Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “parasite”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed2003

Habitat overlap and gastrointestinal parasitism in sympatric African bovids.

Gastrointestinal parasite infections are widespread among wild ungulates. Because many of these parasites infect multiple host species, inter-specific interactions among hosts potentially play an important role in parasite transmission dynamics in ungulate communities. In this study, the effects of inter-specific contact on parasitism rates in 11 sympatric African bovids was examined using habitat overlap among species as a measure of cross-species contact rates. Across individual hosts, strongyle nematode abundance increased with increasing numbers of bovid species occupying a habitat. Furthermore, comparative analyses show a positive association between strongyle prevalence and level of habitat overlap across taxa. These findings suggest that among sympatric bovids, contact between species contributes significantly to the transmission of generalist nematode parasites. For a more host-specific parasite group, coccidia, parasite abundance and individual probability of infection declined in hosts living in bovid rich habitats. This pattern may reflect enhanced interspecific competition among parasites in these areas. Finally, similar to strongyle abundance, individual parasite richness also increased among hosts occupying habitats with higher numbers of bovid species. No association between habitat overlap and parasite richness was detected at higher taxonomic scales, however, which suggests that contact between host species may not contribute to parasite colonization of new host taxa.

Animals↗
PubMed1990

Effects of host age, host density and parent age on reproduction of the filth fly parasite Urolepis rufipes (Hymenoptera: Pteromalidae).

Urolepis rufipes Ashmead, a pteromalid wasp, was recently discovered parasitizing house fly and stable fly pupae in eastern Nebraska dairies. Studies have been conducted on the biology of this parasite to evaluate its potential as a biological control agent of stable flies (Stomoxys calcitrans (L.] and house flies (Musca domestica L.). House fly pupae were suitable as hosts for U.rufipes at all ages; however, significantly higher parasitism occurred on host pupae aged 96-120 h. Parasite-induced mortality (host mortality without progeny production) was higher than for other pteromalid parasites of filth flies under similar conditions. Parasitism increased with parasite--host ratio at 20 degrees C; however, the opposite was noted at 30 degrees C for parasite--host ratios ranging from 5:50 to 50:50. Fly eclosion decreased as parasite--host ratio increased at 20 degrees C, and no host eclosion occurred at the highest parasite--host ratios (20:50 and 50:50) at 30 degrees C. Females produced an average of 18.6 female and 7.6 male progeny. 88% of the progeny were produced during the first 6 days post parental eclosion. The short life span, low progeny emergence rate and high per cent host eclosion, in comparison with other parasite species, suggests that the Nebraska strain of U.rufipes may not an effective biological control agent of house flies.

Age Factors↗
PubMed2002

Modulating the modulators: parasites, neuromodulators and host behavioral change.

Neuromodulators can resculpt neural circuits, giving an animal the behavioral flexibility it needs to survive in a complex changing world. This ability, however, provides parasites with a potential mechanism for manipulating host behavior. This paper reviews three invertebrate host-parasite systems to examine whether parasites can change host behavior by secreting neuromodulators. The parasitic wasp, Cotesia congregata, suppresses host feeding partly by inducing the host (Manduca sexta) to increase the octopamine concentration in its hemolymph. The increased octopamine concentration disrupts the motor pattern produced by the frontal ganglion, preventing the ingestion of food. Polymorphus paradoxus (Acanthocephalan) alters the escape behavior of its host, Gammarus lacustris (Crustacea), possibly through an effect on the host's serotonergic system. The trematode Trichobilharzia ocellata inhibits egg-laying in its snail host (Lymnaea stagnalis), partly by inducing the host to secrete schistosomin. Schistosomin decreases electrical excitability of the caudodorsal cells. The parasite also alters gene expression for some neuromodulators within the host's central nervous system. In at least two of these three examples, it appears that the host, not the parasite, produces the neuromodulators that alter host behavior. Producing physiologically potent concentrations of neuromodulators may be energetically expensive for many parasites. Parasites may exploit indirect less energetically expensive methods of altering host behavior. For example, parasites may induce the host's immune system to produce the appropriate neuromodulators. In many parasites, the ability to manipulate host behavior may have evolved from adaptations designed to circumvent the host's immune system. Immune-neural-behavioral connections may be pre-adapted for parasitic manipulation.

Animals↗
PubMed2003

[Formation and diversity of parasitophorous vacuoles in parasitic protozoa. The Coccidia (Sporozoa, Apicomplexa)].

Data on parasitophorous vacuole (PV) formation in host cells (HC) harbouring different intracellular protozoan parasites have been reviewed and critically analysed, with special reference to the main representatives of the Coccidia. The vacuole membrane (PVM) is the interface between host and parasite, playing a role in nutrient acquisition by the parasite from the HC. The PV phenomenon is regarded as a generalized HC response to the introduction of alien bodies (microorganisms), which eventually reflects the evolutionary established host-parasite relationships at cellular, subcellular and molecular levels. Special attention has been paid to the existing morpho-functional diversity of the PVs within the same genera and species of parasites, and even at different stages of the parasite life cycle. The PVM is generally considered to derive from the HC plasmalemma, whose biochemical composition undergoes significant changes as the intravacuolar parasite grows. The original HC proteins are selectively excluded from the PVM, while those of the parasite are incorporated. As the result, the changed PVM becomes not fusigenic for HC lysosomes. For Toxoplasma gondii and other cyst-forming coccidia (Isospora, Sarcocystis), a definite correlation has been noticed between the extent of rhoptry and dense granule secrets released by a zoite during HC internalization, on the one hand, and the pattern of the PV that forms, on the other one. In T. gondii, tachyzoites, known to discharge abundant secrets, commonly force the development of PVs limited with a single unit membrane and equipped with a tubulovesicular network in the lumen. Unlike, bradyzoites known to be deficient in secretory materials trigger the formation of PVs with a three-membrane lining composed of the changed invaginated plasmalemma in addition to two membranes of endoplasmic reticulum. The two different types of PV harbour, respectively, exoenteric and enteric stages of T. gondii, the latter being confined to the cat intestine only. Unlike, all endogenous stages of the classic intestinal coccidia (Eimeria spp.) develop within PVs limited with a single membrane, with some invaginations extending into the PV lumen. Unusual PV patterns are characteristic of the extracytoplasmic eimerian coccidia (Cryptosporidium, Epieimeria) and adeleid haemogreagarines (Karyolysus). In cyst-forming coccidia, the PVM is actively involved in tissue cyst wall formation, thus protecting the encysted parasites from recognition by the host immune system. All this strongly suggests that the PV is far from being an indifferent membraneous vesicle containing a parasite, but represents a metabolically active compartment in infected cells. Since all the coccidia are obligate intracellular parasites, the mode of their intimate interaction with the HC, largely accomplished via the PV and its membrane, is vital for their survival as biological species.

Animals↗
PubMed1997

Fitness of parasites: pathology and selection.

Parasites improve their fitness as a result of the selection of traits which determine their relationships with their hosts. Some of these relationships are examined briefly. There is a cost of virulence for parasites, paralleling the cost of resistance for hosts, which implies that the good health of the host can be a component of parasite fitness; conversely, some transmission modes imply that the host be markedly weakened by the parasite. Pathogenicity can be influenced by characters such as a transmission of the parasite from parents to offspring, or the demographic characteristics of the host populations. Important components of parasite fitness are: the complexity of the life-cycle; the degree of specialization for a more or less open host range; the conspicuousness or discretion of the infective and parasitic stages. However, the best possible adaptation to a particular host is not always selected: when a parasite exploits several host species, the gene flows between parasites which have developed in different hosts may be responsible for "maladaptation". This may be important for an understanding of the pathogenicity of certain human parasitic diseases.

Animals↗
PubMed1994

The evolution of parasite manipulation of host behaviour: a theoretical analysis.

Parasite-induced modifications of host behaviour are known from a wide range of host-parasite associations. In many cases, these behavioural changes are thought to be adaptive and benefit the parasite by increasing its probability of successful transmission. However, in many cases, energy spent on host manipulation will not be available for other functions, such as growth. These trade-offs suggest that in the absence of other constraints, natural selection will optimize, and not maximize, the influence of parasites on host behaviour. This argument is developed and expanded into theoretical considerations of the evolution of host behaviour manipulation by parasites. Among populations of the same parasite species or among closely-related species, the optimal investment into manipulation, or optimal manipulative effort (ME*), of individual parasites is predicted to increase as (1) typical infrapopulation size decreases, (2) prevalence increases, (3) the longevity of the infected host, or of the parasite in its host, decreases, (4) passive transmission rates decrease, and (5) parasite fecundity decreases. This evolutionary analysis indicates that ecological and life history variables may have played an important role in the evolution of manipulation of host behaviour by parasites.

Adaptation, Physiological↗
PubMed2002

Cleaning symbioses from the parasites' perspective.

Cleaning behaviour has generally been viewed from the cleaner or client's point of view. Few studies, however, have examined cleaning behaviour from the parasites' perspective, yet they are the equally-important third players in such associations. All three players are likely to have had their evolution affected by the association. As cleaner organisms are important predators of parasites, cleaners are likely to have an important effect on their prey. Little, however, is known of how parasites are affected by cleaning associations and the strategies that parasites use in response to cleaners. I examine here what parasites are involved in cleaning interactions, the effect cleaners have on parasites, the potential counteradaptations that parasites have evolved against the predatory activities of cleaner organisms, the potential influence of cleaners on the life history traits of parasites, and other factors affected by cleaners. I have found that a wide range of ectoparasites from diverse habitats have been reported to interact with a wide range of cleaner organisms. Some of the life history traits of parasites are consistent with the idea that they are in response to cleaner predation. It is clear, however, that although many cleaning systems exist their ecological role is largely unexplored. This has likely been hindered by our lack of information on the parasites involved in cleaning interactions.

Adaptation, Physiological↗
PubMed1992

Lipid peroxidation in Plasmodium falciparum-parasitized human erythrocytes.

cis-Parinaric acid (PnA) was used as a fluorescent probe to study lipid peroxidation in nonparasitized and Plasmodium falciparum-parasitized erythrocytes, upon challenge by cumene hydroperoxide and tert-butyl hydroperoxide. Parasitized erythrocytes were less susceptible toward lipid peroxidation than nonparasitized erythrocytes with which they had been cultured. Furthermore, nonparasitized erythrocytes cultured together with parasitized cells, and thereafter isolated on a Percoll gradient, were less susceptible toward lipid peroxidation than erythrocytes kept under the same experimental conditions but in the absence of parasitized cells. We concluded, therefore, that the intracellular development of the parasite leads to an increase in the resistance against oxidative stress, not only of the host cell membrane of the parasitized erythrocyte, but also in the plasma membrane of the neighboring cells. The erythrocyte cytosol of parasitized cells and/or the intraerythrocytic parasite was required for the increased protection of the host cell membrane, since ghosts prepared from parasitized erythrocytes were more susceptible to lipid peroxidation than those prepared from nonparasitized ones. Vitamin E content of parasitized erythrocytes was lower than that of nonparasitized cells. However, parasitized erythrocytes promoted extracellular reduction of ferricyanide at higher rates, which might be indicative of a larger cytosolic reductive capacity. It is suggested that the improved response of intact erythrocytes is due to an increased reduction potential of the host-erythrocyte cytosol. The role of vitamin C as a mediator of this process is discussed.

Animals↗
PubMed1992

Plasmodium chabaudi: association of reversal of chloroquine resistance with increased accumulation of chloroquine in resistant parasites.

The effects of tricyclic antidepressants, desipramine and imipramine, and phenothiazines, chlorpromazine and trifluoperazine, on chloroquine (CQ)-resistant and CQ-sensitive lines of P. chabaudi were examined in vivo. In mice that received daily injections of these drugs the growth of CQ-resistant and CQ-sensitive parasites was unaffected or affected very slightly, if at all. A combination of CQ and each drug suppressed the growth of CQ-resistant parasites in a dose-dependent manner. In addition, in CQ-sensitive parasites each drug also increased the susceptibility to CQ. Measurements of CQ levels by high-performance liquid chromatography showed that CQ accumulated in sensitive parasites to more than twice the level in resistant parasites at 2 to 4 hr after an injection of CQ. Verapamil and desipramine substantially increased CQ levels in both CQ-resistant and CQ-sensitive parasites. These results suggest that not only Ca2+ antagonists but tricyclic antidepressants reverse CQ resistance in CQ-resistant parasites and enhance the inhibitory effect in sensitive parasites by increasing CQ levels in those parasites. The effects of Ca2+ antagonists, tricyclic antidepressants, and phenothiazines on a pyrimethamine-resistant line of P. chabaudi were also studied. None of the Ca2+ antagonists (verapamil, nicardipine, and diltiazem) affected the growth of the parasite in combination with 20 mg/kg pyrimethamine. Tricyclic antidepressants and phenothiazines suppressed pyrimethamine-resistant parasites to some extent. However, the extent of this suppression was less pronounced as compared with that of suppression of CQ resistance by the same drugs.

Animals↗
PubMed1998

Effects of parasitization by Cotesia congregata on the brain-prothoracic gland axis of its host, Manduca sexta.

The ability of prothoracic glands (PTGs) from parasitized and unparasitized Manduca sexta 5th-instars to respond to ecdysiotropic extracts prepared from day-5 5th instar brains was compared. An in vitro bioassay revealed that PTGs from parasitized animals were much less responsive to brain PTTH than glands from unparasitized larvae. However, when incubated in Grace's medium in the absence of brain extract, glands from day-3 and -4 hosts remained active for a much longer period of time than did those dissected from their unparasitized counterparts. Rather than exhibiting reduced (basal) levels of synthesis after the 3rd hour of incubation, glands from these parasitized larvae continued to synthesize/release ecdysteroid into the medium at relatively high rates. The timing of this enhanced secretory activity is coincident with the ecdysteroid peak that occurs just prior to and during wasp emergence. Following parasite emergence, gland activity decreased, and by the third day after emergence, was reduced to low levels. Results suggest that the requirement for PTTH to stimulate ecdysteroid production has been bypassed, i.e. that the parasite has uncoupled the normal mechanisms that permit brain regulation of PTG activity. The ability of brains from parasitized M. sexta to stimulate PTGs from unparasitized day-2 5th instars was also examined. Dose-response analyses performed for the first 7 days of the 5th instar showed that on a per brain basis ecdysiotropic activity in brains from parasitized and unparasitized animals was similar. However, when differences in brain size were considered, ecdysiotropic activity appeared to be more concentrated in brains from day-7 parasitized larvae than in brains from similarly aged unparasitized larvae. Analysis of the size distribution of the ecdysiotropic activity in brains from parasitized larvae revealed a unique form that was larger than the 29kDa standard. This suggests that parasitization may inhibit neuropeptide processing, particularly during the final stages preceding emergence of the wasps from the host. Thus, both an inhibition of prothoracicotropic hormone processing and the inability to respond to this neurohormone may contribute to the developmental arrest characteristic of parasitized 5th instars.

Journal Article↗
PubMed1997

Vector-parasite transmission complexes for onchocerciasis in West Africa.

BACKGROUND: In West Africa, there are two strains of the filarial parasite Onchocerca volvulus, which differ in their ability to induce ocular disease. Transmission studies have suggested that six sibling species of the parasite vector, the black fly Simulium damnosum sensu lato, allow development of the two strains of O volvulus with varying efficiency. We aimed to test the hypothesis of parasite-vector complexes, whereby the two parasite strains, known as forest and savanna, are preferentially transmitted by distinct groups of the species of S damnosum S l. METHODS: During 1993 and 1994, wild black flies were collected from 11 river basins within the area covered by the Onchocerciasis Control Programme (OCP). The flies were dissected and filarial larvae, ovaries, and malpighian tubules removed. Genomic DNA was extracted from larvae, and PCR amplification was used to classify O volvulus parasites as forest or savanna strains. PCR-amplified DNA from ovaries and malpighian tubules was used to distinguish sibling species of S damnosum s l. S yahense and S squamosum were distinguished by body colour. FINDINGS: 214 of 105105 flies dissected were infected with filarial larvae; 84 of these were infected with mature O volvulus parasites. Of the 35 savanna-dwelling infected flies. 17 carried forest-strain parasites and 18 savanna-strain parasites. Of the 45 infected flies identified as the forest dwelling sibling species. 20 carried savanna-strain parasites and 25 forest-strain parasites. No significant differences were found in the numbers of mature larvae of each strain carried by the forest-dwelling species of fly or in the number of forest and savanna larvae in savanna-dwelling vector species. INTERPRETATION: Vector-parasite transmission complexes do not currently play a part in the biology of O volvulus transmission in the area of the OCP in West Africa. This finding has important strategic implications for the future of efforts to control onchocerciasis in West Africa.

Africa, Western↗
PubMed1997

A comparative analysis of parasite species richness of Iberian rodents.

Data on parasites of rodents, collected over an 18-year period on the Iberian peninsula, were used to find the determinants of parasite species richness. A total of 77 species of helminth parasites (nematodes, cestodes and digeneans) was identified among 16 species of rodents. Parasites were classified into groups according to their specificity towards their host and their life-cycle. A working phylogeny of the rodents was proposed on the basis of molecular and paleontological data and for each host the following parameters were recorded: sample size, weight, geographical range, longevity, and life-style. Two comparative methods were used, the independent comparisons method of Pagel (1992) and the distance matrix method of Legendre, Lapointe & Casgrain (1995). The second method has the advantage of measuring the relative contribution of phylogeny. Both methods gave similar results. Overall parasite species richness correlated only with host sample size. Host body size does not correlate with any subset of parasite species richness. However, host phylogeny is a good predicator of specific parasites and the species richness of digeneans correlates with host geographical range. A phylogenetic reconstruction of host relations was performed using the parasites belonging to subgroups in which richness is correlated with host phylogeny. These parasite species were treated as Dollo characters, i.e. we made the assumption that the loss of a parasite species is irreversible. The consensus tree obtained reflects the major phylogenetic divisions of the host group. Finally, this study illustrates the relative importance of processes acting at different temporal and spatial scales (evolutionary time and actual geographical range of hosts) in determining the structure of helminth parasite fauna.

Animals↗
PubMed2002

Diversification and host switching in avian malaria parasites.

The switching of parasitic organisms to novel hosts, in which they may cause the emergence of new diseases, is of great concern to human health and the management of wild and domesticated populations of animals. We used a phylogenetic approach to develop a better statistical assessment of host switching in a large sample of vector-borne malaria parasites of birds (Plasmodium and Haemoproteus) over their history of parasite-host relations. Even with sparse sampling, the number of parasite lineages was almost equal to the number of avian hosts. We found that strongly supported sister lineages of parasites, averaging 1.2% sequence divergence, exhibited highly significant host and geographical fidelity. Event-based matching of host and parasite phylogenetic trees revealed significant cospeciation. However, the accumulated effects of host switching and long distance dispersal cause these signals to disappear before 4% sequence divergence is achieved. Mitochondrial DNA nucleotide substitution appears to occur about three times faster in hosts than in parasites, contrary to findings on other parasite-host systems. Using this mutual calibration, the phylogenies of the parasites and their hosts appear to be similar in age, suggesting that avian malaria parasites diversified along with their modern avian hosts. Although host switching has been a prominent feature over the evolutionary history of avian malaria parasites, it is infrequent and unpredictable on time scales germane to public health and wildlife management.

Animals↗
PubMed2003

Island and taxon effects in parasitism revisited: avian malaria in the Lesser Antilles.

We identify and describe the distribution of 12 genetically distinct malaria parasite lineages over islands and hosts in four common passerine birds in the Lesser Antilles. Combined parasite prevalence demonstrates strong host effects, little or no island effect, and a significant host-times-island interaction, indicating independent outcomes of host-parasite infections among island populations of the same host species. Host- and/or island-specific parasite lineages do not explain these host-parasite associations; rather, individual lineages themselves demonstrate the same type of independent interactions. Unlike overall prevalence, individual parasite lineages show considerable geographic structure (i.e., island effects) as well as species effects indicating that parasite lineages are constrained in their ability to move between hosts and locations. Together, our results suggest an upper limit to the number of host individuals that malaria parasites, as a community, can infect. Within this limit, however, the relative frequency of the different lineages varies reflecting fine scale interactions between host and parasite populations. Patterns of host-parasite associations within this system suggest both historical co-evolution and ecologically dynamic and independent host-parasite interactions.

Animals↗
PubMed2002

Malaria parasites giving rise to recrudescence in vitro.

Recrudescences were simulated in vitro with drug treatment to examine how drug-sensitive parasites survive the treatment. Various numbers of cultured parasites were treated with lethal doses of pyrimethamine or mefloquine for various lengths of time. Recrudescences were observed in parasite populations with larger initial numbers of parasites when the treatment duration was prolonged. Equal numbers of parasitized erythrocytes were treated with various concentrations of pyrimethamine or mefloquine. There was no clear linear relationship between the incidence of recrudescence and the drug concentration. Parasites that had recrudesced were continuously allowed to recrudesce in the succeeding recrudescence experiments. Both the duration from the cessation of treatment to the time at which the recrudescent parasitemia level reached 1% and the growth rate of recrudescent parasites were equal among these recrudescences. The recrudescent parasites in these experiments were as sensitive to the drugs as the parasites tested before treatment were. These results suggest that a parasite culture may contain parasites in some phases that are not killed by drug for up to 10 days, which explains the recrudescences that occur even after treatment.

Animals↗
PubMed2003

Mortality in immatures of the floodwater mosquito Ochlerotatus albifasciatus (Diptera: Culicidae) and effects of parasitism by Strelkovimermis spiculatus (Nematoda: Mermithidae) in Buenos Aires Province, Argentina.

Life tables were constructed for six cohorts of immature stages of the floodwater mosquito Ochlerotatus albifasciatus (Macquart) in a park in Buenos Aires, highlighting the mortality attributable to the parasitic nematode, Strelkovimermis spiculatus Poinar & Camino. Two cohorts were selected to compare parasite incidence in all mosquito stages when low and high parasitism occurred. Development time of Oc. albifasciatus from first instar to adult was 7.7-10 days in the spring, 6 days in the summer, and 10.9-21.9 days in the fall. Survival was estimated as 0-1.4% in the spring, 2% in the summer and 0.2-4.4% in the fall. The highest "K" value (Killing power) occurred during a fall cohort when prevalence of the parasite was 86.9%, and the lowest in a spring cohort. Parasitism occurred during all seasons, but S. spiculatus persisted to adult only in the summer and fall, when adult mosquitoes developed from parasitized third and fourth instars larvae. The abundance of S. spiculatus differed between old and young larvae only when parasite prevalence was the highest. Although pupae and adults of Oc. albifasciatus were parasitized, no pupal mortality attributable to parasitism was recorded. The proportion of parasitized adults ranged from 14.2% and 5.7% in the two cohorts compared. Pupal wet weight and adult wing lengths did not differ between parasitized and unparasitized individuals.

Animals↗
PubMed2001

The role of parasitic diseases as causes of mortality in small ruminants in a high-potential farming area in central Kenya.

A 15-year retrospective study was performed to determine the role of parasitic diseases in causing mortalities in small ruminants. In total, 115 (32 %) sheep were diagnosed as having been killed by parasitic diseases out of 366 that died as a result of disease. The major cause of mortality was helminthosis (63 % of all parasitic cases). Most of the helminthosis cases were attributed to haemonchosis (40% of parasitic cases). Heartwater was the second most important parasitic disease (27% of all parasitic cases). Ninety-five (26%) goats were diagnosed to have been killed by parasitic diseases out of 365 cases presented at the post mortem facility. Helminthosis was the most frequent cause of mortality (55% of the total parasitic diseases). Twenty-six goats were killed by haemonchosis (27% of all parasitic diseases). Heartwater was the second most important parasitic disease, accounting for about 20% of all parasitic diseases. These findings indicate that viable helminth and tick control strategies should be devised in order to reduce mortality caused by helminthosis and heartwater and thereby achieve improved productivity.

Animals↗
PubMed1994

Antimalarial action of hydrophilic drugs: involvement of aqueous access routes to intracellular parasites.

The antimalarial action and intracellular distribution of the hydrophilic agents phloridzin (PHL) (a bioflavonoid glycoside) and desferrioxamine (DFO) (an iron chelator) were studied in cultures of Plasmodium falciparum-infected human erythrocytes. When added to cultures, these agents arrested parasite growth with IC50 values of 12 microM (PHL) and 22 microM (DFO). At 37 degrees, PHL (40 microM) was virtually impermeant to uninfected cells but permeated with a mean t1/2 of 1.5 hr in trophozoites (30% accessible cell volume) and 8 hr in rings (10% of accessible cell volume). PHL, in analogy with DFO, was demonstrably permeant to infected cells harboring mature forms of the parasites. Permeation was restricted to only a fraction of the infected cell volume. PHL elicited inhibition of nucleic acid synthesis within 1 hr of exposure of trophozoites to PHL (40 microM) and in > 8 hr of exposure of rings. Red cell containers into which millimolar concentrations of PHL or DFO were encapsulated demonstrably supported parasite invasion and subsequent parasite growth and maturation (48-hr incubation). Under culture conditions, uninfected or parasite-infected red cell containers that were loaded with either agent retained the drugs for at least 42 hr at hundred-micromolar concentrations. The agent present in the cells was fully active after release from cells and administration to test cultures of parasites. PHL added to parasite cultures was active at micromolar concentrations, but when present intracellularly it was virtually inactive even at millimolar concentrations. The data presented are consistent with direct access of hydrophilic agents from medium to parasite, a process referred to as fenestration. Permeation into parasites might constitute the rate-limiting step in drug uptake and drug-mediated arrest of parasite growth by PHL and DFO. The putative role of the parasitophorous duct in providing aqueous access routes from medium to parasites is discussed.

Animals↗