Activity of praziquantel against Hymenolepis nana, at different development stages, in experimentally infected mice

Single doses of praziquantel were administered by oral route, at various time intervals, following the experimental infection of mice with Hymenolepis nana eggs (2000 per animal), to investigate the drug action against different development stages of the parasite. It was shown that either 25 or 50 mg/kg given on the 4th day after inoculation had just a partial effect against the cysticercoids. Moreover, 25 mg/kg given on the 7th day was not able to kill all juvenile forms as well. However, this dose administered on the 10th day, when the parasites had reached maturity taut oviposition was not yet initiated was 100% efficacious. The same degree of efficacy was achieved with the administration of 25 mg/kg on the 14th day when the fully mature worms already lay eggs. These animal findings indicate that in the treatment of human hymenolepiasis praziquantel, 25 mg/kg, should be taken twice, 10 days apart, so that the second dose kills the larval and juvenile forms which have survived the first one. This should be particularly recommended for treating H. nana infection in close communities.

Schistosoma mansoni: importance of skin and pulmonary phases to concomitant immunity in albino mice

Fourteen-day-old schistosomula obtained from mice previously infected were surgically transferred to the portal vein of receptor mice. Another group of mice was infected with cercariae by transcutaneous route. After 90 days, those groups were challenged with 100 cercariae, transcutaneously, as well as a control group. Two weeks later the animals were perfused and mature and immature worms counted separately. Statistically significant differences were observed in the recovery of immature worms, when the control group was compared with those twice infected. No statistical difference was detected between the group infected transcutaneously, and that infected by worm inoculation in portal vein. Results demonstrated that suppression of skin and lung migration of the parasite does not interfere with the development of the so called concomitant immunity.

Anaphylaxis with Schistosoma mansoni extracts in normal and infected mice

Methods generally utilized for studies on anaphylaxis to protein antigens such as determination of histamine release to the blood, hemoconcentration, histamine release from peritoneal mast cells and passive cutaneous anaphylaxis (PCA) were used to investigate some aspects of the anaphylaxis to parasite antigens in Schistosoma mansoni infected mice. The release of histamine to the blood and significant rates of hemoconcentration were induced by intravenous injection of schistosomula or cercarial extracts into 10-13 weeks infected mice. Cercarial, schistosomula, worm tegument and soluble egg antigens were able to trigger histamine release from peritoneal mast cells from chronically infected mice. In spite of the PCA reaction beeing detected within 2 hours of sensitization (IgG1antibodies) in 6 of 8 tested sera from chronically infected mice, no detectable reactions were obtained after 48 hours sensitization (IgE antibodies). Although IgE was not detected in the circulation, by the PCA technique, the results indicate that the infected mice contained IgE antibodies bound to their mast cells.

Hexachlorophene as a topically applied chemical for prophylaxis against Schistosoma mansoni infections in mice

Treatment of mouse tail skins with hexachlorophene (1.25% w/v) in absolute methanol or 70% isopropanol suppressed Schistosoma mansoni infections by more than 95% even when the application was performed up to three days prior to exposure to cercarial suspensions by tail immersion. Treatment with concentrations of 0.313% or higher one day prior to exposure provided at least 98% protection when the treated surface was not subjected to water washes of greater duration than 1/2 hour. Tail immersion application of 1.25% hexachlorophene one day prior to exposure still provided 87-92% protection after 3 hours water wash. Wipe application of 1.25% hexachlorophene three days prior to exposure still provided 93% protection following 3 hours water wash. High cercarial recoveries from exposure tubes at the end of exposure periods indicated high antipenetrant activity for hexachlorophene. Sufficient hexachlorophene leached from treated tail skins into the surrounding water to affect subsequently added cercariae so that they were no longer infective to untreated mice.

Protection of athymic (Nu/Nu) BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ +) BALB/c mice

Athymic BALB/c (Nu/Nu) mice died at 7-13 days after inoculation (DAI) of Plasmodium berghei NK65, whereas their heterozygous (Nu/+) littermates died at 7-8 DAI. Nude (Nu/Nu) mice, reconstituted with 2 x 10(7) splenocytes from uninfected heterozygous (Nu/+) littermates at 20 days before parasite inoculation (DBI), died about 2 days earlier than control nude mice; nude mice reconstituted at 10 or 2 DBI lived 2 to 4 days longer than control nudes; and nude mice reconstituted 2 DAI lived even longer and some survived. These findings indicate that P. berghei NK65 induces at least two T-cell dependent immune phenomena, one suppressive and the other stimulatory. Reconstitution of nude mice with T-cells from BALB/c (Nu/+) mice appeared to reduce or bypass suppressive T-cell activities which allowed the formation of a protective immune response by some of the nude mice.

Trypanosoma (Herpetosoma) rangeli Tejera, 1920: intracellular amastigote stages of reproduction in white mice

The method, site, and stage of multiplication of Trypanosoma (Herpetosoma) rangeli Tejera, 1920 has not hitherto been known. "We have now observed many intracellular nests or pseudocysts, containing amastigotes and trypomastigotes of this parasite in the heart, liver, and spleen of suckling (5.0 g) male white mice (NMRI strain) inoculated i.p. with 9 x 10(4) metatrypomastigotes/g body weight from a 12-day-old culture of the "Dog-82" strain of T. rangeli. At the peak of parasitemia (1.9 x 10(6) trypomastigotes/ml blood, 3 days post-inoculation) various tissues were taken for sectioning and staining. The heart was most intensely parasitized. The amastigotes were rounded or ellipsoidal, with a rounded nucleus and the kinetoplast in the form of a straight or curved bar; the average maximum diameter of 50 measured amastigotes was 4.2 p. Binary fission was seen in the nucleus and kinetoplast of some amastigotes; no blood trypomastigotes were seen in division. The above characteristics, as well as the location of the pseudocysts in the tissues, are similar to T. cruzi. Comparison of these results with those reported for other Herpetosoma suggest study of the taxonomic position of T. rangeli.

Schistosomiasis mansoni: evidence for a milder response in germfree mice

Germfree (GF and conventional (CV) mice were infected intraperitoneally with GF cercariae of Schistosoma mansoni and kept for six weeks. Twenty four hours before killing, they were injected with [³H]-thymidine. Schistosoma worms, harvested after perfusion of portal system, were counted as well as eggs from liver and intestines. Liver was also used for DNA, protein, and collagen determinations. [³H] -Thymidine incorporation and collagen determinations were used to establish the indices given by the difference between their contents in infected and control animals and expressed per thousand eggs in liver. The recovery of worms in GF mice was around twice as much as in CV ones, and the total number of eggs was higher in the liver of GF animals. No hypertrophy of liver cells was observed by the ratio protein/DNA, but [³H]-thymidine incorporation into DNA was higher than in controls in both GF and CV infected animals. The [³H]-thymidine and collagen indices were lower in GF animals which indicate a more discrete cellular replication and smaller collagen content in relation to the number of eggs present in livers of these mice. It was concluded that the disease seems to be less severe in GF animals.

American trypanosomiasis (Chagas' disease) in conventional and germfree rats and mice

Germfree (GF) and conventional (CV) CFW (LOB) mice and Wistar and Sprague-Dawley rats were infected with Trypanosoma cruzi. The disease was more severe in the GF than in the CV animals as revealed by: (1) an earlier and more intense parasitemia; (2) a more precocious mortality; (3) a twice enlarged spleen: (4) a more intense cell and tissue parasitism; (5) visceral signs of cardiac failure.

Cutaneous leishmaniasis in germfree, gnotobiotic, and conventional mice

Cutaneous leishmaniasis was much more severe in conventional than in gnotobiotic mice as revealed by macro and microscopic examination. An inoculum of Leishmania mexicana amazonensis was used.

: acquired resistance in mice by implantation of young irradiated worms into the portal system

In two distinct experiments, immature S. mansoni worms (LE strain, Belo Horizonte, Brazil), aged 20 days, obtained from the portal system of white outbred mice, were irradiated with 14 and 4 Krad, respectively. Afterwards, the worms were directly inoculated into the portal vein of normal mice. Inoculation was performed with 20 irradiated worms per animal. Fifty days after inoculation, the mice that received 4 and 14 Krad-irradiated worms and their respective controls were infected with S. mansoni cercariae (LE strain), by transcutaneous route. Twenty days after this challenge infection, the animals were sacrificed and perfused for mature irradiated (90-day-old) and immature (20-day-old) worm counts. Analysis of the results showed that statistically significant protection against cercariae occurred in both groups with irradiated worms.

Kinectics of the pulmonary phase of Schistosoma mansoni in mice treated with dexamethasone

In the experimental schistosomiasis mansoni glucocorticoids cause a reduction in the worm burden when administered in the week of infection or, the longest, at the next week. In order to determinate the probable(s) site(s) of reduction of the worm burden, mice were infected with cercariae of LE strain of S. mansoni and dexamethasone was administered daily (50 mg/kg, subcutaneously) starting 1 hour before infection until the eighth day. Mice were sacrificed daily starting on the third day after infection until the ninth day, and schistosomula from lungs were collected. Six weeks after infection, the remaining mice were sacrificed and perfused for adult worm recovery. Analysis of the results showed that the non-treated mice presented larger numbers of lung larvae than the treated ones, and this difference was also found later in the worm burden in the portal system. This difference may reflect the early death of larvae in treated animals, before or after reaching the lungs.

Liver morphology with emphasis on bile ducts changes and survival analysis in mice submitted to multiple Schistosoma mansoni infections and chemotherapy

In an attempt to be as close as possible to the infected and treated patients of the endemic areas of schistosomiasis (S. mansoni) and in order to achieve a long period of follow-up, mice were repeatedly infected with a low number of cercariae. Survival data and histological variables such as schistosomal granuloma, portal changes, hepatocellular necrosis, hepatocellular regeneration, schistosomotic pigment, periductal fibrosis and chiefly bile ducts changes were analysed in the infected treated and non treated mice. Oxamniquine chemotherapy in repeatedly infected mice prolonged survival significantly when compared to non-treated animals (chi-square 9.24, p = 0.0024), thus confirming previous results with a similar experimental model but with a shorter term follow-up. Furthermore, mortality decreased rapidly after treatment suggesting an abrupt reduction in the severity of hepatic lesions. A morphological and immunohistochemical study of the liver was carried out. Portal fibrosis, with a pattern resembling human Symmers fibrosis was present at a late phase in the infected animals. Bile duct lesions were quite close to those described in human Mansonian schistosomiasis. Schistosomal antigen was observed in one isolated altered bile duct cell. The pathogenesis of the bile duct changes and its relation to the parasite infection and/or their antigens are discussed.

Schistosoma mansoni: acquired immunity in mice after the use of oxamniquine at the evolutive skin and pulmonary phases

Mice infected with 350 cercariae of Schistosoma mansoni (LE strain) were treated with oxamniquine, at the dose of 400 mg/kg, 24, 48, 72, and 96 h after infection. Forty days after the treatment, the animals were submitted to a challenge infection with 80 cercariae, through the abdominal and ear skins. The number of immature worms in the animal groups treated 24 and 96 h after the first infection was found to be lower than that in the control group, thus showing that the death of schisto-somes by chemotherapy, at the skin and pulmonary phases, causes an acquired resistance state.

Evolution of subpatent parasitaemia in Trypanosoma cruzi chronically infected mice with the help of a cyclophosphamide amplification transfer assay

We have evaluated the sensitivity of the classical blood subinoculation method, modified through cyclophosphamide treatment of transferred mice, for the detection of occult parasitaemias in Trypanosoma cruzi chronically infected mice. Besides its simplicity, the method was shown to be highly sensitive for both the "chronic" phase parasites (99% of chronic cases were shown to harbour occult parasitaemias) and for the acute phase parasites (T. cruzi could be detected in 53.8% of animals transferred with one Y strain parasite and in 20% of animals transferred with one CL strain parasite). Using acute phase bloodforms, the assay proved to be more sensitive than conventional subinoculation when dealing with the CL, but not the Y strain of the parasite. With the help of this parasite detection tool, we have studied during a one year period, the evolution of subpatent parasitaemias in a group of mice which survived through chemotherapy from lethal acute phase of T. cruzi infection. Cyclophosphamide transfer assay revealed occult parasitaemias in 100% of the chronic animals, nevertheless, continuous and discontinuous patterns of positivity were observed.

Trypanossoma cruzi: course of infection in platelets-depleted mice

The effect of platelet depletion on the course of Trypanosoma cruzi infection in BALB/c mice was investigated. Thrombocytopenia was achieved by inoculation of rabbit anti-platelet IgG during the parasitemic phase of the infection. The number of parasites in the blood of anti-platelet IgG treated was significantly higher than that of non-treated control mice, during the phase of high parasitemia. Cumulative mortality of platelet-depleted mice was consistently but not significantly higher than that of control mice up to the 32nd day of infection; from the 33rd day on they were equivalent, no mortalities occurring from then on, until observations were discontinued on the 60th day. These results suggest that platelets participate of the mechanisms of parasites removal from the bloodstream, but do not have an effective role in the mechanisms of defence against T. cruzi, during the acute phase of infection.