Synergistic action of praziquantel and host specific immune response against Schistosoma mansoni at different phases of infection.

The interaction between specific immune response to Schistosoma mansoni and praziquantel (PZQ) was studied in mice. In mice harboring concomitant immunity, 6-day-old parasites treated with PZQ were more effectively removed than 24 h treated parasites despite both had a significant worm burden reduction when compared with respective treated controls. These results show that PZQ can be effective at the skin and lung stages of parasite's development mainly acting with a established specific immune response, and particularly at the lung phase.

[Effects of cyclosporin A or betamethasone on experimental murine toxocariasis]. / Efeitos da ciclosporina A e betametasona na toxocaríase murina experimental.

The effects of administration of either cyclosporin A or betamethasone 15 days before or 45 days after experimental infection with Toxocara canis on mice had been studied. The dynamics of IgG antibody production, employing an enzyme-linked immunosorbent assay, was studied 60 and 90 days after mice infection by Toxocara canis. In the 90th day after infection all surviving mice were sacrificed and the tissue trapped larvae recovered by acid digestion in the muscles, lungs, liver and brain. A significative delay in the production of IgG antibodies anti-Toxocara was observed in all the mice treated with cyclosporin A or betamethasone 15 days before infection. On the other side, mice treated with cyclosporine 15 days before infection, but not with betamethasone, showed a significative higher number of trapped Toxocara canis larvae in the examined tissues.

[Neuroimmunomodulatory effect of highly toxic organophosphorus compound on the development of Trichinella spiralis infection]. / Dzialanie neuroimmunomodulacyjne wysokotoksycznego zwiazku fosforoorganicznego na rozwój infekcji Trichinella spiralis.

The highly toxic organophosphorus compound (isopropylmethylphosphonofluoridate--IMPF) belonging to the group of the so called toxic of warfare agents can impair immune effector mechanisms determining the development of parasitic infection. Preliminary studies have demonstrated that IMPF delays elimination of adults Trichinella spiralis forms from the intestine of C57B1/6 mice and B6C3F1 hybrids. Besides, the studied compound modifies the proliferative activity of T-cells in the above mentioned mice and reduces the production of anti-SRBC antibodies in C57B1/6 strain. The mechanisms are discussed of the organophosphorus compound effect on neuroimmunological processes connected with antiparasitic immunity, paying attention also to the function of these processes by the parasitic infection itself, in host-parasite relationship. The probability is also considered of increased sensitivity to Leishmania infection in humans poisoned with IMPF and/or other organophosphorus compounds.

In vitro cellular and humoral responses to Schistosoma mansoni vaccine candidate antigens.

Few studies comparing schistosomiasis vaccine candidate antigens between laboratories have been carried out and published. Generally, only the investigators who discovered the molecules have evaluated them in either experimental animal models or in human correlate studies. In an attempt to identify responses against specific antigens and investigate their association with resistance versus susceptibility to re-infection, we studied the serological reactions and the cytokine responses stimulated by a panel of 10 candidate vaccine molecules in 225 long-term residents of an area endemic for Schistosoma mansoni in Egypt. The panel consisted of four recombinant antigens (Sm62-Irv5, Sm37-G3PDH, Sm28-GST and Sm14-FABP), one full-length native protein (Sm97-paramyosin), two synthetic peptides (MAP3 and MAP4) and three unpublished antigens (PR52-filamin, PL45-phosphoglycerate kinase, PN18-cyclophilin). Two different study designs, one based on retrospective and the other on prospective parasitological data were applied in the evaluation of the immune responses. Using historical data collected over the previous 5 years, correlations between frequency of re-infection and antigen-specific immune responses were investigated. In the prospective arm of the study, the subjects were followed over time after treatment with praziquantel with periodic immunological tests and stool examinations. Thus, highly specific humoral and cellular immune reactions in response to the 10 antigens described above could be correlated, both prospectively and retrospectively, with detailed epidemiological data covering a 66-month period. The immune response profiles produced were unique to each antigen but no clear "winner" or "winners" were identified. However, markers for both resistance and susceptibility to re-infection were identified for each molecule indicating which types of responses to aim for in vaccination and which ones to avoid. The insights gained from this approach should be useful for antigen selection and ultimately for vaccine formulation prior to Phase I/II trials in humans.

Effect of carnosine administration on the immune response of rabbit to Schistosoma mansoni antigens.

SDS-PAGE separation of soluble worm antigen preparation (SWAP), cercarial antigen preparation (CAP), and soluble egg antigen (SEA) of Schistosoma mansoni showed obvious qualitative and quantitative differences. The shared polypeptides of the three stages of S. mansoni were 116, 72.768 and 32.367 kDa under reducing conditions. The different anti-sera raised in rabbits against the different stages of antigens were recognized by electroimmune transfer blotting (EITB). Each of the 3 groups separated eight bands. Carnosine treatment of rabbits immunized with SWAP, CAP or SEA resulted in the disappearance of two bands in SWAP group and one band in CAP group in comparison with the non-treated immunized groups. This indicated that the carnosine modulated immune response of rabbits against S. mansoni antigens.

Effect of glucan immunomodulator on the immune response and larval burdens in mice with experimental toxocarosis.

Glucan immunomodulator, combined with immunoglobulin and zinc (GI), was tested in mice infected with Toxocara canis for its effects on the immune response and parasite recovery. Infection with 2 500 T. canis eggs per mouse induced a short-term depression of the proliferative response of T cells to phytohemaglutinin from Day 35 to a Day 49 post infection (p.i.). GI given in two doses at the start of the experiment markedly stimulated and restored cell proliferation at Days 21-63 p.i. Infection resulted in significant increase in specific circulating antibody level at Days 21 and 35 p.i. A striking reduction in the number of T. canis larvae, after GI administration was observed in the muscles of the GI-treated mice, compared with the untreated animals.

Experimental studies on early treatment of schistosomal infection with artemether.

An early treatment with artemether given in appropriate regimens was tested in mice, rabbits and dogs for prevention purposes. Artemether was administered intragastrically (ig) to the hosts on day 7 after infection with Schistosoma japonicum cercariae at a single dose, and the same dose of artemether was repeated every 1 or 2 weeks for 2-4 times. As a result, most of the female worms were killed before their oviposition with female worm reduction rates of 90-100%, resulting in protection of the host from damage induced by schistosome eggs. When rabbits were treated ig with artemether 10 mg kg-1 on day 7 after infection, followed by repeated dosing every week for 4 times, some parameters related to acute schistosomiasis, such as temperature, eosinophil count and eggs in the feces were negative, and low specific antigen and antibody levels in serum were seen. Further study showed that the appropriate regimens of Artemether were also effective in early treatment of reinfection with cercariae. When rabbits infected with 48-52 cercariae once every other day for 5 times were treated ig with artemether 15 mg kg-1, followed by repeated dosing every 1 or 2 week for 2- 3 times, the female worm reduction rates were 92.1-98.4%. Histopathological examination of the livers showed that the above-mentioned early treatment with Artemether exhibited a promising protective effect on dogs and rabbits. The major features included normal appearance of the liver resembling those of uninfected dogs and rabbits; few or no dispersed miliary egg tubercles appeared on the surface of the liver; the structure of the hepatic lobules was normal with normal arrangement of the liver bundles; few or no eggs appeared in the portal vein area and there was apparent diminution of total egg granuloma, comprising inflammatory, fibrous or scarred egg granuloma. On the basis of above-mentioned results, early treatment with Artemether could be recommended for field trial for controlling acute schistosomiasis, reducing infection rate and intensity of infection.

Effect of chemotherapy on immune response to egg antigens of Schistosoma mansoni in chronically infected children from areas of low transmission.

In an attempt to identify antigenic molecules from Schistosoma mansoni eggs, a serological study was performed on children of a Venezuelan town (Caraballeda) in which the transmission of schistosomiasis had been interrupted two years prior to sera sampling. Infected children received treatment with Praziquantel and, based on the disappearance of eggs in the stools plus negativization of the circumoval precipitin test (COPT) one year after treatment, they were classified as either responders or non-responders to chemotherapy. Western blots of soluble egg antigen (SEA) with a very sensitive chemiluminescent substrate were performed. Sera from responder children recognized a 25 kDa band of SEA which diminished significantly after treatment. This was less frequent in non-responder children. When the sera of responder and non-responder children were compared before treatment, we found that the recognition of the 40 and 41 kDa proteins could be predictive of response to chemotherapy. All these antigens, used in ELISA-type techniques, might be of importance in the evaluation and follow-up of large scale schistosome control programmes.

Impaired host resistance to Trichinella spiralis as a consequence of prenatal treatment of rats with diazepam.

In utero exposure of Long Evans rats to low dosages of diazepam has previously been found to result in depression of cellular and humoral immune responses until adulthood, with marked changes in cytokine release by splenocytes and splenic macrophages. In order to assess the significance of these alterations in immune cells with regard to host resistance, we investigated the resistance of adult offspring towards Trichinella spiralis. Time-pregnant rats were treated with diazepam (1.25 mg/kg/day) or vehicle from gestational day 14 to 20. Male offspring were infected with T. spiralis at 2 months of age. This infection model tests the participation of T- and B-cell populations and of macrophages. Prenatally diazepam-exposed animals exhibited an impaired defence towards T. spiralis. The number of muscle larvae was increased as determined in digested carcasses and by morphometric analysis of the tongue. Moreover, antibody titers were altered, i.e., IgG was decreased and IgA was elevated in the prenatally diazepam-exposed group. These results demonstrate an impaired defense towards T. spiralis in adult rats after prenatal exposure to diazepam.

Efficacy of milbemycin oxime in chemoprophylaxis of dirofilariasis in cats.

Although cats are less susceptible to infection with Dirofilaria immitis than are dogs, the possibility of severe consequences from infection or adulticidal treatment renders preventive treatment a desirable alternative in endemic areas. To evaluate the efficacy of milbemycin oxime as a chemoprophylactic agent in cats, 48 cats were inoculated with infective D immitis larvae. Single oral treatment with 2.3 mg of milbemycin oxime (0.5 to 0.9 mg/kg of body weight) at 30 or 60 days after inoculation with infective larvae gave strong but incomplete protection. Treatment at 60, as well as 90, days after inoculation with infective larvae was completely effective in preventing development of infection. A control group of inoculated, but untreated, cats was monitored biweekly for hematologic changes and for changes in parasite-specific serum antigen and antibody concentrations. Pronounced increases in total leukocyte counts and eosinophil numbers were associated with the estimated time of in vivo molting from fourth- to fifth-stage larvae. Antibody reactivity correlated with infection status, but serum antigen concentrations through 161 days after inoculation were undetectable.