Microbial source tracking and antimicrobial resistance in one river system of a rural community in Bahia, Brazil / Rastreamento de fontes microbianas e resistência antimicrobiana em um sistema fluvial de uma comunidade rural da Bahia, Brasil

Use of antibiotics inevitably leads to antimicrobial resistance. Selection for resistance occurs primarily within the gut of humans and animals as well as in the environment through natural resistance and residual antibiotics in streams and soil. We evaluated antimicrobial resistance in Gram negative bacteria from a river system in a rural community in Bahia, Brazil. Water was collected from the Jiquiriçá and Brejões rivers and the piped water supply. Additionally, stools were collected from a random sample of residents, cows, pigs and horses near the river. The samples were screened for bacteria resistant to ciprofloxacin, cefotaxime, and meropenem and identified biochemically at the genus and species levels. Microbial source tracking demonstrated that ruminant and human fecal contamination increased as the rivers neared the village center and decreased after the last residence. Antibiotic bacteria were identified from all samples (n = 32). No bacteria were resistant to carbapenems, but the majority of the enterobacteria were resistant to ciprofloxacin, even though this class of antibiotics is not commonly used in food animals in this region. Considering these facts, together with the pattern of human fecal contamination, a human source was considered most likely for these resistant isolates.

O uso de antibióticos inevitavelmente leva à resistência antimicrobiana. A seleção para resistência antimicrobiana ocorre principalmente no intestino de seres humanos e animais, bem como no meio ambiente, através da resistência natural e resíduos de antibióticos nos esgotos e no solo. Avaliamos a resistência antimicrobiana em bactérias Gram-negativas de um sistema fluvial em uma comunidade rural da Bahia, Brasil. A água foi coletada nos rios Jiquiriçá e Brejões e no abastecimento de água encanada. Além disso, foram coletadas amostras randomizadas de fezes de moradores, vacas, porcos e cavalos próximos ao rio. As amostras foram triadas para bactérias resistentes à ciprofloxacina, cefotaxima e meropenem e identificadas bioquimicamente nos níveis de gênero e espécie. O rastreamento de fontes microbianas demonstrou que a contaminação fecal de ruminantes e humanos aumentou à medida que os rios se aproximavam do centro da vila e diminuía após a última residência. Bactérias resistentes a antibióticos foram identificadas em todas as amostras (n = 32). Nenhuma bactéria demonstrou ser resistente aos carbapenêmicos testados, contudo, foi encontrado enterobactérias resistentes à ciprofloxacina, ainda que essa classe de antibióticos não seja comumente usada na medicina veterinária dos animais dessa região. Considerando esses fatos, juntamente com o padrão de contaminação fecal avaliado, a fonte de contaminação humana foi considerada a mais provável na interação desses isolados resistentes.

Microbial source tracking and antimicrobial resistance in one river system of a rural community in Bahia, Brazil

Abstract Use of antibiotics inevitably leads to antimicrobial resistance. Selection for resistance occurs primarily within the gut of humans and animals as well as in the environment through natural resistance and residual antibiotics in streams and soil. We evaluated antimicrobial resistance in Gram negative bacteria from a river system in a rural community in Bahia, Brazil. Water was collected from the Jiquiriçá and Brejões rivers and the piped water supply. Additionally, stools were collected from a random sample of residents, cows, pigs and horses near the river. The samples were screened for bacteria resistant to ciprofloxacin, cefotaxime, and meropenem and identified biochemically at the genus and species levels. Microbial source tracking demonstrated that ruminant and human fecal contamination increased as the rivers neared the village center and decreased after the last residence. Antibiotic bacteria were identified from all samples (n = 32). No bacteria were resistant to carbapenems, but the majority of the enterobacteria were resistant to ciprofloxacin, even though this class of antibiotics is not commonly used in food animals in this region. Considering these facts, together with the pattern of human fecal contamination, a human source was considered most likely for these resistant isolates.

Resumo O uso de antibióticos inevitavelmente leva à resistência antimicrobiana. A seleção para resistência antimicrobiana ocorre principalmente no intestino de seres humanos e animais, bem como no meio ambiente, através da resistência natural e resíduos de antibióticos nos esgotos e no solo. Avaliamos a resistência antimicrobiana em bactérias Gram-negativas de um sistema fluvial em uma comunidade rural da Bahia, Brasil. A água foi coletada nos rios Jiquiriçá e Brejões e no abastecimento de água encanada. Além disso, foram coletadas amostras randomizadas de fezes de moradores, vacas, porcos e cavalos próximos ao rio. As amostras foram triadas para bactérias resistentes à ciprofloxacina, cefotaxima e meropenem e identificadas bioquimicamente nos níveis de gênero e espécie. O rastreamento de fontes microbianas demonstrou que a contaminação fecal de ruminantes e humanos aumentou à medida que os rios se aproximavam do centro da vila e diminuía após a última residência. Bactérias resistentes a antibióticos foram identificadas em todas as amostras (n = 32). Nenhuma bactéria demonstrou ser resistente aos carbapenêmicos testados, contudo, foi encontrado enterobactérias resistentes à ciprofloxacina, ainda que essa classe de antibióticos não seja comumente usada na medicina veterinária dos animais dessa região. Considerando esses fatos, juntamente com o padrão de contaminação fecal avaliado, a fonte de contaminação humana foi considerada a mais provável na interação desses isolados resistentes.

Microbial source tracking and antimicrobial resistance in one river system of a rural community in Bahia, Brazil.

Use of antibiotics inevitably leads to antimicrobial resistance. Selection for resistance occurs primarily within the gut of humans and animals as well as in the environment through natural resistance and residual antibiotics in streams and soil. We evaluated antimicrobial resistance in Gram negative bacteria from a river system in a rural community in Bahia, Brazil. Water was collected from the Jiquiriçá and Brejões rivers and the piped water supply. Additionally, stools were collected from a random sample of residents, cows, pigs and horses near the river. The samples were screened for bacteria resistant to ciprofloxacin, cefotaxime, and meropenem and identified biochemically at the genus and species levels. Microbial source tracking demonstrated that ruminant and human fecal contamination increased as the rivers neared the village center and decreased after the last residence. Antibiotic bacteria were identified from all samples (n = 32). No bacteria were resistant to carbapenems, but the majority of the enterobacteria were resistant to ciprofloxacin, even though this class of antibiotics is not commonly used in food animals in this region. Considering these facts, together with the pattern of human fecal contamination, a human source was considered most likely for these resistant isolates.

Pubertal stage and brain anatomy in girls.

Studies of puberty have focused primarily on changes in hormones and on observable physical bodily characteristics. Little is known, however, about the nature of the relation between pubertal status and brain physiology. This is particularly important given findings that have linked the onset of puberty with both changes in cognitive functioning and increases in the incidence of depression and anxiety. The present study examined relations between pubertal stage, as assessed by Tanner staging, and brain anatomy in a sample of 54 girls aged 9-15 years. Brain morphometric analysis was conducted using high-resolution magnetic resonance imaging (MRI). The hippocampus and amygdala were manually traced on MRI scans in all participants. Stepwise regression analyses were conducted with total intracranial volume (ICV), age, and pubertal status as the predictor variables and hippocampus and amygdala volumes as outcome variables. Pubertal status was significantly associated with left amygdala volume, after controlling for both age and ICV. In addition, puberty was related to right hippocampus and amygdala volumes, after controlling for ICV. In contrast, no significant associations were found between age and hippocampal and amygdala volumes after controlling for pubertal status and ICV. These findings highlight the importance of the relation between pubertal status and morphometry of the hippocampus and amygdala, and of limbic and subcortical structures that have been implicated in emotional and social behaviors.

Microsatellite analysis of pooled Schistosoma mansoni DNA: an approach for studies of parasite populations.

Human parasites are often distributed in metapopulations, which makes random sampling for genetic epidemiology difficult. The typical approach to sampling Schistosoma mansoni involves laboratory passage to obtain individual worms with small sample size and selection bias as a consequence. By contrast, the naturally pooled samples from egg output in stool or urine directly represent the genetic composition of current populations. To test whether pooled samples could be used to estimate population allele frequencies, DNA from individual cloned parasites was pooled and amplified by PCR for 7 microsatellites. By polyacrylamide gel analysis, the relative band intensities of the products from the major alleles in the pooled samples differed by 0-6% from the summed intensities of the individual clones (mean = 2.1%+/-2.1% S.D.). The number of PCR cycles (25-40) did not influence the accuracy of the estimate. Varying the frequency of 1 allele in pooled samples from 32 to 69% likewise did not affect accuracy. Allele frequency estimates from aggregate samples such as eggs will be a better foundation for studies of parasite population dynamics as well as the basis for large-scale association studies of host and parasite characteristics.

Childhood stunting in Northeast Brazil: the role of Schistosoma mansoni infection and inadequate dietary intake.

OBJECTIVE: To evaluate the relationship between stunting, Schistosoma mansoni infection and dietary intake in schoolchildren. DESIGN: This is a cross-sectional study. Two stool samples were obtained from each child and examined quantitatively for the presence of S. mansoni, Ascaris lumbricoides and Trichuris trichiuria eggs. Information on dietary intake, and demographic, biologic and socioeconomic variables was elicited during the in-home survey. Logistic regression was used to evaluate the association between stunting (height for age < -2s.d.), parasitic infection and food consumption. SETTING: The study was carried out in the city of Nazaré, located in the Recôncavo region of the State of Bahia, Northeastern Brazil. SUBJECTS: The sample consisted of 461 children 7-14 y old, 228 boys and 233 girls, recruited from public schools. RESULTS: Of the children studied, 55.1% presented with S. mansoni infection and 22.1% were stunted. The median protein, lipid and carbohydrates intake were 47.8, 36.0 and 248.2 g/day, respectively. The median caloric consumption was 1527.0 kcal (6388.97 kJ/day). The analysis indicated that children heavily infected (> or = 400 eggs/g of stool) with S. mansoni had a 2.74-fold (95% CI: 1.32-5.67) higher risk of stunting than uninfected children, and those with inadequate intake of lipid (< 36 g/day) had a 1.83-fold (95% CI: 1.05-3.20) increased risk of stunting compared to those with adequate diets. CONCLUSION: Heavy S. mansoni infection and inadequate dietary intake of fat in schoolchildren play a significant and independent role in the development of stunting. This meaning that nutritional interventions in this age group in S. mansoni endemic areas must include the diagnosis and treatment of the infection associated with dietary measures. SPONSORSHIP: This study was supported by the Thrasher Foundation. Sandra Maria Conceição Pinheiro is a National Council on Technological Development Scholarship Awardee (CNPq), #302228/81-0.

Probabilistic approaches for atlasing normal and disease-specific brain variability.

The extreme variability in the structural conformation of the human brain poses significant challenges for the creation of population-based atlases. The ability to statistically and visually compare and contrast brain image data from multiple individuals is essential to understanding normal variability within a particular population as well as differentiating normal from diseased populations. This paper introduces the application of probabilistic atlases that describe specific subpopulations, measures their variability and characterizes the structural differences between them. Utilizing data from structural MRI, we have built atlases with defined coordinate systems creating a framework for mapping data from functional, histological and other studies of the same population. This paper describes the basic approach and a brief description of the underlying mathematical constructs that enable the calculation of probabilistic atlases and examples of their results from several different normal and diseased populations.

Medial temporal lobe in childhood-onset schizophrenia.

The majority of anatomic and neuroimaging studies in adult-onset schizophrenia demonstrate decreased volumes of the medial temporal lobe when compared with findings in normal individuals. The goal of this study was to investigate the hypothesis that subjects with childhood-onset schizophrenia would show decreased volumes of the medial temporal lobe when compared to normal children. Thirteen children meeting DSM-III-R criteria for schizophrenia (mean age 14.2+/-3.8 years) and 20 normal children (mean age 12.0+/-2.8 years) were investigated. MRI scans were performed on a 1.5-T GE Signa MR scanner using a coronal plane SPGR at 1.4-mm slice thickness. Volumes were assessed by manually tracing bilateral hippocampus, amygdala and temporal lobes. After adjustment for age and total brain volume, the amygdala was significantly larger in the schizophrenics than in the control subjects, and this volume increase was more pronounced on the left side. Hippocampus volumes did not differ significantly across groups. There was a nearly significant left-greater-than-right asymmetry of the amygdala in the schizophrenic group but not in the normal group. A nearly significant right-greater-than-left asymmetry was found in the anterior hippocampus for both schizophrenic and control groups. These findings are consistent with previous reports of at least initial sparing of temporal lobe regions in childhood-onset schizophrenia.

Mapping cortical asymmetry and complexity patterns in normal children.

This study reports the first comprehensive three-dimensional (3D) maps of cortical patterns in children. Using a novel parametric mesh-based analytic technique applied to high-resolution T1-weighted MRI scans, we examined age (6-16 years) and gender differences in cortical complexity (the fractal dimension or complexity of sulcal/gyral convolutions) and asymmetry of 24 primary cortical sulci in normally developing children (N=24). Three-dimensional models of the cerebral cortex were extracted and major sulci mapped in stereotaxic space. Given the documented age-related changes in frontal lobe functions and several neuroimaging studies that have reported accompanying volumetric changes in these regions, we hypothesized that, with age, we would find continued modifications of the cerebrum in frontal cortex. We also predicted that phylogenetically older regions of the cerebrum, such as olfactory cortex, would be less variable in anatomic location across subjects and with age. Age-related increases in cortical complexity were found in both left and right inferior frontal and left superior frontal regions, possibly indicating an increase in secondary branching with age in these regions. Moreover, a significant increase in the length of the left inferior frontal sulcus and a posterior shifting of the left pre-central sulcus was associated with age. Three-dimensional asymmetry and anatomic variability maps revealed a significant left-greater-than-right asymmetry of the Sylvian fissures and superior temporal sulci, and increased variance in dorsolateral frontal and perisylvian areas relative to ventral regions of the cortex. These results suggest increases in cortical complexity and subtle modifications of sulcal topography of frontal lobe regions, likely reflecting ongoing processes such as myelination and synaptic remodeling that continue into the second decade of life. More studies in a larger sample set and/or longitudinal design are needed to address the issues of normal individual variation and sulcal development.

Prevalence and familial aggregation of schistosomal liver morbidity in Kenya: evaluation by new ultrasound criteria.

Severe periportal fibrosis is not an inevitable consequence of infection with Schistosoma mansoni. Genetic predisposition may be a deciding factor in the development of disease. To assess the contribution of genetic factors in the severity of hepatic fibrosis, the degree of familial aggregation was determined in a Kenyan population. Schistosomal fibrosis was identified with hepatic ultrasound and newly proposed World Health Organization criteria, which include both qualitative and quantitative observations. These 2 aspects of the criteria correlated well with one another. The peak prevalence of ultrasound proven fibrosis trailed 5-10 years behind peak prevalence of infection and declined sharply after age 50 years. This pattern was consistent with either resolution of severe fibrosis over 10-20 years or early death of those severely affected. Genetic predisposition appears to be a weak factor in the development of severe disease in this population, since no household or familial aggregation could be identified.

Cortical change in Alzheimer's disease detected with a disease-specific population-based brain atlas.

We report the first detailed population-based maps of cortical gray matter loss in Alzheimer's disease (AD), revealing prominent features of early structural change. New computational approaches were used to: (i) distinguish variations in gray matter distribution from variations in gyral patterns; (ii) encode these variations in a brain atlas (n = 46); (iii) create detailed maps localizing gray matter differences across groups. High resolution 3D magnetic resonance imaging (MRI) volumes were acquired from 26 subjects with mild to moderate AD (age 75.8+/-1.7 years, MMSE score 20.0+/-0.9) and 20 normal elderly controls (72.4+/-1.3 years) matched for age, sex, handedness and educational level. Image data were aligned into a standardized coordinate space specifically developed for an elderly population. Eighty-four anatomical models per brain, based on parametric surface meshes, were created for all 46 subjects. Structures modeled included: cortical surfaces, all major superficial and deep cortical sulci, callosal and hippocampal surfaces, 14 ventricular regions and 36 gyral boundaries. An elastic warping approach, driven by anatomical features, was then used to measure gyral pattern variations. Measures of gray matter distribution were made in corresponding regions of cortex across all 46 subjects. Statistical variations in cortical patterning, asymmetry, gray matter distribution and average gray matter loss were then encoded locally across the cortex. Maps of group differences were generated. Average maps revealed complex profiles of gray matter loss in disease. Greatest deficits (20-30% loss, P<0.001-0.0001) were mapped in the temporo-parietal cortices. The sensorimotor and occipital cortices were comparatively spared (0-5% loss, P>0.05). Gray matter loss was greater in the left hemisphere, with different patterns in the heteromodal and idiotypic cortex. Gyral pattern variability also differed in cortical regions appearing at different embryonic phases. 3D mapping revealed profiles of structural deficits consistent with the cognitive, metabolic and histological changes in early AD. These deficits can therefore be (i) charted in a living population and (ii) compared across individuals and groups, facilitating longitudinal, genetic and interventional studies of dementia.

Lower hookworm incidence, prevalence, and intensity of infection in children with a Bacillus Calmette-Guérin vaccination scar.

Bacillus Calmette-Guérin (BCG), the most common vaccine worldwide, has broad effects on the immune system. Hookworm infections are a major source of morbidity. In response to a preliminary report of BCG vaccination protection against nematodes in human immunodeficiency virus-infected adults, data from an ongoing prospective study were analyzed to determine the intensity (eggs per gram of stool), prevalence, and incidence of different helminths in children with and without a BCG vaccination scar. Adjusted prevalence and incidence ratios were estimated by using logistic regression. Children with a BCG vaccination scar were found to have statistically significantly lower hookworm prevalence (41%), incidence (37%), and mean egg counts (39%), after controlling for age, sex, and socioeconomic factors. There was no BCG association with incidence, prevalence, or intensity of infection with Schistosoma mansoni, Ascaris lumbricoides, or Trichuris trichiura. Such protection would have implications for public health and for research on mechanisms behind human immunological responses to hookworm.

Brain abnormalities in early-onset schizophrenia spectrum disorder observed with statistical parametric mapping of structural magnetic resonance images.

OBJECTIVE: The purpose of this study was to assess neuroanatomic abnormalities in children and adolescents with childhood-onset schizophrenia by using whole-brain voxel-based morphometric analyses. Previous volumetric studies of brain abnormalities in childhood-onset schizophrenia have revealed anomalies similar to those in subjects with adult-onset schizophrenia. Specifically, low cerebral volume, high ventricular volume, and thalamic, basal ganglia, callosal, and temporal lobe abnormalities have been observed in childhood-onset schizophrenia. Relatively few anatomical structures have been delineated and measured in this rare population, partly because of the labor involved in the slice-by-slice region definition required of conventional volumetric image analyses. METHOD: The subjects were 10 normal children and adolescents and nine children and adolescents with early-onset schizophrenia (mean age at diagnosis, 11.0 years; range, 7-16 years). The authors conducted voxel-by-voxel and volumetric statistical analyses of high-resolution structural magnetic resonance images. RESULTS: Statistical parametric maps of gray matter, white matter, and CSF differences between the groups revealed that the subjects with early-onset schizophrenia had larger ventricles, predominantly in the posterior horns of the lateral ventricles, and midcallosal, posterior cingulate, caudate, and thalamic abnormalities. Volumetric analyses of the lateral ventricles in native image data space confirmed significantly higher volume in posterior, but not anterior, regions. Randomization tests confirmed the overall statistical significance of the group differences and validity of the parametric maps. CONCLUSIONS: These findings are generally consistent with the findings of other research groups, but localization of enlarged ventricles specific to the posterior region may be a new finding in the literature on childhood-onset schizophrenia.

Repeated exposure induces periportal fibrosis in Schistosoma mansoni-infected baboons: role of TGF-beta and IL-4.

Recently, we observed that repeated Schistosoma mansoni infection and treatment boost Th2-associated cytokines and TGF-beta production in baboons. Other studies have shown that some chronically infected baboons develop hepatic fibrosis. Because TGF-beta, IL-2, and IL-4 have been shown to participate in development of fibrosis in murine schistosomiasis, the present study examined whether repeated exposure stimulates hepatic fibrosis in olive baboons. To test this hypothesis, animals were exposed to similar numbers of S. mansoni cercariae given once or repeatedly. After 19 wk of infection, animals were cured with praziquantel and reinfected once or multiple times. Hepatic granulomatous inflammation and fibrosis were assessed from serial liver biopsies taken at weeks 6, 9, and 16 after reinfection and egg Ag (schistosome egg Ag)-specific cytokine production by PBMC were measured simultaneously. Periportal fibroblast infiltration and extracellular matrix deposition (fibrosis), angiogenesis, and biliary duct hyperplasia developed in some animals. The presence and amount of fibrosis directly correlated with the frequency of exposure. Fibrosis was not associated with adult worm or tissue egg burden. The amount of fibrosis correlated with increased schistosome egg Ag-driven TGF-beta at 6, 9, and 16 wk postinfection (rs = 0.9, 0.8, and 0.54, respectively, all p < 0.01) and IL-4 production (p = 0.02) at 16 wk postinfection and not IFN-gamma, IL-2, IL-5, or IL-10. These data suggest that repeated exposure is a risk factor for periportal fibrosis by a mechanism that primes lymphocytes to produce increased levels of profibrotic molecules that include TGF-beta and IL-4.

Cytokine control of the granulomatous response in Schistosoma mansoni-infected baboons: role of exposure and treatment.

Variations in exposure and treatment may contribute to heterogeneity in immunity and granuloma-induced pathology in human schistosomiasis. To examine this hypothesis, olive baboons were either repeatedly infected with Schistosoma mansoni cercariae or received an equivalent dose in a single infection. They were then cured with praziquantel and reinfected with a single exposure. Serial liver biopsies were obtained throughout the course of the experiment, and cytokine responses by peripheral blood mononuclear cells were measured every 2 to 3 weeks. Reinfection after treatment resulted in a twofold-smaller granuloma size at 6 and 9 weeks after infection compared to the size for the same period after primary infection (P < 0.001) but had no effect at 16 or 19 weeks postinfection. The pattern of exposure did not influence granuloma size. During primary infection schistosome-soluble egg antigen (SEA)-induced cytokine production correlated with granulomatous inflammation. Cytokine levels peaked during the acute infection, declined with chronic infection, and became undetectable after treatment. Reinfection after treatment stimulated a two- to three-fold increase in SEA-specific interleukin-4 (IL-4), IL-5, IL-10, IL-2, and transforming growth factor beta (TGF-beta) production and a marked rise in SEA-specific immunoglobulin E (IgE) and IgG regardless of the type of exposure. Cytokine production was significantly greater in repeatedly exposed animals (P < 0.001). SEA-induced gamma interferon production, however, did not increase with reinfection after treatment. SEA-induced TGF-beta was the only cytokine that remained elevated as the infection become chronic and correlated with diminished hepatic granuloma size, implying its participation in down-modulation. These studies demonstrate that baboons partially retain their ability to down-modulate the granulomatous response after treatment.

Purification and crystallization of a novel membrane-anchored protein: the Schistosoma haematobium serpin.

A unique serine-protease inhibitor (serpin) of the blood fluke S. haematobium has been crystallized. It is an antitrypsin with an unusual residue (phenylalanine) at its reactive center. Unlike any known member of this gene family, it is a membrane-anchored protein on the surface of the parasite. The location of this serpin and immunological response to the protein indicate that it may play a important role in host-parasite interaction. The crystals belong to the trigonal space group P3221 or P3121 with unit-cell parameters a = b = 64.7, c = 186.7 A, alpha = 90.0, beta = 90.0, gamma = 120.0 degrees. There is one molecule per asymmetric unit and the crystals diffracted to 2.2 A.

Role of adult worm antigen-specific immunoglobulin E in acquired immunity to Schistosoma mansoni infection in baboons.

Allergic-type immune responses, particularly immunoglobulin E (IgE), correlate with protective immunity in human schistosomiasis. To better understand the mechanisms of parasite elimination we examined the immune correlates of protection in baboons (Papio cynocephalus anubis), which are natural hosts for Schistosoma mansoni and also develop allergic-type immunity with infection. In one experiment, animals were exposed to a single infection (1,000 cercariae) or were exposed multiple times (100 cercariae per week for 10 weeks) and subsequently were cured with praziquantel prior to challenge with 1, 000 cercariae. Singly and multiply infected animals mounted 59 and 80% reductions in worm burden, respectively (P < 0.01). In a second experiment, animals were inoculated with S. mansoni ova and recombinant human interleukin 12 (IL-12). This produced a 37 to 39% reduction in adult worm burden after challenge (P < 0.05). Parasite-specific IgG, IgE, IgM, and peripheral blood cytokine production were evaluated. The only immune correlate of protection in both experiments was levels of soluble adult worm antigen (SWAP)-specific IgE in serum at the time of challenge infection and/or 6 weeks later. Baboons repeatedly infected with cercariae or immunized with ova and IL-12 developed two- to sixfold-greater levels of SWAP-specific IgE in serum than did controls, and this correlated with reductions in worm burden (r2, -0.40 to -0.64; P, <0. 01). Thus, in baboons and unlike mice, adult worm-specific IgE is uniquely associated with acquired immunity to S. mansoni infection. This similar association of parasite-specific IgE and protection among primates infected with schistosomiasis, along with similar pathology, anatomy, and genetic make-up, indicates that baboons provide an excellent permissive experimental model for better understanding the mechanisms of innate and acquired immunity to schistosomiasis in humans.

Schistosoma mansoni infection and nutritional status in schoolchildren: a randomized, double-blind trial in northeastern Brazil.

Brazilian schoolchildren with mild- to moderate-intensity schistosome infections (<400 Schistosoma mansoni eggs/g stool) were randomly allocated to a treatment (oxamniquine) or placebo group in a double-blind fashion. Anthropometric measurements were made at baseline, 6 mo, and 1 y for 353 students. At baseline, the groups were not significantly different with respect to nutritional status or selected socioeconomic and biological characteristics, including anthropometric measures. One year later, significant differences were noted only in the nutritional status of boys treated for schistosome infection. Treated boys had greater measurements for weight, triceps skinfold thickness, midarm circumference, arm muscle area, and body mass index than untreated boys. They also showed significant increases over the year in weight, height, midarm circumference, and body mass index. The rates of improvement in weight and height were more accelerated in the first 6 mo after therapy than the last. These results indicate that, at least in boys, chronic S. mansoni infection at any intensity is detrimental to short-term growth and development.

Oxfendazole treatment for cystic hydatid disease in naturally infected animals.

Few chemotherapeutic agents are available for the medical management of hydatid disease caused by the parasite Echinococcus granulosus. In order to test the potential of oxfendazole for the treatment of infection with this parasite, nine infected goats and four sheep were given oxfendazole twice weekly at a dose of 30 mg/kg of body weight for 4 weeks and monitored by ultrasound for an additional 4 weeks. Efficacy was finally evaluated by postmortem examination, including determination of protoscolex viability and cyst wall histology. In treated animals, protoscolices were dead or absent in 97% of cysts from oxfendazole-treated animals compared to 28% of cysts from untreated control animals. On postmortem examination, 53% of cysts from treated animals were found to be grossly degenerate. A sample of those cysts that appeared potentially viable all demonstrated evidence of severe damage to the cyst wall. By light microscopy, cysts showed severe disorganization of the adventitial layer with invasion of inflammatory cells and in some cases frank necrosis with no apparent adventitial layer. The follow-up period for assessment of the drug's ability to cause complete degeneration and resorption of cysts was relatively short. This study, however, indicates that oxfendazole is at least as effective as and is easier to administer than albendazole for the treatment of hydatid disease.

Schistosoma mansoni: development and modulation of the granuloma after or multiple exposures in the baboon (Papio cynocephalus anubis).

The ability of the host to modulate the granulomatous response around ova trapped in tissues determines the severity of disease to schistosome infections. Multiple factors may affect this modulation such as age, prior sensitization, history of treatment, and exposure. The present study examines the effect of different patterns of exposure on the sequential development and modulation of granuloma in juvenile Kenyan baboons (Papio cynocephalus anubis) after receiving either a single infection (SI) of 1500 Schistosoma mansoni cercariae or multiple infections (MI) of 150 cercariae, once a week for 10 weeks. Prior to sacrifice at 17 weeks postinfection (p.i.), liver biopsies were obtained at Weeks 0, 6, 9, and 13. SI animals experienced more prolonged dysentery and greater weight loss compared to MI animals. Peak hepatic granuloma size (mean 355 +/- 65.5 microns diameter), the maximum percentage of eosinophils in the granuloma (61%), and severity of disease occurred at 6 weeks in SI animals. Peak granuloma size and pathology did not appear until Week 9 in the MI animals (mean 317.7 +/- 67.3 microns diameter). Granuloma size, tissue eosinophilia, and gross pathology diminished by Week 13 p.i. and were virtually absent in both groups by Week 17. The decrease in granuloma size, pathology, and clinical illness resolved more rapidly in the MI baboons. Singly infected baboons were more susceptible to infection (83 +/- 12% of cercariae developed into adult worms) compared to MI baboons (67 +/- 7%, P < 0.01). Eggs recovered from tissues at necropsy were primarily confined to the large intestine (85% of total egg recovered), followed by liver (10%) and small intestine (5%). Significantly more eggs were recovered from MI compared to SI animals, indicating a higher fecundity of female worms in the MI baboons. These date demonstrate that granulomatous responses develop more slowly and modulate more rapidly with repeated infection compared to a single heavy infection and suggest the type of exposure may affect the pathologic response to infection.