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.     

Further studies on the effect of cyclosporin A on the course of Paragonimus infection in rats

Paragonimus ohirai-infected rats were treated with cyclosporin A (CyA) at different times during the course of infection. CyA (5 x 80 mg/kg) affected the worm recovery, growth and maturation rates of P. ohirai with respect to control values. This tendency was most remarkable in animals treated 15 days and more after infection with CyA (groups B, +15 to +19 days; C, +25 to +29; D, +35 to +39 and E, +45 to +49). In group A (0 to +4), however, the drug did not affect markedly the growth and maturation of worms, although it significantly lowered worm recovery rates. CyA administration also affected normal migration of P. ohirai in the highly susceptible host (rat), when the drug was administered during the peritoneal and/or liver phase of infection. Thus, in this P. ohirai/rat model, CyA significantly reduced worm recovery rates, and affected the growth, maturation and migration of the worms depending on the time of administration.     

Antifilarial activity of intravenous suramin and oral diethylcarbamazine citrate on subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata

The known filaricides, suramin and diethylcarbamazine citrate, were tested against subperiodic Brugia malayi infection in the leaf-monkey, Presbytis cristata. As expected, intravenous suramin at 10 mg/kg daily x 5 days or 17 mg/kg weekly x 5 weeks, did not show any microfilaricidal activity, but substantially reduced the recovery of live adult worms to 50.6% and 13.6% of controls respectively. Oral diethylcarbamazine citrate at 6 mg/kg daily x 6 or 10 days reduced final microfilarial counts to 30% of initial counts four weeks post-treatment and adult worm recovery was reduced to 4.5% and 0% of controls respectively. Although the antifilarial activity of these drugs against the infection in this non-human primate model appears to be similar to that seen in man, these results have to be confirmed using larger groups of animals.     

Effects of praziquantel and oxamniquine on a Saudi Arabian strain of Schistosoma mansoni in mice

The prophylactic and curative effects of praziquantel and oxamniquine on a Saudi Arabian strain of Schistosoma mansoni in MF-1 mice were assessed. The drugs were administered orally. At 240 mg/kg praziquantel, there was a reduction of 89.1% in adult worm recovery and a marked reduction in tissue deposited eggs. The reduction in adult worm recovery after dosing with 50 mg/kg oxamniquine was 89.2%. At low doses (40 mg/kg praziquantel and 30 mg/kg oxamniquine) administered at 11 days, 5 days and 3 h before and 5, 21 and 49 days after infection, the reduction in adult worm recovery was 0.0%, 65.1%, 58.8%, 33.6%, 0.0% and 76.0% for praziquantel and 0.0%, 66.0%, 60.0%, 41.3%, 10.8% and 79.0% for oxamniquine. Numbers of lung schistosomula and the size of hepatic granulomata were also reduced.     

Increased susceptibility of lead exposed chickens to experimental infection of Ascaridia galli

Two sets of one day old, white leghorn (Victoria Strain) chickens were each orally exposed to 1.0 mg lead nitrate daily for 7 days and subsequently infected with 15 and 30 A. galli eggs. These experimental chickens exposed to lead harboured significantly greater worm burden when compared to unexposed controls leading strong support to the view that lead exposure significantly suppressed their immune response to A. galli infection. It also indicated that exposure of lead prior to infection greatly impaired weakened the immune capability of such chickens.     

Validation of sensitivity to praziquantel using Schistosoma mansoni worm muscle tension and Ca2+-uptake as possible in vitro correlates to in vivo ED50 determination

Schistosome worm muscle tension and [45Ca2+]-uptake were tested as possible correlates of susceptibility to praziquantel (PZQ) assessed by estimating the drug ED50. Schistosoma mansoni cercariae of PZQ sensitive (S-CD, S-MOC and S-GP) and insensitive S. mansoni isolates (I-EE2, I-BANL and I-Senegal 47) were used to infect batches of CD-1 Swiss albino mice. Seven weeks after infection, animals of each batch were divided into six groups. Five of them received PZQ in doses of 12.5, 25, 50, 100 or 200 mg/kg PZQ, respectively, for five consecutive days, while the sixth was left as untreated controls. Two weeks after treatment mice were sacrificed, perfused and PZQ ED50's were estimated. Male worms recovered from infected untreated controls were examined for their muscle tension increase in response to PZQ using a physiological recorder coupled to a photooptic transducer. [45Ca2+]-uptake of male worms in the presence and absence of PZQ was determined using a liquid scintillation beta counter. Data revealed that PZQ insensitive isolates had significantly higher drug ED50 (>130 mg/kg) than PZQ sensitive isolates with ED50's <100 mg/kg. Moreover, in response to PZQ they were found to possess significant reductions in their worm muscle tension and their [45Ca2+]-uptake were <100%. Both parameters showed a significant negative correlation to PZQ ED50 in vivo and a significant positive correlation to each other.     

Effects of a 100 metacercarial cyst inoculum on the host-parasite relationship of Echinostoma caproni and ICR mice

The host-parasite relationship of a 100 metacercarial cyst inoculum of Echinostoma caproni in the ICR mouse was examined. Three groups of mice, A, B and C, each with six mice per group were used and all mice were necropsied at 14 days postinfection (p.i.), at which time the worms were ovigerous. Group A consisted of uninfected controls, whereas group B received 25 cysts per mouse (low dose) and group C received 100 cysts per mouse (high dose). There was no significant difference in food consumption between any of the groups from 0 to 14 days p.i. Control mice increased their body weight by 12%, group B by 5%, and group C showed a less than 1% increase in body weight between 0 and 14 days p.i. Echinostome parasitism caused a significant increase in the diameter of the mouse gut, with the gut of group C being more significantly dilated than that of either group A or B. The average worm recovery from group B was 20 worms per host, compared to 72 worms per host from group C. The mean wet and dry weights per worm from group B were 2.4 and 0.4 mg, respectively as compared to 0.6 and 0.2 mg respectively for group C. The mean number of uterine eggs per worm from group B was 180 compared to 125 for worms from group C. Worms from group C were more widely distributed in the small intestine than those from group B. Crowding effects associated with the high dose infection were clearly demonstrated in E. caproni from ICR mice.     

Alteration in the endogenous intestinal flora of Swiss Webster mice by experimental Angiostrongylus costaricensis infection

The association between worm infections and bacterial diseases has only recently been emphasized. This study examined the effect of experimental Angiostrongylus costaricensis infection on endogenous intestinal flora of Swiss Webster mice. Eight mice aging six weeks were selected for this experiment. Four were infected with A. costaricensis and the other four were used as controls. Twenty eight days after the worm infection, all mice in both groups were sacrificed and samples of the contents of the ileum and colon were obtained and cultured for aerobic and anaerobic bacteria. In the mice infected with A. costaricensis there was a significant increase in the number of bacteria of the endogenous intestinal flora, accompanied by a decrease in the number of Peptostreptococcus spp. This alteration in the intestinal flora of mice infected by the nematode may help to understand some bacterial infections described in humans.     

Effects of concurrent infections on growth, development, distribution, and infectivity of adult Philophthalmus megalurus and Philophthalmus gralli

Chickens were infected concurrently with 10 and 20 metacercariae/eye of Philophthalmus megalurus and Philophthalmus gralli. After 14 and 34 days of growth, the adults were removed and worm lengths, return rates, stage of development, and distribution within the host recorded. In a second experiment, chickens infected on day 1 with 10 metacercariae/eye of P. megalurus were concurrently infected with a similar dose of P. gralli on day 14. At day 34, the worms were removed and evaluated for the same parameters as in the first study. The effect of concurrent infections on worm length of P. gralli but not P. megalurus was significant when compared to single species control groups. In all cases recovery rates of P. megalurus in concurrent infections were significantly lower than controls, whereas P. gralli adults were recovered at lower rates only in 20-metacercariae--14-day infections. Maturation of eggs was delayed in both species in concurrent infections at the higher infection levels. Normal distribution was disrupted more for P. gralli at the higher infection levels and longer growth periods. Philophthalmus megalurus adults rarely left their normal habitat in the conjunctival sac. A delayed infective dose of P. gralli affected both species by disrupting normal distribution patterns, delaying egg development, and, in the case of P. megalurus, reducing the recovery rate. The possible role of crowding and antagonistic effects is discussed.     

Effect of BCG on the resistance of rats to infection with Fasciola hepatica

The effects of three different doses of BCG, given at various periods before infection, on the subsequent establishment of Fasciola hepatica metacercariae were studied. Although evidence was found to suggest that rats which received BCG had mounted a cell mediated immune response, there were no significant differences in worm recovery between BCG-treated rats and controls. The significance of these results in the light of current knowledge on immunity to F. hepatica in rats is discussed.     

In vivo and in vitro egg production by Nematospiroides dubius during primary and challenge infections in resistant and susceptible strains of mice

Experiments were conducted to examine adult worm burdens, fecal egg output, and in vitro fecundity of Nematospiroides dubius in resistant LAF1 and susceptible CBA mice 12, 15, 18, and 21 days following primary and challenge infections. A strong correlation was obtained on the number of eggs produced by worms cultured in vitro and the egg production as assessed by fecal egg count. Worm counts, fecal egg counts, and in vitro fecundity were similar on all days studied following a primary infection in both mouse strains. However, after challenge infection, LAF1 mice showed lower worm burdens, fecal egg output, and in vitro egg production when compared to CBA mice. Although the egg production of surviving female worms from immune LAF1 mice was decreased, it never fell below a threshold of 100 eggs/day. The reduced fecundity may be a manifestation of a general anti-worm response rather than responses directed specifically at worm reproduction.     

Biochemical effects of thiabendazole and cambendazole on Hymenolepis diminuta (Cestoda) in vivo

An investigation of the chemotherapeutic and biochemical effects of two benzimidazole anthelmintics, thiabendazole (TBZ) and cambendazole (CBZ), on Hymenolepis diminuta in experimentally infected rats is reported. Thiabendazole was active against H. diminuta at a relatively high dosage. A single oral dose of TBZ at 250 mg/kg body weight on day 15 of infection eliminated 100% of the tapeworms as determined at necropsy 5 days after treatment. The chemotherapeutic actions of TBZ on H. diminuta were accompanied by marked changes in worm weight and chemical composition. Tapeworms recovered from rats that had received a therapeutically effective dose of TBZ 24 hr earlier were significantly smaller and contained much less glycogen (as a percent of the wet weight) than worms from unmedicated controls. Protein concentrations increased in TBZ-treated worms and at a rate sufficient to offset the decline in glycogen concentration. Glycogen/protein ratios in TBZ-treated worms were significantly lower than the corresponding control values. Cambendazole proved to be five times more potent than TBZ against H. diminuta and produced the same basic changes in worm weight and chemical composition within 18 hr of treatment of the host. Administration of a single oral dose of TBZ or CBZ to the host produced in H. diminuta another change, the onset of which coincided with, or preceded, the gross alterations in worm weight and chemical composition. That change, observed in in vitro studies carried out 14 hr after treatment, revealed that tapeworms from drug-treated rats absorbed and metabolized much smaller quantities of exogenous glucose than did the controls, and the ability of the worm to accumulate glucose against a concentration difference was significantly depressed.     

The mucosal cellular response to infection with Ancylostoma ceylanicum

Although hookworms are known to stimulate inflammatory responses in the intestinal mucosa of their hosts, there is little quantitative data on this aspect of infection. Here we report the results of experiments conducted in hamsters infected with Ancylostoma ceylanicum. Infection resulted in a marked increase in goblet cells in the intestinal mucosa, which was dependent on the number of adult worms present and was sustained as long as worms persisted (over 63 days) but returned to baseline levels within 7 days of the removal of worms by treatment with ivermectin. Increased mast cell responses were also recorded. Levels were again dependent on the intensity of worm burdens and lasted as long as 63 days after infection. When worms were eliminated, mast cell numbers took over 2 weeks to return to normal. Paneth cell numbers fell soon after infection, the degree of reduction being dependent on the worm burden. After clearance of worms, Paneth cell numbers returned to normal within a week, but then rebounded and numbers rose to higher levels than those in control na?ve animals. The time course of the response was similar whether animals experienced a chronic low-intensity infection without loss of worms or a higher intensity infection during the course of which worm burdens were gradually reduced. Clearly, A. ceylanicum was able to induce a marked inflammatory response in its host's intestine which was sustained for over 9 weeks after infection, and which hamsters appeared able to tolerate well. Our data draw attention to the resilience of hookworms which, unlike many other nematodes, are able to survive for many weeks in a highly inflamed intestinal tract.     

The mortality and fecundity of Haemonchus contortus in parasite-naive and parasite-exposed sheep following single experimental infections.

Parasite-exposed lambs and their parasite-naive controls were experimentally infected once only with 30,000 H. contortus larvae at 3, 9, 12, and 20 weeks following termination of a moderate immunizing infection of 30,000 H. contortus larvae. Previously exposed lambs, challenged at 3 weeks, had a significant reduction in the total H. contortus worm burden as compared to parasite-naive controls. No difference in the total H. contortus worm burden was found between parasite-exposed or parasite-naive lambs challenged at 9 weeks or thereafter. Female worms were found to be significantly smaller in lambs previously exposed to the parasite as compared to those found in parasite-naive lambs. The average parasite fecundity was 4700 eggs per female worm per day. Previous exposure of the lambs to the parasite had no effect on parasite fecundity. Various mathematical models were used to examine parasite fecundity. Parasite fecundity was found to increase in the initial post-challenge period reaching a constant value approximately 58 days after challenge infection. No density-dependent constraints on fecundity were observed.     

The effect of cyclosporin A on Angiostrongylus cantonensis infection and eosinophilia in mice

Male BALB/c mice were infected with Angiostrongylus cantonensis and at various times p.i. treated with cyclosporin A (CsA) either for 5 days continuously or intermittently, or for 12–16 days on alternate days. They were monitored for peripheral blood eosinophilia and at necropsy examined for CSF and bone marrow eosinophilia, and worm recovery. CsA treatment provoked a transient inhibition of peripheral blood eosinophilia in all groups examined, followed by rebounding eosinophilia. There was no significant difference in bone marrow and CSF eosinophilia between CsA- and vehicle-treated groups. Mice treated with CsA on alternate days yielded lower intracranial worm recovery with small-sized worms at days 7, 21 and 30 p.i. than vehicle-treated groups did. No significant reduction in worm recovery was noted in mice treated for 5 days either continuously or intermittently, although worms, especially female ones, harvested from groups treated with CsA from days — 1 to 3 or from days 13 to 17 were significantly smaller than those from vehicle-treated groups. CsA-treatment suppressed blastogenic responses of spleen cells against Con A or worm antigen at days 7 and 21 p.i. In vitro treatment of the 3rd stage larvae with CsA did not adversely influence survival of A. cantonensis in mice. These data indicate that CsA exerts antiparasitic effects against A. cantonensis in mice.     

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.     

Brugia pahangi: granulomatous lesion development in jirds following single and multiple infections

The development of adult worm burdens and microfilaremias were determined in jirds which received 2, 3, or 4 subcutaneous inoculations of 50 Brugia pahangi infective larvae. Parasite burdens in multiply inoculated jirds were compared to those in four different groups of jirds which received single inoculations of 50 infective larvae. One of each of these singly inoculated groups was infected on the same day that one of the inoculations was given to the multiply infected jirds. Thus, the duration of the infections in the four groups of jirds receiving one inoculation was 54, 118, 189, and 254 days. The development of lymphatic lesions and granulomatous hypersensitivity to B. pahangi antigen was assessed in all jirds at necropsy. The percentage recoveries of adult worms and their locations did not differ in the singly inoculated jirds with infections of different durations. A protective resistance to reinfection, as measured by adult worm recovery in multiply infected jirds, did not occur. The lymphatic lesion scores and numbers of intralymphatic thrombi was greatest in singly inoculated jirds examined 54 days after infection. Pulmonary granuloma areas around adult filarial antigen coated beads embolized in the lungs of jirds 3 days prior to necropsy were also greatest in singly inoculated jirds examined 54 days after infection. Using criteria of lesion scores and lymph thrombi numbers to assess lymphatic lesion severity, a decrease in lesion severity as well as pulmonary granuloma size around antigen coupled beads was seen by 118 days after infection in singly inoculated jirds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunity to Heligmosomoides polygyrus induced by subcutaneous vaccination with post-infection larvae

The objective of this study was to investigate, using the Heligmosomoides polygyrus (= Nematospiroides dubius)-mouse model, whether live post-infection trichostrongylid larvae recovered from the intestinal wall of donor animals and placed subcutaneously would serve as vaccine protecting against oral challenge by third-stage (infective) larvae (L3). Experiments were conducted to determine the effect of number and age of post-infective larvae as well as age and sex of host on vaccination. Vaccinated BALB/cByJ mice were challenged with 30 L3 and total adult worm burdens compared between vaccinated groups and sham-treated controls (greater than 90% infection rates). All mice subcutaneously vaccinated with either five or 10 larvae harbored significantly fewer challenge parasites in their intestines than did sham-treated controls (P less than 0.001). Both young and mature mice were significantly protected against challenge by the subcutaneous larval vaccine. Adult female mice had significantly (P less than 0.05) fewer parasites than adult male mice. The age of the larvae (indicated as the days between infection and harvesting of the larvae) was important in that day-4 or day-6 larvae (L4) were significantly more protective (P less than 0.001) than day-2 (L3) or day-8 larvae (L5-preadult). Reduction in worm burden for young vaccinated animals ranged from 31 to 39% (P less than 0.001) and for mature animals from 88 to 100% (P less than 0.001). Passive transfer to serum resulted in the reduction of worm burdens by 26-40% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ivermectin against larval stages of Dirofilaria repens in dogs

The prophylactic efficacy of ivermectin against Dirofilaria repens infections in dogs was investigated. A first trial was carried out on 15 dogs exposed to four inoculations of L3 larvae at 15-day intervals and treated, in groups of five, with 0, 6 or 12 micrograms/kg body weight of ivermectin given per os 30 and 60 days after the first inoculation. Necropsy, performed about 9 months later, revealed that worm burdens were reduced by 86.6 and 92.8% for the 6 and 12 micrograms/kg dose levels, respectively. In a second trial with an otherwise identical protocol, a dose rate of 24 micrograms/kg of ivermectin was tested in 12 dogs. Only one of the six treated dogs was found worm free at necropsy. The worm burden was reduced by 87.9% in treated animals as opposed to controls. A lengthening of the prepatent periods, which might be considered dose related, was apparent in all treated groups. Ivermectin was not completely effective in preventing establishment of experimental infections with D. repens in dogs.