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One small previous study found that praziquantel reduced hookworm infection. In this study, 607 subjects were enrolled in a longitudinal study. At enrollment and every 3 months for 18 months, three stool samples were collected, and the intensity of infection with Schistosoma japonicum and soil-transmitted helminths (STHs) was quantified. All subjects were treated with 60 mg/kg praziquantel at baseline. Three months post-treatment, the percent of subjects who were hookworm-infected decreased to 46.5% from 61% at baseline. The putative cure rate was 23.7%. The 95% confidence interval around the change in hookworm egg counts from baseline to 6 and 12 months post-treatment was negative and did not include zero. The percent reduction in hookworm egg counts from baseline to 3 months post-treatment was 40.8%. Praziquantel treatment did not decrease the infection intensity of STHs. Control programs using praziquantel may have the added benefit of reducing hookworm infection and anemia in areas of coendemnicity.

Schistosomiasis is associated with undernutrition, but the mechanisms involved remain unknown. We analyzed baseline and follow-up data from a longitudinal treatment-reinfection study in N 477 Schistosoma japoni- cum-infected subjects 7-20 years of age from Leyte, the Philippines. After baseline treatment with praziquantel, follow-up visits were scheduled every 3 months for 18 months; stool, venous blood, and anthropometric measurements were collected at each visit. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with specific S. japonicum antigens was measured once 4 weeks after treatment. After adjustment for confounders, S. japonicum intensity was associated with decreased serum albumin and Z-scores (all P < 0.05) and with increased serum C-reactive protein (CRP) and interleukin (IL)-6. CRP was associated with decreased albumin and Z-scores (all P < 0.01). Production of IL-1b and tumor necrosis factor (TNF)- in response to worm antigen was associated with decreased albumin (both P < 0.005) and height-for-age Z-score (TNF- only, P 0.05). S. japonicum-associated undernutrition may, in part, result directly from inflammation.

A dynamic model of Schistosoma japonicum transmission is presented that incorporates effects of infection intensity, age, and sex. We use four infection intensity classes to investigate the impact of ecologic changes and public health interventions on the burden of infection within communities. Age- and sex-specific infection data from three disease-endemic villages in the Philippines are used to estimate the parameters of the model. The model gives good qualitative agreement with observed fecal egg counts adjusted for the accuracy of the Kato-Katz examination. Our results suggest that differences in infection burden between villages are caused by differences in both the infection process and the recovery process in humans. We describe the potential impact of mass treatment of all humans on the numbers with high infection. Furthermore, we show that a sudden reduction in snail population size would affect high prevalence and low prevalence communities in different ways.

The objectives of this study were 1) to provide more accurate estimates of the relationship between Schistosoma japonicum infection and both protein energy malnutrition (PEM) and anemia through better adjustment for potential confounders such as socioeconomic status (SES) and geo-helminth infections and 2) to assess the role of occult blood loss in mediating S. japonicum-associated anemia. We examined cross-sectionally 729 individuals (86.7% S. japonicum-infected and 13.3% S. japonicum-uninfected) aged 7-30 years in Leyte, The Philippines. The main outcome measures were height-for-age Z-score (HAZ), body-mass-index Z-score (BMIZ), triceps skinfold Z-score, hemoglobin, and fecal occult blood loss. Multivariate models were created to assess the relationship between S. japonicum infection and nutritional status after adjusting for age, gender, other helminths, and SES. After controlling for confounders, intensity of S. japonicum infection was inversely related to hemoglobin in all age groups (P < 0.0001) and HAZ among children

The objective of this study was to examine the independent effect of infection with each of four helminths (Ascaris lumbricoides, Schistosoma japonicum, Necator americanus, and Trichuris trichiura) on cognitive function after adjusting for the potential confounders nutritional status, socioeconomic status (SES), hemoglobin, sex, and the presence of other helminthes. This cross-sectional study was carried out in a rural village in Leyte, The Philippines in 319 children 7–18 years old. Three stools were collected and read in duplicate by the Kato Katz method. Infection intensity was defined by World Health Organization criteria. Cognitive tests were culturally adapted and translated. Learning and memory cognitive domains were each defined by three subscales of the Wide Range Assessment of Memory and Learning, which had an inter-rater reliability ≥ 0.92 and test-retest reliabilities ranging from 0.61 to 0.89. A household SES questionnaire was administered. A logistic regression model was used to quantify the association between performance in different cognitive domains (learning, memory, verbal fluency, and the Philippine Non-Verbal Intelligence Test) and helminth infections. After adjusting for age, sex, nutritional status, hemoglobin, and SES, S. japonicum infection was associated with poor performance on tests of learning (odds ratio [OR] = 3.04, 95% confidence interval [CI] = 1.1–6.9), A. lumbricoides infection was associated with poor performance on tests of memory (OR = 2.2, 95% CI = 1.04–4.7), and T. trichiura infection was associated with poor performance on tests of verbal fluency (OR = 4.5, 95% CI = 1.04–30). Helminth infection was associated with lower performance in three of the four cognitive domains examined in this study. These relationships remained after rigorous control for other helminths and important confounding covariates.

Schistosoma japonicum has been related to anemia, but the mechanisms mediating this relationship remain unresolved. The primary objective of this study was to assess the role of occult blood loss in mediating S. japonicum-associated anemia after adjusting for age, sex, socioeconomic status (SES), and other helminth infections. The secondary objective was to identify intensity categories of risk for occult blood loss for Trichuris and hookworm after adjustment for the presence of other helminth infections. The role of occult blood loss in mediating S. japonicum-associated anemia was studied cross-sectionally in 729 individuals 8-30 years old in Leyte, The Philippines. Three stool specimens were examined in duplicate for helminth eggs. Hemoglobin, fecal occult blood loss, and anemia were measured and related to the presence and intensity of helminths. Multivariate models were made to adjust for confounding by other helminths and SES. In multivariate models, hemoglobin significantly decreased with increasing infection intensity of S. japonicum, hookworm, and T. trichuria (P < 0.0031, P < 0.0001, and P < 0.0001, respectively). Individuals with higher intensities S. japonicum and T. trichuria were significantly more likely to be fecal occult positive (odds ratio [OR] = 3.54; P = 0.008 and OR = 2.68; P = 0.013, respectively), although this was not true for individuals with hookworm. Additionally, individuals with higher intensities of S. japonicum, hookworm, and T. trichuria were all more likely to be anemic (OR = 3.7, P = 0.0002; OR = 5.3, P = 0.0003; and OR = 1.6, P = 0.021, respectively). It is likely that occult blood loss plays a role only at heavier intensity S. japonicum infections and some other mechanism, such as anemia of inflammation, may be contributing to anemia.

A double-blind, placebo-controlled, treatment trial was conducted in Sichuan, China to investigate the unique and combined effects on the cognitive function (working memory) of children after treating geohelminth infections with albendazole and treating Schistosoma japonicum infection with praziquantel. One hundred eighty-one children 5-16 years of age participated. At baseline, the praziquantel and placebo groups were similar in all background characteristics. Three months after praziquantel treatment, there was a significant reduction in the prevalence and intensity of S. japonicum infection. There were significant age group by praziquantel treatment interaction effects in three of the five cognitive tests, Fluency, Picture Search, and Free Recall, with effects being strongest in the youngest children (5-7 years old). Exploratory analysis within the youngest children showed a significant positive main effect of treatment on Fluency (P < 0.001), after controlling for sex, anthropometric, and parasitic and iron status. There was also a treatment by height-for-age interaction (P = 0.03) and a treatment by iron status interaction (P = 0.024) on Fluency. There was a treatment by S. japonicum intensity interaction (P < 0.001) on Free Recall, but the main effect of treatment on Picture Search was not significant (P = 0.058). Younger children and those who are physically the most vulnerable are likely to benefit the most from the treatment of S. japonicum infection in terms of improved performance on tests of working memory.

Schistosomiasis japonica differs significantly from Schistosoma mansoni infection in several epidemiologic, immunologic, and operational characteristics for control. Because of numerous nonhuman hosts, transmission remains high despite aggressive case finding and treatment of human cases. Diagnosis of infection using the Kato-Katz stool technique is less sensitive and specific in this than in other species of human schistosomes, making case finding and treatment a less effective approach to control. Clinically, morbidity induced by S. japonicum appears unrelated to intensity of infection, and is more severe than that of S. mansoni in terms of liver pathology and stunting of child growth and development. Both hepatic enlargement and fibrosis appear to be reversible and preventable with aggressive treatment but several operational characteristics for control of infection due to S. japonicum make the community impact of case-finding and treatment with praziquantel less pronounced than would have been predicted by the analysis of individual cases. In the Philippines, rebound morbidity following reinfection mandates short treatment intervals between screening and treatment to have a significant impact on morbidity, while in China inapparent infection (infection not diagnosed by a single stool examination) appears to be a common cause for persistent hepatic pathology. The authors conclude that for S. japonicum, mass treatment or targeted mass treatment is a more cost-effective approach than case-finding and treatment for control.

The hypothesis that infection with Schistosoma japonicum causes decreased nutritional status was studied in a randomized trial among 170 males and females, mean (SD) age 11.4 (3.5) years, residing in an endemic region of northeastern Leyte, Philippines. The S. japonicum-infected children were randomized to receive praziquantel or placebo and followed-up six months after randomization. Stature, weight, triceps, subscapular, and calf skinfold thicknesses and their sum, and hemoglobin level were measured at baseline and follow-up. Schistosoma japonicum eggs were detected in Kato-Katz stool smears and the intensity of infection was assessed by quantitative egg count. Intensities of hookworm, ascaris, and trichuris infections were also measured. The six-month levels of the anthropometric measures and hemoglobin were adjusted for age and their baseline levels and then compared between the praziquantel and placebo groups. Treatment interactions were also analyzed by sex. Baseline anthropometric and hemoglobin levels and parasite infection intensities were the same in the two groups. At six months, the praziquantel group had significantly higher hemoglobin levels (P < 0.001) and sum of skinfolds (P < 0.001) than the placebo group. Males had a significantly greater increase in hemoglobin levels with treatment than did females. The hemoglobin increase was not due to changes in hookworm intensity. The results show that schistosomiasis japonica caused decreased nutritional status in children and probably is partly responsible for the malnutrition and reduction in growth for age described in prior cross-sectional studies.

The association between schistosomiasis japonica and nutritional status and child growth was studied cross-sectionally in 239 males and females (age range 4-19.9 years) residing in Jishan Island in Po Yang Lake in an endemic region of Jiangxi, China. The presence of Schistosoma japonicum eggs in Kato stool smears and the intensity of schistosomiasis as assessed by quantitative egg count were determined, as were the presence of hookworm, Ascaris, and Trichuris eggs. Anthropometric measures included stature, weight, weight-for-height, upper arm muscle area, and the sum of triceps and subscapular skinfold thickness. The association between schistosomiasis and nutritional status and growth was analyzed with multivariable models adjusted for the influence of age, age2, and polyparasitism. The prevalence of schistosomiasis was approximately 70% in both males and females. Current schistosomiasis and its intensity were significantly related to reduced stature, weight, weight-for-height, and the sum of skinfolds (all P < 0.01) in females across the entire age-span. The greatest age-specific differences were during adolescence in females: 4 cm in height and 5 kg in weight. In males, intensity of schistosomiasis was related (P < 0.03) only to the sum of skinfolds. The cross-sectional associations between anthropometric reductions and schistosomiasis japonica in childhood and adolescence indicate a strong independent effect of infection on malnutrition and growth in this population from a highly endemic region of China.

Difficulty in controlling human Schistosoma japonicum infection is partly attributed to the presence of non-human definitive hosts. Water buffaloes are a major reservoir for transmission of S. japonicum to humans in China. However, in the Philippines, reports based on microscopic examination of buffalo stool identified a low prevalence of S. japonicum, and mathematical models using these data concluded that water buffaloes are not a major reservoir for transmission of S. japonicum to humans. We collected stool from 81 buffaloes in Macanip, Leyte, the Philippines, and assayed for S. japonicum infection by the Danish Bilharziasis Laboratory technique, the Kato-Katz technique, miracidia hatching, and a highly validated real-time polymerase chain reaction. The prevalence defined by each assay was 3.7%, 3.7%, 0%, and 51.5% respectively. Our results demonstrate that microscopic-based techniques dramatically underestimate the prevalence of S. japonicum infection in water buffaloes in the Philippines and warrant reexamination of the role of bovines in transmission of S. japonicum to humans in the Philippines.

Schistosomiasis is associated with undernutrition, but the mechanisms involved remain unknown. We analyzed baseline and follow-up data from a longitudinal treatment-reinfection study in N = 477 Schistosoma japonicum-infected subjects 7-20 years of age from Leyte, the Philippines. After baseline treatment with praziquantel, follow-up visits were scheduled every 3 months for 18 months; stool, venous blood, and anthropometric measurements were collected at each visit. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with specific S. japonicum antigens was measured once 4 weeks after treatment. After adjustment for confounders, S. japonicum intensity was associated with decreased serum albumin and Z-scores (all P0.05) and with increased serum C-reactive protein (CRP) and interleukin (IL)-6. CRP was associated with decreased albumin and Z-scores (all P0.01). Production of IL-1b and tumor necrosis factor (TNF)-alpha in response to worm antigen was associated with decreased albumin (both P0.005) and height-for-age Z-score (TNF-alpha only, P = 0.05). S. japonicum-associated undernutrition may, in part, result directly from inflammation.

Little is known about the prevalence of hepatitis C virus (HCV) in Pacific islands. In this study, serum specimens collected in 1985 and 2002 among the general populations of Samoa and American Samoa were tested for antibody to HCV by a third-generation enzyme immunoassay and a recombinant immunoblot assay. Of the 3,466 specimens tested, 8 (0.2%; 95% confidence interval = 0.07-0.4%) were positive for antibody to HCV. Prevalence did not vary by location or demographic characteristic. Thus, HCV is present in the Samoas but at a low prevalence.

A dynamic model of Schistosoma japonicum transmission is presented that incorporates effects of infection intensity, age, and sex. We use four infection intensity classes to investigate the impact of ecologic changes and public health interventions on the burden of infection within communities. Age- and sex-specific infection data from three disease-endemic villages in the Philippines are used to estimate the parameters of the model. The model gives good qualitative agreement with observed fecal egg counts adjusted for the accuracy of the Kato-Katz examination. Our results suggest that differences in infection burden between villages are caused by differences in both the infection process and the recovery process in humans. We describe the potential impact of mass treatment of all humans on the numbers with high infection. Furthermore, we show that a sudden reduction in snail population size would affect high prevalence and low prevalence communities in different ways.

The objective of this study was to examine the independent effect of infection with each of four helminths (Ascaris lumbricoides, Schistosoma japonicum, Necator americanus, and Trichuris trichiura) on cognitive function after adjusting for the potential confounders nutritional status, socioeconomic status (SES), hemoglobin, sex, and the presence of other helminthes. This cross-sectional study was carried out in a rural village in Leyte, The Philippines in 319 children 7–18 years old. Three stools were collected and read in duplicate by the Kato Katz method. Infection intensity was defined by World Health Organization criteria. Cognitive tests were culturally adapted and translated. Learning and memory cognitive domains were each defined by three subscales of the Wide Range Assessment of Memory and Learning, which had an inter-rater reliability ≥ 0.92 and test-retest reliabilities ranging from 0.61 to 0.89. A household SES questionnaire was administered. A logistic regression model was used to quantify the association between performance in different cognitive domains (learning, memory, verbal fluency, and the Philippine Non-Verbal Intelligence Test) and helminth infections. After adjusting for age, sex, nutritional status, hemoglobin, and SES, S. japonicum infection was associated with poor performance on tests of learning (odds ratio [OR] = 3.04, 95% confidence interval [CI] = 1.1–6.9), A. lumbricoides infection was associated with poor performance on tests of memory (OR = 2.2, 95% CI = 1.04–4.7), and T. trichiura infection was associated with poor performance on tests of verbal fluency (OR = 4.5, 95% CI = 1.04–30). Helminth infection was associated with lower performance in three of the four cognitive domains examined in this study. These relationships remained after rigorous control for other helminths and important confounding covariates.

The objectives of this study were 1) to provide more accurate estimates of the relationship between Schistosoma japonicum infection and both protein energy malnutrition (PEM) and anemia through better adjustment for potential confounders such as socioeconomic status (SES) and geo-helminth infections and 2) to assess the role of occult blood loss in mediating S. japonicum-associated anemia. We examined cross-sectionally 729 individuals (86.7% S. japonicum-infected and 13.3% S. japonicum-uninfected) aged 7-30 years in Leyte, The Philippines. The main outcome measures were height-for-age Z-score (HAZ), body-mass-index Z-score (BMIZ), triceps skinfold Z-score, hemoglobin, and fecal occult blood loss. Multivariate models were created to assess the relationship between S. japonicum infection and nutritional status after adjusting for age, gender, other helminths, and SES. After controlling for confounders, intensity of S. japonicum infection was inversely related to hemoglobin in all age groups (P0.0001) and HAZ among children/= 12 years (P = 0.03), but not to BMIZ (P = 0.52) or triceps skinfold Z-score (P = 0.11). Individuals with high-intensity S. japonicum infection were 3.5 times more likely to have occult blood in the stool. Adjustment for occult blood did not attenuate the relationship between S. japonicum and hemoglobin, suggesting other mechanisms are involved. Adjustment for SES allows more accurate assessment of the relationship between S. japonicum and both PEM and anemia. Exploration of the mechanisms of S. japonicum-associated anemia suggests that processes other than extracorporeal blood loss, such as anemia or inflammation, may be involved.

Schistosoma japonicum has been related to anemia, but the mechanisms mediating this relationship remain unresolved. The primary objective of this study was to assess the role of occult blood loss in mediating S. japonicum-associated anemia after adjusting for age, sex, socioeconomic status (SES), and other helminth infections. The secondary objective was to identify intensity categories of risk for occult blood loss for Trichuris and hookworm after adjustment for the presence of other helminth infections. The role of occult blood loss in mediating S. japonicum-associated anemia was studied cross-sectionally in 729 individuals 8-30 years old in Leyte, The Philippines. Three stool specimens were examined in duplicate for helminth eggs. Hemoglobin, fecal occult blood loss, and anemia were measured and related to the presence and intensity of helminths. Multivariate models were made to adjust for confounding by other helminths and SES. In multivariate models, hemoglobin significantly decreased with increasing infection intensity of S. japonicum, hookworm, and T. trichuria (P0.0031, P0.0001, and P0.0001, respectively). Individuals with higher intensities S. japonicum and T. trichuria were significantly more likely to be fecal occult positive (odds ratio [OR] = 3.54; P = 0.008 and OR = 2.68; P = 0.013, respectively), although this was not true for individuals with hookworm. Additionally, individuals with higher intensities of S. japonicum, hookworm, and T. trichuria were all more likely to be anemic (OR = 3.7, P = 0.0002; OR = 5.3, P = 0.0003; and OR = 1.6, P = 0.021, respectively). It is likely that occult blood loss plays a role only at heavier intensity S. japonicum infections and some other mechanism, such as anemia of inflammation, may be contributing to anemia.

Little is known about the prevalence of hepatitis C virus (HCV) in Pacific islands. In this study, serum specimens collected in 1985 and 2002 among the general populations of Samoa and American Samoa were tested for antibody to HCV by a third-generation enzyme immunoassay and a recombinant immunoblot assay. Of the 3,466 specimens tested, 8 (0.2%; 95% confidence interval = 0.07-0.4%) were positive for antibody to HCV. Prevalence did not vary by location or demographic characteristic. Thus, HCV is present in the Samoas but at a low prevalence.

The impact of annual screening and treatment with praziquantel on schistosomiasis japonica was examined on Jishan Island in Po Yang Lake, Jiangxi Province. China. Prevalence of infection in the community decreased from 39% in year 1 to 33% in year 3 with a corresponding decrease in the geometric mean egg count from 51 eggs per gram of stool (epg) to 31 epg. The most dramatic changes in infection status and intensity of infection were observed in younger individuals (0-19 years of age). The prevalence of hepatosplenomegaly also significantly decreased, again primarily in younger individuals. No change in the community prevalence of schistosome-induced hepatic fibrosis was observed as determined by ultrasonography. Longitudinal cohort analysis, however, demonstrated significant improvement in treated individuals with advanced hepatic fibrosis. These data indicate that annual screening and treatment had a significant impact on infection status and morbidity and suggest that community therapy may be an effective approach to control schistosomiasis japonica in lake regions and marshlands in China. Further studies are necessary to determine the optimal and most cost-effective approach for drug delivery.

The association between schistosomiasis japonica and child growth was studied cross-sectionally in 1,561 males and females aged 4-19.9 years residing in an endemic region of northeastern Leyte, The Philippines. Stature, weight, upper arm muscle area, and sum of triceps and subscapular skinfold thicknesses were measured and related to presence of Schistosoma japonicum eggs in Kato stool smears and to the intensity of infection assessed by quantitative egg count. The presence of hookworm, ascaris, and trichuris eggs was also measured. Multivariable models were used to control for the effects of age, age2, and polyparasitism on growth. The prevalence of schistosomiasis was 31% in males and 22% in females, with the maximum prevalence in adolescence. In 8-19-year-old subjects, the intensity of schistosomiasis japonica was significantly related in males to reduced arm muscle area and sum of skinfolds (both P less than 0.01) and in females to reduced stature, weight, arm muscle area, and sum of skinfolds (all P less than 0.01). The greatest age-specific differences were during adolescence in both males and females. The growth retarding effects of intensity of schistosomiasis japonica were independent of the influence of other parasites, notably hookworm. Due to the magnitude of the schistosomiasis-associated growth differences in adolescence, adult body size, function and productivity may be affected.