During their complex life cycles, the Apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii employ several layers of regulation of their gene expression. One such layer is mediated at the level of translation through upstream open reading frames (uORFs). As uORFs are found in the upstream regions of a majority of transcripts in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant genes, including var2csa in P. falciparum, and ApiAT1 in T. gondii, that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of these genome-wide datasets, taking into account uORFs associated with each gene, will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

The British Society for Parasitology (BSP) holds a biannual symposium devoted to the kinetoplastids, and seeks to cover the full gamut of research into these important organisms, and alternates with the Woods Hole Kinetoplastid Molecular Cell Biology meeting that serves a similar community. While normally embedded within the main BSP Spring meeting, on several occasions the symposium has enjoyed the opportunity of being hosted on mainland Europe. In 2020, the BSP was fortunate to spend some time in Granada in Spain, where a superb meeting with excellent science in a spectacular setting was overshadowed by news of an emerging novel coronavirus. In this editorial, we hope to have captured some of that excellent science and to highlight aspects of the many great papers and reviews in this special issue, as well as provide a few images from the meeting, which we hope for this who attended will bring back some fond memories.

Toxoplasma gondii (T. gondii) is known for its ability to infect warm-blooded vertebrates. Although T. gondii does not appear to parasitize cold-blooded animals, the occurrence of T. gondii infection in marine mammals raises concerns that cold-blooded animals (frogs, toad, turtles, crocodiles, snakes, and fish) and shellfish are potential sources of T. gondii. Therefore, this systematic review aimed to determine the prevalence of T. gondii in mollusks and cold-blooded animals worldwide. We searched PubMed, ScienceDirect, ProQuest, Scopus, and Web of Science from inception to 1 August 2020 for eligible papers in the English language and identified 26 articles that reported the prevalence of T. gondii in mollusks and cold-blooded animals. These articles were subsequently reviewed and data extracted using a standard form. In total, 26 studies [involving 9 cross-sectional studies including 2988 samples of cold-blooded animals (129 positive cases for T. gondii) and 18 cross-sectional studies entailing 13 447 samples of shellfish (692 positive cases for T. gondii)] were included in this study. Although this study showed that shellfish and cold-blooded animals could be potential sources of T. gondii for humans and other hosts that feed on them, further investigations are recommended to determine the prevalence of T. gondii in shellfish and cold-blooded animals.

Ascaris lumbricoides, the roundworm, and Trichuris trichiura, the whipworm, are human intestinal nematode parasites; both are soil-transmitted helminths, are often placed together in an epidemiological context and both remain neglected despite high prevalence. Our understanding of parasitic disease continues to be enhanced through animal models. Despite the similarities between whipworm and roundworm, there are key differences between the two species and these have influenced the application of their respective animal models. In the case of T. trichiura, the fact that a murine equivalent, T. muris completes its life cycle in a mouse model has greatly enhanced our knowledge of whipworm biology, pathogenicity and immunology. In contrast, A. lumbricoides and its porcine equivalent, Ascaris suum, lack a rodent model in which the life cycle is completed. However, evidence continues to accumulate demonstrating that mice represent useful models of early Ascaris infection, a key stage of the life cycle. The use of mouse models for both Ascaris and Trichuris has a long history with early pioneers discovering fundamental aspects of each parasite's biology. Novel technologies and perspectives, as outlined in this special issue, demonstrate how through the prism of mouse models, we can continue to explore the similarities and differences between roundworms and whipworms.

Echinococcus granulosus sensu lato (s.l.) is a zoonotic parasite that causes cystic echinococcosis (CE) in humans. However, E. granulosus sensu stricto (s.s.) is considered the predominant species in CE infections worldwide. According to the population genetic diversity and structure of E. granulosus s.l., gene flow can explain the parasite drift among the neighbouring countries of Pakistan. The mitochondrial (mt) co1 (n = 47), nadh1 (n = 37) and cytb (n = 35) nucleotide sequences of E. granulosus s.l. isolates from Pakistan, Iran, China and India were retrieved from the National Centre for Biotechnology Information database to determine the genealogical relationships. The sequences were grouped as the mt-co1 (genotypes G1 and G3, G6-G7), mt-cytb (genotypes G1 and G3), and mt-nadh1(genotypes G1 and G3). The data were analysed using bioinformatic tools. A total of 19 polymorphic sites for the mt-co1 sequence (374 bp) were observed of which 31.6% (6/19) were parsimony-informative sites. Unique singleton haplotypes within the E. granulosus s.s. haplotype network based on the mt-co1 gene were highly prevalent (68.4%; 13/19) in Pakistani isolates followed by Chinese, Indian and Iranian isolates; four polymorphic sites were detected in the E. canadensis (G6/G7). In E. canadensis mt-co1 haplotype network, 75% (3/4) unique singleton haplotypes were from the Iranian isolates. Twelve polymorphic sites were found using the mt-cytb sequence (547 bp); 25% (3/12) were parsimony-informative and there were 66.7% (8/12) unique singleton haplotypes within the mt-cytb haplotype network in E. granulosus s.s. with the most reported from Pakistan followed by Iran and China. 20 polymorphic sites were detected in E. granulosus s.s. mt-nadh1 sequences (743 bp); 20% (4/20) were parsimony-informative. There were 66.7% (8/12) main single haplotypes within the mt-nadh1 haplotype network, with the most reported from Pakistan followed by that from India, Iran and China. The sequence analyses show low nucleotide diversity and high haplotype diversity in general.

Cystic echinococcosis (CE) occurs in the intermediate host's liver, assuming a bladder-like structure surrounded by the host-derived collagen capsule mainly derived from activated hepatic stellate cells (HSCs). However, the effect of CE on liver natural killer (NK) cells and the potential of transforming growth factor-β (TGF-β) signalling inhibition on alleviating CE-related liver damage remain to be explored. Here, by using the CE-mouse model, we revealed that the inhibitory receptors on the surface of liver NK cells were up-regulated, whereas the activating receptors were down-regulated over time. TGF-β1 secretion was elevated in liver tissues and mainly derived from macrophages. A combination of TGF-β signalling inhibitors SB525334 and pirfenidone could reduce the expression of TGF-β1 signalling pathway-related proteins and collagen production. Based on the secretion of TGF-β1, only the pirfenidone group showed a depressing effect. Also, the combination of SB525334 and pirfenidone exhibited a higher potential in effectively alleviating the senescence of the hepatocytes and restoring liver function. Together, TGF-β1 may be a potential target for the treatment of CE-associated liver fibrosis.

Galectins are a family of proteins that bind β-galactosides and play key roles in a variety of cellular processes including host defence. They have been well studied in hosts but less so in gastrointestinal nematodes. Both host and parasite galectins are present in the gastrointestinal tract following infection. Parasite galectins can both bind antibody, especially highly glycosylated IgE and be bound by antibody. Parasite galectins may act as molecular sponges that soak up antibody. Host galectins promote mast cell degranulation while parasite galectins inhibit degranulation. Host and parasite galectins can also bind mucins and influence mucus viscosity. As the protective response against gastrointestinal nematode infection is partly dependent on IgE mediated mast cell degranulation and mucus, the interactions between host and parasite galectins play key roles in determining the outcome of infection.

Various host and parasite factors interact to determine the outcome of infection. We investigated the effects of two factors on the within-host dynamics of malaria in mice: initial infectious dose and co-infection with a helminth that limits the availability of red blood cells (RBCs). Using a statistical, time-series approach to model the within-host ‘epidemiology’ of malaria, we found that increasing initial dose reduced the time to peak cell-to-cell parasite propagation, but also reduced its magnitude, while helminth co-infection delayed peak cell-to-cell propagation, except at the highest malaria doses. Using a mechanistic model of within-host infection dynamics, we identified dose-dependence in parameters describing host responses to malaria infection and uncovered a plausible explanation of the observed differences in single vs co-infections. Specifically, in co-infections, our model predicted a higher background death rate of RBCs. However, at the highest dose, when intraspecific competition between malaria parasites would be highest, these effects of co-infection were not observed. Such interactions between initial dose and co-infection, although difficult to predict a priori, are key to understanding variation in the severity of disease experienced by hosts and could inform studies of malaria transmission dynamics in nature, where co-infection and low doses are the norm.

Metchnikovellids are a deep-branching group of microsporidia, parasites of gregarines inhabiting the alimentary tract of polychaetes and some other invertebrates. The diversity and phylogeny of these hyperparasites remain poorly studied. Modern descriptions and molecular data are still lacking for many species. The results of a light microscopy study and molecular data for Metchnikovella spiralis Sokolova et al., 2014, a hyperparasite of the eugregarine Polyrhabdina sp., isolated from the polychaete Pygospio elegans, were obtained. The original description of M. spiralis was based primarily on the analysis of stained preparations and transmission electron microscopy images. Here, the species description was complemented with the results of in vivo observations and phylogenetic analysis based on the SSU rRNA gene. It was shown that in this species, free sporogony precedes sac-bound sporogony, as it occurs in the life cycle of most other metchnikovellids. Spore sacs are entwined with spirally wound cords, and possess only one polar plug. Phylogenetic analyses did not group M. spiralis with M. incurvata, another metchnikovellid from the same gregarine species, but placed it as a sister branch to Amphiacantha. The paraphyletic nature of the genus Metchnikovella was discussed. The taxonomic summary for M. spiralis was emended.

The morbidity due to congenital toxoplasmosis in humans is very high. Most of these infected children are likely to develop symptoms of clinical toxoplasmosis. Sequelae in fetus resulting from Toxoplasma gondii infections in women who become infected with this parasite during pregnancy can be devastating and enormous efforts are directed in some countries to prevent these consequences. Here, an update on congenital toxoplasmosis in humans, especially the rate of congenital infections in humans worldwide, is provided. Although several countries have surveillance programmes, most information on the rate of congenital transmission is from France and Brazil. Because of compulsory national screening programme in France to detect and treat women with recently acquired T. gondii infection with anti-toxoplasma therapy, the rate of congenital transmission and the severity of disease in children are declining. Infections by this parasite are widely prevalent in Brazil. The severity of clinical toxoplasmosis in Brazilian children is very high and may be associated with the genetic characteristics of T. gondii isolates prevailing in animals and humans in Brazil. Virtually little or no information is available on this topic from China, India and other countries in Asia.