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Infection of the peritoneal cavity with cestode larvae, presumptively diagnosed as tetrathyridia of the genus Mesocestoides, was found by exploratory celiotomy in a dog with clinical signs consisting of episodic anorexia, vomiting, and depression. Lymphopenia and hypoalbuminemia were associated clinicopathologic abnormalities. Dystrophic calcification and midline duodenal displacement were found on abdominal radiographs. Therapy with mebendazole was instituted after recurrence of the initial episodic clinical signs postoperatively. Daily use of mebendazole for intermittent periods of up to 3 months led to remission of gastrointestinal signs for 30 months. However, 17 months after the initial diagnosis, infection of the vaginal tunic of the testicle with similar cestode larvae necessitated castration and removal of the vaginal tunic to the inguinal ring. Mebendazole therapy was reinstituted and continued for 31/2 months postoperatively. The dog was free of clinical signs of infection during and for the 16 months since this period of treatment.

This article discusses the anthelmintics now in common use and describes their mode of action and toxic side effects. The drugs reviewed include: pyrantel pamoate, mebendazole, piperazine, thiabendazole, niclosamide, praziquantel, niridazole, oxamniquine and diethylcarbamazine. Most of the common roundworm intestinal infections respond to treatment with pyrantel pamoate, which has the advantage of single-dose therapy. Trichuriasis requires therapy with mebendazole, while the filariases are treated with diethylcarbamazine. There is no specific therapy for trichinellosis, but its symptoms can be alleviated. Intestinal cestode infections respond to treatment with niclosamide and cerebral cysticercosis to praziquantel, but echinococcal hydatid disease still requires surgical intervention in certain cases, although prolonged treatment with mebendazole shows promise. The greatest recent advance in the therapy of helminthiases is the development of praziquantel which effectively treats the most severe of these infections.

The fifth case of human infection with Mesocestoides in the United States is reported in a 17-month-old child living in Mississippi. The child was asymptomatic and the source of the infection in unknown. Stools examined after treatment with paromomycin sulfate (Humatin) revealed no further evidence of infection. This is the 18th case of Mesocestoides infection in man reported in the literature.

A controlled blind test was performed in 1984 to evaluate the anthelmintic activity of experimental formulations of compound F28249-alpha against gastrointestinal parasites in lambs in Kentucky. Twenty-five lambs were allotted to 5 groups of 5 lambs/group. The drug was administered SC to 2 groups (A, 0.2 mg/kg of body weight; B, 0.3 mg/kg) and orally to 2 groups (C, 0.2 mg/kg; D, 0.3 mg/kg). Group E received a placebo subcutaneously. Lambs were euthanatized 7 days after treatment for necropsy and identification and enumeration of worm parasites in the gastrointestinal tract. Group-E lambs harbored 7 genera (including 10 species) of nematodes and 1 genus of tapeworms. Worm collection data for group-A lambs indicated 97% to 100% of the mature Haemonchus, Ostertagia, Trichostrongylus, and Trichuris, and immature Haemonchus were removed; and 23% to 73% of the mature Cooperia, Nematodirus, and Strongyloides, and immature Nematodirus were removed. In group-B lambs, 94% to 100% of the mature Haemonchus, Nematodirus, Ostertagia, Trichostrongylus, and Trichuris, and immature Haemonchus were removed as were 70% to 84% of mature Strongyloides and immature Nematodirus, respectively, and 0% for mature Cooperia. The percentage of all nematodes removed in group C and D was 100%, except for Cooperia (95%) in group C and immature Nematodirus (93% and 95%), respectively. Toxicosis was not apparent. Small fibrotic or blood streaked lesions were observed at necropsy in muscle at the injection site of 2 lambs in group B and 1 lamb in group E.

This article describes the drugs used in helminthic infections and their therapeutic indications, mode of action, toxicity and other details of each of the recommended drugs, and discusses the nature and treatment of infection by helminths important in human medicine. Infestation due to the roundworms Enterobius vermicularis, Ascaris lumbricoides and the hookworms, Ancylostoma duodenale and Necator americanus can all be treated effectively with pyrantel pamoate. For Enterobius vermicularis, however, a newer drug, mebendazole, is equally as effective. The advantage of these drugs in the indicated circumstances is that they can be administered in a single dose. Unfortunately, pyrantel pamoate is not a panacea and in the case of Necator it is not as effective as in the other roundworms. In that situation the use of tetrachlorethylene is preferable. For treatment of Strongyloides stercoralis, and important human parasite, because it can become disseminated and lead to fatal infections in immunoincompetent hosts, the only effective drug is thiabendazole. In treatment of Trichuris trichiura infection, mebendazole, administered over a period of 3 days, is the most effective available drug. For the roundworms inhabiting tissues--either as aberrant infections of man or as the normal part of their life cycle in man--therapy tends to be largely non-specific. For example, in visceral larva migrans, caused by the dog roundworm Toxocara canis, only palliative therapy with systemic anti-inflammatory agents and corticosteroids may be helpful. Cutaneous larva migrans, caused by the dog hookworms Ancylostoma brasiliensis and Ancylostoma caninum, is also treated primarily with symptomatic measures, but there is a suggestion that thiabendazole may kill the larvae and thus be effective. Trichinella spiralis may cause severe, even fatal infections in man, but only symptomatic therapy can be offered. Therapy for filarial infections is regrettably complicated and not completely effective. Diethylcarbamazine remains the best available drug, but in some of these infections local surgical excision may also be used. It is important to bear in mind that release of antigens from dying or dead worms may cause systemic inflammatory and allergic reactions that may require therapy with corticosteroids. Therapy for Cestodes is achieved most effectively with niclosamide, but the antimicrobial agent paromomycin has also been effective. For the aberrant cestode infections of man, such as echinococcal cysts or Taenia solium cycticerci, treatment is surgical if the affected areas are accessible. Treatment of schistosomal infections is quite toxic and, therefore, it is mandatory to determine viability of the worms before recommending therapy. If therapy is required, then Schistosoma mansoni infections are treated with stibophen and S. japonicum with antimony potassium tartrate, taking care in both of these instances to watch for the early signs of antimony toxicity; therapy of S. haematobium infections is based on administration of niridazole...

A review has been made of the advances in knowledge on the treatment of tapeworm infections of man and animals from the time of the introduction to dichlorophen in 1956. This opened up the era of out-patient treatment for human tapeworm infections. The drugs studied have been compared, where possible, on the basis of estimates of the single dose ED90 or the number of treatments required to reach that efficacy at safe dose levels. During the period under review, niclosamide, introduced in 1960 has been regarded as the drug of choice for the treatment of human tapeworm infections with paromomycin as a possible alternative. The bunamidine salts, introduced in 1966 permitted the treatment of Echinococcus spp in dogs. Several treatments were required to achieve acceptable efficacy. In 1975 praziquantel was introduced and based on the ED90, a single dose at no more than 10mg/kg removed all tapeworms responsible for the cestode zoonoses and for which data are available with the exception of H. nana and D. latum; these require a higher dose rate. In the mid 1970s, several benzimidazoles and praziquantel were shown to have activity against metacestodes. This has opened up a new field of research promising a practical outcome. No progress has been made during the period under review in finding effective ovicides.

A 13-year assessment has been made of the effectiveness of a monthly drug treatment programme for the control of tapeworms in dogs in order to prevent hydatidosis (Echinococcus granulosus) and cysticercosis (Taenia hydatigena and T. ovis) in sheep. The age-specific prevalence of T. hydatigena in lambs was used as the principal indicator. The trial was carried out in the Styx Valley of the Maniototo Plain in the South Island of New Zealand.Over an 8-year period dogs were treated monthly with bunamidine hydrochloride at about 25 mg/kg with little effect on the prevalence of T. hydatigena in lambs. The addition of niclosamide at 50 mg/kg for 1 year also had little effect. Eggs appeared to survive from one season to the next. Those shed prior to the lamb-rearing season gave rise to endemic-type patterns; whereas patent infections occurring during this period rapidly gave rise to an epidemic-type pattern or a "cysticercosis storm". In this 9-year period there were 16 "cysticercosis storms" and all susceptible lambs were infected. These storms did not necessarily give rise to a similar prevalence on neighbouring farms, but may have contributed to the overall infective pattern. A similar situation occurred in the first year that nitroscanate at 100 mg/kg was introduced. During this 10-year period, arecoline surveillance of the dog population was undertaken in the remainder of the county and many dogs were found to harbour tapeworms. Both resident and introduced dogs may have contributed to the infective patterns in the Styx Valley.Treatment with nitroscanate was continued monthly in the Styx Valley and niclosamide was used in the remainder of the County for a further 3 years. There was a marked reduction in the age-specific prevalence and lambs on many farms were free from T. hydatigena at slaughter. However, one "breakdown" occurred and this was almost certainly autochthonous.Comparisons with an earlier period when arecoline surveillance was used in the Styx Valley, indicate that the present evidence favours a drug-orientated treatment programme of the definitive host for the control of cysticercosis. However, "breakdowns" caused by either autochthonous or itinerant sources have profound effects, since they involve all susceptible age-cohorts including those that have never been infected and those that have lost the immunity induced by an earlier infection.

In the 5-year period 1973-1977, 43 patients infected with Dipylidium caninum and 43 patients infected with Hymenolepis diminuta were treated with Yomesan (niclosamide) in the dosages recommended by the Parasitic Disease Drug Service, Center for Disease Control. The first post-treatment stool specimen and 1-week and 3-month specimens were examined in 13 patients with D. caninum and 19 patients with H. diminuta. One hundred percent (13/13) of those with D. caninum and 89% (17/19) of those with H. diminuta had negative examinations at 3 months and were considered cured. Two patients with persistent H. diminuta were cured with a second course of drug without changing the dosage or time schedule. Four of these cases had been unresponsive to an initial course of quinacrine hydrochloride. Thus, niclosamide seems to be an effective, relatively nontoxic drug for the initial therapy of these cestode infections.

A total of 59 equids (54 horses and five Shetland ponies) were treated with pyrantel pamoate once, at the dose rate of approximately 6.6 mg base kg-1, during the period November 1985-January 1988. The drug was administered as a paste formulation (51 equids) intraorally or as a suspension formulation by stomach tube (eight equids). The purpose of treatment was to evaluate the activity of pyrantel pamoate (at the therapeutic dose rate) for removal of the tapeworm, Anoplocephala perfoliata, by a modified (24-h) critical test. The presence or absence of tapeworms was not determined for the equids before treatment. Twenty-three (39%) of the 59 treated equids were found to be infected with A. perfoliata (from one to 180 specimens per infected equid) at necropsy. Removals varied from 67 to 100% (average 88%) for the 18 infected equids treated with the paste formulation. For the five infected equids treated with the suspension, removals were 58-100% (average 75%). The combined average removal of A. perfoliata for both formulations was 87%. Two abnormal (triradiate) specimens of A. perfoliata were recovered; one from each of two different equids.

Febantel was administered as a 3.4% paste to 45 dogs infected with 1 or more nematode species, which included Ancylostoma caninum and Trichuris vulpis. Dosage levels of 5, 10, or 15 mg/kg of body weight daily for 3 consecutive days for a total of 15, 30, or 45 mg/kg were administered. At 15 mg/kg, all dogs were completely cleared of all nematode and cestode infections, including A caninum, T vulpis, Uncinaria stenocephala, Toxocara canis, Toxascaris leonina, Taenia sp, and Dipylidium caninum, except for 1 Physaloptera sp adult. The 2 other dosage levels produced somewhat lower efficacy, with the 5 mg/kg being the least effective. The paste appeared palatable to the dogs and there were no apparent adverse effects.

The anthelmintic efficacy of resorantel against Thysaniezia giardi and Avitellina spp. was tested in sheep at a dosage rate of 65 mg kg-1 live mass. The reduction obtained was 100% in at least 80% of the treated flock.

A diagnosis of coenuriasis was made in a spectacled langur raised in captivity. Multiple cysts removed from the subcutaneous tissues and later from the abdominal cavity were identified as coenuri, typical of the genus Taenia. Post-surgical treatment of the remaining cysts with praziquantel was assessed with whole body computerized tomography (CT). CT at 6 weeks post-treatment revealed a reduction in size and increased calcification of abdominal cysts as compared to pretreatment CT. Cyst fluid antigens in ELISA assays showed a high titer (1:5, 120) IgG response in the langur serum, while no IgM response could be detected. No decrease in IgG titer was seen 6 weeks after treatment. Immunoblot analyses identified several parasite-specific antigens with apparent molecular weights of greater than 92.5 (3 bands), 88, 41, 37, and 34 kDa.

Praziquantel is a new type of acylated isoquinoline-pyrazine. A single, low oral or subcutaneous dose of the compound is reliably effective against all tested juvenile and adult cestodes in cats, dogs and sheep. Praziquantel is the first cestodicide which is also effective on bile duct cestodes. In cats and dogs, 5 mg praziquantel per kg is completely effective on all stages of Taenia hydatigena, T pisiformis, T ovis, T taeniaeformis, Dipylidium caninum, Mesocestoides corti, Echinococcus multilocularis and E granulosus. Because of its very wide therapeutic index praziquantel is thus particularly suited for eradication programmes, eg, echinococcosis.

The anthelmintic activity of and patient tolerance to albendazole, a broad-spectrum anthelmintic, were studied in a multicenter trial involving 480 patients ranging in age from 2 to 60 years. The patients had single or mixed infections caused by pinworms, roundworms, hookworms, whipworms, threadworms, or tapeworms. The stools were examined by the direct method, and ova were counted by means of the Kato-Katz technique. A Graham-Scotch test was also done in patients infected with Enterobius vermicularis. Most patients received a single 400-mg dose of albendazole; adults were given two tablets, and children were given a 2% suspension. All patients with Hymenolepis nana and about half of those with Taenia infections were treated for three successive days. Patients were carefully evaluated before and after treatment to assess the efficacy and safety of the drug. After a single dose of albendazole, the cure rate was 95.3% in ascariasis, 92.2% in ancylostomiasis, 90.5% in trichuriasis, 64.9% in taeniasis, and 100% in enterobiasis. Among patients receiving 400 mg of albendazole for three days, the cure rate was 63.4% in hymenolepiasis and 86.1% in taeniasis. The drug was well tolerated, and no significant side effects were reported.

Critical tests were completed on six horses to evaluate the antiparasitic activity of a paste formulation mixture of morantel citrate and trichlorfon, administered intraorally at the dose rate of 6 mg morantel base kg-1 and trichlorfon at 30 mg kg-1. Aggregate average removals were: 78% for two horses infected with 2nd instar Gasterophilus intestinalis; 100% for one infected with 2nd instar G. nasalis; 96% for six infected with 3rd instar G. intestinalis; 100% for four infected with 3rd instar G. nasalis; 100% for five infected with Parascaris equorum; 100% for one infected with mature Oxyuris equi; 100% for five infected with Strongylus vulgaris; 72% for five infected with S. edentatus; and partial removal (25%) of Anoplocephala perfoliata infection from one infected animal. Pre- and post-treatment EPG and LPG data indicated a reduction of 97% of the mature small strongyle infections. Evidence of toxicosis was not observed in any of the horses.

Oral administration of mebendazole at a rate of 1 g/kg feed (approximately 50 mg/kg body weight/day) for 14 days killed mature and immature cysticerci of Taenia pisiformis in rabbits, and multiplying tetrathyridia of Mesocestoides corti in mice. Progressive degrees of parasite damage caused by mebendazole treatment could be assessed by histological examination of calcereous corpuscles. A single subcutaneous injection of 10 percent mebendazole in carrier, at a rate of 100 mg/kg body weight, resulted in the death of all M. corti tetrathyridia in mice within 4 weeks, but the drug in saline was slowly mobilized and was relatively ineffective. Neither subcutaneous injections of mebendazole in saline or in carrier could kill cysticerci of T. pisiformis within 5 weeks, but the drug in carrier was effective after several months. Mebendazole in saline was effective when injected intraperitoneally, but adhesions often resulted from this route of administration. Echinococcus granulosus protoscoleces administered to mice by intraperitoneal injection were rapidly encapsulated by host lymphoid cells. The vesiculating protoscoleces were all contained within a fibrous capsule for more than 2 months after infection, but by 4 months almost all had grown free of the host reaction. Treatment of the encapsulated protoscoleces with mebendazole in feed for 14-21 days caused collapse of the outer cysts and death of the germinal membrane of all but the innermost protoscoleces. Six weeks later, however, cysts had regrown from surviving germinal tissue and a further treatment with mebendazole in feed for 14-21 days again did not destroy all germinal cells. Treatment of the 4-month-old scoleces with mebendazole in feed for 14 days caused all cysts to collapse and destroyed practically all E. granulosus germinal tissue. Three subcutaneous injections of mebendazole at fortnightly intervals, of drug in saline at 500 mg/kg body weight, or in carrier at 100 mg/dg body weight, were required in order apparently to kill all secondary cysts of E. granulosus. Host lymphoid cells were not able to traverse the laminated membrane of either untreated or collapsed cysts, and it has been shown that only a small amount of living germinative tissue is required to produce a new E. granulosus cyst. These factors could contribute to the relative ability of E. granulosus cysts to recover from mebendazole treatment, compared with cysticerci or tetrathyridia. The effectiveness of mebendazole thus seemed to depend on the formulation of the drug and its route of administration. Mebendazole is probably the first anthelmintic to have a lethal effect on larval cestodes. When applied orally there do not appear to be any adverse effects due to treatment.

The streptothrinin antibiotics SQ 21,704 was evaluated against naturally occurring Taenia pisiformis and Dipylidium caninum infections in dogs when they were given at a dose level of 37.5 mg/kg of body weight in four different rations: loaf-type canned meat; chunk-type canned meat; dry (gravy-type) meal; and dry (pelleted) meal. The SQ 21,704 was 100% efficacious against both T pisiformis and D caninum infections when given with the chunk, gravy, and pelleted rations. When given with the loaf-type canned meat, it was 100% effective against T pisiformis and 60% efficacious against D caninum. The SQ 21,704 was effective against both tapeworm species when given orally as a liquid at a dose level of 37.5 mg/kg, formulated as an aqueous suspension containing 94 mg of activity per milliter. The SQ 21,704 was also tested in dogs when given orally in gelatin capsules at a dose level of 37.5 mg/kg without fasting, and was 100% efficacious against both tapeworm species. The results of a comparative taeniacidal study demonstrated that SQ 21,704 was 100% effective in removing both T pisiformis and D caninum when administered orally at a dose level of 37.5 mg/kg, whereas niclosamide and bunamidine hydrochloride were only partially effective at their recommended dose levels. One of five dogs treated with niclosamide at a dose level of 157 mg/kg was positive at necropsy, giving an orally efficacy of 80%. Three of five dogs treated with bunamidine hydrochloride at a dose level of 49 mg/kg were positive at necropsy, giving an overall efficacy of 40%.

4-Isothiocyanato-4'-nitrodiphenylamine possessed anthelmintic activity against Nippostrongylus dubius and Hymenolepis nana in mice and H. diminuta in rats as determined by both egg counts and recovery of parasites at autopsy. No activity was detected against the cestode. Spirometra mansonoides, in cats.

Mesocestoides tapeworm is a common cestode in carnivorous mammals, but human infection with the tapeworm of this genus have been infrequent. We have recently observed the 13th case of human infection with Mesocestoides lineatus in Japan. A 35-year-old man living in Gifu prefecture was admitted to our University Hospital with chief complaints of general fatigue and discharge of cestode segments in his stool. The patient gave a history of drinking blood and eating the raw liver of a snake Agkistrodon halys for medicinal purposes as same as the previous cases of all reported in Japan. The segments were identified as those of M. lineatus. He was treated orally 3 g of paromomycin sulfate. Stool examination after treatment with paromomycin sulfate revealed no evidence of parasitism. The present case may be the 2nd to have been successfully treated with paramomycin sulfate and the 21st case of Mesocestoides tapeworm infection in man described in the literature.

CBA/H mice were given the immunomodulator lentinan in multiple, ascending doses before (prophylactic) or after (therapeutic) inoculation with tetrathyridia of Mesocestoides corti or as a single prophylactic dose. The latter was without effect, but increasing multiple prophylactic and therapeutic doses of lentinan resulted in a marked reduction in the numbers of parasites in the peritoneal cavity, particularly in those mice that received lentinan therapeutically. In mice that received multiple doses of lentinan, liver granulomas were larger than in controls and there was more collagen deposition and fibrosis. Encapsulated parasites were dead or dying, and such damage appeared to be mediated by increased numbers of macrophages and giant cells.

The in vivo activity of two cyclosporins, cyclosporin A (CsA) and a non-immunosuppressive derivative of dihydrocylosporin A (DHCsA-d) against three tapeworms, Hymenolepis microstoma, H. diminuta and Mesocestoides corti, has been assessed. CsA reversibly reduced the dry weight of H. microstoma in the mouse, briefly delayed oviposition and had a statistically significant effect on worm numbers recovered. Oral and subcutaneous treatments of both CsA and DHCsA-d were effective in reducing worm weight; juvenile worms were most susceptible but worms of all ages responded to drug by a dramatic reduction in weight from which they recovered. Multiple courses of CsA were no more active than single courses of treatment but dose response suggested that a threshold level of drug was necessary to evoke activity. By contrast, H. diminuta in the rat was completely unaffected by CsA but no explanation for the differences in drug response by these two closely related helminths is forthcoming. Mesocestoides corti responded reversibly to CsA in the mouse by a reduction in asexual proliferation of both liver and peritoneal cavity tetrathyridia. The data presented argue in favour of a range of anti-parasitic activities by cyclosporins but the details of the various putative modes of action remain to be defined.

In a series of 5 trials, in which 115 artificially infected calves were used, larval anthelmintic tests were done to assess the activity of oxfendazole at 4, 5 mg/kg against all 3 parasitic stages of 6 species of namatodes. An efficacy of over 98% was demonstrated against the 4th stage larvae (L4), 5th and adult stages of Haemonchus placei, Ostertagia ostertagi, Cooperia pectinata, Bunostomum Phlebotomum and Oesophagostomum radiatum and the 3rd larval stage (L3) of H. placei and C. pectinata. Against the L3 of O. ostertagi, B. phlebotomum and O. radiatum efficacies of 81,7%, 92,4% and 97,3% respectively were shown. Against Dictyocaulus viviparus adult, 5th, L4 and L3 efficacies were recorded of 100%, 96,7%, 95,4% and 89,1% respectively. A test for ovicidal activity confirmed that cattle can be safely moved to clean pasture 8 hours after dosing. Complete removal of strobilia of Moniezia benedeni from 25 naturally infested calves followed a dose rate of oxfendazole at 4,5 mg/kg, but of these each of 4 calves retained one scolex.

The efficacy of different dose rates of Praziquantel (Droncit R) in tablet and liquid (injectable) form against Raillietina tetragona in the domestic fowl was studied. A dose of 10 mg kg-1 of Praziquantel in tablet form and 0.15 ml kg-1 in liquid form was found to be effective against R. tetragona infection irrespective of age, sex and intensity of infestation of the host. Intramuscular (IM) administration of liquid Praziquantel was found to be more effective than subcutaneous (SC) administration. Susceptibility of the parasite to this drug increased with age.

Although improved sanitation in the United States has resulted in a general diminution in the prevalence of intestinal parasitic infections, some, such as enterobiasis, are not reduced by improved environmental or water sanitation and others, such as amebiasis and hookworm infection, persist in foci. Other infections, notably giardiasis, have increased due to the travels of American tourists in other countries where environmental sanitation is poor. North American physicians, therefore, may expect at some time to have to treat parasitic infections. Favored chemotherapeutic agents currently are: for amebiasis--metronidazole and diiodohydroxyquin; for giardiasis--metronidazole; for tapeworm infections--niclosamide; for enterobiasis--pyrantel pamoate, piperazine citrate, or pyrvinium pamoate; for ascariasis--piperazine citrate; for stronglyoidiasis--thiabendazole; for trichuriasis--mebendazole; for hookworm infection--pyrantel pamoate; for schistosomiasis japonica--tartar emetic; and for schistosomiasis mansoni--niridazole.