Characterisation of Plasmodium berghei NK65 Infection in ICR Mice as a Severe Malarial Infection Model

Severe malaria is commonly caused by Plasmodium falciparum infection. Plasmodium falciparum infection in human can cause organ damage, severe anaemia, serious complications, coma and death. For the purpose of understanding the pathogenesis of severe malaria, an animal model was used in this study to examine whether the combination of host-parasite from ICR mice with Plasmodium berghei NK65 caused severe malaria infection in the host. Characterisation of P. berghei ANKA infection has been performed previously on ICR mice, however, the detailed histopathological view of P. berghei NK65 infection on ICR mice in this study was first reported. Inoculation of the P. berghei NK65-infected red blood cells (RBCs) (2x10(7) parasitised RBCs (pRBC)/mL) were performed on ICR mice by intraperitoneal injection. Changes in physical characteristics such as body weight, temperature, mortality, post-mortem, histopathology and levels of inflammatory cytokines resulting after infection were recorded for analysis. The P. berghei NK65 strain produced a severe level of infection in ICR mice i.e., the degree of parasitaemia exceeded 50% on day-10 after infection followed by death. Histopathological analysis showed that the infection caused changes in cerebral tissue, accumulation of leukocytes to the endothelium and sequestration of pRBCs in the cerebral blood vessels as well as intravascular haemorrhage. After infection, pRBC sequestration and accumulation of malaria pigments were also observed in the major organs. In addition, pulmonary oedema, hyaline membrane formation in the lungs and cortical haemorrhage in the kidneys were seen in infected mice. Proinflammatory cytokines (TNF-alpha, IFN-gamma, and IL-18) and anti-inflammatory cytokines (IL-10 and IL-4) were also increased in the serum of infected mice. In summary, the ICR mice-P. berghei NK65 infection model used in this study showed characteristics of severe malaria infection in human. The insights from this study can be used as a basis for understanding the pathogenesis of severe malaria in human and models of rodent malarial infection in the future.

Automated summary

This study used an animal model to investigate the effects of host-parasite combination on severe malaria infection. The results showed that mice infected with P. berghei NK65 exhibited various pathological changes associated with severe malaria, including organ damage, leukocyte accumulation, and intravascular hemorrhage. Additionally, increased levels of inflammatory cytokines were observed in the serum of infected mice.