Comparative assessment of the SjSAP4-incorporated gold immunochromatographic assay for the diagnosis of human schistosomiasis japonica.

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.

Development and assessment of a novel gold immunochromatographic assay for the diagnosis of schistosomiasis japonica.

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.

Cost analysis for "The Magic Glasses Philippines" health education package to prevent intestinal worm infections among Filipino schoolchildren.

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.

Short-, Mid-, and Long-Term Epidemiological and Economic Effects of the World Bank Loan Project on Schistosomiasis Control in the People's Republic of China.

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.

Soil-transmitted helminth infections and nutritional indices among Filipino schoolchildren.

BACKGROUND: Soil-transmitted helminth (STH) infections are still prevalent among schoolchildren in the Philippines. We evaluated the risk factors associated with STH and the relationship between STH and nutritional indices among schoolchildren aged 9-10 years in Laguna province, the Philippines. METHODS: We used the baseline data from 40 schools enrolled in a randomised controlled trial of the Magic Glasses Philippines health education package. Data on demographic and socio-economic variables, and STH related knowledge, attitudes and practices, were obtained through a questionnaire. Stool samples were collected and assessed for STH egg presence using the Kato-Katz technique. Haemoglobin levels and height and weight of study participants were also determined. The generalized estimating equations approach was used to construct logistic regression models to assess STH-associated risk factors, and the association between any STH infection and anaemia, child stunting, wasting and being underweight. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000508471). FINDINGS: Among 1,689 schoolchildren, the prevalence of any STH was 23%. The prevalence of anaemia, stunting, being underweight and wasting was 13%, 20.2%, 19% and 9.5%, respectively. Age, socio-economic status, rural/urban classification of schools and knowledge of STH were significant risk factors for acquiring a STH infection. Moreover, infections with any STH were significantly associated with stunting (P = <0.001) and being underweight (P = <0.003), but not wasting (P = 0.375) or anaemia (P = 0.462) after controlling for confounding covariates. CONCLUSION: The study findings emphasise the need for sustainable deworming in tandem with other measures such as the provision of health education, improvements in sanitation and hygiene, and nutritional programs in order to control STH infections and improve morbidity outcomes in schoolchildren. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616000508471).

The Tao survivorship of schistosomes: implications for schistosomiasis control.

Schistosomiasis, caused by blood flukes of the genus Schistosoma, is a major public health problem which contributes substantially to the economic and financial burdens of many nations in the developing world. An array of survival strategies, such as the unique structure of the tegument which acts as a major host-parasite interface, immune modulation mechanisms, gene regulation, and apoptosis and self-renewal have been adopted by schistosome parasites over the course of long-term evolution with their mammalian definitive hosts. Recent generation of complete schistosome genomes together with numerous biological, immunological, high-throughput "-omics" and gene function studies have revealed the Tao or strategies that schistosomes employ not only to promote long-term survival, but also to ensure effective life cycle transmission. New scenarios for the future control of this important neglected tropical disease will present themselves as our understanding of these Tao increases.

Five-year longitudinal assessment of the downstream impact on schistosomiasis transmission following closure of the Three Gorges Dam.

BACKGROUND: Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC), with about 800,000 people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that, long-term, the Three Gorges Dam (TGD) will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes. METHODOLOGY/PRINCIPAL FINDINGS: We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages of the three transmission modes below the TGD across four provinces (Hunan, Jiangxi, Hubei and Anhui) to determine whether there was any immediate impact of the TGD on schistosomiasis transmission. Eight sentinel villages were selected to represent both province and transmission mode. The primary end point measured was human incidence. Here we present the results of this five-year longitudinal cohort study. Results showed that the incidence of human S. japonicum infection declined considerably within individual villages and overall mode over the course of the study. This is also reflected in the yearly odds ratios (adjusted) for infection risk that showed significant (P<0.01) downward trends in all modes over the follow-up period. CONCLUSIONS/SIGNIFICANCE: The decrease in human S. japonicum incidence observed across all transmission modes in this study can probably be attributed to the annual human and bovine PZQ chemotherapy. If an increase in schistosome transmission had occurred as a result of the TGD, it would be of negligible size compared to the treatment induced decline seen here. It appears therefore that there has been virtually no immediate impact of the TGD on schistosomiasis transmission downstream of the dam.

Comparison of two approaches for measuring household wealth via an asset-based index in rural and peri-urban settings of Hunan province, China.

BACKGROUND: There are growing concerns regarding inequities in health, with poverty being an important determinant of health as well as a product of health status. Within the People's Republic of China (P.R. China), disparities in socio-economic position are apparent, with the rural-urban gap of particular concern. Our aim was to compare direct and proxy methods of estimating household wealth in a rural and a peri-urban setting of Hunan province, P.R. China. METHODS: We collected data on ownership of household durable assets, housing characteristics, and utility and sanitation variables in two village-wide surveys in Hunan province. We employed principal components analysis (PCA) and principal axis factoring (PAF) to generate household asset-based proxy wealth indices. Households were grouped into quartiles, from 'most wealthy' to 'most poor'. We compared the estimated household wealth for each approach. Asset-based proxy wealth indices were compared to those based on self-reported average annual income and savings at the household level. RESULTS: Spearman's rank correlation analysis revealed that PCA and PAF yielded similar results, indicating that either approach may be used for estimating household wealth. In both settings investigated, the two indices were significantly associated with self-reported average annual income and combined income and savings, but not with savings alone. However, low correlation coefficients between the proxy and direct measures of wealth indicated that they are not complementary. We found wide disparities in ownership of household durable assets, and utility and sanitation variables, within and between settings. CONCLUSION: PCA and PAF yielded almost identical results and generated robust proxy wealth indices and categories. Pooled data from the rural and peri-urban settings highlighted structural differences in wealth, most likely a result of localized urbanization and modernization. Further research is needed to improve measurements of wealth in low-income and transitional country contexts.

Impact of increased economic burden due to human echinococcosis in an underdeveloped rural community of the People's Republic of China.

BACKGROUND: Ningxia is located in western People's Republic of China, which is hyperendemic for human cystic echinococcosis (CE) throughout the entire area with alveolar echinococcosis (AE) hyperendemic in the south. This is in part due to its underdeveloped economy. Despite the recent rapid growth in P.R. China's economy, medical expenditure for hospitalization of echinococcosis cases has become one of the major poverty generators in rural Ningxia, resulting in a significant social problem. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed the 2000 inpatient records with liver CE in surgical departments of hospitals from north, central and south Ningxia for the period 1996-2002. We carried out an analysis of health care expenditure of inpatient treatment in public hospitals, and examined the financial inequalities relating to human echinococcosis and the variation in per capita income between various socioeconomic groups with different levels of gross domestic product for different years. Hospital charges for Yinchuan, NHAR's capital city in the north, increased approximately 35-fold more than the annual income of rural farmers with the result that they preferred to seek health care in local county hospitals, despite higher quality and more efficient treatment and diagnosis available in the city. Household income levels thus strongly influenced the choice of health care provider and the additional expense impeded access of poor people to better quality treatment. CONCLUSIONS/SIGNIFICANCE: Information on socioeconomic problems arising from echinococcosis, which adds considerably to the burden on patient families and communities, needs to be collected as a prerequisite for developing policies to tackle the disease in rural Ningxia.

A pilot study for control of hyperendemic cystic hydatid disease in China.

BACKGROUND: Cystic hydatid disease (CHD) is a global parasitic zoonosis caused by the dog tapeworm, Echinococcus granulosus. The disease is hyperendemic in western China because of poor economic development; limited community knowledge of CHD; widespread, small-scale household animal production; home killing of livestock; and the feeding of dogs with uncooked offal. METHODOLOGY/PRINCIPAL FINDINGS: A control program focusing on monthly praziquantel (PZQ) treatment of all registered dogs and culling unwanted and stray dogs has been designed to control CHD in hyperendemic areas in China. A pilot field control project in two counties (Hutubi and Wensu) in Xinjiang, China showed that after 4 years of treatment, the prevalence of dogs with E. granulosus was reduced from 14.7% and 18.6%, respectively, to 0%, and this caused a 90%-100% decrease of CHD in sheep born after commencement of the control program. CONCLUSIONS/SIGNIFICANCE: The strategy aimed at preventing eggs being released from dogs into the environment by treating animals before adult tapeworms are patent can decrease E. granulosus transmission and considerably reduce hyperendemic CHD. Monthly treatment of dogs with PZQ and culling unwanted and stray dogs have been shown to be an efficient, highly cost-effective and practicable measure for implementation in rural communities. As a result, the Chinese Ministry of Health has launched an extensive CHD control program in 117 counties in western China using this control strategy.

Landscape composition and spatial prediction of alveolar echinococcosis in southern Ningxia, China.

BACKGROUND: Alveolar echinococcosis (AE) presents a serious public health challenge within China. Mass screening ultrasound surveys can detect pre-symptomatic AE, but targeting areas identified from hospital records is inefficient regarding AE. Prediction of undetected or emerging hotspots would increase detection rates. Voles and lemmings of the subfamily Arvicolinae are important intermediate hosts in sylvatic transmission systems. Their populations reach high densities in productive grasslands where food and cover are abundant. Habitat availability is thought to affect arvicoline population dynamic patterns and definitive host-intermediate host interactions. Arvicoline habitat correlates with AE prevalence in Western Europe and southern Gansu Province, China. METHODS AND FINDINGS: Xiji County, Ningxia Hui Autonomous Region, borders southern Gansu. The aims of this study were to map AE prevalence across Xiji and test arvicoline habitat as a predictor. Land cover was mapped using remotely sensed (Landsat) imagery. Infection status of 3,205 individuals screened in 2002-2003 was related, using generalised additive mixed models, to covariates: gender; farming; ethnicity; dog ownership; water source; and areal cover of mountain pasture and lowland pasture. A Markov random field modelled additional spatial variation and uncertainty. Mountain pasture and lowland pasture were associated with below and above average AE prevalence, respectively. CONCLUSIONS: Low values of the normalised difference vegetation index indicated sub-optimality of lowland pasture for grassland arvicolines. Unlike other known endemic areas, grassland arvicolines probably did not provide the principal reservoir for Echinococcus multilocularis in Xiji. This result is consistent with recent small mammal surveys reporting low arvicoline densities and high densities of hamsters, pikas and jerboas, all suitable intermediate hosts for E. multilocularis, in reforested lowland pasture. The risk of re-emergence is discussed. We recommend extending monitoring to: southern Haiyuan County, where predicted prevalence was high; southern Xiji County, where prediction uncertainty was high; and monitoring small mammal community dynamics and the infection status of dogs.

Applications and outcomes of periodic epidemiological surveys for schistosomiasis and related economic evaluation in the People's Republic of China.

The great success in schistosomiasis control in China is attributable to a range of factors. Periodic epidemiological surveys (PES) used for monitoring and adapting control interventions over time are an integral feature of the national schistosomiasis control programme. PES have enabled the dynamic trends of schistosomiasis epidemics to be closely pursued and have assisted in analysing subtle changes in endemicity. The results can be summarised mathematically allowing the variation in efficacy of control measures to be readily determined and enabling control strategies to be adjusted and updated. PES have been used in both cross-sectional and longitudinal pilot studies selected by appropriate sampling methods. In the early 1990s, when the World Bank Loan Project for schistosomiasis control commenced, economic evaluations were initiated in parallel. Cost-effectiveness analysis became a necessary tool to identify the most financially feasible yet effective options among a range of alternative control strategies. There was, however, a lack of standardised approaches rendering study comparisons across sites difficult. The global burden of disease study established the disability adjusted life year (DALY) as a measure of population health, combining in a single indicator years lost from premature death and years of life lived with disability. However, a recent meta-analysis reveals that the burden of schistosomiasis is underestimated, and hence, needs to be revised. It is envisaged that after the revision of DALYs lost due to schistosomiasis japonica, they will become an essential measure in future schistosomiasis control assessments in China and in other schistosome-endemic areas of the world.

Immune correlate study on human Schistosoma japonicum in a well-defined population in Leyte, Philippines: I. Assessment of 'resistance' versus 'susceptibility' to S. japonicum infection.

This study describes the categorical classification of 155 individuals living in an endemic village in Macanip, Leyte, Philippines as 'resistant' or 'susceptible' to Schistosoma japonicum infection using available exposure, infection and reinfection data collected from a 3-year water contact (WC) study. Epidemiological parameters including age, sex, and infection intensities in relation to observed reinfection patterns are also described. This classification was used in subsequent immunological studies described in two accompanying papers to identify protective immune mechanisms among resistant individuals induced by defined candidate vaccine molecules for S. japonicum. The study suggests that individuals who were most vulnerable to rapid reinfection were children belonging to the 5-14 age group. A drop in incidence at age group 15-19 and decreased intensity of infection starting at this age group and older (15+) suggests development of immunity. Controlling for the effect of the other variables, a multivariate analysis showed significant association for sex, in that females were more likely to be resistant. This implies that other than acquired immunity to infection, some age-dependent host factors may also play an important role in the overall changes of reinfection patterns seen in schistosomiasis japonica in this population.