RESUMEN

BACKGROUND: Helminths 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. OBJECTIVE: The 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. METHODS: Schoolchildren 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. RESULTS: The 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. CONCLUSIONS: This 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 REGISTRATION: Australian 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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

RESUMEN

Background: Schistosomiasis, a disease caused by parasites of the genus Schistosoma, remains a global public health threat. This study aimed to validate the diagnostic performance of a recently developed gold immunochromatographic assay (GICA) for the detection of S. japonicum infection in a rural endemic area of the Philippines. Methods: Human clinical samples were collected from 412 subjects living in Laoang and Palapag municipalities, Northern Samar, the Philippines. The presence of Schistosoma-specific antibodies in serum samples was tested with the SjSAP4-incorporated GICA strips and the results were converted to fully quantitative data by introducing an R value. The performance of the established GICA was further compared with other diagnostic tools, including the Kato-Katz (KK) technique, point-of-care circulating cathodic antigen (POC-CCA), droplet digital (dd) PCR, and enzyme-linked immunosorbent assays (ELISAs). Results: The developed GICA strip was able to detect KK positive individuals with a sensitivity of 83.3% and absolute specificity. When calibrated with the highly sensitive faecal ddPCR assay, the immunochromatographic assay displayed an accuracy of 60.7%. Globally, the GICA assay showed a high concordance with the SjSAP4-ELISA assay. The schistosomiasis positivity rate determined by the GICA test was similar to those obtained with the SjSAP4-ELISA assay and the ddPCR assay performed on serum samples (SR_ddPCR), and was 2.3 times higher than obtained with the KK method. Conclusion: The study further confirms that the developed GICA is a valuable diagnostic tool for detecting light S. japonicum infections and implies that this point-of-care assay is a viable solution for surveying endemic areas of low-intensity schistosomiasis and identifying high-priority endemic areas for targeted interventions.

Asunto(s)

RESUMEN

BACKGROUND: Schistosomiasis remains a public health issue and the need for accurate and affordable diagnostics is crucial in the elimination of the disease. While molecular diagnostics are highly effective, they are expensive, with the main costs been associated with DNA extraction. The DNA dipstick is a rapid, affordable and simple purification method that allows DNA to be extracted from diagnostic samples within 30 s. We aimed to optimise the DNA dipstick method for samples from mice and egg-spiked human samples. METHODS: Urine, blood and faeces were collected from mice exposed to Schistosoma japonicum infection at weekly intervals from Day 0 to Day 42. Urine and faecal samples were also collected from volunteer, uninfected humans and spiked with S. japonicum eggs. All samples were subject to several optimisation procedures and DNA extracted with the DNA dipstick. Amplification of the target DNA was carried out using LAMP and visualised using agarose gel electrophoresis and flocculation. RESULTS: The DNA dipstick successfully identified S. japonicum from infected mice and human clinical samples spiked with cracked eggs or genomic DNA from S. japonicum. Amplification was observed from week 4 post infection in infected mice. For human samples, amplification was observed in sieved faecal samples, filtered urine samples heated at 95 °C for 30 min, and sera samples heated at 95 °C for 30 min. CONCLUSIONS: The DNA dipstick combined with LAMP has huge potential in providing cost-effective, simple and accurate detection of schistosomiasis infection in endemic regions. This will allow for rapid treatment, tracking outbreaks-such as occur after typhoons, leading to better health outcomes and contributing to control and eventual elimination of schistosomiasis.

Asunto(s)

RESUMEN

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).

Asunto(s)

RESUMEN

Background: The 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. Methods: A 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. Results: Phosphate-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. Conclusions: The 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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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) showing 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 education (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 affordable 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.

RESUMEN

OBJECTIVE: Schistosomiasis is a neglected tropical parasitic disease caused by blood flukes of the genus Schistosoma. Schistosoma japonicum is zoonotic in China, the Philippines, and Indonesia, with bovines acting as major reservoirs of human infection. The primary objective of the trial was to examine the impact of a combination of human mass chemotherapy, snail control through mollusciciding, and SjCTPI bovine vaccination on the rate of human infection. METHODS: A 5-year phase IIIa cluster randomized control trial was conducted among 18 schistosomiasis-endemic villages comprising 18,221 residents in Northern Samar, The Philippines. RESULTS: Overall, bovine vaccination resulted in a statistically significant decrease in human infection (relative risk [RR] = 0.75; 95% confidence interval [CI] = 0.69 to 0.82) across all trial follow-ups. The best outcome of the trial was when bovine vaccination was combined with snail mollusciciding. This combination resulted in a 31% reduction (RR = 0.69; 95% CI = 0.61 to 0.78) in human infection. CONCLUSION: This is the first trial to demonstrate the effectiveness of a bovine vaccine for schistosomiasis in reducing human schistosome infection. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12619001048178).

Asunto(s)

RESUMEN

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. An effective antiparasite vaccine platform is required to assess the effectiveness of novel vaccine candidates at high throughput. By exploiting the approach that has recently been used successfully to produce highly protective COVID mRNA vaccines, we anticipate a new wave of research to advance the use of mRNA vaccines to prevent parasitic infections in the near future. This article considers the characteristics that are required to develop a potent antiparasite vaccine and provides a conceptual foundation to promote the development of parasite mRNA-based vaccines. We review the recent advances and challenges encountered in developing antiparasite vaccines and evaluate the potential of developing mRNA vaccines against parasites, including those causing diseases such as malaria and schistosomiasis, against which vaccines are currently suboptimal or not yet available.

Asunto(s)

RESUMEN

Schistosomiasis is a neglected tropical disease of humans caused by blood flukes of the genus Schistosoma, the only dioecious parasitic flatworm. Although aspects of sex determination, differentiation and reproduction have been studied in some Schistosoma species, almost nothing is known for Schistosoma japonicum, the causative agent of schistosomiasis japonica. This mainly reflects the lack of high-quality genomic and transcriptomic resources for this species. As current genomes for S. japonicum are highly fragmented, we assembled and report a chromosome-level reference genome (seven autosomes, the Z-chromosome and partial W-chromosome), achieving a substantially enhanced gene annotation. Utilizing this genome, we discovered that the sex chromosomes of S. japonicum and its congener S. mansoni independently suppressed recombination during evolution, forming five and two evolutionary strata, respectively. By exploring the W-chromosome and sex-specific transcriptomes, we identified 35 W-linked genes and 257 female-preferentially transcribed genes (FTGs) from our chromosomal assembly and uncovered a signature for sex determination and differentiation in S. japonicum. These FTGs clustering within autosomes or the Z-chromosome exhibit a highly dynamic transcription profile during the pairing of female and male schistosomula, thereby representing a critical phase for the maturation of the female worms and suggesting distinct layers of regulatory control of gene transcription at this development stage. Collectively, these data provide a valuable resource for further functional genomic characterization of S. japonicum, shed light on the evolution of sex chromosomes in this highly virulent human blood fluke, and provide a pathway to identify novel targets for development of intervention tools against schistosomiasis.

Asunto(s)

RESUMEN

Background: Recent studies on CRISPR/Cas9-mediated gene editing in Schistosoma mansoni have shed new light on the study and control of this parasitic helminth. However, the gene editing efficiency in this parasite is modest. Methods: To improve the efficiency of CRISPR/Cas9 genome editing in schistosomes, we used lentivirus, which has been effectively used for gene editing in mammalian cells, to deliver plasmid DNA encoding Cas9 nuclease, a sgRNA targeting acetylcholinesterase (SmAChE) and a mCherry fluorescence marker into schistosomes. Results: MCherry fluorescence was observed in transduced eggs, schistosomula, and adult worms, indicating that the CRISPR components had been delivered into these parasite stages by lentivirus. In addition, clearly changed phenotypes were observed in SmAChE-edited parasites, including decreased SmAChE activity, reduced hatching ability of edited eggs, and altered behavior of miracidia hatched from edited eggs. Next-generation sequencing analysis demonstrated that the lentiviral transduction-based CRISPR/Cas9 gene modifications in SmAChE-edited schistosomes were homology-directed repair predominant but with much lower efficiency than that obtained using electroporation (data previously published by our laboratory) for the delivery of CRISPR components. Conclusion: Taken together, electroporation is more efficient than lentiviral transduction in the delivery of CRISPR/Cas9 into schistosomes for programmed genome editing. The exploration of tactics for enhancing CRISPR/Cas9 gene editing provides the basis for the future improvement of programmed genome editing in S. mansoni.

RESUMEN

The current study developed and evaluated the performance of a urine-based enzyme-linked immunosorbent assay (ELISA) for the screening of Schistosoma japonicum infection in a human cohort (n = 412) recruited from endemic areas, Northern Samar, the Philippines. The diagnostic performance of the urine ELISA assay was further compared with the Kato-Katz (KK) technique, serum-based ELISA assays, point-of-care circulating cathodic antigen (POC-CCA) urine cassette test, and droplet digital (dd)PCR assays performed on feces, serum, urine, and saliva samples, which were designated as F_ddPCR, SR_ddPCR, U_ddPCR, and SL_ddPCR, respectively. When urine samples concentrated 16× were assessed, the SjSAP4 + Sj23-LHD-ELISA (U) showed sensitivity/specificity values of 47.2/93.8% for the detection of S. japonicum infection in KK-positive individuals (n = 108). The prevalence of S. japonicum infection in the total cohort determined by the urine ELISA assay was 48.8%, which was lower than that obtained with the F_ddPCR (74.5%, p < 0.001), SR_ddPCR (67.2%, p < 0.001), and SjSAP4 + Sj23-LHD-ELISA (S) (66.0%, p < 0.001), but higher than that determined by the Sj23-LHD-ELISA (S) (24.5%, p < 0.001), POC-CCA assay (12.4%, p < 0.001), and SL_ddPCR (25.5%, p < 0.001). Using the other diagnostic tests as a reference, the urine ELISA assay showed a sensitivity between 47.2 and 56.9%, a specificity between 50.7 and 55.2%, and an accuracy between 49.3 and 53.4%. The concentrated urine SjSAP4 + Sj23-LHD-ELISA developed in the current study was more sensitive than both the KK test and POC-CCA assay, and showed a comparable level of diagnostic accuracy to that of the U_ddPCR. However, its diagnostic performance was less robust than that of the F_ddPCR, SR_ddPCR, and SjSAP4 + Sj23-LHD-ELISA (S) assays. Although they are convenient and involve a highly acceptable non-invasive procedure for clinical sample collection, the insufficient sensitivity of the three urine-based assays (the urine ELISA assay, the U_ddPCR test, and the POC-CCA assay) will limit their value for the routine screening of schistosomiasis japonica in the post mass drug administration (MDA) era, where low-intensity infections are predominant in many endemic areas.

RESUMEN

It is widely acknowledged that the 10-year World Bank Loan Project (WBLP) on schistosomiasis control in the People's Republic of China played an important role in raising the public and political profile of schistosomiasis, particularly regarding its prevention, control, and elimination. The WBLP adopted large-scale administration of praziquantel as the main control measure. At the end of the 10-year project in 2001, data from high-, medium-, and low-endemic areas suggested that the infection rates of both humans and domestic animals had fallen to the expected levels. However, major floods in the Yangtze River basin, coupled with reduced funding for schistosomiasis control, resulted in a rebound of the disease in endemic areas. Since 2005, a steady decline in infection rates was observed and it was hypothesized that the experiences and technological advances accumulated during the WBLP played a role. Nonetheless, relatively little is known about the long-term effects of the WBLP on schistosomiasis, particularly management mechanisms, technological innovations, epidemiological changes, and long-term economic impact. To fill these gaps, we systematically searched the literature for articles in English and Chinese on the WBLP on schistosomiasis from 1 January 1992 to 30 July 2022. Relevant studies were analyzed for short-, mid-, and long-term epidemiological and economic effects of the WBLP on schistosomiasis prevention, control, and elimination. Overall, 81 articles met our inclusion criteria, of which 17 were related to management mechanism reform, 20 pertained to technological innovation, and 44 examined epidemiological changes and economic effects. Most papers documented the WBLP as a positive contribution to schistosomiasis prevention and control in the People's Republic of China. Regarding the long-term effects, there was a significant contribution to the national schistosomiasis control and elimination programme in terms of renewed management mechanisms, talent development, and technological innovation. In conclusion, the WBLP contributed to enhanced control of schistosomiasis and shaped the ultimate response towards schistosomiasis elimination in the People's Republic of China. Experiences and lessons learned might guide schistosomiasis control and elimination elsewhere.

RESUMEN

Understanding the spatial distribution of schistosome infection is critical for tailoring preventive measures to control and eliminate schistosomiasis. This study used spatial analysis to determine risk factors that may impact Schistosoma japonicum infection and predict risk in Hunan and Jiangxi Provinces in the People's Republic of China. The study employed survey data collected in Hunan and Jiangxi in 2016. Independent variable data were obtained from publicly available sources. Bayesian-based geostatistics was used to build models with covariate fixed effects and spatial random effects to identify factors associated with the spatial distribution of infection. Prevalence of schistosomiasis was higher in Hunan (12.8%) than Jiangxi (2.6%). Spatial distribution of schistosomiasis varied at pixel level (0.1 × 0.1 km), and was significantly associated with distance to nearest waterbody (km, ß = -1.158; 95% credible interval [CrI]: -2.104, -0.116) in Hunan and temperature (°C, ß = -4.359; 95% CrI: -9.641, -0.055) in Jiangxi. The spatial distribution of schistosomiasis in Hunan and Jiangxi varied substantially and was significantly associated with distance to nearest waterbody. Prevalence of schistosomiasis decreased with increasing distance to nearest waterbody in Hunan, indicating that schistosomiasis control should target individuals in close proximity to open water sources as they are at highest risk of infection.

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic idiopathic disease characterized by inflammation-related epithelial barrier damage in the intestinal tract. Helminth infection reduces autoimmune disease symptoms through regulation of inflammatory responses based on hygiene theory. However, the underlying mechanisms remain unclear. METHODS: BALB/c mice were infected with microcysts of E. granulosus sensu stricto and drank water containing 3.5% dextran sodium sulfate (DSS) at the 100th day post-infection. After 7 days of drinking DSS, the mouse body weight change and disease activity index (DAI) were recorded every day, and colon length and histological score were evaluated after sacrifice. After injection with antigen B (AgB), inducible nitric oxide synthase (iNOS) and Fizz1 expression and F4/80+CD11c+ M1 and F4/80+CD206+ M2 in the peritoneal cells and colon tissues were analysed by qPCR and flow cytometry, respectively. Gut microbiota were profiled by 16S rRNA sequencing of the mouse faecal samples. For in vitro assay, RAW264.7 macrophages were cultured in medium containing AgB before induction by lipopolysaccharide (LPS). Then, NO in the supernatant was measured, and the expression of cytokine genes associated with macrophages were determined by qRT-PCR. RESULTS: Echinococcus granulosus s.s. infection and AgB significantly reduced the symptoms and histological scores of IBD induced by DSS (P < 0.05). Flow cytometry showed that AgB inoculation increased F4/80+ and CD206+ in peritoneal cells. The results of qPCR showed that AgB significantly decreased iNOS and increased Fizz1 expression in the colon of mice inoculated by DSS (P < 0.05). Furthermore, AgB injection led to significant changes in the profiles of five genera (Paraprevotella, Odoribacter, Clostridium cluster XlVa, Oscillibacter, and Flavonifractor) in faecal samples. In vitro analysis showed that AgB reduced NO levels (P < 0.01), with a significant decrease in iNOS expression (P < 0.05) in RAW264.7 cells induced by LPS. CONCLUSIONS: Echinococcus granulosus infection and AgB may improve IBD conditions by inducing an M2-predominant cellular (F4/80+ CD206+) profile and decreasing type 1 macrophages (F4/80+CD11c+) in the intestinal lamina propria. In addition, AgB intervention induced changes in the microbiota condition of the gastrointestinal duct and reversed NO expression. Thus, AgB may be a drug candidate for IBD treatment.

Asunto(s)

RESUMEN

Schistosomiasis, caused by infection with Schistosoma digenetic trematodes, is one of the deadliest neglected tropical diseases in the world. The Schistosoma lifecycle involves the miracidial infection of an intermediate freshwater snail host, such as Biomphalaria glabrata. Dispersing snail host-derived Schistosoma miracidia attractants has been considered a method of minimising intermediate host infections and, by extension, human schistosomiasis. The attractiveness of B. glabrata to miracidia is known to be reduced following infection; however, the relationship between duration of infection and attractiveness is unclear. Excretory-secretory proteins (ESPs) most abundant in attractive snail conditioned water (SCW) are key candidates to function as miracidia attractants. This study analysed SCW from B. glabrata that were naïve (uninfected) and at different time-points post-miracidia exposure (PME; 16h, 1-week, 2-weeks and 3-weeks PME) to identify candidate ESPs mediating Schistosoma mansoni miracidia behaviour change, including aggregation and chemoklinokinesis behaviour (random motion, including slowdown and increased turning rate and magnitude). Miracidia behaviour change was only observed post-addition of naïve and 3W-PME SCW, with other treatments inducing significantly weaker behaviour changes. Therefore, ESPs were considered attractant candidates if they were shared between naïve and 3W-PME SCW (or exclusive to the former), contained a predicted N-terminal signal peptide and displayed low identity (<50%) to known proteins outside of the Biomphalaria genus. Using these criteria, a total of 6 ESP attractant candidates were identified, including acetylcholine binding protein-like proteins and uncharacterised proteins. Tissue-specific RNA-seq analysis of the genes encoding these 6 ESPs indicated relatively high gene expression within various B. glabrata tissues, including the foot, mantle and kidney. Acetylcholine binding protein-like proteins were highly promising due to their high abundance in naïve and 3W-PME SCW, high specificity to B. glabrata and high expression in the ovotestis, from which attractants have been previously identified. In summary, this study used proteomics, guided by behavioural assays, to identify miracidia attractant candidates that should be further investigated as potential biocontrols to disrupt miracidia infection and minimise schistosomiasis.

Asunto(s)