Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide 1 . No vaccines are available, and treatment relies on one drug, praziquantel 2 . Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer 1,3 and as a predisposing factor for HIV/AIDS 4,5 . The parasite is transmitted to humans from freshwater snails 1 . Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease 6 and induce squamous cell carcinoma 7 . Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites 8,9 . We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.

Parasitic nematodes of the genus Toxocara are socioeconomically important zoonotic pathogens. These parasites are usually directly transmitted to the human host via the faecal-oral route and can cause toxocariasis and associated complications, including allergic and neurological disorders. Although tens of millions of people are estimated to be exposed to or infected with Toxocara spp, global epidemiological information on the relationship between seropositivity and toxocariasis is limited. Recent findings suggest that the effect of toxocariasis on human health is increasing in some countries. Here we review the salient background on Toxocara and biology, summarise key aspects of the pathogenesis, diagnosis, and treatment of toxocariasis, describe what is known about its geographic distribution and prevalence, and make some recommendations for future research towards the prevention and control of this important disease.

BackgroundThe barber's pole worm, Haemonchus contortus, is one of the most economically important parasites of small ruminants worldwide. Although this parasite can be controlled using anthelmintic drugs, resistance against most drugs in common use has become a widespread problem. We provide a draft of the genome and the transcriptomes of all key developmental stages of H. contortus to support biological and biotechnological research areas of this and related parasites.ResultsThe draft genome of H. contortus is 320 Mb in size and encodes 23,610 protein-coding genes. On a fundamental level, we elucidate transcriptional alterations taking place throughout the life cycle, characterize the parasite's gene silencing machinery, and explore molecules involved in development, reproduction, host-parasite interactions, immunity, and disease. The secretome of H. contortus is particularly rich in peptidases linked to blood-feeding activity and interactions with host tissues, and a diverse array of molecules is involved in complex immune responses. On an applied level, we predict drug targets and identify vaccine molecules.ConclusionsThe draft genome and developmental transcriptome of H. contortus provide a major resource to the scientific community for a wide range of genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological, and epidemiological investigations, and a solid foundation for biotechnological outcomes, including new anthelmintics, vaccines and diagnostic tests. This first draft genome of any strongylid nematode paves the way for a rapid acceleration in our understanding of a wide range of socioeconomically important parasites of one of the largest nematode orders.

Due to major problems with drug resistance in parasitic nematodes of animals, there is a substantial need and excellent opportunities to develop new anthelmintics via genomic-guided and/or repurposing approaches. In the present study, we established a practical and cost-effective whole-organism assay for the in vitro-screening of compounds for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm). The assay is based on the use of exsheathed L3 (xL3) and L4 stages of H. contortus of small ruminants (sheep and goats). Using this assay, we screened a panel of 522 well-curated kinase inhibitors (GlaxoSmithKline, USA; code: PKIS2) for activity against H. contortus by measuring the inhibition of larval motility using an automated image analysis system. We identified two chemicals within the compound classes biphenyl amides and pyrazolo[1,5-α]pyridines, which reproducibly inhibit both xL3 and L4 motility and development, with IC50s of 14-47 μM. Given that these inhibitors were designed as anti-inflammatory drugs for use in humans and fit the Lipinski rule-of-five (including bioavailability), they show promise for hit-to-lead optimisation and repurposing for use against parasitic nematodes. The screening assay established here has significant advantages over conventional methods, particularly in terms of ease of use, throughput, time and cost. Although not yet fully automated, the current assay is readily suited to the screening of hundreds to thousands of compounds for subsequent hit-to-lead optimisation. The current assay is highly adaptable to many parasites of socioeconomic importance, including those causing neglected tropical diseases. This aspect is of major relevance, given the urgent need to deliver the goals of the London Declaration (http://unitingtocombatntds.org/resource/london-declaration) through the rapid and efficient repurposing of compounds in public-private partnerships.