Article

Genetic and Household Determinants of Predisposition to Human Hookworm Infection in a Brazilian Community

Institute of Integrative and Comparative Biology, University of Leeds, Leeds, United Kingdom.
The Journal of Infectious Diseases (Impact Factor: 5.78). 09/2010; 202(6):954-61. DOI: 10.1086/655813
Source: PubMed

ABSTRACT 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.
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).
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.
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.

0 Followers
 · 
125 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron-deficiency anemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. We report sequencing and assembly of the N. americanus genome (244 Mb, 19,151 genes). Characterization of this first hookworm genome sequence identified genes orchestrating the hookworm's invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, some of which we highlight as potential treatments against inflammatory diseases. We also used a protein microarray to demonstrate a postgenomic application of the hookworm genome sequence. This genome provides an invaluable resource to boost ongoing efforts toward fundamental and applied postgenomic research, including the development of new methods to control hookworm and human immunological diseases.
    Nature Genetics 01/2014; DOI:10.1038/ng.2875 · 29.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Children in rural areas experience the interrelated problems of poor growth, anemia and parasitic infections. We investigated the prevalence of and associations between intestinal helminth and protozoan infections, malnutrition and anemia in school-age Venezuelan children. This cross-sectional study was conducted in 390 children aged 4-16 years from three rural areas of Venezuela: the Amazon Region, Orinoco Delta and Carabobo State. Stool samples were collected for direct parasitic examinations. Anthropometric indicators of chronic (height-for-age Z score) and acute (weight-for-height and Body Mass Index (BMI)-for-age Z score in respectively children under 5 years of age and children aged 5 years and above) malnutrition were calculated. Multivariate linear and logistic regression models were built to determine factors associated with nutritional status and polyparasitism. Hookworm and Strongyloides stercoralis prevalences were highest in children from the Amazon rainforest (respectively 72% and 18%) while children from the Orinoco Delta and Carabobo State showed higher rates of Ascaris lumbricoides (respectively 28% and 37%) and Trichuris trichiura (40% in both regions). The prevalence of Giardia lamblia infection was not significantly different between regions (average: 18%). Anemia prevalence was highest in the Amazon Region (24%). Hemoglobin levels were significantly decreased in children with a hookworm infection. Malnutrition was present in respectively 84%, 30% and 13% of children from the Amazon Region, Orinoco Delta and Carabobo State. In multivariate analysis including all regions, G. lamblia and helminth infections were significantly and negatively associated with respectively height-for-age and weight-for-height/BMI-for-age Z scores. Furthermore, hemoglobin levels were positively associated with the height-for-age Z score (0.11, 95% CI 0.02 - 0.20). In rural populations in Venezuela helminthiasis and giardiasis were associated with acute and chronic nutritional status respectively. These data highlight the need for an integrated approach to control transmission of parasites and improve the health status of rural Venezuelan children.
    PLoS ONE 10/2013; 8(10):e77581. DOI:10.1371/journal.pone.0077581 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Equine internal parasites, mostly cyathostomins, affect both horse welfare and performance. The appearance of anthelmintic-resistant parasites creates a pressing need for optimizing drenching schemes. This optimization may be achieved by identifying genetic markers associated with host susceptibility to infection and then to drench carriers of these markers. The aim of our study was to characterize the genetics of horse resistance to strongyle infection by estimating heritability of this trait in an Arabian pure blood population. A population of 789 Arabian pure blood horses from the Michałów stud farm, Poland were measured for strongyle egg excretion twice a year, over 8 years. Low repeatability values were found for faecal egg counts. Our analyses showed that less than 10% of the observed variation for strongyle faecal egg counts in this population had a genetic origin. However, additional analyses highlighted an age-dependent increase in heritability which was 0.04 (± 0.02) in young horses (up to 3 years of age) but 0.21 (± 0.04) in older ones. These results suggest that a significant part of the inter-individual variation has a genetic origin. This paves the way to a genomic dissection of horse-nematode interactions which might provide predictive markers of susceptibility, allowing individualised drenching schemes. Copyright © 2015. Published by Elsevier Ltd.
    International Journal for Parasitology 01/2015; DOI:10.1016/j.ijpara.2014.11.003 · 3.40 Impact Factor

Full-text (2 Sources)

Download
42 Downloads
Available from
May 30, 2014