Guanling Wu

Epidemiology of Schistosomiasis in the People’s Republic of China, 2004

Although the number of human infections decreased, human prevalence increased from 4.9% in 1995 to 5.1% in 2004.

Double-Blind Placebo-Controlled Study of Concurrent Administration of Albendazole and Praziquantel in Schoolchildren with Schistosomiasis and Geohelminths

A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in>1500 children with high prevalences of geohelminths and schistosomiasis. The study sites were in China and the Philippines, including 2 strains of Schistosoma japonicum, and 2 different regions of Kenya, 1 each with endemic Schistosoma mansoni or Schistosoma haematobium. Neither medication affected the cure rate of the other. There was no difference between the side effect rate from albendazole or the double placebo. Praziquantel-treated children had more nausea, abdominal pain, and headache but these side effects were statistically more common in children with schistosomiasis, suggesting a strong influence of dying parasites. The subjects were followed for 6 months for changes in infection status, growth parameters, hemoglobin, and schistosomiasis morbidity. In all 4 sites, a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel, strongly supporting population-based mass treatment.

Association between IgE antibody against soluble egg antigen and resistance to reinfection with Schistosoma japonicum.

There is evidence that immunoglobulin (Ig) E antibody may be a critical component of protective immunity against Schistosoma mansoni and S. haematobium reinfection. In the present study, 555 individuals aged 3-67 years infected with S.japonicum received praziquantel treatment before the transmission season commenced; 45 d later, blood samples from 265 individuals who had no S. japonicum egg in their stool were examined by enzyme-linked immunosorbent assay for specific isotypic antibodies. Single, non-conditional logistic regression analysis showed that exposure intensity, age, soluble egg antigen (SEA)-IgE, SEA-IgM and soluble adult worm antigen-IgG4 were relevant to reinfection; multiple, non-conditional logistic regression analysis showed that exposure intensity was still a significant factor for reinfection while the SEA-IgE antibody level was associated with resistance to reinfection with S. japonicum, with a protective index of 2.00. It is suggested that this population in an area endemic for schistosomiasis japonica exhibits acquired immunity.

Morbidity due to schistosomiasis japonica in the People's Republic of China

Transmission and morbidity induced by Schistosoma japonicum were evaluated in 825 individuals undergoing periodic treatment with praziquantel on Jishan island, Jiangxi Providence, in the Peoples Republic of China. Eggs of S. japonicum were found in the stools of 39.4% of the population; 70% of those infected were less than 20 years of age. Hepatomegaly greater than 3 cm in the midsternal line was detected by physical examination and ultrasonography in 75% and 90% of individuals, respectively, regardless of infection status. Symmers clay pipe-stem fibrosis of the liver was detected by ultrasonography in 20% of all individuals. Hepatitis B surface antigen and antibody to hepatitis C were found in 11% and less than 1% of the population, respectively. Our study suggests that, despite intermittent chemotherapy, morbidity due to S. japonicum is still a significant problem in China.

Schistosomiasis japonica on Jishan Island, Jiangxi Province, People's Republic of China: persistence of hepatic fibrosis after reduction of the prevalence of infection with age

Hepatic fibrosis due to schistosomiasis japonica was examined by ultrasonography in a cross-sectional community study of 825 individuals on Jishan Island, Jiangxi Province, China. The prevalence of active infection was 39.4% with peak infection in the 10-19.9 years age group followed by a significant decline. A similar pattern was observed for intensity of infection. The prevalence of hepatomegaly in the midsternal line > or = 6 cm peaked at 60% in the fourth decade and remained elevated. A progressive increase in the severity of hepatic periportal fibrosis was observed with age, with advanced fibrosis peaking in the fifth decade. The proportion of individuals with advanced fibrosis was significantly greater in males than in females despite equivalent prevalence and intensity of schistosome infection. In addition, a positive association (P < 0.01) was found between periportal fibrosis and both hepatomegaly > or = 6 cm and splenomegaly. This study suggests that the natural history of schistosomiasis japonica in this hyperendemic community in China is marked by persistence of hepatomegaly and schistosome-induced periportal fibrosis in adults despite a decrease in the prevalence of infection.

Application of DNA-based diagnostics in detection of schistosomal DNA in early infection and after drug treatment

BackgroundResearch is now focused on identification of sensitive and specific diagnostic tests for early identification of schistosomal infection and evaluation of chemotherapy in field situations in China.ResultsThis study compared loop-mediated isothermal amplification (LAMP) with conventional PCR as DNA-based diagnostic techniques for the early detection of schistosomal DNA and the evaluation of chemotherapy. The results showed that both PCR and LAMP assays targeting a 301 base pair (bp) sequence of the highly repetitive retrotransposon, SjR2, amplified DNA from schistosomes but were unable to distinguish between schistosome species. LAMP and conventional PCR were shown to amplify the target sequence of the SjR2-pCR2.1 recombinant plasmid template with limits of detection of 10-4 ng and 10-2 ng, respectively, thus demonstrating the superior sensitivity of the LAMP method. Schistosoma japonicum DNA was detected in all serum samples obtained from the three experimental groups at 1 week post-infection by LAMP assay, while the rate of detection by conventional PCR ranged from 50% to 66%. The potential application of PCR and LAMP assays for the evaluation of artesunate and praziquantel chemotherapy was investigated. PCR was shown to be less sensitive for detection of schistosomal DNA in drug-treated rabbit sera than the LAMP method.ConclusionsThe data presented here indicate that LAMP is suitable for the detection of early infection in the groups primarily infected with Schistosoma japonicum, such as migrants, travellers, military personnel and the younger age groups. However, it is less suitable for evaluation of the efficacy of chemotherapy in the early stages because of its high sensitivity.

Immune Events Associated with High Level Protection against Schistosoma japonicum Infection in Pigs Immunized with UV-Attenuated Cercariae

Background The vaccination of radiation-attenuated Schistosoma japonicum cercariae can induce effective protection in artiodactyl, but the immune events related to protective immunity are not fully understood. To provide a paradigm for a human recombinant antigen vaccine, we have undertaken a vaccination and challenge experiment in pigs, which was recognized as an appropriate animal model in this type of study because of their similarity to human in immunology, and investigated the relative immune events induced by the radiation-attenuated S. japonicum cercariae. Methods and Findings We found that pigs immunized once with 400 µw UV-irradiated cercariae exhibited 63.84% and 71.82% reductions in worm burden and hepatic eggs respectively. Protective immunity in vaccinated pigs was associated with high level productions of IgM, total IgG, IgG1 and IgG2; IgG2 was significantly increased in the acute infection. IFN-γ levels could be elicited by immunization. At week 6 post-infection, IFN-γ, IL-4 and IL-10 levels also showed a dramatic rise synchronously in vaccinated pigs. Moreover, the granzyme b, nk-lysin, ifnγ, il4 and il10 mRNA levels in early skin-draining lymph nodes of immunized pigs were higher than those in pigs with non-irradiated cercariae infection. In addition, cytotoxicity-related genes in the mesenteric lymph nodes were significantly upregulated in vaccinated pigs in the acute infection. Conclusion/Significance Our results demonstrated that IFN-γ and IgG2 antibody production, as well as genes related to cytotoxicity are associated with the high level protection induced by UV-irradiated Schistosoma japonicum vaccine. These findings indicated that optimal vaccination against S. japonicum required the induction of IFN-γ, IgG2 antibody related to Th1 responses and cytotoxicity effect.

Multiple vaccinations with UV- attenuated cercariae in pig enhance protective immunity against Schistosoma japonicum infection as compared to single vaccination

BackgroundSchistosomiasis japonica is a major public health problem in the endemic areas of China, the Philippines, and Indonesia. To date, a vaccine has not been developed against this disease but immunization with UV-attenuated cercariae can induce a high level of protective immunity in Landrace/Yorkshire/Duroc crossbred pigs. To compare the efficacy of a single vaccination and multiple vaccinations with UV-attenuated Schistosoma japonicum cercariae, two groups of pigs received either one or three exposures to 10,000 cercariae attenuated with 400 μw UV.ResultsPigs with a single immunization had a 59.33% reduction in adult worm burden, a 89.87% reduction in hepatic eggs and a 86.27% reduction in fecal eggs at eight weeks post-challenge (P < 0.01). After three immunizations, protection increased to 77.62%, 88.8% and 99.78% reduction in adult worms, hepatic eggs and fecal eggs, respectively (P < 0.01). Humoral and cellular immunological parameters measured indicated that schistosome-specific IgG1 and IgG2 levels in the vaccinated groups were higher than in the infection-control group. Triple vaccinations resulted in higher levels of antibodies, especially IgG2, compared with a single vaccination and IFN-γ levels increased with repeated immunization with UV-irradiated cercariae.ConclusionThe high levels of protection against S. japonicum infection can be achieved with a UV-attenuated vaccine in pigs, and that three vaccinations were possibly more effective than a single vaccination. Moreover, triple vaccinations evoked a more vigorous IFN-γ response and a stronger antibody-mediated response, especially an increase in the levels of IgG2 antibodies.

Toll‐like receptor (TLR) 2 and TLR4 deficiencies exert differential in vivo effects against Schistosoma japonicum

Little is known about the functions of Toll‐like receptor 2 (TLR2) and TLR4 in innate/acquired responses to Schistosoma japonicum. Through in vivo study, the contributions of TLR2 and TLR4 to host immune responses during S. japonicum infection were investigated. Early infection experiments showed higher protein and mRNA levels of IL‐12, IFN‐γ and IL‐4 in dermal tissues and retroauricular draining lymph nodes respectively in TLR2−/− mice on day four post‐infection and opposite changes in TLR4−/− mice. In the acute infection with S. japonicum for 6 weeks, TLR2−/− mice manifested lower egg burden as well as the enhancement of T cell activation and upregulated expression of some cytotoxic genes, as assayed by Th1/Th2 cytokine secretion and DNA microarray analysis. Also, the opposite parasitological and immunological effects were observed in TLR4−/− mice. These results demonstrate that during S. japonicum infection, TLR2 and TLR4 might direct distinct adaptive immune responses since the early stage, which may lead to different infection outcomes.

Evaluation of IgG-ELISA for the diagnosis of Schistosoma japonicum in a high prevalence low intensity endemic area of China.

Antibody-based diagnostic methods for detecting infection with Schistosoma japonicum have been developed and integrated into the national control program in China; however, the utility of these methods compared with conventional coprological methods remains unclear. In two consecutive years, we compared the performance characteristics of Kato-Katz with a commercially available enzyme-linked immunosorbent assay (ELISA) that detects anti-egg antigen IgG antibodies in a high prevalence, low intensity village in China (1025 subjects in 2005 and 652 subjects in 2006). In comparison with Kato-Katz based on duplicate stool specimens, each read in triplicate, the sensitivity of IgG-ELISA was high, ranging from 79.3% to 87.4% but with a relatively low specificity of 38.9% to 53.5%. The positive predictive value ranged from 20.8% to 24.6% while the negative predictive value ranged from 93.1% to 94.4%. When analyzed as continuous variables, there was a poor correlation between EPG (eggs per gram feces) and antibody level in both years (r(2005)=0.23 and r(2006)=0.41). We detected a trend toward reduced sensitivity at lower infection intensity as measured by Kato-Katz in 2005 (P=0.262) and 2006 (P=0.287). We evaluated changes in antibody levels and the prevalence of positive antibody in the cohort of subjects examined in both 2005 and 2006 (n=565). The prevalence of positive antibody but not the continuous antibody level, decreased in individuals who were uninfected at both time points or who transitioned from infected to uninfected as assessed by Kato-Katz. In this cohort, the distribution of antibody levels measured in 2006 among individuals who were positive by Kato-Katz in 2006 broadly overlapped with the distribution of antibody levels in individuals who were negative by Kato-Katz in both 2005 and 2006. Our results indicate fairly poor performance characteristics of the anti-egg antigen IgG-ELISA for the detection of active infection with S. japonicum in our community based sample and are in contrast with other reports based on more selected populations. The high prevalence but low intensity of S. japonicum in our study community reflects the evolving epidemiology of schistosomiasis in communities receiving intermittent treatment with praziquantel in China. We suggest marked caution in implementing anti-egg antigen IgG-ELISA based diagnosis for either individual level diagnosis or population-based targeting for national control programs.