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PubMed1997

Residue avoidance after topical application of veterinary drugs and parasiticides.

Deriving adequate withdrawal intervals for extralabel use of veterinary topical products is difficult because there are limited published data, and data for approved drugs and pesticides are usually proprietary. Where possible, approved products and doses labeled for the specific indication at hand should be used and label withdrawal times should be adhered to. When determining whether topical application of these chemicals may violate tolerance levels in meat and milk, the veterinarian often is limited to empirical data. In the decision-making process, factors, such as type of drug and pesticide formulations used, method of topical application, presence of hair or wool, environmental conditions, and animal species treated, should be considered. In many cases a conservative estimate for the slaughter withdrawal interval can be derived, despite the data gaps. Such recommendations should not be used for routine extralabel use, but are meant to apply to situations in which the drug or pesticide has been used, and human food safety concerns must be addressed.

Administration, Topical↗
PubMed2004

Toxicological effects of malachite green.

This review summarises the wide range of toxicological effects of malachite green (MG), a triarylmethane dye on various fish species and certain mammals. MG is widely used in aquaculture as a parasiticide and in food, health, textile and other industries for one or the other purposes. It controls fungal attacks, protozoan infections and some other diseases caused by helminths on a wide variety of fish and other aquatic organisms. However, the dye has generated much concern regarding its use, due to its reported toxic effects. The toxicity of this dye increases with exposure time, temperature and concentration. It has been reported to cause carcinogenesis, mutagenesis, chromosomal fractures, teratogenecity and respiratory toxicity. Histopathological effects of MG include multi-organ tissue injury. Significant alterations occur in biochemical parameters of blood in MG exposed fish. Residues of MG and its reduced form, leucomalachite green have been reported from serum, liver, kidney, muscles and other tissues as also from eggs and fry. Toxicity occurs in some mammals, including organ damage, mutagenic, carcinogenic and developmental abnormalities. However, despite the large amount of data on its toxic effects, MG is still used as a parasiticide in aquaculture and other industries. It is concluded that the potential of alternative parasiticides, like humic acid, chlorine dioxide and Pyceze, should be explored to replace MG. Until then, MG should be used with extreme care at suitable concentrations and at times when the temperature is low. Removal of residual MG in treatment ponds should also be considered.

Aniline Compounds↗
PubMed1999

Integrated and biological control of parasites in organic and conventional production systems.

Organic and other non-intensive animal production systems are of growing importance in several countries worldwide. In contrast to conventional farms, parasite control on organic farms is affected by several of the prescribed changes in management e.g. access to the outdoors in the summer and in most countries, a ban on preventive medication, including use of anti-parasiticides. Organic animal production relies heavily on grazing, and pasture or soil related parasites are thus of major importance. Several studies in northern temperate climate have indicated that outdoor production of pigs, primarily sows, and laying hens results in heavier and more prevalent helminth infections compared to conventional intensive production under indoor conditions. In organic dairy cattle, parasitic gastroenteritis in heifers may be more prevalent. In a short to medium term perspective, integrated control may combine grazing management with biological control using nematophagous micro-fungi, selected crops like tanniferous plants and on conventional farms, limited use of anti-parasiticides. At present, the non-chemotherapeutic control of pasture related infections is based mainly on grazing management strategies. Preventive strategies, where young, previously unexposed stock, are turned out on parasite-free pastures, can be used for grazing first season dairy heifers and in all-in-all-out poultry production. Evasive strategies aim at avoiding disease producing infections of a contaminated area by moving to a clean area and may be relevant for ruminants and pigs. In cattle, effective control of nematodes can be achieved by repeated moves of the herd or alternate grazing with other species. High stocking rates seem to be an important risk factor. In pig production, the effect of paddock rotation on parasite infections is largely unknown and studies are warranted. Control of nematodes by larvae-trapping fungi, or perhaps in the future by egg-destroying fungi, looks promising for ruminants and certain monogastric animals but delivery systems and practical dosing regimes integrated with grazing management have to be developed. In conclusion, good prospects are expected for acceptable parasite control without a heavy reliance on anti-parasiticides through integration of the above mentioned procedures but future studies are needed to confirm their efficacy under practical farming conditions.

Animal Husbandry↗
PubMed1988

Killing of blood-stage Plasmodium falciparum by lipid peroxides from tumor necrosis serum.

The multiplication of Plasmodium falciparum in culture, as measured by [3H]hypoxanthine incorporation, was inhibited in a dose-dependent manner by rabbit tumor necrosis serum. The regimen by which tumor necrosis serum is produced caused significant increases in the levels of triglycerides and lipid peroxides, with the latter being indicated by the level of malondialdehyde in the serum. When tumor necrosis serum was depleted of lipoproteins by aerosil (fumed silica), no parasiticidal activity remained, and when it was separated by ultracentrifugation, more than 70% of the parasiticidal activity was found in the lipoprotein fraction. This suggests that lipid peroxides may account for most of the parasiticidal activity in tumor necrosis serum but that a nonlipid toxic factor may also be present.

Animals↗
PubMed2002

Efficacy of a combination febantel-praziquantel-pyrantel product, with or without vaccination with a commercial Giardia vaccine, for treatment of dogs with naturally occurring giardiasis.

OBJECTIVE: To determine efficacy of treatment with a combination febantel-praziquantel-pyrantel product, with or without vaccination with a commercial Giardia vaccine, in dogs with naturally occurring giardiasis. DESIGN: Prospective trial. ANIMALS: 16 Beagles naturally infected with Giardia duodenalis. PROCEDURES: During phase 1, 6 dogs were treated with the parasiticide for 3 days (4 were also vaccinated). Four weeks later, all 6 dogs were treated with the parasiticide again for 5 days and were bathed and moved to clean cages after the last treatment (phase 2). Nine dogs were treated with the parasiticide for 3 (n = 4) or 5 (5) days and bathed and moved to clean cages after the last treatment (phase 3). Fecal samples were collected twice weekly for 24 days after treatment and tested for cysts with a quantitative zinc sulfate flotation technique and for Giardia antigen with an immunoassay. RESULTS: Dogs in phase 1 were all shedding cysts again by day 24. In phase 2, only 1 dog shed cysts after treatment, and shedding was transient (day 17). In phase 3, neither cysts nor antigen was detected in fecal samples from 2 of 4 dogs treated for 3 days and 4 of 5 dogs treated for 5 days. In 18 of 57 (31.6%) fecal samples, cysts were seen, but results of the immunoassay were negative. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that when a combination febantel-praziquantel-pyrantel product is used to treat dogs with giardiasis, bathing and changing the environment after treatment may be more important in preventing recurrence than duration of treatment.

Animals↗
PubMed1983

Purification of a major membrane protein of Toxoplasma gondii by immunoabsorption with a monoclonal antibody.

The principal iodinatable surface protein (P30) of our cloned RH strain of Toxoplasma gondii has an apparent molecular weight of 30,000, as measured by acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate under reducing conditions. Monoclonal antibody B specifically immunoprecipitated protein P30 from a detergent extract of surface radioiodinated T. gondii. Monoclonal antibody B in the presence of complement was also parasiticidal for T. gondii, and this parasiticidal effect could be blocked by protein P30. Monoclonal antibody B was purified from mouse ascitic fluid and linked to cyanogen bromide-activated Sepharose. The resulting immunoabsorbent was used to purify 1.7 mg of protein P30 from a large number of parasites. The efficiency of recovery of protein P30 was measured by assays of radioactivity and of parasiticidal blocking activity. Protein P30 represented 3 to 5% of the total protein. It is also present in a recently isolated strain of T. gondii. A convalescent human antitoxoplasma serum immunoprecipitated radiolabeled protein P30. Three convalescent antisera when quantitated by an ELISA test had a high anti-protein P30 titer. Charge shift electrophoresis showed that protein P30 has an extensive hydrophobic region and thus is probably an integral membrane protein. Electrophoresis under nonreducing conditions showed no evidence that protein P30 exists as a disulfide linked homo- or heterodimer, although it probably has intramolecular disulfide bonds.

Absorption↗
PubMed2006

Use of nitazoxanide for gastrointestinal tract infections: treatment of protozoan parasitic infection and beyond.

The United States Food and Drug Administration has approved the parasiticidal agent nitazoxanide for treatment of diarrhea caused by Giardia lamblia/intestinalis or Cryptosporidium parvum. This novel agent has a broad spectrum of activity against many other gastrointestinal pathogens, including bacteria, roundworms, flatworms, and flukes. Nitazoxanide is used in many areas of the world, especially in Central and South America, as a broad-spectrum parasiticidal agent in adults and children. Nitazoxanide appears to be well tolerated, has a relatively low incidence of adverse effect, and displays no significant known drug-to-drug interactions. Recently, preliminary reports indicate that nitazoxanide may be an effective treatment for Clostridium difficile-associated diarrhea as well. Future work will likely solidify and further expand the role of nitazoxanide in the treatment of a wide range of intestinal pathogens.

Journal Article↗
PubMed1983

Activation of macrophages by culture fluid of antigen-stimulated spleen cells collected from chickens immunized with Eimeria tenella.

The effect of spleen cell factors on the activation of macrophages was investigated in chickens immunized with Eimeria tenella. The abilities of peritoneal macrophages obtained from normal chickens to kill sporozoites of E. tenella and to inhibit intracellular development of Toxoplasma gondii were enhanced by exposing them to 33 and 50% culture fluid of antigen-stimulated spleen cells of chickens immunized with E. tenella. The parasiticidal activity of normal macrophages was also distinctly enhanced by the treatment with culture fluid of phytohemagglutinin-stimulated normal spleen cells. On the other hand, the parasiticidal activity of normal macrophages could not be enhanced by the treatment with culture fluid of antigen-stimulated normal spleen cells under conditions similar to those of culture fluid of antigen-stimulated immune spleen cells. It thus appears that the macrophage activator was induced from immune spleen cells in response to the stimulation by the antigen.

Animals↗
PubMed2003

Determination of acidic pharmaceuticals, antibiotics and ivermectin in river sediment using liquid chromatography-tandem mass spectrometry.

Analytical methods have been developed for the determination of eight acidic pharmaceuticals and two metabolites, seven antibiotics and the parasiticide ivermectin in a selected river sediment. The sediments were solvent extracted with ultrasonic assistance. A solid phase extraction (SPE) clean-up step was performed thereafter. The acidic compounds clofibric acid, diclofenac, fenoprofen, gemfibrozil, ibuprofen, 2-hydroxy-ibuprofen, indomethacin, ketoprofen, naproxen and the parasiticide ivermectin were measured in the negative mode by LC-APCI-tandem MS, whereas the antibiotics clarithromycin, erythromycin, roxithromycin, sulfadiazine, sulfamethazine, sulfamethoxazole and trimethoprim were detected in the positive mode by LC-ESI-tandem MS. Bezafibrate could not be determined in the sediment using the method developed. The limit of quantification (LOQ) ranged from 0.4 to 8 ng g(-1) for the acidic pharmaceuticals, sulfadiazine and ivermectin and was 20 ng g(-1) for the other antibiotics.

Acids↗
PubMed2001

Cyathostome fecal egg count trends in horses treated with moxidectin, ivermectin or fenbendazole.

Commercial preparations of fenbendazole (Safe-Guard, Intervet), ivermectin (Eqvalan, Merial) or moxidectin (Quest, Fort Dodge) were administered once to horses scheduled for routine parasiticide treatment. In total, 93 horses from six cooperating farms were used in the study. Computer generated, random allocation of horses to treatment group was conducted at each farm. Fecal egg counts were determined for all horses on trial days 0, 56, 84 and 112, with corresponding calendar dates that were unique to each farm. Only strongyle egg counts from animals which were positive at day 0 were used for analysis of variance and comparisons. Counts for the three treatment groups were similar at day 0, moxidectin<ivermectin<fenbendazole for days 56 and 84, and moxidectin<ivermectin=fenbendazole on day 112 (P<0.05). Reductions of geometric mean egg counts from day 0 levels were 99.1, 97.6 and 94.9% for moxidectin, 16.4, -27.0 and -32.0% for fenbendazole and 85.9, 24.2 and -8.1% for ivermectin on trial days 56, 84 and 112, respectively. Adverse reactions to treatment were not observed for any of the parasiticides.

Animals↗
PubMed2000

WAAVP/Pfizer award for excellence in veterinary parasitology research. My involvement in, and some thoughts for livestock parasitological research in Australia.

Being presented with the WAAVP Pfizer award for excellence in parasitological research is the pinnacle of my career. In accepting I acknowledge the support that I have received from workmates, colleagues, friends and family over the years that I have been involved in this field of endeavour. Parasitic disease is the most significant threat to the Australian sheep industry. A lack of understanding of drug action, the absence of epidemiologically-based treatment programs and incorrect or excessive chemical use has resulted in the development of worm, lice and blowfly parasites which are resistant to most existing chemotherapeutic compounds. During the past decade, difficulties in sustainable control of parasitic disease, the decline in demand for wool products and competition from less expensive synthetic fibre has halved the sheep population and profitability of the industry. Notwithstanding this, a 'right-sized', sustainable industry is emerging which will require effective chemotherapy to be the cornerstone of parasite control. Chemical intervention in parasitic disease is therefore here to stay but the paucity of new antiparasitic products in the short term dictates that present therapeutics are all that producers will have for the foreseeable future. This situation will necessitate innovative practices and formulations to provide more cost effective, efficient drug performance and to extend parasiticide life. However, the development of multiple drug resistance and reduction in funds for parasitological research seriously compromises our ability to confront these demands. With the patent life of all but the most recent macrocyclic lactone (ML) compounds lapsing, low cost development of bioequivalent generic formulations and options for innovative strategies to increase performance and market share are eagerly sought. The key to efficient drug use lies in a detailed understanding of the pharmacokinetic principles of drug action and the host animal's physiological responses to identify procedures which maximise drug availability--in essence giving the drug the best chance to work. It is therefore evident that the how, where and why of drug exchange between the bloodstream and the gastrointestinal tract are of such interest. Of particular importance is identification of the kinetic and dynamic behaviour of drug in the gastrointestinal tract (GIT) and the role of biliary secretion and metabolic fate of biliary (and non-biliary) compounds. The extent to which biliary secreted parent drug and/or metabolites are presented to the gut lumen, reabsorbed as free compound or after deconjugation by large bowel bacteria, and participate in the enterohepatic cycle is a major contributor to parasite exposure. Integrating parasiticide disposition with host physiology, particularly relating to such aspects as gastrointestinal function, feed intake and body condition has demonstrated the value of 'whole body' pharmacokinetic studies to identify processes to increase drug efficacy. Novel formulation modifications to provide 'targeted' drug delivery including carrier technology, sustained release devices and site-directed formulations can manipulate pharmacokinetic disposition to direct or extend drug availability to the parasite infection. These research directions should be undertaken as collaborative projects between research organisations and the veterinary pharmaceutical industry. With the identification of methods to improve drug action, emphasis must then be directed towards effective communication for their implementation. It will be vital that parasitologists move out of the laboratory to actively disseminate knowledge to the producer. We are ambassadors for our profession and if we fail to communicate well the perception, and indeed the value, of our work can be at risk.

Animals↗
PubMed2005

In vitro and in vivo effects of progesterone on Trichinella spiralis newborn larvae.

We have previously demonstrated that during pregnancy there exists an increased parasiticide activity against Trichinella spiralis newborn larvae (NBL) in infected rats. In this work we analysed the contribution of peritoneal cells from noninfected pregnant rats to the mortality of the NBL in cytotoxicity assays, and evaluated the role of progesterone in this effector mechanism. Our findings suggest that progesterone can induce activation of effector peritoneal cells to destroy the NBL in a rapid and antibody-independent manner. The administration of progesterone to ovariectomized rats also led to a significant decrease in the parasite load of the animals, thus demonstrating that progesterone induces the increase of the parasiticide activity of the leukocytes involved in the mechanisms of NBL death.

Animals↗
PubMed2002

Novel animal-health drug targets from ligand-gated chloride channels.

The world's three best-selling veterinary antiparasitic drugs ('parasiticides') act on ligand-gated ion channels. The sequencing of the complete genomes of the invertebrate genetic model organisms Caenorhabditis elegans and Drosophila melanogaster has led to the recent cloning of new subunits of 5-hydroxytryptamine-gated and histamine-gated chloride channels. Together with L-glutamate-gated chloride channels, which are important targets of known parasiticides, and acetylcholine-gated chloride channels, these new classes of ligand-gated chloride channels, which are known only from invertebrates, add to our understanding of inhibitory neural signalling. They could offer the prospect of being targets for a new generation of selective drugs to control nematode and insect parasites.

Amino Acid Sequence↗
PubMed1987

Isolation and characterization of a monoclonal anti-P30 antibody resistant mutant of Toxoplasma gondii.

Of the possible iodine-labelled Toxoplasma gondii surface proteins, P30 (apparent Mr 30,000) is the principal one recognized by acute and convalescent anti-toxoplasma sera. This protein which comprises from 3 to 5% of the total parasite protein was used to raise a panel of parasiticidal monoclonal anti-P30 antibodies. One of these monoclonal antibodies was able to select a resistant mutant from a large population of chemically mutagenized wild-type P strain parasites. This mutant retained the wild type sensitivity to other non-P30 parasiticidal monoclonal antibodies as well as polyclonal anti-P30 rabbit sera. Analysis of surface radioiodinated wild type and mutant parasites showed that the mutant had a quantitative reduction in the amount of P30. A comparison of surface biotin labelled wild type and resistant parasites by two dimensional electrophoresis showed that the mutant lacked one and possibly two of several proteins that make up wild type P30. Western blot analysis indicated that the mutant was devoid of antigenically reactive P30. These findings further support the hypothesis that antigenic variants of T. gondii can be induced and may involve the major surface membrane antigens of the parasite.

Animals↗
PubMed2001

Echinococcus multilocularis alkaline phosphatase as a marker for metacestode damage induced by in vitro drug treatment with albendazole sulfoxide and albendazole sulfone.

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis. The disease affects the human liver and occasionally other organs and is fatal if treatment is unsuccessful. The present chemotherapy of AE is based on the administration of benzimidazole carbamate derivatives, such as mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some cases, parasitostatic rather than parasiticidal, and the recurrence rate is rather high. Therefore, chemotherapy usually involves the lifelong uptake of massive doses of albendazole and new treatment options are urgently needed. In order to avoid costly and time-consuming animal experimentation, a first step in searching for novel parasiticidal compounds could be the in vitro drug screening of novel compounds by employing metacestode cultivation. However, presently used techniques (e.g., transmission electron microscopy) for determination of parasite viability involve costly equipment and time-consuming preparation of rather large amounts of parasite material. We therefore searched for a parasite marker which can be easily traced and the presence or absence of which is indicative of parasite viability. In this study we show that the increase of E. multilocularis alkaline phosphatase activity in culture supernatants during in vitro drug treatment with albendazole derivatives correlates with the progressive degeneration and destruction of the metacestode tissue. The inexpensive and rapid assay presented here will serve as an ideal tool for performing first-round in vitro tests on the efficacy of a large number of antiparasitic compounds.

Albendazole↗
PubMed2003

Quinine pharmacokinetic-pharmacodynamic relationships in uncomplicated falciparum malaria.

The relationships between the pharmacokinetic properties of quinine during a 7-day treatment course and the therapeutic response were studied in 30 adult patients with uncomplicated falciparum malaria monitored for > or = 28 days. All patients received a 7-day oral quinine regimen either alone (n = 22) or in combination with rifampin (n = 8). The median fever clearance time was 58.5 h, and the mean +/- standard deviation parasite clearance time was 73 +/- 24 h. After recovery, six patients had recrudescences of Plasmodium falciparum malaria and seven had delayed appearances of P. vivax infection between days 16 and 23. Between the patients with and without recrudescences, there were no significant differences either in fever clearance time or parasite clearance time or in the overall pharmacokinetics of quinine and 3-hydroxyquinine. Patients for whom the area under the concentration-time curve from 3 to 7 days for quinine in plasma was <20 microg.day/ml had a relative risk of 5.3 (95% confidence interval = 1.6 to 17.7) of having a subsequent recrudescence of infection (P = 0.016). Modeling of these data suggested an average minimum parasiticidal concentration of quinine in plasma of 3.4 microg/ml and an MIC of 0.7 microg/ml for uncomplicated falciparum malaria in Thailand. To ensure a cure, the minimum parasiticidal concentration must be exceeded during four asexual cycles (>6 days).

Adult↗
PubMed1998

Influence of antibodies in mother's milk on antigenic variation of Giardia lamblia in the murine mother-offspring model of infection.

In the present study, neonatal ZU.ICR mice and their mothers were infected with trophozoites of Giardia lamblia clone GS/M-83-H7 expressing the variant surface protein (VSP) H7. The infection experiments included a detailed analysis of the specificities of anti-Giardia immunoglobulin A (IgA) antibodies in mother's milk and a determination of the effects of the milk antibodies on both the growth of the parasite during in vitro cultivation and colonization of the parasite within the intestine of suckling offspring. These investigations revealed that transiently emerging milk IgA antibodies against a variant-specific 314-amino-acid N-terminal region of VSP H7 exhibit a strong parasiticidal effect on VSP H7-type trophozoites both in vitro and in vivo. These findings indicated that parasiticidal effects of local IgA antibodies against the N-terminal part of VSP H7 select for new variant types within the intestinal parasite population of suckling mice. The selective influence of such antibodies promotes in vivo antigenic variation of G. lamblia clone GS/M-83-H7 and modulates the early course of parasite infection in these animals.

Animals↗
PubMed2006

[Acute toxoplasmosis: clinical and laboratory data in eleven patients].

INTRODUCTION: The clinical and laboratory data of immunocompetent patients with acute toxoplasmosis (AT) are described. PATIENTS AND METHODS: We performed a retrospective study of patients with AT attended between 1996 and 2004. Diagnostic criteria consisted of compatible clinical findings (generalized and cervical lymphadenopathies) and specific serology against Toxoplasma gondii (high IgG and IgM and/or reactive IgA). IgG and IgM determinations were performed by ELFA and IgA determinations by ELISA. IgM-CMV, heterophil antibodies, hemogram, hepatic chemistry were also determined and funduscopic examination was performed. RESULTS: Eleven immunocompetent patients with AT were evaluated. The mean age was 8.8 years (95 % CI: 3.6-12.9). The patients were evaluated between the first and the third month after symptom onset. Of the 11 patients, hard elastic lymphadenopathies were found in 10, single cervical lymphadenectomy in three and generalized lymphadenectomy in seven. One patient showed no symptoms. In one patient, nodal histology showed the Piringer-Kuchinka triad. None of the patients showed alterations in the hemogram, hepatic chemistry or funduscopic examination. The mean IgG value was 4.143 UI/ml (95 % CI: 2.570 and 5.717). IgM was reactive in nine of the 11 patients (81.8 %) and IgA in seven out of 10 patients (70 %). In all patients, at least one of these two immunoglobulins was reactive. In all patients, clinical outcome was favorable without parasiticide treatment. CONCLUSION: Except for one asymptomatic patient, all the patients had generalized lymphadenopathies and only 27.2 % showed cervical lymphadenopathies. A negative IgM or IgA result does not rule out a diagnosis of AT. Parasiticide treatment is unnecessary in this entity. Acute toxoplasmosis should be considered early in children with lymphadenopathies to avoid invasive procedures.

Acute Disease↗