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Chemotherapy and immunity in opportunistic parasitic infections in AIDS.

Parasitic diseases are endemic in parts of the tropics, but there is no convincing evidence that their prevalence or incidence is increasing due to the HIV epidemic. Available scientific data on parasitic infections in patients with the Acquired Immunodeficiency Syndrome (AIDS) suggests a predominance of Pneumocystis carinii, Toxoplasma gondii and Cryptosporidium spp. For reasons which are unclear, parasitic infections such as Plasmodium falciparum, Strongyloides stercoralis and Entamoeba histolytica, where cell-mediated immune responses are also thought to be significant, do not appear to be opportunists of importance. It is being increasingly recognized that chemotherapy for parasitic diseases has a host-dependent component, although scientific data on this subject remain scanty. The management of opportunistic parasitic infections in patients infected with HIV is dogged by failures and relapses, aptly illustrating the notion of the relationship between chemotherapy and the immune response. This review discusses the immunity and chemotherapy of opportunistic parasite infections in patients infected with the Human Immunodeficiency Virus (HIV).

AIDS-Related Opportunistic Infections↗

Interactions between malaria parasites infecting the same vertebrate host.

Several species of malarial protozoans commonly parasitize the same host population and often the same individual host. This paper reviews the evidence for interactions among such host-sharing parasites. Field studies measuring the cross-sectional prevalence of malarial species often record fewer mixed infections than expected by chance, suggesting that one parasite has excluded another or suppressed its parasitaemia to undetectable levels. Prevalences may vary reciprocally between seasons, with one species increasing in prevalence while another decreases, despite parallel increases in the transmission rates of both, again suggesting suppression of one species by another. However, longitudinal studies of individual hosts indicate that malarial parasites may also favourably affect the host environment for each other, perhaps due to their depressive effect on the immune system: this is shown by the recrudescence of a latent malarial species immediately before or after the parasitic wave of another species. The suppression hypothesis is supported by data derived from the simultaneous inoculation of two Plasmodium species into laboratory animals; many studies have shown that one or both species are suppressed. This may be mediated by competition for host cells or nutrients, or by heterologous immunity. However, the suppressed species rebounds after the other species has abated, and may show a prolonged infection. Experimental evidence that one species can facilitate the recrudescence of another is minimal, but this may reflect the paucity of investigations of this phenomenon. Laboratory studies show only minor cross-resistance between host-sharing species, which is consistent with the hypothesis that their co-occurrence has led to antigenic divergence or that species showing strong heterologous resistance cannot co-exist in the same host population. Such complementarity occurs not only with the host immune response but also with many other life-history characteristics of host-sharing parasites, such as host cell preference. I conclude that malarial species have been important in each other's evolution, particularly in the tropics where multi-species complexes are common.

Animals↗

Interference in general immune function by parasite infections; African trypanosomiasis as a model system.

Many parasitic diseases are accompanied by an immunosuppression which may affect only parasite-specific responses in some infections or lead to a general dysfunction of the immune system in others. African trypanosomiasis causes a particularly severe disorder of the immune system and this serves as a model system for analysis of the cellular basis of a parasite-induced general immune dysfunction affecting nearly all T- or B-lymphoid cell subpopulations. The nature of the parasite products causing havoc in the immune system may well vary in different infections and still remains to be defined. Trypanosome membrane fractions are active in vitro or in vivo but we have no evidence for a direct action on B- or T-cells. In vitro, both in man and mouse, T-cells are stimulated, but only in the presence of accessory cells. This points to the importance of host-derived immunosuppressive factors in the immune dysfunction. We have evidence that macrophages, after uptake of parasites in the presence of antibodies, are at least one target cell for parasite action. They can mediate immunosuppression and undergo changes in phenotype and mediator release during the course of infection. The macrophages show all the characteristic signs of activation, which can also be induced by other means and other infective agents such as BCG. Thus, macrophage activation would provide a common pathway for induction of a general immunosuppression in different infections.

Animals↗

Variation and polymorphism in helminth parasites.

There are strong biological, evolutionary and immunological arguments for predicting extensive polymorphism among helminth parasites, but relatively little data and few instances from which the selective forces acting on parasite diversity can be discerned. The paucity of information on intraspecific variation stands in contrast to the fine detail with which helminth species have been delineated by morphological techniques, accentuating a trend towards considering laboratory strains as representative of a relatively invariant organism. However, in the fast-moving evolutionary race between host and parasite one would predict a monomorphic species would be driven to extinction. We review the arena of intraspecific variation for the major helminth parasites, ranging from biological properties such as host or vector preference, to biochemical and immunological characteristics, as well as molecular markers such as DNA sequence variants. These data are summarized, before focusing in more detail on polymorphisms within protein-coding genes of potential relevance to the host-parasite relationship, such as vaccine candidates. In particular, we discuss the available data on a number of major antigens from the filarial nematode Brugia malayi. Information is currently too sparse to answer the question of whether there is antigenic variation in filariasis, but the indications are that proteins from the blood-borne microfilarial stage show significant intraspecific variability. Future work will define whether polymorphisms in these antigens may be driven by exposure to the host immune response or reflect some other facet of parasite biology.

Animals↗

Activation of host constitutive immune defence by an intestinal trypanosome parasite of bumble bees.

Many parasites, including important species that affect humans and livestock, must survive the harsh environment of insect guts to complete their life-cycle. Hence, understanding how insects protect themselves against such parasites has immediate practical implications. Previously, such protection has been thought to consist mainly of mechanical structures and the action of lectins. However, recently it has become apparent that gut infections may interact with the host immune system in more complex ways. Here, using bumble bees, Bombus terrestris and their non-invasive gut trypanosome, Crithidia bombi, as a model system we investigated the effects of parasitic infection, host resources and the duration of infections on the host immune system. We found that infection doubled standing levels of immune defence in the haemolymph (the constitutive pro-phenoloxidase system), which is used as a first, general defence against parasites. However, physical separation of the parasite from the haemolymph suggests the presence of a messenger system between the gut and the genes that control the pro-phenoloxidase system. Surprisingly, we found no direct effect of host resource-stress or duration of the infection on the immune system. Our results suggest a novel and tactical response of insects to gut infections, demonstrating the complexity of such host-parasite systems.

Animals↗

Parasite specialization from a phylogenetic perspective: a new index of host specificity.

The host specificity of a parasite is not merely a function of how many host species it can exploit, but also of how closely related these host species are to each other. Here, a new index of host specificity is proposed, one that takes into account the average taxonomic or phylogenetic distance between pairs of host species used by a parasite. The index is derived from measures of taxonomic distinctness used in biodiversity studies. It is easy to compute and interpret, ranging from a minimum value of 1 when all host species are members of the same genus, to a maximum of 5, when all host species belong to different classes. The variance of this measure can also be computed, and provides additional information on the taxonomic or phylogenetic structure of the host assemblage. Using data on helminth parasites of Canadian freshwater fishes, we show that the new index, unlike the mere number of known host species, is independent of study effort i.e. the number of published records of a parasite. Although the index and the number of known hosts are not entirely independent statistically, each captures a different aspect of host specificity. For instance, although acanthocephalans infect significantly more host species than trematodes, cestodes or nematodes, there is no difference in the average index value among these 4 helminth taxa, suggesting that the average taxonomic distances between the host species of a parasite do not vary among these higher taxa. We recommend the use of our new index in future comparative studies of host specificity, in particular when the focus is on the evolutionary history of parasites and of their past colonizations of host lineages.

Animals↗

Parasite resistance and avoidance behaviour in preventing eye fluke infections in fish.

This paper examines the efficiency of acquired resistance in protecting the fish host, rainbow trout (Oncorhynchus mykiss), against the trematode parasite Diplostomum spathaceum, and the hypothesis that fish recognize areas where infective stages are aggregated and show avoidance behaviour. We found that when fish with a low level of infection were held in restricted cages in natural conditions they became infected and developed cataracts as a result of this infection. This suggests that acquired resistance is insufficient in protecting fish against the parasite or the deleterious effects of infection in conditions where fish could not avoid the parasite. Behavioural experiments in the laboratory showed that fish reacted to the parasite cercariae by avoiding the infection source, which decreased the rate of parasite establishment. We conclude that by using a combination of behavioural avoidance and physiological resistance, fish could defend against the parasite more effectively.

Animals↗

Geographical variations in infectivity and susceptibility in the host-parasite system Schistosoma mansoni/Biomphalaria glabrata: no evidence for local adaptation.

We investigated local adaptation in the spatially structured natural Biomphalaria glabrata/Schistosoma mansoni host-parasite system in the marshy forest focus of Guadeloupe using cross-transplantation experiments. We demonstrated strong and highly significant variations in susceptibility/infectivity of host and parasite populations, respectively, but found no evidence of local adaptation neither for S. mansoni nor for B. glabrata. Environmental as well as genetic factors are discussed to explain susceptibility/infectivity variations between both host and parasite populations. The absence of local adaptation is discussed in relation to the metapopulation dynamics of both host and parasite, in particular their relative rates of dispersal at the scale under scrutiny. Our study constitutes the first cross-transplantation experiment concerning this host-parasite system of which both hosts and parasites came directly from the wild, excluding laboratory generations and experimental host passages.

Adaptation, Biological↗

Interactions between parasites of the cockle Austrovenus stutchburyi: hitch-hikers, resident-cleaners, and habitat-facilitators.

The patterns of association between parasites within a particular host are determined by a number of factors. One of these factors is whether or not infection by one parasite influences the probability of acquiring other parasite species. This study investigates the pattern of association between various parasites of the New Zealand cockle Austrovenus stutchburyi. Hundreds of cockles were collected from one locality within Otago Harbour, New Zealand and examined for trematode metacercariae and other symbionts. Two interspecific associations emerged from the study. First, the presence of the myicolid copepod Pseudomyicola spinosus was positively associated with higher infection intensity by echinostomes. The side-effect of the copepod's activities within the cockle is suggested as the proximate mechanism that facilitates infection by echinostome cercariae, leading to a greater rate of accumulation of metacercariae in cockles harbouring the copepod. Second, a positive association was also found between infection intensity of the metacercariae of foot-encysting echinostomes and that of gymnophallid metacercariae. This supports earlier findings and suggests that the gymnophallid is a hitch-hiker parasite because, in addition to the pattern of positive association, it (a) shares the same transmission route as the echinostomes, and (b) unlike the echinostomes, it is not capable of increasing the host's susceptibility to avian predation. Thus, both active hitch-hiking and incidental facilitation lead to non-random infection patterns in this parasite community.

Animals↗

Horizontal transfer of parasitic sex ratio distorters between crustacean hosts.

Parasitic sex distorters were artificially transferred within and between crustacean host species in order to study the effects of parasitism on host fitness and sex determination and to investigate parasite host specificity. Implantation of Nosema sp. to uninfected strains of its Gammarus duebeni host resulted in an active parasite infection in the gonad of recipient females and subsequent transovarial parasite transmission. The young of artificially infected females were feminized by the parasite, demonstrating that Nosema sp. is a cause of a sex ratio distortion in its host. In contrast, we were unable to cross-infect Armadillidium vulgare with the feminizing microsporidian from G. duebeni or to cross-infect G. duebeni with the feminizing bacterium Wolbachia sp. from A. vulgare.

Adrenal Glands↗

Segregation of a microsporidian parasite during host cell mitosis.

We investigated the segregation of an intracellular microsporidian parasite during host cell division. A time-course experiment was carried out to examine the distribution of parasites relative to host chromosomal DNA via light and electron microscopy. Fluorescent light microscopy and EM studies showed that the parasite lay in the perinuclear zone of the host cell during interphase and segregated to daughter cells at mitosis. At metaphase, the parasite was frequently closely associated with host microtubules and mitochondria. Electron-dense bridges were observed between the parasites and the host microtubules and also between host mitochondria and microtubules. The study suggests that both the parasite and the host cell organelles segregate in association with spindle microtubules.

Animals↗

Parasitic infections among Southeast Asian labourers in Taiwan: a long-term study.

Parasitic infections have been reported to be relatively common among the Southeast Asian labourers in Taiwan. This study, conducted in 1992-6, was designed to determine the temporal changes of the prevalence. Faecal specimens were examined by the formalin-ethyl acetate sedimentation technique and blood samples screened using the quantitative buffy coat technique and confirmed by Giemsa stained blood smear. The overall prevalence of intestinal parasitic infections was 10.3%. The annual prevalence decreased from 33.3% in 1992-3 to 4.6% in 1995-6. The Thai (12.0%) and Indonesian (11.1%) had a higher prevalence than the Malaysian (6.7%) and Filipinos (5.9%). Opisthorchis viverrini was the most important parasite in the Thai and Trichuris trichiura in the remaining groups. Moreover, no blood parasites were found in the labourers. The dramatic temporal decline in the intestinal parasitic infections suggests that limiting the entry of infected persons, periodic follow-ups, and immediate treatment of sporadic cases are necessary in preventing transmission of non-indigenous parasites through large population change.

Adult↗

Towards a model of host-parasite relationships.

The question asked in this article is: "what is a parasite?". Defining a parasite requires defining its host at the same time. A difficult question therefore arises about host-parasite relationships. The object of general parasitology is in fact to study the relationship between a host and its parasite. The initial question "what is a parasite?" has to be reformulated within a conceptual framework, that of "relationship". This article is an attempt to transpose into parasitology some concepts which have been profitable in the fields of physics and chemistry. The studies of R. Thom about the individual are also used. Concepts like that of field and principles like that of minimization are probably operational on a high level of organization. The description of host-parasite relationships could benefit from these concepts.

Adaptation, Physiological↗

An eco-epidemiological study of contamination of soil with infective forms of intestinal parasites.

The objectives of the present work were to screen topsoil samples collected from public squares in two cities within the Argentine Patagonia for the presence of infective forms of intestinal parasites and to examine the possible relationship between positive findings and the environmental, socioeconomic, and cultural conditions of that region. For this purpose we studied 13 public squares, their 13 custodians, and 44 family groups within their respective surrounding areas. Of the 226 topsoil samples analyzed, 44.3% proved positive for infective forms of intestinal parasites, with 17.3% of these containing more than one species. The frequency of appearance of positive samples was dependent on the season of the year (p < 0.001), while presence of the parasites was related to the soil pH (p < 0.05) but independent of the soil relative humidity (p > 0.05). Some of the organisms detected are associated with zoonoses. We observed the presence of Capillaria spp. and Spirocerca spp. under cool desert climatic conditions. Within the group of custodians we detected hematologic alterations one positive serology for toxoplasmosis and documented behavior conducive to risk of infection with the parasites found in those squares. Within the family group an acquaintance with parasitic zoonoses and their prevention was an inconsistent finding, with toxocarosis and toxoplasmosis being the diseases associated with the greatest degree of ignorance. Furthermore, we consider the failure to de-parasitize pets and the practice of feeding them with raw meat, as typically found in our family survey, to be factors contributing to a greater likelihood of public square contamination. From the results obtained here, we propose a spatial organization approach for the purpose of detecting zones at risk of contracting zoonotic parasitoses within urban environments.

Adolescent↗

Testing the hypothesis of recent population expansions in nematode parasites of human-associated hosts.

It has been predicted that parasites of human-associated organisms (eg humans, domestic pets, farm animals, agricultural and silvicultural plants) are more likely to show rapid recent population expansions than are parasites of other hosts. Here, we directly test the generality of this demographic prediction for species of parasitic nematodes that currently have mitochondrial sequence data available in the literature or the public-access genetic databases. Of the 23 host/parasite combinations analysed, there are seven human-associated parasite species with expanding populations and three without, and there are three non-human-associated parasite species with expanding populations and 10 without. This statistically significant pattern confirms the prediction. However, it is likely that the situation is more complicated than the simple hypothesis test suggests, and those species that do not fit the predicted general pattern provide interesting insights into other evolutionary processes that influence the historical population genetics of host-parasite relationships. These processes include the effects of postglacial migrations, evolutionary relationships and possibly life-history characteristics. Furthermore, the analysis highlights the limitations of this form of bioinformatic data-mining, in comparison to controlled experimental hypothesis tests.

Animals↗

Associations between mycophagous Drosophila and their Howardula nematode parasites: a worldwide phylogenetic shuffle.

Little is known about what determines patterns of host association of horizontally transmitted parasites over evolutionary timescales. We examine the evolution of associations between mushroom-feeding Drosophila flies (Diptera: Drosophilidae), particularly in the quinaria and testacea species groups, and their horizontally transmitted Howardula nematode parasites (Tylenchida: Allantonematidae). Howardula species were identified by molecular characterization of nematodes collected from wild-caught flies. In addition, DNA sequence data is used to infer the phylogenetic relationships of both host Drosophila (mtDNA: COI, II, III) and their Howardula parasites (rDNA: 18S, ITS1; mtDNA: COI). Host and parasite phylogenies are not congruent, with patterns of host association resulting from frequent and sometimes rapid host colonizations. Drosophila-parasitic Howardula are not monophyletic, and host switches have occurred between Drosophila and distantly related mycophagous sphaerocerid flies. There is evidence for some phylogenetic association between parasites and hosts, with some nematode clades associated with certain host lineages. Overall, these host associations are highly dynamic, and appear to be driven by a combination of repeated opportunities for host colonization due to shared breeding sites and large potential host ranges of the nematodes.

Animals↗

Revisiting host/parasite interactions: molecular analysis of parasites collected during longitudinal and cross-sectional surveys in humans.

This paper summarizes the first conclusions arising from an analysis of parasite diversity in blood samples collected during longitudinal surveys conducted in Senegal. Parasite typing was carried out using a PCR-based molecular analysis of allelic polymorphism. The parasite populations circulating in the village of Dielmo during periods of intense transmission (when the inoculation rate was 0.5-1 infective bite/night) are characterized by a considerable allelic diversity of the MSP-1, MSP-2 and TRAP loci. A large proportion of blood samples contained several MSP-1 or MSP-2 alleles. In asymptomatic carriers, the complexity of the infections (number of alleles and genetic diversity of these alleles) was age-dependent. In children, the trend was for a reduced complexity during clinical episodes. Molecular typing showed that successive clinical episodes experienced by children were caused by genetically distinct parasites. Longitudinal analysis of asymptomatic carriers indicated that in the absence of transmission, the same parasite types were carried for long periods, while rapidly changing profiles were observed during intense transmission season. The consequences of these findings on our understanding of acquired anti-parasite immunity in humans living in endemic are discussed.

Alleles↗

Screening for intestinal parasites in recently arrived children from East Africa.

BACKGROUND: Intestinal parasitic carriage is common in East African populations with a wide spectrum of clinical severity. There are scant data on the rates of carriage in East African immigrants to Australia. This study describes the prevalence of and risk factors for intestinal parasite carriage among children recently arrived from East African countries. METHODS: Children aged 0-17 years, who attended an outpatient clinic, were born in East Africa and had immigrated since 1998 were eligible to participate. A single preserved stool specimen was collected for faecal microscopy, and blood tests were conducted for Strongyloides and Schistosoma serology, full blood examination and serum ferritin. RESULTS: One hundred and thirty-five children (median age 8.1 years, range 1.0-17.5) participated, of whom 133 (99%) provided a stool specimen. Parasites were detected in 50% of samples, and 18% of children carried a possibly pathogenic species. No child was symptomatic at diagnosis. Positive or equivocal serology occurred in 11% of children for Strongyloides and 2% for Schistosoma. Anaemia and iron deficiency were detected in 16% of all children. Those carrying an intestinal parasite were older (mean age 9.8 vs 7.4 years, P= 0.002) and less likely to be anaemic (odds ratio 0.37, 95% confidence interval 0.14-0.96) than those who were not carriers. CONCLUSIONS: Carriage of intestinal parasites is common among children from East Africa. Those carrying pathogenic organisms require treatment and follow up to ensure eradication. The results of this survey support the need for routine assessment of newly arrived immigrants from East Africa for intestinal parasites, anaemia and iron deficiency.

Adolescent↗