A baseline study on the importance of bovines for human Schistosoma japonicum infection around Poyang Lake, China.

We hypothesize that bovine infections are responsible for the persistence of human schistosomiasis transmission in the Yangtze marshlands of China. To test this hypothesis, we are carrying out a comparative intervention among four administrative villages in the Poyang Lake region, Jiangxi Province, two of which are experimental and two are control. The primary design involves treating, at the onset of the study, all the inhabitants in all four villages with praziquantel and all the bovines in two villages (the experimental or intervention villages). Following treatment, rates of reinfection in people of all villages, and in bovines in the experimental villages, will be assessed as will the ongoing prevalence of infection in bovines in the control villages. Before treatment, the prevalence and intensity of infection among humans and bovines was ascertained in the four villages. Our study design and baseline information are presented here, along with a description of the ecology of the study villages.

Human susceptibility to Schistosoma japonicum in China correlates with antibody isotypes to native antigens.

Antibody isotypic responses (IgE, IgA, IgG1, IgG2, IgG3 and IgG4) to Schistosoma japonicum antigens--adult worm (AWA), soluble egg (SEA) and the recombinant proteins TEG (22.6-kDa tegumental antigen, Sj22) and PMY (paramyosin, Sj97)--were measured (in 1998) in a cohort of 179 Chinese subjects 2 years post-treatment. Subjects in the highest intensity re-infection group (> 100 eggs per gram faeces) had significantly higher levels of IgG1 and IgG4 against AWA. Analysis of IgG4/IgE ratios for AWA and SEA linked IgG4 excess to re-infection and IgE excess to non-re-infection. Two years after chemotherapeutic cure, 29 subjects, who were re-infected or never infected but highly water-exposed, were classified as epidemiologically susceptible (n = 15) or epidemiologically insusceptible to infection (n = 14). IgG4 levels against native antigens (AWA and SEA) were higher in susceptible and IgE levels were higher in insusceptible but antibody responses to the recombinant proteins (PMY and TEG) showed no clear pattern or difference between susceptibility groups. These and earlier findings provide evidence that immunity develops against schistosomiasis japonica in China and that susceptibility/resistance correlates with antibody isotypes against native schistosome antigens.

Dam worms.

Human and animal infection rates with the Oriental schistosome have steadily declined in China over the last half-century, but the Three Gorges Dam may reverse this decline by creating new, or enlarging existing, ideal environments for the worm and its aquatic snail intermediate host.

HLA class II antigens positively and negatively associated with hepatosplenic schistosomiasis in a Chinese population.

To identify possible associations between host genetic factors and the onset of liver fibrosis following Schistosoma japonicum infection, the major histocompatibility class II alleles of 84 individuals living on an island (Jishan) endemic for schistosomiasis japonica in the Poyang Lake Region of Southern China were determined. Forty patients exhibiting advanced schistosomiasis, characterised by extensive liver fibrosis, and 44 age and sex-matched control subjects were assessed for the class II haplotypes HLA-DRB1 and HLA-DQB1. Two HLA-DRB1 alleles, HLA-DRB1*0901 (P=0.012) and *1302 (P=0.039), and two HLA-DQB1 alleles, HLA-DQB1*0303 (P=0.012) and *0609 (P=0.037), were found to be significantly associated with susceptibility to fibrosis. These associated DRB1 and DQB1 alleles are in very strong linkage disequilibrium, with DRB1*0901-DQB1*0303 and DRB1*1302-DQB1*0609 found as common haplotypes in this population. In contrast, the alleles HLA-DRB1*1501 (P=0.025) and HLA-DQB1*0601 (P=0.022) were found to be associated with resistance to hepatosplenic disease. Moreover, the alleles DQB1*0303 and DRB1*0901 did not increase susceptibility in the presence of DQB1*0601, indicating that DQB1*0601 is dominant over DQB1*0303 and DRB1*0901. The study has thus identified both positive and negative associations between HLA class II alleles and the risk of individuals developing moderate to severe liver fibrosis following schistosome infection.

Schistosomiasis in the People's Republic of China: prospects and challenges for the 21st century.

Schistosomiasis japonica is a serious communicable disease and a major disease risk for more than 30 million people living in the tropical and subtropical zones of China. Infection remains a major public health concern despite 45 years of intensive control efforts. It is estimated that 865,000 people and 100,250 bovines are today infected in the provinces where the disease is endemic, and its transmission continues. Unlike the other schistosome species known to infect humans, the oriental schistosome, Schistosoma japonicum, is a true zoonotic organism, with a range of mammalian reservoirs, making control efforts extremely difficult. Clinical features of schistosomiasis range from fever, headache, and lethargy to severe fibro-obstructive pathology leading to portal hypertension, ascites, and hepatosplenomegaly, which can cause premature death. Infected children are stunted and have cognitive defects impairing memory and learning ability. Current control programs are heavily based on community chemotherapy with a single dose of the drug praziquantel, but vaccines (for use in bovines and humans) in combination with other control strategies are needed to make elimination of the disease possible. In this article, we provide an overview of the biology, epidemiology, clinical features, and prospects for control of oriental schistosomiasis in the People's Republic of China.

Determinants of hepato- and spleno-megaly in Hunan, China: cross-sectional survey data from areas endemic for schistosomiasis.

In order to understand the determinants of schistosome-related hepato- and spleno-megaly better, 14,002 subjects aged 3-60 years (59% male; mean age = 32 years) were randomly selected from 43 villages, all in Hunan province, China, where schistosomiasis caused by Schistosoma japonicum is endemic. The abdomen of each subject was examined along the mid-sternal (MSL) and mid-clavicular lines, for evidence of current hepato- and/or spleno-megaly, and a questionnaire was used to collect information on the medical history of each individual. Current infections with S. japonicum were detected by stool examination. Almost all (99.8%) of the subjects were ethnically Han by descent and most (77%) were engaged in farming. Although schistosomiasis appeared common (42% of the subjects claiming to have had the disease), only 45% of the subjects said they had received anti-schistosomiasis drugs. Overall, 1982 (14%) of the subjects had S. japonicum infections (as revealed by miracidium-hatching tests and/or Kato-Katz smears) when examined and 22% had palpable hepatomegaly (i.e. enlargement of at least 3 cm along the MSL), although only 2.5% had any form of detectable splenomegaly (i.e. a Hackett's grade of at least 1). Multiple logistic regression revealed that male subjects, fishermen, farmers, subjects aged > or = 25 years, subjects with a history of schistosomiasis, and subjects who had had bloody stools in the previous 2 weeks were all at relatively high risk of hepato- and/or spleno-megaly. In areas moderately endemic for Schistosoma japonicum, occupational exposure and disease history appear to be good predictors of current disease status among older residents. These results reconfirm those reported earlier in the same region.

The prevalence of viral hepatitis (HAV, HBV and HCV) in the Christchurch community.

AIM: To determine the prevalence of hepatitis A (HAV), hepatitis B (HBV) and hepatitis C (HCV) in adults randomly selected from the Christchurch community. METHODS: A list of names was randomly generated from the Christchurch electoral roll and subjects were sequentially contacted and invited to participate. A blood sample was taken and tested for hepatitis A (IgG anti-HAV antibody), hepatitis B (HBsAg and anti-HBc) and HCV (anti-HCV antibody) using Abbott Elisa kits. Subjects positive for HBsAg were also tested for HBeAg/HBV DNA. Those positive for anti-HBc were tested for anti-HBs. HCV antibody positive samples were tested for HCV RNA using PCR. RESULTS: 1064 subjects (30.3% of those invited) participated in the study. The prevalence of HAV antibodies was 27.9%, and increased with age. The overall prevalence of HBV markers was 42/1064 (4.2%), and of these 0.3% were HBsAg positive and 3.9% were considered immune. No gender or ethnic differences in these proportions were observed. The seroprevalence of HVC antibody was 3/1064 (0.3%), two of whom were also PCR positive for HCV RNA. CONCLUSION: In the Christchurch community there was a high prevalence of antibodies to HAV, which increased with age. The prevalence of HBsAg and antibody to HCV were both low at 0.3%.

[Quality and health care reform in Latin America and the Caribbean]. / La calidad y la reforma del sector de la salud en América Latina y el Caribe.

Improving the quality of basic health services, together with the search for equity, efficiency, sustainability, and social participation, has been one of the guiding principles of health sector reform initiatives ever since the I Summit of the Americas was held in 1994. This article addresses some basic concepts, examines the status of quality control within health systems and services in Latin America and the Caribbean, and analyzes the most important trends observed in the Region in the establishment of quality assurance programs. Finally, ways of improving and monitoring quality continuously and sustainable are recommended.

Two-year impact of praziquantel treatment for Schistosoma japonicum infection in China: re-infection, subclinical disease and fibrosis marker measurements.

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. japonicum infection before treatment were 28% and 192 eggs per gram faeces (epg), respectively. Two years after cure, 22% of the cohort were re-infected, but with a lighter intensity (67 epg). Sixty-four subjects (37%) showed significant improvement in ultrasound parenchyma images after treatment and 51 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 1. Two years post-treatment a dilated portal vein became less frequent, but the decline was not significant (16% vs 11%, P < 0.05). The serum levels of laminin and collagen IV associated with re-infection 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. japonicum 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.

Measuring exposure to Schistosoma japonicum in China. III. Activity diaries, snail and human infection, transmission ecology and options for control.

We used activity diaries and snail detection to relate water contact and Schistosoma japonicum infection among a cohort of 178 residents on two islands in the Dongting Lake, China. Water exposure to each of 12 mapped water zones around the islands was calculated (m(2) min/day) for each subject. Infected Oncomelania hupensis hupensis snails in this area are focal and were found in only five of the 12 zones, with the highest rate being 5.7%. Thirty-one subjects (17%) were re-infected with a mean intensity of 63.2 epg. Mean water contact was 7.9 m(2) min/day; 98% of water exposure was due to economic activity and only 2% due to swimming or bathing, washing and other necessities of daily life. Males had more exposure and infection than females (P<0.05). Infected subjects had more exposure (10.2 m(2) min/day) than those not infected (7.44 m(2) min/day) (P<0.05). Compared with uninfected subjects, those infected had 2.9 times more exposure in infected-snail zones (P<0.01). Also, human infection intensity (epg) correlated well with exposure to infected snail zones (r=0.552, P<0.01). People <20 years old had the highest re-infection (21.4%) and intensity (3.77 epg). Median exposure for 20-49-year-olds (9.00 m(2) min/day) was nearly double that of those aged <20 or >50 years old (5.5 m(2) min/day). We conclude that map-referenced water contact and snail evaluation boosts accuracy of activity-diary measurements in large transmission foci for the Asian schistosome. Protecting against faecal contamination of snail inhabited sites, and against occupational exposure for island residents, should be a priority of future research. Potential strategies for migrating buffaloes and families living on visiting fishing boats are explored.

Epidemiology of Schistosoma japonicum in China: morbidity and strategies for control in the Dongting Lake region.

Dongting Lake, covering a very large surface water area of 2691km(2), is located in Hunan Province in the southern part of the People's Republic of China. It is the second-largest freshwater lake in China and plays an important role in regulating the amount of water in the Yangtze River, China's longest river. The annual water level of the lake changes by as much as 15m, rising in summer and falling in winter. Asian schistosomiasis has been endemic in the Dongting Lake region for centuries and it has had a devastating effect on the public health of the local people. After a difficult struggle for more than four decades, a concerted programme, supported by the World Bank Loan and instigated in 1992, has resulted in remarkable progress in the control of the disease in many endemic areas of the region. However, the great challenge remains to consolidate and maintain the achievements made to date. The Schistosoma japonicum intermediate host (Oncomelania hupensis hupensis) snail habitats are huge, estimated at 1768km(2) in 1996; these are increasing at a rate of 34.7km(2) annually due to high silt deposition from the Yangtze River itself and from the connecting rivers in Hunan province, and construction of embankments in the Dongting Lake region. It is anticipated that the construction of the Three Gorges Super Dam, the largest engineering project ever undertaken, will substantially extend the range of the snail habitats and increase the number of new schistosomiasis cases. In many areas, human re-infections with S. japonicum after drug (praziquantel) treatment remain unacceptably high (up to 20% of those treated are re-infected annually) due to occupational (mainly fishing) water contact. This paper reviews the history and the current status of schistosomiasis control in the lake region, it explores the epidemiological factors which influence the prevalence of the infection and the disease it causes, and it provides insight into future approaches to control which might finally eradicate the infection.

Is there immunity to Schistosoma japonicum?

The Oriental schistosome, Schistosoma japonicum, unlike the other two major schistosomes that infect humans (S. mansoni and S. haematobium), is a zoonotic species. The transmission dynamics and the potential effects of host-related regulatory factors, including immunity, are likely to be distinct for this parasite. Here, Allen Ross and collaborators from Australia, China and the Philippines discuss recently published and established epidemiological and laboratory data bearing on anti-infection immunity to Asian schistosomiasis, and contrast these findings with the emerging picture of development of anti-infection immunity against the African schistosomes. Implications for vaccines and other control strategies for schistosomiasis japonica are also discussed.

Antibody isotype responses, infection and re-infection for Schistosoma japonicum in a marshland area of China.

Antibody isotype responses to adult worm antigen (AWA) of Schistosoma japonicum and two recombinant proteins (paramyosin (PMY) and a 22 kDa tegumental membrane-associated antigen (TEG)) were analyzed in 137 individuals from an area moderately endemic for schistosomiasis in the Dongting Lake region, Hunan Province, China. The prevalence and geometric mean (GM) intensity of infection before the implementation of curative chemotherapy were 28.5% and 234.4 epg, respectively, but 9 months after treatment the prevalence (6.6%) and intensity (38.3 epg) had decreased. There was no significant difference in either the prevalence or intensity of infection between males and females. Specific IgG (total), IgG4, IgG2, IgA and IgE responses to AWA, PMY and TEG were measured by ELISA. Males produced significantly (P < 0.05) more anti-AWA total IgG, IgE, IgA, IgG4 and IgG2 antibodies, and anti-TEG IgG2 antibody than their female counterparts. The OD450 levels of anti-AWA, PMY and TEG antibody isotypes did not present clear age-dependent trends except for peak levels of anti-AWA IgG4 antibodies evident among subjects 20-29 years of age. The total IgG and IgG4 antibody profiles against AWA correlated well with current S. japonicum infections while anti-AWA IgG2, IgA and IgE antibodies did not show such an association. Anti-AWA-specific IgE antibody levels were positively correlated (r = 0.55) with anti-AWA specific IgG4 antibody levels. In addition, the overall percentage of responders (using a cut-off value obtained from normal controls) to all isotypes to AWA were higher than those observed for both the recombinant antigens. Only 18.2%, 16.8% and 7.3% of the study population were IgE responders to AWA, PMY and TEG. A longer follow-up period is required before we can more fully understand the role of IgE, if any, in protective immunity against schistosomiasis japonica.

Highlights on the World Bank Loan Schistosomiasis Control Program in China (1991-1998): a special focus on Hunan Province.

A region-wide sampling survey was conducted in 1995 in order to evaluate the current epidemiological status of schistosomiasis japonica in Hunan Province, China. A total of 45,590 humans and 3,726 domestic animals, from 52 villages, were examined parasitologically and/or serologically for current Schistosoma japonicum infections. In uncontrolled endemic areas (43 villages) the overall human prevalence of S. japonicum was 7.81% across the different geographical subtypes. The geometric mean intensity of infection was 17.71 eggs per gram (epg) among infected individuals and only 1.25 epg in the general population. The bovine prevalence, as determined by the hatching test, was 9.63% in the uncontrolled endemic villages. Only one sero-positive (by indirect hemagglutination assay) child was found among 1,072 children tested aged 10-14 years in the 9 endemic villages under effective control. No infection was confirmed by the Kato-Katz thick smear stool examination. When the results of this survey were compared to those seen at baseline (1989) an overall reduction of 45.65% was seen in the human prevalence but no significant change was apparent in the lake-beach ecotype. Additionally, there was more than a 60% reduction in the prevalence among bovines over the same sampling period. The results demonstrate that the World Bank Loan Schistosomiasis Program was successful in achieving its most basic objectives for this province - to reduce human and bovine infections by 40%.

Production of interleukin-10 by peripheral blood mononuclear cells from residents of a marshland area in China endemic for Schistosoma japonicum.

Interleukin-10 (IL-10) cytokine production was assessed using peripheral blood mononuclear cells (PBMC) from 67 individuals living in an area endemic for schistosomiasis japonica in China (Dongting Lake, Hunan Province), and 11 control subjects from a non-endemic part of the same Province. Production of IL-10 was measured following in vitro stimulation of PBMC using whole parasite extract (SWAP) or a panel of recombinant Schistosoma japonicum antigens (22-kDa tegumental membrane-associated antigen, glyceraldehyde-3-phosphate dehydrogenase, paramyosin, 14-kDa fatty acid-binding protein and 28-kDa glutathione S-transferase) which are of recognized interest in the development of protective immunity to schistosomiasis. Significantly, PBMC isolated from the exposed population compared with the non-exposed population produced higher levels of IL-10. There was a trend towards higher mean levels of IL-10 release in putatively resistant (insusceptible) (consistently egg negative but highly exposed) individuals compared with susceptible (egg-positive) subjects from the exposed population. Analysis of individual exposure (the duration of water contact and the percent body surface area in contact with water, expressed as m2 h/day) vs. IL-10 production indicated a weak but consistent and statistically significant inverse correlation, with lower levels of exposure being associated with higher levels of IL-10. These results suggest an association between IL-10 production and resistance to S. japonicum in subjects from this Chinese population exposed to infection.

A 2-year prospective study in China provides epidemiological evidence for resistance in humans to re-infection with Schistosoma japonicum.

In 1996, 250 people living in the Dongting-Lake region of China were selected for a 2-year study. All had been or were infected with Schistosoma japonicum. All were treated with praziquantel, although eggs of S. japonicum were only detected in stool samples from 75 of the subjects. In 1998, 213 (85.5%) of these subjects, then with a mean (S.D.) age of 40.2 (14.2) years, provided stool samples for final assessment. Forty-nine (23%) of the 213 were found to be re-infected in 1998, with a geometric mean intensity of infection among the infected of 64.5 eggs/g faeces. The rate of re-infection was highest among those aged < 10 years, declining with increasing age, and higher in males than females (27.3% v. 8.3%; P < 0.005). The mean intensity of infection among the infected males was also higher than that among the infected females [72.4 (4.8) v. 17.8 (2.5) eggs/g; P < 0.005]. Water contact by the subjects was estimated from activity diaries, for 141 days over the 2-year study period, and expressed as skin exposure, in m2-min/day. The mean exposure of a group of subjects was calculated by detransforming the mean of the fourth-root-transformed (i.e. normalized) values for the exposures of each subject within the group. Overall, the 213 individuals had a mean exposure of 6.2 m2-min/day. Differences in occupation led to males having much higher mean water exposures than females (9.2 v. 1.1 m2-min/day). As there was an inverse association between age-specific exposure and age-specific re-infection intensity, the marked reduction seen in intensity of re-infection with increasing age is not attributable to decreasing exposure to water. Instead, the results of this 2-year cohort study provide evidence for age-dependent resistance to re-infection with S. japonicum. The 213 subjects who were followed up were classified, according to epidemiological outcome at the end of the study and the data on water contact, as 'susceptible' (N = 49; 23%), 'insusceptible' (N = 29; 13.6%) or of 'uncertain status' (N = 135; 63.4%). Thus, 78 subjects who are potentially informative in terms of immunogenetics were identified. Further investigation of these individuals should help to shed some light on the role of immunogenetic status in human immunity to Schistosoma japonicum.

Diagnosis of schistosomiasis japonica in Chinese schoolchildren by administration of a questionnaire.

This paper describes a rapid, simple, cost-effective questionnaire for screening school-aged children at risk for Asian schistosomiasis in China. Five hundred and thirty-two children, aged 8-14 years, were selected from 3 schools in an area moderately endemic for Schistosoma japonicum in Hunan province. The questionnaire, comprising 15 multiple-choice questions, was administered by teachers in order to collect both ethnographic and epidemiological data relevant to current S. japonicum infections. This was followed by Kato-Katz thick smear stool examinations, miracidium hatching tests, and soluble egg antigen-enzyme linked immunosorbent assays in order to validate the efficacy of the questionnaire approach. The results from a combination of all 3 procedures indicated that the overall schistosomiasis prevalence in the 3 schools was 29.9% (138/472). Six risk factors (episodes of diarrhoea, frequency of water contact, school grade attained, weakness, past history of S. japonicum infection(s), and whether a subject had been previously treated for schistosomiasis) in the questionnaire were determined by logistic regression to be highly statistically significant predictors of individual current infection. The sensitivity (93.7%), specificity (91.9%) and low cost (c. US$ 0.6/true positive case) associated with the 6 variables model make the questionnaire approach a very useful diagnostic tool for screening marshland and lake communities at high risk for schistosomiasis in China before selective treatment with praziquantel or diagnostic follow-up. An even simpler 3 variables 'yes/no' model was derived from the questionnaire and found to be nearly as good at predicting individual infection (sensitivity 86.2% and specificity exceeding 97.6%) and extremely simple to use. If validated in other ecological settings in China the questionnaire, modified or as presented here, could be adopted by the national schistosomiasis control programme.

Five year impact of chemotherapy on morbidity attributable to Schistosoma japonicum infection in the Dongting Lake region.

OBJECTIVE: To determine changes in the last 5 years of the fraction of acute and chronic symptoms attributable to schistosomiasis japonica in fishing communities with moderate endemicity in the Dongting Lake region of China. METHOD: Complete medical histories, physical examinations, and stool samples were obtained from 1909 individuals (53% male) ranging in age from 4 to 81 years. Age, sex, occupation, frequency of water contact, number of times treated for schistosomiasis, and last year of treatment were tested as potential effect modifiers and confounders. RESULTS: Overall, there were very few infected cases and very little variation in any prevalence ratio with infection intensity, sex, age, year of last treatment, number of times treated or frequency of water contact. The attributable fraction of liver enlargement in one village was estimated at 0.114 (11.4%), although this was not significantly > 0(95% CI; -0.008-0.237). CONCLUSION: The chemotherapy-based schistosomiasis control programme in this locality has succeeded in reducing attributable morbidity to undetectable levels, but many uncertainties remain about sustaining control efforts in the future. Both old and new control strategies will have to be examined if the health and well-being of these people are to be maintained into the next millennium, given that periodic chemotherapy will not be accepted indefinitely.

Faecal egg aggregation in humans infected with Schistosoma japonicum in China.

In this study we examine the variation in Schistosoma japonicum egg counts caused by differences in worm loads between individuals and the variability of egg counts within individuals with a given worm load. Six villages were selected from an area moderately endemic for Asian schistosomiasis in the Dongting Lake region (Hunan province), China. From a total population of 3451 individuals (53.8% male; x = 31 years), 163 subjects were identified as consistently stool egg-positive based on three successive positive Kato-Katz (KK) smears (41.67 mg/smear) obtained from one stool specimen. The distribution of eggs among individuals was found to be strongly aggregated (k = 0.27), but the distribution within the three smears was found to be only slightly aggregated (k = 2.59), indicating only minor clustering of eggs in stools. The relatively slight clustering of eggs within stool specimens suggests that a single KK smear may be quite adequate for detecting individuals moderately to heavily infected (> 100 eggs/g stool (epg)), as needed for a strategy of morbidity control. However, for estimating the true prevalence of infection in a community, or for obtaining an accurate estimate of egg excretion for research studies, multiple KK smears are warranted.