Experimental infection of pigs with three dose levels of Trichuris suis

The objective of the study was to follow the course of Trichuris suis infection in pigs given infective eggs at low (400 eggs), medium (4,000 eggs) and high inoculation dose (40,000 eggs), respectively. Interestingly, despite a 100-fold difference in dose level no significant difference was found in either blood parameters, total faecal egg excretion, fecundity or worm burdens at necropsy 12 weeks post inoculation. The highest and lowest median faecal egg output was found in the medium and high dose group, respectively. With increasing dose level, worm size, establishment and prevalence of T. suis positive pigs decreased while worms were dislocated aborally. In addition there was a highly significant correlation between female worm burden and faecal egg excretion.     

Response of intestinal epithelial cells to Trichuris suis excretory-secretory products and the influence on Campylobacter jejuni invasion under in vitro conditions

We previously developed a swine animal model in which natural host resistance to Campylobacter jejuni is altered by experimental infection with low numbers of the nematode Trichuris suis. Pigs naturally colonized with C. jejuni experience colitis because of the invasion of the bacterium approximately 21 days after exposure to T. suis. To better understand the mechanism of T. suis-dependent C. jejuni colitis, we evaluated the effects of T. suis excretory-secretory products (ESPs) on intestinal epithelial cells (IECs) and the influence of ESP on C. jejuni invasion in IECs under in vitro conditions. Viability assays revealed a dose-dependent cytotoxic response in ESP-treated IECs, particularly IPEC-1 and INT407 cells. Transepithelial electrical resistance dropped significantly in IPEC-1 cells treated on apical and basolateral surfaces, but not in those treated only on apical surfaces. Using the gentamicin-killing assay, reduced numbers of intracellular C. jejuni were recovered from IECs treated with ESP at 1 mg protein/ml concentration. This observation can be at least partially explained by a novel antibacterial activity in ESP. Contrary to our hypothesis, ESP at subtoxic concentrations did not enhance invasion. In addition to mechanical damage from worms, these results suggest that soluble products released by T. suis contribute to IEC damage at the site of worm attachment.     

Concomitant and protective immunity in mice exposed to repeated infections with Echinostoma malayanum

Concomitant immunity and its consequence against infection play roles in regulating worm burdens in helminthiasis. Under natural conditions, this immunity is generated by exposure to repeated low dose or trickle infection. In this study, concomitant immunity was induced in mice exposed repeatedly to infection with Echinostoma malayanum and its protective effect on a challenge infection evaluated. A profile of worm burden from exposure to 10 metacercariae/mouse/week rose rapidly during the first 2 weeks reaching a plateau from week 3 to 8 post infection. Based on a cumulative dose of infection, worm recoveries were around 75% in the first 2 weeks, dropped to 50% at week 3 and 19% at week 8. After week 2, adult worm burden was constant and no juvenile worms were found after week 3 of the experiment. To examine the effect of resistance against reinfection, mice in the experimental group were primarily infected with 10 metacercariae/week for 5 weeks, treated with praziquantel and were challenged with 75 metacercariae/animal. The number of worms recovered from the experimental groups was significantly lower than that from naïve control groups beginning from 24 h to 28 days post challenge. The worms in the experimental group showed growth retardation and the proportion of adult worms was lower than that in the control animals especially during the first 3 weeks of the experiment. Parasite fecundity was also suppressed compared with that in the control group. The selective effects of protective immunity on establishment, growth, and fecundity of challenged worms affected the population dynamics of E. malayanum which is a similar phenomenon to concomitant immunity in schistosomiasis.     

Serological responses to Ascaris suum adult worm antigens in Iberian finisher pigs

Adult Ascaris suum were dissected to obtain different worm components (body wall, body fluid, ovaries, uterus and oesophagus) which were used as antigens when testing 95 sera of naturally A. suum-infected Iberian pigs by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). Pigs with patent Ascaris infections had significantly lower ELISA optical density values than pigs without adult worms when using the body fluid and the body wall as antigens. A poor negative correlation was found between adult intestinal worm burden or eggs in faeces and specific antibody responses, measured by ELISA and WB using all antigens. By WB, the recognition of specific bands was variable, but three groups of bands with molecular weights of 97 kDa, 54-58 kDa and 42-44 kDa were generally recognized by sera from naturally infected pigs as well as from hyperimmunized pigs when using the five antigen extracts. The ELISA and WB techniques may be used for immunodiagnosis, using somatic adult worm antigens, to declare young pigs to be Ascaris-free but cannot be used for individual Ascaris-diagnosis in adult Iberian pigs.     

Worm burden-dependent disruption of the porcine colon microbiota by Trichuris suis infection

Helminth infection in pigs serves as an excellent model for the study of the interaction between human malnutrition and parasitic infection and could have important implications in human health. We had observed that pigs infected with Trichuris suis for 21 days showed significant changes in the proximal colon microbiota. In this study, interactions between worm burden and severity of disruptions to the microbial composition and metabolic potentials in the porcine proximal colon microbiota were investigated using metagenomic tools. Pigs were infected by a single dose of T. suis eggs for 53 days. Among infected pigs, two cohorts were differentiated that either had adult worms or were worm-free. Infection resulted in a significant change in the abundance of approximately 13% of genera detected in the proximal colon microbiota regardless of worm status, suggesting a relatively persistent change over time in the microbiota due to the initial infection. A significant reduction in the abundance of Fibrobacter and Ruminococcus indicated a change in the fibrolytic capacity of the colon microbiota in T. suis infected pigs. In addition, ∼10% of identified KEGG pathways were affected by infection, including ABC transporters, peptidoglycan biosynthesis, and lipopolysaccharide biosynthesis as well as α-linolenic acid metabolism. Trichuris suis infection modulated host immunity to Campylobacter because there was a 3-fold increase in the relative abundance in the colon microbiota of infected pigs with worms compared to naïve controls, but a 3-fold reduction in worm-free infected pigs compared to controls. The level of pathology observed in infected pigs with worms compared to worm-free infected pigs may relate to the local host response because expression of several Th2-related genes were enhanced in infected pigs with worms versus those worm-free. Our findings provided insight into the dynamics of the proximal colon microbiota in pigs in response to T. suis infection.     

Eosinophil responses of permissive and nonpermissive hosts to the young adult worms of Angiostrongylus cantonensis

Blood and bone marrow eosinophilia was assessed in nonpermissive (guinea pigs) and permissive (rats) hosts following the pulmonary arterial transfers of live or dead young adult worms of Angiostrongylus cantonensis. Guinea pigs showed a marked eosinophilic response to live worms but only a slight response to dead worms. Neither IgE nor haemagglutinating antibodies correlated with the induction of this eosinophilia. In contrast, the rat responded to neither form of the young adult worm. When the guinea pig and the rat were injected with whole worm extract (WWE) of the young adult worms either by an osmotic mini-pump connected to the jugular vein or by intermittent intravenous injections, the former animal showed blood eosinophilia but the latter failed to do so. Guinea pigs also developed blood eosinophilia after continuous exposure to the excretory and secretory products of the young adult worms, administered by the mini-pump. Eosinophil responses to WWE could be induced both in athymic CD-1 (ICR) nude mice and in its heterozygous litter mates, suggesting that T cell-independent mechanism(s) could be involved in the induction of blood eosinophilia in the nonpermissive, mouse host. These data clearly indicate that the eosinophilia-inducing factor(s) and the mechanism of eosinophilia are different in permissive and nonpermissive hosts.     

Merino ewes bred for parasite resistance reduce larval contamination onto pasture during the peri-parturient period

The peri-parturient period is crucial for controlling worms as the acquired immunity of ewes is disrupted, resulting in an increase in faecal worm egg counts. Two hypotheses were tested in this experiment - that ewes bred for worm resistance would have lower faecal worm egg counts than unselected control ewes, during late pregnancy and lactation, under similar but separate grazing areas; and also that numbers of infective nematode larvae would be lower on pastures grazed by resistant ewes than pastures grazed by unselected control ewes. Faecal samples were collected from resistant and unselected ewes in late pregnancy and early lactation, during the winter rainfall season, and analysed for numbers of Trichostrongylus colubriformis and Teladorsagia circumcincta. Pasture samples were taken 1 week before and 7 weeks after lambing started and analysed for infective larvae. In all sheep, worm egg counts rose 2 weeks prior to lambing and continued into lactation. Worm egg counts were significantly lower in the resistant ewes from 1 week before lambing to 2 weeks after lambing. There were no differences in egg counts between single- and twin-bearing ewes in the resistant line. However, twin-bearing control ewes had significantly higher egg counts than single-bearing control ewes. Following lactation, plots grazed by resistant ewes had substantially less contamination with T. colubriformis larvae, but there were no differences in numbers of T. circumcincta larvae. Our results demonstrate that sheep bred for worm resistance has lower worm burdens during the peri-parturient phase and that lambs born to resistant ewes face a lower larval challenge during their introduction to grazing. In our environment, selection for low worm egg counts has produced sheep highly resistant to T. colubriformis, but has had less impact on resistance towards T. circumcincta.     

Selection for anthelmintic resistance by macrocyclic lactones in Haemonchus contortus.

Two morphologically marked strains of Haemonchus contortus, CAVRS (smooth-macrocyclic lactone resistant) and McMaster (linguiform-macrocyclic lactone susceptible), were used to investigate the selection for anthelmintic resistance following exposure to ivermectin (IVM), a non-persistent anthelmintic. and a more persistent anthelmintic, oral moxidectin (MOX). Three types of selection were investigated: (1) selection of resident worms at the time of treatment (Head selection); (2) selection of incoming-larvae post-treatment (Tail selection); and (3) selection of both resident population and incoming larvae (Head + Tail selection). The experimental animals were adult sheep and lambs. In the controls where there was no anthelmintic selection, the proportion of CAVRS in the adult worm population was the same as the proportion in larvae given to both adults and lambs indicating that CAVRS and McMaster H. contortus were equally infective. There was a significant effect of anthelmintic on total worm numbers in adult sheep with MOX treated adults having less worms, but selection type was non-significant. Anthelmintic type had a significant effect on numbers of resistant worms in adult sheep with less resistant worms in the MOX treated groups, but selection type had no effect. Analysis of variance of arcsine-transformed proportions of resistant worms found that the type of anthelmintic had a highly significant effect, with MOX treated adults having a higher proportion of resistant worms, while type of selection was not significant. In the lambs, nil treated controls and IVM Head + Tail and Tail selected groups had similar geometric mean total worm burdens while Head selected had less total worms. In the MOX treated lamb groups the worm burdens were similar within selection type but less than the IVM treated groups. In the lambs, the types of selection that resulted in more resistant worms were IVM Tail, MOX Head + Tail and MOX Tail. Resistant worm numbers were similar in both adult and lamb groups with Head selection by either MOX or IVM. Moxidectin selected out higher proportions of resistant worms than did IVM in the lambs, with Tail and Head + Tail being stronger selectors than Head. Computer simulations were used to estimate the rate at which resistance developed in the field using the information generated in the present study. The anthelmintic treatments used in the simulation followed a strategic parasite control program for H. contortus in which all sheep receive three Closantel (CLS) treatments in summer. all sheep receive a broad-spectrum (BS) drench or capsule at weaning and lambs receive an additional two BS drenches insummer or no further treatment in the case of the capsule. Moxidectin, IVM-capsule and IVM were the broad spectrum anthelmintics simulated. All simulations were run four times assuming high or low efficacy against resident resistant worms and in the presence or absence of CLS resistance. The simulations indicated that the presence of CLS resistance hastened selection for macrocyclic lactone (ML) resistance. While the IVM-capsule will select most rapidly for ML resistance, IVM oral is expected to be least selective. Moxidectin treatment is intermediate, except in simulations with no CLS resistance and when MOX is assumed to be highly effective against resident ML-resistant worms, in which case MOX can be expected to select more slowly than IVM oral treatments.     

The consequences of short-term grazing of bioactive forages on established adult and incoming larvae populations of Teladorsagia circumcincta in lambs

The objective of this study was to investigate the consequences of short-term grazing on bioactive forages on (i) the viability and fecundity of established adult Teladorsagia circumcincta population and (ii) the establishment and development of incoming T. circumcincta infective larvae. Forty-eight, parasite naive, 3-month old, grazing lambs were artificially infected with 8000 infective larvae of T. circumcincta on day 1 of the experiment. On day 21 p.i., lambs were allocated to one of three bioactive forage grazing treatments; chicory (Cichorium intybus), sulla (Hedysarum coronarium), lotus (Lotus pedunculatus), and the control grass/clover (Lolium perenne/Trifolium repens) forage. On day 28 of the experiment a second dose of 8000 T. circumcincta infective larvae was administered to the lambs to investigate the effects of forages on the ability of infective larvae to establish within the host. All animals were slaughtered for worm recovery on day 35, while liveweight gain, feacal egg counts (FEC) and total worm egg output were monitored regularly throughout the experiment. Although FEC or total egg output were similar among the groups, adult worm burdens at slaughter were significantly affected (P<0.05) by forage treatment during the 2 week grazing period. Lambs grazing chicory had the lowest adult worm burdens and significantly lower numbers of male worms compared to those grazing on grass/clover (P<0.01), while the lambs grazing on sulla or lotus had similar adult populations to grass/clover fed animals. The results from the worm recoveries of the second dose (immature worm burdens) were affected by physiologically and/or immunologically mediated mechanisms, which reduced larval establishment in all treatments. Nevertheless, immature worm burdens at slaughter were similar between chicory, sulla and grass/clover group, while the immature worm recoveries from the lotus group were significantly higher (P<0.05) compared to those from lambs grazing grass/clover. Overall, the results of the present study support the view that chicory can be a promising candidate species in pasture management practices to control T. circumcincta burdens.     

Localization of protective antigens in Trichostrongylus colubriformis

In order to localize protective antigens in Trichostrongylus colubriformis, adult worms were microdissected and the capacity of worm tissues to protect guinea pigs against infection examined. The results suggest that T. colubriformis protective antigens are widely distributed in the body and are not concentrated in the intestine or glandular structures.     

Experimental Oesophagostomum dentatum infection in the pig: Worm populations resulting from single infections with three doses of larvae

This report describes the effect of different dose levels of infection upon worm burdens and development and fecundity of the parasites. Three groups each of 40, 9-week-old, helminth naïve pigs were inoculated once with either 2000 (group A), 20,000 (group B), or 200,000 (group C) infective third stage larvae of Oesophagostomum dentatum. Subgroups of 5 pigs from each major group were killed 3, 6, 11, 14, 18, 25, 34 and 47 days post inoculation (p.i.) and the large intestinal worm burdens were determined. Faecal egg counts were determined at frequent intervals after day 13 p.i. There were no overt clinical signs of gastrointestinal helminthosis during the experiment. Faecal egg counts became positive in groups A and B at around day 19 p.i., whereas most pigs in the high dose group C did not have positive egg counts until day 27–33 p.i. and some pigs remained with zero egg counts until the end of the study. Throughout the experiment the worm populations in group C consisted mainly of immature larval stages, while those in groups A and B were predominantly adult stages after days 14–18. Adult worms from the low dose group A were significantly longer than those from group C. At high population densities, stunted development of worms and reduced fecundity among female worms were found. Furthermore, there was a tendency for the distribution of the worms within the intestine to be altered with increasing population size.     

Angiostrongylus cantonensis: Development following pulmonary arterial transfers into permissive and nonpermissive hosts

The survival, growth, and egg-laying capacity of young adult Angiostrongylus cantonensis, surgically transferred from intracranial sites into pulmonary arteries, were studied. A variety of experimental animals (rats, guinea pigs, mice, and mastomys) were chosen as donor animals and as recipient hosts (rats, guinea pigs, and rabbits). These species were specifically chosen to span the spectrum of host permissiveness relative to worm development in an attempt to understand the mechanisms which underlie species-dependent resistance. Recipient animals were monitored not only for the development of parasites per se but also for antibody production and histopathologic changes. The results indicated that these procedures were technically feasible, with good worm development following intra-rat transfers, as early as 15 days after initial exposure. Studies were performed to analyze the constraints of development both on initial, i.e., prelung and subsequent i.e., postlung development. When worms were obtained from permissive species such as rat or mastomys, transfer into rats resulted in good growth and development; however, worms which developed initially in exposed mice or guinea pigs developed less well in the rat. Conversely, worms which developed initially in permissive host such as the rat, when transferred into a variety of less permissive hosts such as the guinea pig and rabbit, apparently did not survive and caused significant morbidity and mortality within the nonpermissive host. Histopathologic evaluation revealed a strong eosinophilic perivascular and peribronchiolar infiltration as well as granulomatous reactions surrounding the worms in the lungs of recipient guinea pigs and rabbits, changes not observed in the lungs of permissive rat recipients. As reaginic antibody responses were also more prominent in nonpermissive than in permissive animals, it is possible that IgE responses may be more directly related to the phenomenon of morbidity and/or permissiveness than are other aspects of immune response. In support of this contention was the finding of nearly equivalent hemagglutinating antibody production between permissive rats and nonpermissive guinea pigs and rabbits.     

Intraepithelial infiltration of eosinophils and their contribution to the elimination of adult intestinal nematode,Strongyloides venezuelensis in mice

Eosinophils were examined for the capacity of attacking Strongyloides venezuelensis adult worms in the intestinal mucosa by using interleukin (IL)-5 transgenic mice. In IL-5 transgenic mice, most of the subcutaneously inoculated infective larvae were killed during migration, and only a few worms could reach the small intestine. When the same number of adult worms were surgically implanted in the small intestine of IL-5 transgenic and control mice, fecal egg output as well as the number of adult worms recovered from the intestine was significantly lower in IL-5 transgenic mice. In the intestinal mucosa of IL-5 transgenic mice, large number of eosinophils was present in the lamina propria even before adult worm implantation. The number of eosinophils increased significantly as early as 24 h after implantation and tripled by day 3, whereas mucosal eosinophilia remained low in wild-type mice. Most notably, eosinophils infiltrated into the intestinal epithelium and surrounded adult worms in IL-5 transgenic mice, which was never seen in wild-type control mice. However, IL-5 transgenic mice required the same period as normal mice to completely expel implanted adult worms. The amount of specific IgA as well as total IgA in the stool was high in IL-5 transgenic mice before adult worm implantation, and dropped rapidly after adult worm implantation. The present study suggests that eosinophils are capable of attacking adult nematodes in the intestinal epithelia, probably in conjunction with secretory IgA, although they are not enough for the complete worm expulsion.     

Natural death of adult Onchocerca volvulus and filaricidal effects of doxycycline induce local FOXP3+/CD4+ regulatory T cells and granzyme expression

Immunosuppression in human filarial disease involves regulatory T cells. We hypothesized that natural or worm antigen-induced FOXP3 regulatory T cells could be involved locally, suppressing effector cells via granzymes. Natural and treatment-induced death of worms implies enhanced exposure to worm antigens. Therefore, we examined FOXP3+T cells and granzyme expression in onchocercomas harbouring adult Onchocerca volvulus worms, with respect to worm viability, productivity, the patient's immune status and filaricidal treatment. The immunohistological analysis revealed that dead adult worms were strongly associated with FOXP3+T cells in generalized hyporeactive onchocerciasis. FOXP3+ cells hardly expressed granzymes, but cell contacts with granzyme A+ or B+ cells were frequent. While suramin directly kills most adult worms within 6 months, the Wolbachia depleting antibiotic doxycycline indirectly causes adult worm degeneration within 18 months. Contrary to suramin, depletion of Th1-driving endobacteria most strongly promoted FOXP3+T cells and granzyme-expressing cells. In hyperreactive patients, FOXP3+ cells were less frequent. This is the first demonstration of local FOXP3+Treg cells in human filariasis and their induction by natural worm death and anti-parasitic treatment. We newly report granzyme responses to helminths and their association with immunosuppression. FOXP3+Treg and granzyme+ cells might locally suppress defence against newly acquired worms.     

Growth performance, carcass characteristics and bioavailability of isoflavones in pigs fed soy bean based diets

A growth trial with 38 weaners (castrated male pigs) was designed to compare the growth performance and carcass quality of pigs fed diets containing either soy bean meal or soy protein concentrate in a pair-feeding design. Soy bean meal (SBM) and soy protein concentrate (SPC) differed in isoflavone (daidzein plus genistein) content (782 microg/g in SBM and 125 microg/g in SPC, respectively). During the experiment, all pigs were fed four-phases-diets characterized by decreasing protein concentrations with increasing age (weaner I, weaner II, grower, finisher diets). Rations of control and experimental groups were isoenergetic, isonitrogenous, and isoaminogen. The weanling pigs with an initial live weight of 8.4 +/- 1.1 kg were allotted to flat deck boxes. During the growing/finishing period (days 70-170 of age), the pigs were housed in single boxes. Both, the weaning and the grower/finishing performances (daily body weight gain, feed intake, feed conversion ratio) were similar in both groups. No differences were found between the groups in carcass composition (percentages of cuts, tissues, and protein/fat), and meat quality of pigs. Moreover, the IGF-1R mRNA expression in longissimus muscle was not influenced by the kind of soy product. However, circulating levels of isoflavones were clearly different between pigs fed SBM (genistein 239 +/- 44; daidzein 162 +/- 42; equol 12 +/- 4 ng/ml plasma) and animals fed SPC (genistein 22 +/- 9 and daidzein 8 +/- 3, and equol 10 +/- 3 ng/ml plasma). The results confirm the expected differences in the bioavailability of soy isoflavones, yet, there were no significant differences in performance of pigs fed either soy bean meal or soy protein concentrate.     

Partial cross-resistance between Strongyloides venezuelensis and Nippostrongylus brasiliensis in rats.

Rats were immunized through an initial infection with 1,000 filariform larvae (L3) of Nippostrongylus brasiliensis and after complete expulsion of worms they were challenged with 1,000 L3 of Strongyloides venezuelensis to investigate whether cross-resistance developed against a heterologous parasite. Nippostrongylus brasiliensis-immunized rats developed a partial cross-resistance against S. venezuelensis migrating larvae (MSL3) in the lungs and adult worms in the small intestine. The population of MSL3 in the lungs were significantly lower (P < 0.05) in immunized rats (22.0 +/- 7.4) compared with controls (105.0 +/- 27.6). The populations of adult worms, egg output and fecundity were initially decreased but from day 14 post-challenge they did not show any significant difference between immunized and control rats. However, the length of worm in immunized rat was revealed as retardation. Peripheral blood eosinophilia was significantly decreased (P < 0.05) on day 7 post-challenge and then gradually increased, which peaked on day 42 post-challenge when most of the worms were expelled. These results suggest that peripheral blood eosinophilia is strongly involved in the worm establishment and expulsion mechanisms.     

Growth performance,carcass characteristics and bioavailability of isoflavones in pigs fed soy bean based diets

A growth trial with 38 weaners (castrated male pigs) was designed to compare the growth performance and carcass quality of pigs fed diets containing either soy bean meal or soy protein concentrate in a pair-feeding design. Soy bean meal (SBM) and soy protein concentrate (SPC) differed in isoflavone (daidzein plus genistein) content (782?μg/g in SBM and 125?μg/g in SPC, respectively). During the experiment, all pigs were fed four-phases-diets characterized by decreasing protein concentrations with increasing age (weaner I, weaner II, grower, finisher diets). Rations of control and experimental groups were isoenergetic, isonitrogenous, and isoaminogen. The weanling pigs with an initial live weight of 8.4?±?1.1?kg were allotted to flat deck boxes. During the growing/finishing period (days 70?–?170 of age), the pigs were housed in single boxes. Both, the weaning and the grower/finishing performances (daily body weight gain, feed intake, feed conversion ratio) were similar in both groups. No differences were found between the groups in carcass composition (percentages of cuts, tissues, and protein/fat), and meat quality of pigs. Moreover, the IGF-1R mRNA expression in longissimus muscle was not influenced by the kind of soy product. However, circulating levels of isoflavones were clearly different between pigs fed SBM (genistein 239?±?44; daidzein 162?±?42; equol 12?±?4?ng/ml plasma) and animals fed SPC (genistein 22?±?9 and daidzein 8?±?3, and equol 10?±?3?ng/ml plasma). The results confirm the expected differences in the bioavailability of soy isoflavones, yet, there were no significant differences in performance of pigs fed either soy bean meal or soy protein concentrate.     

Effects of spleen cells and serum on transfer of immunity to Strongyloides venezuelensis infection in hypothymic (nude) mice

The course of Strongyloides venezuelensis infection in congenitally hypothymic (nu/nu) mice and their heterozygous thymus-bearing littermates (nu/+) was followed. Unlike the infected nu/+ mice, the nu/nu mice were unable to expel the worms until the end of the observation period (98 days post-infection). In addition, about three times as many eggs were counted at the peak level of infection in faeces of the infected nu/nu mice in comparison with the nu/+ mice. No acquired resistance to rechallenge was observed among the nu/nu mice. Auto-reinfection within the infected nu/nu mice could not be supposed in the present study. The worm expulsion mechanism was generated by nu/nu mice which had been given syngeneic spleen cells from intact +/+ mice. The expulsion of adult worms, as well as the protection against migrating larvae, occurred anamnestically when spleen cells from immune +/+ mice were transferred. The serum transfer, however, only caused a retardation of larval migration. The results support the hypothesis that direct worm immunity and worm expulsion are a T cell-dependent phenomenon.     

Nematospiroides dubius: arrested development of larvae in immune mice.

When immune NIH mice were killed 10 days after a challenge infection with Nematospiroides dubius, approximately 10% of the inoculated larvae were recovered from the intestinal lumen, irrespective of the dose administered. When such mice were treated with cortisone from Day 10 for a period of 8 to 14 days and were subsequently killed for worm counts, it was found that they had significantly more worms than the immune control mice killed on Day 10. During the week following the beginning of treatment with cortisone there was little change in the low worm burdens in immune mice. However, 9 to 11 days after this treatment worm counts indicated that worms were accumulating in the intestinal lumen, and concurrently eggs were recorded in the feces of the mice. These observations indicated that a period of 9 to 11 days was required after the initiation of cortisone treatment on Day 10 for the worms in immune mice to complete their development to the adult lumen-dwelling stage. It is suggested that the larvae in the challenge infection became arrested early in their development in the intestinal wall and that growth resumed only after cortisone treatment. When treatment with cortisone was initiated later after challenge, it was still effective in reactivating arrested worms, but the lower worm recoveries in these mice indicated that the arrested larvae were being slowly rejected by the host. In subsequent experiments it was established that the arrested larvae of N. dubius were insusceptible to the activity of pyrantel embonate, an anthelmintic which is 99% effective against adult worms in the intestinal lumen. The mechanism whereby the larvae of N. dubius became arrested in immune mice and subsequently resumed their development after cortisone treatment is discussed.