adjuvant effects of IL-12 and BCG on autoclaved leishmania major vaccine in experimental cutaneous leishmaniasis

Cutaneous leishmaniasis is a universal disease causing skin ulceration and deformity. A reliable vaccine remains to be a possible practical means of control. The amastigotes multiply intracellulary in macrophages provoking a cell-mediated type of immune response. IL-12 is the central cytokine of CMI. It is produced by sensitized macrophages, stimulates both Th 1 and NK cells to secrete IFN-gamma which in turn activates the intracellular killing of Leishmania in macrophages via increased oxygen radicals. This work aimed mainly at studying the adjuvant effect of IL- 12 on autoclaved L. major [ALM] vaccine, compared to that of BCG in L. major infection. The material included five groups of Swiss albino mice; the test group infected after receiving ALM + IL-12, a non-infected control group, and three other control groups infected after receiving ALM + BCG, IL-12 alone and BCG alone L. major was cultured to provide promastigotes for vaccine and infection. The measured parameters included the lesion size, type and progress; the parasite density and the level of IFN-gamma in serum. The results showed that the best protection against challenge infection was obtained by ALM + IL-12 followed by ALM + BCG. The former is recommended for use as a vaccine with regards to its proved efficacy and known safety

Experimental trichinosis: parasitological, electrophysiological and biochemical studies

Trichinosis is a parasitic infection affecting the gut and the muscles causing mild gastrointestinal symptoms followed by periorbital oedema, muscle pains, fever and eosinophilia. The infection evokes functional disturbances in physiological effector systems. Furthermore, several biochemical changes are associated with the infection. Therefore, this work was carried out to study the electrophysiological changes in intestine, striated and cardiac muscles by electromyography [EMG] and to assess the biochemical changes through measurement of serum cholinesterase and intestinal myeloperoxidase activity [MPO] in both light and heavy infected experimental animals by Trichinella spiralis [T. spiralis]. Electrophysiological results showed increased contractility of the smooth muscle layers of the intestine only early in the infection, whereas both striated and cardiac muscles showed increase in the contractility with the progress of infection in both light and heavy infection. Significant myocardial dysfunction in the form of bradycardia, in addition to major histopathological changes in the heart occurred from the beginning of the infection and increased till the end of the study. Biochemical study showed gradual increase in serum cholinesterase, while, the intestinal MPO showed increase only in the early stage of the infection. It was noticed that all changes were more pronounced in the heavily infected group than the lightly infected one

comparative efficacy study of praziquantel and albendazole treatment in experimental schistosomiasis

The currently used drug for chemotherapeutic control of schistosomiasis is praziquantel [PZQ]. Albendazole is a broad spectrum antiparasitic drug that showed trematocidal activity. The present study aimed at testing the effect of albendazole on experimental schistosomiasis mansoni infection using PZQ as therapeutic control. Swiss strain albino mice were infected with Schistosoma mansoni [S. mansoni] cercariae. Drugs were given orally on the 45[th] day post infection [PI] for 2 successive days. Mice were sacrificed on the 47[th] day PI and subjected to parasitological and scanning electron microscopic [SEM] studies. Albendazole caused a significant reduction in worm load and those recovered were shorter as measured by the camera lucida. By SEM, perfused S. mansoni albendazole treated worms showed surface tegumental changes. Albendazole is a promising drug for treatment of schistosomiasis

Vaccination trial against experimental trichinellosis using autoclaved trichinella spiralis larvae vaccine [ATSLV]

The autoclaved Trichinella spiralis larvae vaccine [ATSLV] was tested and showed unpredictable effect on the immune system of mice experimentally infected with T. spiralis. The vaccine was given with Bacillus Calmette-Guerin [BCG] as an adjuvant at different durations and by different routes of administration. The best result was achieved by given the vaccine twice intradermally with two-week interval as evidenced by a significant reduction in adult and larval count, as well as reproductive capacity index. Histopathologically, there was a significant reduction in the number of the encysted larvae, which showed degeneration and hyalinization of the cyst wall accompanied by early pericystic fibrosis

Ultrastructural and immunological features of experimental cutaneous leishmaniasis after treatment with intralesional hypertonic sodium chloride and CO2 laser rays

This study investigated the mechanism of action and efficacy of CO2 laser rays and hypertonic sodium chloride [NaCl] with different concentrations in the treatment of cutaneous leishmaniasis [CL] as assessed clinically, parasitologically, histopathologically by light and transmission electron microscopy [TEM] and immunologically by RT- PCR for gene expression of interleukin-13 [IL-13]. Eighty mice were divided into four groups: The first was non-infected control group [n=16], the second was infected and served as non-treated control [n=16] as well as the third [n=32] and fourth groups [n=16] were subjected to NaCl injection and CO2 laser, respectively. The results showed that the clinical healing by CO2 laser was nearly similar to the normal appearance, but differed according to the concentration of NaCl as confirmed by the ultrastructure and immunohistopathologic features of the host cells and surrounding skin tissue. IL-13 mRNA was significantly decreased after treatment denoting that Th2 cytokine [IL-13] is important for the development of strategies to prevent the induction of the pathologic processes. It was concluded that CO2 laser and 7% NaCl are good modalities for CL treatment and were recommended, wherever possible

possible antifibrotic effect of theophylline, diltiazem, deferoxamine and minoxidil on the development of murine schistosomal hepatic fibrosis

The effects of theophylline, diltiazem, deferoxamine and minoxidil with and without praziquantel [PZQ] were tested on Schistosoma mansoni infected mice to investigate their possible effect on the progression of hepatic granulomatous reaction into fibrosis in murine schistosomiasis. 66 male Swiss strain albino mice were used in the study. They were divided into 4 groups; control group; infected and treated with PZQ [1000 mg/kg/day] orally for two successive days; infected and treated for 2weeks with deferoxamine [25 mg/kg/day], diltiazem [24 mg/kg/day], theophylline [30 mg/kg/day], or minoxidil [1.0 mg/kg/day]; infected and treated with each of the previous drugs combined with PZQ. At the 10[th] week postinfection, animals were subjected to splenic pulp pressure measurement. The pathological changes in the liver were examined by routine H and E and Masson Trichrome stains. Livers were examined for egg count, granulomas number and size. Liver collagen deposition was also determined. Statistical correlation of the results was done. Praziquantel significantly reduced liver egg count, granulomas number and size. It decreased liver fibrosis assessed histopathologically, liver collagen content and portal venous pressure but not to significant levels. None of the tested drugs [deferoxamine, theophylline, diltiazem, or minoxidil] succeeded to reduce schistosoma egg deposition or granulomas number and size in livers of schistosoma-infected mice. However, significant reduction in these parameters was achieved only when PZQ was added to the treatment regimen. Deferoxamine, theophylline, and minoxidil significantly decreased level of hepatic fibrosis, collagen deposition and portal venous pressure. These effects were significantly augmented when PZQ was combined with any of these drugs. Diltiazem alone or in combination with PZQ failed to decrease liver collagen content or hepatic fibrosis induced by schistosoma infection. However, diltiazem alone or in combination with PZQ could significantly reduce portal venous pressure. Accordingly, it is recommended to extend this animal study to human to investigate the possible mitigation of the deleterious effects of schistosomiasis on the liver by the addition of deferoxamine, theophylline, or minoxidil to its treatment regimen. Diltiazem can also be used to reduce portal venous pressure

novel macrolide in mixed protozoal infection in immunosuppressed mice

As the number of immunocompromized patients is increasing, there will be an increasing need for a reliable therapy efficacious against the opportunistic intestinal protozoa. The present work aimed to study the efficacy of azithromycin as a single weapon directed against mixed intestinal protozoal infection induced in immunosuppressed mice. In the infected treated group of mice, there was a marked amelioration of the pathological changes provoked by the four parasites Cryptosporidia, Enterocytozoon bieneusi, Giardia lamblia and Entamoeba histolytica. As long as the mice were receiving azithromycin, there was a significant reduction of all parasitic stages with the complete absence of spore forming protozoa. One week after the drug was stopped Giardia lamblia and Entamoeba histolytica stages were progressively reduced but oocysts of cryptosporidia and spores of Entercytozoon bieneusi reappeared in situ. Azithromycin therapy should be continued as long as the individual is immunosuppressed

Iron chelators and experimental cutaneous leishmaniasis

Swiss albino mice infected with Leishmania parasite in their hind footpad were used to study the effect of experimental cutaneous leishmaniasis on the host iron metabolic parameters. Exogenous iron was given to the infected animals to study its influence on the course of this parasitic disease. Furthermore, in search for a safe and effective drug therapy, the two iron chelators [desferrioxamine [DFO] and pyridoxal isonicotinoyl hydrazone [PIH]] were tested as potential anti-leishmanial drugs. Infection with Leishmania parasite produced a significant decrease in serum iron, transferrin% saturation [Tf%], hemoglobin concentration [Hb] and hematocrit value [Ht] and a significant increase in serum ferritin and non-heme iron content of the liver and spleen. Iron treated infected animals showed exacerbation of cutaneous lesion with a significant increase in the hind footpad thickness and parasite score

Ultrastructure study of experimental cutaneous leishmaniasis before and after dapsone intake

Leishmania strain was isolated from a human case of cutaneous leishmaniasis and inoculated into experimental animals. Group of infected animals were given dapsone at a dose of 25 mg/kg for 3 weeks. Results showed that infected animals suffered from autoamputation of the inoculated foot pad. On the other hand, those receiving dapsone showed complete clinical cure. Transmission electron microscope of both groups revealed the fine structure of Leishmania amastigotes. Those given dapsone showed considerable reversible changes, which did not affect parasitic virulence. The latter has been demonstrated by their ability to infect experimental animals leading to pathological lesion. It should be pointed out that patients treated with this drug and showed marked clinical response must be very carefully examined for fear of residual parasites, which may be the cause of relapse later on

Confirmation of clinical differentiation of three Leishmania strains by computerized image analyser system

Three human strains of Leishmania, one visceral and two cutaneous leishmaniasis, were prepared from both culture and tissue of infected animals and subjected to analysis by computerized image analyzer system. The results showed differences in the morphology and nucleic acid contents of the three strains

Evidence of sexual reproduction in the protozoan parasite Leishmania of the old world

Three Leishmania strains of the old world were included in this study. Both the amastigote and promastigote stages were subjected to staining by Feulgen procedure and examined by computerized image analyzer system to determine their nuclear DNA content. Results of this study showed that in the promastigote stage, there is a single cell population; whereas in the amastigote stage, there are two populations of parasite nuclei, one with low level of DNA resembling that of the promastigote and a second population with double DNA level. The latter is formed when apparently two nuclei fused and form one with double DNA level. The data obtained in the present study indicated that Leishmania of the old world can undergo nuclear fusion, which is a strong evidence for the presence of sexual reproduction in the parasite