Hymenolepis diminuta: The origin of protective antigens

Mice were infected orally with 1,6, or 30 cysticercoids of Hymenolepis diminuta. These were allowed to develop for different periods of time before elimination with anthelminthic, thus exposing the hosts to antigens from the prestrobilate, early strobilate, or fully strobilate worms. Other groups of mice were immunized by intraperitoneal (ip) implantation of a live strobilate worm or by ip implantation of live worms from cysticercoids excysted in vitro. Strong protection against challenge with a surgically transplanted strobilate worm was achieved by prior infection with 6 or 30 worms eliminated as early as Day 3 of infection. By this time these worms would not have strobilated. Conversely, a single worm, strobilating extensively over 16 days, stimulated only weak protection. Parenteral implantation of excysted worms protected mice but parenteral implantation of a strobilate worm had no effect. It is suggested that (i) the tapeworm protective antigens are primarily related to the scolex and/or the germinative region; (ii) the number of worms and the duration of antigenic stimulation in an immunizing infection determine the magnitude of a protective secondary response.     

Course of heavy primary infections and earlier immunologically mediated rejection of secondary infections of Hymenolepis diminuta in mice

Roepstorff A. and Andreassen J. 1982. Course of heavy primary infections and earlier immunologically mediated rejection of secondary infections of Hymenolepis diminuta in mice. International Journal for Parasitology12: 23–28. The worms of heavy (50–100 worms) primary Hymenolepis diminuta infections in inbred C57-mice were 1–2 mm long when growth ceased about day 4. Thereafter the mean length decreased by shrinkage and/or ‘decollation’, the worms moved backwards in the small intestine and were rejected from day 6 to day 10. Heavy secondary infections given 14 days after a heavy primary infection were severely stunted (0.2–0.3 mm) but normally situated in the intestine on day 2 and nearly all were rejected by day 4. Even when the time between the primary and secondary infections was increased to 21 or 42 days, therecovery, position and length of the secondary worms were significantly different from primary infections. These results show that an immunologically mediated memory was involved, and that functional antigens can be released from the scolex and/or the neck alone.     

The frequency distribution of Hymenolepis diminuta cysticercoids in natural,sympatric populations of Tenebrio molitor and T. obscurus

Rau M. E. 1979. The frequency distribution of Hymenolepis diminuta cysticercoids in natural, sympatric populations of Tenebrio molitor and T. obscurus. International Journal for Parasitology9: 85–87. Natural, sympatric populations of Tenebrio molitor and T. obscurus were examined for cysticercoids of Hymemlepis diminuta. The distribution of cysticeroids in both species and both sexes conformed to the negative binomial. Cysticeroids were more prevalent and the mean intensity of infection was higher in T. obscurus than in T. molitor. No differences in the intensity of infection were detected between the sexes. Larvae of both beetle species were always very lightly infected. The significance of these factors in the transmission of the infection to the rat definitive host is discussed.     

Hymenolepis diminuta (Cestoda): Effects of parasite density and temperature on the water balance of Tenebrio molitor and subsequent infectivity of the cysticercoids

The effects of the density of Hymenolepis diminuta and the effects of thermal acclimation on the water balance of Tenebrio molitor were examined. Also, the subsequent infectivity of the cysticercoids for rats were investigated. T. molitor beetles were fed known numbers of H. diminuta eggs and then were kept at 15° or 25°C for 14 days. After 14 days, beetles were desiccated and water loss was determined. Parasite density did not significantly affect transpiratory water loss in T. molitor kept at 15° or 25°C following 24 or 48 hr of desiccation. However, after 72 hr of desiccation, beetles maintained at 15°C evidently could not regulate water efficiently since there was a significant increase in the transpiratory water loss as parasite density increased. Beetles acclimated at 15°C produced fewer cysticercoids than did beetles maintained at 25°C. Also, fewer adult worms were recovered from rats intubated with cysticercoids from heavily infected, 15°C-acclimated beetles. Apparently, heavily infected beetles acclimated to 15°C do not produce viable cysticercoids.     

Immunity to tapeworms: acquired resistance to Hymenolepis citelli in the mouse

The dynamics of secondary infections with Hymenolepis citelli in mice are described. A primary infection of one and six cysticercoids for 21 days sensitized CFLP male mice against homologous challenge infections. Acquired resistance was manifested mainly as stunting/destrobilation of secondary worms. The severity of stunting depended on the intensity of the primary infection. Secondary worms were not expelled more rapidly than primary worms but the protective response retards growth early in challenge infections. Sensitization of mice for seven days with six or 24 cysticercoids did not confer a measurable protective response, whereas priming by the same regime for 21 days induced a significant protective response. Acquired resistance to challenge waned with time in the absence of the primary worms. The growth and survival of a six-cysticercoid primary infection was enhanced by the administration of the immunosuppressant drug cortisone acetate. Worms from cortisone-treated mice were heavier than those from untreated controls. Acquired resistance to homologous challenge was also partially ablated in cortisone-treated mice. It is suggested that rejection of primary infections and stunting/destrobilation of secondary worms may be immunologically mediated.     

Reduced fecundity of Hymenolepis nana due to thymus-dependent immunological responses in mice

Reduced fecundity of Hymenolepis nana due to thymus-dependent immunological responses in mice. International Journal for Parasitology16: 81–85. The fecundity of the dwarf tapeworm, Hymenolepis nana, was enhanced in congenitally athymic nude CD-1 (ICR) mice but depressed to the same degree as in phenotypically normal littermates when they were reconstituted with thymocytes before infection. The reduction in fecundity of this parasite was clear only when H. nana were recovered from those strains of mice which demonstrate a “late response” against luminal cysticercoid challenge before the established worms become fully mature (within 15 days of initial immunizing egg inoculation). The fecundity of H. nana in dd mice, which acquire the late response within 30–40 days, was greatly advanced than that in BALB/c or CD-1 (ICR) mice and somewhat better than even that in the nude CD-1 (ICR) mice and appeared to be little, or not at all, depressed. The fecundity and longevity of this parasite, highly variable among mouse strains, is discussed in terms of variations in the rapidity of expression of protective immunity against the lumen phase.     

Intestinal immunity suppresses carrying capacity of rats for the model tapeworm, Hymenolepis diminuta

Hymenolepis diminuta is a parasitic tapeworm of the rat small intestine and is recognized as a useful model for the analysis of cestode-host interactions. In this study, we analyzed factors affecting the biomass of the tapeworm through use of rat strains carrying genetic mutations, namely X-linked severe combined immunodeficiency (xscid; T, B and NK cells deficiency), nude (rnu; T cell deficiency), and mast cell deficient rats. The worm biomass of F344-xscid rats after infection with 5 cysticercoids was much larger than control F344 rats from 3 to 8?weeks. The biomass of F344-rnu rats was also larger than the controls, but was intermediate between F344-xscid and control rats. These observations demonstrated that host immunity can control the maximal tapeworm biomass, i.e., carrying capacity, of the rat small intestine. Both T cell and other immune cells (B and NK cells) have roles in determining the carrying capacity of tapeworms. Total worm biomass and worm numbers in mast cell deficient rats (WsRC-Ws/Ws) were not significantly different from control WsRC-+/+ rats after 3 and 6?weeks of primary infection. Mast cell deficient rats displayed reinfection resistance for worm biomass but not worm expulsion. These findings suggest that the mast cell has a role for controlling the biomass of this tapeworm in reinfection alone, but does not affect the rate of worm expulsion. Overall, our findings indicate that the mast cell is not a major effector cell for the control of the carrying capacity of tapeworms. The identity of the major effector cell remains unknown.     

Immunological aspects in the rejection process of Hymenolepis muris-sylvaticae from CFLP and NMRI mice

When mice were treated with 1.25 mg cortisone acetate thrice weekly, recovery of Hymenolepis muris-sylvaticae was significantly higher than in untreated controls, both in oral infections with six cysticercoids and surgical transplantations of one 7-day or 8-day-old worm. Cortisone treatment also resulted in the worms being located more anteriorly in the small intestine. Evidence of an immunological response against the tapeworm in the intestine is given by: an accelerated rejection of a secondary oral cysticercoid infection and a significant difference of the dry weights of the worms recovered on day 10 in CFLP mice; an accelerated rejection of a secondary surgical infection on days 4 and 6 in CFLP mice and on days 3 and 4 in NMRI mice; an accelerated rejection of a secondary surgical infection given 3 and 6 months after the primary immunizing infection in SWISS-albino mice.     

The role of serine in the lipid metabolism of the rat tapeworm Hymenolepisdiminuta

Webb R. A. and Mettrick D. F. 1973. The role of serine in the lipid metabolism of the rat tapeworm Hymenolepis diminuta. International Journal for Parasitology3: 47–58. The inter-relationship between the amino acid serine and lipid metabolism in the rat tapeworm Hymenolepis diminuta has been studied under in vitro conditions. The label from U-¹⁴C-serine, U-¹⁴C-glucose and 1-¹⁴C-oleic acid was rapidly incorporated into worm tissue phospho- and glycolipids, the latter illustrating the synthesis of cerebrosides by H. diminuta. Activity from U-¹⁴C-serine was recovered in phosphatidylserine, phosphatidylethanolamine, cerebrosides and several unidentified lipid-like compounds. The majority of the label recovered in phosphatidylethanolamine was associated with the ethanolamine moiety; in the cerebrosides with the sphingosine moiety. The sugar moiety of the cerebrosides was galactose.Pulse label studies showed a serine flux phenomenon, and a rapid rate of turnover of some of the unidentified compounds.Exogenous ethanolamine had no detectable effect upon absorption and conversion of serine to tissue phosphatidylethanolamine. Incubation of H. diminuta homogenates with phosphatidyl U-¹⁴C-serine resulted in the recovery of considerable activity in phosphatidylethanolamine. The results show that the major pathway of phosphatidylethanolamine synthesis is by decarboxylation of phosphatidylserine.     

Immunosuppressive activity in serum from mice infected with Nematospiroides dubius following passive serum transfer

Dobson C. and Cayzer C. J. R. 1982. Immunosuppressive activity in serum from mice infected with Nematospiroides dubius following passive serum transfer. International Journal for Parasitology12: 561–566. Anti-N. dubius antibody titres increased with time after primary and secondary infections with 100 larvae in mice and 4 days after anthelmintic termination of a 28 day infection. Mice injected with serum from infected mice harboured fewer, smaller worms with reduced fecundities compared with control mice; the difference was greater with serum from donors given two compared with those given one infection.Mice injected with serum from donors infected for 14 days had fewer N. dubius than recipients of serum from mice infected for 28 days. Serum taken from mice 4 days after termination of a primary infection of 28 days duration was more protective when passively transferred to mice than serum from mice infected for 28 days. Serum from mice infected with 50 N. dubius larvae was more protective than serum, with a higher anti-N. dubius antibody titre, from, mice infected with 400 larvae. These observations are discussed in relation to immunosuppressive activities in the donated serum and associated with N. dubius.     

Kinetics of primary and secondary infections with Strongyloides ratti in mice

Dawkins H. J. S. and Grove D. I. 1981 Kinetics of primary and secondary infections with Strongyloides ratti in mice. International journal for Parasitology11: 89–96. The kinetics of infection with S. ratti were quantitated in normal and previously exposed C57B1 /6 mice. In primary infections, larvae penetrated the skin rapidly and were seen in peak numbers 12 h after infection. By 24 h after infection, larval numbers had declined appreciably and there was a slow decrease in numbers thereafter. Larvae were first observed in the lungs at 24 h and maximal recovery occurred at 48 h. It is thought that larval migration through the lungs is rapid. Worms were first seen in the intestines two days after infection. Maximum numbers were seen on the fifth day and worm expulsion was complete by day 10. Two moults took place in the small intestine during days 3 and 4 after infection. Rhabditiform larvae were first noted on the fourth day after infection. Mice exposed to S. ratti four weeks previously had significantly less larvae in the skin 4 and 12 h after infection but by 24 h there was no difference when compared with mice with primary infections. Peak recovery of larvae from the lungs occurred 24 h after infection; significantly less larvae were recovered on days 2 and 3 when compared with normal mice. There was a marked reduction in the adult worm burden in the gut; the number of worms recovered was less than one fifth of that seen in primary infections. Those worms which did mature were less fecund and were expelled from the intestines within 7 days of infection. It is suggested that in previously exposed animals, the migration of larvae from the skin is hastened, many of these larvae are destroyed in the lungs and that expulsion of worms which do mature in the intestines is accelerated.     

Hymenolepis microstoma: direct life cycle in immunodeficient mice

The mouse bile duct tapeworm Hymenolepis microstoma requires beetles as the obligatory intermediate host. However, when congenitally athymic NMRI-nu mice were infected with the mature tapeworm and allowed to eat their own faeces with tapeworm eggs, the oncospheres penetrated the intestinal tissue and developed to cysticercoids. After excysting, growth to adult worms occurs in the lumen of the small intestine and bile duct. Furthermore, the same happened when NMRI-nu mice, non-obese diabetic severe combined immunodeficiency (NOD/Shi-scid) mice and NOD/Shi-scid, IL-2 Rgamma(null) (NOG) mice were orally inoculated with shell-free eggs of this parasite. Differences between the cysticercoids of H. microstoma and H. nana developed in the mouse intestinal tissues were: (i) the time course for the development of fully matured cysticercoids of H. microstoma in mice was about 11 days but only 4 days for H. nana; and (ii) cysticercoids of H. microstoma developed in mice had a tail while those of H. nana had none.     

Some influences of population density on Hymenolepis diminuta in rats.

When measured 56 days postinfection the length, wet weight and dry weight of Hymenolepis diminuta were all found to decrease with increasing number of cysticercoids given up to 20. The mean position of the worms in 10, 12 and 20 worm infections is significantly posterior to that of 1, 2 and 5 worm infections and the worms are attached over a wider area of the intestine. Egg production by the worms was followed up to day 56 postinfection; the number of eggs produced per worm and even per rat decreased with increasing population density. Thus the best way to get most eggs and to maintain the parasite in the laboratory is to have rats infected with only one tapeworm. Rats given 1-20 cysticercoids showed a mean recovery of 100-65%, while rats given 40-200 cysticercoids showed a mean recovery ranging from 13 to 2%. In addition to 'normal' worms, defined as worms greater than 10 mm, small, most probably destrobilated, worms were found. In the 50 and 100 cysticercoid infections, worm recoveries were, respectively, 8% 'normal', 16% small, and 2% 'normal', 5% small. From the significantly lower recovery from heavy infections it is concluded that a deleterious factor is operating during the 8 weeks after the infection.     

Influence of primary infection on the population dynamics of Nematospiroides dubius after challenge infections in mice

Dobson C., Sitepu P. and Brindley P. J. 1985. Influence of primary infection on the population dynamics of Nematospiroides dubius after challenge infections in mice. International Journal for Parasitology15: 353–359. Similar proportions of the inoculum of Nematospiroides dubius larvae reached sexual maturity by 14 days after administration of 50–400 larvae but more adult worms had been expelled by day 63 after infection from those mice infected with 50 vs 400 larvae. There was a significant correlation between time and worm expulsion for all inoculum size groups except for mice given 400 larvae.In mice reinfected with 100 larvae, after termination of primary infections derived from 10 through 400 larvae, more worms from the challenging dose were recovered from mice given greater compared with those given smaller numbers of larvae at primary infection. The N. dubius population size after challenge infection was correlated positively both with number of larvae administered as the primary infection and with the resultant population size during that infection. The serum anti-N. dubius antibody titres after reinfection were higher in mice given 400 compared with those given fewer larvae at primary infection, and the fecundity and female to male sex ratio of the N. dubius populations decreased in proportion to these antibody titres.Protective immunity against challenge N. dubius infection, in mice which had been drenched free of adult worms established from 400 larvae for 5 down to 1 weeks before reinfection, increased from 45% (1 week) to 80% (5 weeks). There was a negative correlation between the population size of N. dubius during challenge infection and the duration between anthelmintic treatment and challenge infection.     

Nematospiroides dubius in mice selected for liability to infection: Modification of parasite biology through host selection

Brindley P. J. and Dobson C. 1982. Nematospiroides dubius in mice selected for liability to infection: modification of parasite biology through host selection. International Journal for Parasitology12: 573–578. Mice selected as liable (L) and refractory (R) over ten generations voided significantly more and less Nematospiroides dubius eggs compared with randomly mated (Rd) mice after primary infections with 100 larvae. There was little difference between the number of parasite eggs voided g^?1 faeces (epg) by individual mice on day 14 compared with day 15 after infection.However there was a significant diurnal variation in the egg values for individual mice but the mean differences observed between the R, Rd and L mice were maintained over a 24 h period. There was a strong correlation between both the total number and the number of female worms, surviving 21 days after infection, and the mean epg 14 and 15 days after infection. Female N. dubius produced more eggs in L mice and fewer eggs in R mice compared with worms in Rd mice. Similarly, worms grew longer in L mice and were shorter in R mice compared with parasites in Rd mice.     

Strongyloides ratti: reversibility of immune damage to adult worms

Transplantation experiments were conducted to assess the reversibility or irreversibility of the damage sustained by Strongyloides ratti during infections in the rat host. Worms of different ages from primary and secondary infections were recovered from their original hosts and transplanted surgically into naive rats. The size and fecundity of normal (Days 6–11 postinfection) worms were maintained after transfer. Damaged worms from primary infection (Days 22–26) showed complete recovery of size and fecundity within 10 days of transfer; damaged worms from a secondary infection (Days 6–7) also showed functional recovery but to a lesser extent. The ultrastructural changes observed mainly in the intestine of damaged worms from primary infections, prior to their transfer, were, however, only partially ameliorated following transplantation into new naive hosts; there was no complete return to structural normality. On the other hand, second infection worms did show almost complete ultrastructural recovery. The course of a transplanted infection established with either damaged or normal worms was similar to infections established percutaneously. Increase in the size of transplanted infections from 100 to 250 worms per recipient did not alter the dynamics of the host/parasite relationship. There was no evidence of adaptation in S. ratti and damaged worms, when transplanted into naive rats, were as successful as normal worms in protecting the host against a subcutaneous larval infection. The implications of this work on the present understanding of the phenomenon of autoinfection in experimental rodent strongyloidiasis are discussed.     

Enhanced resistance to infection with Haemonchus contortus in sheep treated with a corticosteroid

Adams D. B. and Davies H. I. 1982. Enhanced resistance to infection with Haemonchus contortus in sheep treated with a corticosteroid. International Journal for Parasitology12: 523–529. Fewer worms established from experimental infections with Haemonchus contortus in either immune or naive sheep or in sheep of undefined immune status given the corticosteroid, dexamethasone, around the time of challenge. In four experiments, the number of adult worms present in sheep treated with dexamethasone ranged from 32 to 36% of that in untreated animals. That the phenomenon did not stem from direct action of dexamethasone on the worms themselves was demonstrated by comparing continuous treatment with the drug from infection until patency with treatment given at infection and four days later. Sheep continuously treated with dexamethasone harboured similar numbers of worms as the infection controls whereas fewer parasites were found in sheep given dexamethasone around the time of infection. The results imply that active regulation of immunological unresponsiveness operates in sheep during infection with H. contortus and that disruption of immunoregulation by dexamethasone released protective responses thereby decreasing worm burdens. Because suppressor lymphocytes are implicated, cellular perturbations following treatment with dexamethasone were investigated. Dexamethasone did not cause marked lymphopenia. It, however, reduced blastogenic responses by lymphocytes to con A but not PHA. Comparison of responses to these mitogens in cells from blood and lymph demonstrates that con A and PHA-reactivity resides in identifiably different cell populations in sheep.     

Hymenolepis diminuta: lack of pathogenicity in the healthy rat host.

Whether Hymenolepis diminuta (Cestoda: Cyclophyllidea) might affect adversely the growth of its host under normal conditions was studied. Rats were divided into four experimental groups: (1) rats infected with the tapeworm and fed ad libitum, (2) uninfected rats fed ad libitum, (3) and infected rats fed isocalorically with (4) uninfected rats. Growth rates of infected rats did not differ from infected animals. Infected, meal fed rats limited to 15 g synthetic diet/day grew as rapidly as their uninfected counterparts, and infected rats fed ad libitum did not consume more food than the comparable infected group. There were no significant differences in consumption or in excrement produced between groups (1) and (2) and groups (3) and (4). Weights attained by the worms were not affected by mode of host feeding (ad libitum or meal fed), whether expressed as wet or dry weight. Since H. diminuta appears not to affect nutrient utilization or consumption in a healthy, unstressed host, at least on a gross level, it probably should be considered an endocommensal.     

Immunologic studies on Heligmosomoides polygyrus infection in the mouse: the dynamics of single and multiple infections and the effect of DDT upon acquired resistance

Neilson J.T. McL., Forrester D.J. and Thompson N.P. 1973. Immunologic studies on Heligmosomoides polygyrus infection in the mouse: The dynamics of single and multiple infections and the effect of DDT upon acquired resistance. International Journal for Parasitology3: 371–378. Swiss Webster mice were given infections of 100,200, 300 and 400 Heligmosomoides polygyrus (= Nematospiroides dubius) larvae respectively at intervals of 4 weeks. Where appropriate, the preceding infection was terminated with anthelmintic 7 days prior to the subsequent infection. Animals were killed at regular inteivals following each infection and the worm burdens compared with those found in control mice given a primary infection of similar size. The expulsion of worms in mice given three previous infections occurred after day 3 and before day 7 postinfection indicating that those larvae moulting from the fourth to fifth stages may be most susceptible to the host's resistance mechanisms. The administration of p,p'-DDT to hyperinfected mice did not interfere with the immunologic expulsion of worms.