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The diagnosis of schistosomiasis currently relies on microscopic detection of schistosome eggs in stool or urine samples and serological assays. The poor sensitivity of standard microscopic procedures performed in routine laboratories, makes molecular detection methods of increasing interest. The aim of the study was to evaluate two in-house real-time Schistosoma PCRs, targeting respectively S. mansoni [Sm] and S. haematobium [Sh] in excreta, biopsies and sera as potential tools to diagnose active infections and to monitor treatment efficacy. Schistosoma PCRs were performed on 412 samples (124 urine, 86 stools, 8 biopsies, 194 sera) from patients with suspected schistosomiasis, before anti-parasitic treatment. Results were compared to microscopic examination and serological assays (enzyme-linked immunosorbent assay (ELISA), indirect haemagglutination (HA) and Western Blot (WB) assay). Compared to microscopy, PCRs significantly increased the sensitivity of diagnosis, from 4% to 10.5% and from 33.7% to 48.8%, for Sh in urine and Sm in stools, respectively. The overall sensitivity of PCR on serum samples was 72.7% and reached 94.1% in patients with positive excreta (microscopy). The specificity of serum PCR was 98.9%. After treatment, serum PCR positivity rates slowly declined from 93.8% at day 30 to 8.3% at day 360, whereas antibody detection remained positive after 1 year. Schistosoma PCRs clearly outperform standard microscopy on stools and urine and could be part of reference methods combined with WB-based serology, which remains a gold standard for initial diagnosis. When serological assays are positive and microscopy is negative, serum PCRs provide species information to guide further clinical exploration. Biomarkers such as DNA and antibodies are of limited relevance for early treatment monitoring but serum PCR could be useful when performed at least 1 year after treatment to help confirm a cured infection.

Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas 1 . Novel medicines and vaccines are urgently needed 2 , 3 . An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324 ), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3–10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4 + T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis. A new human challenge model of schistosomiasis, which affects more than 290 million people globally, will aid development of novel therapies and vaccines for this neglected tropical disease.

Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This 'gold standard' has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings. In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive. Six Kato-Katzs (two/stool from three stools) and/or one POC-CCA are required for M&E or drug-efficacy studies. Although unable to measure egg reduction rates, one POC-CCA appears to be more sensitive than six Kato-Katzs at four-weeks-post-praziquantel (drug efficacy) and six-months-post-praziquantel (M&E).

MicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. Here, we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infection. We used Exiqon miRNA microarrays to profile miRNA expression in the livers of mice infected with S. mansoni at 7 weeks post-infection. Thirty-three mouse miRNAs were differentially expressed in infected compared to naïve mice (>2 fold change, p<0.05) including miR-199a-3p, miR-199a-5p, miR-214 and miR-21, which have previously been associated with liver fibrosis in other settings. Five of the mouse miRNAs were also significantly elevated in serum by twelve weeks post-infection. Sequencing of small RNAs from serum confirmed the presence of these miRNAs and further revealed eleven parasite-derived miRNAs that were detectable by eight weeks post infection. Analysis of host and parasite miRNA abundance by qRT-PCR was extended to serum of patients from low and high infection sites in Zimbabwe and Uganda. The host-derived miRNAs failed to distinguish uninfected from infected individuals. However, analysis of three of the parasite-derived miRNAs (miR-277, miR-3479-3p and bantam) could detect infected individuals from low and high infection intensity sites with specificity/sensitivity values of 89%/80% and 80%/90%, respectively. This work identifies parasite-derived miRNAs as novel markers of S. mansoni infection in both mice and humans, with the potential to be used with existing techniques to improve S. mansoni diagnosis. In contrast, although host miRNAs are differentially expressed in the liver during infection their abundance levels in serum are variable in human patients and may be useful in cases of extreme pathology but likely hold limited value for detecting prevalence of infection.

Schistosoma mansoni infection is associated with hepatic inflammation and fibrosis, but its systemic metabolic effects remain poorly understood. This study aimed to investigate changes in the serum lipidomic profile associated with S. mansoni infection and parasite load in individuals from an endemic area. This cross-sectional analysis was nested within a longitudinal cohort study conducted in northeastern Brazil. Parasitological diagnosis and quantification were performed using the Kato–Katz technique. A total of 45 individuals were selected and divided into three groups: high parasite load (HL), low parasite load (LL), and uninfected controls (NegE). Serum samples were analyzed using mass-spectrometry-based lipidomics. The most abundant lipid subclasses across all groups were phosphatidylcholines (PC), triacylglycerols (TAG), and phosphatidylethanolamines (PE). However, individuals in the HL group exhibited distinct lipidomic profiles, with increased levels of specific phosphatidylinositols (PI) and reduced levels of certain TAG species compared to the NegE group. These changes may reflect host–parasite interactions and immune–metabolic alterations driven by intense infection. Our findings suggest that S. mansoni infection, particularly at higher parasite burdens, can influence the host’s serum lipid profile and may contribute to metabolic disturbances in endemic populations.

Metabolism of praziquantel (PZQ), a racemic mixture and the only drug approved to treat S. mansoni infection, is mediated by genetically polymorphic enzymes. Periodic school-based mass drug administration (MDA) with PZQ is the core intervention to control schistosomiasis. However data on the impact of pharmacogenetic variation, nutrition, and infection status on plasma PZQ exposure is scarce. We investigated genetic and non-genetic factors influencing PZQ plasma concentration and its metabolic ratios ( trans -4-OH-PZQ/PZQ and cis -4-OH-PZQ/PZQ). Four hundred forty-six school children aged 7–15 years from four primary schools in southern Ethiopia who received albendazole and PZQ preventive chemotherapy through MDA campaign were enrolled. Genotyping for common functional variants of CYP3A4 ( *1B ) , CYP3A5 ( *3, *6 ) , CYP2C19 ( *2, *3, *17 ) , CYP2C9 ( *2, *3 ), and CYP2J2*7 was performed. Plasma concentrations of PZQ, trans -4-OH-PZQ, and cis -4-OH-PZQ were quantified using UPLCMS/MS. Carriers of CYP2C19 defective variant alleles ( *2 and *3 ) had significantly higher mean PZQ plasma concentration than CYP2C19*1/*1 or *17 carriers (p = 0.005). CYP2C19*1/*1 and CYP2C19*17 carriers had higher trans -4-OH-PZQ/PZQ and cis -4-OH-PZQ/PZQ metabolic ratios compared with CYP2C19*2 or *3 carriers (p < 0.001). CYP2J2*7 carriers had lower mean PZQ plasma concentration (p = 0.05) and higher trans -4-OH-PZQ/PZQ and cis -4-OH-PZQ/PZQ metabolic ratios. Male participants had significantly higher PZQ concentration (p = 0.006) and lower metabolic ratios (p = 0.001) than females. There was no significant effect of stunting, wasting, S. mansoni or soil-transmitted helminth infections, CYP3A4 , CYP3A5 , or CYP2C9 genotypes on plasma PZQ or its metabolic ratios. In conclusion, sex, CYP2C19 and CYP2J2 genotypes significantly predict PZQ plasma exposure among Ethiopian children. The impact of CYP2C19 and CYP2J2 genotypes on praziquantel treatment outcomes requires further investigation.

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.

BackgroundCurrently available schistosomiasis diagnostic and monitoring tools are limited, and the development of novel technologies is necessary to enhance disease diagnostic and surveillance by supporting elimination efforts. Novel disease-specific biomarkers can facilitate the development of these technologies. Through the comparison of parasite burden and host factors, we assessed whether host plasma cytokines could be used as robust biomarkers for intestinal schistosomiasis and associated pathology in school-aged children (SAC) living in endemic areas.MethodsLevels of host plasma cytokines were measured in SAC from a low-to-moderate burden region five months deworming with praziquantel, using Luminex assay for exploration analysis and ELISA for validation.ResultsThe concentration of GM-CSF, IL-2, and VEGF in plasma was significantly lower in schistosome-infected compared to non-infected children, as determined by Luminex assay. Further evaluation by ELISA revealed a negative correlation between GM-CSF plasma levels, but not those of IL-2 or VEGF, and S. mansoni egg burdens in infected individuals. Common coinfections in the study area such as geohelminths, hepatitis or malaria failed to alter plasma GM-CSF levels arguing in favor of a potential specific effect of S. mansoni infection on this cytokine. Receiver operating characteristic analysis confirmed GM-CSF as an acceptable predictive marker of S. mansoni infection, with an area under the curve (AUC) of 75%. Finally, the adjunct use of plasmatic GM-CSF thresholds for screening S. mansoni at-risk children and identify S. mansoni -infected ones increased the sensitivity of a single Kato-Katz test by averagely 15%.ConclusionsOur findings highlight the potential of using plasma GM-CSF levels to biomark S. mansoni infection and improve the sensitivity of single Kato-Katz based diagnostic for low- to-moderate burden infections.

Background Schistosomiasis is a parasitic disease that causes coagulation disorders and biochemical abnormalities. This is due to liver failure, platelet destruction, disruption of blood flow, and endothelial function by the schistosomes. However, there is no adequate data on biochemical and coagulation profiles and platelet count of patients infected with Schistosoma mansoni in Dembiya Selected Health Institutions. Hence, the aim of this study was to assess the effect of Schistosoma mansoni infection on selected biochemical and coagulation profiles and platelet count. Method An institutional-based comparative cross-sectional study was conducted from March to August 2022 at Dembiya Primary Hospital, Chuahit Health Center, and Abrija Health Center, Northwest Ethiopia. A total of 70 individuals were enrolled in the study using convenient sampling techniques. A stool sample was collected for Schistosoma mansoni detection. Likewise, a blood sample was collected for biochemical and coagulation profiles and platelet count analysis. The data were analyzed using SPSS version 25. A p-value less than 0.05 was considered statistically significant. Results Median values for alanine aminotransferase, aspartate aminotransferase, creatinine, total bilirubin, and direct bilirubin values were significantly higher, while total protein and glucose were significantly lower in Schistosoma mansoni infected than in the healthy control participants ( P  < 0.05). Prothrombin time, activated partial thromboplastin time, and international normalization ratio were significantly higher, while the platelet count was significantly lower in the Schistosoma mansoni infected than healthy control participants ( P  < 0.05). The values of alanine aminotransferase, aspartate aminotransferase, creatinine, total bilirubin, direct bilirubin, prothrombin time, activated partial thromboplastin time, and international normalization ratio were significantly higher, while total protein, glucose, and platelet count were significantly lower in those with moderate and heavy Schistosoma mansoni infection intensity compared to healthy control participants ( P  < 0.05). The number of Schistosoma mansoni eggs per gram of stool had a positive correlation with biochemical and coagulation profiles, except for total protein, glucose, and platelet count, which were correlated negatively in Schistosoma mansoni infected participants ( P  < 0.05). Conclusion Biochemical and coagulation profiles, including alanine aminotransferase, aspartate aminotransferase, creatinine, total bilirubin, direct bilirubin, glucose, total protein, prothrombin time, activated partial thromboplastin time, international normalization ratio, and platelet count, were significantly altered in S. mansoni infected participants compared to controls ( p  < 0.05). These findings underscore the need for routine biochemical and coagulation monitoring in endemic areas.

Schistosoma mansoni ( Sm ) infection has been linked with an increased risk of HIV acquisition in women. Therefore, defining the mechanism(s) by which Sm alters HIV susceptibility might lead to new HIV prevention strategies. Here, we analyze the impact of standard Sm therapy in HIV-uninfected Sm + Ugandan adult women on genital HIV susceptibility and mucosal and systemic immunology. Schistosomiasis treatment induces a profound reduction of HIV entry into cervical and blood CD4+ T cells that is sustained for up to two months, despite transient systemic and mucosal immune activation and elevated genital IL-1α levels. Genital IFN-α2a levels are also elevated post-treatment, and IFN-α2a blocks HIV entry into primary CD4+ T cells ex vivo. Transcriptomic analysis of blood mononuclear cells post- Sm treatment shows IFN-I pathway up-regulation and partial reversal of Sm- dysregulated interferon signaling. These findings indicate that Sm therapy may reduce HIV susceptibility for women with Sm infection, potentially through de-repression of IFN-I pathways. Schistosoma mansoni infection has been linked with an increased risk of HIV acquisition in women. Here, the authors show that standard S. mansoni infection treatment causes a reduction of HIV entry into cervical and blood CD4+ T cells, which is sustained for up to two months and is associated with de-repression of IFN-I signaling.