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
Ascaris spp. infection affects 800 million people worldwide, and half of the world population is currently at risk of infection. Recurrent reinfection in humans is mostly due to the simplicity of the parasite life cycle, but the impact of multiple exposures to the biology of the infection and the consequences to the host’s homeostasis are poorly understood. In this context, single and multiple exposures in mice were performed in order to characterize the parasitological, histopathological, tissue functional and immunological aspects of experimental larval ascariasis. The most important findings revealed that reinfected mice presented a significant reduction of parasite burden in the lung and an increase in the cellularity in the bronchoalveolar lavage (BAL) associated with a robust granulocytic pulmonary inflammation, leading to a severe impairment of respiratory function. Moreover, the multiple exposures to Ascaris elicited an increased number of circulating inflammatory cells as well as production of higher levels of systemic cytokines, mainly IL-4, IL-5, IL-6, IL-10, IL-17A and TNF-α when compared to single-infected animals. Taken together, our results suggest the intense pulmonary inflammation associated with a polarized systemic Th2/Th17 immune response are crucial to control larval migration after multiple exposures to Ascaris.
We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from the adult hookworm Ancylostoma caninum, and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac-GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac-GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac-GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac-GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac-GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac-GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac-GST-1 is a possible drug and vaccine target for hookworm infection.Hookworm infection is a major cause of disease burden for animals and humans. An estimated 740 million cases of human hookworm infection occur worldwide (12). Most of the pathology attributed to hookworm infection results from intestinal blood loss caused by the adult stages of the parasite (21, 32). The adult hookworm is specially adapted to ingest red blood cells and feed on the intracellular contents and has evolved to produce a battery of molecules for this purpose (22,42). For instance, the parasite uses its buccal capsule to attach to the intestinal mucosa and submucosa, where it mechanically ruptures capillaries and arterioles. From unique cephalic glands, the adult hookworm releases anticoagulants and anti-platelet-aggregating agents into the attachment site (10, 34). The parasite subsequently ruptures red blood cells through the action of a unique hemolysin (13) and then degrades the released hemoglobin through a carefully orchestrated cascade of hemoglobinases (43). This sequence of events is central to the pathogenesis of hookworm disease, which results almost entirely from hookworm-induced blood loss leading to iron deficiency anemia (35).The trichostrongyle Hemonchus contortus is a major cause of anemia and weight loss in small ruminants. Like hookworms, H. contortus produces numerous mechanistically distinct proteases that are thought to digest hemoglobin (27). Recently, adult H. contortus was shown to produce a novel glutathione S-transferase (Hc-GST-1), which has a high-affinity binding site for hematin ...
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