Donald P. Mcmanus

Background: Opisthorchis viverrini (OV) and soil-transmitted helminths (STH) are two of the most common helminths contributing to the Neglected Tropical Disease (NTDs) burden in the Lower Mekong Basin. Although mass drug administration is the cornerstone of control programs to reduce morbidity caused by these infections, this approach has limitations in preventing re-infections. Elimination requires additional measures such as reservoir host treatment, improved hygiene and health education to reinforce MDA's impact. This study aims to examine the impact of a scalable multi-component One Health Helminth Elimination program in the Lower Mekong Basin (HELM) that combines human praziquantel (PZQ) and albendazole (ALB) treatment with a program that includes the "Magic Glasses" and the "Lawa Model" interventions with health promotion at their core. Methods: This study will employ a cluster randomized controlled trial (cRCT) in 18 rural communities (with sub-district or villages as cluster units) across Cambodia, Laos and Thailand. The control arm will receive one round of PZQ/ALB treatment, while in the intervention arm, multi-component HELM program will be implemented, which includes PZQ/ALB treatment together with the Magic Glasses and Lawa Model interventions. OV and STH infections levels will be evaluated in individuals aged 5-75 years at baseline and will be repeated at follow-up (12 months after the HELM intervention), using modified formalin ethyl-acetate concentration technique and quantitative PCR. The primary outcome of the study will be cumulative incidence of human OV and STH infections. Outcomes between the study arms will be compared using generalized linear mixed models, accounting for clustering. Conclusions: Evidence from this trial will quantify the impact of a multi-component One Health control strategy in interrupting Ov and STH infections in the Lower Mekong Basin. Background: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000353796. Prospectively registered 28 February 2022.

Herein, we explore the potential influence of Schistosoma mansoni Sambon, 1907 soluble egg antigen (SmSEA) on the immunopathology of COVID-19 in K18-hACE2 mice infected with an Omicron BA.5 isolate of SARS-CoV-2. SmSEA treatment was delivered in a single dose by intraperitoneal injection, shortly after intrapulmonary inoculation of SARS-CoV-2. RNA-seq identified 36 differentially expressed genes in the spleens of virus-infected mice treated with SmSEA vs. PBS on day 5 post infection. Ingenuity Pathway Analysis of these genes suggested marginal modulation of cytokine responses, with upregulation of the IL-10 and IL-4 signatures and downregulation of the IFNγ signature. However, cytokine responses and histopathology in the lungs were largely unaffected. Future work will require purification of active helminth compounds and dosing and scheduling optimisation.

Over 1 billion people globally are infected with helminths, and understanding the impact of these infections on human health is crucial for further developing effective interventions. We investigated potential associations between helminth infection status and the abundance of fecal bile acids: a group of metabolites known to impact gut physiology and function and have immunomodulatory capabilities. Fecal samples were collected from school-age children in Uganda and used to determine helminth infection status (Kato-Katz technique) and to quantify the fecal bile acid pool (UPLC-MRM/MS). We found that helminth infection status was associated with changes to the fecal bile acid pool and that these differences were dependent on the biological sex of study participants. Females who were coinfected with schistosomes and hookworms had higher levels of unconjugated secondary bile acids than helminth-negative individuals. In males, no significant associations were detected between helminth infection status and levels of unconjugated secondary bile acids, however, there were reduced levels of some species of conjugated primary bile acids in schistosome-infected individuals compared to helminth-negative individuals. Further research into the specific mechanisms underlying these associations and the functional consequences of bile acid perturbations during helminth infection may provide valuable insights into the pathophysiology of helminth infections.

Background: Zoonotic schistosomiasis, caused by Schistosoma japonicum, is prevalent in China, the Philippines and Indonesia. Rapid point-of-care (POC) diagnostics are attractive and promising tools for evaluating the efficacy of intervention strategies for schistosomiasis control. Methods: The diagnostic potential of five recombinant antigens was tested by enzyme-linked immunosorbent assay (ELISA) using sera from individuals with positive Kato-Katz (KK) results for S. japonicum (n = 28) and non-endemic controls (n = 12). A latex microsphere (LM)-based lateral flow immunoassay (LFIA) incorporating the recombinant SjSAP4 (rSjSAP4) was developed for the diagnosis of schistosomiasis japonica. The test conditions including diluent, dilution factor and reaction time, were optimised for the developed LFIA. Under the optimised conditions, serum samples from individuals living in a barangay endemic for S. japonicum (n = 549) and non-endemic controls (n = 50) were tested with the established LFIA cassettes. The results were imaged by a smartphone and analysed by the ImageJ program. The intensity ratio of the test line to the control line (T/C ratio) was calculated for each cassette. Results: ELISA confirmed that rSjSAP4 was the optimal candidate for serological diagnosis of schistosomiasis japonica. Under optimal testing conditions, the developed LFIA strips had a sensitivity of 80.6% and a specificity of 98.0% at a cut-off T/C ratio of 0.1031. Moreover, the results of the LM-based LFIA was positively correlated with those obtained from the rSjSAP4-ELISA (r = 0.8270, 95% CI, 0.7990-0.8514; p < 0.0001). The schistosomiasis prevalence determined by the LFIA strips was about 1.8 times greater than that obtained with the 6-slide KK procedure performed on three stool samples. Conclusions: The developed LFIA represents a POC diagnostic tool that is suitable for onsite screening of human S. japonicum infection with minimal equipment needed. The established immunochromatographic assay complies with most of the WHO's ASSURED criteria for POC diagnostics.

MicroRNAs (miRNAs) are a class of small regulatory RNA that are generated via core protein machinery. The miRNAs direct gene-silencing mechanisms to mediate an essential role in gene expression regulation. In mollusks, miRNAs have been demonstrated to be required to regulate gene expression in various biological processes, including normal development, immune responses, reproduction, and stress adaptation. In this study, we aimed to establishment the requirement of the miRNA pathway as part of the molecular response of exposure of Biomphalaria glabrata (snail host) to Schistosoma mansoni (trematode parasite). Initially, the core pieces of miRNA pathway protein machinery, i.e., Drosha, DGCR8, Exportin-5, Ran, and Dicer, together with the central RNA-induced silencing complex (RISC) effector protein Argonaute2 (Ago2) were elucidated from the B. glabrata genome. Following exposure of B. glabrata to S. mansoni miracidia, we identified significant expression up-regulation of all identified pieces of miRNA pathway protein machinery, except for Exportin-5, at 16 h post exposure. For Ago2, we went on to show that the Bgl-Ago2 protein was localized to regions surrounding the sporocysts in the digestive gland of infected snails 20 days post parasite exposure. In addition to documenting elevated miRNA pathway protein machinery expression at the early post-exposure time point, a total of 13 known B. glabrata miRNAs were significantly differentially expressed. Of these thirteen B. glabrata miRNAs responsive to S. mansoni miracidia exposure, five were significantly reduced in their abundance, and correspondingly, these five miRNAs were determined to putatively target six genes with significantly elevated expression and that have been previously associated with immune responses in other animal species, including humans. In conclusion, this study demonstrates the central importance of a functional miRNA pathway in snails, which potentially forms a critical component of the immune response of snails to parasite exposure. Further, the data reported in this study provide additional evidence of the complexity of the molecular response of B. glabrata to S. mansoni infection: a molecular response that could be targeted in the future to overcome parasite infection and, in turn, human schistosomiasis.