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Nippostrongylus brasiliensis infections in mice: the immunological basis of worm expulsion.

Nippostrongylus brasiliensis infections in mice were terminated more rapidly than in rats and immunologically induced damage occurred earlier. Like rats, mice expelled damaged worms more rapidly than normal worms. Recipients of cells from the spleen or mesenteric node of immune mice expelled their worms by day 8 of the infection. Recipients of cells alone or antiserum alone did not expel their worms by day 5 but mice given both cells and antiserum expelled their worms by this stage of the infection. Damaged worms were expelled more rapidly than normal worms from mice given immune cells, This work indicated that antibodies and cells collaborate to expel N. brasiliensis from mice as has been shown to occur in rats.

Ancylostomatoidea↗

Schistosoma mansoni: morphology and ultrastructure of adult worms recovered from cyclosporin A-treated mice.

Cyclosporin A administered to Schistosoma mansoni-infected mice at around day 20 of infection reduces the worm burden by greater than 60%, as assessed by portal perfusion on days 28 and 86. Those worms recovered at perfusion have been examined by light and electron microscopy for drug-induced changes in morphology. Gross parasite damage was characterized by massive bolus formation and subsequent herniation of the gut. This event was attributed to the abnormal accumulation of crystalline structures in the lumen; the crystals were closely associated with lipid droplets, and were shown by X-ray micro-analysis to contain iron. Such crystals were seen only rarely in the intestines of control worms, but they too gave small iron peaks when examined by X-ray micro-analysis. In some drug-treated worms the caecal epithelium had ruptured, thereby releasing luminal contents throughout the worm body. In addition, herniations of the gut were seen protruding through the tegument causing surface deformation and disruption of tegumental and parenchymal tissues. The structural integrity of the worm was ultimately compromised allowing access to cytotoxic effector cells of the host. The combined effects of drug action and cellular cytotoxicity presumably account for the very significant levels of worm killing achieved by CsA treatment of the host.

Animals↗

Density dependence in establishment, growth and worm fecundity in intestinal helminthiasis: the population biology of Trichuris muris (Nematoda) infection in CBA/Ca mice.

The results are presented of an experimental study of the population biology of chronic Trichuris muris (Nematoda) infection in cortisone-treated CBA/Ca mice. Attention is focused upon both the validity of the common use of faecal egg counts to demonstrate density dependence in helminth fecundity, and the identification of other possible density-dependent mechanisms that may regulate worm numbers in chronic trichuriasis. The results show that faecal egg counts, although demonstrating high daily variation, are not an artefact of host faecal output but a significant density-dependent function of worm burden. This finding contrasts with the observations on Heligmosomoides polygyrus infection in outbred MFI mice, but accords with similar studies in a wide variety of host - helminth systems. Worm establishment in the murine host is found to be a density related function of infection dose. This is attributed to the probable existence of a physical gut-carrying capacity in the murine host for T. muris. Worm distribution in the gut is also shown to the density dependent, with worms being displaced from the caecum to the colon at increasing intensities of infection. The sex ratio of the adult parasites, however, is found to be both unitary and independent of worm burden. Evidence for a significant density-dependent decline in female T. muris growth or size is presented. The results also show a significant positive association between female T. muris weight and per capita fecundity. These findings indicate that the stunted growth of individual worms at high parasite densities may be a potential mechanism underlying density dependence in helminth fecundity.

Animals↗

Immune dependence of schistosomicidal chemotherapy: an ultrastructural study of Schistosoma mansoni adult worms exposed to praziquantel and immune serum in vivo.

This study examines the immune-dependence of praziquantel (PZQ) for the treatment of Schistosomiasis mansoni in mice. We have shown elsewhere from worm recovery data that the efficacy of PZQ is significantly enhanced when mice are treated concomitantly with antisera raised against antigens released from adult schistosomes, even though such antisera show no intrinsic helminthotoxic activity (Doenhoff et al. 1987, Doenhoff, Modha & Lambertucci 1988). Moreover, indirect immunofluorescence assays have shown that male worms exposed to the dual treatment regime in vivo bind antiserum to their dorsal surfaces in a pattern that seems to follow the outline of the dorsal tubercles. Scanning and transmission electron microscopy have now been used to further define the features of damage inflicted upon worms through exposure to antiserum alone, drug alone, or the two treatments in combination. Such investigations revealed that the antiserum induces a classical membrane repair process in worms of both sexes, but little other damage. PZQ causes the formation of spherical protuberances on the dorsal tubercles of male worms, while the dual treatment regime induces both kinds of damage in male schistosomes, but with much enhanced severity. The protuberances show evidence of explosion and some regions of the tegument become completely destroyed. Regions other than the dorsal surfaces of the male worms do not exhibit comparable trauma, and neither do the females. These data are discussed in relation to the known schistosomicidal activity of PZQ, the notion that male and female worms exhibit regional and sexual differences in susceptibility, documented evasive strategies of the parasite and the interdependence of immuno- and chemotherapy.

Animals↗

Characterization of monoclonal antibodies against eosinophil chemotactic factors from young adult worms of Angiostrongylus cantonensis.

Two kinds of IgG1 monoclonal antibodies against eosinophil chemotactic factors (ECFs) derived from Angiostrongylus cantonensis young adult worms (YA) were established. Western blot analyses demonstrated that one monoclonal antibody recognized a 16.1 kD component of YA-whole worm extract, and the other an 85 kD component. These antibodies did not show any cross reactions against several helminth antigens, as assessed by ELISA. The chemotactic activity of YA-whole worm extract for guinea-pig-eosinophils was significantly inhibited by previous incubation of the extract with these monoclonal antibodies; the monoclonal antibody recognizing the 16.1 kD component inhibited 56-61% of the ECF activity whilst the antibody recognizing the 85 kD component inhibited 20-34% of the activity. The combination of both monoclonal antibodies showed a stronger inhibitory effect (71-81%) than either antibody alone. Similar magnitudes of inhibition were noted when the chemotactic activity for human eosinophils was measured using YA-whole worm extract preincubated with these monoclonal antibodies. Neither monoclonal antibodies inhibited the chemotactic activity of whole worm extracts of A. cantonensis first stage larvae, Metastrongylus apri adult worms, Spirometra erinacei plerocercoids and Fasciola sp. adult worms. These data suggest that the two monoclonal antibodies will be useful for the isolation and purification of ECF-YA as well as for elucidating the possible in vivo role of ECF-YA.

Angiostrongylus cantonensis↗

The antibody responses to adult-worm antigens of Schistosoma haematobium, among infected and resistant individuals from an endemic community in southern Ghana.

Antibody responses to antigens from adult Schistosoma haematobium were investigated in an endemic community in Ghana, using microplate-ELISA. The results of a survey of egg output in urine and of a questionnaire-based investigation of water-contact activities were used to select 'endemic normal' (EN) and patently infected (PI) individuals as subjects. The plasma levels of antibodies reacting with the adult-worm antigens were determined and compared and the correlations between these levels and the age, water-contact index and egg output of each subject were evaluated. Compared with the EN subjects, the PI generally had higher levels of anti-worm IgG and IgE but lower levels of anti-worm IgA. When the data for the EN and PI groups were combined, the levels of anti-worm IgG and IgE were found to be positively correlated with egg output and with each other. Whichever the antibody class considered, levels of anti-worm antibodies were never negatively correlated with egg output. These results indicate that anti-worm IgE and IgG could be used as markers to reflect current infection intensity, and that anti-worm antibodies may not act as protective antibodies in the natural course of urinary schistosomiasis.

Adult↗

In vitro effects of antibiotics on Brugia malayi worm survival and reproduction.

Recent studies have suggested that intracellular Wolbachia spp. endobacteria are necessary for the reproduction and survival of filarial nematodes. The effects of antibiotics that are active against related bacteria on adult worms and microfilariae (Mf) of Brugia malayi in vitro were investigated. Antibiotics tested were doxycycline (Doxy), tetracycline (Tet), rifampicin (Rif), azithromycin (Azith), and chloramphenicol (Chlor). Doxy, Tet, Rif, and Azith reduced release of Mf by adult female worms. The minimum effective concentrations that reduced Mf release by 50% were 5 microg/ml for Doxy, 20 microg/ml for Tet, 40 microg/ml for Rif, and 100 microg/ml for Azith. The same drugs (at higher concentrations) killed adult worms and Mf. Embryograms showed that Tets blocked embryogenesis in female worms. Electron microscopy (EM) showed that the Tets, Rif, and Azith cleared Wolbachia spp. from adult worms and damaged developing embryos. These studies show that antibiotics active against Rickettsiaceae affect adult B. malayi worms and Mf in vitro. Additional studies will be needed to elucidate the mechanisms of action of these antibiotics on Wolbachia and filarial worms.

Animals↗

Life history and spatial distribution of the enchytraeid worm Cognettia sphagnetorum (Oligochaeta) in metal-polluted soil: below-ground sink-source population dynamics?

We studied the life history, metal-avoidance behavior, spatial distribution, and population growth of enchytraeid worms (Cognettia sphagnetorum [Oligochaeta]) originating from two sites: one uncontaminated, and another patchily polluted by heavy metals. Effects of patchy soil contamination on populations were studied in microcosms. In uncontaminated soil, worms from the polluted site had lower viability and reduced growth rate as juveniles but higher growth rate as adults compared to worms from the unpolluted site. They were also smaller in size at fragmentation (reproduction). Worms from the polluted site reached a larger population size than worms from the unpolluted site. Hence, worms from the polluted site seemed to allocate more energy to reproduction, because such a strategy can be highly adaptive when living in a less-polluted patch (the source) in, on average, a highly polluted environment. The C. sphagnetorum actively avoided Cu-contaminated soil, with the response being stronger in individuals from the contaminated site. When an unpolluted patch (the source) was surrounded by a toxic environment (the sink), worms were found in the sink, either because intraspecific competition overrode the avoidance behavior or because of random walk migration. As a result, total population size in these microcosms were as high as those in totally uncontaminated microcosms. Our results indicate that avoidance behavior and increased allocation to reproduction, together with the observed dispersal pattern, can be an adaptive strategy for C. sphagnetorum in the presence of small, less-polluted patches in, on average, a hostile environment. Hence, sink-source population regulation can explain spatial distribution and survival of C. sphagnetorum in patchily polluted field soils. When such population dynamics occur, this pattern should be taken into account when population densities in the field are monitored for ecological risk-assessment procedures concerning toxicants.

Adaptation, Physiological↗

The onchocercal nodule: interrelationship of adult worms and blood vessels.

This study of onchocercal nodules reveals an intimate relationship between the cuticle of Onchocerca volvulus and the capillaries of the host. Perfusion of blood vessels with India ink and other special techniques reveal a proliferation of capillaries around the worms and communication between small vessels and the spaces around the worms. The space around the worm is continuous with the central fibrin lake. These findings, together with the fact that the worm's gut contains hemosiderin, suggest that the worm subverts the vascular reaction and causes within the nodule a controlled hemorrhage that serves the worm's nutritional needs. We believe this explains, in part, how worms survive in fibrous nodules for many years.

Animals↗

[Chronobiological studies on effect of cyclosporin A (CsA) against adult male worms of Schistosoma mansoni in vitro].

AIM: To study the action mode of cyclosporin A (CsA) against Schistosoma mansoni in vitro. METHODS: MF1 mice were infected with Schistosoma mansoni cercariae for 6 weeks when the adult worms were recovered by portal perfusion. The male worms of S. mansoni recovered were exposed to varying concentrations of CsA at 8, 16, and 24 h in vitro. Drug induced damage to the male worm surface was chrono-biologically observed throughout these experiments by SEM. RESULTS: After the male worms of S. mansoni were incubated with 1 microgram/ml CsA for 8-24 h, the tegument showed swelling of ridges with appearance of holes on their surface and detachment of a part of spines. The above damage of the tegument became more evident in male worms after incubation with 10, 15, 20 micrograms/ml CsA for 8-24 h. Moreover, incubation of male worms with 25 micrograms/ml CsA for 8-24 h resulted in significant deformation and disruption of tegument, rupture of ridges and detachment of spines. The tegumental damage of male worms of S. mansoni was dose- and time-dependent. CONCLUSION: The antischistosomal action of CsA is direct, the schistosome tegument appears to be the main site for CsA attack.

Animals↗

Oltipraz treatment in experimental schistosomiasis mansoni. I. Morphological changes among S. mansoni worms induced by high dose oral therapy in mice.

Worms recovered from Oltiparz treated group of mice (500 mg/kg. body weight) show, suntedness, absent or poorly developed tuberculations, destroyed or poorly developed suckers, absence or severe atrophy of testes, complete absence or severe atrophy of ovaries, small or empty vitelline follicles and slightly or not pigmented intestines as compared with controls; the female worms are more affected than males. The morphological changes are apparent after 5 days, 7 days, 20 days and 30 days from drug administration, but are reversible in some surviving worms especially male worms after 60 days from therapy. The previous findings indicate that the drug causes severe degenerative changes in the structure of both S. mansoni male and female worms and that resistance to the drug develops among the Egyptian strain of S. mansoni worms with prolongation the period of worms exposure to the drug. The present results are discussed with those of others with some recommendations.

Animals↗

Transplanted Dipetalonema viteae in the jird: effect of worm burden on parturition rates and microfilaremia.

Dipetalonema viteae was studied in the jird, Meriones unguiculatus, to determine the mechanism controlling the level of peripheral microfilaremia. Jirds killed 40 days after infection served as donors of female worms of known age and reproductive status. These worms were transplanted into uninfected jirds and the resultant microfilaremias were monitored. After approximately 100 days, the recipient jirds were killed and 58% of the transplanted worms were recovered alive but depleted of sperm and microfilariae, regardless of the total number implanted in a given host. A direct linear relationship between microfilaremia and the number of recovered adult worms was found. Based on the uniform absence of sperm and microfilariae in the recovered worms it was concluded that female worms, under the conditions of the present study, do not control the peripheral microfilaremia in multi-worm infections through a reduced parturition rate.

Animals↗

Efficacy of fenbendazole against the swine kidney worm Stephanurus dentatus.

Fenbendazole in ground feed was fed on 3 successive days at the rate of 3 mg/kg of body weight to 15 sows naturally infected with kidney worm (Stephanurus dentatus). Fifteen similar sows were used as nontreated controls. A total of 49 kidney worms were recovered from daily urine samples collected from 10 of the 15 treated sows within 5 days after the 3rd dose of treatment. One control sow passed 10 kidney worms on the 2nd and 3rd days. Urine samples from treated sows became negative for kidney worm eggs by the 5th to 12th posttreatment days, except for urine samples from 1 sow that contained a few eggs on the 12th day and another sow that contained a few eggs on the 19th and 33rd posttreatment days. Urine samples from control sows contained approximately the same number of kidney worm eggs in the posttreatment period as earlier. Compared with that in control sows, the hatchability of the parasite eggs from treated sows was greatly reduced. Kidney worms were not recovered at necropsy from the treated sows and a total of 860 kidney worms were recovered from the control sows (57 av).

Animals↗

[Therapeutic effect of paromomycin sulfate in the treatment of Diphyllobothrium latum infections and an observation on the worm tissues affected by the drug].

Paromomycin sulfate (aminosidine) at a single dose of 32 to 53 mg/kg was orally given to 24 cases with proven diphyllobothriasis. Evaluation of efficacy of the drug was based on stool examination for the eggs after 3--4 weeks of treatment. The cure rate was obtained as 96% (23/24), and 30 worms were expelled from 24 patients. Only 1 unsuccessfully treated case of 34-year-old man was retreated at the same dose of the drug 3 weeks later to obtain the cure. Thirty worms were composed of a single worm each from 21 patients, 2 worms from a patient, 3 from 1, and 4 from 1. Scolices of 7 (23.3%) out 30 worms were found. Vomiting as side effect of the drug was observed in only a case of 4-year-old girl at 40 minutes after administration of the drug but it was mild and transient. Clinical symptoms or complaints before treatment were as follows; abdominal discomfort in 12 cases, abdominal pain in 7, diarrhea in 4, fatigue in 2, tinnitus, vomiting and frequent stool in 1 each. Seven cases were almost asymptomatic. Morphological changes of the worms immersed in paromomycin solution (aminosidine) (1.66 mg/ml) for 1, 2 and 3 hours were observed in comparison with worms kept in physiological saline solution. The destructive effects were fragmentation, dissolution and desquamation of the outer cuticle and basement membrane with PAS stain at 3 hours of the experiment. The damages were also demonstrated in subcuticular tissues composing of muscle layer and parenchymal cells.

Adolescent↗

Comparison of the protective efficacy on mekongi schistosomiasis in mice induced by antigens derived from cercariae, schistosomulae and adult worms.

Protective efficacy of the extracts of cercariae, schistosomulae and adult worms of S. mekongi was studied in mice receiving immunizations with these extracts emulsified with Freund's complete adjuvant initially and incomplete adjuvant subsequently, and compared with mice receiving physiological saline with or without adjuvants as controls. After challenge with cercariae, the animals were sacrificed and the larvae or adult worms harvested by lung recovery and perfusion techniques on day 5 and weeks 6-8, respectively. Worm reduction rates were significantly higher in mice receiving extracts of schistosomula (59%) and adult worms (51%) than in those receiving the cercarial extracts (31%). Similar findings were obtained with the perfusion technique showing worm reduction rates of 57%, 53% and 30% in mice receiving extracts of schistosomulae, adult worms and cercariae, respectively. ELISA antibody titers were correspondingly increased in mice receiving extracts of schistosomulae and adult worms, but not in those receiving cercariae. This apparent association may be inadequate to suggest that the increase in ELISA titer be used as an indicator for resistance in mekongi schistosomiasis.

Animals↗

The effect of the intestinal worms and migrating L1 larvae of Trichinella spiralis on the production of antiparasitic IgE antibodies.

The effect of the adult worms and migrating L1 larvae of Trichinella spiralis on the production of specific IgE antibodies was determined in BCF1 mice. To achieve this, we combined the effect of two anthelminthics: thiabendazole, to produce chemosterilization of adult females, and napthalophos, to expel adult worms from the intestine of infected mice on the desired day. Our results demonstrate that when the natural route of infection is used the production of IgE antibodies is not dependent on the infection dose or the number of migrating L1 larvae, and that both intestinal worms and migrating L1 larvae contribute to the production of reaginic antibodies. In addition to this, an extended period of antigenic stimulation (10-12 days) is required for the induction of a detectable, specific IgE response by adult worms. Finally, our results seem to indicate that although the effects of adult worms and migratory L1 larvae on the IgE production are not additive, the presence of adult worms in the intestine of mice may stimulate a secondary exposure to common antigens released by the migrating L1 larvae.

Animals↗

Time course of the effect of praziquantel on Schistosoma mansoni attachment in vitro: comparison with its effects on worm length and motility.

We report herein that praziquantel inhibits the capacity of adult male Schistosoma mansoni to attach to the bottom of a glass dish and produces a diminution of worm length and motility, acting under a similar concentration and time dependency. After removal of 1 microM praziquantel from the medium, the worms progressively recuperated their initial length and motility without recovering their attachment capability. The absence of calcium or presence of 1 microM verapamil did not change the praziquantel-induced effect on worm attachment, causing only a transient decrease in worm length and motility. The present data indicate that the diminution of motility induced by praziquantel results from the progressive contraction of the longitudinal musculature of the worm. In contrast, the loss of attachment should not be causally related to the contraction of the worm since these two praziquantel-induced effects have distinct patterns of response under some experimental conditions.

Animals↗

Schistosoma mansoni: onset of chemoattraction in developing worms.

Heterosexual chemoattraction studies on juvenile worms showed that 20- and 21-day-old worms do not attract each other, whereas 23- and 28-day-old worms are attracted to each other and pair with worms of the opposite sex. This onset of chemoattraction in vitro corresponds to the time when worms begin pairing in vivo. The ability of single worms to locate each other and mate is presumably mediated by chemoreceptors.

Animals↗