Brain-eating Amoebae: Biology and Pathogenesis of Naegleria fowleri
"explains the current knowledge and research" (ProtoView)
Caister Academic Press
, Ibne Karim M. Ali2
, Jennifer R. Cope2
and Naveed Ahmed Khan1
1Sunway University, Selangor, Malaysia; 2Centers for Disease Control and Prevention, Atlanta, USA
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Naegleria fowleri is a eukaryotic protist pathogen that causes primary amoebic meningoencephalitis. It is one of the world's deadliest known parasites with a mortality rate higher than 90%: infection almost always results in death. A greater scientific understanding of this parasite, how it lives in the environment and its pathogenic mechanism, is crucial for the development of preventative and therapeutic strategies against this fatal, albeit rare disease.
This concise book on N. fowleri serves as a quick guide for clinical practitioners, health professionals, researchers and students working with this parasite. Divided into easy-to-follow sections, the book covers all aspects of research into N. fowleri as an organism ranging from clinical and laboratory diagnosis to growth and life cycle. It is essential reading for all microbiologists, immunologists, physicians, public health officials and researchers (both new and experienced) involved with N. fowleri.
This book is an invaluable reference for everyone working in the field of basic and medical microbiology and a recommended acquisition for all parasitology, microbiology and medical libraries.
"explains the current knowledge and research on the parasite" from ProtoView
Table of contents
0. Introduction to Naegleria
1. Primary Amoebic Meningoencephalitis
Since the discovery of N. fowleri several decades ago, major efforts have failed to prevent and successfully treat primary amoebic meningoencephalitis. It is considered as one of the most aggressive parasitic infections, that almost always leads to death within a few days. The clinical course is dramatic exhibiting headache, stiff neck, seizures, coma, and death. The trophozoite enters the nose via contaminated water or dust, travels along the olfactory neuroepithelial route to reach the central nervous system and to provoke haemorrhagic necrosis. With the devastating nature of this disease and problems associated with its chemotherapy, here we describe the clinical features, pathophysiology and risk factors associated with primary amoebic meningoencephalitis.
2. Clinical and Laboratory Diagnosis
As the clinical course of primary amoebic meningoencephalitis is rapid, prompt detection of amoebae is crucial to increase the likelihood of patient survival by initiating early treatment. In general, due to non-specific and overlapping signs and symptoms of primary amoebic meningoencephalitis with those of bacterial or viral meningitis, and the rarity of N. fowleri infections, most primary amoebic meningoencephalitis cases are diagnosed retrospectively, i.e., during the autopsy examination of brain tissues. However, in live patients, primary amoebic meningoencephalitis is commonly diagnosed through microscopic examination of cerebrospinal fluid specimens. It is time critical to diagnose primary amoebic meningoencephalitis and begin empiric antimicrobial therapy. The diagnosis of primary amoebic meningoencephalitis depends on clinical features together with microscopic and/or molecular identification of the parasites in the cerebrospinal fluid specimens. This overview presents the diagnostic approach to primary amoebic meningoencephalitis.
3. Chemotherapeutic and Disinfection Strategies
While it is fortunate that primary amoebic meningoencephalitis is a rare disease, its rarity makes rigorous studies to find the most effective treatment difficult. The majority of studies rely on in vitro laboratory testing, mouse models of primary amoebic meningoencephalitis, and the few case reports of primary amoebic meningoencephalitis survivors to inform treatment recommendations for primary amoebic meningoencephalitis. In addition, the acquisition of drug resistance is a constant threat due to challenges in developing novel drugs. This chapter will present current treatment recommendations based on recent survivor case reports followed by a discussion of the drugs, treatment interventions used, promising new therapies and disinfection strategies.
Primary amoebic meningoencephalitis usually occurs after the inhalation of water containing amoebae or flagellates. It also has been suggested that inhaling cysts, during dusts storms, for example, could lead to infection. Amoeba penetrate the nasal mucosa and the cribiform plate and travel along the olfactory nerves to the brain. Amoebae first invade the olfactory bulbs and then spread to the more posterior regions of the brain. Within the brain they provoke inflammation and cause extensive damage to the tissue. In view of the devastating nature of N. fowleri infection and the problems associated with successful prognosis, here we describe current understanding of the pathogenesis of primary amoebic meningoencephalitis, as well as factors that affect virulence of N. fowleri, with an eye to identify potential therapeutic targets.
5. The Host-damage Response to N. fowleri
Primary amoebic meningoencephalitis is a product of N. fowleri virulence factors and collateral damage from the host immune responses. Immune-mediated host damage is particularly important within the central nervous system, where the immune responses may exacerbate cerebral edema and neurological damage, leading to coma and death. Given the challenges associated with the availability of effective antimicrobial chemotherapy, here we discuss existing knowledge of the role of immune response to N. fowleri. Consideration of the underlying mechanisms of host responses can provide critical insights into host damage that can be exploited to develop adjunctive therapies to improve disease outcome.
6. Cell Biology and Speciation
N. fowleri is a free-living opportunistic protist. Although the ability of N. fowleri to produce infection of the central nervous system has gained significant attention as an important human pathogen, producing fatal primary amoebic meningoencephalitis, however it also has fascinating biology exhibiting three life forms, and may play an important role in the ecosystem. The study of the cell and molecular biology of ancestral eukaryotic single-celled protists such as Naegleria, can provide fundamental insight of molecular pathways that evolved in multicellular organisms, as well as understanding of the causal relationships between genotype and phenotype.
7. Cellular Differentiation in N. fowleri
N. fowleri has a fascinating biology and exhibits three life forms. It reproduces in the amoeboid form, transforms into a flagellate to travel long distance to search for food, and switches into a dormant cyst to withstand harsh conditions. As a flagellate, it is a useful model organism to study motility processes of flagellates; as an amoeba, it is a useful model to study molecular biology of phagocytosis; and its ability to transform into cysts that remain viable for months to years, makes it an attractive model to study cellular differentiation processes of cell dormancy. In this chapter, we discuss the present knowledge of cellular differentiation processes in N. fowleri and associated factors.
8. Growth and Lfe Cycle
N. fowleri belongs to the genus Naegleria, family Vahlkampfiidae in the class Heterolobosea. It is a free-living protist that feeds mostly on bacteria. N. fowleri has a simple life cycle that includes asexual reproduction by binary fission, however its ability to respond to changing environments and remain viable is both complex and intriguing. While there are invasive free living stages, proliferation and differentiation are highly regulated events. Here, we describe the present knowledge of aspects of the parasite's life cycle, and associated factors that influence its growth.
The knowledge of the ecology of N. fowleri, its environmental niches, the effect of climate change or thermal pollution, or the role of man-made environments such as recreational waters, on the growth and distribution of amoebae abundance in the environment is critical to our understanding of its biology, as well as to develop preventative measures and create public awareness. To this end, N. fowleri is ubiquitous. It has been isolated from diverse natural environments including soil, water, and air, as well as man-made environments, and human tissues. Here, we summarize the distribution of N. fowleri in various environments.
10. War of the Microbial Worlds
N. fowleri harbours microbial organisms including viruses, and bacteria, some of which are potential pathogens. The precise nature of this symbiosis is not clear, but it is suggested that such interactions enable pathogenic microbes to survive hostile conditions and this association can lead to their transmission to susceptible hosts to establish infection. In this context, Naegleria can act as vehicles for the multiplication and dispersal of pathogenic microbes as well as providing shelter for such bacteria from antibiotic and disinfection treatments. These findings suggest that employing anti-amoebic approaches in eradicating bacterial pathogens may be an effective strategy to counter threat from both Naegleria as well as bacterial pathogens. For example, Naegleria-Legionella interactions have gained significant attention by the scientific and the medical community.
11. Conclusions and Future Studies
The diagnosis of N. fowleri infections is not straightforward and treatment is problematic. Further research is needed for prevention, pathogenesis and therapy and in particular for the development of rapid, cost-effective, and non-invasive assays for early diagnosis. Moreover, epidemiology studies are needed to determine the true burden of N. fowleri infection, both in humans and animals, and whether disease patterns differ around the world. There is a need to determine the effect of environmental factors, demographic factors, socioeconomic factors, in the spread, transmission, and prevalence of the parasite, as well as host susceptibility in contracting N. fowleri infection. The precise molecular mechanisms underlying N. fowleri pathogenesis and the role of inflammation and immune response need to be elucidated, as well as the understanding of mechanisms of flagellation, encystation, excystation, and associated metabolic pathways. In addition, there is a need for improvement of educational efforts to raise awareness among the public as well as the medical community (neurologists, physicians) of this devastating infection.
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(EAN: 9781910190531 9781910190548 Subjects: [medical microbiology] [microbiology] [parasitology] )