Amoebiasis In Hamsters Research Articles

Effect of bovine lactoferrin in a therapeutic hamster model of hepatic amoebiasis1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.

Entamoeba histolytica is the causative agent of amoebiasis, a disease that produces dysentery as a result of the perforation of the large intestine. This parasite often invades other organs, primarily the liver, leading to an amoebic liver abscess (ALA), which can cause death. Metronidazole is the drug of choice for the treatment of ALA; however, it produces toxic side effects in patients. Lactoferrin (Lf) is a glycoprotein of the innate immune response that sequesters iron in the mucosae. Lf possesses immune-regulatory properties, such as antiinflammatory and antioxidant activities. Moreover, the microbicidal activity of apoLf, which lacks bound iron, has been shown. In this study, we evaluated the therapeutic effect of bovine Lf (bLf) against ALA in a model of hepatic amoebiasis in hamsters. Interestingly, hamsters treated intragastrically with Lf (2.5 mg/100 g mass) over a period of 8 days showed no clinical signs of disease and ALA was effectively decreased, with only 0.63% detectable lesion, compared with 63% in untreated animals. Furthermore, liver function and blood cells approached normal levels among those receiving bLf treatment. These results suggest that bLf may aid in the therapy of amoebiasis, likely without producing undesirable effects in patients.

Melatonin reduces the severity of experimental amoebiasis

BackgroundMelatonin has immunomodulatory effects but very little is known about its influence in protozoan infections, such as Entamoeba histolytica, which causes amoebiasis, a disease with significant morbidity and mortality. In this study, we evaluated the effects of exogenous melatonin interference in experimental amoebiasis and on interactions between human blood cells and E. histolytica trophozoites.MethodsThe effect of melatonin was investigated in models of experimental amoebiasis in hamsters and rats by evaluating the area of necrosis induced by E. histolytica. The activity of melatonin on the interactions between leukocytes and amoebae was determined by examining leukophagocytosis. For in vitro tests, polymorphonuclear and mononuclear human blood leucocytes were incubated with E. histolytica trophozoites.ResultsThe areas of amoebic necrosis were significantly reduced in animals treated with melatonin. Melatonin treatment increased leukophagocytosis but was associated with a greater number of dead amoebae.ConclusionsThese results suggest that melatonin may play a beneficial role in the control of amoebic lesions, raising the possibility that this drug may be used as an adjuvant in anti-amoebic therapy.

A pcDNA- Ehcpadh vaccine against Entamoeba histolytica elicits a protective Th1-like response in hamster liver

DNA vaccines are promising tools to fight parasitic diseases, including amoebiasis caused by the protozoan Entamoeba histolytica. Here we studied the immunogenicity and protective efficacy of a DNA vaccine against this parasite composed by the EhCPADH surface complex encoding genes ( Ehcp112 and Ehadh112). EhCPADH is formed by an adhesin (EhADH112) and a cysteine proteinase (EhCP112), both involved in the parasite virulence. We evaluated transcription, protein expression, immunological response and protection against hepatic amoebiasis in hamsters intradermally and intramuscularly immunized with a mixture of pcDNA- Ehadh112 and pcDNA- Ehcp112 plasmids. RT-PCR and immunohistochemical assays showed that both antigens were differentially expressed in spleen and liver of immunized animals. No significant antibody immune response was induced by either route. However, intradermally inoculated hamsters presented a robust Th1-like immune response, characterized by high levels of INF-γ and TNF-α cytokines, detected in the liver of animals challenged with virulent trophozoites. Animals showed significant protection against amoebiasis manifested by a higher survival rate and a significant prevention of liver abscess formation. We conclude that a refinement of this DNA vaccine could be a good choice to control hepatic amoebiasis.

Morbidity due to Schistosoma mansoni - Entamoeba histolytica coinfection in hamsters (Mesocricetus auratus)

Data on Schistosoma mansoni-Entamoeba histolytica coinfection are scarce in the literature. In the present study, hamsters that had been infected for 70 days with Schistosoma mansoni (LE strain) were inoculated via the portal vein with two strains of trophozoites of Entamoeba histolytica: ICB-EGG (highly virulent) and ICB-RPS (non-virulent). The most evident result of coinfection was increased morbidity and mortality, in comparison with either of the infections alone. Histologically, there were no evident signs of interaction between these two infections. The morphological findings of schistosomal granuloma and amoebic abscesses in the liver were similar to those seen in the respective single-infection controls. However, there was severe wasting of the animals with both infections and greater numbers of amoebic lesions in their livers. The results obtained indicated that schistosomiasis aggravates the course of amoebiasis in hamsters.

Improved method of producing amoebic liver abscesses in hamsters for screening of systemically active amoebicides.

An improved method of producing hepatic amoebiasis in hamsters has been developed. A serially liver-passaged strain of Entamoeba histolytica from experimentally-infected hamsters was used for infection. Small pieces from the infected liver were examined for the presence of amoebae and contained approximately 20,000 active trophozoites per piece. Such liver pieces, when used as an inoculum, produced infection in all of the animals. The method has been successfully employed for screening of known amoebicides such as emetine, dehydroemetine, metronidazole, tinidazole, chloroquine, mepacrine, amodiaquine and ambilhar.

Passive transfer of immunity against hepatic amoebiasis in the hamster by cells.

The role of passive cell-mediated transfer of immunity in hepatic amoebiasis in hamsters was studied. The transfer of peritoneal cells from hamsters vaccinated against or protected from hepatic amoebiasis and from those with hepatic amoebiasis, as well as of spleen cells from vaccinated or protected, but not from infected hamsters, conferred immunity against hepatic amoebiasis in recipient normal hamsters. Treatment of the spleen cells from protected hamsters with anti T-cell serum abolished their ability to transfer immunity. It appears that the effector mechanism in this system is T-cell dependent.

Effect of complement depletion on hepatic amoebiasis in hamsters

Depletion of complement in hamsters by means of treatment with cobra venom factor resulted in an aggravation of pathology resulting from experimentally induced hepatic amoebiasis, such that animals inoculated intrahepatically with 1 × 10 5 Entamoeba histolytica trophozoites (but not with 4 × 10 4 trophozoites) had a significantly reduced survival time and significant loss of body weight, as compared with normal controls. Complement-depleted hamsters inoculated with both doses of amoebae developed significantly bigger amoebic liver abscesses and amoebic metastatic foci than their respective controls, not depleted of complement.

Macrophage requirement for host defence against experimental hepatic amoebiasis in the hamster.

The role of macrophages in hepatic amoebiasis in hamsters has been investigated by means of their treatment with bacille Calmette-Guérin (BCG) for activation, and with silica for elimination of these cells. Silica-treated animals inoculated intrahepatically with 1 x 10(5) trophozoites of Entamoeba histolytica developed amoebic abscesses in the liver and more metastases to other organs than control animals, and this effect was silica-dose-dependent. In contrast, BCG-treated animals developed significantly smaller abscesses in the liver and fewer metastatic foci. These data suggest that macrophages are involved in host defence against the establishment of amoebic liver abscess and metastatic dissemination of amoebae.

Effect of immunosuppression on the size and metastasis of amoebic liver abscesses in hamsters.

The effect of T-cell depletion on experimental hepatic amoebiasis in hamsters was investigated. Thymectomized and anti-T-cell (ATS) treated animals as well as sham-operated and unoperated controls were inoculated intrahepatically, following laparotomy, at 7 weeks of age with 1 x 10(5) axenic trophozoites of Entamoeba histolytica. In neonatally thymectomized hamsters the mean weight of the liver abscess 10 days post-inoculation was significantly greater than in neonatally sham-operated or unoperated controls, but there was no significant difference between these groups of animals in the size of metastatic foci to other organs. On the other hand, a combination of neonatal thymectomy and ATS treatment enhanced both the size of the primary abscess in the liver and the size of metastases to other sites. Adult thymectomy did not have a significant effect either on the size of the primary abscess or on metastatic dissemination of amoebae from the liver. Treatment of hamsters with ATS shortly before or after intrahepatic challenge increased significantly the size of the abscess, but similar treatment 2-3 weeks prior to challenge had no effect. These observations suggest that thymus-dependent cell-mediated immunity plays an important role in the host response to E. histolytica infection.

Effect of splenectomy on the size of amoebic liver abscesses and metastatic foci in hamsters.

The role of the spleen in hepatic amoebiasis in hamsters was studied. In hamsters receiving an intrahepatic inoculation of 10(5) trophozoites of axenic Entamoeba histolytica at 7 or 14 days postsplenectomy, the mean weight of metastatic foci increased significantly when compared with sham-splenectomized or intact controls. In contrast, when both splenectomy and intrahepatic inoculation with amoebae were carried out at the same time, there was not only a significant increase in the mean weight of metastatic foci but also in the liver abscess. It is suggested that the spleen is important for host defense against E. histolytica infection, especially in the reduction in the degree of metastatic spread from the primary site.