Infections by the protozoan parasite Toxoplasma gondii are widely prevalent in humans and other animals worldwide. However, information from eastern European countries is sketchy. In many eastern European countries, including Romania, it has been assumed that chronic T. gondii infection is a common cause of infertility and abortion. For this reason, many women in Romania with these problems were needlessly tested for T. gondii infection. Most papers on toxoplasmosis in Romania were published in Romanian in local journals and often not available to scientists in other countries. Currently, the rate of congenital infection in Romania is largely unknown. In addition, there is little information on genetic characteristics of T. gondii or prevalence in animals and humans in Romania. In the present paper we review prevalence, clinical spectrum and epidemiology of T. gondii in humans and animals in Romania. This knowledge should be useful to biologists, public health workers, veterinarians and physicians.

Scabies is an infectious disease that is endemic in poorly resourced communities, and also common in industrialized countries. Although the disease, which is caused by infestation of Sarcoptes scabiei, is generally mild, the need for a vaccine against S. scabiei is proposed. The immunological mechanisms that control S. scabiei infection are discussed and the current status of scabies vaccine development reviewed. Future directions for scabies vaccine development are also addressed.

In recent years, an extensive collection of Toxoplasma gondii samples have been typed using a set of 10 PCR-RFLP genetic markers. Here we summarize the data reported until the end of 2012. A total of 1457 samples were typed into 189 genotypes. Overall, only a few genotypes dominate in the northern hemisphere, which is in stark contrast to the southern hemisphere where hundreds of genotypes coexist with none being notably dominant. PCR-RFLP genotype #1 (Type II clonal), #2 (Type III), #3 (Type II variant) and #10 (Type I) are identified globally. Genotypes #2 and #3 dominate in Africa, genotypes #9 (Chinese 1) and #10 are prevalent in Asia, genotypes #1, #2 and #3 are prevalent in Europe, genotypes #1, #2, #3, #4 and #5 dominate in North America (#4 and #5 are collectively known as Type 12). In Central and South America, there is no clear dominance of any genotype even though a few have relatively higher frequencies. Statistical analysis indicates significant differences among populations in Africa, Asia, Europe, North America, and Central and South America, with only Europe and North America exhibiting similar diversity. Collectively, the results revealed distinct population structures and geographical patterns of diversity in T. gondii.

Erythrocytes are extensively remodelled by the malaria parasite following invasion of the cell. Plasmodium falciparum encodes numerous virulence-associated and host-cell remodelling proteins that are trafficked to the cytoplasm, the cell membrane and the surface of the infected erythrocyte. The export of soluble proteins relies on a sequence directing entry into the secretory pathways in addition to an export signal. The export signal consisting of five amino acids is termed the Plasmodium export element (PEXEL) or the vacuole transport signal (VTS). Genome mining studies have revealed that PEXEL/VTS carrying protein families have expanded dramatically in P. falciparum compared with other malaria parasite species, possibly due to lineage-specific expansion linked to the unique requirements of P. falciparum for host-cell remodelling. The functional characterization of such genes and gene families may reveal potential drug targets that could inhibit protein trafficking in infected erythrocytes. This review highlights some of the recent advances and key knowledge gaps in protein trafficking pathways in P. falciparum-infected red cells and speculates on the impact of exported gene families in the trafficking pathway.

Echinococcus species are important parasites of wildlife, domestic animals and people worldwide; however, little is known about the prevalence, intensity and genetic diversity of Echinococcus tapeworms in Canadian wildlife. Echinococcus tapeworms were harvested from the intestines of 42% of 93 wolves (Canis lupus) from five sampling regions in the Northwest Territories, Manitoba and Saskatchewan, and visually identified to genus level by microscopic examination. Genetic characterization was successful for tapeworms from 30 wolves, and identified both Echinococcus canadensis and Echinococcus multilocularis in all sampling locations. Mixed infections of E. canadensis/E. multilocularis, as well as the G8/G10 genotypes of E. canadensis were observed. These findings suggest that wolves may be an important definitive host for both parasite species in western Canada. This represents the first report of wolves naturally infected with E. multilocularis in North America, and of wolves harbouring mixed infections with multiple species and genotypes of Echinococcus. These observations provide important information regarding the distribution and diversity of zoonotic species of Echinococcus in western North America, and may be of interest from public health and wildlife conservation perspectives.

Fast response and decision making about containment, management, eradication and prevention of diseases, are increasingly important aspects of the work of public health officers and medical providers. Diseases and the agents causing them are spatially and temporally distributed, and effective countermeasures rely on methods that can timely locate the foci of infection, predict the distribution of illnesses and their causes, and evaluate the likelihood of epidemics. These methods require the use of large datasets from ecology, microbiology, health and environmental geography. Geodatabases integrating data from multiple sets of information are managed within the frame of geographic information systems (GIS). Many GIS software packages can be used with minimal training to query, map, analyse and interpret the data. In combination with other statistical or modelling software, predictive and spatio-temporal modelling can be carried out. This paper reviews some of the concepts and tools used in epidemiology and parasitology. The purpose of this review is to provide public health officers with the critical tools to decide about spatial analysis resources and the architecture for the prevention and surveillance systems best suited to their situations.

Research on the interactions between the field voles (Microtus agrestis) of Kielder Forest and their natural parasites dates back to the 1930s. These early studies were primarily concerned with understanding how parasites shape the characteristic cyclic population dynamics of their hosts. However, since the early 2000s, research on the Kielder field voles has expanded considerably and the system has now been utilized for the study of host–parasite biology across many levels, including genetics, evolutionary ecology, immunology and epidemiology. The Kielder field voles therefore represent one of the most intensely and broadly studied natural host–parasite systems, bridging theoretical and empirical approaches to better understand the biology of infectious disease in the real world. This article synthesizes the body of work published on this system and summarizes some important insights and general messages provided by the integrated and multidisciplinary study of host–parasite interactions in the natural environment.

Cryptosporidium is increasingly recognized as one of the major causes of moderate to severe diarrhoea in developing countries. With treatment options limited, control relies on knowledge of the biology and transmission of the members of the genus responsible for disease. Currently, 26 species are recognized as valid on the basis of morphological, biological and molecular data. Of the nearly 20 Cryptosporidium species and genotypes that have been reported in humans, Cryptosporidium hominis and Cryptosporidium parvum are responsible for the majority of infections. Livestock, particularly cattle, are one of the most important reservoirs of zoonotic infections. Domesticated and wild animals can each be infected with several Cryptosporidium species or genotypes that have only a narrow host range and therefore have no major public health significance. Recent advances in next-generation sequencing techniques will significantly improve our understanding of the taxonomy and transmission of Cryptosporidium species, and the investigation of outbreaks and monitoring of emerging and virulent subtypes. Important research gaps remain including a lack of subtyping tools for many Cryptosporidium species of public and veterinary health importance, and poor understanding of the genetic determinants of host specificity of Cryptosporidium species and impact of climate change on the transmission of Cryptosporidium.

The need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs. The transfer of knowledge from the Pharmaceutical industry relating to the importance of understanding how to target drugs successfully within the body, and improved understanding of how pathogens interact with their hosts, is driving a series of new paradigms in anti-infective drug design. Here we provide an overview of those processes as an introduction to a series of articles from experts in this area that emerged from a meeting entitled “Emerging Paradigms in Anti-Infective Drug Design” held in London on the 17th and 18th September 2012. The symposium was organised jointly by British Society for Parasitology (BSP) and the Biological & Medicinal Chemistry sector of the Royal Society of Chemistry (RSC) and held at the London School of Hygiene & Tropical Medicine. The symposium set out to cover all aspects of the identification of new therapeutic modalities for the treatment of neglected and tropical diseases. We aimed to bring together leading scientists from all the disciplines working in this field and cover the pharmacology, medicinal chemistry and drug delivery of potential new medicines. Sessions were held on: “Target diseases and targets for drugs”, “Target based medicinal chemistry”, “Bioavailability and chemistry”, “Targeting intracellular microbes”, “Alternative approaches and models”, and “New anti-infectives – how do we get there?”

This symposium was organised by Simon Croft (LSHTM) and Mike Barrett (University of Glasgow) for the BSP, and David Alker (David Alker Associates) and Andrew Stachulski (University of Liverpool) for the Biological & Medicinal Chemistry sector of the RSC.

There are many reasons why detection of parasites of medical and veterinary importance is vital and where novel diagnostic and surveillance tools are required. From a medical perspective alone, these originate from a desire for better clinical management and rational use of medications. Diagnosis can be at the individual-level, at close to patient settings in testing a clinical suspicion or at the community-level, perhaps in front of a computer screen, in classification of endemic areas and devising appropriate control interventions. Thus diagnostics for parasitic diseases has a broad remit as parasites are not only tied with their definitive hosts but also in some cases with their vectors/intermediate hosts. Application of current diagnostic tools and decision algorithms in sustaining control programmes, or in elimination settings, can be problematic and even ill-fitting. For example in resource-limited settings, are current diagnostic tools sufficiently robust for operational use at scale or are they confounded by on-the-ground realities; are the diagnostic algorithms underlying public health interventions always understood and well-received within communities which are targeted for control? Within this Special Issue (SI) covering a variety of diseases and diagnostic settings some answers are forthcoming. An important theme, however, throughout the SI is to acknowledge that cross-talk and continuous feedback between development and application of diagnostic tests is crucial if they are to be used effectively and appropriately.

By interactions with other microbes, free-living amoebae play a significant role in microbiology, environmental biology, physiology, cellular interactions, ecology and evolution. Here, we discuss astonishing interactions of bacteria and amoebae, in the light of evolution and functional aspects impacting human health. In favourable environmental conditions, the interaction of Acanthamoeba with non-virulent bacteria results in lysis of the bacteria. However, the interaction with weak-virulent bacteria results in a symbiotic relationship or amoebal lysis may occur. The microbial survival of amoebae in harsh environments, ability to interact with bacteria, and their ability to aid transmission to susceptible hosts is of great concern to human, animal and ecosystem health.

Delimiting species of malaria parasites (Haemosporida) has become increasingly problematic as new lineages of parasites are identified solely by molecular information, particularly mitochondrial cytochrome b sequence data. In this review, we highlight some of the issues, both historical and contemporary, that have hindered the development of objective criteria to diagnose, delimit and define species of haemosporidians. Defining species is not the focal interest of most researchers, most of whom merely wish to determine whether lineages identified in their samples match those of other researchers, and if so, where and in which host species. Rather than revisiting all the issues with respect to delimiting and naming species, we instead focus on finding a practical near-term resolution to the ‘species problem’ that utilizes the community's largest resource: mitochondrial cytochrome b DNA sequences. We recommend a standardized procedure to ‘tag’ these sequences, based on per cent sequence similarity, that will allow researchers to directly assess the novelty, known hosts and geographic distribution of avian malaria parasite lineages.

Fungal pathogens pose a major threat to human health worldwide. They infect billions of people each year, leading to at least 1·5 million deaths. Treatment of fungal infections is difficult due to the limited number of clinically useful antifungal drugs, and the emergence of drug resistance. A promising new strategy to enhance the efficacy of antifungal drugs and block the evolution of drug resistance is to target the molecular chaperone Hsp90. Pharmacological inhibitors of Hsp90 function that are in development as anticancer agents have potential to be repurposed as agents for combination antifungal therapy for some applications, such as biofilm infections. For systemic infections, however, effective combination therapy regimens may require Hsp90 inhibitors that can selectively target Hsp90 in the pathogen, or alternate strategies to compromise function of the Hsp90 chaperone machine. Selectively impairing Hsp90 function in the pathogen could in principle be achieved by targeting Hsp90 co-chaperones or regulators of Hsp90 function that are more divergent between pathogen and host than Hsp90. Antifungal combination therapies could also exploit downstream effectors of Hsp90 that are critical for fungal drug resistance and virulence. Here, we discuss the progress and prospects for establishing Hsp90 as an important therapeutic target for life-threatening fungal infections.

Leishmania are protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world, resulting in an estimated 1·3 million new cases and 30 000 deaths annually. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective in several endemic regions. To date there is no vaccine against leishmaniasis, although extensive evidence from studies in animal models indicates that solid protection can be achieved upon immunization. This review focuses on immune responses to Leishmania in both cutaneous and visceral forms of the disease, pointing to the complexity of the immune response and to a range of evasive mechanisms utilized by the parasite to bypass those responses. The amalgam of innate and acquired immunity combined with the paucity of data on the human immune response is one of the major problems currently hampering vaccine development and implementation.

Plant cysteine proteinases (CPs) from papaya (Carica papaya) are capable of killing parasitic nematode worms in vitro and have been shown to possess anthelmintic effects in vivo. The acute damage reported in gastrointestinal parasites has not been found in free-living nematodes such as Caenorhabditis elegans nor among the free-living stages of parasitic nematodes. This apparent difference in susceptibility might be the result of active production of cysteine proteinase inhibitors (such as cystatins) by the free-living stages or species. To test this possibility, a supernatant extract of refined papaya latex (PLS) with known active enzyme content was used. The effect on wild-type (Bristol N2) and cystatin null mutant (cpi-1−/− and cpi-2−/−) C. elegans was concentration-, temperature- and time-dependent. Cysteine proteinases digested the worm cuticle leading to release of internal structures and consequent death. Both cystatin null mutant strains were highly susceptible to PLS attack irrespective of the temperature and concentration of exposure, whereas wild-type N2 worms were generally resistant but far more susceptible to attack at low temperatures. PLS was able to induce elevated cpi-1 and cpi-2 cystatin expression. We conclude that wild-type C. elegans deploy cystatins CPI-1 and CPI-2 to resist CP attack. The results suggest that the cpi-1 or cpi-2 null mutants (or a double mutant combination of the two) could provide a cheap and effective rapid throughput C. elegans-based assay for screening plant CP extracts for anthelmintic activity.

Monepantel (MOP), a new anthelmintic drug from a group of amino-acetonitrile derivatives, has been intensively studied during last years. Many authors examined this new drug from different perspectives, e.g. efficacy against different species and stages of parasites, mode of action, metabolism, pharmacokinetics, toxicity, resistance, ecotoxicity, etc. MOP is an anthelmintic for livestock (currently only sheep and goats), with molecular mode of action which is different to all other anthelmintics. MOP has a broad-spectrum of activity against gastrointestinal nematodes of sheep, including adults and L4 larvae of the most important species. The key feature of MOP is its full effectiveness against strains of nematodes resistant to benzimidazoles, levamisole, macrocyclic lactones and closantel. After oral administration, MOP is quickly absorbed into the bloodstream and quickly metabolized to MOP sulfone that has a similar efficacy as the parent molecule. Several other MOP metabolites formed in ovine hepatocytes were described. MOP and its metabolites are considered to be non-toxic to environment and its components, such as soil microflora, aquatic organisms, dung organisms, vegetation, etc. The aim of the presented review was not to collect all reported data but to bring an overview of various approaches in the study of MOP and to evaluate their principal results.

Plasmodium falciparum malaria is responsible for over 250 million clinical cases every year worldwide. Severe malaria cases might present with a range of disease syndromes including acute respiratory distress, metabolic acidosis, hypoglycaemia, renal failure, anaemia, pulmonary oedema, cerebral malaria (CM) and placental malaria (PM) in pregnant women. Two main determinants of severe malaria have been identified: sequestration of parasitized red blood cells and strong pro-inflammatory responses. Increasing evidence from human studies and malaria infection animal models revealed the presence of host leucocytes at the site of parasite sequestration in brain blood vessels as well as placental tissue in complicated malaria cases. These observations suggested that apart from secreting cytokines, leucocytes might also contribute to disease by migrating to the site of parasite sequestration thereby exacerbating organ-specific inflammation. This evidence attracted substantial interest in identifying trafficking pathways by which inflammatory leucocytes are recruited to target organs during severe malaria syndromes. Chemo-attractant cytokines or chemokines are the key regulators of leucocyte trafficking and their potential contribution to disease has recently received considerable attention. This review summarizes the main findings to date, investigating the role of chemokines in severe malaria and the implication of these responses for the induction of pathogenesis and immunity to infection.

Toxoplasma gondii is a widely spread protozoon in humans, mammals and poultry. Regarding the latter, nothing is known yet about the duration of T. gondii persistence and distribution over a conventional fattening cycle of turkeys and chickens. Twenty-four turkeys and 12 broiler chickens were infected intravenously with 1×106T. gondii tachyzoites (strain NED). Serum antibody levels were determined weekly by ELISA (turkeys) or immunofluorescent antibody test (chickens). Turkeys were slaughtered at 4, 8, 12 and 16 weeks post-infection (p.i.), and chickens 5 or 10 weeks p.i. (n = 6 per group). Sixteen different tissue samples per bird were analysed for T. gondii by PCR. All infected animals showed seroconversion. In turkeys, 15·9% of all samples were tested positive for T.-gondii-DNA. Among the edible tissues (drumstick, thigh, breast muscle, heart, liver and gizzard) 7·8% tested positive. Among poultry slaughtered after different periods of time after infection no significant differences (P>0·05) regarding the number of positive samples were observed. Only 4 out of 192 samples (2·1%) from infected chickens contained detectable T. gondii DNA.The PCR findings suggested that T. gondii may persist in poultry. Particularly in turkey it was shown that edible tissues stay infected for at least 16 weeks p.i. which indicates a potential risk for consumers of undercooked turkey meat whereas chickens appear less susceptible to T. gondii infection.