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Schistosomiasis is caused by dioecious helminths of the genus Schistosoma. Recent work indicated that unpaired female and male schistosomes can survive within their definitive host for at least 1 year, although the viability or fertility of these worms after subsequent pairing remained untested. We performed two experiments on laboratory mice, one with female Schistosoma japonicum exposure first and male schistosomes second and another vice versa. After surviving as single-sex unpaired forms for up to 1 year, 58.5% of male and 70% of female schistosomes were able to mate and produce viable eggs. This highlights an additional biological challenge in achieving elimination of schistosomiasis.

Oncomelania hupensis hupensis is the only intermediate host of Schistosoma japonicum, the causative agent of schistosomiasis in China and is therefore of significant medical and veterinary health importance. Although tremendous progress has been achieved, there remains an understudied area of approximately 2.06 billion m2 of potential snail habitats. This area could be further increased by annual flooding. Therefore, an understanding of population genetics of snails in these areas may be useful for future monitoring and control activities. We sampled snails from Hexian (HX), Zongyang (ZY) and Shitai (ST) in Anhui (schistosomiasis transmission control), and from Hengtang (HT), Taicang (TC), Dongsan (DS) and Xisan (XS) in Jiangsu (schistosomiasis transmission interrupted), downstream of Anhui. ST, DS and XS are classified as hilly and mountainous areas, and HX, ZY, TC and HT as lake and marshland areas. The mitochondrial cytochrome c oxidase subunit I gene were sequenced. Out of 115 snails analyzed, 29 haplotypes were identified. We observed 56 (8.72%) polymorphic sites consisting of 51 transitions, four transversions and one multiple mutational change. The overall haplotype and nucleotide diversity were 0.899 and 0.01569, respectively. Snail populations in Anhui had higher genetic diversity than in Jiangsu. 73.32% of total variation was distributed among sites and 26.68% within sites. Snails were significantly separated according to eco-epidemiological settings in both network and phylogenetic analyses. Our results could provide important guidance towards assessing coevolutionary interactions of snails with S. japonicum, as well as for future molluscan host monitoring and control activities.

Background As China is moving onto schistosomiasis elimination/eradication, diagnostic methods with both high sensitivity and specificity for Schistosoma japonicum infections in humans are urgently needed. Microscopic identification of eggs in stool is proven to have poor sensitivity in low endemic regions, and antibody tests are unable to distinguish between current and previous infections. Polymerase chain reaction (PCR) technologies for the detection of parasite DNA have been theoretically assumed to show high diagnostic sensitivity and specificity. However, the reported performance of PCR for detecting S. japonicum infection varied greatly among studies. Therefore, we performed a meta-analysis to evaluate the overall diagnostic performance of variable-temperature PCR technologies, based on stool or blood, for detecting S. japonicum infections in humans from endemic areas. Methods We searched literatures in eight electronic databases, published up to 20 January 2021. The heterogeneity and publication bias of included studies were assessed statistically. The risk of bias and applicability of each eligible study were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2). The bivariate mixed-effects model was applied to obtain the summary estimates of diagnostic performance. The hierarchical summary receiver operating characteristic (HSROC) curve was applied to visually display the results. Subgroup analyses and multivariate regression were performed to explore the source of heterogeneity. This research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered prospectively in PROSPERO (CRD42021233165). Results A total of 2791 papers were retrieved. After assessing for duplications and eligilibity a total of thirteen publications were retained for inclusion. These included eligible data from 4268 participants across sixteen studies. High heterogeneity existed among studies, but no publication bias was found. The pooled analyses of PCR data from all included studies resulted in a sensitivity of 0.91 (95% CI: 0.83 to 0.96), specificity of 0.85 (95% CI: 0.65 to 0.94), positive likelihood ratio of 5.90 (95% CI: 2.40 to 14.60), negative likelihood ratio of 0.10 (95% CI: 0.05 to 0.20) and a diagnostics odds ratio of 58 (95% CI: 19 to 179). Case-control studies showed significantly better performances for PCR diagnostics than cross-sectional studies. This was further evidenced by multivariate analyses. The four types of PCR approaches identified (conventional PCR, qPCR, Droplet digital PCR and nested PCR) differed significantly, with nested PCRs showing the best performance. Conclusions Variable-temperature PCR has a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas. More high quality studies on S. japonicum diagnostic techniques, especially in low endemic areas and for the detection of dual-sex and single-sex infections are required. These will likely need to optimise a nested PCR alongside a highly sensitive gene target. They will contribute to successfully monitoring endemic areas as they move towards the WHO 2030 targets, as well as ultimately helping areas to achieve these goals., Author summary Schistosoma japonicum is a parasite that can cause serious intestinal schistosomiasis. The infection is mainly diagnosed by parasitological and immunological methods, such as Kato-Katz test and indirect hemagglutination assay. However, both of these are not sensitive enough to accurately assess schistosomiasis elimination/eradication. PCR assays, detecting parasite DNA, are theoretically a highly suitable, sensitive and specific, alternative. However, reported performance varies greatly among studies. Therefore, we performed this meta-analysis (PROSPERO, registered No. CRD42021233165) to analyze and summarize the data from relevant studies of variable-temperature PCR for the diagnosis of S. japonicum infections, using stool or blood samples from humans in endemic areas. We retrieved a total of 13 eligible articles including data from 4268 participants across 16 studies. There was high heterogeneity among studies, but no publication bias was found. Analyses revealed that PCR techniques had a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas, with both high sensitivity and specificity. Further research on S. japonicum diagnostic techniques, especially in low endemicity areas and for detection of dual-sex and single-sex infections are required. These may be best using highly sensitive gene targets in nested PCR reactions.

Background Schistosomiasis, caused by Schistosoma japonicum, remains one of the most important parasitic diseases, and detection of S. japonicum infections in humans plays a crucial role in control and treatment. However, comparisons between the parasitological and the immunological examinations in the fields of China are lacking. Therefore we performed a meta-analysis to compare the seroprevalence of Schistosoma japonicum, as determined by IHA or ELISA, with coprological prevalence, as determined by Kato-Katz, and estimate the ratio of the serological to the egg-positive prevalence in order to evaluate the potential threat of egg-negative but worm-positive schistosomiasis. Methods Studies published up to July 2018 on the parasitological and immunological examinations of schistosomiasis in the fields of China were searched in five databases including CNKI, WanFang, VIP, PubMed and Web of Science. The ratio of the serological to the egg-positive prevalence and its 95%CI for each study were calculated, and then point estimates and their 95%CIs of pooled prevalence ratio were meta-analyzed. Subgroup meta-analyses were also performed according to potential influential factors. Results A total of 23 articles were included. The prevalence ratio varied from 0.57 to 48.83 for IHA to Kato-Katz and ranged from 0.38 to 13.97 for ELISA to Kato-Katz. The pooled ratio was 4.72 (95%CI: 3.87~ 5.76) for IHA to KK and 4.65 (95%CI: 3.50~ 6.17) for ELISA to KK. Subgroup analyses implied that the ratio of the serological to the egg-positive prevalence may decrease with the endemic levels. The highest prevalence ratio was observed when Kato-Katz was performed with three slides per stool or in hilly and mountainous regions. Conclusions The worm-determined prevalence by IHA or ELISA is 4- to 5-fold higher than the egg-determined prevalence by Kato-Katz, which implied Kato-Katz may largely underestimate the prevalence of S. japonicum in China. The degree of underestimation was greater when Kato-Katz with three slides per stool was carried out, especially in low endemic areas or in hilly and mountainous regions. Therefore, more attention should be paid to those egg-negative but worm-positive patients with the aim of final elimination of S. japonicum in China. Electronic supplementary material The online version of this article (10.1186/s12879-018-3320-5) contains supplementary material, which is available to authorized users.

Praziquantel (PZQ), the only choice of chemotherapy for schistosomiasis recommended by World Health Organization (WHO), has been widely used over 40 years. The long-term, and rapid expansion of, PZQ use for disease control across a large populations continues to raise concern regarding the potential for emergence and establishment of drug resistance. Recent research has also proposed that the long survival and low sensitivity of unpaired worms, derived from either incomplete treatment cure rates or single-sex schistosome infections within final hosts, could exacerbate the risk of PZQ resistance (PZQ-R) emerging. With the aim of assessing whether PZQ efficacy amongst S. japonicum may have changed over time in China, we performed a unique systematic review and meta-analyses on datasets which evaluated the efficacy of PZQ via laboratory assays of field S. japonicum isolates on experimental mice over time. Relevant published literatures from four electronic bibliographic databases and lists of article references were searched. Two indexes, d, a measure used in meta-analyses for worm burden difference between two groups, and r, a traditional measure for worm reduction percentage after treatment but without considering sample size were calculated for each study. A total of 25 papers including 127 experimental studies with eligible data on 2230 mice were retrieved. The pooled d (D) was 3.91 (3.56-4.25) and pooled r (R) was 54.52% (52.55%-56.52%). D significantly increased over time, whereas R non-significantly decreased; both estimates were significantly associated with the total drug dose. Such findings suggested no evidence of PZQ-R emergence S. japonicum to date. However, we consider the potential role of parasite origins, PZQ dosage, and single versus mixed gender infections of the results published to date, and the avenues now needed for further research.

Background Schistosomiasis japonica is a zoonotic parasitic disease. After nearly 70 years of control efforts in China, Schistosomiasis transmission has been reduced to a much lower level. The absence or near absence of infections in humans or livestock, based on traditional fecal and serological tests, has made the targets and priorities of future control efforts difficult to determine. However, detection of schistosome cercariae in waters using sentinel mice could be an alternative way of identifying remaining foci of infection, or even serve as a tool for evaluation of control efficacy. This method has been employed in China over last forty years. We therefore performed a meta-analysis of the relevant research to investigate if infections in sentinel mice mirror the ongoing trend of schistosomiasis transmission in China. Methods We conducted a meta-analysis of studies reporting infection rates of S. japonicum in sentinel mice in China before Sep 1, 2018 in accordance with the PRISMA guidelines. We retrieved all relative studies based on five databases (CNKI, WanFang, VIP, PubMed and Web of Science) and the reference lists of resulting articles. For each individual study, the infection rate in sentinel mice is presented together with its 95% confidence interval (CI). Point estimates of the overall infection rates and their 95% CIs were calculated. Subgroup analyses were performed according to study periods, seasons or regions. Results We identified 90 articles, including 290 studies covering eight endemic provinces. The overall rate in sentinel mice was 12.31% (95% CI: 10.14–14.65%) from 1980 to 2018. The value of 3.66% (95% CI: 2.62–4.85%) estimated in 2004 to 2018 was significantly lower than in 1980 to 2003 (22.96%, 95% CI: 19.25–26.89%). The estimate was significantly higher in the middle and lower reaches than in the upper reaches of the Yangtze River. The highest estimates were obtained in Hunan (30.11%, 95% CI: 25.64–34.77%) followed by Anhui (26.34%, 95% CI: 12.88–42.44%) and then Jiangxi (13.73%, 95% CI: 6.71–22.56%). Unlike the other provinces in the middle and lower reaches, no significant reduction was seen in Hubei after 2003. Even in Hubei two studies carried out after 2014 reported infections in sentinel mice, although no infected snails were reported across the province. Infections were most found in April (17.40%, 95% CI: 1.13–45.49%), July (24.98%, 95% CI: 15.64–35.62%) and October (17.08%, 95% CI 5.94–32.05%). High degrees of heterogeneity were observed. Conclusion This meta-analysis provides a comprehensive analysis of schistosome infection in sentinel mice across China. The estimates largely mirror the ongoing trends of transmission in terms of periods and regions. Infections were most likely to occur in April, July and October. In areas where no infected snails were reported infections in sentinel mice were still observed. Due to the presence of snails and infected wildlife, detection of schistosomes in waters using such a highly sensitive method as the deployment of sentinel mice, remains of importance in schistosomiasis monitoring. We would suggest the current criteria for transmission interruption or elimination of schistosomiasis in China be adjusted by integrating the results of sentinel mice based surveys., Author summary With the continued activities of the prevention and control programme in China, the prevalence and intensity of Schistosoma japonicum infection have been reduced to low levels. This makes it impossible to detect any infections in humans or livestock using the traditional approach of fecal and serological testing, so as to evaluate properly the risk map of infection. However, detection of existence of schistosome cercariae in waters could be an alternative way of detecting a potential focus of transmission. We therefore performed a meta-analysis of studies performed over the last 40 years to estimate the overall infection rates of S. japonicum in sentinel mice. The estimate across China in 2004 to 2018 was 3.66%, significantly lower than in 1980 to 2003. The highest estimates were observed in Hunan, followed by Anhui and Jiangxi. Two studies conducted in Hubei in 2015 and 2016 respectively, reported infected sentinel mice where no infected snails had been reported across the province since 2014. Transmission was found be most likely in April, July and October. The estimates largely mirror the ongoing trends of S. japonicum infections in terms of periods and regions. Due to the presence of snails and other infected wildlife, detection of schistosome cercariae in waters with a highly sensitive tool remains of great importance in schistosomiasis monitoring and evaluation. To the authors’ knowledge, this is the first time that the potential threat of S. japonicum in nature, to humans and livestock has been assessed in this manner. We would suggest that the current criteria for transmission interruption or elimination of S. japonicum in China be adjusted by integrating the results of sentinel mice.

Schistosomiasis is caused by the genus Schistosoma and affected more than 250 million people worldwide. Schistosoma japonicum was once seriously endemic in China and nearly 60 years of efforts has seen great success in disease control. However, due to its zoonotic nature and complex life cycle, the schistosomiasis transmission control and final elimination would require, besides an intersectoral approach, deep understanding of population genetics of the parasite. We therefore performed a snail survey in two marshland villages of Anhui province of China and collected S. japonicum cercariae from infected snails. By using the recent developed microsatellite panel comprising seven loci, we genotyped the sampled parasites and analyzed the population genetic diversity and structure. The results showed much lower infection prevalence of S. japonicum in snails and low infected snail density in either marshland village. Through population genetic analyses, a considerable genetic diversity of parasites was revealed, whereas a small number of clusters were inferred and the sign of bottleneck effect was detected in each village. For the first time in S. japonicum in two villages, we provided estimates of effective population sizes with two different approaches. The results indicated that the parasite in two villages could eventually be eradicated with the ongoing integral control measures, but with potential risk of reinvasion of immigrant parasites through the Yangtze River. Such would be of great importance in assessment of the effects of ongoing control measures and prediction of the transmission capability for S. japonicum, thus guiding decisions on the choice of further control work.

China once suffered greatly from schistosomiasis japonica, a major zoonotic disease. Nearly 70 years of multidisciplinary efforts have achieved great progress in disease control, with infections in both humans and bovines significantly reduced to very low levels. However, reaching for the target of complete interruption of transmission at the country level by 2030 still faces great challenges, with areas of ongoing endemicity and/or re-emergence within previously ‘eliminated’ regions. The objectives of this study were, by using meta-analytical methods, to estimate the overall prevalence of Schistosoma japonicum infections in abundant commensal rodent species in mainland China after the introduction of praziquantel for schistosomiasis treatment in humans and bovines in 1980s. In doing so we thereby aimed to further assess the role of wild rodents as potential reservoirs in ongoing schistosome transmission. Published studies on infection prevalence of S. japonicum in wild rodents in mainland China since 1980 were searched across five electronic bibliographic databases and lists of article references. Eligible studies were selected based on inclusion and exclusion criteria. Risks of within and across study biases, and the variations in prevalence estimates attributable to heterogeneities were assessed. The pooled infection prevalence and its 95% confidence intervals (CIs) were calculated with the Freeman-Tukey double arcsine transformation. We identified a total of 37 relevant articles involving 61 field studies which contained eligible data on 8,795 wild rodents across mainland China. The overall pooled infection prevalence was 3.86% (95% CI: 2.16–5.93%). No significant change in the overall pooled prevalence was observed between 1980–2003 (n = 23 studies) and 2004-current (n = 38 studies). However, whilst the estimated prevalence decreased over time in the marshland and lake regions, there was an apparent increase in prevalence within hilly and mountainous regions. Among seven provinces, a significant prevalence reduction was only seen in Jiangsu where most endemic settings are classified as the marshland and lakes. These estimates changed over season, ranging from 0.58% in spring to 22.39% in winter, in association with increases in rodent density. This study systematically analyzed S. japonicum infections in wild rodents from the published literature over the last forty years after the introduction of praziquantel for schistosomiasis treatment in humans and bovines in 1980s. Although numbers of schistosomiasis cases in humans and bovines have been greatly reduced, no such comparable overall change of infection prevalence in rodents was detected. Furthermore, there appeared to be an increase in S. japonicum prevalence in rodents over time within hilly and mountainous regions. Rodents have been projected to become the dominant wildlife in human-driven environments and the main reservoir of zoonotic diseases in general within tropical zones. Our findings thus suggest that it is now necessary to include monitoring and evaluation of potential schistosome infection within rodents, particularly in hilly and mountainous regions, if we are ever to reach the new 2030 elimination goals and to maximize the impact of future public, and indeed One Health, interventions across, regional, national and international scales., Author summary Consistent with the revised WHO Global Goals, China has set the target of complete interruption of transmission (elimination) of zoonotic Schistosoma japonicum by 2030 at the entire country level. Much remains to be known, however, regarding the complex multi-host disease dynamics of schistosomiasis. Multi-disciplinary disease control programs within China, including mass treatment with praziquantel for over 40 years, have successfully targeted human and bovine definitive hosts, significantly reducing infection prevalence to extremely low levels. However, S. japonicum has at least 40 species of potential definitive host reservoirs. Most notably, and perhaps most challenging in terms of targeted control, high prevalence of S. japonicum has been detected in rodent wildlife within recent years, particularly in hilly and mountainous regions of China. Molecular/phylogenetic studies have revealed matched S. japonicum genotypes indicative of shared transmission between rodents and humans. Similarly, mathematical models, incorporating parasitological and molecular data, have indicated that rodents may be sufficient to maintain ongoing transmission of schistosomiasis within some Chinese regions, most notably that of hilly and mountainous habitats. In order to help elucidate further the potential association between prevalence of S. japonicum in humans with rodent wildlife across China, and to assess whether this balance may be changing following the introduction of mass drug administration with praziquantel to humans (and bovines) in the 1980s, we performed a meta-analyses aimed to estimate the overall prevalence of S. japonicum infections in commensal species rodents in China over this period. Published studies on S. japonicum infections in wild rodents in China since 1980 were searched for across five electronic bibliographic databases, together with lists of cited articles. We identified a total of 37 relevant articles involving 61 studies with eligible data on 8795 rodents. The pooled prevalence level was 3.86% (95% CI: 2.16–5.93%). No significant change in overall pooled prevalence levels within rodents was observed between 1980–2003 and 2004-current, despite the integrated control strategies performed across China within the latter period. However, whilst the prevalence estimates did decrease within marshland and lake regions since 2004, in the hilly and mountainous regions, in contrast, there was a significant increase in the rodent infection prevalence. The estimate increased from the smallest 0.58% in spring to the highest 22.39% in winter. It also increased with the density of rodents. Therefore, we suggest that future systematic monitoring of schistosome infection levels within potential wildlife reservoirs, particularly within hilly and mountainous regions within China and/or areas aiming for verification of interruption of transmission, should be incorporated in order to reliably evaluate impact, risk and ultimately help ensure the sustainability of elimination interventions across, regional, national and international scales.

Schistosomiasis remains one of the world’s most significant neglected tropical diseases, second only to malaria in terms of socioeconomic impact. In 2014, China proposed the goal of schistosomiasis japonicum elimination by 2025. However, one major challenge is the widely distributed, and in certain cases potentially increasing, habitats of Oncomelania hupensis, the snail intermediate hosts of S. japonicum. Therefore, an understanding of population genetics of O. hupensis in new or re-emerged habitats, together with that of the established habitats with snail persistence, would be valuable in controlling and predicting the future transmission dynamics of schistosomiasis in China. Using nine microsatellite loci, we conducted population genetic analyses of snails sampled from one habitat where snails were detected for the first time, one (previously eliminated) habitat with re-emerged snails, and one habitat with established snail persistence. Results showed lower diversities, in terms of number of observed alleles per locus (Na), number of effective alleles per locus (NeA), observed (Ho) and expected heterozygosity (He), in snails from new or re-emerged snail habitats than from the habitat with snail persistence. The smallest effective population size was inferred in the re-emerged snail habitat, but the largest was in the new habitat rather than in the habitat with snail persistence. No bottleneck effects were detected in new or re-merged habitats. No or low sub-structure was inferred in new and persistent snail habitats. Snails from the three sites were clearly separated and low gene flow was estimated between sites. We propose that snails at the new habitat may have been introduced through immigration, whereas snails at the re-emerged habitat may be the consequence of those few snails remaining subsequently expanding through reproduction. We discuss our results in terms of their theoretical and applied implications.

PROSPERO (CRD42017067941): A meta-analysis of the ratio of seroprevalence to egg-positive prevalence of Schistosoma japonicum in China. (PDF 117 kb)

Background Toxoplasmosis is caused by Toxoplasma gondii which can infect all warm-blooded animals. As the most common feline definitive host, cats play a vital role in the transmission of T. gondii. However, national estimates of the seroprevalence of T. gondii in cats in mainland China are lacking, and therefore a systematic review and meta-analysis were performed to provide insight into national environmental transmission levels and potential transmission to humans. Methods Studies published up until July 1, 2016, on T. gondii seroprevalence in cats within mainland China were searched for in CNKI, WanFang, CBM, PubMed, Embase and through the reference lists of resulting articles. The seroprevalence with its 95% confidence interval (CI) for each individual study was presented, and then point estimates and their 95% confidence intervals (CIs) of pooled seroprevalence were calculated. Subgroup analyses were performed according to potential risk factors. Results A total of 38 eligible studies, published between 1995 to 2016, covering fifteen provinces and municipalities, and involving 7,285 cats, were included. The seroprevalence in cats per study ranged from 3.9 to 79.4% with a median of 20.3%. As substantial heterogeneity existed among studies, a random-effects model was used to estimate the pooled seroprevalence. The value of the point estimate seroprevalence was 24.5% (95% CI: 20.1–29.0). Seroprevalence in stray cats was significantly higher than in pet cats (OR = 3.00, 95% CI: 1.60–5.64). The seroprevalence increased significantly with cat age (P = 0.018) with 17.4% (95% CI: 7.6–27.2) in the group of ≤ 1 year old, 19.5% (95% CI: 12.7–26.3) in the group of ≤ 3 year-old and 31.6% (95% CI: 22.9–40.3) in the group of > 3 year-old. Conclusions The seroprevalence of T. gondii in cats in mainland China was moderate and was associated with cat ownership and age. Due to the increasing prevalence of pet cats in China and the intimate relationship between these cats and humans, this might present a significant exposure risk, particularly for China’s large susceptible population. Therefore, further research is needed into the links between cat ownership and human T. gondii infection and how to reduce T. gondii exposure in humans via cat contacts and the environmental contamination with T. gondii oocysts by cats. Electronic supplementary material The online version of this article (doi:10.1186/s13071-017-1970-6) contains supplementary material, which is available to authorized users.

Schistosomiasis japonicum is one of the most serious communicable diseases, and the transmission of the parasite is dependent of its complex life cycle on which many factors can have an impact. Multiple infections comprising both male and female schistosome within snail intermediate hosts, for example, would facilitate parasite transmission. However, no research on Schistosoma japonicum communities in field-collected Oncomelania hupensis hupensis in relation to schistosome sex has been reported. Therefore, snail survey was performed in a hilly region of Anhui, China, and single- or mixed-sex schistosome infections of snails were detected with final host mouse infection. A total of 8,563 snails were sampled in the field, and 67 were identified with schistosome infections. Of these infected snails, 46 were selected for final host infection. From this, 21 snails were infected with female schistosome, 23 with males and 2 with both males and females. More worms were recovered for snails with mixed-sex infections than with single-sex infection and for snails with male schistosome infection than with female infection (P

About 46 mammal species have been suspected as reservoir hosts for Schistosoma japonicum and therefore the track of the target parasites, in relation to definitive host species, may be of great importance in terms of theoretical and practical implications. The circadian rhythm of cercariae emergence, a genetically controlled behavior for parasites to adapt to their definitive hosts, may seem to be a perfect biological marker for S. japonicum. In this study, a late (or nocturnal) cercarial emergence pattern was observed on the parasites from one hilly region in Anhui of China, where rodents serve as reservoirs, and on the first generation of the parasites. Moreover, by using the circular statistics, the homogeneity of parasites in such trait was also demonstrated. All these provide evidence for the genetically controlled biological trait, which seems essential in the investigation of macro- or micro-dynamics of parasite transmission of interest. This is particularly true in the case of S. japonicum when multiple parasite isolates or strains are more likely to exist.

Toxoplasmosis, caused by Toxoplasma gondii, is one of the most common zoonosis in the world, and can cause severe adverse consequences in pregnant women and immunosuppressed people. Throughout the world dogs are popular companion animals, however they are also important intermediate host of T. gondii and may play an instrumental role in mechanically transmitting Toxoplasma infection to humans. Therefore, an assessment of the level of T. gondii infection in pet dogs is of public health importance. To estimate the overall serological prevalence of toxoplasmosis in pet dogs in mainland China, we performed a meta-analysis using five bibliographic databases: CNKI, WanFang, VIP Chinese Journal Databases, PubMed and Google Scholar. A total of 60 articles, including data on 78719 pet dogs, published between 1998 and 2016 fulfilled the final eligibility criteria. The overall seroprevalence of T. gondii infection in pet dogs was 11.1% (95% CI: 10.1% to 12.1%). The seroprevalence of toxoplasmosis in >one-year-old dogs was 1.59 times more than that in ≤one-year-old group (RR=1.59, 95%CI=1.15, 2.21). There was no significant difference observed in pooled seroprevalence between male and female dogs (RR=1.02, 95%CI=0.91, 1.16). In terms of geographical regions, the lowest seroprevalence of toxoplasmosis infection (5.8%) was in North China and the highest (16.8%) was in Southwest of China. Results from this study showed that toxoplasmosis is common in pet dogs in mainland China, indicating that control measures by owners may reduce human exposure to T. gondii via dog contacts.

More sensitive methods for diagnosing infection with Schistosoma japonicum are needed as control becomes more effective. We compared a real-time polymerase chain reaction (PCR) for stool samples with conventional diagnostic methods in a study of 1,727 persons from Anhui Province, China. Seroprevalence determined by using an indirect hemagglutination assay (IHA) was much higher (26.1%) than the prevalence in stool-based tests, which were 5.3%, 3.2%, and 3.0% for PCR, hatching test, and Kato-Katz thick smear, respectively. A large proportion of the positive stool samples were only positive in one or two tests. The PCR showed better agreement with IHA than the other two stool-based tests. A commonly used diagnostic algorithm with initial screening for antibodies and subsequent testing with the Kato-Katz thick smear of the seropositive results would have resulted in treatment of 22 people compared with 50 people if the PCR replaced the Kato-Katz thick smear. As prevalence and intensity decrease, the benefit of increased sensitivity using the PCR must be weighed against additional costs.

Schistosoma japonicum, a parasite of significant public health importance in parts of China and Southeast Asia, is a true generalist pathogen with over 40 species of mammals suspected as definitive host reservoirs. In order to characterize levels of parasite gene flow across host species and identify the most important zoonotic reservoirs, S. japonicum larvae (miracidia) were sampled from a range of definitive host species in two contrasting habitat types within Anhui Province, China: a low-lying marshland region, and a hilly region, where animal reservoir populations may be predicted to differ substantially. Miracidia samples were genotyped using seven multiplexed microsatellite markers. Hierarchical F-statistics and clustering analyses revealed substantial geographical structuring of S. japonicum populations within Anhui, with strong parasite genetic differentiation between habitat types. Within most villages, there was very little or no parasite genetic differentiation among host species, suggesting frequent S. japonicum gene flow, and thus also transmission, across species. Moreover, the data provide novel molecular evidence that rodents and dogs are potentially very important infection reservoirs in hilly regions, in contrast to bovines in the marshland regions. The parasite genetic differentiation between habitat types might therefore be associated with contrasting host reservoirs. The high levels of parasite gene flow observed across host species in sympatric areas have important implications for S. japonicum control, particularly in hilly regions where control of infection among wild rodent populations could be challenging.

Schistosome japonicum remains one main public concern in China. This is exemplified in the hilly region in Anhui Province, where rodents have served as reservoirs for the parasite and no effective intervention could target such wild animals. The closer relationship between the hilly region and the near marshland induces the worry of spread of the hill parasite to the marshland region. Therefore, the level of snail-parasite compatibility between the hill parasite and snail populations from the Yangtze River valley was investigated. The results of this study demonstrated that both the hill (Shitai, Anhui) and the marshland (Wuxi, Jiangsu) strains of parasite were more infective to the marshland strains of snail (Zongyang and Hexian, Anhui) than to the hill strain of snail (Shitai, Anhui). When snails were individually exposed to one single miracidium, the longest prepatent period for cercarial development was observed in the combination of Shitai schistosome/Shitai snail. A nocturnal cercarial emergence pattern was observed for the hill parasite, either harbored in the hill or the marshland strain of snails. The results suggested a high compatibility between the marshland strains of snail and both the hill and the marshland strains of parasite. This would have practical implications. Moreover, the fact of the lower compatible relationship between the hill parasite and its local intermediate hosts warranted more studies.

SUMMARYSchistosoma japonicum remains highly endemic in many counties in China and has recently re-emerged, to a large extent, in previously controlled areas. To test the hypothesis that small rodents and less agriculturally important domestic animals such as dogs and cats may play an important role in the transmission and potential re-emergence of this disease, an annual investigation of S. japonicum among humans, domestic animals and rodents, combined with detailed surveys of the snail intermediate host, was performed across 3 marshland villages and 3 hilly villages in Anhui province of China over 2 consecutive years. The highest infection prevalence and intensity observed across all mammals was in rodents in the hilly region; while in the marshland, bovines were suspected as the main reservoirs. However, relatively high infection prevalence levels were also found in dogs and cats in both regions. Such results may have implications for the current human- and bovine-oriented control policy for this medically and veterinarily important disease, particularly within the hilly regions of mainland China.

Background The endemic countries are in a diagnostic dilemma concerning Schistosoma japonicum with increasing difficulties in diagnosing the infected individuals. The formol-ethyl acetate sedimentation concentration technique is preferred by many clinical microbiology laboratories for the detection of parasites in stool samples. It is potentially more sensitive than the diagnostic methods traditionally used. Methodology/Principal Findings We evaluated the technique for detection of low-intensity S. japonicum infections in 106 stool samples from China and used a commercial kit, Parasep Midi Faecal Parasite Concentrator. One stool sample and one serum sample were collected from each person. As reference standard we used persons positive by indirect hemagglutination in serum and positive by Kato-Katz thick smear microscopy (three slides from a single stool), and/or the hatching test. We found the sedimentation technique to have a sensitivity of only 28.6% and specificity of 97.4%. Conclusion/Significance This study indicates that the sedimentation technique has little to offer in the diagnosis of low-intensity S. japonicum infections, at least when only a single stool sample is examined., Author Summary Schistosoma japonicum is parasitic fluke (worm) found in China, Indonesia and the Philippines. A lot of effort has been put into combating the parasite, and the result has been a large drop in the number of infected people over the last decades. The average infected person also now has few worms, and hence excretes few eggs in stool. This has made it increasingly difficult to get a correct diagnosis by the diagnostic tests traditionally used. Tests based on detecting eggs in stool can be false-negative and tests detecting antibodies can be false-positive due to persisting antibodies or antibodies from other worm infections. Hence there is a need for new diagnostic strategies. Formol-ethyl acetate sedimentation concentration is a technique for detecting eggs in stool by microscopy, but has not to our knowledge been evaluated for S. japonicum. We compared the technique, using a single stool sample and a commercial preparation kit, with three tests traditionally used in the endemic countries (Kato-Katz thick smear, hatching test and indirect hemagglutination antibody detection). The sedimentation technique detected disappointing few positives and seems not to be an advantage in the diagnosis of low-intensity S. japonicum infection, compared to the traditionally used tests.

Background Schistosoma japonicum, which remains a major public health problem in the Philippines and mainland China, is the only schistosome species for which zoonotic transmission is considered important. While bovines are suspected as the main zoonotic reservoir in parts of China, the relative contributions of various non-human mammals to S. japonicum transmission in the Philippines remain to be determined. We examined the population genetics of S. japonicum in the Philippines in order to elucidate transmission patterns across host species and geographic areas. Methodology/Principal Findings S. japonicum miracidia (hatched from eggs within fecal samples) from humans, dogs, pigs and rats, and cercariae shed from snail-intermediate hosts, were collected across two geographic areas of Samar Province. Individual isolates were then genotyped using seven multiplexed microsatellite loci. Wright's FST values and phylogenetic trees calculated for parasite populations suggest a high frequency of parasite gene-flow across definitive host species, particularly between dogs and humans. Parasite genetic differentiation between areas was not evident at the definitive host level, possibly suggesting frequent import and export of infections between villages, although there was some evidence of geographic structuring at the snail–intermediate host level. Conclusions/Significance These results suggest very high levels of transmission across host species, and indicate that the role of dogs should be considered when planning control programs. Furthermore, a regional approach to treatment programs is recommended where human migration is extensive., Author Summary Schistosomiasis is a disease caused by parasitic worms known as schistosomes, which infect about 200 million people worldwide. In the Philippines, as in China, the species of schistosome (Schistosoma japonicum) which causes the disease infects not only humans, but also many other species of mammals. In China, bovines are thought to be particularly important for harboring and transmitting S. japonicum, whereas in the Philippines infections in bovines are relatively rare. However, dogs, rats and pigs are often infected with S. japonicum in the Philippines, although the extent to which infections in these animals may give rise to human infections is unclear. To help answer this question, we characterized the genetic variation of the parasite in Samar province of the Philippines, and found that S. japonicum samples from humans, dogs, rats and pigs were genetically very similar, with no significant genetic difference between samples from humans and dogs. This suggests that in the Philippines this parasite is frequently transmitted between different mammalian species, particularly between dogs and humans. Reducing levels of infections in dogs may therefore help to reduce infections in humans. The results also suggest high levels of transmission between geographic areas, thus regional co-ordination of treatment programs is recommended.

Schistosomiasis, caused by trematode blood flukes of the genus Schistosoma, is the second most prevalent disease after malaria in the tropical and subtropical world. Among five schistosome species, Schistosoma japonicum is the most serious, mainly because of its high egg output [1]. This parasite is mainly endemic in mainland China, the Philippines, and Indonesia. Advanced schistosomiasis, due to either an infection without chemotherapy or repeated infections over time, is the most serious form of schistosomiasis and is usually characterized by periportal liver fibrosis, spleen enlargement and congestion, portal hypertension, and other serious consequences [2]. The suffering for an advanced patient caused by schistosomes could last for a lifetime, as the associated pathological changes on the host, if not properly treated, could develop toward a more serious condition. In addition, S. japonicum in humans has been estimated to be able to live for an average of 4.5 years [3]. Prolonged survival of the parasite to as long as about 47 years has been seen in an American who emigrated from the Philippines and continued to show active eggs in rectal biopsies [4]. These eggs can continue to produce damages to organs where they are deposited. Therefore, the treatment of the disease usually includes both anti-schistosome treatment and symptomatic therapy. The former is based on fecal examinations and serological tests, which are usually negative in most cases [5], or endoscopic examination. The etiological treatment is comparatively easier when without any serious complication, and therefore, much more attention and financial aids are going to the latter. In the Zhejiang province of China for example, in 2003 there remained 1,187 advanced cases who still needed medical assistance, although the disease there had been interrupted a decade ago [6]. Such a looming problem has been suggested to exist for perhaps as long as another half century in China [7]. Fortunately, with the economic development and well-improved standards of living over the last decades in China, in 2004 the government of China redefined schistosomiasis control, together with the control of HIV/AIDS and tuberculosis, as one of its highest priorities in communicable disease control [8]. As one main part of the integrated control measures, the project for treatment of advanced schistosomiasis has been initiated across the endemic regions of China. Box 1 lists a series of regulations on that aspect made by the government. The main point of this is that a screening system for advanced schistosomiasis among local residents will be set up in each endemic county and, if a farmer is diagnosed with advanced schistosomiasis (see Box 2 for the diagnosis criteria), the involved medical expense will be mostly covered by different levels of government. Figure 1 shows the numbers of advanced cases and newly found cases in each province and, as the consequence of the project, the increasingly rising coverage rate of advanced cases [9]. The direct or long-term estimated benefit from this project, as estimated by the work [10], would be quite considerable. Here we presented a case observed in a nonendemic area within the Anhui Province of China to point out the demerit of the ongoing project and raise some aspects yet to improve. This follow-up investigation was approved by an ethics committee in both the Anhui Institute of Parasitic Diseases and Soochow University. A consent form was obtained from the patient, and she gave consent to have her case details published. Open in a separate window Figure 1 Numbers of advanced schistosomiasis japonica in China. (A) In each province by 2008; (B) in each province by 2003 and new cases found from 2004 to 2008; and (C) the coverage rates of the aid-project in the cases at the levels of nation or province (Anhui) over 2004 to 2008.

Meta-analyses on the seroprevalence of T. gondii in cats adjusted with sensitivity and specificity of each test. (DOC 188Â kb)

Background Schistosomiasis japonica remains a major public health problem in China. Integrating molecular analyses, such as population genetic analyses, of the parasite into the on-going surveillance programs is helpful in exploring the factors causing the persistence and/or spread of Schistosoma japonicum. However, genotyping errors can seriously affect the results of such studies, unless accounted for in the analyses. Methods We assessed the genotyping errors (missing alleles or false alleles) of seven S. japonicum microsatellites, using a pedigree data approach for schistosome miracidia, which were stored on Whatman FTA cards. Results Among 107 schistosome miracidia successfully genotyped, resulting in a total of 715 loci calls, a total of 31 genotyping errors were observed with 25.2 % of the miracidia having at least one error. The error rate per locus differed among loci, which ranged from 0 to 9.8 %, with the mean error rate 4.3 % over loci. With the parentage analysis software Cervus, the assignment power with these seven markers was estimated to be 89.5 % for one parent and 99.9 % for a parent pair. One locus was inferred to have a high number of null alleles and a second with a high mistyping rate. Conclusion To the authors’ knowledge, this is the first time that S. japonicum pedigrees have been used in an assessment of genotyping errors of microsatellite markers. The observed locus-specific error rate will benefit downstream epidemiological or ecological analyses of S. japonicum with the markers. Electronic supplementary material The online version of this article (doi:10.1186/s13071-015-1074-0) contains supplementary material, which is available to authorized users.

Meta-analyses on the seroprevalence of T. gondii in cats adjusted with sensitivity and specificity of each test. (DOC 188Â kb)