Pathogenesis of Plasmodium berghei ANKA infection in the gerbil (Meriones unguiculatus) as an experimental model for severe malaria.

Quazim Olawale Junaid,Yee Ling Lau,Rohela Mahmud,Loke Tim Khaw,Jonathan Wee Kent Liew,Prajakta Uttam Borade,Sinnadurai Sivanandam,Kum Thong Wong,Indra Vythilingam,Kien Chai Ong

doi:10.1051/parasite/2017040

Quazim Olawale Junaid, Yee Ling Lau + Show 8 more

Open Access

https://doi.org/10.1051/parasite/2017040

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Abstract

Background: As the quest to eradicate malaria continues, there remains a need to gain further understanding of the disease, particularly with regard to pathogenesis. This is facilitated, apart from in vitro and clinical studies, mainly via in vivo mouse model studies. However, there are few studies that have used gerbils (Meriones unguiculatus) as animal models. Thus, this study is aimed at characterizing the effects of Plasmodium berghei ANKA (PbA) infection in gerbils, as well as the underlying pathogenesis. Methods: Gerbils, 5-7 weeks old were infected by PbA via intraperitoneal injection of 1 × 106 (0.2 mL) infected red blood cells. Parasitemia, weight gain/loss, hemoglobin concentration, red blood cell count and body temperature changes in both control and infected groups were monitored over a duration of 13 days. RNA was extracted from the brain, spleen and whole blood to assess the immune response to PbA infection. Organs including the brain, spleen, heart, liver, kidneys and lungs were removed aseptically for histopathology. Results: Gerbils were susceptible to PbA infection, showing significant decreases in the hemoglobin concentration, RBC counts, body weights and body temperature, over the course of the infection. There were no neurological signs observed. Both pro-inflammatory (IFNγ and TNF) and anti-inflammatory (IL-10) cytokines were significantly elevated. Splenomegaly and hepatomegaly were also observed. PbA parasitized RBCs were observed in the organs, using routine light microscopy and in situ hybridization. Conclusion: Gerbils may serve as a good model for severe malaria to further understand its pathogenesis.

Highlights

According to the World Health Organization (WHO), an estimated 214 million new cases of malaria and 438,000 deaths were recorded in the year 2015 [76]
Gerbils showed high susceptibility to Plasmodium berghei ANKA (PbA) infections with 100% mortality recorded at all concentrations of parasitized red blood cells (pRBCs) tested within 30 days post-infection, with the exception of 102 pRBCs, showing 80% mortality by day 27 pi (Figure 1a)
This study shows that gerbils did not respond early to PbA infection as revealed by expressions of inflammatory cytokines such as Interferon gamma (IFN-g) and TNF (Figure 6)

Summary

Introduction

According to the World Health Organization (WHO), an estimated 214 million new cases of malaria and 438,000 deaths were recorded in the year 2015 [76]. To reduce this threat, there is still a need to better understand the underlying processes that result in severe disease outcome and mortality. The clinical features and pathogenesis of severe malaria were attributed to either severe anemia due to destruction of red blood cells (RBC) or cerebral malaria (CM), which is caused by obstruction of small vessels of the brain by sequestered parasites [50]. The host has evolved a mechanism in controlling the degree of RBC destruction, which is beneficial to some, while detrimental to others

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