Human Hookworm Infection Enhances Mycobacterial Growth Inhibition and Associates With Reduced Risk of Tuberculosis Infection.

Soil-transmitted helminths and Mycobacterium tuberculosis frequently coincide geographically and it is hypothesized that gastrointestinal helminth infection may exacerbate tuberculosis (TB) disease by suppression of Th1 and Th17 responses. However, few studies have focused on latent TB infection (LTBI), which predominates globally. We performed a large observational study of healthy adults migrating from Nepal to the UK (n = 645). Individuals were screened for LTBI and gastrointestinal parasite infections. A significant negative association between hookworm and LTBI-positivity was seen (OR = 0.221; p = 0.039). Hookworm infection treatment did not affect LTBI conversions. Blood from individuals with hookworm had a significantly greater ability to control virulent mycobacterial growth in vitro than from those without, which was lost following hookworm treatment. There was a significant negative relationship between mycobacterial growth and eosinophil counts. Eosinophil-associated differential gene expression characterized the whole blood transcriptome of hookworm infection and correlated with improved mycobacterial control. These data provide a potential alternative explanation for the reduced prevalence of LTBI among individuals with hookworm infection, and possibly an anti-mycobacterial role for helminth-induced eosinophils.

Copro-molecular identification of infections with hookworm eggs in rural Lao PDR.

The prevalence of hookworm eggs in fecal samples, by modified cellophane thick-smear technique, was found to be 30.0% (61/203 samples) in Lahanam Village, Savannakhet Province, Lao PDR. The hookworm eggs were morphologically heterogeneous, so that identification was confirmed by copro-PCR with specific primers for hookworms and Trichostrongylus spp.; 12 samples were positive for Necator americanus, 19 for Ancylostoma spp., with one mixed infection of both. Sequencing of the Ancylostoma spp. copro-PCR products found A. duodenale, and also the animal hookworms, A. caninum and A. ceylanicum. Moreover, Trichostrongylus spp.-specific copro-PCR revealed a significant rate of infection (43/203; 21.2%). Sequencing confirmed the zoonotic species, T. colubriformis. PCR/sequencing is useful for differentiating parasite species. The positives by the Kato-Katz method, and by the combined hookworm/Trichostrongylus specific-PCR, were comparable, although the agreement between the two methodologies was only 50%.

Genetic and household determinants of predisposition to human hookworm infection in a Brazilian community.

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.

Spatial and genetic epidemiology of hookworm in a rural community in Uganda.

There are remarkably few contemporary, population-based studies of intestinal nematode infection for sub-Saharan Africa. This paper presents a comprehensive epidemiological analysis of hookworm infection intensity in a rural Ugandan community. Demographic, kinship, socioeconomic and environmental data were collected for 1,803 individuals aged six months to 85 years in 341 households in a cross-sectional community survey. Hookworm infection was assessed by faecal egg count. Spatial variation in the intensity of infection was assessed using a Bayesian negative binomial spatial regression model and the proportion of variation explained by host additive genetics (heritability) and common domestic environment was estimated using genetic variance component analysis. Overall, the prevalence of hookworm was 39.3%, with the majority of infections (87.7%) of light intensity (

Hookworm infection, anaemia and genetic variability of the New Zealand sea lion.

Hookworms are intestinal blood-feeding nematodes that parasitize and cause high levels of mortality in a wide range of mammals, including otariid pinnipeds. Recently, an empirical study showed that inbreeding (assessed by individual measures of multi-locus heterozygosity) is associated with hookworm-related mortality of California sea lions. If inbreeding increases susceptibility to hookworms, effects would expectedly be stronger in small, fragmented populations. We tested this assumption in the New Zealand sea lion, a threatened otariid that has low levels of genetic variability and high hookworm infection rates. Using a panel of 22 microsatellites, we found that average allelic diversity (5.9) and mean heterozygosity (0.72) were higher than expected for a small population with restricted breeding, and we found no evidence of an association between genetic variability and hookworm resistance. However, similar to what was observed for the California sea lion, homozygosity at a single locus explained the occurrence of anaemia and thrombocytopenia in hookworm-infected pups (generalized linear model, F = 11.81, p < 0.001) and the effect was apparently driven by a particular allele (odds ratio = 34.95%; CI: 7.12-162.41; p < 0.00001). Our study offers further evidence that these haematophagus parasites exert selective pressure on otariid blood-clotting processes.

Heritability of human hookworm infection in Papua New Guinea.

Hookworms infect approximately 740 million humans worldwide and are an important cause of morbidity. The present study examines the role of additive genetic effects in determining the intensity of hookworm infection in humans, and whether these effects vary according to the sex of the host. Parasitological and epidemiological data for a population of 704 subjects in Papua New Guinea were used in variance components analysis. The 'narrow-sense' heritability of hookworm infection was estimated as 0.15+/-0.04 (P<0.001), and remained significant when controlling for shared environmental (household) effects. Allowing the variance components to vary between the sexes of the human host consistently revealed larger additive genetic effects in females than in males, reflected by heritabilities of 0.18 in females and 0.08 in males in a conservative model. Household effects were also higher in females than males, although the overall household effect was not significant. The results indicate that additive genetic effects are an important determinant of the intensity of human hookworm infection in this population. However, despite similar mean and variance of intensity in each sex, the factors responsible for generating variation in intensity differ markedly between males and females.

The bandit, a new DNA transposon from a hookworm-possible horizontal genetic transfer between host and parasite.

BACKGROUND: An enhanced understanding of the hookworm genome and its resident mobile genetic elements should facilitate understanding of the genome evolution, genome organization, possibly host-parasite co-evolution and horizontal gene transfer, and from a practical perspective, development of transposon-based transgenesis for hookworms and other parasitic nematodes. METHODOLOGY/PRINCIPAL FINDINGS: A novel mariner-like element (MLE) was characterized from the genome of the dog hookworm, Ancylostoma caninum, and termed bandit. The consensus sequence of the bandit transposon was 1,285 base pairs (bp) in length. The new transposon was flanked by perfect terminal inverted repeats of 32 nucleotides in length with a common target site duplication TA, and it encoded an open reading frame (ORF) of 342 deduced amino acid residues. Phylogenetic comparisons confirmed that the ORF encoded a mariner-like transposase, which included conserved catalytic domains, and that the bandit transposon belonged to the cecropia subfamily of MLEs. The phylogenetic analysis also indicated that the Hsmar1 transposon from humans was the closest known relative of bandit, and that bandit and Hsmar1 constituted a clade discrete from the Tc1 subfamily of MLEs from the nematode Caenorhabditis elegans. Moreover, homology models based on the crystal structure of Mos1 from Drosophila mauritiana revealed closer identity in active site residues of the catalytic domain including Ser281, Lys289 and Asp293 between bandit and Hsmar1 than between Mos1 and either bandit or Hsmar1. The entire bandit ORF was amplified from genomic DNA and a fragment of the bandit ORF was amplified from RNA, indicating that this transposon is actively transcribed in hookworms. CONCLUSIONS/SIGNIFICANCE: A mariner-like transposon termed bandit has colonized the genome of the hookworm A. caninum. Although MLEs exhibit a broad host range, and are identified in other nematodes, the closest phylogenetic relative of bandit is the Hsmar1 element of humans. This surprising finding suggests that bandit was transferred horizontally between hookworm parasites and their mammalian hosts.

Quantitative genetic analysis of susceptibility to hookworm infection in a population from rural Zimbabwe.

Overdispersion is a common feature of population distribution patterns for hookworm infection in humans. Genetic factors may be partially responsible for this observed increased susceptibility in a fraction of the exposed population. However, the hypothesis that there are genetic components to susceptibility to this infectious disease has not been tested explicitly. The purpose of this study is to quantify the influence of genetic factors on patterns of hookworm infection in a rural population in Zimbabwe. A quantitative measure of hookworm load, number of hookworm eggs per gram of feces, as determined by the Kato thick smear technique, was available for 289 individuals. Of these, 279 individuals were members of 62 nuclear families and 10 were independent individuals. We analyzed the hookworm data in combination with the pedigree structure of the sampled individuals using quantitative genetic analysis techniques. Using this variance decomposition approach, we estimated the heritability of hook worm load to be 0.37 +/- 0.09 (p < 0.0001). This significant heritability indicates that 37% of the variation (after correcting for the effects of covariates) in hookworm eggs per gram observed in this population is attributable to genetic factors. The results suggest that further investigation and characterization of the genetic components influencing susceptibility to hookworm infection are warranted.