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An hypothesis to explain why cell-mediated immunity alone can contain infections by certain intracellular parasites and how immune class regulation of the response against such parasites can be subverted.

Cells with a low density of parasite-specific antigens on their surface are postulated to be susceptible to a cell-mediated attack but not to effector mechanisms normally activated following the binding of specific antibody to the infected cell. It is further postulated that such infected cells normally induce a cell-mediated response, and that cells infected with slow-growing intracellular parasites have a low density of parasite-specific antigens on their surface. Despite these general postulates, cell-mediated immunity is not invariably induced following natural infection by certain slow-growing parasites, such as those responsible for leprosy, tuberculosis, and the leishmaniases, and antibody can be induced that is exclusive of a strong, cell-mediated response. It is proposed that certain events in such cases subvert the normal regulatory processes that control the class of immunity induced. In these cases, the parasite-infected cells, bearing a low representation of parasite antigens, induce antibody even though they are not susceptible to antibody-dependent effector mechanisms, and so they are not eliminated. In this case, chronic infection and uncontrolled growth of the parasite occurs, often with fatal consequences.

Animals↗

Comparative genetic diversity of parasites and their hosts: population structure of an urban cockroach and its haplo-diploid parasite (oxyuroid nematode).

Few studies have investigated the genetic structure of both host and parasite populations at a level of populations and at a level of individuals. We investigated the genetic structure of the urban cockroach Blattella germanica and its oxyuroid parasite Blatticola blattae. Random amplified polymorphic DNA (RAPD) markers were used to quantify genetic diversity between and within four populations (from two cities in France) of the host and its parasite. Diversity based on phenotypic frequencies was calculated for each RAPD marker using Shannon-Wiener's index. We used multivariate analyses to test the significance of genetic differentiation between host and parasite populations. Analysis of molecular variance was also used. Both methods gave similar results. Diversity between pairs of individuals was estimated by Nei & Li's index. Genetic diversity was higher within host or parasite populations (80% and 82%, respectively, of explained diversity) than between host or parasite populations (20% and 18%, respectively, explained diversity). The genetic distances between pairs of parasite populations (or individuals) were not correlated with the genetic distances between the corresponding pairs of host populations (or individuals).

Animals↗

Correlated evolution between host immunity and parasite life histories in primates and oxyurid parasites.

Maturation time is a pivotal life-history trait of parasitic nematodes, determining adult body size, as well as daily and total fecundity. Recent theoretical work has emphasized the influence of prematurational mortality on the optimal values of age and size at maturity in nematodes. Eosinophils are a family of white blood cells often associated with infections by parasitic nematodes. Although the role of eosinophils in nematode resistance is controversial, recent work has suggested that the action of these immune effectors might be limited to the larval stages of the parasite. If eosinophils act on larval survival, one might predict, in line with theoretical models, that nematode species living in hosts with large eosinophil numbers should show reduced age and size at maturity. We tested this prediction using the association between the pinworms (Oxyuridae, Nematoda) and their primate hosts. Pinworms are highly host specific and are expected to be involved in a coevolutionary process with their hosts. We found that the body size of female parasites was negatively correlated with eosinophil concentration, whereas the concentration of two other leucocyte families-neutrophils and lymphocytes-was unrelated to female body size. Egg size of parasites also decreased with host eosinophil concentration, independently of female size. Male body size was unrelated to host immune parameters. Primates with the highest immune defence, therefore, harbour small female pinworms laying small eggs. These results are in agreement with theoretical expectations and suggest that life histories of oxyurid parasites covary with the immune defence of their hosts. Our findings illustrate the potential for host immune defence as a factor driving parasite life-history evolution.

Animals↗

Trichobius joblingi, Aspidoptera falcata, and Megistopoda proxima (Diptera : Streblidae) parasitic on Carollia perspicallata and Sturnia lillium (Chiroptera : Phyllostomidae) in southeastern Brazil: sex ratios, seasonality, host site preference, and effect of parasitism on the host.

This note examines the effect of parasitism on host size, the preference of the parasite for a specific host body area, and the seasonal abundance for the 3 most abundant bat flies (i.e., Trichobius joblingi Wenzel, a parasite of the bat Carollia perspicillata [Linnaeus], and Aspidoptera falcata Wenzel and Megistopoda proxima [Séguy], parasites on Sturnira lilium [Geoffroy]). Trichobius joblingi and A. falcata are moderately dorsoventrally flattened and were collected on the wing membranes of their hosts, and M. proxima is moderately laterally compressed, has long, thin hind legs, and was collected in the body fur of the host. These 3 parasites also showed distinct seasonal patterns. There was a significant negative correlation between the simultaneous occurrence of A. falcata and M. proxima on the host. Parasitism by M. proxima was correlated with a significant weight loss in male S. lilium, which may reflect the large size, high activity, and constant feeding of this parasite, thereby causing a significant negative effect on the host. Sex ratios favoring male flies could be explained by the tendency of female flies to leave the host immediately before the bat leaves the shelter in search for food or immediately after bats are collected but could also be a consequence of higher mortality among females, especially gravid ones. Finally, collecting may have influenced the skewed sex ratio because male flies, being more active, were more evident to the collector.

Age Distribution↗

Effect of temperature and host-parasite ratio on sex differentiation of Romanomermis iyengari (Welch), a mermithid parasite of mosquitoes.

The effect of temperature and host-parasite ratio on the percentage infection and sex differentiation of R. iyengari was studied. Significant differences were observed in the percentage infection due to different host-parasite ratios and temperatures. At 25 degrees and 30 degrees C, the host parasite ratio of 1:3 resulted in 86-92% infection of Culex quinquefasciatus larvae. At 20 degrees and 35 degrees C, a higher host-parasite ratio was required to get this level of infection. More number of post-parasites per mosquito larva emerged at 20 degrees (1.5-5.8) and 25 degrees C (1.9-6.3) than at 30 degrees (1.5-3.9) and 35 degrees C (1.6-3.6). More than 50% of the post-parasites were females at 20 degrees and 25 degrees, 30 degrees and 35 degrees C at 1:1-1:10, 1:1-1:4 and 1:1-1:3 host-parasite ratios, respectively.

Animals↗

[Nationwide survey of the distribution of human parasites in China--infection with parasite species in human population].

The infection rate of main species of parasites and their character by first nationwide survey of human parasites was made. The overall infection rate of human intestinal parasite and the infection rate of most species of parasites were higher in females than that in males. The infection rate according to the age group, the highest infection rate was found in the group aged 5-14 years. With regard to the relation between parasitic infections and occupations of the infected persons, the highest infection rates of Ascaris lumbricoides were exhibited in school children, of hookworm and Clonorchis sinensis were in halfpeasants and halfmerchant and vegetable grower; of Trichuris trichiura were in fishers, of Giardia lamblia, Entamoeba histolytica and Taenia were in herdsmen and halfherdsmen and halfpeasants. In this survey it is also shown that each nationality has their main species of parasites. The family clustering of some main parasites were proved by some province/autonomous region/municipality.

Adolescent↗

[The occurrence of tumors in the minnow Phoxinus phoxinus (L.), their influence upon the parasite fauna, component community of parasites, and organism of the host].

The occurrence of tumors, their influence upon the organism of Phoxinus phoxinus (L.), its parasite fauna, and parasite component community were investigated in the upstream of the Pechora River. According to the data obtained, tumors could occur in the fishes of every age group, but one-year (0+) or two-year (1+) old minnow is affected by tumors more frequently. The tumors lesion extensiveness ranges from 0.02 to 3 %. From 1 to 3 tumors were recorded on one fish specimen. The investigated tumors were in progressive stage (Georgiev, 2000), since the vascular ingrowth and dissemination (in few cases) of the tumors were observed. Tumors are colored in intensive-black and taupe. The taupe tumors usually have a compact capsule at its peripheries, which isolates affected tissue from muscle fibers. In the intensive-black tumors the invasion of tumor cells to the adjacent transversal striated musculature is observed. Distinct symptoms of necrosis are revealed in all slides of the new growths. Blood vessels are formed in most tumors, and the blood flow is recorded before the completion of the vessels forming, that apparently supplies the tumors feeding. Metastases in different organs revealed in several minnow specimens. Tumor affected individuals of the minnow has parasite species complex practically identical (by species list and quantity) with the same of the even-aged unaffected fishes. However, the parasite component communities of the affected individuals are characterized by 4 groups of species, while the parasite component communities of the intact individuals--by 3 groups. The parasite communities of affected and unaffected one-year fishes are similar by the number of the groups of species, but differ in the number of species.

Animals↗

On becoming a parasite: evaluating the role of wall oxidases in parasitic plant development.

BACKGROUND: The temporal and spatial control of the transition from vegetative to parasitic growth is critical to any parasite, but is essential to the sessile parasitic plants. It has been proposed that this transition in Striga spp. is controlled simply by an exuded oxidase that converts host cell-surface phenols into benzoquinones which act as developmental signals that mediate the transition. An understanding of this mechanism may identify the critical molecular events that made possible the evolution of parasitism in plants. RESULTS: PoxA and PoxB are identified as the only apoplastic phenol oxidases in Striga asiatica seedlings, and the genes encoding them have been cloned and sequenced. These peroxidase enzymes are capable of oxidizing the 60 known inducing phenols into a small set of benzoquinones, and it is these quinones that induce parasitic development. Analysis of the reaction requirements and comparisons to host enzymes, however, lead us to argue that PoxA and PoxB are not necessary for host recognition. CONCLUSIONS: A new model is proposed where constitutive production of an activated oxygen species (in the case of Striga, H2O2) mediates host recognition. This strategy would allow a parasite to exploit abundant host enzymes to produce the diffusible recognition signals by converting a standard host defense into a parasitic offense.

Amino Acid Sequence↗

Estimation of the sequestered parasite load in severe malaria patients using both host and parasite markers.

The virulence of the malaria parasite Plasmodium falciparum is due, in part, to its ability to cytoadhere in deep vascular beds. Our inability to quantify the load of sequestered parasites hampers our understanding of the pathophysiological mechanisms involved in disease progression and complicates diagnosis. In this study we evaluate potential biochemical markers of sequestered load by comparing them with estimates of the sequestered load from a statistical model fitted to longitudinal patterns of peripheral parasite densities in a series of 22 patients with severe Plasmodium falciparum malaria. The markers comprised the host factors: haematocrit, circulating host DNA, sTNF-R75 and parasite derived products HRP2, pLDH, pigments and circulating parasite DNA. We investigated the suitability of these markers in determining sequestered loads in patients on quinine treatment. Observed peripheral parasitaemia, plasma levels of sTNF-R75 and circulating parasite DNA were most strongly correlated with estimates of sequestered loads on admission. However the dynamics of both sTNF-R75 and circulating parasite DNA during follow-up were very different from those of the estimated sequestered mass. These analyses suggest that none of the markers gave reliable estimates of the current sequestered load, though they may reflect the history of infection. Longitudinal analyses are needed that allow for the clearance rates of the marker molecules and for variations between hosts in the history of parasitaemia.

Animals↗

The treatment of Plasmodium falciparum-infected erythrocytes with chloroquine leads to accumulation of ferriprotoporphyrin IX bound to particular parasite proteins and to the inhibition of the parasite's 6-phosphogluconate dehydrogenase.

Ferriprotoporphyrin IX (FPIX) is a potentially toxic product of hemoglobin digestion by intra-erythrocytic malaria parasites. It is detoxified by biomineralization or through degradation by glutathione. Both processes are inhibited by the antimalarial drug chloroquine, leading to the accumulation of FPIX in the membranes of the infected cell and their consequent permeabilization. It is shown here that treatment of Plasmodium falciparum-infected erythrocytes with chloroquine also leads to the binding of FPIX to a subset of parasite proteins. Parasite enzymes such as aldolase, pyrimidine nucleaside monophosphate kinase and pyrimidine 5'-nucleotidase were inhibited by FPIX in vitro, but only the activity of 6-phosphogluconate dehydrogenase was reduced significantly in cells after drug treatment. Additional proteins were extracted from parasite cytosol by their ability to bind FPIX. Sequencing of these proteins identified heat shock proteins 90 and 70, enolase, elongation factor 1-alpha, phoshoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase, L-lactate dehydrogenase and gametocytogenesis onset-specific protein. The possible involvement of these proteins in the antimalarial mode of action of chloroquine is discussed. It is concluded that drug-induced binding of FPIX to parasite glycolytic enzymes could underlie the demonstrable inhibition of glycolysis by chloroquine. The inhibition of 6-phosphogluconate dehydrogenase could explain the reduction of the activity of the hexose monophosphate shunt by the drug. Inhibition of both processes is deleterious to parasite survival. Binding of FPIX to other proteins is probably inconsequential to the rapid killing of the parasite by chloroquine.

Animals↗

A survey of internal parasites and parasite control on North Island deer farms.

AIM: To evaluate internal parasite control practices and their effectiveness, and to investigate relationships between indices of parasitism and production outcomes by analysis of data collected during a deer herd health and production profiling project. METHODS: A longitudinal study of 15 red deer farms in the North Island of New Zealand was carried out from March 1992 to April 1994. Anthelmintic usage was recorded. Sentinel weaner, yearling and adult hinds and stags were blood and faecal sampled in early autumn, winter, spring and summer for serum pepsinogen and faecal egg and larval counts. A descriptive analysis of control programmes and egg and larval counts was produced. In addition, further measurements of parasitism and parasite control, including faecal egg count and faecal larval count data, individual pepsinogen concentrations, timing and numbers of anthelmintic treatments, and a farm calf faecal lungworm larvae count index were firstly subjected to univariate statistical association with production outcomes, followed by stepwise multivariable logistic regression analysis. Timing and numbers of anthelmintic treatments, along with other farm, herd or animal management risk factors, were included into path models. RESULTS: A wide range of anthelmintic programmes in all age groups, within farms between years and between farms was recorded. Weaner deer received three to nine treatments in their first year. Many farmers treated older deer in only one of the years of study. Older stags were treated more often than younger stags. Oxfendazole, ivermectin and moxidectin were the most commonly used anthelmintics. Egg and larval counts varied between properties and between years in some seasons but a higher proportion of deer shed larvae than eggs. In winter the number of weaners shedding eggs was the same as in autumn, but fewer shed lungworm larvae. Counts were lower at 12 months of age. Counts in older stags and hinds were highest in early spring, and counts were higher in yearling stags than in adult stags. Geometric mean pepsinogen concentration was lowest in weaners and rose to adult levels by early spring. Statistical analyses showed a lower weaning weight associated with higher faecal larval count index, and a reduced number of anthelmintic treatments prior to weaning. Weaners grew faster in spring after late winter anthelmintic treatment than those without treatment or with later treatments. There were inverse relationships between both farm mean weaner and adult serum pepsinogen and summer growth of weaners, and weaning percentage of adult hinds, respectively. CONCLUSION: This study has highlighted current parasite control practices, relationships between indices of parasitism and production outcomes, and has identified areas for further research into parasitism in farmed deer.

Journal Article↗

Genetic complexity of Plasmodium vivax parasites in individual human infections analyzed with monoclonal antibodies against variant epitopes on a single parasite protein.

Monoclonal antibodies against variant epitopes of a highly polymorphic protein (PV200) in schizonts of Plasmodium vivax have been used to analyze the variety of genetically distinct populations of parasites present in the peripheral blood of individual P. vivax infections in Sri Lanka. In 9 out of 10 isolates of freshly drawn P. vivax infected blood from different individuals, parasites of only 1 PV200 serotype was found within each individual infection, even though parasites were serotypically distinct between individuals. In 1 isolate parasite population, 3 distinct PV200 serotypes were identified. Thus, most P. vivax infections appeared to consist of a single genetically homogeneous population of parasites within the detection limits of the technique. The prevalence of P. vivax infections in an area of malaria transmission in southern Sri Lanka and the densities of oocysts in mosquitoes fed on P. vivax infected individuals indicated that parasite populations would be transmitted many times before encountering parasites of other origins, and that individual populations would tend to reduce to genetic homogeneity during transmission. These expectations are consistent with the high proportion of genetically homogeneous P. vivax isolates observed.

Adult↗

Circumsporozoite protein gene from Plasmodium reichenowi, a chimpanzee malaria parasite evolutionarily related to the human malaria parasite Plasmodium falciparum.

We have cloned and sequenced the gene encoding the circumsporozoite (CS) protein of Plasmodium reichenowi a Plasmodium falciparum-like malaria parasite of chimpanzees. Comparison of the two CS proteins reveals both similarities and differences in these two evolutionarily related parasites that have adapted to different hosts. The P. reichenowi CS protein has a new repeat sequence, NVNP, in addition to the P. falciparum-like NANP and NVDP repeats. In the immunodominant TH2R and TH3R regions of the CS protein, the amino acid sequences are similar in both parasite proteins. The differences in the two proteins exist in domains around the conserved regions, Region I and Region II, which are otherwise conserved in the CS proteins of P. falciparum analyzed to date. Studies of parasite protein genes of evolutionarily related malaria parasites, together with other immunologic and biologic characteristics, will help better understand the evolution and host parasite relationship of malaria parasites and may provide a tool for identifying protein determinants for malaria vaccine development.

Amino Acid Sequence↗

Parasite antigen-specific interleukin-10 and antibody reponses predict accelerated parasite clearance in Plasmodium falciparum malaria.

Using strict inclusion criteria, we conducted a hospital-based, case-control study in which 100 Gabonese children with severe Plasmodium falciparum malaria were matched for age, gender and provenance with 100 children presenting with mild malaria. Parasite antigen-specific cellular and humoral immunological responses were measured and compared with post-treatment parasite clearance times in each group. Significantly faster parasite clearance times were associated with in vitro production of IL-10 by acute-phase peripheral blood mononuclear cells (PBMC) in response to both liver and asexual stage parasite antigens, but not with proliferative, IFN-gamma, or TNF responses to the same antigens. In addition, in those children with mild malaria, higher levels of acute-phase antibody responses to liver stage antigen-1 (LSA-1) were associated with faster parasite clearance times, and were correlated with the presence of IL-10 responses to the same antigen. No such associations were found for IL-10 or antibody responses to a range of asexual blood stage antigens. Those with severe malaria had significantly lower levels of anti-LSA-1 antibodies compared to their counterparts with mild malaria. In conclusion, the results of this study suggest that parasite antigen-specific IL-10-mediated antibody responses may play a role in the control of asexual stage parasite multiplication in P. falciparum malaria.

Amino Acid Sequence↗

Host genes, parasites and parasitic infections.

Resistance to infection of mammalian hosts by parasites is under genetic control at many different levels: between species, between races, breeds and lines of single species and between individuals. These genetic effects have been described in many host-parasite systems. Here we review the interaction between three elements: host genes, parasites and the environment in which parasitic infections develop. Already livestock industries exploit genetic variation between breeds, particularly for the control of trypanosomiasis and tick infestation in cattle. In most populations, and to many diseases, resistance is heritable and selective breeding for resistance in commercial livestock species has been successful experimentally. Attempts at utilizing genetic variation are placed in the broad context of the coevolution of host and parasite, the limited knowledge we have of the mode of action of resistance genes and our ability to use genetic information to predict resistance to parasites.

Animals↗

Selection for plasmid post-segregational killing depends on multiple infection: evidence for the selection of more virulent parasites through parasite-level competition.

Is the virulence of parasites an outcome of optimized infection? Virulence has often been considered an inevitable consequence of parasite reproduction when the cost incurred by the parasite in reducing the fitness of its current host is offset by increased infection of new hosts. More recent models have focused on how competition occurring between parasites during co-infection might effect selection of virulence. For example, if co-infection was common, parasites with higher intrinsic growth rates might be selected, even at the expense of being optimally adapted to infect new hosts. If growth rate is positively correlated with virulence, then competition would select increased virulence. We tested these models using a plasmid-encoded virulence determinant. The virulence determinant did not contribute to the plasmid's reproduction within or between hosts. Despite this, virulent plasmids were more successful than avirulent derivatives during selection in an environment allowing within-host competition. To explain these findings we propose and test a model in which virulent parasites are selected by reducing the reproduction of competitors.

Animals↗

Growth factor receptors in helminth parasites: signalling and host-parasite relationships.

Parasitic helminths remain major pathogens of both humans and animals throughout the world. The success of helminth infections depends on the capacity of the parasite to counteract host immune responses but also to exploit host-derived signal molecules for its development. Recent progress has been made in the characterization of growth factor receptors of various nematode and flatworm parasites with the demonstration that transforming growth factor beta (TGF-beta), epidermal growth factor (EGF) and insulin receptor signalling pathways are conserved in helminth parasites and potentially implicated in the host-parasite molecular dialogue and parasite development.

Animals↗

Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions.

Experimenta naturae, like the glucose-6-phosphate dehydrogenase deficiency, indicate that malaria parasites are highly susceptible to alterations in the redox equilibrium. This offers a great potential for the development of urgently required novel chemotherapeutic strategies. However, the relationship between the redox status of malarial parasites and that of their host is complex. In this review article we summarise the presently available knowledge on sources and detoxification pathways of reactive oxygen species in malaria parasite-infected red cells, on clinical aspects of redox metabolism and redox-related mechanisms of drug action as well as future prospects for drug development. As delineated below, alterations in redox status contribute to disease manifestation including sequestration, cerebral pathology, anaemia, respiratory distress, and placental malaria. Studying haemoglobinopathies, like thalassemias and sickle cell disease, and other red cell defects that provide protection against malaria allows insights into this fine balance of redox interactions. The host immune response to malaria involves phagocytosis as well as the production of nitric oxide and oxygen radicals that form part of the host defence system and also contribute to the pathology of the disease. Haemoglobin degradation by the malarial parasite produces the redox active by-products, free haem and H(2)O(2), conferring oxidative insult on the host cell. However, the parasite also supplies antioxidant moieties to the host and possesses an efficient enzymatic antioxidant defence system including glutathione- and thioredoxin-dependent proteins. Mechanistic and structural work on these enzymes might provide a basis for targeting the parasite. Indeed, a number of currently used drugs, especially the endoperoxide antimalarials, appear to act by increasing oxidant stress, and novel drugs such as peroxidic compounds and anthroquinones are being developed.

Animals↗