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This study quantifies the rate and intensity of re-infection with human hookworm and Schistosoma mansoni infection 12 months following successful treatment, and investigates the influence of socio-economic, geographical and environmental factors. A longitudinal study of 642 individuals aged over 5 years was conducted in Minas Gerais State, Brazil from June 2004 to March 2006. Risk factors were assessed using interval censored regression for the rate and negative binomial regression for intensity. The crude rate and intensity of hookworm re-infection was 0·21 per year (95% confidence interval (CI) 0·15-0·29) and 70·9 epg (95% CI 47·2-106·6). For S. mansoni the rate was 0·06 per year (95% CI 0·03-0·10) and intensity 6·51 epg (95% CI 3·82-11·11). Rate and intensity of re-infection with hookworm were highest among males and positively associated with previous infection status, absence of a toilet and house structure. Rate and intensity of S. mansoni re-infection were associated with previous infection status as well as geographical, environmental and socio-economic factors. The implications of findings for the design of anti-helminth vaccine trials are discussed.

Background: Predisposition to heavy or light human hookworm infection is consistently reported in treatment-reinfection studies. A significant role for host genetics in determining hookworm infection intensity has also been shown, but the relationship between host genetics and predisposition has not been investigated., Methods: A treatment-reinfection study was conducted among 1302 individuals in Brazil. Bivariate variance components analysis was used to estimate heritability for pretreatment and reinfection intensity and to estimate the contribution of genetic and household correlations between phenotypes to the overall phenotypic correlation (ie, predisposition)., Results: Heritability for hookworm egg count was 17% before treatment and 25% after reinfection. Predisposition to heavy or light hookworm infection was observed, with a phenotypic correlation of 0.34 between pretreatment and reinfection intensity. This correlation was reduced to 0.23 after including household and environmental covariates. Genetic and household correlations were 0.41 and 1, respectively, and explained 88% of the adjusted phenotypic correlation., Conclusions: Predisposition to human hookworm infection in this area results from a combination of host genetics and consistent differences in exposure, with the latter explained by household and environmental factors. Unmeasured individual-specific differences in exposure did not contribute to predisposition.

Strong statistical associations between soil-transmitted helminths and schistosomes are frequently observed in co-endemic human populations, although the underlying explanations remain poorly understood. This study investigates the contribution of host genetics and domestic environment to hookworm and Schistosoma mansoni infection intensity and evaluates the role of genetic and non-genetic factors in co-variation of infection intensity. Detailed genealogical information allowed assignment of 1303 individuals living in the Brazilian community of Americaninhas, Minas Gerais state, to 25 pedigrees (containing between two and 1159 members) residing in 303 households. The prevalence of co-infection with both hookworms and schistosomes was high (38.5%), with significant correlation between Necator americanus and S. mansoni faecal egg counts. Bivariate variance component analysis demonstrated a modest but significant species-specific heritability for intensity of N. americanus (h(2)=0.196) and S. mansoni infection (h(2)=0.230). However, after accounting for demographic, socio-economic and household risk factors, no evidence for common genetic control of intensity of hookworm and schistosome infection was observed. There was some evidence for residual clustering within households but the majority (63%) of the covariance between N. americanus and S. mansoni infection intensity remained specific to the individual and could not be explained by shared genes, shared environment or other shared demographic, socio-economic or environmental risk factors. Our results emphasize the importance of exposure to hookworm and schistosome infection in driving the association between levels of infection with these species in hosts resident in areas of high transmission and suggest that much of this common exposure occurs outside the home., (2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the nutritional status of individuals from a rural area of Brazil, and associations with helminth infections in an age-stratified sample., Method: A total of 1113 individuals aged from 6 months to 83 years from the rural community of Americaninhas in Minas Gerais were investigated. Assessments comprised anthropometric measurements of weight, height and body composition, examining faecal samples for helminth eggs, and peripheral blood assays for albumin, haemoglobin and ferritin concentrations., Results: Ten percent of the participants were underweight, 12.8% were overweight and 28.3% of the children and adolescents were stunted. 11.6% had low lean body mass and 28.8% had low fat body mass. Hypoalbuminaemia was seen in 5.5%, anaemia in 12.5% and iron deficiency in 13.1%, although the prevalence of these two indices increased with age. Multivariate analysis showed that, after controlling for age, sex and socio-economic status, stunting was significantly associated with Ascaris lumbricoides infection among children and adolescents, whereas low body mass was significantly associated with hookworm infection among adults and the elderly., Conclusions: Helminth infections are associated with undernutrition in endemic populations, with important differences between the effects of hookworm and A. lumbricoides on age-related nutritional status.

Background: Individuals living in areas endemic for helminths are commonly infected with multiple species. Despite increasing emphasis given to the potential health impacts of polyparasitism, few studies have investigated the relative importance of household and environmental factors on the risk of helminth co-infection. Here, we present an investigation of exposure-related risk factors as sources of heterogeneity in the distribution of co-infection with Necator americanus and Schistosoma mansoni in a region of southeastern Brazil., Methodology: Cross-sectional parasitological and socio-economic data from a community-based household survey were combined with remotely sensed environmental data using a geographical information system. Geo-statistical methods were used to explore patterns of mono- and co-infection with N. americanus and S. mansoni in the region. Bayesian hierarchical models were then developed to identify risk factors for mono- and co-infection in relation to community-based survey data to assess their roles in explaining observed heterogeneity in mono and co-infection with these two helminth species., Principal Findings: The majority of individuals had N. americanus (71.1%) and/or S. mansoni (50.3%) infection; 41.0% of individuals were co-infected with both helminths. Prevalence of co-infection with these two species varied substantially across the study area, and there was strong evidence of household clustering. Hierarchical multinomial models demonstrated that relative socio-economic status, household crowding, living in the eastern watershed and high Normalized Difference Vegetation Index (NDVI) were significantly associated with N. americanus and S. mansoni co-infection. These risk factors could, however, only account for an estimated 32% of variability between households., Conclusions: Our results demonstrate that variability in risk of N. americanus and S. mansoni co-infection between households cannot be entirely explained by exposure-related risk factors, emphasizing the possible role of other household factors in the heterogeneous distribution of helminth co-infection. Untangling the relative contribution of intrinsic host factors from household and environmental determinants therefore remains critical to our understanding of helminth epidemiology.

We describe how hookworms interact with their human hosts by comparing lymphocyte phenotyping, proliferative responses, and cytokine and chemokine secretion patterns in adults who are either mono-infected with Necator americanus or egg-negative controls resident in an area of high transmission in Brazil. Cellular immune responses against crude hookworm antigen extracts from different developmental stages were evaluated simultaneously. Principal component analysis (PCA) was used to reduce the standardized immune responses. Random effects multivariate regression was then used to investigate whether principal components (PC) differ between the two groups once potential confounders and effect modifiers have been accounted for. Although hookworm patients had reduced percentages of T and B cells, they had higher levels of activated CD4(+) T and CD19(+) B cells. This state of 'immune activation' coincided with lower proliferative responses, especially to third-stage larval antigen. Cytokine levels in mono-infected adults were also lower and characterized by a mixed Th1/Th2-type profile. Excretory/secretory antigen from adult worms was a potent modulator of the immune response, resulting in diminished TNF-alpha and IL-10 secretion in peripheral blood mononuclear cells (PBMC) from hookworm infected patients. We propose that the longevity of hookworms in their human hosts results from a stage-specific, down-modulation of the immune response.

Surprisingly few detailed age-stratified data exist on the epidemiology of hookworm and iron status, especially in Latin America. We present data from a cross-sectional survey examining 1332 individuals aged 0-86 years from a community in south-east Brazil for hookworm, anaemia and iron deficiency. Sixty-eight percent of individuals were infected with the human hookworm Necator americanus. The force of infection (lambda=0.354) was similar to estimates from other areas of high hookworm transmission. Individuals from poorer households had significantly higher prevalence and intensity of infection than individuals from better-off households. The prevalence of anaemia, iron deficiency and iron-deficiency anaemia was 11.8%, 12.7% and 4.3%, respectively. Anaemia was most prevalent among young children and the elderly. Univariate analysis showed that haemoglobin and serum ferritin were both significantly negatively associated with hookworm intensity among both school-aged children and adults. Multivariate analysis showed that, after controlling for socio-economic status, iron indicators were significantly associated with heavy hookworm infection. Our results indicate that, even in areas where there is a low overall prevalence of anaemia, hookworm can still have an important impact on host iron status, especially in school-aged children and the elderly.

Marked heterogeneity exists in the patterns of parasitic infection between individuals, households and communities. Analysis of parasite distributions within populations is complicated by the fact that parasite distributions are highly aggregated and few studies have explicitly incorporated this distribution when investigating small-scale spatial heterogeneities. This study aimed to quantify the small-scale (within- and between-household) heterogeneity of helminth infection in an area of Minas Gerais State, Brazil, with rural and urban sectors. Parasitological data from a cross-sectional survey of 1,249 individuals aged 0-86 years from 242 households were analysed. Within-household clustering of infection was assessed using random effect logistic regression models and between-household spatial heterogeneity was assessed using a Bayesian negative binomial spatial model. The overall prevalence of hookworm (Necator americanus) was 66.9%, the prevalence of Schistosoma mansoni was 44.9% and the prevalence of Ascaris lumbricoides was 48.8%. Statistical analysis indicated significant (within) household and (between household) spatial clustering of hookworm in both rural and urban areas and of S. mansoni in rural areas. There was no evidence of either household or spatial clustering of S. mansoni in urban areas. The spatial correlation of S. mansoni was estimated to reduce by half over a distance of 700 m in the rural area. Rural hookworm had a much smaller half-distance (28 m) and urban hookworm showed an even smaller half-distance (12 m). We suggest that such species-specific differences in patterns of infection by environment are primarily due to variation in exposure and parasite life cycle, although host genetic factors cannot be ruled out.

Objective: To identify possible synergistic associations of hookworm and other helminths., Method: Cross-sectional survey of all households within 10 km2 of Americaninhas, a rural community in Minas Gerais, Brazil. We determined the prevalence and intensity of single and multiple helminth species infection in an age-stratified sample of 1332 individuals from 335 households., Results: Hookworm was the most prevalent helminth infection (68.2%), followed by Ascaris lumbricoides (48.8%) and Schistosoma mansoni (45.3%). Overall, 60.6% of individuals harboured mixed helminth infections. Multivariate analysis indicated significant positive associations for co-infection with hookworm and S. mansoni and for co-infection with hookworm and A. lumbricoides. Co-infections with hookworm and A. lumbricoides resulted in higher egg counts for both, suggesting a synergistic relationship between these species, although, we found important age differences in this relationship. However, the intensity of S. mansoni or A. lumbricoides co-infection did not differ from that of mono-infection., Conclusion: These results have implications for the epidemiology, immunology and control of multiple helminth infections. More research is needed to examine the rates of re-infection and immune responses after chemotherapy, and to what extent the effects of polyparasitism are altered by chemotherapy.

Much research points to the importance of the household in the study of water-borne diseases such as schistosomiasis. An important aspect of the household is the clustering of domestic activities associated with water collection, storage and usage. Such activities can result in the sharing of water-contact sites and water-contact behaviour, which expose household members to similar risks of infection. In previous studies, we determined that shared residence accounted for 28% of the variance in Schistosoma faecal egg excretion rates. We now quantify the effect of shared residence on the variation in water-related health behaviours. We found that shared residence accounted for 30% of the variation in total water contacts per week. It also accounted for a large proportion of the variation in individual water-contact behaviour: e.g. agricultural contacts (63%), washing limbs (56%) or bathing (41%). These results implicate the household as an important composite measure of the complex relationships between socioeconomic, environmental and behavioural factors that influence water-contact behaviour and, therefore, the transmission of schistosomiasis. Our results also support a focus on the household in the implementation of schistosomiasis prevention and control efforts.