T12) months after praziquantel treatment. All sera samples were tested with the UCP-LF CAA assay.Results: Forty-eight patients were included, 23 confirmed and 25 possible cases. The percentage seropositivity and median antibody titers did not change significantly during follow-up. UCP-LF CAA was positive in 86.9% of confirmed and 20% of possible cases. The percentage positivity and median CAA levels decreased significantly post-treatment, with only two patients having positive CAA levels at T12.Conclusions: The UCP-LF CAA assay proved useful for the diagnosis of active infection with Schistosoma spp. and highly valuable for post-treatment monitoring in migrants, encouraging the development of a commercial test. Show less
Schistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV... Show moreSchistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV acquisition and have not been studied in schistosome infection. We collected cervical swabs from Tanzanian women with and without S. mansoni and S. haematobium to determine effects on cervicovaginal microbiota. Infected women were treated, and follow-up swabs were collected after 3 months. 16S rRNA sequencing was performed on DNA extracted from swabs. We compared 39 women with S. mansoni with 52 uninfected controls, and 16 with S. haematobium with 27 controls. S. mansoni-infected women had increased abundance of Peptostreptococcus (p = 0.026) and presence of Prevotella timonesis (p = 0.048) compared to controls. High-intensity S. haematobium infection was associated with more diverse cervicovaginal bacterial communities than uninfected controls (p = 0.0159). High-intensity S. mansoni infection showed a similar trend (p = 0.154). At follow-up, we observed increased alpha diversity in S. mansoni (2.53 vs. 1.72, p = 0.022) and S. haematobium (2.05 vs. 1.12, p = 0.066) infection groups compared to controls. Modifications in cervicovaginal microbiota, particularly increased diversity and abundance of taxa associated with bacterial vaginosis and HIV (Peptostreptococcus, Prevotella), were associated with schistosome infection. Show less
Casacuberta Partal, M.; Janse, J.J.; Schuijlenburg, R. van; Vries, J.J.C. de; Erkens, M.A.A.; Suijk, K.; ... ; Roestenberg, M. 2020
Background: Travellers infected with Schistosoma spp. might be pauci- or even asymptomatic on first presentation. Therefore, schistosomiasis may remain undiagnosed in this population. Active... Show moreBackground: Travellers infected with Schistosoma spp. might be pauci- or even asymptomatic on first presentation. Therefore, schistosomiasis may remain undiagnosed in this population. Active infection, as evidenced by the presence of the tissue-dwelling worm, can be demonstrated via the detection of adult worm-derived circulating anodic antigen (CAA) utilising a robust well-described lateral flow-(LF) based test applying background-free up-converting reporter particles (UCP). In this prospective study, we assessed the diagnostic value of serum and urine UCP-LF CAA test in comparison with two Schistosoma-specific serological assays detecting antibodies against adult worm antigen-immuno fluorescence assay (AWA-IFA) and against soluble egg antigen-enzyme-linked immunosorbent assay (SEA-ELISA) antigens in travellers.Methods: Samples were collected from 106 Dutch travellers who reported freshwater contact in sub-Saharan Africa and who were recruited up to 2 years after return. Subjects were asked to complete a detailed questionnaire on travel history, water contact, signs and symptoms compatible with schistosomiasis.Results: Two travellers were positive by serum CAA and an additional one by urine CAA. A total of 22/106 (21%) samples were antibody positive by AWA-IFA and 9/106 (9%) by SEA-ELISA. At follow-up 6 weeks and 6 months after praziquantel treatment, all seropositives remained antibody positive whereas CAA was cleared. Seropositivity could not be predicted by the type of fresh water-related activity, country visited or symptoms reported.Conclusion: The low number of UCP-LF CAA positives suggests that in travellers, active infections often do not establish or have very low worm burden. Based on our high seroconversion rates, we conclude that the AWA-IFA assay is the most sensitive test to detect schistosome exposure. Given the lack of predictive symptoms or risk factors, we recommend schistosomiasis screening at least by serology in all travellers with reported freshwater contact in high-endemic areas. Show less
Hoekstra, P.T.; Partal, M.C.; Amoah, A.S.; Lieshout, L. van; Corstjens, P.L.A.M.; Tsonaka, S.; ... ; Dam, G.J. van 2018
BackgroundLarge scale administration of the anthelminthic drug praziquantel (PZQ) to at-risk populations is the cornerstone of schistosomiasis control, although persisting high prevalence of... Show moreBackgroundLarge scale administration of the anthelminthic drug praziquantel (PZQ) to at-risk populations is the cornerstone of schistosomiasis control, although persisting high prevalence of infections in some areas and growing concerns of PZQ resistance have revealed the limitations of this strategy. Most studies assessing PZQ efficacy have used relatively insensitive parasitological diagnostics, such as the Kato-Katz (KK) and urine-filtration methods, thereby overestimating cure rates (CRs). This study aims to determine the efficacy of repeated PZQ treatments against Schistosoma mansoni infection in school-aged children in Cote d'Ivoire using the traditional KK technique, as well as more sensitive antigen- and DNA-detection methods.MethodsAn open-label, randomised controlled trial will be conducted in school-aged children (5 to 18years) from the region of Taabo, Cote d'Ivoire, an area endemic for S. mansoni. This 8-week trial includes four two-weekly standard doses of PZQ in the intense treatment intervention group and one standard dose of PZQ in the standard treatment control group. The efficacy of PZQ will be evaluated in stool samples using the KK technique and real-time PCR as well as in urine using the point-of-care circulating cathodic antigen test and the up-converting phosphor, lateral flow, circulating anodic antigen assay. The primary outcome of the study will be the difference in CR of intense versus standard treatment with PZQ on individuals with a confirmed S. mansoni infection measured by KK. Secondary outcomes include the difference in CR and intensity reduction rate between the intense and standard treatment groups as measured by the other diagnostic tests, as well as the accuracy of the different diagnostic tests, and the safety of PZQ.DiscussionThis study will provide data on the efficacy of repeated PZQ treatment on the clearance of S. mansoni as measured by several diagnostic techniques. These findings will inform future mass drug administration policy and shed light on position of novel diagnostic tools to evaluate schistosomiasis control strategies.Trial registrationThe study is registered at EudraCT (2016-003017-10, date of registration: 22 July 2016) and (NCT02868385, date of registration: 16 August 2016). Show less
Hoekstra, P.T.; Partal, M.C.; Amoah, A.S.; Lieshout, L. van; Corstjens, P.L.A.M.; Tsonaka, S.; ... ; Dam, G.J. van 2018
Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most... Show moreSchistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. In this tehsis we adressed the spatial and temporal expression of glycans expressed during the critical larval stages of schistosome development and we studied the (protective) antibody responses against these glycans in animals and infected human populations. Together these studies thereby contribute to an important basis for the understanding of the anti-glycan antibody responses towards Schistosoma in general and towards the vulnerable schistosomulum in particular. Show less
Downs, J.A.; Corstjens, P.L.A.M.; Mngara, J.; Lutonja, P.; Isingo, R.; Urassa, M.; ... ; Dam, G.J. van 2015
