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PubMed1992

Efficacy of the morantel sustained release trilaminate bolus against gastrointestinal nematodes and its influence on immunity in calves.

An experiment was conducted in calves to investigate the efficacy of a morantel sustained release trilaminate bolus (MSRT) to control gastrointestinal parasitism and to assess the development of immunity during the use of MSRT. Two groups (M and U) of four calves each were infected three times a week with a mixed Ostertagia ostertagi and Cooperia oncophora infection for 12 weeks. Calves of Group M received an MSRT at the start of the experiment. Twenty weeks after the start of the experiment, all animals, including a previously uninfected control group (C), received a challenge with 100,000 Ostertagia and 100,000 Cooperia. After a further 4 weeks all calves were necropsied for worm counts. During the trial calves were weighed and faecal egg counts, larval differentiation and pepsinogen concentrations were determined. The results demonstrated the high level of efficacy of the MSRT in reducing the faecal egg output and preventing parasitic gastroenteritis under conditions of a continuous high rate of infection. Efficacy of treatment was higher for Cooperia than for Ostertagia. Post-mortem worm counts suggested a partially impaired immunity build-up in Group M, at least for Cooperia.

Animals↗
PubMed2006

Role of the employment status and education of mothers in the prevalence of intestinal parasitic infections in Mexican rural schoolchildren.

BACKGROUND: Intestinal parasitic infections are a public health problem in developing countries such as Mexico. As a result, two governmental programmes have been implemented: a) "National Deworming Campaign" and b) "Opportunities" aimed at maternal care. However, both programmes are developed separately and their impact is still unknown. We independently investigated whether a variety of socio-economic factors, including maternal education and employment levels, were associated with intestinal parasite infection in rural school children. METHODS: This cross-sectional study was conducted in 12 rural communities in two Mexican states. The study sites and populations were selected on the basis of the following traits: a) presence of activities by the national administration of albendazole, b) high rates of intestinal parasitism, c) little access to medical examination, and d) a population having less than 2,500 inhabitants. A total of 507 schoolchildren (mean age 8.2 years) were recruited and 1,521 stool samples collected (3 per child). Socio-economic information was obtained by an oral questionnaire. Regression modelling was used to determine the association of socio-economic indicators and intestinal parasitism. RESULTS: More than half of the schoolchildren showed poliparasitism (52%) and protozoan infections (65%). The prevalence of helminth infections was higher in children from Oaxaca (53%) than in those from Sinaloa (33%) (p < 0.0001). Giardia duodenalis and Hymenolepis nana showed a high prevalence in both states. Ascaris lumbricoides, Trichuris trichiura and Entamoeba hystolitica/dispar showed low prevalence. Children from lower-income families and with unemployed and less educated mothers showed higher risk of intestinal parasitism (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.6-22.6; OR 4.5, 95% CI 2.5-8.2; OR 3.3, 95% CI 1.5-7.4 respectively). Defecation in open areas was also a high risk factor for infection (OR 2.4, 95% CI 2.0-3.0). CONCLUSION: Intestinal parasitism remains an important public health problem in Sinaloa (north-western Mexico) and Oaxaca (south-eastern Mexico). Lower income, defecation in open areas, employment status and a lower education level of mothers were the significant factors related to these infections. We conclude that mothers should be involved in health initiatives to control intestinal parasitism in Mexico.

Analysis of Variance↗
PubMed1989

Toxicity and pharmacokinetics of the antibiotic fumagillin in yearling rainbow trout (Salmo gairdneri).

Yearling trout were administered fumagillin dicyclohexylamine (FDCH), an antibiotic that has shown promise for controlling myxozoan parasites in fish. FDCH was fed at 0.25 or 1 g/kg food at 1.5% body weight per day for 60 days, and gill, liver, kidney, spleen, thymus, intestine, and heart were examined histologically. In both treatment groups the hematopoietic tissue of the kidney and spleen was reduced and hematocrit was significantly lower relative to controls. No alteration was found in liver, intestine, heart, thymus, or gill. FDCH was also administered to trout through an indwelling catheter placed in the dorsal aorta. Plasma FDCH was measured using reverse-phase HPLC, and clearance microconstants were estimated. At the highest doses (60 and 30 mg/kg body wt) fumagillin was lethal within about 6 hr, and histological examination revealed extensive toxic alteration in liver and posterior kidney. Plasma clearance at 6 and 3 mg/kg fit a two-compartment model with a rapid alpha phase (i.e., 20 min) but a prolonged beta phase (5.4 days). Although these fish survived for at least 96 hr, renal tubular alteration remained.

Animals↗
PubMed2003

ABC transporters and drug resistance in parasitic protozoa.

Parasitic protozoa are responsible for a wide spectrum of diseases in humans and domestic animals. The main line of defence available against these organisms is chemotherapy. However, the application of chemotherapeutic drugs has resulted in the development of resistance mechanisms, which limit the number of antiprotozoal drugs that are effective in the treatment and control of parasitic diseases. Knowledge about the resistance mechanisms involved may allow the development of new drugs that minimise or circumvent drug resistance or may identify new targets for drug development. This review focuses on the role of protozoal ATP-binding cassette (ABC) transporters in drug resistance. These membrane proteins mediate the ATP-dependent transport of a wide variety of chemotherapeutic drugs away from their targets inside the parasites. The genome sequence of Plasmodium falciparum and Plasmodium yoelii has recently been completed, and the sequencing of other parasitic genomes are now underway. As a result, many new membrane transporters belonging to the ABC superfamily are being discovered. We review the ABC transporters in major parasitic protozoa, including Plasmodium, Leishmania, Trypanosoma and Entamoeba species. Transporters with an established role in drug resistance have been emphasised, but newly discovered transporters with a significant amino acid sequence identity to established ABC drug transporters have also been included.

ATP-Binding Cassette Transporters↗
PubMed1985

Novel retinoid-binding proteins from filarial parasites.

The present study deals with the discovery and partial characterization of specific binding proteins for retinol and retinoic acid from filarial parasites (worms of the superfamily Filarioidea), including those from two species of Onchocerca. These binding proteins, which are distinct in their physicochemical properties and in the mode of ligand interactions from the host-tissue retinoid-binding proteins, may be involved in the mediation of the putative biological roles of retinoids in the control of parasitic growth, differentiation and reproduction. Parasite retinol-binding protein and retinoic acid-binding protein exhibited specificity for binding retinol and retinoic acid respectively. Both the binding proteins showed an s20,w value of 2.0 S. On gel filtration, both proteins were retarded to a position corresponding to the same molecular size (19.0 kDa). On preparative columns, the parasite binding proteins exhibited isoelectric points at pH 5.7 and 5.75. Unlike the retinoid-binding proteins of mammalian and avian origin, the parasite retinoid-binding proteins showed a lack of mercurial sensitivity in ligand binding. The comparative amounts of retinoic acid-binding protein in five parasites, Onchocerca volvulus, Onchocerca gibsoni, Dipetalonema viteae, Brugia pahangi and Dirofilaria immitis, were between 2.7 and 3.1 pmol of retinoic acid bound/mg of extractable protein. However, the levels of parasite retinol-binding protein were between 4.8 and 5.8 pmol/mg, which is considerably higher than the corresponding levels of cellular retinol-binding protein of mammalian and avian origin. Both retinol- and retinoic acid-binding-protein levels in O. volvulus-infected human nodules and O. gibsoni-infected bovine nodules were similar to their levels in mammalian tissues. Also, these nodular binding proteins, like the host-binding proteins, exhibited mercurial sensitivity to ligand interactions.

4-Chloromercuribenzenesulfonate↗
PubMed1999

Biochemical aspects of egg hatch in endo- and ectoparasites: potential for rational drug design.

Control of parasites through rational drug design requires a thorough understanding of the parasite's lifecycle encompassing the biochemical and physiological processes which contribute to normal parasite homeostasis. The hatching of parasite eggs for example, represents an important process in the development of a parasitic infection. Previous studies in helminths have indicated that secreted enzymes often facilitate successful endoparasite egg hatch. In contrast, there are relatively few examples demonstrating a role for secreted enzymes in the egg hatching process of insects. An analysis of this process in the ectoparasite Lucilia cuprina suggests a role for secreted enzymes in the hatching of sheep blowfly eggs. Characterisation of the proteases collected at the time of egg hatch indicates the presence of serine proteases. Further purification and characterisation of these proteases may enable the design of specific inhibitors to interfere with the egg hatch process and therefore provide a novel means of control.

Animals↗
PubMed1996

Malaria parasite infection during pregnancy and at delivery in mother, placenta, and newborn: efficacy of chloroquine and mefloquine in rural Malawi.

Despite international recommendations to use malaria treatment and prevention in pregnant women in malaria-endemic areas, few studies have evaluated the efficacy of available antimalarial regimens. This issue is of particular concern in the face of spreading chloroquine (CQ)-resistance of Plasmodium falciparum in malarious areas of sub-Saharan Africa. In a prospective trial in rural Malawian pregnant women, we examined three regimens using CQ (including the existing national policy regimen) and one regimen using mefloquine (MQ). The efficacy of the regimens was determined by comparing rates of clearance of initial parasitemia; prevention of breakthrough infection; and parasitemia at delivery in maternal peripheral blood, placental blood, and in infant umbilical cord blood. Among 1,528 parasitemic women at enrollment, 281 (18.4%) had persistent infections; and among 1,852 initially aparasitemic women, 320 (17.3%) had breakthrough parasitemia on one or more follow-up visits. Compared with women on MQ, women on a CQ regimen were at significantly greater risk of persistent and breakthrough infection (odds ratios [OR] = 30.9 and 11.1, respectively, P < 10(-6)). Other significant risk factors for persistent and breakthrough infections in a multivariate model included first pregnancy; enrollment in the rainy or postrainy season; maternal age < or = 25 years; seropositivity to the human immunodeficiency virus (HIV) (persistent infections only); and no use of antimalarial prophylaxis before enrollment (breakthrough infections only). At delivery, compared with women on MQ, women on a CQ regimen were at significantly greater risk of peripheral, placental, or umbilical cord blood parasitemia (OR = 8.7, 7.4, and 4.1, respectively, P < 10(-6)). Additional risk factors for parasitemia at delivery in multivariate models included first pregnancy; delivery in the rainy or postrainy season; HIV-seropositivity; and maternal age < or = 25 years (risk for peripheral and placental blood parasitemia only). Maternal anemia (hematocrit < 30%) at enrollment or at delivery was not associated with persistent or breakthrough parasitemia or parasitemia at deliver in these multivariate models. While factors leading to increased malaria parasite exposure (high transmission seasons) and lowered or altered host immune response (low pregnancy number, young age, and HIV infection) are important risk factors for malaria in pregnant women, the use of an ineffective intervention (CQ in a setting with CQ-resistant parasites) was the most important determinant of P. falciparum parasitemia in these pregnant women. Strategies to reduce the impact of malaria in pregnant women must use efficacious interventions and may need to consider targeting the intervention to the most susceptible women during the seasons of high malaria exposure.

Adolescent↗
PubMed1994

Use of Vernonia amygdalina by wild chimpanzee: possible roles of its bitter and related constituents.

Bitter principles and related constituents have been isolated from Vernonia amygdalina (Compositae), a plant ingested by wild chimpanzees sometimes suffering from parasite-related diseases in the Mahale Mountains National Park, Tanzania. These isolated constituents were the known sesquiterpene lactones (vernodalin, vernolide, hydroxyvernolide), and new stigmastane-type steroid glucosides (vernonioside A1-A4: for bitter tasting constituents and vernonioside B1-B3; for nonbitter related constituents). Antiparasitic activity tests of these constituents together with quantitative analyses of the major active constituents, vernodalin and vernonioside B1, supported the hypothesis that Mahale chimpanzees control parasite-related diseases by ingesting the pith of this plant, found to contain several steroid-related constituents. While the major active steroid-related constituents (vernonioside B1 and its primary aglycone, vernoniol B1) do not taste bitter themselves, it was hypothesized that the highly bitter constituents including vernodalin may play an important role as signals to the ingester guiding their choice of the appropriate plant, plant part, and possibly also as signals which help to control the amount of intake.

Animals↗
PubMed2001

TaCRK3 encodes a novel Theileria annulata protein kinase with motifs characteristic of the family of eukaryotic cyclin dependent kinases: a comparative analysis of its expression with TaCRK2 during the parasite life cycle.

The TaCRK3 gene from the bovine apicomplexan parasite Theileria annulata, encodes a 46 kDa polypeptide with strong homology to the eukaryotic family of cyclin-dependent kinases. TaCRK3 does not show significant alignment with any particular CDK group, other than the Pfmrk kinases from the related apicomplexans Plasmodium falciparum and Plasmodium yoelii. It has a putative bipartite nuclear localization signal and is located to parasite nuclei by IFAT. Protein levels are constitutive throughout differentiation of the intra-lymphocytic macroschizont. This contrasts with the expression pattern of TaCRK2 (Kinnaird et al., 1996, Mol. Microbiol., 22, 293-302) which is closely related to the eukaryotic CDK1 /2 families involved in regulation of cell cycle progression. TaCRK2 is also located to the parasite nuclei but has no nuclear localization signal and exhibits transient up-regulation in protein levels during mid-merogony. However compared to TaCRK3, it shows down-regulation near the end of merogony. We predict that TaCRK3 may have a role in regulation of gene transcription while TaCRK2 is more likely to be involved in control of parasite nuclear division.

Amino Acid Motifs↗
PubMed2006

Warmer does not have to mean sicker: temperature and predators can jointly drive timing of epidemics.

Ecologists and epidemiologists worry that global warming will increase disease prevalence. These fears arise because several direct and indirect mechanisms link warming to disease, and because parasite outbreaks are increasing in many taxa. However, this outcome is not a foregone conclusion, as physiological and community-interaction-based mechanisms may inhibit epidemics at warmer temperatures. Here, we explore this thermal-community-ecology-based mechanism, centering on fish predators that selectively prey upon Daphnia infected with a fungal parasite. We used an interplay between a simple model built around this system's biology and laboratory experiments designed to parameterize the model. Through this data-model interaction, we found that a given density of predators can inhibit epidemics as temperatures rise when thermal physiology of the predator scales more steeply than that of the host. This case is met in our fish-Daphnia-fungus system. Furthermore, the combination of steeply scaling parasite physiology and predation-induced mortality can inhibit epidemics at lower temperatures. This effect may terminate fungal epidemics of Daphnia as lakes cool in autumn. Thus, predation and physiology could constrain epidemics to intermediate temperatures (a pattern that we see in our system). More generally, these results accentuate the possibility that warmer temperatures might actually enhance predator control of parasites.

Animals↗
PubMed1998

Maternal malaria and parasite adhesion.

Malaria during pregnancy continues to be a major health problem in endemic countries, with clinical consequences, including death, for both mother and child. Just as cerebral malaria results from parasite sequestration in the brain, maternal malaria results from parasite sequestration in the placenta, and a distinct subpopulation of parasites which bind chondroitin sulfate A but not CD36 causes the syndrome. Women have little or no immunological experience with this parasite prior to first pregnancy, making primigravid women particularly vulnerable to infection. Parasites adhere to the surface of trophoblastic villi, eliciting the accumulation of inflammatory leukocytes in the intervillous space, and the necrosis of adjacent placental tissue. Maternal malaria results in poor pregnancy outcomes, although the responsible mechanisms have not been defined. In holoendemic areas both placental infection and poor outcome decrease in frequency with successive pregnancies; protection may result from control of parasite adhesion, suggesting an attractive target for new therapies.

Animals↗
PubMed2006

Falstatin, a cysteine protease inhibitor of Plasmodium falciparum, facilitates erythrocyte invasion.

Erythrocytic malaria parasites utilize proteases for a number of cellular processes, including hydrolysis of hemoglobin, rupture of erythrocytes by mature schizonts, and subsequent invasion of erythrocytes by free merozoites. However, mechanisms used by malaria parasites to control protease activity have not been established. We report here the identification of an endogenous cysteine protease inhibitor of Plasmodium falciparum, falstatin, based on modest homology with the Trypanosoma cruzi cysteine protease inhibitor chagasin. Falstatin, expressed in Escherichia coli, was a potent reversible inhibitor of the P. falciparum cysteine proteases falcipain-2 and falcipain-3, as well as other parasite- and nonparasite-derived cysteine proteases, but it was a relatively weak inhibitor of the P. falciparum cysteine proteases falcipain-1 and dipeptidyl aminopeptidase 1. Falstatin is present in schizonts, merozoites, and rings, but not in trophozoites, the stage at which the cysteine protease activity of P. falciparum is maximal. Falstatin localizes to the periphery of rings and early schizonts, is diffusely expressed in late schizonts and merozoites, and is released upon the rupture of mature schizonts. Treatment of late schizionts with antibodies that blocked the inhibitory activity of falstatin against native and recombinant falcipain-2 and falcipain-3 dose-dependently decreased the subsequent invasion of erythrocytes by merozoites. These results suggest that P. falciparum requires expression of falstatin to limit proteolysis by certain host or parasite cysteine proteases during erythrocyte invasion. This mechanism of regulation of proteolysis suggests new strategies for the development of antimalarial agents that specifically disrupt erythrocyte invasion.

Amino Acid Sequence↗
PubMed2002

Polyparasitism with Schistosoma mansoni, geohelminths, and intestinal protozoa in rural Côte d'Ivoire.

Single species infections with schistosomes, geohelminths, and intestinal protozoans are common over large parts of sub-Saharan Africa, and it is expected that polyparasitism affects a considerable proportion of the population, hence posing a great toll on public health. However, few investigations have been carried out to quantify the extent of polyparasitism. Here, a detailed assessment is reported for the epidemiology of Schistosoma mansoni, geohelminths, and intestinal protozoan infections, with particular emphasis on polyparasitism among 260 community members in rural Cĵte d'Ivoire. Schistosoma mansoni, Entamoeba coli, and hookworm were the predominant species with prevalences of 71.5, 64.6, and 51.9%, respectively. Only 8 individuals displayed no infection, whereas two-thirds of the population harbored 3 or more parasites concurrently. There were a series of significant pairwise parasite co-occurrences, e.g., between S. mansoni and hookworms and between S. mansoni and E. coli. It is concluded that polyparasitism in the population studied here was very common, which is probably the case also in other areas of rural Cĵte d'Ivoire and elsewhere in sub-Saharan Africa. These findings call for integrated approaches to effectively control multiple parasitic and protozoan infections.

Adolescent↗
PubMed2006

Leishmania infantum-induced primary and challenge infections in rhesus monkeys (Macaca mulatta): a primate model for visceral leishmaniasis.

Visceral leishmaniasis (VL) was experimentally induced in rhesus macaques (Macaca mulatta) by intravenously inoculating 2 x 10(7)amastigotes/kg of body weight of Leishmania infantum. The macaques developed a systemic disease showing characteristic features of human VL such as fever, diarrhoea, body weight loss, anaemia, hypergammaglobulinaemia and transient lymphocytosis, as well as lymph node, liver and/or spleen enlargement. Nine weeks after infection, one primate showed pronounced weight loss, became moribund and was euthanized. The necropsy findings included granulomas composed of parasite-containing macrophages, lymphocytes and plasma cells in the liver, spleen and lymph nodes. The remaining macaques had a sustained course of infection but developed a mild-to-moderate illness that subsequently showed evidence of self-cure. Of note, pathological findings included a typical cell-mediated immunity-induced granulomatous reaction that had an effect on the control of parasite replication. All infected monkeys responded with increased production of anti-Leishmania-specific IgG antibodies. Despite the fact that clinical resistance to L. infantum was not consistently associated with a parasite-specific cell-mediated immune response, drug-cured macaques from the primary infection acquired immunity to homologous re-infection. These findings point to the feasibility of using the L. infantum macaque model for pre-clinical evaluation of novel chemotherapeutics or vaccine candidates for human VL.

Animals↗
PubMed2000

[Anthelmintic resistance in gastrointestinal Strongylidae in sheep and goats: new data on prevalence, epidemiology, preventive measures and alternatives to anthelmintic drugs].

Anthelmintic-resistant gastrointestinal nematodes represent the major problem in controlling of parasites of small ruminants in central Europe. This article gives a brief update on the prevalence of resistant populations in sheep and goat farms in Europe. New data on the selection and spread of anthelmintic resistance are reported and recommendations are given for minimising further increases in the incidence of resistant populations. New strategies which may play a role in integrated control programs in the future, e.g. vaccination and the development of nematode-resistant breeds of animals or of nematophagous fungi are briefly discussed.

Animals↗
PubMed1996

Randomised trial of pyronaridine versus chloroquine for acute uncomplicated falciparum malaria in Africa.

BACKGROUND: The spread of chloroquine resistance poses a serious problem in Africa, where falciparum malaria transmission is the highest in the world. Pyronaridine, an acridine derivative, has been used successfully to treat malaria in China for over 20 years. We compared the efficacy of pyronaridine and chloroquine in African adult patients with acute uncomplicated falciparum malaria in Yaoundé, Cameroon, where chloroquine resistance is well established. METHODS: 96 patients were randomly assigned treatment with chloroquine 25 mg/kg or pyronaridine 32 mg/kg, both orally and divided over 3 days. Patients were followed up for at least 14 days on an outpatient basis. Analysis was by on-active-treatment. FINDINGS: After losses from follow-up (11) or because of self-medication with quinine (four), 41 patients treated with chloroquine and 40 treated with pyronaridine were analysed. Parasite clearance during the 14-day follow-up with chloroquine and pyronaridine was 44% and 100%, respectively. All patients treated with pyronaridine were afebrile by day 3, and parasitaemia cleared by day 4. No serious drug-related side-effects were noted in pyronaridine-treated patients. INTERPRETATION: Pyronaridine was rapidly effective and well-tolerated in African patients with acute, uncomplicated falciparum malaria and may represent an alternative drug against chloroquine-resistant malaria.

Administration, Oral↗
PubMed2003

Vaccination against Fasciola hepatica infection using a Schistosoma mansoni defined recombinant antigen, Sm14.

Fasciola hepatica is the causative agent of fasciolosis in many areas in America, Europe, Africa, Asia and Australia. There is an urgent need for improved methods to control the parasite's transmission. We describe the use of an experimental vaccine based on a recombinant antigen cloned from another parasite, Schistosoma mansoni (Sm14), that induces high levels of cross protection in mice against both S. mansoni and F. hepatica. Sheep and mice vaccinated with Sm14 were significantly protected against challenge infection with metacercariae of Fasciola hepatica and were completely free of the histopathological hepatic damage related to liver fluke infection. The vaccine will provide a valuable new tool to aid in transmission control of this economically important disease.

Animals↗
PubMed1998

Theileria parasite infection in East Asia and control of the disease.

Bovine piroplasmosis caused by Theileria sergenti is a major cause of economic loss in grazing cattle in Japan. We found that parasite stocks and isolates consist of genetically and antigenically mixed populations. To differentiate among parasite populations bearing 3 allelic forms of p32/34, an immunodominant piroplasmin surface protein, 3 sets of oligonucleotide primers were designed to amplify either of 3 alleles of T. sergenti/T. buffeli/T. orientalis by polymerase chain reaction (PCR). By using this allele-specific PCR, we found that in East Asia the majority of bovines infected with benign Theileria parasites harbored mixed parasite population. As a possible means of controlling Theileria sergenti infection, we produced 2 candidate vaccines; a bactilovirus expressed recombinant p32 and a synthetic peptide containing of Lys-Glu Lys (KEK) motif. Immunization with either of two candidates resulted in lower parasitemia and reduced the severity of clinical symptoms as compared to control calves.

Alleles↗