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PubMed2005

Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs.

This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) following oral and subcutaneous administration (200 microg/kg) over a 40-day period in dogs. Twenty bitches were allocated by weight in to four groups (Groups I-IV) of five animals each. Animals in the first two groups (Groups I and II) received orally the injectable solutions of IVM and DRM, respectively, at the dose of 200 microg/kg bodyweight. The other two groups (Groups III and IV) received subcutaneously injectable solutions at the same dose rate. Blood samples were collected between 1h and 40 days after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that IVM produced a significantly higher maximum plasma concentration (C(max): 116.80+/-10.79 ng/ml) with slower absorption (t(max): 0.23+/-0.09 day) and larger area under the concentration versus time curve (AUC: 236.79+/-41.45 ng day/ml) as compared with DRM (C(max): 86.47+/-19.80 ng/ml, t(max): 0.12+/-0.05 day, AUC: 183.48+/-13.17 ng day/ml) following oral administration of both drugs; whereas no significant differences were observed on the pharmacokinetic parameters between IVM and DRM after subcutaneous administrations. In addition, subcutaneously given IVM and DRM presented a significantly lower maximum plasma concentration (C(max): 66.80+/-9.67 ng/ml and 54.78+/-11.99 ng/ml, respectively) with slower absorption (t(max): 1.40+/-1.00 day and 1.70+/-0.76 day, respectively) and larger area under the concentration versus time curve (AUC: 349.18+/-47.79 ng day/ml and 292.10+/-78.76 ng day/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives ((t(1/2lambda(z)) and mean residence times (MRT) of both molecules. Considering the pharmacokinetic parameters, IVM and DRM could be used by the oral or subcutaneous route for the control of parasitic infection in dogs.

Administration, Oral↗
PubMed1990

Isoprenoid metabolism in Plasmodium falciparum during the intraerythrocytic phase of malaria.

Products of the isoprenoid metabolism were identified upon incubations of extracts from Plasmodium falciparum infected red blood cells with [14C] mevalonate. Uninfected erythrocytes and wild type yeast Saccharomyces cerevisiae extracts were used as controls. In parasitized red blood cells as well as in yeast extracts, mevalonate was converted into the biosynthetic isoprenoid precursors of sterol pathway until farnesyl pyrophosphate. In contrast, no mevalonate conversion was observed in uninfected erythrocyte extracts. The isoprenoid metabolism appeared stage-dependent as shown by the increase of radiolabelled farnesyl pyrophosphate amount at the beginning of the schizogonic phase (30-36 hours).

Acetates↗
PubMed1996

Equine piroplasmosis an update on diagnosis, treatment and prevention.

Two haemoprotozoan parasites, Babesia caballi and Babesia equi, can cause equine piroplasmosis. Due to the presence of potential tick vectors in areas so far unaffected by equine babesias, import and export regulations often require the serum testing of animals for evidence of infection. Although the complement fixation test (CFT) has been recommended for detecting the presence of antibodies to Babesia spp., it has been demonstrated to have several disadvantages, including false-positive results and low sensitivity for detecting latent infections. An enzyme-linked immunosorbent assay (ELISA) may be an alternative for increased and sensitive detection of acute and latent babesial infections, but its development to date has been hindered by a limited antigen supply and poor specificity. In vitro cultivation of both parasite species and the identification of parasite proteins for diagnostic use has facilitated the development of a highly sensitive and specific ELISA. For the direct detection of the parasites, DNA probes are now available. Several drugs are available for the treatment of equine piroplasmosis. For instance, diminazene diaceturate is effective in the chemosterilization of B. caballi and in the elimination of clinical signs in B. equi infections. Antitheilericidal drugs such as buparvaquone have been demonstrated to be effective in combatting disease due to B. equi and may--in combination with imidocarb--also eliminate the parasite. The control of equine piroplasmosis must include effective tick control, seromonitoring of animals and the application of chemotherapy.

Animals↗
PubMed2002

Trypanosoma cruzi: cruzipain and membrane-bound cysteine proteinase isoform(s) interacts with human alpha(2)-macroglobulin and pregnancy zone protein.

Plasmatic levels of pregnancy zone protein (PZP) increase in children with acute Chagas disease. PZP, as well as alpha2-macroglobulin (alpha2-M), are able to interact with Trypanosoma cruzi proteinases. The interaction of alpha2-M and PZP with cruzipain, the major cysteine proteinase of T. cruzi, was investigated. Several molecular changes on both alpha-M inhibitors under reaction with cruzipain were found. PAGE analysis showed: (i) formation of complexes of intermediate mobility and tetramerization of native alpha2-M and PZP, respectively; (ii) limited proteolysis of bait region in alpha2-M and PZP, and (iii) covalent binding of cruzipain to PZP and alpha2-M. Conformational and structural changes experimented by alpha-Ms correlate with modifications of the enzyme electrophoretic mobility and activity. Cruzipain-alpha-M complexes were also detected by gelatin SDS-PAGE and immunoblotting using polyclonal anti-cruzipain antibodies. Concomitantly, alpha2-M and PZP impaired the activity of cruzipain towards Bz-Pro-Phe-Arg-pNA substrate. In addition, alpha-Ms were able to form covalent complexes with membrane isoforms of cysteine proteinases cross-reacting with cruzipain. The present study suggests that both human alpha-macroglobulin inhibitors could prevent or minimize harmful action of cruzipain on host's molecules and hypothetically regulate parasite functions controlled by cruzipain.

Acute-Phase Reaction↗
PubMedDate not supplied

Antigen delivery strategies for mucosal vaccines.

Progress towards effective vaccines to control internal parasites, especially those affecting mucosal compartments, has been inhibited by the combined problems of the antigenic complexity of parasites and the lack of understanding of the host response. However, the accumulation of information regarding regulation of mucosal immunity has enabled a reappraisal of vaccination options to provide appropriate mucosal effector responses. The pivotal role of T cell influences, and in particular the contribution of cytokine signals, has been clearly established from in vitro studies, but data emerging from our laboratories provide evidence for these effects in vivo. We have demonstrated the role of T cells in determining the outcome of an intestinal response and propose a role for local Th2 cytokine production in this regard. To support this proposition, the distribution of cytokine mRNA has been determined by in situ hybridisation techniques in normal and parasitised animals. Further, we have shown that in the absence of Th2 cytokines (using gene knockout animals) mucosal responses are grossly deficient; we have also shown that this defect can be overcome by vector-directed gene therapy. These studies have indicated that new mucosal immunisation opportunities exist by combining traditional immunisation approaches with strategies to upregulate local cytokine production. However, the success of these new strategies will depend on selection of highly immunogenic subunit antigens, coupled with techniques for cytokine manipulation and delivery with appropriate adjuvant/vehicle formulations. This paper reviews delivery technologies available to chaperone labile antigenic and genetic material to appropriate sites for mucosal stimulation after systemic or oral administration.

Animals↗
PubMed2000

PCR assay for the specific amplification of Oesophagostomum bifurcum DNA from human faeces.

Oesophagostomiasis in humans due to infection with Oesophagostomum bifurcum (nodule worm) is of major human health significance in northern Togo and Ghana where the human hookworm, Necator americanus, also exists at high prevalence. Accurate diagnosis of O. bifurcum infection in humans is central to studying the epidemiology and controlling the parasite. To overcome limitations of current copro-diagnostic methods, we have developed an alternative, molecular approach. Utilising genetic markers in the second internal transcribed spacer (ITS-2) of ribosomal DNA, we have established a two-step, semi-nested PCR method for the specific amplification of minute amounts (fg) of O. bifurcum DNA from human faecal samples. Using a panel of 155 well-defined faecal and DNA samples, the assay achieved a sensitivity of 94.6% and a specificity of 100%. This PCR assay will be useful for the diagnosis of O. bifurcum infection and as a molecular tool for elucidating the epidemiology of human oesophagostomiasis.

Animals↗
PubMed2003

Effects of Nosema bombi and its treatment fumagillin on bumble bee (Bombus occidentalis) colonies.

We examined the effects of Nosema bombi (Microsporidia: Nosematidae) on colonies of bumble bees, Bombus occidentalis Greene (Hymenoptera: Apidae), used to pollinate tomatoes in commercial greenhouses. We assessed methods of detecting N. bombi and tested the effectiveness of fumagillin to control this parasite. N. bombi did not affect adult population size or amount of brood in B. occidentalis colonies. Fumagillin was not effective against N. bombi at the doses we tested, and frass samples did not provide accurate estimates of the intensity of N. bombi infections. The number of N. bombi spores per bee was highly variable among bumble bees within colonies, and accurate estimates could only be obtained by sampling a large proportion of bees in each colony. Therefore, whole bee and frass sampling is useful for determining if N. bombi is present or absent, but not for obtaining accurate estimates of the intensity of N. bombi infections.

Animals↗
PubMed2006

Global epidemiology, ecology and control of soil-transmitted helminth infections.

Soil-transmitted helminth (STH) infections are among the most prevalent of chronic human infections worldwide. Based on the demonstrable impact on child development, there is a global commitment to finance and implement control strategies with a focus on school-based chemotherapy programmes. The major obstacle to the implementation of cost-effective control is the lack of accurate descriptions of the geographical distribution of infection. In recent years, considerable progress has been made in the use of geographical information systems (GIS) and remote sensing (RS) to better understand helminth ecology and epidemiology, and to develop low-cost ways to identify target populations for treatment. This review explores how this information has been used practically to guide large-scale control programmes. The use of satellite-derived environmental data has yielded new insights into the ecology of infection at a geographical scale that has proven impossible to address using more traditional approaches, and has in turn allowed spatial distributions of infection prevalence to be predicted robustly by statistical approaches. GIS/RS have increasingly been used in the context of large-scale helminth control programmes, including not only STH infections but also those focusing on schistosomiasis, filariasis and onchocerciasis. The experience indicates that GIS/RS provides a cost-effective approach to designing and monitoring programmes at realistic scales. Importantly, the use of this approach has begun to transition from being a specialist approach of international vertical programmes to becoming a routine tool in developing public sector control programmes. GIS/RS is used here to describe the global distribution of STH infections and to estimate the number of infections in school-age children in sub-Saharan Africa (89.9 million) and the annual cost of providing a single anthelmintic treatment using a school-based approach (US$5.0-7.6 million). These are the first estimates at a continental scale to explicitly include the fine spatial distribution of infection prevalence and population, and suggest that traditional methods have overestimated the situation. The results suggest that continent-wide control of parasites is, from a financial perspective, an attainable goal.

Africa South of the Sahara↗
PubMed2000

Satellite mapping of Loa loa prevalence in relation to ivermectin use in west and central Africa.

For many years, ivermectin has been widely distributed throughout west Africa for the safe and effective control of onchocerclasis. However, recent events in Loa-loa-endemic areas of Cameroon, where severe adverse reactions have occurred, now constrain the public-health use of this drug in the forest habitat of the L. loa vector. We have created a model of L. loa prevalence to identify areas where high endemicity may be associated with the occurrence of such reactions. The model results have been mapped and the areas of overlap between high L. loa prevalence and planned ivermectin distribution for onchocerciasis control identified.

Africa↗
PubMed2002

Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum.

BACKGROUND: The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether or not development of cell-mediated immunity to Plasmodium falciparum blood-stage infection could be induced in human beings by exposure to malaria parasites in very low density. METHODS: We enrolled five volunteers from the staff at our research institute who had never had malaria. We used a cryopreserved inoculum of red cells infected with P falciparum strain 3D7 to give them repeated subclinical infections of malaria that we then cured early with drugs, to induce cell-mediated immune responses. We tested for development of immunity by measurement of parasite concentrations in the blood of volunteers by PCR of the multicopy gene STEVOR and by following up the volunteers clinically, and by measuring antibody and cellular immune responses to the parasite. FINDINGS: After challenge and a extended period without drug cure, volunteers were protected against malaria as indicated by absence of parasites or parasite DNA in the blood, and absence of clinical symptoms. Immunity was characterised by absence of detectable antibodies that bind the parasite or infected red cells, but by the presence of a proliferative T-cell response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of interferon gamma but not interleukin 4 or interleukin 10, induction of high concentrations of nitric oxide synthase activity in peripheral blood mononuclear cells, and a drop in the number of peripheral natural killer T cells. INTERPRETATION: People can be protected against the erythrocytic stage of malaria by a strong cell-mediated immune response, in the absence of detectable parasite-specific antibodies, suggesting an additional strategy for development of a malaria vaccine

Animals↗
PubMed1984

Prolonged incubation improves the micro-scale in-vitro test for drug sensitivity of Plasmodium falciparum.

In the standard micro-scale in-vitro test for detecting resistance of Plasmodium falciparum to chloroquine, isolates are incubated for 24-28 h in medium that does not contain serum. The effect of prolonging incubation to 48 h and of adding human AB serum to the culture medium of P falciparum from Irian Jaya, Indonesia was studied. Addition of serum was not associated with any advantages or disadvantages. Production of schizonts was increased when incubation was prolonged. This facilitated reading of the malaria smears and interpretation of the results. The percentage of successful tests (greater than or equal to 20 schizonts/200 asexual parasites in control wells) increased from 31% at 28 h incubation to 94% at 48 h. Among the 7 (44%) isolates which were chloroquine-resistant in vivo, only 1 met the criteria for a positive test at 28 h incubation, but at 48 h all 7 did. To achieve optimum results from the micro-scale in-vitro test in Jayapura, Irian Jaya, isolates should be incubated for 48 h.

Adolescent↗
PubMed1999

Ribonucleotide reductase: A new target for antiparasite therapies.

New treatments are required urgently for the control of parasitic protozoan diseases of humans and animals. One approach is the development of subunit vaccines; the other focuses on identifying and exploiting specific differences in essential functions between the host and parasite. One enzyme currently attracting attention is ribonucleotide reductase, an essential component in the biosynthesis of DNA. In this article, Geoffrey Ingram and Jane Kinnaird examine differences between the host and parasite enzymes and assess possible means of therapeutic intervention.

Amino Acid Sequence↗
PubMed1998

The effect of repeated moves to clean pasture on the build up of gastrointestinal nematode infections in calves.

The build up of gastrointestinal nematode infections was followed in two grazing experiments. Both experiments included four groups of six calves, a permanently housed non-infected control group and three groups which were grazed from May to October. One of these was moved to aftermath in the beginning of July, the second in the beginning of July and August and the third in the beginning of July, August and September. The build up of gastrointestinal nematode infections was followed by performing faecal egg counts, differentiation of faecal larval cultures, pasture larval counts, serum pepsinogen values, serum antibodies against Cooperia oncophora, weight gain and worm counts. In the second experiment four of the principal trial animals of each group were treated with oxfendazole and subsequently challenged with 100,000 larvae of Ostertagia ostertagi to examine development of immunity against O. ostertagi. The faecal egg counts and the worm counts of the sentinels necropsied in July indicated low initial infections in both experiments. Infection levels in experiment 1 remained low in each group until the beginning of September. However, during the last month, moderate to high infections were acquired by the groups which were moved once or twice. In contrast, low to moderate infections were maintained in the group moved three times. In the second experiment moderate C. oncophora burdens were already observed in the sentinels grazed until the beginning of August. Tracers grazing in August-September with the group moved once acquired high O. ostertagi and C. oncophora infections, whereas those grazed with both other groups acquired moderate infections. In October high infections with both species occurred in the groups moved once and twice, whereas low to moderate infections were observed in the group moved three times. The challenge infection demonstrated a reduction of establishment of O. ostertagi of approximately 70% in all three groups on pasture. The results demonstrate that moving calves at monthly intervals to clean pasture can be an effective method for the control of parasitic gastroenteritis. In addition, the data indicate that it is essential that the last move does not occur more than 1 month before the end of the grazing season.

Age Factors↗
PubMed1998

Field efficacy of doramectin pour-on against naturally-acquired, gastrointestinal nematodes of cattle in North America.

Seven studies were conducted under field conditions in North America to evaluate the therapeutic efficacy of doramectin in a pour-on formulation at a dosage of 500 microg/kg (1 ml/10 kg) for cattle harboring naturally-acquired infections of gastrointestinal nematodes, including species of Haemonchus, Ostertagia, Trichostrongylus, Bunostomum, Cooperia, and Oesophagostomum. In each study, 40 to 100 cattle were randomly allocated to a saline- or doramectin-treated group in a tiered manner based on Day -7 bodyweight. On Day 0, the cattle received either saline or doramectin topically, according to their treatment group. Weather and safety observations were made following treatment. No adverse reaction to treatment was observed at any time during these studies. Fecal egg count (FEC) determinations were carried out on each animal on Days -7, 0, 7, 14, and 21. Reductions in FEC for the doramectin-treated animals compared to saline-treated cattle were > or = 96.0% by Day -7 and > or = 99.0% on Days 14 and 21 for each study. Across all studies regardless of weather conditions, the reduction by Day 21 for the doramectin-treated animals compared to saline controls was 99.7% (p < or = 0.0001) and compared to pretreatment levels in doramectin-treated cattle was 99.9% (p < or = 0.0001). Doramectin pour-on should provide a useful new treatment for controlling nematode parasites of cattle.

Animals↗
PubMed1999

Important parasites in poultry production systems.

Poultry now accounts for 30% of all meat consumed. Parasites are a problem where ever poultry are raised, whether in large commercial operations or in small back-yard flocks, and economic losses can be significant. This paper will briefly review the major protozoan, helminth, and arthropod species in poultry including pathogenesis. Other topics will include the importance of the interaction of other diseases and parasites, and control of the infection by chemotherapy, management, and immunity.

Animal Husbandry↗
PubMed2002

Ethnophysiology and herbal treatments of intestinal worms in Dominica, West Indies.

In rural Dominican ethnophysiology worms reside in a human organ called the 'worm bag'. Unchecked, worms can cause illness by growing in size and number, spreading out of the worm bag and into other organs. In this study of 'bush medicine', we use a measure of cognitive salience in free-listing tasks, which reveals five plants commonly used to treat intestinal worms. These were Ambrosia hispida (Asteraceae), Aristolochia trilobata (Aristlochiaceae), Chenopodium ambrosioides (Chenopodiaceae), Portulaca oleracea (Portulacaceae), and Artemisia absinthium (Asteraceae). Bioactive compounds appear to be present in all of these plants. The cognitive salience of these plant remedies coupled with evidence of biochemical properties suggest that they provide efficacious treatments for controlling intestinal parasite loads.

Dominica↗