Impact of Next-Generation Technologies on Exploring Socioeconomically Important Parasites and Developing New Interventions [chapter]

Cinzia Cantacessi, Andreas Hofmann, Bronwyn E. Campbell, Robin B. Gasser
2014 Msphere  
2 Summary High-throughput molecular and computer technologies have become instrumental for systems biological explorations of pathogens, including parasites. For instance, investigations of the transcriptomes of different developmental stages of parasitic nematodes give insights into gene expression, regulation and function in a parasite, which is a significant step to understanding their biology, as well as interactions with their host(s) and disease. This chapter gives (i) a background on
more » ... a background on some key parasitic nematodes of socio-economic importance, (ii) describes sequencing and bioinformatic technologies for large-scale studies of the transcriptomes and genomes of these parasites, (iii) provides some recent examples of applications, and (ivii) emphasizes the prospects of fundamental biological explorations of parasites using these technologies for the development of new interventions to combat parasitic diseases. Running head: Next-generation technologies to understand parasites and develop new interventions 4 Brief background on parasitic nematodes As one of the most diverse phyla in the animal kingdom, the phylum Nematoda includes > 28,000 species, of which > 16,000 are parasites of animals or plants (14, 20) . This phylum consists of two main classes, the Adenophorea and the Secernentea (21). Within the Secernentea, species within the orders Ascaridida, Oxyurida, Spirurida and Strongylida are parasites of humans and other vertebrates (14). Within the latter order, the superfamily Strongyloidea includes, amongst others, some intestinal parasites of pigs, ruminants (Chabertiidae) and equids (family Strongylidae) (14). Members of this superfamily are characterized by complex buccal capsules, often with a series of leaf-like structures on the border of the labial region (= corona radiata) (22). In contrast, the buccal capsule, lips and corona radiata of species of parasitic nematodes of the superfamily Trichostrongyloidea are greatly reduced or absent (23-25). Members of theis latter superfamily Trichostrongyloidea ('trichostrongyles') are common parasites of mammals, particularly ruminants (14, 26). The superfamily Ancylostomatoidea ('hookworms') includes blood-feeding nematodes, characterized by large, globular buccal capsules, which enable them to attach to the intestinal wall to feed on blood (14). According to a molecular classification proposed by Blaxter et al. (27), members of the Strongylida, such as trichostrongyles and hookworms, as well as the freeliving nematodes of the sub-order Rhabditina (e.g., Caenorhabditis elegans) and order Diplogasterida (e.g., Pristionchus pacificus), belong to 'clade V' of the Nematoda. Selected examples of nematodes (order Strongylida) of major socio-economic importance Trichostrongyles Within the superfamily Trichostrongyloidea, Haemonchus contortus (barber's pole worm) and Trichostrongylus spp., for example, are responsible for substantial production losses in the 5 livestock industries worldwide (10, 28). H. contortus is the most important nematode of small ruminants in subtropical and tropical (summer rainfall) areas, whereas some Trichostrongylus spp. are often dominant in winter rainfall areas due to their ability to develop and survive at lower temperatures than H. contortus does (29). The life cycles of H. contortus and T. colubriformis are similar and direct, with eggs (26, 30, 31) being laid by females in the abomasum (H. contortus) or small intestine (Trichostrongylus) of the host (30, 31). Under suitable environmental conditions (30, 32), first-stage larvae (L1s) hatch from eggs to develop, via the second-stage larvae (L2s), to infective, third-stage larve (L3s). The cuticle of the L2 is retained as a sheath around the L3 and protects it from desiccation (14, 30, 32). Small ruminants acquire the infection by ingesting L3s from contaminated pastures. The L3s pass through the forestomachs and undergo an exsheathment process to then establish, via the parasitic fourthstage larvae (L4s), as adult males and females in the abomasum (H. contortus) or small intestine (Trichostrongylus) within ~3 weeks (14, 26, 30, 32). The exsheathment process is triggered by stimuli within the host and may include (depending on the species of nematode) dissolved gaseous CO2 and undissociated carbonic acid (H. contortus) or hydrochloric acid and pepsin (T. colubriformis) in the abomasum.; Tthe L3s respond to these stimuli by producing an exsheathment fluid which determines the detachment of the sheath from the bodies of the larvae (5, 33-35). The adults of H. contortus feed on blood from vessels in the gastric wall. Consequently, the main clinical signs of acute haemonchosis are anaemia, variable degrees of oedema, as well as lethargy, decreased live-weight gain, impaired wool/milk production and decreased reproductive performance, often leading to death in severely affected animals (36, 37). Trichostrongylosis is triggered by the presence of adult parasites in mucus-covered tunnels in the epithelial surface of the small intestine (38), usually associated with extensive villous atrophy, combined with hyperplasia of the sub-mucosal glands, mucosal thickening and erosion as well as infiltration of lymphocytes and neutrophils into affected areas (38)(39)(40)(41)(42). Clinical signs of trichostrongylosis 6 include malabsorption, weight loss, progressive emaciation and diarrhoea (= scouring or 'black scour'). Hookworms The hookworms N. americanus and An. duodenale of humans are estimated to infect ~1 billion people in rural regions of the subtropics and tropics (1), with the highest prevalence (~17%) recorded in areas of sub-Saharan Africa and China (1, 43, 44 ), and causing an estimated disease burden of 22 million disability-adjusted life years (DALYs) (45). Although N. americanus is the most widely distributed hookworm of humans globally (1), a related species, An. caninum, is a cosmopolitan hookworm of the small intestine of dogs and other canids (14, 26). The life cycle of these nematodes is direct, with female hookworms excreting thin-shelled eggs, which are passed in the faeces of the host (26, 46). Under suitable environmental conditions (i.e., 23-33 °C) the L1s hatch from the eggs (26, 46) , feed on microbes and, within 2 days, moult to L2s, and then to L3s within 4-5 days. The L3 stage retains the cuticle of the L2 (i.e., sheath) and is called a 'filariform' larva (46). Infection occurs when the L3s penetrate the skin of the vertebrate host following cuticular shedding (47); then, larvae enter the subcutaneous tissues and migrate via the circulatory system to the heart and lungs, where they moult to fourth-stage larvae (L4s). From the lungs, the larvae migrate (via the airways and pharynx) to the small intestine, where they develop to adult males and females within 2-7 weeks, depending on species (14, 26, 48, 49) . The adult stages attach by their buccal capsule to the intestinal mucosa, rupture capillaries and feed on blood (50, 51). Although skin penetration is considered the main route, ingestion of L3s might also lead to infection (52). L3s of Ancylostoma spp. can undergo hypobiosis (= developmental arrest) in the somatic tissues of the vertebrate host and, following activation during pregnancy, undergo transmammary transmission to the offspring (53-55). Hookworm disease relates mainly to the blood-feeding activity by the adult worms within the host (50). Focal lesions caused by the attachment of the worms are characterized by local haemorrhage, tissue cytolysis and neutrophilic immune response (50). The clinical expression of
doi:10.1007/978-1-4939-2004-4_31 pmid:25399114 fatcat:viyzkpcf2fcn5exyx2ixq3cfw4