COMPARISON OF PATHOGENESIS OF P. BERGHEI INFECTION IN MOUSE AND RAT MODELS
Voon Kin ChinWing Chui ChongNorshariza NordinTze Yan LeeZakaria Zainul AmiruddinHaniza HassanRusliza Basir
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Background: The cytokine cascade in the immunopathogenesis of malaria infection had been widely studied. However, their specific association with survival and severe infection remained obscure. Methods: The study investigated the cytokine profiles and histopathological features of malaria in the severe infection and survival models by using male ICR mice and male Sprague Dawley rats respectively. Results: The severe model, the infected ICR mice, exhibited a high parasitemia with 100% mortality after peak parasitemia at day 5 post-infection. The survival model, the infected Sprague Dawley rats, showed mild parasitemia with full recovery by day 14 of infection. Both severe and survival models showed similar histopathological severity during peak parasitemia. The severe model produced highly elevated levels of proinflammatory cytokines, TNF-α and IL-1α, and low levels of the anti-inflammatory cytokine, IL-4; while the survival model showed low levels of TNF-α and IL-1α with high levels of IL-4. Conclusion: There were differences in the pathogenesis of the severe and survival models of malaria infection. These could be a basis for immunotherapy of malaria in the future. Keywords:
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Malaria is an infectious disease caused by protozoa of the genus Plasmodium and transmitted through the bite of a female Anopheles mosquito. Plasmodium berghei ANKA is a species of rodent malaria parasite that is commonly used to study malaria pathology and the immune system against infections. Parasitaemia in malaria is the figure of malaria pathology due to some numbers of parasite-infected erythrocytes present in the peripheral blood. Hemoglobin (HGB) and hematocrit (HCT) levels are the parameters of anemia and some hematological changes caused by malaria infection. This study aimed to determine the correlation between parasitemia and anemia in BABL/c mice infected with Plasmodium berghei ANKA. Two uninfected and infected mice groups were compared for parasitemia, HGB, and HCT levels. Analysis statistics showed a significant difference in HGB and HCT between uninfected and infected groups. Pearson correlation analysis showed no significant correlation between parasitemia and HGB and HCT levels in infected mice. Anemia in mice infected with Plasmodium berghei ANKA can occur when parasitemia is even low; the higher parasitemia worsens the hamatological condition. Parasitemia plays a role independently in the severity of anemia. Plasmodium berghei infection in mice is useful for studying malaria anemia.
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We investigated the in vivo activity of crude water extracts of Ajuga remota Benth (Labiatae) against Plasmodium berghei in mice using plants harvested from two areas in Kenya where the plant is commonly used to treat malaria. The extract was tested using a 4-day test at a dose of 30 mg/kg/day (equivalent to 0.2 ml solution per mouse). Wet leaf extract was the most effective with 90.4% suppression of parasitemia. Extract from air-dried and powdered flowers were the least effective with 17.2% suppression of parasitemia.
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Parasitemia in young rats infected with Plasmodium berghei can be monitored by electronic counting of particles in blood lysates. The number of particles so obtained provides an estimate of the number of parasitized cells in the blood sample. The method is highly reproducible as compared to conventional techniques, especially as applied to low levels of parasitemia. The further advantage of rapidity is also inherent in the procedure.
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Summary Parasitemia in young rats infected with Plasmodium berghei can be monitored by electronic counting of particles in blood lysates. The number of particles so obtained provides an estimate of the number of parasitized cells in the blood sample. The method is highly reproducible as compared to conventional techniques, especially as applied to low levels of parasitemia. The further advantage of rapidity is also inherent in the procedure.
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Humoral immunity
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Cerebral Malaria
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The effect of lowered host-environmental temperature upon the development and maturation of the preerythrocytic tissue stages of rodent malaria parasites has been investigated in two strains of Plasmodium berghei originating from the highlands of Katanga. Young albino rats inoculated with massive sporozoite doses of P. berghei NK 65 and maintained for 48 hours at 12° C developed small, stunted tissue schizonts, averaging 11 × 15 microns, of a distinct morphology. Control rats kept at room temperature of 27° C showed mature tissue schizonts of normal growth averaging 24 × 29 microns. Blood from the rats kept at lower temperature for 48 to 50 hours failed to produce parasitemia when inoculated into susceptible recipient mice. All the mice given blood from control rats developed parasitemia. However, when sporozite-inoculated rats were kept for 96 hours or longer at 12° C they developed parasitemia and their liver showed maturation of 10% of the preerythrocytic schizonts. Experiments with the ANKA strain of P. berghei did not show significant differences in size and morphology between parasites in rats kept for 46.5 hours at 9° C and 12° C and those in controls kept at 20° C. However, subinoculation of blood from the low temperature experimental groups into recipient mice at 46.5 hours after intravenous sporozoite inoculation failed to produce parasitemia, whereas all the recipient mice from the control groups developed parasitemia in 4 or 5 days. The findings are discussed in the light of the evolution of plasmodia and the phenomena of relapse and delayed primary attack in certain malaria infections.
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Parasitemia counts established that 22 degrees C-acclimated mice subjected to cold exposure for a short time (-35 degrees C for 30 min) during Plasmodium berghei infection had significantly higher parasitemia levels than parasitized mice continuously housed at 22 degrees C. Parasitized 5 degrees C-acclimated mice also demonstrated higher parasitemia levels than parasitized 22 degrees C-acclimated mice. There was no correlation between plasma free fatty acid (PFFA) concentration and parasitemia in mice infected with P. berghei. The effect of clofibrate (an agent known to reduce PFFA levels in rats) in reducing PFFA levels in mice was inconclusive. However, the P. berghei-infected mice treated with clofibrate demonstrated significantly lower parasitemia when compared to parasitized mice that were not treated with clofibrate.
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