Oral artesunate prevents Plasmodium berghei Anka infection in mice

Artesunate, a semi-synthetic derivative of a naturally occurring anti-malarial artemisinin was compared with chloroquine in C57BL/6 mice infected with Plasmodium berghei Anka (PbA). A 7-day oral administration of artesunate prevented parasitaemia at 10 mg/kg/day. However, recrudescence of parasitaemia and cerebral malaria occurred upon cessation of treatment followed by death within 28 days. However, a 14-day course of artesunate (100 mg/kg/day) prevented completely the development of parasitaemia and cerebral malaria with a survival of more than 60-days as did 10 mg/kg/day chloroquine. These data demonstrate that oral artesunate inhibits PbA and prevents cerebral malaria, but needs to be administered at high dose and for prolonged time to eradicate PbA infection in mice.     

Oxidative damage of mice erythrocytes infected with Plasmodium berghei

By using the model of infection with plasmodium berghei in white mice the attempt was made to explain the oxidative damages of red blood cells as a cause for haemolysis. In addition to a diminished new formation of erythrocytes there was an increased cell lysis under the impact of infection. Without any changes of the Met-Hb-percentage and of Heinz bodies an increase of GSH and GSSG could be measured. The conclusion was drawn that a damage of red blood cells caused by oxidation may occur by changing the relation of reduced tripeptides to oxidised ones.     

Differences in Plasmodium berghei development in nude and normal mice

Mcguire R. W. 1984. Differences in Plasmodium berghei development in nude and normal mice. International Journal for Parasitology14: 57–61. Parasitemia is a cumulative index of hostparasite responses which constitutes a dynamic cycle of affector-effector mechanisms. Therefore, it is necessary to view these responses as host or parasite in nature and this investigation focused on parasite responses. This study supports previous findings, i.e., congenitally athymic (nu/nu) mice maintain higher parasitemias than control (nu/+) animals. Analysis of these differences demonstrate that, in the erythrocytic phase, the frequency of schizonts, the frequency of multiple-infected red blood cells and the number of nuclei per schizont are dependent on the immunological state of the host. Collectively, parasite developmental characteristics suggest that Plasmodium berghei has a greater reproductive capability and possibly a higher degree of sequestration while developing in nude mice.     

Plasmodium berghei berghei: Irradiated sporozoites of the ANKA strain as Immunizing Antigens in mice

Mice were protected against challenge with infective Sporozoites following immunization with X-ray irradiated Sporozoites. The immunity lasted at least 8 weeks. Mice immune against sporozoite challenge remained fully susceptible to challenge with erythrocytic stages. Immunization of mice with extracts of mosquito thorax failed to protect them, indicating that mosquito antigens were not directly responsible for the immunity observed in the basic experiments.     

Plasmodium berghei: biological variation in immune serum-treated mice.

Antiserum was obtained from mice which had been immunized with irradiated Plasmodium berghei parasitized erythrocytes and which survived subsequent challenge. This antiserum suppressed P. berghei infections in mice; parasitemia and mortality were delayed 7–8 days as compared to those of control animals. Parasites surviving in antiserum-treated animals were isolated by inoculation of blood into normal recipients. When antiserum was tested against this derived parasite population, there was no observable effect on parasitemia or mortality. The derived parasites also exhibited a decreased virulence for mice. This work confirms the previous observation that antiserum treatment can result in a biologically variant population of P. berghei.     

Plasmodium berghei: antiparasitic effects of orally administered hypoestoxide in mice

Hypoestoxide (HE) is a diterpene isolated from Hypoestes rosea (Acanthaceae), a plant indigenous to Nigeria. Previous studies demonstrated that HE exhibited potent anti-inflammatory and anti-cancer activities in well established animal models but weak in vitro activities in both the anti-inflammation and anti-cancer in vitro screening systems. We now report a similar observation in the in vitro and in vivo screening systems for antimalarial activity. The results indicate that while HE exhibits a relatively weak in vitro activity (IC(50) = 10 microM versus 0.11 microM for chloroquine) against different strains of cultured P. falciparum parasites, the dose of HE required to reduce parasitemia by 90% in Plasmodium berghei-infected mice, is much lower than standard antimalaria drugs (SD(90) = 250 microg/kg versus 5mg/kg for chloroquine). Furthermore, lower doses of HE were much more effective than higher doses in inhibiting parasite development. The implications of these findings are discussed.     

Iron deficiency influences the course of malaria in Plasmodium berghei infected mice

Iron deficiency accelerates suicidal erythrocyte death, which is evident from phosphatidylserine exposure. The present study explored whether iron deficiency compromises intraerythrocytic growth of Plasmodium and enhances death of infected erythrocytes thus influencing the course of malaria. As a result, phosphatidylserine exposure is increased in Plasmodium falciparum infected human erythrocytes, an effect significantly more marked in iron deficiency. Moreover, iron deficiency impairs in vitro intraerythrocytic growth and infection of erythrocytes. In mice, iron-deficient erythrocytes are more rapidly cleared from circulating blood, an effect increased by infection with Plasmodium berghei. Parasitemia in P. berghei infected mice was significantly decreased (from 54% to 33% of circulating erythrocytes 20 days after infection) and mouse survival significantly enhanced (from 0% to 20% 30 days after infection) in iron-deficient mice. In conclusion, iron deficiency favourably influences the course of malaria, an effect partially due to accelerated suicidal death and subsequent clearance of infected erythrocytes.     

Stimulation by adjuvants of cell-mediated immune response in Plasmodium berghei infected mice

Immunological adjuvants (alum, liposomes and saponin) were utilized to stimulate cell-mediated immune response in Plasmodium berghei infected Balb/c mice. It was shown that malaria antigen mixed with adjuvant induced appreciably delayed type hypersensitivity and production of migration inhibition factor compared to antigen alone.