Elimination Of Worms Research Articles

Schistosoma mansoni: the survival and reproductive status of mature infections in mice treated with oxamniquine.

A single oral dose of 50 mg/kg of oxamniquine administered to mice with mature infections of Schistosoma mansoni gave rise to a hepatic shift and almost total elimination of the male worms. Regression of the reproductive system and a conspicuous reduction in size took place in the residual females which eventually resembled sexually immature adults. A second dose of oxamniquine had no apparent effect on these females within a period of 28 days following this treatment and it is suggested that this change in reproductive status is the result of discontinued male stimulation.

Macrophage-mediated damage to filarial worms (Dipetalonema setariosum) in vivo.

An adult female Dipetalonema setariosum (Mönnig 1926) recovered from the pleural cavity of Meriones libycus and bearing an adherent cell mass examined by means of electron microscopy. The host reaction consisted exclusively of macrophages and was associated with disruption of the cuticular membrane and invasion of the cuticle itself. There was no evidence of prior activity by other cell types. Initiation of damage appeared to be associated with the release of lysosomal enzymes by the macrophages. Within the reaction a localized breaching of the cuticle had occurred and cells had penetrated the internal tissues of the worm. It is suggested that macrophages may play a role in the elimination of effect worms from an established population.

Attrition of schistosomes in an irradiation-attenuated cercarial immunization model of Schistosoma mansoni.

The attrition of Schistosoma mansoni challenge worms was studied in irradiation-attenuated cercaria-immunized mice as a function of site and time. The peak recovery of schistosomula from the lungs of immunized mice was delayed 2 days in comparison with non-immunized controls. The difference between the peak recoveries of control and immunized mice accounted for about half of the final attrition observed at the 7-week adult worm stge. Hepatic-mesenteric vein worm recoveries obtained 10 to 42 days after challenge were reduced in most cases at least as much as the 49-day counts. Somewhat higher reductions were observed at 14 to 28 days than at 49 days, confirming the evidence of delayed migration obtained at the lung phase. These findings, coupled with histologic observations, indicate that at least half of the worm elimination attributable to immunization occurs 8 or more days after the challenge infection.

Effects of host endocrine gland removal on the permissive status of laboratory rodents to infection by Schistosoma mansoni

Knopf P. M. and Soliman M. 1980. Effects of host endocrine gland removal on the permissive status of laboratory rodents to infection by Schistosoma mansoni. International Journal for Parasitology, 10: 197–204. The capacity of Schistosoma mansoni to complete its life cycle was compared in CD-1 mice (permissive hosts) and Sprague-Dawley rats (nonpermissive hosts) from which the pituitary gland had been removed prior to infection with cercariae. Except for a modest decrease in egg burden, none of the parameters of worm life cycle assessed were affected in hypophysectomized mice. In contrast, all these parameters were affected in hypophysectomized rats, e.g. onset of adult worm elimination was delayed, worm development improved, oviposition increased and miracidia developed. Effects of removal from rats of the thyroid/parathyroid glands on the parasite life cycle were similar to hypophysectomy; adrenalectomy or gonadectomy were without affect. Differences between thyroidectomized and thymectomized rats are discussed. It is concluded that host hormones contribute to the nonpermissive status of rats to Schistosoma mansoni infections.

Schistosoma mansoni: Peripheral and tissue eosinophilia in infected rats

Peripheral eosinophilia is induced in Sprague-Dawley rats following infection with cercariae of Schistosoma mansoni. Beginning 3 weeks after infection, peripheral eosinophil levels rise above the baseline range; they reach peak values during the fifth week. Following a decline from peak values, peripheral eosinophil levels remain elevated and are observed to fluctuate for the next 5 months. The magnitudes of both the initial peak response at 5 weeks and the subsequent chronic level of peripheral eosinophils are dependent upon dose of cercariae. The initial peak response phase of peripheral eosinophilia coincides in time with the period of adult worm elimination (Weeks 4–6) in the schistosome-infected rat. Histological examination of the liver at 5 weeks after infection reveals eosinophil-rich inflammatory reactions associated with both live and dead worms residing in the portal blood vessels. Around live worms the inflammatory cells are localized in a perivascular arrangement; around dead worms these cells are in the vascular lumen in contact with destroyed worms. The chronic phase of peripheral eosinophilia is associated, in part, with inflammatory reactions surrounding eggs deposited in the liver by the few worm pairs which survive more than 6 weeks and remain within the liver. Histological examination during this period reveals granulomatous lesions within the liver surrounding eggs and dead worms. The granulomas are predominately monocytic (lymphocytes, macrophages) at 11 and 16 weeks. The initial peak response phase of peripheral eosinophilia appears to be a marker for tissue-localized reactions of eosinophils with worms. There are relationships between inflammatory reactions and survival of adult worms.

NITROSCANATE* A NEW BROAD SPECTRUM ANTHELMINTIC AGAINST NEMATODES AND CESTODES OF DOGS AND CATS

SUMMARY: The efficiency of the broad spectrum anthelmintic nitroscanate against tapeworm and nematode infections of dogs was tested in artificially or naturally infected dogs. The safety of the compound was also evaluated in acute, subacute and chronic toxicity tests.At the recommended single dose rate of 50 mg/kg given to the dogs with food, nitroscanate was 98% efficient against Taenia hydatigena, T. ovis and T. pisiformis. The drug was highly efficient against Echinococcus granulosus only at the dose rate of 200 mg/kg given twice but total elimination of worms was not achieved. Natural infections of Dipylidium caninum, Ancylostoma spp and Uncinaria stenocephala were totally eliminated from all dogs at the dose rate of 25 mg/kg or higher.Nitroscanate was 97% efficient against adult Toxocara canis at a single dose of 50 mg/kg. When the dose was repeated 24 hours later total elimination of both mature worms and immature worms in puppies aged 2 weeks was achieved. The repeated dose of 100 mg/kg removed 98% of early immature worms from puppies aged 3 days. The drug was 100% efficient against adult Toxascaris leonina at a single dose of 50 mg/kg and 90.5% efficiency was achieved against early 4th stage larvae by two doses of 50 mg/kg. Nitroscanate was not efficient against Trichuris vulpis.The drug was efficient for the removal of Toxocara cati and Ancylostoma tubaeforme from cats.Nitroscanate caused no serious symptoms of toxicity at dose rates up to 10,000 mg/kg in single or repeated doses in young or older adult dogs. The drug was safely given to dogs during pregnancy, to young puppies and to cats. The regular use of nitroscanate as a broad spectrum anthelmintic for the prevention and control of parasitic infections of dogs is discussed.

Quantitation of immediate and delayed hypersensitivity responses in Trichinella-infected mice. Correlation with worm expulsion.

The developmental relationships between active cutaneous or local anaphylaxis, delayed hypersensitivity and worm expulsion were quantitatively examined in Trichinella-infected mice. The onset of both types of hypersensitivities and increase in sensitivity to antigen following an initial infection correlated with the onset and rate of elimination of adult worms. Mice passively sensitized with serum containing both IgG1 and IgE antibodies, but not IgG1 alone, expelled their worms at a faster rate in comparison to the controls. On the basis of these findings it is suggested that local allergic reactions mediated by anaphylactic antibodies are involved in the development of resistance to Trichinella infection.

Schistosoma mansoni: Relationship between parasite age and time of spontaneous elimination from the rat

Laboratory rats infected with Schistosoma mansoni invariably reject the majority of parasites between the fourth and sixth week after infection (self-cure). This investigation was designed to determine whether the timing of rejection is dictated by the rat or by the parasite. Schistosomes were perfused from rats infected 2, 3, or 4 weeks previously and were transferred into the mesenteric veins of normal rats. Recipient animals were perfused at weekly intervals after transfer, and the timing of worm elimination was determined in recipients. It was found that 2-week-old worms were rejected 2 weeks after transfer, 3-week-old worms 1 week after transfer, and 4-week-old worms immediately after transfer. Schistosomes perfused from mice or hamsters and transferred into rats showed the same pattern of worm elimination. It is concluded that at the fourth week of normal schistosome development there is a critical event which makes virtually impossible any further survival of the parasite in laboratory rats.

Trichinella spiralis: Effects on the host-parasite relationship in mice of BCG (attenuated Mycobacterium bovis)

The effects of BCG (Bacillus Calmette-Guérin, i.e., attenuated Mycobacterium bovis) on the host-parasite relationship in murine trichinosis were examined. A total of 2 × 10 7 colony forming units of BCG given iv 1 week prior to Trichinella spiralis infection delayed the expulsion of adult worms from the gut. The suppression of adult worm elimination was proportional to the dose of BCG given. This finding was associated with a reduction in the degree of partial villous atrophy induced in the small bowel by T. spiralis. Adult female worms were fecund when they were examined 1, 2, and 3 weeks after infection of mice with T. spiralis. Despite the prolongation of fecund adult worms in the gut, there were no significant differences in muscle larval counts 4 and 6 weeks after infection. When newborn larvae were cultivated in vitro and injected iv, there was a significant 25% reduction in larval numbers recovered from the muscles of BCG-treated mice 4 weeks later. The administration of BCG had no effect on the inflammatory reaction around larvae in the muscles 4 and 6 weeks after infection. It is concluded that BCG alters the host-parasite relationship producing retention of adult worms in the gut, reduction in the severity of partial villous atrophy, and increased nonspecific resistance to the systemic larval phase of this parasite.

The susceptibility to praziquantel of Schistosoma haematobium in the baboon (Papio anubis) and of S. japonicum in the vervet monkey (Cercopithecus aethiops)

Baboons infected with S. haematobium and vervet monkeys infected with S. japonicum were treated orally with different dosage regimens of praziquantel. The progress of the infections in the primates was followed by weekly faecal and urine egg counts before and after treatment. The response to treatment was also monitored by observing oogram changes in rectal snips. The baboons and vervet monkeys were autopsied and perfused 3–4 months after treatment. The results of the praziquantel treatments of baboons infected with S. haematobium show that a single administration of 100 mg/kg in one day was as effective as 50 mg/kg for five consecutive days in producing a complete cure. A single dose of 30 mg/kg failed to stop egg laying but retreatment with 50 mg/kg administered in one day resulted in cessation of egg laying 12 days after treatment and only one immature female worm and 33 male worms were recovered at autopsy. A baboon treated with 30 mg/kg administered at 10 mg/kg three times in one day was not cured, but when retreated with 75 mg/kg, administered in three separate doses of 25 mg/kg in one day, egg laying stopped 15 days afterwards and only three male worms were recovered at autopsy. The results suggest that a single oral dose of 75–100 mg/kg bwt is likely to be effective against S. haematobium in the baboon. An intramuscular injection of 200 mg/kg bwt was well tolerated by one animal. The results obtained with praziquantel against S. japonicum in the vervet monkey show that a complete cure was obtained in the animal given 50 mg/kg on five consecutive days, but the regimens of a single dose of 20 mg/kg followed by two separate doses of 10 mg/kg during one day, and of 10 mg/kg given three times during one day, resulted in only partial parasitological cures. The results based upon faecal egg output studies and the oograms taken after treatment suggested that praziquantel is more effective against S. japonicum than S. haematobium in the doses given, but the subsequent autopsies showed that some S. japonicum adult worms had survived treatment. A baboon naturally infected with S. mansoni, with a daily egg output of 150 eggs, was completely cured by a single oral dose of 50 mg/kg of praziquantel. This dose however failed to cure another naturally infected animal with a daily egg output of 1,800 eggs. It is considered that a predominant characteristic in the pathology of the animals given a curative dose of praziquantel was the total resolution of cellular reaction and fibrosis in the tissues containing known numbers of dead residual eggs. In the baboons with S. haematobium, the ureters and bladder had recovered their functional integrity and in the vervet monkeys infected with S. japonicum, a similar resolution of pathology in the liver and bowel was apparent. The results show that praziquantel is effective against patent S. haematobium and S. mansoni infections in baboons and against S. japonicum in vervet monkeys, in relatively low dosage regimens (100 mg/kg and < 100 mg/kg) applied in one day, as shown by suppression of egg laying and reduction or complete elimination of adult worms. Female worms of S. haematobium are apparently more susceptible to the compound than male worms. The classic hepatic shift of adult schistosomes was observed in all of the primates treated in the present series, but histopathological studies showed that numerous worms also died in situ, while only a few were found in the lungs.

Effects on murine trichinosis of niridazole, a suppressant of cellular but not humoral immunological responses

Two groups of mice infected with Trichinella spiralis were treated with niridazole (100 mg/kg), one on alternate days, the other daily. Both regimens failed to influence the numbers of adult worms in the intestines or larvae in the muscles compared with untreated control mice. Mice treated with niridazole daily, but not those treated on alternate days, showed a significant reduction in the inflammatory reaction to larvae in the muscles. Immediate footpad swelling in response to injection of soluble Trichinella larval antigen was not affected by niridazole treatment. Niridazole appears to have a highly selective action on immunological responses suppressing cell-mediated reactions but leaving humoral antibody formation relatively intact. Elimination of worms may require the presence of both cellular and humoral immune mechanisms, while inflammation around larvae in the muscles may be largely a cellular reaction.

Studies on immune responses to parasite antigens in mice. III. Nippostrongylus brasiliensis infections in hypothymic nu/nu mice.

Normal mice of several strains reject the nematode worm Nippostronglyus brasiliensis from the intestine within 14 days (and most often within 10 days) of injection of high numbers of infective third stage larvae (L3). Previously-infected mice are markedly resistant to a second infection. Hypothymic, nu/nu ('nude') mice continue to harbor worms long after intact mice have rejected the worm burden and an inoculum of T cells at the time of, or several days after L3 injection, leads to worm elimination within 14 days in nu/nu mice. As yet no evidence is available to indicate whether or not T cells with specificity for parasite antigens are required in a reconstitutive inoculum in nu/nu mice. Pretreatment of normal mice with cyclophosphamide, at doses reported to lead to temporary B cell hypofunction, does not result in delayed rejection of worms but the participation of B cell products (antibodies) cannot be discounted on the basis of this result. The nu/nu mouse - N. brasiliensis system will be useful in the search for, and characterization of, parasite antigens which gain access to the lymphoid organs and circulation of parasitized mice and in the analysis of T cell subtypes (both functional and surface Thy and Ly alloantigenic subtypes) involved in worm elimination.

Nippostrongylus brasiliensis: Phospholipase in nonsensitized and sensitized rats after challenge

Rats given an initial infection with Nippostrongylus brasiliensis showed greatly elevated phospholipase B levels in the small intestines and lungs from 8 through 22 days after challenge. The rise in enzyme concentration occurred earlier (Days 8–11) in the proximal half of the intestine, but at Days 22, 29, and 36 the levels were much higher in the distal segments. This shift in activity correlates with the known elimination of worms and a diminishing inflammatory response in the proximal areas. The increase in enzyme activity in the intestine and lungs was associated with an increased production of eosinophils in the bone marrow 11–22 days after challenge. Rats sensitized with one stimulating infection before challenge showed an anamnestic type of response, as measured by enzyme levels in the small intestines and lungs and by the numbers of eosinophils in the bone marrow. The results are discussed in light of our similar data reported earlier from animals infected with Trichinella spiralis.

Studies on the immunity of sheep to Oesophagostomum columbianum: effects of different and successive doses of larvae on worm burdens, worm growth and fecundity.

The effects of different and repeated doses of Oesophagostomum columbianum larvae on the survival of the adult parasite, its length and the fecundity of the female worm in sheep were studied. Adult worm burdens were dependent on the numbers of larvae administered when sheep were infected once, but not when they were infected twice. It was concluded that these effects were caused by non-specific elimination of worms following a single infection, related to competition for space among larvae and to inflammatory reactions stimulated by them in the gut mucosa which increased with the numbers of larvae given. When sheep were infected once with large numbers of larvae or when they were infected twice the surviving adult population was also influenced by the adaptive immune responses of the host. Parasites recovered from sheep given a single infection of 5000 larvae were stunted compared with worms from sheep given fewer larvae. After a second infection all the worms were stunted and the females produced fewer eggs than did female worms following a single infection; but the numbers of larvae administered did not influence these effects. Egg production was also delayed after a second infection. The reduced fecundity of female worms in the immune host was not related to stunting of the worms, because stunted female worms from sheep infected once with 5000 larvae produced as many eggs as females from sheep infected once with smaller numbers of larvae. It is suggested that the different manifestations of protective immunity in sheep were elicited when threshold levels of infection were exceeded. These levels were represented by between 2000 and 5000 larvae in first, and fewer than 500 larvae in second infections.

Experiments on the control of anchor worm ( Lernaea cyprinacea)

1. 1. Life history study on Lernaea cyprinacea showed that the first copepodid stage appeared 3–4 days after hatching and there are six copepodid stages similar to those reported in other studies on this species. The life cycle from egg to mature adult was completed in 13–14 days at 22–25°C. 2. 2. Complete elimination of anchor worms was achieved by the use of 0.8: 10 000 formalin and 0.3 to 1 ppm of dipterex. 3. 3. Dipterex gave an effective control of anchor worms in ponds after four bi-weekly treatments at a rate of 1 ppm.

Resistance Potential of Certain Breeds of Domestic Fowl Exposed to Raillietina tetragona Infections: 6. Effects of Starvation of the Host Chicken on the Tapeworm Raillietina Tetragona

Effects of short periods of starvation on the fowl cestode, Raillietina tetragona, developed in four breeds of chickens, White Leghorn, White Rock, Desi and Hybrid (White Leghorn × Desi) are reported. The data based on 40 birds revealed significant reduction in segment discharge, depletion of glycogen reserve of the worms, elimination of entire worms and reduction in worm weight, almost correlated with the duration of starvation.

Nippostrongylus brasiliensis in the rat: failure to relate intestinal histamine and mast cell levels with worm expulsion.

This paper describes experiments to determine whether intestinal tissue mast cells and/or intestinal histamine are involved in the second, expulsive step of worm elimination. In neonatal rats, intestinal tissue contains only very little histamine and mature mast cells are encountered only sporadically. From birth to the adult age, there was a gradual rise in both intestinal mast cells and histamine.DuringNippostrongylus brasiliensisinfection in the adult rat, the concentration of histamine in the small intestine was clearly lower than in uninfected controls.Especially low histamine values were found to occur on days 6–12 of a primary infection in the region where the main worm burden was located. Similarly, the number of tissue mast cells present in the epithelium of the jejunum was decreased in the same region and during the same period of time. From the observation that the bulk of the parasites are expelled at a time when histamme and mast cell levels are low, it was concluded that mast cells and their constituents were not an essential factor in the second step of worm eliminationThis work was supported by the Schweizerische Nationalfonds zur Förderung der wissenschaftlichen Forschung (Grant 5200.3). The skilful technical assistance of Miss I. Beeger, Miss R. Keist and Miss M. Iseli is gratefully acknowledged. I thank Mr H. Berchtold, Biostatistisches Zentrum der Universität Zürich, for the statistical evaluation of the data.

Studies on the Resistance of Pigs to Infestation with Hyostrongylus rubidus (Hassall & Stiles, 1892): I. Infection Experiments in Non-sensitised and Previously Sensitised Growing Animals

SUMMARY Single infections and reinfections with variable numbers of H. rubidus larvae have been studied in growing pigs. Clinical symptoms of infection have only been seen following infection with 200,000 or 500,000 larvae. Worm counts following similar infection rates were higher in colostrum deprived S.P.F. pios than in conventionally reared M.D. pigs. Initial infections became patent in 18 to 21 days and reinfections from 32 to 35 days. Reinfection of pigs which had had initial infections of 200,000 or 500,000 larvae did not become patent. Reinfections of animals which had initially been infected with 20,000 larvae or less became patent though egg production was low and of short duration. Worms recovered from a 3 to 5 week initial infection were significantly longer than worms from 10-week-old infections or 4½-week-old reinfections. Evidence is provided which shows that the degree of immunity following initial infection is related to the level and persistence of that infection. Worms may be inhibited in development as either fourth or fifth stage larvae and the fecundity of established worms considerably reduced in the immune animal. There is also a gradual elimination of worms as infection progresses.

Immunity to Dictyocaulus viviparus infection in the guinea pig produced by normal and triethylene melamine-attenuated larvae

Third stage larvae were demonstrated in the lungs of guinea pigs, dosed with 4,000 to 10,000 normal Dictyocaulus viviparus, 14 hours after infection. Development to the early fifth stage occurred, but the numbers of worms fell rapidly after day 10 and the infection was eliminated after 16 days. Immunisation with two doses of 4,000 normal larvae resulted in a high level of resistance. In such immune animals the challenge dose of larvae developed normally until day 4 after which the majority were eliminated and the remainder retarded in size. Guinea pigs dosed with 4,000 larvae attenuated by exposure to 0·7 per cent. triethylene melamine (TEM) had macroscopic lung lesions similar to animals receiving normal larvae, but the numbers of worms present at day 10 was reduced by 96 per cent. and their size reduced by 17 per cent. compared with controls. A dose of 4,000 larvae attenuated by 0·7 per cent. TEM followed by a second dose of 2,000 larvae 14 days later conferred a 95 per cent. immunity in guinea pigs compared with 99 per cent. for the same regime of normal larvae when challenged with 10,000 larvae. Guinea pigs dosed twice with 4,000 normal larvae or larvae attenuated by concentrations of 1, 2 and 4 per cent. TEM showed varying degrees of immunity to challenge with 4,000 larvae. The challenge worm burden was reduced after day 4 in the normal larvae group and after days 6, 8 and 10 in the 1, 2 and 4 per cent. TEM attenuated groups respectively. This onset of worm elimination was related to the number of worms of the immunizing dose present at day 6 which was greatest in the normal larvae group and fell progressively in the 1, 2 and 4 per cent. TEM groups.

Schistosoma mansoni Infection in the Rat. II. Effects of Immunosuppression and Serum and Cell Transfer on Innate and Acquired Immunity

The reproducible pattern of Schistosoma mansoni infection in the rat was confirmed. A peak worm burden was reached at the 4th week after exposure and was followed by a rapid reduction in the number of adults between the 4th and 8th weeks; thereafter a low, stable worm burden level was maintained. This pattern was not altered by X-irradiation of the rats either prior to or 3 weeks after exposure to S. mansoni. Immunosuppression by thoracic duct drainage, antilymphocytic globulin (ALG), or a combination of ALG and Imuran failed to alter the susceptibility of the rat to S. mansoni infection, as determined by worm burdens present 4 weeks after infection. ALG was not able to alter the immune state of the host acquired as the result of previous infection. The transfer of serum or cells from immune donors did not confer protection to isologous recipients. Experiments in which a combination of immune serum and sensitized cells were transferred gave equivocal results. Infection with Schistosoma mansoni in the laboratory rat follows a reproducible pattern. The host responds to the infection by a rapid reduction in adult worm burden between the 4th and 8th weeks (Stirewalt et al., 1951; Ritchie et al., 1963; Smithers and Terry, 1965a, b). After the decline in worm burden, the animal is refractory to reexposure with cercariae (Ritchie et al., 1963; Sadun and Bruce, 1964; Erickson and Caldwell, 1965; Smithers and Terry, 1965b). The mechanism responsible for initiating the worm loss or for maintaining acquired immunity has not been elucidated. Maddison et al. (1970), using five serologic tests and the passive cutaneous anaphylaxis reaction, could not show a correlation between antibody development and the rapid loss of worms. Vogel and Minning (1953), working with S. japonicum in the rhesus monkey, Stirewalt and Evans (1953), working with S. mansoni in mice, and Kagan (1958), working with Schistosomatium douthitti in mice, could not demonstrate passive transfer of immunity with hyperimmune serum. Ogilvie et al. (1966) showed that intradermal injection of specific antischistosomal reaginic antibody afforded protection to rats that were exposed to cercariae placed over the antibody depot. The same type of antibody was not protective in the skin of the rhesus monkey. We have attempted to study the immune Received for publication 9 December 1969. mechanisms responsible for the elimination of worms and for the acquired immunity in the rat. Animals were subjected to immunosuppression before primary infection, and, in one instance, before secondary exposure. Hyperimmune serum, lymphocytes from immune rats, and a combination of these two factors were investigated for their ability to confer protection to normal recipients. The results of these experiments are now reported. MATERIALS AND METHODS Inbred Lewis and ACI strains of rats (obtained from Microbiological Associates), weighing 150 to 200 g, were employed. The sexes of the cell donors and respective recipients were in accord with the sex compatibility X and Y chromosomes. Randombred Sherman rats were raised in our laboratory. In each experiment, treated and control animals were exposed at the same time to 1,000 cercariae of a Puerto Rican strain of S. mansoni by the ring method, and the worm burdens were determined by perfusion following the technique used by Smithers and Terry (1965a). The rats were exsanguinated at the time of killing 4, 6, 8, 10, or 12 weeks after exposure, and the sera were stored at -20 C.