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Showing papers in "Parasitology in 2016"


Journal ArticleDOI
TL;DR: This review provides a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance.
Abstract: Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms.

282 citations


Journal ArticleDOI
TL;DR: The results show that there have been some notable successes in integrating theory and data but also that theory and empiricism in this field do not ‘speak’ to each other very well.
Abstract: Why is it that some parasites cause high levels of host damage (i.e. virulence) whereas others are relatively benign? There are now numerous reviews of virulence evolution in the literature but it is nevertheless still difficult to find a comprehensive treatment of the theory and data on the subject that is easily accessible to non-specialists. Here we attempt to do so by distilling the vast theoretical literature on the topic into a set of relatively few robust predictions. We then provide a comprehensive assessment of the available empirical literature that tests these predictions. Our results show that there have been some notable successes in integrating theory and data but also that theory and empiricism in this field do not 'speak' to each other very well. We offer a few suggestions for how the connection between the two might be improved.

252 citations


Journal ArticleDOI
TL;DR: Angiostrongylus cantonensis is a metastarongyloid nematode found widely in the Asia-Pacific region, and the aetiological agent of angiostrinongyliasis; a disease characterized by eosinophilic meningitis as mentioned in this paper.
Abstract: Angiostrongylus cantonensis is a metastrongyloid nematode found widely in the Asia-Pacific region, and the aetiological agent of angiostrongyliasis; a disease characterized by eosinophilic meningitis. Rattus rats are definitive hosts of A. cantonensis, while intermediate hosts include terrestrial and aquatic molluscs. Humans are dead-end hosts that usually become infected upon ingestion of infected molluscs. A presumptive diagnosis is often made based on clinical features, a history of mollusc consumption, eosinophilic pleocytosis in cerebral spinal fluid, and advanced imaging such as computed tomography. Serological tests are available for angiostrongyliasis, though many tests are still under development. While there is no treatment consensus, therapy often includes a combination of anthelmintics and corticosteroids. Angiostrongyliasis is relatively rare, but is often associated with morbidity and sometimes mortality. Recent reports suggest the parasites' range is increasing, leading to fatalities in regions previously considered Angiostrongylus-free, and sometimes, delayed diagnosis in newly invaded regions. Increased awareness of angiostrongyliasis would facilitate rapid diagnosis and improved clinical outcomes. This paper summarizes knowledge on the parasites' life cycle, clinical aspects and epidemiology. The molecular biology of Angiostrongylus spp. is also discussed. Attention is paid to the significance of angiostrongyliasis in Australia, given the recent severe cases reported from the Sydney region.

153 citations


Journal ArticleDOI
TL;DR: A taxonomic revision of the dixenous trypanosomatids currently classified as Endotrypanum and Leishmania is proposed, including parasites that do not fall within the subgenera L. deanei, L. enriettii and L. martiniquensis.
Abstract: We propose a taxonomic revision of the dixenous trypanosomatids currently classified as Endotrypanum and Leishmania, including parasites that do not fall within the subgenera L. (Leishmania) and L. (Viannia) related to human leishmaniasis or L. (Sauroleishmania) formed by leishmanias of lizards: L. colombiensis, L. equatorensis, L. herreri, L. hertigi, L. deanei, L. enriettii and L. martiniquensis. The comparison of these species with newly characterized isolates from sloths, porcupines and phlebotomines from central and South America unveiled new genera and subgenera supported by past (RNA PolII gene) and present (V7V8 SSU rRNA, Hsp70 and gGAPDH) phylogenetic analyses of the organisms. The genus Endotrypanum is restricted to Central and South America, comprising isolates from sloths and transmitted by phlebotomines that sporadically infect humans. This genus is the closest to the new genus Porcisia proposed to accommodate the Neotropical porcupine parasites originally described as L. hertigi and L. deanei. A new subgenus Leishmania (Mundinia) is created for the L. enriettii complex that includes L. martiniquensis. The new genus Zelonia harbours trypanosomatids from Neotropical hemipterans placed at the edge of the Leishmania-Endotrypanum-Porcisia clade. Finally, attention is drawn to the status of L. siamensis and L. australiensis as nomem nudums.

133 citations


Journal ArticleDOI
TL;DR: This review provides an overview of the biosynthesis of the prominent cell wall components, highlighting the inhibitory mechanisms of existing clinical drugs and illustrating the potential of other unexploited enzymes as future drug targets.
Abstract: Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB), is recognized as a global health emergency as promoted by the World Health Organization. Over 1 million deaths per year, along with the emergence of multi- and extensively-drug resistant strains of Mtb, have triggered intensive research into the pathogenicity and biochemistry of this microorganism, guiding the development of anti-TB chemotherapeutic agents. The essential mycobacterial cell wall, sharing some common features with all bacteria, represents an apparent ‘Achilles heel’ that has been targeted by TB chemotherapy since the advent of TB treatment. This complex structure composed of three distinct layers, peptidoglycan, arabinogalactan and mycolic acids, is vital in supporting cell growth, virulence and providing a barrier to antibiotics. The fundamental nature of cell wall synthesis and assembly has rendered the mycobacterial cell wall as the most widely exploited target of anti-TB drugs. This review provides an overview of the biosynthesis of the prominent cell wall components, highlighting the inhibitory mechanisms of existing clinical drugs and illustrating the potential of other unexploited enzymes as future drug targets.

129 citations


Journal ArticleDOI
TL;DR: This review summarizes the antimalarial antibody responses detected in infants and how they change over time and will briefly mention Plasmodium vivax responses in infants.
Abstract: Malaria is one of the most serious infectious diseases with most of the severe disease caused by Plasmodium falciparum (Pf). Naturally acquired immunity develops over time after repeated infections and the development of antimalarial antibodies is thought to play a crucial role. Neonates and young infants are relatively protected from symptomatic malaria through mechanisms that are poorly understood. The prevailing paradigm is that maternal antimalarial antibodies transferred to the fetus in the last trimester of pregnancy protect the infant from early infections. These antimalarial antibodies wane by approximately 6 months of age leaving the infant vulnerable to malaria, however direct evidence supporting this epidemiologically based paradigm is lacking. As infants are the target population for future malaria vaccines, understanding how they begin to develop immunity to malaria and the gaps in their responses is key. This review summarizes the antimalarial antibody responses detected in infants and how they change over time. We focus primarily on Pf antibody responses and will briefly mention Plasmodium vivax responses in infants.

74 citations


Journal ArticleDOI
TL;DR: The key processes which underpin this knowledge; the amount of Plasmodium spp.
Abstract: With increasing malaria control and goals of malaria elimination, many endemic areas are transitioning from high-to-low-to-no malaria transmission. Reductions in transmission will impact on the development of naturally acquired immunity to malaria, which develops after repeated exposure to Plasmodium spp. However, it is currently unclear how declining transmission and malaria exposure will affect the development and maintenance of naturally acquired immunity. Here we review the key processes which underpin this knowledge; the amount of Plasmodium spp. exposure required to generate effective immune responses, the longevity of antibody responses and the ability to mount an effective response upon re-exposure through memory responses. Lastly we identify research priorities which will increase our understanding of how changing transmission will impact on malarial immunity.

73 citations


Journal ArticleDOI
TL;DR: The relationship between strongyle fecal egg count (FEC) and body condition in a unique, naturalized population of horses that has never been exposed to anthelmintic drugs is investigated.
Abstract: In wild and domestic animals, gastrointestinal parasites can have significant impacts on host development, condition, health, reproduction and longevity. Improving our understanding of the causes and consequences of individual-level variation in parasite load is therefore of prime interest. Here we investigated the relationship between strongyle fecal egg count (FEC) and body condition in a unique, naturalized population of horses that has never been exposed to anthelmintic drugs (Sable Island, Nova Scotia, Canada). We first quantified variation in FEC and condition for 447 individuals according to intrinsic (sex, age, reproductive status, social status) and extrinsic (group size, location, local density) variables. We then quantified the repeatability of measurements obtained over a field season and tested for covariance between FEC and condition. FECs were high relative to other horse populations (mean eggs per gram ± SD = 1543·28 ± 209·94). FECs generally decreased with age, were higher in lactating vs non-lactating females, and unexpectedly lower in males in some part of the island. FECs and condition were both spatially structured, with patterns depending on age, sex and reproductive status. FECs and condition were both repeatable. Most notably, FECs and condition were negatively correlated, especially in adult females.

69 citations


Journal ArticleDOI
TL;DR: This paper summarizes the common uses of GIS technology in the public health sector, emphasizing applications related to mapping and understanding of parasitic diseases, and presents some of the success stories.
Abstract: The uptake and acceptance of Geographic Information Systems (GIS) technology has increased since the early 1990s and public health applications are rapidly expanding. In this paper, we summarize the common uses of GIS technology in the public health sector, emphasizing applications related to mapping and understanding of parasitic diseases. We also present some of the success stories, and discuss the challenges that still prevent a full scope application of GIS technology in the public health context. Geographical analysis has allowed researchers to interlink health, population and environmental data, thus enabling them to evaluate and quantify relationships between health-related variables and environmental risk factors at different geographical scales. The ability to access, share and utilize satellite and remote-sensing data has made possible even wider understanding of disease processes and of their links to the environment, an important consideration in the study of parasitic diseases. For example, disease prevention and control strategies resulting from investigations conducted in a GIS environment have been applied in many areas, particularly in Africa. However, there remain several challenges to a more widespread use of GIS technology, such as: limited access to GIS infrastructure, inadequate technical and analytical skills, and uneven data availability. Opportunities exist for international collaboration to address these limitations through knowledge sharing and governance.

69 citations


Journal ArticleDOI
TL;DR: The results show that both parasites have significant, negative effects on bumblebee health, making them potentially of conservation concern.
Abstract: Many pollinators are currently suffering from declines, diminishing their gene pool and increasing their vulnerability to parasites. Recently, an increasing diversity of parasites has been recorded in bumblebees, yet for many, knowledge of their virulence and hence the risk their presence poses, is lacking. The deformed wing virus (DWV), known to be ubiquitous in honey bees, has now been detected in bumblebees. In addition, the neogregarine Apicystis bombi has been discovered to be more prevalent than previously thought. Here, we assess for the first time the lethal and sublethal effects of these parasites during single and mixed infections of worker bumblebees (Bombus terrestris). Fifteen days after experimental exposure, 22% of bees exposed to A. bombi, 50% of bees exposed to DWV and 86% of bees exposed to both parasites had died. Bumblebees that had ingested A. bombi had increased sucrose sensitivity (SS) and a lower lipid:body size ratio than control bees. While dual infected bumblebees showed no increase in SS. Overall, we find that A. bombi exhibits both lethal and sublethal effects. DWV causes lethal effect and may reduce the sub lethal effects imposed by A. bombi. The results show that both parasites have significant, negative effects on bumblebee health, making them potentially of conservation concern.

61 citations


Journal ArticleDOI
TL;DR: The identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocytes stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.
Abstract: Gametocytes are the specialized form of Plasmodium parasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages of Plasmodium. This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.

Journal ArticleDOI
TL;DR: Results of the present cohort study suggest that latent toxoplasmosis represents a large and so far underrated public health problem.
Abstract: The global seroprevalence of latent toxoplasmosis is estimated to be higher than 30%. The presence of slowly dividing parasites in tissue cysts located mainly in immunoprivileged organs was long considered asymptomatic. Recently, many studies have shown that latent Toxoplasma infections could have serious impacts on human health. Here we ran a cross-sectional study in a population of 1486 volunteers. The results showed that 333 infected subjects scored worse than 1153 controls in 28 of 29 health-related variables. Similarly, they reported higher rates of 77 of a list of 134 disorders reported by at least 10 participants of the study. Toxoplasmosis was associated most strongly with musculoskeletal (τ = 0·107, P < 0·0005), followed by neurological (τ = 0·088, P < 0·0005), immune (τ = 0·085, p < 0·0005), metabolic (τ = 0·079, P < 0·0005), respiratory (τ = 0·068, P = 0·0001), allergic (τ = 0·053, P = 0·004), digestive system (τ = 0·052, P = 0·004) and mental health disorders (τ = 0·050, P = 0·008). Results of the present cohort study, along with the previous data from many case-control studies or ecological studies suggest that latent toxoplasmosis represents a large and so far underrated public health problem.

Journal ArticleDOI
TL;DR: Comparisons with shorter mtDNA datasets revealed that 8274 bp sequences provided significantly higher phylogenetic resolution and thus more power to reveal the genetic relations between different haplotypes, revealing complex phylogeography and high genetic variation of E. granulosus s.
Abstract: Echinococcus granulosus is the causative agent of cystic echinococcosis. The disease is a significant global public health concern and human infections are most commonly associated with E. granulosus sensu stricto (s. s.) genotype G1. The objectives of this study were to: (i) analyse the genetic variation and phylogeography of E. granulosus s. s. G1 in part of its main distribution range in Europe using 8274 bp of mtDNA; (ii) compare the results with those derived from previously used shorter mtDNA sequences and highlight the major differences. We sequenced a total of 91 E. granulosus s. s. G1 isolates from six different intermediate host species, including humans. The isolates originated from seven countries representing primarily Turkey, Italy and Spain. Few samples were also from Albania, Greece, Romania and from a patient originating from Algeria, but diagnosed in Finland. The analysed 91 sequences were divided into 83 haplotypes, revealing complex phylogeography and high genetic variation of E. granulosus s. s. G1 in Europe, particularly in the high-diversity domestication centre of western Asia. Comparisons with shorter mtDNA datasets revealed that 8274 bp sequences provided significantly higher phylogenetic resolution and thus more power to reveal the genetic relations between different haplotypes.

Journal ArticleDOI
TL;DR: The validity of the modified agglutination test for the detection of T. gondii infection in chickens and bioassay in free-range/backyard (FR) chickens is supported.
Abstract: The modified agglutination test (MAT) is one of the most commonly used tests for the detection of antibodies to Toxoplasma gondii in animal and human sera. The objective of the present study was to evaluate the diagnostic accuracy of the MAT and bioassay in free-range/backyard (FR) chickens (Gallus domesticus). Previously-published T. gondii test results from 2066 chickens from 19 countries were compiled for the present study. The frequency of isolation of T. gondii increased for MAT titres between 1:5 and 1:160, and ranged from 61 to 75% for antibody titres of 1:160, 1:320, and ⩾1:640. Twenty-three cats fed pooled hearts from a total of 802 FR seronegative (MAT, <1:5) chickens from several countries did not excrete oocysts, indicating a high negative predictive value of MAT because FR chickens would have been exposed to many microbes; cats are the most sensitive indicators of T. gondii infection in tissues and can excrete millions of oocysts after ingesting even a few bradyzoites. Of the 29 cats in this study, six cats, fed hearts pooled from 15-122 FR chickens, excreted oocysts; but these identifications were likely related to misidentification or prozone. Results of the present study support the validity of MAT for the detection of T. gondii infection in chickens.

Journal ArticleDOI
TL;DR: Where the future lies in terms of advancing the understanding of naturally acquired immunity to P. vivax is discussed, through the use of well-designed longitudinal epidemiological studies and modern tools available to immunologists.
Abstract: Plasmodium vivax is the most geographically widespread of the malaria parasites causing human disease, yet it is comparatively understudied compared with Plasmodium falciparum. In this article we review what is known about naturally acquired immunity to P. vivax, and importantly, how this differs to that acquired against P. falciparum. Immunity to clinical P. vivax infection is acquired more quickly than to P. falciparum, and evidence suggests humans in endemic areas also have a greater capacity to mount a successful immunological memory response to this pathogen. Both of these factors give promise to the idea of a successful P. vivax vaccine. We review what is known about both the cellular and humoral immune response, including the role of cytokines, antibodies, immunoregulation, immune memory and immune dysfunction. Furthermore, we discuss where the future lies in terms of advancing our understanding of naturally acquired immunity to P. vivax, through the use of well-designed longitudinal epidemiological studies and modern tools available to immunologists.

Journal ArticleDOI
TL;DR: Bayesian clustering, using allozymes and EF1 α−1 nDNA markers, has demonstrated that hybridization between A. pegreffii and A. simplex is a contemporary phenomenon in sympatric areas, while no introgressive hybridization takes place between the two species.
Abstract: A multi-marker nuclear genotyping approach was performed on larval and adult specimens of Anisakis spp. (N = 689) collected from fish and cetaceans in allopatric and sympatric areas of the two species Anisakis pegreffii and Anisakis simplex (s. s.), in order to: (1) identify specimens belonging to the parental taxa by using nuclear markers (allozymes loci) and sequence analysis of a new diagnostic nuclear DNA locus (i.e. partial sequence of the EF1 α-1 nDNA region) and (2) recognize hybrid categories. According to the Bayesian clustering algorithms, based on those markers, most of the individuals (N = 678) were identified as the parental species [i.e. A. pegreffii or A. simplex (s. s.)], whereas a smaller portion (N = 11) were recognized as F1 hybrids. Discordant results were obtained when using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs) of the internal transcribed spacer (ITS) ribosomal DNA (rDNA) on the same specimens, which indicated the occurrence of a large number of 'hybrids' both in sympatry and allopatry. These findings raise the question of possible misidentification of specimens belonging to the two parental Anisakis and their hybrid categories derived from the application of that single marker (i.e. PCR-RFLPs analysis of the ITS of rDNA). Finally, Bayesian clustering, using allozymes and EF1 α-1 nDNA markers, has demonstrated that hybridization between A. pegreffii and A. simplex (s. s.) is a contemporary phenomenon in sympatric areas, while no introgressive hybridization takes place between the two species.

Journal ArticleDOI
TL;DR: Some of the recent developments in this area of research are reviewed, focusing on work that has assessed the potential of these molecules as possible vaccine targets.
Abstract: The Plasmodium falciparum erythrocyte membrane protein 1 antigens that are inserted onto the surface of P. falciparum infected erythrocytes play a key role both in the pathology of severe malaria and as targets of naturally acquired immunity. They might be considered unlikely vaccine targets because they are extremely diverse. However, several lines of evidence suggest that underneath this molecular diversity there are a restricted set of epitopes which may act as effective targets for a vaccine against severe malaria. Here we review some of the recent developments in this area of research, focusing on work that has assessed the potential of these molecules as possible vaccine targets.

Journal ArticleDOI
TL;DR: This review addresses the various challenges associated with drug susceptibility and -resistance monitoring in VL, with particular emphasis on the choice of strains, susceptibility model selection and standardization of procedures with specific read-out parameters and well-defined threshold criteria.
Abstract: For decades antimonials were the drugs of choice for the treatment of visceral leishmaniasis (VL), but the recent emergence of resistance has made them redundant as first-line therapy in the endemic VL region in the Indian subcontinent. The application of other drugs has been limited due to adverse effects, perceived high cost, need for parenteral administration and increasing rate of treatment failures. Liposomal amphotericin B (AmB) and miltefosine (MIL) have been positioned as the effective first-line treatments; however, the number of monotherapy MIL-failures has increased after a decade of use. Since no validated molecular resistance markers are yet available, monitoring and surveillance of changes in drug sensitivity and resistance still depends on standard phenotypic in vitro promastigote or amastigote susceptibility assays. Clinical isolates displaying defined MIL- or AmB-resistance are still fairly scarce and fundamental and applied research on resistance mechanisms and dynamics remains largely dependent on laboratory-generated drug resistant strains. This review addresses the various challenges associated with drug susceptibility and -resistance monitoring in VL, with particular emphasis on the choice of strains, susceptibility model selection and standardization of procedures with specific read-out parameters and well-defined threshold criteria. The latter are essential to support surveillance systems and safeguard the limited number of currently available antileishmanial drugs.

Journal ArticleDOI
TL;DR: Different immunotherapy approaches as alternatives to routine drug treatment will be reviewed against leishmaniasis, generally with low-cost, limited side-effects and no possibility to developing resistance.
Abstract: Leishmaniasis is a vector-borne infectious disease caused by multiple Leishmania (L.) species with diverse clinical manifestations. There is currently no vaccine against any form of the disease approved in humans, and chemotherapy is the sole approach for treatment. Unfortunately, treatment options are limited to a small number of drugs, partly due to high cost and significant adverse effects. The other obstacle in leishmaniasis treatment is the potential for drug resistance, which has been observed in multiple endemic countries. Immunotherapy maybe another important avenue for controlling leishmaniasis and could help patients control the disease. There are different approaches for immunotherapy in different infectious diseases, generally with low-cost, limited side-effects and no possibility to developing resistance. In this paper, different immunotherapy approaches as alternatives to routine drug treatment will be reviewed against leishmaniasis.

Journal ArticleDOI
TL;DR: This paper reviews the literature published from 1985 to date on the in vitro and in vivo anti-parasitic potency of the pentacyclic triterpenes made up of the oleanane, ursane, taraxastane, lupane and hopane types and finds more promising compounds especially of plant origin.
Abstract: Parasitic infections are among the leading global public health problems with very high economic and mortality burdens. Unfortunately, the available treatment drugs are beset with side effects and continuous parasite drug resistance is being reported. However, new findings reveal more promising compounds especially of plant origin. Among the promising leads are the pentacyclic triterpenes (PTs) made up of the oleanane, ursane, taraxastane, lupane and hopane types. This paper reviews the literature published from 1985 to date on the in vitro and in vivo anti-parasitic potency of this class of phytochemicals. Of the 191 natural and synthetic PT reported, 85 have shown high anti-parasitic activity against various species belonging to the genera of Plasmodium, Leishmania, Trypanosoma, as well as various genera of Nematoda. Moreover, structural modification especially at carbon 3 (C3) and C27 of the parent backbone of PT has led to improved anti-parasitic activity in some cases and loss of activity in others. The potential of this group of compounds as future alternatives in the treatment of parasitic diseases is discussed. It is hoped that the information presented herein will contribute to the full exploration of this promising group of compounds as possible drugs for parasitic diseases.

Journal ArticleDOI
TL;DR: Most studies support a negative competence–extinction relationship between species’ reservoir competence and local extinction risk, and synthesize the current knowledge on how the diversity–disease relationship can be modified by particular species in community, by the scales of analyses and by the disease risk measures.
Abstract: The dilution effect, that high host species diversity can reduce disease risk, has attracted much attention in the context of global biodiversity decline and increasing disease emergence. Recent studies have criticized the generality of the dilution effect and argued that it only occurs under certain circumstances. Nevertheless, evidence for the existence of a dilution effect was reported in about 80% of the studies that addressed the diversity-disease relationship, and a recent meta-analysis found that the dilution effect is widespread. We here review supporting and critical studies, point out the causes underlying the current disputes. The dilution is expected to be strong when the competent host species tend to remain when species diversity declines, characterized as a negative relationship between species' reservoir competence and local extinction risk. We here conclude that most studies support a negative competence-extinction relationship. We then synthesize the current knowledge on how the diversity-disease relationship can be modified by particular species in community, by the scales of analyses, and by the disease risk measures. We also highlight the complex role of habitat fragmentation in the diversity-disease relationship from epidemiological, evolutionary and ecological perspectives, and construct a synthetic framework integrating these three perspectives. We suggest that future studies should test the diversity-disease relationship across different scales and consider the multiple effects of landscape fragmentation.

Journal ArticleDOI
TL;DR: The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions.
Abstract: The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions.

Journal ArticleDOI
TL;DR: The present work clarifies controversial points concerning T. cruzi development in insect vector, showing that parasite suffers a drastic decrease in population size before epimastigonesis accomplishment in PM.
Abstract: Trypanosoma cruzi, the etiological agent of Chagas disease, is ingested by triatomines during their bloodmeal on an infected mammal. Aiming to investigate the development and differentiation of T. cruzi inside the intestinal tract of Rhodnius prolixus at the beginning of infection we fed insects with cultured epimastigotes and blood trypomastigotes from infected mice to determine the amount of recovered parasites after ingestion. Approximately 20% of the ingested parasites was found in the insect anterior midgut (AM) 3 h after feeding. Interestingly, a significant reduction (80%) in the numbers of trypomastigotes was observed after 24 h of infection suggesting that parasites were killed in the AM. Moreover, few parasites were found in that intestinal portion after 96 h of infection. The evaluation of the numbers of parasites in the posterior midgut (PM) at the same periods showed a reduced parasite load, indicating that parasites were not moving from the AM. Additionally, incubation of blood trypomastigotes with extracts from R. prolixus AMs revealed that components of this tissue could induce significant death of T. cruzi. Finally, we observed that differentiation from trypomastigotes to epimastigotes is not completed in the AM; instead we suggest that trypomastigotes change to intermediary forms before their migration to the PM, where differentiation to epimastigotes takes place. The present work clarifies controversial points concerning T. cruzi development in insect vector, showing that parasite suffers a drastic decrease in population size before epimastigonesis accomplishment in PM.

Journal ArticleDOI
TL;DR: For both, vaccines and drugs, the key for success in preventing vertical transmission lies in the application of bioactive compounds that limit parasite proliferation and dissemination, without endangering the developing fetus not only during an exogenous acute infection but also during recrudescence of a chronic infection.
Abstract: Neospora caninum is a leading cause of abortion in cattle, and is thus an important veterinary health problem of high economic significance. Vaccination has been considered a viable strategy to prevent bovine neosporosis. Different approaches have been investigated, and to date the most promising results have been achieved with live-attenuated vaccines. Subunit vaccines have also been studied, and most of them represented components that are functionally involved in (i) the physical interaction between the parasite and its host cell during invasion or (ii) tachyzoite-to-bradyzoite stage conversion. Drugs have been considered as an option to limit the effects of vertical transmission of N. caninum. Promising results with a small panel of compounds in small laboratory animal models indicate the potential value of a chemotherapeutical approach for the prevention of neosporosis in ruminants. For both, vaccines and drugs, the key for success in preventing vertical transmission lies in the application of bioactive compounds that limit parasite proliferation and dissemination, without endangering the developing fetus not only during an exogenous acute infection but also during recrudescence of a chronic infection. In this review, the current status of vaccine and drug development is presented and novel strategies against neosporosis are discussed.

Journal ArticleDOI
TL;DR: Mapping the second intermediate hosts (fish) onto the species tree suggests that metacercariae of these five species exhibit some level of host specificity towards their fish intermediate host (at the family level), irrespective of geographical distribution.
Abstract: The recent development of genetic methods allows the delineation of species boundaries, especially in organisms where morphological characters are not reliable to differentiate species. However, few empirical studies have used these tools to delineate species among parasitic metazoans. Here we investigate the species boundaries of Clinostomum, a cosmopolitan trematode genus with complex life cycle. We sequenced a mitochondrial [cytochrome c oxidase subunit I (COI)] gene for multiple individuals (adults and metacercariae) from Middle-America. Bayesian phylogenetic analysis of the COI uncovered five reciprocally monophyletic clades. COI sequences were then explored using the Automatic Barcode Gap Discovery to identify putative species; this species delimitation method recognized six species. A subsample was sequenced for a nuclear gene (ITS1, 5·8S, ITS2), and a concatenated phylogenetic analysis was performed through Bayesian inference. The species delimitation of Middle-American Clinostomum was finally validated using a multispecies coalescent analysis (species tree). In total, five putative species are recognized among our samples. Mapping the second intermediate hosts (fish) onto the species tree suggests that metacercariae of these five species exhibit some level of host specificity towards their fish intermediate host (at the family level), irrespective of geographical distribution.

Journal ArticleDOI
TL;DR: A critical and comprehensive assessment of the current knowledge on blood parasites is provided, providing an overview of their biology, host and geographic distribution, epidemiology, pathology and implications for public health and conservation.
Abstract: Blood parasites are considered some of the most significant pathogens for the conservation of penguins, due to the considerable morbidity and mortality they have been shown to produce in captive and wild populations of these birds. Parasites known to occur in the blood of penguins include haemosporidian protozoans (Plasmodium, Leucocytozoon, Haemoproteus), piroplamid protozoans (Babesia), kinetoplastid protozoans (Trypanosoma), spirochete bacteria (Borrelia) and nematode microfilariae. This review provides a critical and comprehensive assessment of the current knowledge on these parasites, providing an overview of their biology, host and geographic distribution, epidemiology, pathology and implications for public health and conservation.

Journal ArticleDOI
TL;DR: The possibility that LH adjustments can occur in response to cancer via maternal/paternal effects and that these changes can be heritable to (adaptively) modify the LH traits of their offspring are raised.
Abstract: Despite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host–parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and their evolution. We raise the possibility that LH adjustments can occur in response to cancer via maternal/paternal effects and that these changes can be heritable to (adaptively) modify the LH traits of their offspring. We conclude that LH adjustments can potentially influence the transgenerational persistence of inherited oncogenic mutations in populations.

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TL;DR: This review concentrates specifically on the application of dynamic models to evaluate and guide management strategies, and identifies some key research gaps, which are further development of models of macroparasites, deciding on appropriate levels of complexity, modelling genetic management and connecting models to data.
Abstract: Modelling wildlife disease poses some unique challenges. Wildlife disease systems are data poor in comparison with human or livestock disease systems, and the impact of disease on population size is often the key question of interest. This review concentrates specifically on the application of dynamic models to evaluate and guide management strategies. Models have proved useful particularly in two areas. They have been widely used to evaluate vaccination strategies, both for protecting endangered species and for preventing spillover from wildlife to humans or livestock. They have also been extensively used to evaluate culling strategies, again both for diseases in species of conservation interest and to prevent spillover. In addition, models are important to evaluate the potential of parasites and pathogens as biological control agents. The review concludes by identifying some key research gaps, which are further development of models of macroparasites, deciding on appropriate levels of complexity, modelling genetic management and connecting models to data.

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TL;DR: Chicory shows promise as an anti-Ostertagia feed for cattle and further studies should investigate its on-farm use.
Abstract: Two experiments studied the effects of dietary chicory against gastrointestinal nematodes in cattle. In Experiment (Exp.) 1, stabled calves were fed chicory silage (CHI1; n = 9) or ryegrass/clover hay (CTL1; n = 6) with balanced protein/energy intakes between groups. After 16 days, all calves received 10 000 Ostertagia ostertagi and 66 000 Cooperia oncophora third-stage larvae (L3) [day (D) 0 post-infection (p.i.)]. In Exp. 2, calves were assigned to pure chicory (CHI2; n=10) or ryegrass/clover (CTL2; n = 10) pastures. After 7 days, animals received 20 000 O. ostertagi L3/calf (D0 p.i.) and were moved regularly preventing pasture-borne infections. Due to poor regrowth of the chicory pasture, CHI2 was supplemented with chicory silage. At D40 p.i. (Exp. 1) and D35 p.i. (Exp. 2) calves were slaughtered for worm recovery. In Exp.1, fecal egg counts (FEC) were similar between groups. However, O. ostertagi counts were significantly reduced in CHI1 by 60% (geometric mean; P < 0·01), whereas C. oncophora burdens were unaffected (P = 0·12). In Exp. 2, FEC were markedly lowered in CHI2 from D22 p.i onwards (P < 0·01). Ostertagia ostertagi adult burdens were significantly reduced in CHI2 by 66% (P < 0·001). Sesquiterpene lactones were identified only in chicory (fresh/silage). Chicory shows promise as an anti-Ostertagia feed for cattle and further studies should investigate its on-farm use.

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TL;DR: The results suggest that cathepsin B might play a role in pathogenesis of Blastocystis by increasing intestinal cell permeability.
Abstract: Blastocystis spp. pathogenic potential remains unclear as these anaerobic parasitic protozoa are frequently isolated from stools of both symptomatic and asymptomatic subjects. In silico analysis of the whole genome sequence of Blastocystis subtype 7 revealed the presence of numerous proteolytic enzymes including cysteine proteases predicted to be secreted. To assess the potential impact of proteases on intestinal cells and gut function, we focused our study on two cysteine proteases, a legumain and a cathepsin B, which were previously identified in Blastocystis subtype 7 culture supernatants. Both cysteine proteases were produced as active recombinant proteins. Activation of the recombinant legumain was shown to be autocatalytic and triggered by acidic pH, whereas proteolytic activity of the recombinant cathepsin B was only recorded after co-incubation with the legumain. We then measured the diffusion of 4-kDa FITC-labelled dextran across Caco-2 cell monolayers following exposition to either Blastocystis culture supernatants or each recombinant protease. Both Blastocystis culture supernatants and recombinant activated cathepsin B induced an increase of Caco-2 cell monolayer permeability, and this effect was significantly inhibited by E-64, a specific cysteine protease inhibitor. Our results suggest that cathepsin B might play a role in pathogenesis of Blastocystis by increasing intestinal cell permeability.