Similarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recent in vitro and immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The ‘trade-off’ between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigens in utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.

The Consortium for Anthelmintic Resistance and Susceptibility (CARS) brings together researchers worldwide, with a focus of advancing knowledge of resistance and providing information on detection methods and treatment strategies. Advances in this field suggest mechanisms and features of resistance that are shared among different classes of anthelmintic. Benzimidazole resistance is characterized by specific amino acid substitutions in beta-tubulin. If present, these substitutions increase in frequency upon drug treatment and lead to treatment failure. In the laboratory, sequence substitutions in ion-channels can contribute to macrocyclic lactone resistance, but there is little evidence that they are significant in the field. Changes in gene expression are associated with resistance to several different classes of anthelmintic. Increased P-glycoprotein expression may prevent drug access to its site of action. Decreased expression of ion-channel subunits and the loss of specific receptors may remove the drug target. Tools for the identification and genetic analysis of parasitic nematodes and a new online database will help to coordinate research efforts in this area. Resistance may result from a loss of sensitivity as well as the appearance of resistance. A focus on the presence of anthelmintic susceptibility may be as important as the detection of resistance.

Objective. The aim of this work was to study the prevalence and genetic diversity of Babesia in Ixodes persulcatus ticks and small mammals from Ural and Siberia in Russia. Methods. In total, 481 small mammals and 922 questing adult I. persulcatus from North Ural (Sverdlovsk region) and West Siberia (Novosibirsk region) were examined for the presence of Babesia by nested PCR based on the 18S rRNA gene. Results. Babesia microti of the ‘Munich’-type was found in 36·2% of blood samples of the small mammals from the Sverdlovsk region and B. microti of the ‘US’-type in 5·3% of the animals from the Novosibirsk region. Babesia DNA was not detected in 133 analysed I. persulcatus from the Sverdlovsk region; however, it was found in 24 of 789 ticks from the Novosibirsk region. Three distinct Babesia species were detected in I. persulcatus. B. microti ‘US’-type was identified in 10 ticks, Babesia closely related to B. divergens/B. capreoli in 2 ticks, and Babesia closely related to B. venatorum (EU1) in 12 ticks. Conclusion. To our knowledge, this is the first detection of Babesia sensu stricto in I. persulcatus ticks and of B. microti in I. persulcatus in the Asian part of Russia.

Introduction. Evaluation of Leishmania drug susceptibility depends on in vitro SbV susceptibility assays, which are labour-intensive and may give a biased view of the true parasite resistance. Molecular markers are urgently needed to improve and simplify the monitoring of SbV-resistance. We analysed here the gene expression profile of 21 L. braziliensis clinical isolates in vitro defined as SbV-resistant and -sensitive, in order to identify potential resistance markers. Methods. The differential expression of 13 genes involved in SbV metabolism, oxidative stress or housekeeping functions was analysed during in vitro promastigote growth. Results. Expression profiles were up-regulated for 5 genes only, each time affecting a different set of isolates (mosaic picture of gene expression). Two genes, ODC (ornithine decarboxylase) and TRYR (trypanothione reductase), showed a significantly higher expression rate in the group of SbV-resistant compared to the group of SbV-sensitive parasites (P<0·01). However, analysis of individual isolates showed both markers to explain only partially the drug resistance. Discussion. Our results might be explained by (i) the occurrence of a pleiotropic molecular mechanism leading to the in vitro SbV resistance and/or (ii) the existence of different epi-phenotypes not revealed by the in vitro SbV susceptibility assays, but interfering with the gene expression patterns.

Giardia lamblia is one of the most prevalent parasites of mankind and is estimated to cause over 200 million infections per year. To screen chemical libraries for compounds that perturb trophozoite proliferation we adapted a conventional culture method to 384-well plates and identified numerous inhibitors. Here we used a modified assay to screen for compounds that promote trophozoite multiplication. Trophozoite growth was reduced by dilution of the culture medium and the growth period was extended to screen 2 compound libraries comprising 1500 compounds. A total of 4 agonists of trophozoite multiplication were identified. In the presence of one of these compounds, strychnine, enhanced growth was accompanied by unusual trophozoite morphology characterized by dividing trophozoites displaying more than the 2 nuclei per cell which are normally observed. The other agonists, although belonging to 2 distinct chemical groups, are known to affect isoprenylation, indicating a link between protein or lipid isoprenylation and growth in culture. Although inhibitors of isoprenylation are known to antagonize proliferation of mammalian cells, an agonistic effect of isoprenylation modulators has to our knowledge not been described previously. These observations illustrate the power of chemical genetics for identifying pathways controlling specific traits in G. lamblia.

In Trypanosoma evansi infections changes in the haemogram are commonly observed, and the enzyme adenosine deaminase (ADA) plays an important role in the production and differentiation of blood cells. Thus, the aim of this study was to evaluate the activity of ADA in serum, erythrocytes and lymphocytes of rats infected with T. evansi compared to non-infected rats. Thirty adult rats were used, divided into 3 uniform groups. The animals in groups A and B were infected intraperitoneally with 2×106 trypomastigotes/rat. Rodents from group C (control group), were not-infected. Blood collection was performed on days 4 and 20 post-infection (p.i.) in order to obtain acute and chronic infection stages of disease. The blood was used to assess the activity of ADA. In the blood, reduced haematocrit and increased lymphocytes were correlated with ADA activity in erythrocytes and lymphocytes. We observed reduction of ADA activity in serum and erythrocytes in rats infected with T. evansi compared to non-infected rats (P<0·05). ADA activity in lymphocytes was decreased after 4 days, when the parasitaemia was high and increased after 20 days, when the number of circulating parasites was low. In conclusion, our results showed that the ADA activity was altered in serum, lymphocytes and erythrocytes of rats, concomitantly with haematological parameters, in experimental infection by T. evansi.

Manipulation of host phenotype (e.g. behaviour, appearance) is suggested to be a common strategy to enhance transmission in trophically transmitted parasites. However, in many systems, evidence of manipulation comes exclusively from laboratory studies and its occurrence in natural host populations is poorly understood. Here, we examined the potential for host manipulation by Diplostomum eye flukes indirectly by quantifying the physiological effects of parasites on fish. Earlier laboratory studies have shown that Diplostomum infection predisposes fish to predation by birds (definitive hosts of the parasites) by reducing fish vision through cataract formation. However, occurrence of cataracts and the subsequent potential for host manipulation in natural fish populations has remained poorly explored. We studied the occurrence of eye fluke-induced cataracts from 7 common fish species (Gymnocephalus cernuus, Rutilus rutilus, Leuciscus leuciscus, Alburnus alburnus, Osmerus eperlanus, Coregonus lavaretus and Gasterosteus aculeatus) from the Bothnian Bay in the Baltic Sea. We found that the parasite-induced cataracts were common in fish and they also reached high levels which are likely to predispose fish to predation. However, we observed such cataracts only in species with the highest parasite abundances, which suggests that only certain hosts may be strongly affected by the infection.

An evaluation of the genetic diversity within Fasciola hepatica (liver fluke) may provide an insight into its potential to respond to environmental changes, such as anthelmintic use or climate change. In this study, we determined the mitochondrial DNA haplotypes of >400 flukes from 29 individual cattle, from 2 farms in the Netherlands, as an exemplar of fasciolosis in a European context. Analysis of this dataset has provided us with a measure of the genetic variation within infrapopulations (individual hosts) and the diversity between infrapopulations within a herd of cattle. Temporal sampling from one farm allowed for the measurement of the stability of genetic variation at a single location, whilst the comparison between the two farms provided information on the variation in relation to distance and previous anthelmintic regimes. We showed that the liver fluke population in this region is predominantly linked to 2 distinct clades. Individual infrapopulations contain a leptokurtic distribution of genetically diverse flukes. The haplotypes present on a farm have been shown to change significantly over a relatively short time-period.

A study has been carried out to determine whether the action of triclabendazole (TCBZ) against the liver fluke, Fasciola hepatica is altered by inhibition of the cytochrome P450 (CYP 450)-mediated drug metabolism pathway. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible fluke isolates were used for these experiments, the basic design of which is given in the paper by Devine et al. (2010a). Piperonyl butoxide (PB) was the CYP P450 inhibitor used. Morphological changes resulting from drug treatment and following metabolic inhibition were assessed by means of transmission electron microscopy. After treatment with either TCBZ or TCBZ.SO on their own, there was greater disruption to the TCBZ-susceptible than TCBZ–resistant isolate. However, co-incubation with PB+TCBZ, but more particularly PB+TCBZ.SO, led to greater changes to the TCBZ-resistant isolate than with each drug on its own, with blebbing of the apical plasma membrane, severe swelling of the basal infolds and their associated mucopolysaccharide masses in the syncytium and flooding in the internal tissues. Golgi complexes were greatly reduced or absent in the tegumental cells and the synthesis and production of secretory bodies were badly disrupted. The mitochondria were swollen throughout the tegumental system and the somatic muscle blocks were disrupted. With the TCBZ-susceptible Cullompton isolate, there was a limited increase in drug action following co-incubation with PB. The results provide evidence that the condition of a TCBZ-resistant fluke can be altered by inhibition of drug metabolism. Moreover, they support the concept that altered drug metabolism contributes to the mechanism of resistance to TCBZ.

Nematodes represent one of the most abundant and species-rich groups of animals on the planet, with parasitic species causing chronic, debilitating infections in both livestock and humans worldwide. The prevalence and success of the nematodes is a direct consequence of the exceptionally protective properties of their cuticle. The synthesis of this cuticle is a complex multi-step process, which is repeated 4 times from hatchling to adult and has been investigated in detail in the free-living nematode, Caenorhabditis elegans. This process is known as moulting and involves numerous enzymes in the synthesis and degradation of the collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally conserved enzymes of the astacin metalloprotease family which, when mutated, result in a phenotype associated with the late-stage moulting defects, namely the inability to remove the preceding cuticle. Extensive genome searches in the gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues†. Significantly, the nas-36 gene from B. malayi could successfully complement the moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double mutants, suggesting a conserved function for NAS-36 between these diverse nematode species. This conservation between species was further indicated when the recombinant enzymes demonstrated a similar range of inhibitable metalloprotease activities.

Larval digeneans have been proposed as indicators of abundance and diversity of vertebrate and other hosts as well as environmental disturbances. To evaluate its response to environmental changes and its potential use as an indicator of environmental fluctuations, the temporal stability of the community of larval digeneans in Heleobia conexa was comparatively analysed in 4 separate years (1996, 1999, 2004 and 2005) in Mar Chiquita coastal lagoon (Buenos Aires province, Argentina). In total, 4579 specimens of H. conexa were collected and 22 digenean species were observed. Overall prevalence presented inter-annual and seasonal differences. These differences correlate with seasonal changes in composition of the vertebrate definitive host community and with the elimination of the preferred habitat of H. conexa in 1999. In general, the larval digenean community of H. conexa showed a yearly re-establishment following the annual cycle of H. conexa and the presence of definitive hosts. This annual restructuring allowed inferences about the effects of short-term environmental changes in the lagoon. According to these observations, the larval digenean community of H. conexa could be considered as a good bio-indicator with quick response to environmental disturbances.

Larval helminths exploit the physiology of their intermediate hosts: first, as a resource for energy and space and second by altering the immune system activity to ensure their survival. Whereas the growth pattern under parasite competition has been investigated, the effect of multiple infections on the level of parasite-induced immunodepression in a trophically transmitted helminth has been neglected. In this study, amphipods Gammarus pulex were infected in the laboratory by the acanthocephalan Pomphorhynchus laevis to investigate how parasite density in the intermediate host affected (i) cystacanth growth and (ii) the level of parasite-induced alterations of the host immune defences, two traits strongly linked to host exploitation. The study highlights that sharing a host is costly. As parasite intensity increases, competition for resources translates into a reduction in cystacanth volume. Immune manipulation is also modulated by density. Interestingly, immunodepression is higher in double-infected hosts compared to hosts with a single infection, suggesting an opportunity for cooperative immune manipulation. However, in higher multiple infections, parasites do not further down-regulate the host immune response, possibly to avoid additional costs that may outweigh the benefits of immunodepression.