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.

AbstractFood allergy (FA) is considered the ‘second wave’ of the allergy epidemic in developed countries after asthma and allergic rhinitis with a steadily growing burden of 40%. The absence of early childhood pathogen stimulation embodied by the hygiene hypothesis is one explanation, and in particular, the eradication of parasitic helminths could be at play. Infections with parasites Schistosoma spp. have been found to have a negative correlation with allergic diseases. Schistosomes induce regulatory responses to evade immune detection and ensure their long‐term survival. This is achieved via excretory/secretory (E/S) products, consisting of proteins, lipids, metabolites, nucleic acids and extracellular vesicles, representing an untapped therapeutic avenue for the treatment of FA without the unpleasant side‐effects and risks associated with live infection. Schistosome‐derived immunotherapeutic development is in its infancy and novel discoveries are heavily technology dependent; thus, it is essential to better understand how newly identified molecules interact with host immune systems to ensure safety and successful translation. This review will outline the identified Schistosoma‐derived E/S products at all life cycle stages and discuss known mechanisms of action and their ability to suppress FA.

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. 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. 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. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000353796. Prospectively registered 28 February 2022.

BackgroundHelminths are a major global health issue, impacting health, educational, and socioeconomic outcomes. Infections, often starting in childhood, are linked to anemia, malnutrition, cognitive deficit, and in chronic cases of Opisthorchis viverrini (OV), cholangiocarcinoma. The main control strategy for helminth infection is mass drug administration; however, this does not prevent reinfection. As such, prevention strategies are needed. The “Magic Glasses” is a school-based cartoon health education package that has demonstrated success in improving knowledge, attitudes, and practices (KAP) surrounding soil-transmitted helminths (STH) in China and the Philippines. This study is designed to assess the acceptability and impact of the 2 new versions of the Magic Glasses targeting STH and OV designed for the Lower Mekong audience in Cambodia, Lao People’s Democratic Republic (PDR), and Thailand. ObjectiveThe objective of this study is to evaluate the acceptability of the “Magic Glasses Lower Mekong” and “Magic Glasses Opisthorchiasis” education packages among schoolchildren in the Lower Mekong Basin, and the impact of these education packages on students’ KAP surrounding STH and OV, respectively. MethodsSchoolchildren will be recruited into a cluster randomized controlled trial with intervention and control arms in rural schools in Cambodia, Lao PDR, and Thailand. Schoolchildren’s initial acceptability of the intervention will be evaluated using an adapted questionnaire. Sustained acceptability will be assessed at 9-month follow-up through focus group discussions with students and interviews with teachers. Impact will be evaluated by KAP questionnaires on STH and OV. KAP questionnaires will be administered to children at baseline and at follow-up. Indirect impact on parents' KAP of OV and STH will be assessed through focus group discussions at follow-up. ResultsThe trial is in progress in Lao PDR and Thailand and is expected to commence in Cambodia in January 2024. The results of the study are expected to be available 18 months from the start of recruitment. We hypothesize that participants enrolled in the intervention arm of the study will have higher KAP scores for STH and OV, compared with the participants in the control arm at follow-up. We expect that students will have initial and sustained acceptability of these intervention packages. ConclusionsThis trial will examine the acceptability of the “Magic Glasses Opisthorchiasis” and “Magic Glasses Lower Mekong” interventions and provide evidence on the effectiveness of the “Magic Glasses” on KAP related to OV and STH among schoolchildren in the Lower Mekong Basin. Study results will provide insight on acceptability and impact indicators and inform a scaling up protocol for the “Magic Glasses” education packages in Cambodia, Lao PDR, and Thailand. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12623000271606; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385315&isReview=true International Registered Report Identifier (IRRID)DERR1-10.2196/55290

BackgroundZoonotic 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.MethodologyThe 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.Main findingsELISA 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/significanceThe 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.

Background: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. Methods: A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups. Findings: There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE. Conclusions: The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection.

Schistosomiasis is caused by parasitic flatworms (Schistosoma). The disease in humans can be caused by seven different species of Schistosoma: S. mansoni, S. japonicum, S. haematobium, S. malayensis, S. mekongi, S. guineensis and S. intercalatum, as well as by hybrids between species, including livestock schistosome species. People are infected when exposed to infested water and the parasite larvae penetrate the skin. Poor and rural communities are typically the most affected, and the general population who lives in affected areas and is exposed to contaminated water is at risk. Areas with poor access to safe water and adequate sanitation are also at heightened risk. About 236.6 million people required treatment for schistosomiasis in 2019—mostly people living in poor, rural communities, especially fishing and agricultural communities.This ‘Vaccine Value Profile’ (VVP) for schistosomiasis is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic, and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships, and multi-lateral organizations. All contributors have extensive expertise on various elements of the schistosomiasis VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Food allergy (FA) is considered the ‘second wave’ of the allergy epidemic in developed countries after asthma and allergic rhinitis with a steadily growing burden of 40%. The absence of early childhood pathogen stimulation embodied by the hygiene hypothesis is one explanation, and in particular, the eradication of parasitic helminths could be at play. Infections with parasites Schistosoma spp. have been found to have a negative correlation with allergic diseases. Schistosomes induce regulatory responses to evade immune detection and ensure their long-term survival. This is achieved via excretory/secretory (E/S) products, consisting of proteins, lipids, metabolites, nucleic acids and extracellular vesicles, representing an untapped therapeutic avenue for the treatment of FA without the unpleasant side-effects and risks associated with live infection. Schistosome-derived immunotherapeutic development is in its infancy and novel discoveries are heavily technology dependent; thus, it is essential to better understand how newly identified molecules interact with host immune systems to ensure safety and successful translation. This review will outline the identified Schistosoma -derived E/S products at all life cycle stages and discuss known mechanisms of action and their ability to suppress FA.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has resulted in devastating health and economic consequences worldwide. Vaccination has been a central pillar for COVID-19 prevention and control. Understanding the immunomodulatory effects of helminth infections on COVID-19 vaccine-induced immune responses and vaccine efficacy is crucial to the development and deployment of effective vaccination strategies in low- and middle-income countries with a high prevalence of worms.MethodsIn September 2022, we conducted a cross-sectional, population-based survey in five Schistosoma mansoni endemic villages in Mayuge District, Uganda (n = 450). The prevalence of schistosomiasis and soil-transmitted helminths was determined by the Kato-Katz (KK) technique on two stool samples collected from each participant. A subset of individuals (n = 204) were interviewed in a COVID-19 vaccination survey. IgG levels against the SARS-CoV-2 spike S1 subunit (anti-S1 IgG) were measured by enzyme-linked immunosorbent assay (ELISA) in collected serum samples.ResultsThe overall schistosomiasis and hookworm prevalence rates in the five villages were 36.4% (166/450) and 36.9% (168/450), respectively. Within the cohort, 69.78% (314/450) of the subjects had a positive anti-S1 IgG response. COVID-19 vaccination coverage among the interviewed participants was 93.14% (190/204; 95% CI, 88.8% − 95.9%). However, 81% (154/190) of COVID-19 vaccinees had an anti-S1 IgG titre ≤200. In an adolescent group receiving a single dose of the BNT162b2 mRNA vaccine (n = 23), an inverse correlation was observed between anti-S1 IgG antibody level/titre and faecal egg count. Within the above group, anti-S1 IgG levels/titres were significantly lower in subjects with moderate or heavy S. mansoni infection (n = 5) than those in KK-negative individuals (n = 9).ConclusionAlthough the acceptance rate of COVID-19 vaccination was high, the majority of participants received only a single vaccine dose and the overall anti-S1 IgG titres in confirmed vaccinees were low. Moderate-to-heavy schistosome infections blunted the antibody responses following vaccination with a single dose of BNT162b2. These observations confirm the necessity for a second COVID-19 vaccine dose for two-dose primary immunization series and call for implementation research that may inform the development of a ‘treat and vaccinate’ policy during vaccination roll-out in regions with heavy worm burdens.

Introduction: Coronavirus disease 2019 (COVID-19) pandemic precipitated devastating health and economic consequences globally. Vaccination has been a central pillar for COVID-19 prevention and control. Understanding the immunomodulatory effects of helminth infections on COVID-19 vaccine-induced immune responses and vaccine efficacy is crucial to the development and deployment of effective vaccination strategies in low- and middle-income countries with high prevalence of worms. Methods: In September 2022, we conducted a cross-sectional, population-based survey in five Schistosoma mansoniendemic villages in Mayuge District, Uganda (n=450). The prevalence of schistosomiasis and soil-transmitted helminths was determined by the Kato-Katz (KK) technique on two stool samples collected from each participant. A subset of individuals (n=204) were interviewed in a COVID-19 vaccination survey. IgG levels against the SARS-CoV-2 spike S1 subunit (Anti-S1 IgG) were measured by enzyme-linked immunosorbent assay (ELISA) assays using collected serum samples. Results: The overall schistosomiasis and hookworm prevalence in the five villages was 36.4% (166/450) and 36.9% (168/450), respectively. Within the cohort, 69.78% (314/450) subjects showed a positive anti-S1 IgG response. COVID-19 vaccination coverage in interviewed participants was 93.14% (190/204; 95% CI, 88.8% − 95.9%). However, 81% (154/190) COVID-19 vaccinees had an anti-S1 IgG titer ≤ 200. In an adolescent group receiving a single dose of BNT162b2 vaccine (n=23), an inverse correlation was observed between anti-S1 IgG antibody levels/titers and faecal egg counts. Within the above group, anti-S1 IgG levels/titers were significantly low in subjects with a moderate-to-heavy S. mansoni infections (n=5) compared with KK-negative individuals (n=9). IgG1 was the dominant IgG subclass in sub-groups vaccinated with a single dose of the BNT162b2 (n=23) or Ad26.COV2.S (n=18). Conclusion: Although the acceptance rate of COVID-19 vaccination was high, the majority of participants received only a single vaccine dose and the overall anti-S1 IgG titers in confirmed vaccinees were low. Moderate-to-heavy intensity schistosome infections blunted the antibody response following vaccination with a single dose of BNT162b2. These observations confirm the necessity for a second vaccine dose for two-dose primary immunization series and call for implementation research that may inform the development of a ‘treat and vaccinate’ policy during vaccination roll-out in regions with heavy worm burdens.

Soil-transmitted helminths continue to be a serious problem causing disease and morbidity globally. Children, mostly school-aged, are more at risk of these infections. The main strategy for control remains to be the mass drug administration (MDA) of antihelminthic drugs. With the limitation of MDA to prevent re-infection, the need for additional approaches such as hygiene education and improvements in water, sanitation and hygiene (WASH) infrastructure are required. Although the importance of health education as a crucial component of an integrated approaches to STH control is highlighted, this component has often been disregarded because the other more complex solutions have been the focus of most studies and programmes. We performed literature searches from four bibliographic databases - Scopus, PubMed, Web of Science and Cochrane Library - to determine availability of studies on the impact of health education interventions targeting STH infections on schoolchildren in Southeast Asia. Our review found only three studies that evaluated health education interventions targeting children. The current lack of evidence in this area suggests the need for more studies assessing the impact of health education intervention for STH control. A successful health education programme for STH called "The Magic Glasses" has been developed targeting schoolchildren in China and the Philippines. This public health intervention displayed significant impact in terms of improving knowledge, attitude and practices, reducing prevalence of STH infections in schoolchildren and encouraging compliance to MDA. This article details the successes and benefits of the Magic Glasses programme as a promising control tool for STH in the Southeast Asian region.

Employing the flatworm parasite Schistosoma mansoni as a model, we report the first application of CRISPR interference (CRISPRi) in parasitic helminths for loss-of-function studies targeting the SmfgfrA gene which encodes the stem cell marker, fibroblast growth factor receptor A (FGFRA). SmFGFRA is essential for maintaining schistosome stem cells and critical in the schistosome-host interplay. The SmfgfrA gene was targeted in S. mansoni adult worms, eggs and schistosomula using a catalytically dead Cas9 (dCas9) fused to a transcriptional repressor KRAB. We showed that SmfgfrA repression resulted in considerable phenotypic differences in the modulated parasites compared with controls, including reduced levels of SmfgfrA transcription and decreased protein expression of SmFGFRA, a decline in EdU (thymidine analog 5-ethynyl-2’-deoxyuridine, which specifically stains schistosome stem cells) signal, and an increase in cell apoptosis. Notably, reduced SmfgfrA transcription was evident in miracidia hatched from SmfgfrA-repressed eggs, and resulted in a significant change in miracidial behavior, indicative of a durable repression effect caused by CRISPRi. Intravenous injection of mice with SmfgfrA-repressed eggs resulted in granulomas that were markedly reduced in size and a decline in the level of serum IgE, emphasizing the importance of SmFGFRA in regulating the host immune response induced during schistosome infection. Our findings show the feasibility of applying CRISPRi for effective, targeted transcriptional repression in schistosomes, and provide the basis for employing CRISPRi to selectively perturb gene expression in parasitic helminths on a genome-wide scale.

BACKGROUND:Schistosomiasis is a disease that significantly impacts human health in the developing world. Effective diagnostics are urgently needed for improved control of this disease. CRISPR-based technology has rapidly accelerated the development of a revolutionary and powerful diagnostics platform, resulting in the advancement of a class of ultrasensitive, specific, cost-effective and portable diagnostics, typified by applications in COVID-19/cancer diagnosis. METHODS:We developed CRISPR-based diagnostic platform SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the detection of Schistosoma japonicum and S. mansoni by combining recombinase polymerase amplification (RPA) with CRISPR-Cas13a detection, measured via fluorescent or colorimetric readouts. We evaluated SHERLOCK assays by using 150 faecal/serum samples collected from Schistosoma-infected ARC Swiss mice (female), and 189 human faecal/serum samples obtained from a S. japonicum-endemic area in the Philippines and a S. mansoni-endemic area in Uganda. FINDINGS:The S. japonicum SHERLOCK assay achieved 93-100% concordance with gold-standard qPCR detection across all the samples. The S. mansoni SHERLOCK assay demonstrated higher sensitivity than qPCR and was able to detect infection in mouse serum as early as 3 weeks post-infection. In human samples, S. mansoni SHERLOCK had 100% sensitivity when compared to qPCR of faecal and serum samples. INTERPRETATION:These schistosomiasis diagnostic assays demonstrate the potential of SHERLOCK/CRISPR-based diagnostics to provide highly accurate and field-friendly point-of-care tests that could provide the next generation of diagnostic and surveillance tools for parasitic neglected tropical diseases. FUNDING:Australian Infectious Diseases Research Centre seed grant (2022) and National Health and Medical Research Council (NHMRC) of Australia (APP1194462, APP2008433).

Despite intensive long-term efforts, with very few exceptions, the development of effective vaccines against parasitic infections has presented considerable challenges, given the complexity of parasite life cycles, the interplay between parasites and their hosts, and their capacity to escape the host immune system and to regulate host immune responses. For many parasitic diseases, conventional vaccine platforms have generally proven ill suited, considering the complex manufacturing processes involved and the costs they incur, the inability to posttranslationally modify cloned target antigens, and the absence of long-lasting protective immunity induced by these antigens.

Schistosomiasis is a neglected tropical disease of humans caused byblood flukes of the genus Schistosoma – the only dioecious parasiticflatworms. Although aspects of sex determination, differentiation andreproduction have been studied in some Schistosoma species, almostnothing is understood for Schistosoma japonicum - the causative agent ofschistosomiasis japonica. This relates mainly to a lack of high-qualitygenomic and transcriptomic resources for this species. As current draftgenomes for S. japonicum are highly fragmented, we assembled here achromosome-level reference genome (seven autosomes, the Z-chromosome andpartial W-chromosome), achieving a substantially enhanced geneannotation. Utilising this genome, we discovered that the sexchromosomes of S. japonicum and its congener S. mansoni independentlysuppressed recombination during evolution, forming four and two‘strata’, respectively. By exploring the W-chromosome and sex-specifictranscriptomes, we identified 35 W-linked genes and 257female-preferentially transcribed genes (FTGs) and identified asignature for sex determination and differentiation in S. japonicum.These FTGs cluster within autosomes or the Z-chromosome and exhibit ahighly dynamic transcription profile during the pairing of female andmale schistosomules (advanced juveniles), representing a critical phasefor the maturation of the female worms, suggesting distinct layers ofregulatory control of gene transcription at this stage of development.Collectively, these data provide a valuable resource for furtherfunctional genomic characterisation of S. japonicum, shed light on theevolution of sex chromosomes in this highly virulent human blood flukeand provide a pathway to identify novel targets for development ofintervention tools against schistosomiasis.

BACKGROUND:Schistosoma japonicum remains endemic in China and the Philippines. Substantial progress has been made in the control of Japonicum in both China and the Philippines. China is reaching elimination thanks to a concerted effort of control strategies. Mathematical modelling has been a key tool in the design of control strategies, in place of expensive randomised-controlled trials. We conducted a systematic review to investigate mathematical models of Japonicum control strategies in China and the Philippines.METHODS:We conducted a systematic review on July 5, 2020, in four electronic bibliographic databases - PubMed, Web of Science, SCOPUS and Embase. Articles were screened for relevance and for meeting the inclusion criteria. Data extracted included authors, year of publication, year of data collection, setting and ecological context, objectives, control strategies, main findings, the form and content of the model including its background, type, representation of population dynamics, heterogeneity of hosts, simulation period, source of parameters, model validation and sensitivity analysis. Results After screening, 19 eligible papers were included in the systematic review. Seventeen considered control strategies in China and two in the Philippines. Two frameworks were identified; the mean-worm burden framework and the prevalence-based framework, the latter of which increasingly common. Most models considered human and bovine definitive hosts. There were mixed additional elements included in the models, such as alternative definitive hosts and the role of seasonality and weather. Models generally agreed upon the need for an integrated control strategy rather than reliance on mass drug administration alone to sustain reductions in prevalence.CONCLUSIONS:Mathematical modelling of Japonicum has converged from multiple approaches to modelling using the prevalence-based framework with human and bovine definitive hosts and find integrated control strategies to be most effective. Further research could investigate the role of other definitive hosts and model the effect of seasonal fluctuations in transmission.

BackgroundThe neglected zoonosis, schistosomiasis japonica, remains a major public health problem in the Philippines. The current study aims to develop a novel gold immunochromatographic assay (GICA) and evaluate its performance in the detection of Schistosoma japonicum infection.MethodsA GICA strip incorporating a S. japonicum saposin protein, SjSAP4 was developed. For each GICA strip test, diluted serum sample (50 µl) was loaded and strips were scanned after 10 min to convert the results into images. ImageJ was used to calculate an R value, which was defined as the signal intensity of the test line divided by the signal intensity of the control line within the cassette. After determination of optimal serum dilution and diluent, the GICA assay was evaluated with sera collected from non-endemic controls (n = 20) and individuals living in schistosomiasis-endemic areas of the Philippines (n = 60), including 40 Kato Katz (KK)-positive participants and 20 subjects confirmed as KK-negative and faecal droplet digital PCR assay (F_ddPCR)-negative at a dilution of 1:20. An ELISA assay evaluating IgG levels against SjSAP4 was also performed on the same panel of sera.ResultsPhosphate-buffered saline (PBS) and 0.9% NaCl were determined as optimal dilution buffer for the GICA assay. The strips tested with serial dilutions of a pooled serum sample from KK-positive individuals (n = 3) suggested that a relatively wide range of dilutions (from 1:10 to 1:320) can be applied for the test. Using the non-endemic donors as controls, the GICA strip showed a sensitivity of 95.0% and absolute specificity; while using the KK-negative and F_ddPCR-negative subjects as controls, the immunochromatographic assay had a sensitivity of 85.0% and a specificity of 80.0%. The SjSAP4-incorperated GICA displayed a high concordance with the SjSAP4-ELISA assay.ConclusionsThe developed GICA assay exhibited a similar diagnostic performance with that of the SjSAP4-ELISA assay, yet the former can be performed by local personnel with minimal training with no requirement for specialised equipment. The GICA assay established here represents a rapid, easy-to-use, accurate and field-friendly diagnostic tool for the on-site surveillance/screening of S. japonicum infection.

Background Soil-transmitted helminth (STH) infections are a significant public health problem affecting over 900 million people globally. Health education has been shown to complement mass drug administration (MDA) for the control of these intestinal worms. We reported recently results of a cluster randomised control trial (RCT) show-ing the positive impact of the "The Magic Glasses Philippines (MGP)" health education package in reducing STH infections among schoolchildren in intervention schools with <= 15% STH baseline prevalence in Laguna province, the Philippines. To inform decision making on the economic implications of the MGP, we evaluated the in-trial costs and then quantified the costs of scaling up the intervention both regionally and nationally.Methods Costs were determined for the MGP RCT conducted in 40 schools in Laguna province. We estimated the total cost and the costs incurred per student for the actual RCT and the total costs for regional and national scale-up in all schools regardless of STH endemicity. The costs associated with the implementation of standard health educa-tion (SHE) activities and mass drug administration (MDA) were determined with a public sector perspective.Findings The cost per participating student in the MGP RCT was Php 58.65 (USD 1.15) but if teachers instead of research staff had been involved, the estimated cost would have been considerably lower at Php 39.45 (USD 0.77). Extrapolating the costs for regional scale-up, the costs per student were estimated to be Php 15.24 (USD 0.30). As it is scaled up at the national level to include more schoolchildren, the estimated cost was increased at Php 17.46 (USD 0.34). In scenario 2 and 3, consistently, labour/salary costs associated with the delivery of the MGP contributed most to overall programme expenditure. Furthermore, the estimated average cost per student for SHE and MDA were Php 117.34 (USD 2.30) and Php 58.17 (USD 1.14), respectively. Using national scale up estimates, the cost of combining the MGP with SHE and MDA was Php 192.97 (USD 3.79). Interpretation These findings suggest that the integration of MGP into the school curriculum would be an afford-able and scalable approach to respond to the continuous burden of STH infection among schoolchildren in the Philippines.Funding National and Medical Research Council, Australia, and the UBS-Optimus Foundation, Switzerland.Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)