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Scanning electron-microscopic study of the uptake of Leishmania parasites by macrophages.

The interaction of promastigotes of the protozoan parasite Leishmania tropica with mouse peritoneal macrophages in vitro was studied by scanning electron microscopy. Motile promastigotes attached to host cells by their flagellar tips to which the macrophages responded by producing rather closely fitting lamellar sheaths and progressively enveloping first the flagellum and then the body of the parasite. Lamellar advance during engulfment was rapid in the first 10 min but much slower later on. Fully engulfed parasites could be seen after 1 h but most parasites associated with host cells remained extracellular even after 4 h. On the other hand, parasites immobilized by fixation adhered by either their flagellar or somatic ends. Engulfment proceeded at a steady rate, and by 4 h most of them were completely engulfed. Both the attachment and engulfment stages of parasite uptake were inhibited by low temperature, cytochalasin D and mild fixation of macrophages. The rheological features of the host cells' response to parasite adherence indicate that invasion by parasites is through phagocytosis rather than penetration.

Animals

Complement activation by parasites. A review.

Activation of complement by parasites (living parasites or purified parasite antigens) is involved in several mechanisms of the host parasite relationship. In most of the experiments performed in vitro, complement activation was found to be lethal for the parasites, but sometimes it could be essential for the development of parasitemia. Both classical and alternative complement pathways may be activated by parasites; the classical pathway nearly always requires the involvement of antibodies whereas the alternative pathway is activated directly by products released by the parasites or present in their teguments. Activation of complement, especially via the alternative pathway may also be a prerequisite for cellular adherence to parasites which can then cause their death.

Animals

[Parasitic rheumatism].

The joint manifestations of parasitic diseases are rare. They may be due to the presence of a parasite within one or severed joints, to involvement of a neighbouring joint, or distant involvement due to an immuno-allergic mechanism. The latter category constitutes what one may call parasitic rheumatism. The latter is characterised by arthropathies of inflammatory type with raised sedimentation rate, marked but inconstant hypereosinophilia, and total inefficacy of antirheumatic treatments. The diagnosis of parasitic rheumatism depends on these criteria, on the diagnosis of the parasitic disease in question, above all filariasis but also other parasitic diseases, and above all the great efficacy of specific anti-parasitic treatments.

Adult

Parasite clearance in patients with Plasmodium vivax monoinfection treated with artesunate in Cambodia: an observational secondary analysis of trial data.

BACKGROUND: Artemisinin-based combination therapies are the frontline drugs for the treatment of malaria infections, but, for Plasmodium falciparum, the efficacy of artemisinin is threatened by the spread of resistance. Plasmodium vivax is the second most common cause of human malaria, but there is little information on its susceptibility to artemisinin due to the lack of an in-vitro culture system. This study aims to characterise the response of P vivax to artesunate using clinical, genomic, and transcriptomic data from infected individuals in Cambodia. METHODS: We analysed 161 P vivax infections from 87 patients (six female and 81 male; median age 20 years [IQR 17-26]) enrolled between Nov 10, 2021, and Nov 18, 2022, in a drug efficacy study in Cambodia and treated with 2 mg/kg/day of artesunate for 7 days. To determine clearance rates, we measured parasitaemia before, and 1 h, 2 h, 4 h, 8 h, and 16 h after the first dose of artesunate, and then at 24-h intervals during the 7 days of artesunate therapy. We also examined the parasites' genome sequences and used RNA sequencing of 31 infections to analyse changes in parasite gene expression upon treatment. FINDINGS: All infections were successfully cleared by day 3. However, 49 of the infections displayed a slow clearance after treatment, including nine (6%) infections with a parasite clearance slope half-life greater than 5 h. We observed no significant association between slow clearance and either patient or infection characteristics (including the infection's stage composition). Analyses of gene expression showed that, while fast-clearing parasites displayed significant changes in gene expression immediately upon treatment, slow-clearing parasites had a delayed gene expression response characterised notably by a downregulation of genes associated with haemoglobin endocytosis and digestion. INTERPRETATION: Some Cambodian P vivax parasites clear slowly after artesunate treatment, possibly due to a downregulation of haemoglobin metabolism that might reduce the efficiency of the artesunate. The slow clearance could allow parasites to outlast artesunate treatment and facilitate emergence of resistance to the artemisinin-combination therapy partner drug, threatening malaria elimination effort. FUNDING: US National Institutes of Health.

Adolescent

Studies on enzyme variation in the murine malaria parasites Plasmodium berghei, P. yoelii, P. vinckei and P. chabaudi by starch gel electrophoresis.

Electrophoretic variation of the enzymes glucose phosphate isomerase, 6-phosphogluconate dehydrogenase, lactate dehydrogenase and glutamate dehydrogenase (NADP-dependent) has been studied in the African murine malaria parasites Plasmodium berghei, P. yoelii, P. vinckei and P. chabaudi and their subspecies. Horizontal starch gel electrophoresis was used throughout. The number of isolates examined in each subspecies varied from 1 (P. y. nigeriensis) to 24 (P. c. chabaudi). Extensive enzyme variation was found among isolates of most of the subspecies from which more than two such isolates were available for study. It is clear that the phenomenon of enzyme polymorphism is of common occurrence among malaria parasites. With the exception of P. berghei and P. yoelii, of which all isolates share an identical electrophoretic form of lactate dehydrogenase, no enzyme forms are shared between any of the 4 species of murine plasmodia. By contrast, within each species common enzyme forms are shared among each of the subspecies. The subspecies are nevertheless, distinguished from each other by the electrophoretic forms of at least one enzyme. The distribution and reassortment of enzyme variation among isolates of a single subspecies is in accordance with the concept of malaria parasites as sexually reproducing organisms. The study of variation among parasites present in individual wild-caught rodent hosts demonstrates that natural malarial infections usually comprise genetically heterogeneous populations of parasites. Nevertheless, the number of genetically distinct types of parasite of any one species present in a single infected host appears to be small. Generally not more than 2 or 3 clones of parasite of distinct genetic constitution are present in a single infected animal.

Animals

Surface properties of extracellular malaria parasites: electrophoretic and lectin-binding characteristics.

The surface charge and lectin-binding capacity of isolated malaria parasites and host erythrocytes were analyzed and compared by chromatographic, electrophoretic, and cytochemical methods. Results indicated that at physiological pH values both freshly prepared and glutaraldehyde-fixed parasites and erythrocytes possess a net negative surface charge. Both cell types were strongly bound to cation-exchange resins and underwent cathode-directed electrophoretic migration. The isoelectric points for erythrocyte-free parasites and uninfected erythrocytes were approximately 3.0 and 4.0, respectively. The different effects of selective enzymatic digestion and solvent extraction on the electrophoretic mobilities of free parasites and erythrocytes suggested that the chemical constituents responsibile for the net negative surface charges on each type of cell are different. The surface charge of the free parasites seemed mainly to be a function of ionized phospholipids rather than of the ionogenic sialic acid moieties, which are the major contributors to the negative charge on erythrocytes. Results of lectin-binding studies indicated that specific glycosidimoieties (i.e., glucose, galactose, mannose, and n-acetyglucosamine), common to the erythrocyte surface, were either absent or in low concentration at the parasite's surface. These observations suggest that the normally intracellular malaria parasites have surface characteristics, differing from those of the host cell, characterized by a scarcity of lectin-binding receptors and sialic acid residues and by the major contribution of lipids to their surface charge.

Absorption

Isolation of Plasmodium berghei by hemolysin lysis of infected erythrocytes and evidence for a parasite hexokinase.

A rapid and simple procedure has been developed for the isolation of Plasmodium berghei parasites from infected-mouse erythrocytes employing the heat stable hemolysin produced by Pseudomonas aeruginosa. Using parasites isolated by this method, the presence of a parasite specific hexokinase has been demonstrated, providing an explanation for the increased glucose consumption observed with infected cells. Enzyme assays and serology were employed in determining the purity and yield of purified parasites. The enzyme assays showed that about 25% of the parasites in infected RBCs were recovered in the purified state. The purified parasites were not agglutinated by rabbit-anti-mouse RBC serum which indicated the purified parasites were not contaminated by RBC components.

Animals

Food-borne parasitic infections--old stories and new facts.

A review is presented of food-borne parasitic infections. Parasitic infections with public health hazards both from conventional slaughter animals and from seafood (fish and shellfish) are discussed. The former category includes cysticercosis, echinococcosis, and trichinosis, the latter category covers various trematode, cestode, nematode, and possibly also protozoan infections. Examples of trematode infections are heterophyidiasis, transmitted to man by marine fish, and Paragonimus spp parasites, transmitted by crustaceans. Cestode infections include diphyllobothriasis transmitted by both fresh water fish and fish from brackish waters. Special attention is drawn to the condition known as sparganosis. Of the nematode infections, the eosinophilic granulomatous enteritis due to the genera Anisakis, Phocanema, and Contracaecum, transmitted to man by either marine fish or crustaceans, is mentioned. Two other nematode infections. Angiostrongylus cantonensis and Capillaria philippinensis, can also be transmitted to man by marine fish. Free living amoebae (a.o. Naegleria) may be transmitted to man via shellfish as vehicles. Apart from a possible direct effect of these parasites, chemical alterations in seafood resulting from the presence of parasites may also be deleterious to the consumer. Special attention is drawn to a newly developed serological detection method, the enzyme-linked immunosorbent assay, which makes detection of infection possible not only at the slaughterhouse but also at the farm or in large herds. Strategies to control parasitic infections both in conventional slaughter animals and in seafood are discussed.

Animals

Effect of age and sex on the prevalence of intestinal parasitism in dogs.

The effects of age, sex, and neutering on the prevalence of canine intestinal parasitism were evaluated by fecal examination of 1,468 pet dogs admitted to the University of Missouri Veterinary Teaching Hospital during 1975. Evidence of hookworm infection was encountered in 35.8% of the dogs examined, whipworms in 18.5%, ascarids in 17.9%, tapeworms in 5.2%, and coccidia in 4.5%. Evidence of intestinal parasitism was not detected in 653 (44.4%) dogs. Whipworm infections were detected less often in young dogs than in older ones, whereas ascarid and coccidial infections were more prevalent in pups that in mature dogs. In dogs more than 6 months old, hookworm infections were the most common parasitism. Tapeworm infections were diagnosed sporadically in all age groups. For most of these parasites, castrated males and spayed females had decreased prevalence of infection, compared with their respective intact counterparts. There were significant (P less than 0.05) differences in the prevalence of both ascarid and hookworm infections between intact and spayed female dogs. Also, there were significant (P less than 0.001) differences between age categories for all parasites observed. Overall, parasitism tended to decrease with age.

Age Factors

Molecular mechanisms underlying drug resistance in protozoan parasites: emerging mechanisms and therapeutic perspectives.

Protozoan parasitic infections, including malaria, leishmaniasis, and human African trypanosomiasis, remain major global public health challenges. In the absence of highly effective vaccines, disease control relies primarily on chemotherapy; however, the emergence and spread of drug-resistant parasite populations increasingly threaten treatment efficacy. This review synthesizes current evidence on the molecular mechanisms underlying drug resistance in Plasmodium, Leishmania, and Trypanosoma species through a systematic analysis of literature. The review identifies four interconnected mechanisms that drive the evolution of drug resistance. First, altered drug transport enables parasites to regulate intracellular drug concentrations through mutations, loss, or amplification of membrane transporters, including PfCRT in Plasmodium and AQP2 in Trypanosoma brucei. Second, target modification and genomic plasticity promote resistance through point mutations in drug targets, such as dhfr and dhps in Plasmodium, while kinetoplastids, particularly Leishmania, exploit extensive genomic plasticity, including aneuploidy, gene amplification, and translational reprogramming, to facilitate rapid adaptation under drug pressure. Third, metabolic reprogramming enhances parasite survival by increasing intracellular thiol production, strengthening antioxidant defense systems, and reshaping central carbon and lipid metabolism to mitigate drug-induced stress. Finally, stress response and persistence mechanisms enable subpopulations of parasites to enter dormant, persister-like states characterized by reduced metabolic activity and slowed proliferation, thereby evading both host immune responses and chemotherapeutic agents. Collectively, these findings demonstrate that drug resistance is a dynamic, multifactorial evolutionary process rather than a single molecular event. Addressing this growing challenge requires integrating genomic surveillance, molecular diagnostics, mathematical modeling of resistance transmission, and mechanistic insights into parasite persistence into future drug discovery and disease control strategies. Such an integrated approach is essential for improving the durability of antiprotozoal therapies and advancing global efforts to control neglected protozoan diseases.

antiprotozoal therapy

[The effect of lactation on the parasitism of rats by Strongyloides ratti (author's transl)].

In lactating females of many animal species infested by Nematoda, the self-cure is, if not suppressed, at least very distinctly delayed. It does not appear that an immunological deficiency is the cause of this. We show that this phenomenon also exists in lactating female rats with Strongyloides ratti parasites. In fact, for Strongyloides ratti, the maintenance of the worms is not the only notable modification determined by lactation; much more important is the decrease in the intensity of the parasitism. This aspect is not mentioned by writers who have only studied the different parasitic states in their final phase. Parallel to these alterations in the parasitism, the evolution of the corticosteronemy differs, from two points of view, from that described in infested virgin rats: --Suppression of the hypercorticosteronemy which normally appears 48 hours after infestation; --Attenuation of the hypocorticosteronemy which usually sets in from the tenth day of infestation. This opposition of lactation to the variations in the corticosteronemy induced by the worms is explained by the effect of lactation on the secretion of gluco-cortico-steroids, described under the term of "buffer effect of lactation". The decrease in the intensity of the parasitism may be explained by the fact that lactation, by preventing the hypercorticosteronemy normally caused by larval migration, permits the intervention of aspecific defences. As for the prolongation of the parasitism, it would seem to result on one hand, from a reduced solicitation of the means of defence owing to a smaller number of worms and, on another hand, from the slowing down of the hypocorticosteronemy through the buffer effect of lactation with all the consequences flowing from this at the level of the specific and aspecific defence reactions.

Adrenal Cortex Hormones

Incidence of intestinal parasites in children of different socio-economic population of Dacca city.

Stool samples of 1500 children of different socio-economic status of Dacca city was examined for the presence of intestinal parasites. Samples were collected on voluntary basis which may be treated as randomised. Out of these 1500 children, 816 were male and 684 were female. The overall incidence of parasites was 65.80%, the male children slightly prepondering over the female children. Children of age group 6-10 years showed high incidence of almost all the parasites. Children of Basti area showed the highest incidence (about 90%) and most of them harboured multiple parasites. About 27.13% of infants under the age of one year (mostly from Basti area) harboured parasites. Intestinal parasites were observed that both housing and economic status played vital roles in the occurrence of intestinal parasitosis but the housing and environmental conditions were found to be in a stronger position than economic status.

Adolescent

The conflicting role of parasitic infections in modulating the prevalence of asthma.

Nothwithstanding difficulties associated with the limitations of survey techniques and methodology employed to define asthma, the evidence accumulated to date suggests that the reported differences in the prevalence rates of this disease from country to country and within local populations of the one country are real. It is accepted that allergy is not the sole cause of asthma but nonetheless hypersensitivity to environmental allergens is a significant triggering factor in most countries of the world. Comparisons between countries might therefore be influenced by the time of the year when the survey is taken since the prevalence of seasonal asthma would be higher in the period of pollinosis. Environmental factors, and in particular the relative atmospheric concentrations of pollens and the density of house dust mite (D. pteronyssinus and D. farinae) in dwellings, must therefore be considered when accumulating prevalence data. The prevalence rate for childhood asthma is high in Australia, United Kingdom, United States of America and New Zealand, and medium to low in the Scandinavian countries and Switzerland. It is not clear what factors contribute toward these differences since several studies indicate that racial characteristics per se are not pre-eminent in defining susceptibility to asthma. Most surveys indicate that the prevalence of childhood asthma is low to very low among low-income populations living in tropical areas. While it is possible to implicate inadequate diagnosis, genetic factors, nutritional status and allergen exposure as factors contributing towards the low prevalence, it has become fashionable to attribute this observation to the influence of certain helminthic infections. Parasites stimulate the production of high levels of serum IgE, the bulk of which has as yet an undetermined specificity. The suggestion that this IgE blocks mast cell receptors leaving insufficient sites available for sensitization by allergen-specific IgE antibody is attractive. However, since the kinetics of binding to mast cell receptors is unlikely to be the same for all IgE molecules, irrespective of their specificity, this hypothesis appears to be an oversimplification of the problem. It is more likely that parasitic infections repress the synthesis of IgE antibody to environmental allergens, although the mechanism for this is unclear. Circumstantial evidence suggests that the time course of exposure to parasites versus sensitization by environmental allergens may be critical. Another possibility is that parasitic infections in some way nullify the effect of allergens at the level of the target organ, perhaps through the modulating role of eosinophils. If it is established that parasitic infections, particularly in early childhood, suppress the capacity of potentially atopic children to develop asthma and other allergic disorders, there would be some justification in attempting to circumvent allergic disorders in susceptible individuals by a harmless preparation of parasite antigens.

Adolescent

Parasitic relationships between Pythium oligandrum Drechsler and some other species of the Oomycetes class.

Parasitic relationships between Pythium oligandrum Drechsler and some phytopathogenic species of the Oomycetes class were investigated on agar plates. A high parasitic ability of Pythium oligandrum on Pythium ultimum Trow, P. debaryanum Hesse, and Aphanomyces laevis De By species was proved in this study of relationships among these fungi, commonly populating the rhizosphere of emerging sugar beet. P. oligandrum produces numerous thin haustorial threads, searching the hyphae of host species and enwrapping them during the parasitation. In a later parasitation stage the host organs were enwrapped by thicker hyphae of P. oligandrum as well. P. oligandrum grew through the colony of parasitized species mostly within 24 hours after inoculation and was able to destroy it entirely within 5--6 days. P. oligandrum produced numerous fructification organs in contradistinction to parasitized species. P. oligandrum oospores germinated abundantly when host species were present. Hyperparasitism of P. oligandrum was found both in cultivation with a single host and in common cultivation with all three host species simultaneously.

Agar

Parasites in Bulinus senegalensis (Mollusca: Planorbidae) and their detection.

Isoelectric focusing studies on enzyme variation between populations of the snail Bulinus senegalensis revealed that parasitic infections in the snails contributed additional bands of enzyme activity, particularly in the glucose phosphate isomerase (GPI) and malate dehydrogenase (MDH) systems. The patterns due to the parasite enzymes were, in most cases, clearly distinct from those of the host and different from each other. Parasites encountered included Schistosoma haematobium, S. bovis, Paramphistomum microbothrium, another amphistome probably belonging to the group which infect amphibians, Echinostoma revolutum, another echinostome (probably Echinoparyphium sp.), strigeids, xiphidiocercariae (these were resolved into 3 distinct types by the enzyme data) and ciliate protozoa. The 7 host populations which were examined showed marked differences in both the prevalence and variety of their parasitic infections and these variations were tentatively related to environmental differences in their respective habitats and to the nature of human contact patterns. Seasonal changes in the parasite fauna were also noted and some of the implications of the parasite load on the host population are briefly mentioned.

Animals

Plasmodium knowlesi-induced antigens in membranes of parasitized rhesus monkey erythrocytes.

Highly purified Plasmodium knowlesi schizonts were used to produce a hyperimmune anti-parasite serum in a rhesus monkey. Proteins of membranes from normal and P. knowlesi-infected erythrocytes, as well as purified schizonts, were solubilized in 1% Triton X-100 and analyzed by bidimensional electrophoretic techniques. Of seven parasite-specific antigens identified in membranes of parasitized erythrocytes by crossed immune electrophoresis against monkey anti-parasite serum, only three could be detected in the purified schizonts. Bidimensional focusing-dodecyl sulfate/polyacrylamide gel electrophoresis of membranes from parasitized cells revealed three proteins, in the 55,000-90,000 molecular weight region, with isoelectric points between pH 4.5 and pH 5.2, that could not be detected in normal membranes or purified schizonts. Membranes of normal erythrocytes and uninfected erythrocytes that had been incubated with sera from monkeys with 25-50% parasitemia did not react with the monkey anti-parasite serum.

Animals

Electron microscope cytochemistry of host-parasite membrane interactions in malaria.

Two membrane-bound enzymes were localized by electron microscope cytochemical techniques in Plasmodium lophurae and its host erythrocyte. Parasites were prepared by saponin lysis, French pressure cell lysis, or anti-red blood cell serum lysis; infected and uninfected erythrocyte ghosts were prepared by saponin or French pressure cell lysis. Enzyme incubations were performed on unfixed cells. Adenosinetriphosphatase (EC 3.6.1.3) activity was found on the inside of the ghost membrane and on the inside of the outer parasite membrane. NADH oxidase was found on the outside of the erythrocyte membrane and on the outside of the parasite outer membrane. The parasite plasma membrane was negative for both enzymes. The location of both enzymes on the outer parasite membrane were reversed from what one would have expected if the outer membrane had remained merely an invaginated erythrocyte membrane. It is concluded that the outer membrane, although derived from the red cell membrane, has been altered by its association with the malarial parasite.

Adenosine Triphosphatases

Variations in structure and function during the life cycle of malarial parasites.

The fine structure of malarial parasites is reviewed and the function of the intracellular organelles is discussed. When the erythrocytic, exoerythrocytic, and mosquito stages of plasmodia are compared, substantial differences are seen. The major differences involve the amount of surface coat of the motile forms, the structure and function of the mitochondria, and the ingestion and digestion of nutrients. Significant structural differences are also observed between comparable stages of mammalian and avian parasites. These differences indicate that malarial parasites adapt themselves to the different environments in which the parasite resides.When host cell changes induced by malarial parasite infection are reviewed, alterations characteristic of the infecting plasmodia are observed in erythrocytes. Erythrocyte changes include caveola-vesicle complexes, excrescences, and clefts. The caveola-vesicle complexes possess malarial antigens and exhibit pinocytotic activities. The excrescences form focal junctions with adjacent cells and may be responsible for infected erythrocyte sequestration in organs. The significance of these host cell changes specific to certain species of malarial parasite is still unknown.

Animals