We studied a community cohort of 193 individuals exposed to endemic Schistosoma japonicum infection in the Dongting Lake region of China to assess subclinical morbidity and the 2-year benefit of curative therapy (praziquantel) administered in 1996. Prevalence and intensity of S. juponicum infection before treatment were 28% and 192 eggs per gram faeces (epg), respectively. Two years after cure, 22% of the cohort were reinfected, but with a lighter intensity (67 epg). Sixty-four subjects (37%) showed significant improvement in ultrasound parenchyma images after treatment and 5 1 subjects (54%) showed significant improvement of periportal fibrosis, Left-lobe enlargement also reversed (P < 0.05) and splenomegaly reversed in 6 of 8 cases and developed in only I. Two years post-treatment a dilated portal vein became less frequent, but the decline was not significant (16% vs 1 1 %, P > 0.05). The serum levels of laminin and collagen IV associated with reinfection and intensity and hyaluronic acid levels correlated with ultrasound findings (P < 0.01). Overall, treatment induced a marked decrease in subclinical hepatosplenic morbidity attributable to S. japonicum although low-intensity re-infection after treatment remained relatively frequent. Stratified analysis and logistic models evaluated potential confounding factors for assessment of treatment effects on hepatic fibrosis. S. juponicum infection and moderate-heavy alcohol intake interacted: improvement in parenchymal morbidity was impeded among drinkers (P < 0.05). Chemotherapy focused on at-risk residents controls prevalent subclinical hepatic fibrosis but re-infection indicates the need for complementary control strategies.
We report the 5-year impact (1996)(1997)(1998)(1999)(2000)(2001) of repeated praziquantel chemotherapy on subclinical morbidity related to Schistosoma japonicum infection. We repeated stool examinations and hepatosplenic ultrasonography in a cohort of 120 individuals living on an island with endemic infection in Dongting Lake, China. Prevalence of schistosome infection fell by 43% and intensity (geometric mean eggs per gram) declined by 80% over the 5 years. However, transmission persisted at a dangerously high rate of 13% per year for re-infection or new infection in the cohort. The prevalence of left-lobe enlargement and dilated portal vein fell significantly (P < 0.01) to about half initial levels although a few patients progressed during the study period. At study endpoint, infection was nearly twice as common if the portal vein was dilated (23% versus 13%, respectively), but this association was not statistically significant (P > 0.05). However, endpoint infection was even more strongly associated with left-lobe enlargement (57% versus 15%, P < 0.01). The proportions of subjects with improved parenchymal and periportal tibrosis were much higher than the proportions of subjects that progressed (P < 0.05). Reduction of prevalence and intensity of infection, and improvement of subclinical morbidity, were benefits of repeated treatments. Further research is needed to understand why some patients developed fibrosis despite substantial reductions in egg counts and to evaluate the functional importance of residual subclinical morbidity after chemotherapy-based control in the lake and marshland area of China.
This study conducted in 1999/2000 was designed to evaluate the efficacy of praziquantel against Schistosoma japonicum in an area with repeated chemotherapy (Area A) compared with a newly identified endemic focus (Area B) in Hunan Province, China. The population size was 2015 and 2180 in Areas A and B, respectively, of which 1129 and 1298 subjects received stool examination. A total of 230 subjects were identified by the Kato-Katz technique (4 smears per person) as being infected with S. japonicum, 124 in Area A (prevalence 11%) and 106 in Area B (prevalence 8.2%). They were treated with a single oral dose of praziquantel (40 mg/kg) in the non-transmission season. A follow-up stool examination was made 50 days after treatment. Among the 220 cases followed, 22 were found stool-egg-positive, with an overall cure rate of 90%, and 99% reduction of infection intensity (eggs per gram stool). No significant difference was found in cure rates between the 2 areas (89.7% vs 90.3%). The efficacy of the drug in the area with repeated chemotherapy was not significantly different from that in the newly identified endemic focus. This study, therefore, suggests that the efficacy of praziquantel against S. japonicum has not changed in the Dongting Lake region after more than 14 years of mass chemotherapy, and there is no evidence of tolerance or resistance of S. japonicum against praziquantel.
To demonstrate the dynamics of specific antibody isotypes against schistosome adult worm (AWA) and soluble egg (SEA) antigens, we evaluated (in 1999-2000) 112 subjects infected with Schistosoma japonicum from 2 regions of Hunan Province, China. Fifty-eight subjects were from Area A, a well-known endemic area with repeated chemotherapy. Area B (n = 54) is a new endemic focus in another part of the same province. Serum samples were collected prior to praziquantel (PZQ) chemotherapy, and at 2 and 12 months post-treatment. IgM, IgA, IgG, IgG2, IgG4 and IgE antibodies to AWA and SEA were measured by quantitative enzyme-linked immunosorbent assay (ELISA). Pre-treatment antibody isotype levels from Area A, except IgA against AWA and SEA, were significantly higher than those from Area B. In response to chemotherapy, most antibody isotype levels fell or remained stable. However, in Area A there was a significant increase in the IgA, IgE and IgG4 responses to AWA 2 months after PZQ--which fell to approach pre-treatment levels by 12 months. A similar response was seen in Area B with IgE and IgG4 to AWA. Levels of all AWA-specific IgE and IgG4 were significantly higher in subjects from Area A compared with Area B at all time-points. AWA-IgE levels demonstrated significant linear correlations with age and number of previous PZQ treatments in Area A only. All SEA-specific isotypes in both areas fell significantly in response to treatment--except IgE, which remained stable in both area. All SEA-specific isotype levels (except IgA) were significantly higher from Area A at baseline. This significant difference was maintained through 12-months follow-up for IgE, IgG2 and IgG4 only. This study suggests that multiple episodes of schistosome infection may be required to generate antibody isotype levels that have been associated with resistance to re-infection in other studies. Further, a surrogate marker of successful chemotherapy (AWA-IgG4) performed less effectively in patients with previous treatment courses.
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