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[Experimental infection of Naegleria fowleri in mice]
T Kuroki1, K Yagita, H Sugiyama
1Department of Bacteriology and Pathology, Kanagawa Prefectural Public Health Laboratory.
Abstract:
Ten SPF mice (ddY, 4w-old, female) were infected by nasal instillation with an isolate of Naegleria fowleri that was first isolated from a patient with primary amoebic meningoencephalitis (PAM) in Japan. Of these mice, 2 showed clinical signs typical for PAM on the 4th day. On the next day, 5 mice became very ill and remained immobile; their movement and response to painful stimuli diminished progressively. All the infected mice were then examined histopathologically on the same day regardless of their clinical signs. Pathological changes due to invasion and/or proliferation of amoebae were observed in 5 mice with clinical signs. Swelling of the nasal mucosa and ulcerated nasal epithelium with inflammatory cells were observed. Proliferation of amoebae was detected to a lesser extent in nasal cavity including mucous membrane and nasal epithelium. Olfactory lobes and arteriolar hemisphere were necrotic with haemorrhage and filled with amoebae. From these findings the pathogenicity of the isolate was confirmed to develop PAM in experimental animals. It was also observed that the olfactory neuroepithelium was the route of invasion in PAM due to N. fowleri and consequently migration occurred through olfactory lobes into the cerebrum.
Insights
This study confirms the pathogenicity of Naegleria fowleri, causing primary amoebic meningoencephalitis (PAM) in mice. The olfactory neuroepithelium serves as the invasion route, leading to severe brain pathology.
Area of Science:
- Microbiology
- Pathology
- Neuroscience
Context:
- Naegleria fowleri is a free-living amoeba responsible for primary amoebic meningoencephalitis (PAM), a rare but fatal infection.
- Understanding the pathogenesis and route of infection is crucial for developing potential treatments.
Purpose:
- To confirm the pathogenicity of a specific Naegleria fowleri isolate in a mouse model.
- To investigate the histopathological changes and route of invasion associated with PAM.
Summary:
- SPF mice were infected intranasally with Naegleria fowleri. Clinical signs of PAM appeared by day 4, with rapid deterioration observed. Histopathological examination revealed amoebic invasion and proliferation in the nasal cavity, olfactory lobes, and cerebrum.
- Pathological changes included nasal mucosal swelling, ulcerated epithelium, necrosis, and hemorrhage in the olfactory lobes and cerebrum, confirming the isolate's virulence.
- The olfactory neuroepithelium was identified as the primary entry point, with subsequent migration to the brain via the olfactory lobes.
Impact:
- This research validates the use of this Naegleria fowleri isolate in experimental models for PAM research.
- It elucidates the critical role of the olfactory neuroepithelium in the pathogenesis of PAM, providing insights for future diagnostic and therapeutic strategies.