WO2003084328A1

WO2003084328A1 - Parasite infections

Info

Publication number: WO2003084328A1
Application number: PCT/US2003/010012
Authority: WO
Inventors: George B. Stefano; Patrick Cadet; Stephan Pryor; Wei Zhu
Original assignee: The Research Foundation Of State University Of New York
Priority date: 2002-04-02
Filing date: 2003-04-02
Publication date: 2003-10-16
Also published as: AU2003218487A1

Abstract

The invention provides methods and materials involved in treating animals infected with a parasitic species. For example, the invention involves administering one or more opiate antagonists to an animal having a parasite infection.

Description

PARASITE INFECTIONS

Statement as to U.S. Federally Sponsored Research Funding for the work described herein was provided by the U.S. federal government, which may have certain rights in the invention.

BACKGROUND

1. Technical Field

The invention relates to methods and materials involved in treating parasite infections.

2. Background Information

Free-living and parasitic invertebrates produce several opioid peptide precursors such as prodynorphin, proopiomelanocortin (POMC), and proenkephalin. These mammalian-like opioid peptides exhibit high sequence identity to their mammalian counterparts. For example, Mytilus (bivalve mollusk) adrenocorticotropin has greater than 90% sequence identity with its mammalian counterpart. In addition, a morphine-like molecule was identified in Schistosoma mansoni, and the pig intestinal parasite Ascaris suum has been shown to produce and contain morphine by mass spectroscopy. Thus, it would appear that signaling molecule families have been conserved during evolution.

SUMMARY

The invention provides methods and materials involved in treating animals infected with a parasitic species such as a Dracunculus species (e.g., Dracunculus medinensi), a Schistosoma species (e.g., Schistosoma mansoni), and/or an Ascaris species (e.g., Ascaris suum). h one embodiment, the invention involves administering one or more opiate antagonists to an animal having a parasite infection. The opiate antagonist can be an antagonist that inhibits one or more of the actions of morphine. For example, the antagonist can be naloxone or naltrexone. The administration can be any type of administration. For example, the administration can be to the site of the parasite infection or it can be systemic. In general, one aspect of the invention features a method for treating an animal (e.g., a mammal) having a parasite infection. The method includes administering an opiate antagonist to the animal under conditions wherein the parasite infection is reduced. The mammal can be selected from the group consisting of dogs, cats, goats, cows, sheep, pigs, monkeys, and humans. The parasite infection can be selected from the group consisting of Schistosoma, Ascaris, and Dracunculus infections. The opiate antagonist can be a morphine antagonist (e.g., naloxone and/or naltrexone). The administration can be selected from the group consisting of oral, intravenous, interstitial, and intramuscular administrations. In some embodiments, more than one opiate antagonist can be administered to the animal. For example, naloxone and naltrexone can be administered to the animal. In other embodiments, the animal can be a farm animal, and the opiate antagonist can be administered to the farm animal via its drinking water.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control, hi addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.

DESCRIPTION OF DRAWINGS Figure 1. Purification of morphine from Dracunculus. Morphine was isolated by

HPLC. Running conditions: Range: 5nA; Filter: 0.02 Hz; Potential: 500 mV; Flow rate: 500 μL/minute; A buffer: 100 mM Sodium acetate, 10 mM Sodium Chloride, 0.5 mM EDTA, pH 5.0; B buffer: same as A buffer with 50 % Acetonitrile. Gradient: time 0 minute, 0% of B; time 10 minutes, 10% of B; time 20 minutes, 30 % of B; time 25 minutes, 100% of B. A. Injection of Dracunculus extract (0.15 g of tissue). B. external standards (10 ng Morphine and 10 ng Morphine 6-/3-D-Glucuronide). Insert: Standard curve of low morphine concentrations. C. Chromatogram of Schistosoma extract (0.2 g of tissue). M; morphine, M6G; Morphine 6-jQ-D-Glucuronide.

Figure 2. Characterization of Dracunculus and Schistosoma morphine. Q-TOF- MS spectrums of morphine and M6G: A mass spectra analysis of HPLC Fraction (Dracunculus extraction of 0.15 g/wet tissue) corresponding to morphine, B Fraction of same HPLC run corresponding to M6G, C Fragmentation analysis of authentic morphine after HPLC run, D Fragmentation of Dracunculus morphine ion, E. Fragmentation of authentic M6G ion, F Fragmentation of M6G ions purified from Dracunculus. G. mass spectra analysis of Schistosoma HPLC run corresponding to morphine. H. Fragmentation analysis of Schistosoma morphine ion.

DETAILED DESCRIPTION

The invention provides methods and materials related to treating parasite infections. In general, the invention involves administering one or more opiate antagonists to an animal having a parasite infection. The term "opiate antagonist" as used herein refers to any molecule that inhibits one or more of the actions of an opiate. For example, an opiate antagonist can be a molecule that inhibits one or more of the actions of morphine such as naloxone (e.g., naloxone benzoylhydrazone, naloxone hydrochloride dihydrate, and naloxone methiodide), naltrexone (e.g., naltrexone hydrochloride dihydrate), and Cys(2)-Tyr(3)-Orn(5)-Pen(7)-amide (D-Phe-Cys-Tyr-D-Trp-Orn-Thr- Pen-Thr-NH₂; CTOP). Opiate antagonists can be obtained commercially from chemical companies such as Sigma- Aldrich (St. Louis, MO). The administration can be any type of administration. For example, an opiate antagonist can be administered to the site of the parasite infection or it can be systemically administered. Other types of administration that can be used include, without limitation, oral, intravenous, intraperitoneal, intracranial, interstitial, and intramuscular administrations.

In some embodiments, a single opiate antagonist can be administered to the animal having a parasite infection to reduce or eliminate that infection. In other embodiments, multiple opiate antagonists can be administered. For example, both naloxone and naltrexone can be administered to an animal having a parasite infection to reduce or eliminate that infection. In such cases, the amounts of each opiate antagonist can be the same or different. For example, one opiate antagonist can be administered at a dose that is one, two, three, four, five, six, seven, eight, nine, ten, or more times greater than the dose of another opiate antagonist. In addition, each opiate antagonist can be administered separately or together. For example, three different opiate antagonists can be used to make a single formulation that is administered to an animal.

The methods and materials described herein can be used to treat parasite infections in any animal. For example, parasite infections in domestic animals (e.g., dogs and cats), farm animals (e.g., horses, goats, cows, chickens, sheep, and pigs), aquatic animals (e.g., fish and lobster), and primates (e.g., monkeys and humans) can be treated using opiate antagonists. In addition, any type of parasite infection can be treated using opiate antagonists including, without limitation, Dracunculus species (e.g., Dracunculus medinensi) infections, Schistosoma species (e.g., Schistosoma mansoni) infections, and Ascaris species (e.g., Ascaris suum) infections. Other types of parasite infections that can be treated as described herein include, without limitation, pinworm, tapeworm, hookworm, and roundworm infections as well as infections caused by Taenia solium, Taenia saginata, Taenia solium, Taenia ovis, Taenia multiceps, Echinococcus granulosus, species in the Strongyloidea, Oxyuroidea, or Ascaroidea family, Nectar americanus, Trichuris trichuirea, Enterobius vermicularis, Ascaridea galliae, Toxocara canis, Haemonchus contortus, Cooperia punctata, Nematodirus spathiger, Metastrongylylidea worms, Dictyocaulus viviparous, Gnathostoma spinigerum, Thelazia callipaeda, Gongylonema pulchrum, Wuchereria bancrofti, Onchocerca volvulus, Loa loa, Dirofilaria immitis, and Trichinella spirales.

Opiate antagonists can be formulated for administration to an animal. Methods for formulating and subsequently administering compositions are well known to those skilled in the art. Dosages typically are dependent on the severity and responsiveness of the disease state to be treated, with the course of treatment lasting from several days to several months, or until a cure is effected or a diminution of the disease state is achieved. Standard pharmacological studies can be used to determine optimum dosages, dosing methodologies, and repetition rates. Optimum dosages can vary depending on the relative potency of individual opiate antagonists, and generally can be estimated based on the amounts found to be effective using in vitro and/or in vivo animal models. Typically, dosage is from 0.01 μg to 100 g per kg of body weight (e.g., from 1 μg to 100 mg, from 10 μg to 10 mg, or from 50 μg to 500 μg per kg of body weight). Opiate antagonists can be given once or more daily, weekly, or even less often. An individual may require maintenance therapy to prevent recurrence of the disease state. Opiate antagonists can be admixed, encapsulated, conjugated or otherwise associated with other molecules, molecular structures, or mixtures of compounds such as antibacterial agents, antifungal agents, and antiviral agents. In addition, opiate antagonists can be used to make oral, rectal, topical, or other formulations for assisting in uptake, distribution, and/or absorption. Opiate antagonists also can be combined with pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers are pharmaceutically acceptable solvents, suspending agents, or any other pharmacologically inert vehicles for delivering one or more opiate antagonists to a subject. Pharmaceutically acceptable carriers can be liquid or solid, and can be selected with the planned manner of administration in mind so as to provide for the desired bulk, consistency, and other pertinent transport and chemical properties, when combined with one or more therapeutic compounds and any other components of a given pharmaceutical composition. Typical pharmaceutically acceptable carriers include, without limitation, water; saline solution; binding agents (e.g., polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose and other sugars, gelatin, or calcium sulfate); lubricants (e.g., starch, polyethylene glycol, or sodium acetate); disintegrates (e.g., starch or sodium starch glycolate); and wetting agents (e.g., sodium lauryl sulfate).

Pharmaceutical compositions containing one or more opiate antagonist can be administered by a number of methods, depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration can be, for example, parenteral (e.g., by subcutaneous, intrathecal, intraventricular, intramuscular, or intraperitoneal injection, or by intravenous drip); oral; topical (e.g., transdermal, sublingual, ophthalmic, or intranasal); or pulmonary (e.g., by inhalation or insufflation of powders or aerosols). Administration can be rapid (e.g., by injection) or can occur over a period of time (e.g., by slow infusion or administration of slow release formulations). As described herein, opiate antagonists can be administered systemically (e.g., intravenously, intraperitoneally, or subcutaneously). In such cases, opiate antagonists can be administered alone (i.e., without any carriers or other additives), or opiate antagonists can be administered together with agents capable of enhancing penetration of the blood/brain barrier. Compositions and formulations for parenteral, intrathecal, or intraventricular administration can include sterile aqueous solutions (e.g., sterile physiological saline), which also can contain buffers, diluents and other suitable additives (e.g., penetration enhancers, carrier compounds, and other pharmaceutically acceptable carriers). Sterile physiological saline is particularly useful. Compositions and formulations for oral administration can include, for example, powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets. Such compositions also can contain thickeners, flavoring agents, diluents, emulsifiers, dispersing aids, or binders.

Formulations for topical administration of opiate antagonists can include, for example, sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions in liquid or solid oil bases. Such solutions also can contain buffers, diluents, or other suitable additives. Pharmaceutical compositions and formulations for topical administration can include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids, and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be useful.

Pharmaceutical compositions containing opiate antagonists include, but are not limited to, solutions, emulsions, aqueous suspensions, and liposome-containing formulations. These compositions can be generated from a variety of components that include, for example, preformed liquids, self-emulsifying solids, and self-emulsifying semisolids. Emulsions often are biphasic systems comprising two immiscible liquid phases that are intimately mixed and dispersed with each other; in general, emulsions are either of the water-in-oil (w/o) or oil-in- water (o/w) variety. Emulsion formulations are particularly useful for oral delivery of therapeutic compositions due to their ease of formulation and efficacy of solubihzation, absorption, and bioavailabihty. Liposomes are vesicles that have a membrane formed from a lipophilic material and an aqueous interior that can contain the composition to be delivered. Liposomes can be particularly useful due to their specificity and the duration of action they offer from the standpoint of drug delivery.

The opiate antagonists described herein can be used in any form including salt forms. For example, opiate antagonists can be formulated into any pharmaceutically acceptable salts, esters, or salts of such esters, or any other compound that is capable of providing (directly or indirectly) a biologically active opiate antagonist. The term "pharmaceutically acceptable salt" refers to physiologically and pharmaceutically acceptable salts of opiate antagonists useful in methods described herein. Examples of pharmaceutically acceptable salts include, but are not limited to, salts formed with cations (e.g., sodium, potassium, calcium, or polyamines such as spermine); acid addition salts formed with inorganic acids (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, or nitric acid); salts formed with organic acids (e.g., acetic acid, citric acid, oxalic acid, palmitic acid, or fumaric acid); and salts formed with elemental anions (e.g., bromine, iodine, or chlorine).

The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.

EXAMPLES Example 1 - Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids High performance liquid chromatography (HPLC) coupled with electrochemical detection and by nano flow electrospray ionization double quadrupole orthogonal acceleration time of flight mass spectrometry (Q-TOF) was used to demonstrate that the human parasite Dracunculus medinensis contains both mo hine and its active opiate alkaloid metabolite morphine 6 glucuronide (M6G) as does Schistosoma mansoni. Thus, parasites may use this potent immunosuppressive and antinociceptive signal molecule to down regulate host and immuno-surveillance responsiveness and pain signaling. Materials and Methods

Dracunculus medinensis

Adult Dracunculus medinensis were obtained in July through early September from villages in Northern Ghana, an area endemic for dracunculiasis. All specimens were pre-emergent worms extracted from patients by a trained Guinea worm extractor, as part of a containment program of the national control program. Local anesthesia was given at the site of wonn emergence, and an incision along side the worm was made using a sterile stainless steel surgical blade. Worms either spontaneously bulged or formed a protrusion, which enabled the worms to be grasped and pulled out. The specimens were first thoroughly rinsed with tap water followed by rinsing in distilled water. The specimens were kept frozen until subjected to procedures to extract morphine.

Schistosoma mansoni

Female C57BL/6 mice were obtained from The Jackson Laboratory (Bar Harbor, ME) and housed in an animal care facilities. Mice were infected by percutaneous exposure to 125 cercariae of a Puerto Rican strain of S. mansoni that had been obtained from Biomphalaria glabrata snails. At 6 weeks of infection, mice were euthanized by injection with 6.5 mg sodium pentobarbital in perfusion buffer (1.5% sodium citrate in 0.85% sodium chloride). The portal vein was severed and mice were perfused with approximately 30 mL of fluid. Adult schistosomes were collected by passing the perfusate through a sieve. Worms were washed twice with perfusion buffer and frozen at -80°C until processing for mass spectrophotometric analysis.

Extraction Extraction experiments using internal or external morphine standards were performed in different rooms to avoid morphine contamination of the biological samples tested. Single use siliconized tubes were used to prevent the loss of morphine. Parasites were extensively washed with phosphate buffered saline (PBS; 0.01M NaCL 0.132 mM, NH₄HCO₃ 0.132 mM; pH 7.2) prior to extraction (3 times in 1 mL) to avoid potential source of morphine contamination. Tissues were weighed and homogenized in IN HCl (O.lg/mL). The resulting homogenates were extracted with 5 mL chloroform/isopropanol 9:1. After 5 minutes at room temperature, homogenates were centrifuged at 3000 rpm for 15 minutes. The supernatant was collected and dried with a Centrivap Console (Labconco, Kansas City, Missouri). The dried extract was then dissolved in 0.05% trifluoroacetic acid (TFA) water before solid phase extraction. Samples were loaded on a Sep-Pak Plus C-18 cartridge (Waters, Milford, MA) previously activated with 100% acetoiiitrile and washed with 0.05% TFA-water. Morphine elution was performed with a 10% acetonitrile solution (water/acetonitrile/ TFA, 89.5%: 10%: 0.05%, v/v/v). The eluted sample was dried with a Centrivap Console and dissolved in water prior to HPLC analysis.

HPLC and electrochemical detection

The HPLC system was performed with a Waters 626 pump (Waters, Milford, MA) and a C-18 Unijet microbore column (BAS). A flow splitter (BAS) was used to provide the low volumetric flow-rates required for the microbore column. The split ratio was 1/9. Operating the pump at 0.5 mL/minute yielded a microbore column flow-rate of approximately 50 / L/minute. The injection volume was 5 μL. Morphine detection was performed with an amperometric detector LC-4C (BAS, West Lafayette, h diana). The microbore column was coupled directly to the detector cell to minimize the dead volume. The electrochemical detection system used a glassy carbon-working electrode (3mm) and a 0.02 Hz filter (500mN; range 10 nA). The cell volume was reduced by a 16-μm gasket. The chromatographic system was controlled by Waters Millennium³² Chromatography Manager N3.2 software, and the chromatograms were integrated with Chromatograph software (Waters).

Morphine was quantified in the tissues by the method described by Zhu et al. (Int. J Mol. Med., 7(4):419-22 (2001)). This method was carried out in the following manner. First, the mobile phases were: Buffer A: 10 mM sodium chloride, 0.5 mM EDTA, 100 mM sodium Acetate, pH 5.0; Buffer B: 10 mM sodium chloride, 0.5 mM EDTA, 100 mM sodium Acetate, 50% acetonitrile, pH 5.0. The injection volume was 5 μL. The running conditions of the gradient were as follows: time 0 minutes, 0% of Buffer B; time 10 minutes, 10% of Buffer B; time 20 minutes, 30 % of Buffer B; time 25 minutes, 100% of Buffer B. Both buffers A and B were filtered through a Waters 0.22 μm filter, and the temperature of the whole system was maintained at 25 °C. Several HPLC purifications were performed between each sample to prevent residual morphine contamination remaining on the column. Furthermore, the fraction of blank chromatography corresponding to the elution of the morphine was checked by Q-TOF mass spectrometry analysis, confirming that no morphine remained.

Q-TOF-MS

Identification of endogenous morphine and M6G by nano electrospray ionization double quadrupole orthogonal acceleration Time of Flight mass spectrometry (Q-TOF- MS) is effective. The methodology was performed using a Q-TOF system (Micromass, UK). One μL of acetonitril/water/formic acid (50:49:1, v,v,v) containing the sample was loaded in a gold coated capillary (micromass F-type needle). This sample was sprayed at a flow rate of 30 nL/minute, giving extended analysis time during which we acquired an MS spectrum as well as several MS/MS spectra. During MS/MS or tandem mass spectrometry fragmentations are generated from a selected precursor ion by collision- induced dissociation (CID). Since not all ions fragment with the same efficiency, the collision energy is typically varied between 20 and 35 N so that the parent ion is fragmented into a satisfying number of different daughter ions. Needle voltage was set at 950, cone voltage at 25. The instrument was operated in the positive mode.

Results

In order to determine if Dracunculus contained the opiate alkaloid morphine, this compound was purified and quantified. Morphine was identified in Dracunculus by reverse phase HPLC using a gradient of acetonitrile following liquid and solid extraction and comparison to an authentic standard (Figure IB). The morphine and M6G extracted from Dracunculus (Figure 1 A) had the identical retention time with authentic morphine and M6G external standard (Figure IB). This finding was repeated in Dracunculus five times, and in all cases there was never exposure to exogenous morphine. The electrochemical detection sensitivity of morphine and M6G in biological samples are at 80 and 100 picogram level. The concentration of morphine was determined using the

Chromatogram Manager 3.2 (Millennium ³², Waters, Milford, MA) and extrapolated from the peak-area calculated for the external standard. The average concentration of morphine in the 5 samples was 11.43 ± 4.57 ng/g wet weight and that of M6G was 5.72 + 2.14 ng/g. Blank runs between morphine HPLC determinations did not show a morphine residue. All fractions corresponding to morphine blank runs were sent for mass spectrometric analysis and were negative. Using the same methods, morphine was also found in Schistosoma extraction (Figure 1C). The level of morphine in Schistosoma was calculated as 6.24 + 2.83 ng/g wet weight. A peak corresponding to M6G was not identified in the HPLC run of Schistosoma extraction.

HPLC coupled to the Q-TOF further characterized the morphine in Dracunculus. The molecular mass attributed to single charged morphine is 286.10 Da (Figure 2 A), which is identical to the authentic standard (Figure 2C) and theoretical value (286.14 Da). Fragmentation of this ion using CID yielded identical fragments compared to authentic morphine (Figure 2D). Furthennore, a single charged ion with a mass of 462.17 Da is also present in the tissue extraction as noted by Q-TOF analysis (Figure 2B). This value is identical to the calculated mass of M6G and is identical to the mass obtained from the analysis of authentic M6G (Figure 2E). Fragmentation of M6G demonstrates that morphine is one of the major fragments of M6G (Figure 2F), confirming that morphine is coupled with glucuronide. This was further confirmed by comparison with the fragmentation spectrum of the authentic compound (Figure 2E). Analysis of HPLC elution of Schistosoma indicates the presence of the morphine ion (Figure 2G).

Fragmentation of this ion also yielded identical fragments comparable to authentic morphine (Figure 2H). M6G was not detected.

These results demonstrate for the first time the presence of morphine and M6G in Dracunculus and its expression under presumed non-stimulated, or basal, conditions. As in the case of Ascaris and Schistosoma, the opiate alkaloids produced by Dracunculus appear to be secreted into the micro-environment where it could be used as a signaling molecule. Morphine can help parasites evade the host's immunosurveillance machinery and thereby increase the stability of their microenvironment and ensure their survival. Local nociception can also be impaired reducing host recognition of parasite presence. The production of morphine appears to be a conserved function in a wide variety of invertebrates, and its function may influence the immune system or the ability of the parasite to maintain itself in the vertebrate host. Successful parasitism, where the host survives for extended periods, can be characterized as an equilibrium between the parasite and the host; more specifically, between the host's immune system and the parasite's ability to create a permissive microenvironment in situ. One mechanism that a parasite may use to modify the host immune response is to down regulate the host's response. This may require chemical communication and the creation of specific micro- environments.

Example 2 - Morphine can increase the ability of parasites to live within animals Mice are infected by percutaneous exposure to cercariae of a Puerto Rican strain of S. mansoni. After infection, the mice are divided into two groups. One group of mice is treated daily with morphine, while the other group of mice is treated with saline. The mice of each group are evaluated daily to assess the degree of the parasite infection. After two months, the surviving mice of each group are sacrificed, and the degree of the parasite infections assessed. The group of mice receiving the daily morphine treatments can have a greater degree of parasite infection than the group not receiving morphine.

Example 3 - Opiate antagonists can reduce the ability of parasites to live within animals Mice are infected by percutaneous exposure to cercariae of a Puerto Rican strain of S. mansoni. After infection, the mice are divided into two groups. One group of mice is treated daily with naloxone or naltrexone, while the other group of mice is treated with saline. The mice of each group are evaluated daily to assess the degree of the parasite infection. After two months, the surviving mice of each group are sacrificed, and the degree of the parasite infections assessed. The group of mice receiving the daily opiate antagonist treatments can have a lesser degree of parasite infection than the group not receiving the opiate antagonist treatments.

Example 4 - Opiate antagonists can reduce the ability of parasites to live within animals Pigs infected with Ascaris suum are divided into two groups. One group of pigs is treated daily with naloxone or naltrexone, while the other group of pigs is treated with saline. The pigs of each group are evaluated daily to assess the degree of the parasite infection. After two months, the surviving pigs of each group are sacrificed, and the degree of the parasite infections assessed. The group of pigs receiving the daily opiate antagonist treatments can have a lesser degree of parasite infection than the group not receiving the opiate antagonist treatments.

OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

WHAT IS CLAIMED IS:

1. A method for treating an animal having a parasite infection, said method comprising administering an opiate antagonist to said animal under conditions wherein said parasite infection is reduced.

2. The method of claim 1 , wherein said animal is a mammal.

3. The method of claim 2, wherein said mammal is selected from the group consisting of dogs, cats, goats, cows, sheep, pigs, monkeys, and humans.

4. The method of claim 1, wherein said parasite infection is selected from the group consisting of Schistosoma, Ascaris, and Dracunculus infections.

5. The method of claim 1, wherein said opiate antagonist is a morphine antagonist.

6. The method of claim 1, wherein said opiate antagonist is selected from the group consisting of naloxone and naltrexone.

7. The method of claim 1, wherein said administration is selected from the group consisting of oral, intravenous, interstitial, and intramuscular administrations.

8. The method of claim 1, wherein more than one opiate antagonist is administered to said animal.

9. The method of claim 1, wherein naloxone and naltrexone are administered to said animal.

10. The method of claim 1, wherein said animal is a farm animal, and wherein said opiate antagonist is administered to said farm animal via its drinking water.