Whipworms are large-intestinal nematode parasites of mammals. The scientific name for whipworms is Trichuris (which means 'hair tail'), a name applied by Johann Georg Roederer in 1761, who mistook the thin front end for the tail. Over 70 Trichuris spp. are recognized, including the medically important human parasite Trichuris trichiura (the aetiological agent of trichuriasis) and the pig whipworm Trichuris suis. Whipworms have been associated with humans for over 8,000 years, as evidenced by the presence of T. trichiura eggs in coprolites (fossilized faeces) found in both Old World and New World archaeological sites 1-3 . Roundworms (Ascaris spp.) are also intestinal nematodes, but, unlike whipworms, they dwell in the small intestine. Ascaris lumbricoides (first described by Carl Linnaeus in 1758) is the causative agent of the human disease ascariasis. In contrast to whipworms, the genus Ascaris differs from the genus Trichuris in that only one other Ascaris species has been described -Ascaris suum, a ubiquitous pathogen of pigs. After considerable debate as to whether these two ascarids are in fact distinct species, the current opinion is that they are two species, closely related at the phylogenetic level but reproductively isolated (that is, they are unable to interbreed successfully) 4 . Like T. trichiura, A. lumbricoides has a long association with its human host, with eggs detected in embalming material from over 7,000 years ago 5 (Fig. 1).Both T. trichiura and A. lumbricoides are highly prevalent helminths (common name for parasitic worms) 6,7 . The infections occur by ingestion of embryonated (containing an embryo) eggs through contaminated soil or food. Both parasites contribute to chronic, longterm nutritional morbidity and affect cognitive development, although there is less evidence supporting this latter effect. Acute complications associated with A. lumbricoides infections of heavy intensity (that is, with a high worm burden) are intestinal obstruction and biliary ascariasis, whereas complications of T. trichiura infections include Trichuris dysentery syndrome (TDS) and rectal prolapse. The main approach to infection control is large-scale provision of anthelminthic treatment to children and girls and women of reproductive age, with accompanying improvements in access to clean water and sanitation, to reduce worm burden-associated morbidity 8 . Whilst largely effective against ascariasis, mass drug administration (MDA) programmes have been substantially less so against trichuriasis, particularly in sub-Saharan Africa 9 .In this Primer, we provide a current view of both T. trichiura and A. lumbricoides infections epidemiology, disease mechanisms, diagnosis, screening and prevention. We also review current management strategies and consider key research areas that may lead to improved control of these two important neglected tropical
The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a highly debilitating human pathology that affects millions of people in the Americas. The sequencing of this parasite's genome reveals that trans-sialidase/trans-sialidase-like (TcS), a polymorphic protein family known to be involved in several aspects of T. cruzi biology, is the largest T. cruzi gene family, encoding more than 1,400 genes. Despite the fact that four TcS groups are well characterized and only one of the groups contains active trans-sialidases, all members of the family are annotated in the T. cruzi genome database as trans-sialidase. After performing sequence clustering analysis with all TcS complete genes, we identified four additional groups, demonstrating that the TcS family is even more heterogeneous than previously thought. Interestingly, members of distinct TcS groups show distinctive patterns of chromosome localization. Members of the TcSgroupII, which harbor proteins involved in host cell attachment/invasion, are preferentially located in subtelomeric regions, whereas members of the largest and new TcSgroupV have internal chromosomal locations. Real-time RT-PCR confirms the expression of genes derived from new groups and shows that the pattern of expression is not similar within and between groups. We also performed B-cell epitope prediction on the family and constructed a TcS specific peptide array, which was screened with sera from T. cruzi-infected mice. We demonstrated that all seven groups represented in the array are antigenic. A highly reactive peptide occurs in sixty TcS proteins including members of two new groups and may contribute to the known cross-reactivity of T. cruzi epitopes during infection. Taken together, our results contribute to a better understanding of the real complexity of the TcS family and open new avenues for investigating novel roles of this family during T. cruzi infection.
BackgroundHookworms infect 730 million people in developing countries where they are a leading cause of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins with the Ancylostoma caninum aspartic protease 1, APR-1.Methods and FindingsWe show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular responses and resulted in significantly reduced hookworm burdens (p = 0.056) and fecal egg counts (p = 0.018) in vaccinated dogs compared to control dogs after challenge with infective larvae of A. caninum. Most importantly, vaccinated dogs were protected against blood loss (p = 0.049) and most did not develop anemia, the major pathologic sequela of hookworm disease. IgG from vaccinated animals decreased the catalytic activity of the recombinant enzyme in vitro and the antibody bound in situ to the intestines of worms recovered from vaccinated dogs, implying that the vaccine interferes with the parasite's ability to digest blood.ConclusionTo the best of our knowledge, this is the first report of a recombinant vaccine from a hematophagous parasite that significantly reduces both parasite load and blood loss, and it supports the development of APR-1 as a human hookworm vaccine.
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