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FEMS Immunology and Medical Microbiology Jun 2007Among the many genera of free-living amoebae that exist in nature, members of only four genera have an association with human disease: Acanthamoeba spp., Balamuthia... (Review)
Review
Among the many genera of free-living amoebae that exist in nature, members of only four genera have an association with human disease: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri and Sappinia diploidea. Acanthamoeba spp. and B. mandrillaris are opportunistic pathogens causing infections of the central nervous system, lungs, sinuses and skin, mostly in immunocompromised humans. Balamuthia is also associated with disease in immunocompetent children, and Acanthamoeba spp. cause a sight-threatening infection, Acanthamoeba keratitis, mostly in contact-lens wearers. Of more than 30 species of Naegleria, only one species, N. fowleri, causes an acute and fulminating meningoencephalitis in immunocompetent children and young adults. In addition to human infections, Acanthamoeba, Balamuthia and Naegleria can cause central nervous system infections in animals. Because only one human case of encephalitis caused by Sappinia diploidea is known, generalizations about the organism as an agent of disease are premature. In this review we summarize what is known of these free-living amoebae, focusing on their biology, ecology, types of disease and diagnostic methods. We also discuss the clinical profiles, mechanisms of pathogenesis, pathophysiology, immunology, antimicrobial sensitivity and molecular characteristics of these amoebae.
Topics: Acanthamoeba; Amebiasis; Amoeba; Animals; Humans; Naegleria fowleri
PubMed: 17428307
DOI: 10.1111/j.1574-695X.2007.00232.x -
Tropical Parasitology 2021is an opportunistic, free-living ameba that is pathogenic to humans. It has a worldwide distribution but is mainly detected in warmer regions. infections are rare but... (Review)
Review
is an opportunistic, free-living ameba that is pathogenic to humans. It has a worldwide distribution but is mainly detected in warmer regions. infections are rare but have been reported in both immunocompetent and immunocompromised individuals of all ages. can enter through wounds on the skin or the nose and cause cutaneous lesions and the usually fatal amebic encephalitis (BAE). Infection usually spreads from the lungs or through nerve fibers, and attacks the central nervous system, forming granulomatous lesions and necrosis in the brain. infection is usually chronic, and patients initially present with nonspecific symptoms, including headache, nausea, myalgia, and low-grade fever. As the disease progresses, the patient becomes paralyzed and comatose, often leading to death. Lack of knowledge of predisposing factors, specific treatment, and standardized detection tools have resulted in a nearly cent percent fatality rate. Although only about 200 cases have been reported worldwide since its characterization in the 1990s, the number of reported cases has increased over the years. BAE is an emerging disease and a major health concern. Few patients have survived infections with antimicrobial treatment that has largely been empirical. Early diagnosis is the key and requires familiarity with the disease and a high degree of suspicion on the part of the diagnostician. There are currently no specific treatment and prevention recommendations. This review highlights our current understanding of in terms of its pathogenicity, genomics, and novel diagnostic and therapeutic approaches against BAE infections.
PubMed: 34765527
DOI: 10.4103/tp.tp_36_21 -
Pathogens and Global Health Mar 2022Pathogenic free-living amoebae affecting the central nervous system are known to cause granulomatous amoebic encephalitis (GAE) or primary amoebic meningoencephalitis...
Pathogenic free-living amoebae affecting the central nervous system are known to cause granulomatous amoebic encephalitis (GAE) or primary amoebic meningoencephalitis (PAM). Although hosts with impaired immunity are generally at a higher risk of severe disease, amoebae such as and can instigate disease in otherwise immunocompetent individuals, whereas species mostly infect immunocompromised people. also cause a sight-threatening eye infection, mostly in contact lens wearers. Although infections due to pathogenic amoebae are considered rare, recently, these deadly amoebae were detected in water supplies in the USA. This is of particular concern, especially with global warming further exacerbating the problem. Herein, we describe the epidemiology, presentation, diagnosis, and management of free-living amoeba infections.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Humans; Naegleria fowleri
PubMed: 34602025
DOI: 10.1080/20477724.2021.1985892 -
Frontiers in Neurology 2023Free-living amoebae (FLA) including spp., and can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM),... (Review)
Review
BACKGROUND
Free-living amoebae (FLA) including spp., and can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China.
METHODS
We used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions.
RESULTS
After excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated.
CONCLUSIONS
This review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.
PubMed: 36846140
DOI: 10.3389/fneur.2023.1100785 -
Journal of Clinical Microbiology Jan 2022Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris result in a variety of clinical manifestations in humans. These amoebae are found...
Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris result in a variety of clinical manifestations in humans. These amoebae are found in water and soil worldwide. spp. and B. mandrillaris cause granulomatous amoebic encephalitis (GAE), which usually presents as a mass, while N. fowleri causes primary amoebic meningoencephalitis (PAM). spp. can also cause keratitis, and both spp. and can cause lesions in skin and respiratory mucosa. These amoebae can be difficult to diagnose clinically as these infections are rare and, if not suspected, can be misdiagnosed with other more common diseases. Microscopy continues to be the key first step in diagnosis, but the amoeba can be confused with macrophages or other infectious agents if an expert in infectious disease pathology or clinical microbiology is not consulted. Although molecular methods can be helpful in establishing the diagnosis, these are only available in referral centers. Treatment requires combination of antibiotics and antifungals and, even with prompt diagnosis and treatment, the mortality for neurological disease is extremely high.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Humans; Naegleria fowleri
PubMed: 34133896
DOI: 10.1128/JCM.00228-21 -
Annals of Agricultural and... May 2017[b]Abstract Introduction[/b]. Among free-living amoebae that are widely distributed in nature only four genera/species are known as agents of human infections:[i]... (Review)
Review
[b]Abstract Introduction[/b]. Among free-living amoebae that are widely distributed in nature only four genera/species are known as agents of human infections:[i] Acanthamoeba spp., Naegleriafowleri, Balamuthia mandrillaris[/i] and[i] Sappiniapedata[/i]. These amoebae are not well adapted to parasitism, and could exist in the human environment without the need for a host. Infections due to these amoebae, despite low morbidity, are characterized by relatively high mortality rate and pose serious clinical problems. [b]Objectve[/b]. This review study presents and summarizes current knowledge about infections due to pathogenic and opportunistic free-living amoebae focused on epidemiology, clinical manifestations, diagnosis and treatment based on global literature. [b]State of knowledge[/b]. All four genera have been recognized as etiologic factors of fatal central nervous system infections and other serious diseases in humans. [i]N. fowleri[/i] causes an acute fulminating meningoencephalitis in children and young adults. [i]Acanthamoeba spp[/i]. and [i]B.mandrillaris[/i] are opportunistic pathogens causing granulomatous amoebic encephalitis and disseminated or localized infections which could affect the skin, sinuses, lungs, adrenals and/or bones. [i]Acanthamoeba spp[/i]. is also the main agent of acute eye infection -[i] Acanthamoeba keratitis, [/i]mostly in contact lens wearers. However, there is only one recognized case of encephalitis caused by [i]S. pedata. [/i] [b]Conclusions[/b]. Amoebic diseases are difficult to diagnose which leads to delayed treatment, and result in a high mortality rate. Considering those issues, there is an urgent need to draw more attention to this type of diseases.
Topics: Amebiasis; Amoeba; Animals; Humans
PubMed: 28664704
DOI: 10.5604/12321966.1233568 -
JMM Case Reports Jun 2016This case report describes a human survivor of infection. This is a free-living amoeba that can cause infection with the devastating consequence of near universally...
INTRODUCTION
This case report describes a human survivor of infection. This is a free-living amoeba that can cause infection with the devastating consequence of near universally fatal encephalitis. We report this case to demonstrate the possibility of recovery.
CASE PRESENTATION
A 26-year-old Hispanic male, a landscape gardener, presented to the hospital in March 2010 with a two month history of headache, visual disturbances and new-onset seizures. Brain imaging identified two enhancing central lesions and was later identified by brain biopsy. He received several months of various antimicrobials including miltefosine, a novel use of the drug in this disease at the time. Seven weeks into therapy, considerations were made to switch him to 'comfort care' because of worsening clinical status and seemingly lack of response to treatment. The patient finally demonstrated clinical and radiological improvement after eight weeks with modified therapy, despite experiencing some debilitating toxic effects likely to be related to antibiotics. Two years after his initial presentation he made a complete recovery.
CONCLUSION
amoebic encephalitis is considered an almost universally fatal disease; this case demonstrates the possibility of recovery. This report outlines his treatment, drug toxicities and includes additional information regarding the therapeutic use of the drug miltefosine. Whether his survival is related to the specific antimicrobials used in this case is unknown and further investigation is warranted.
PubMed: 28348755
DOI: 10.1099/jmmcr.0.005031 -
International Journal For Parasitology.... Dec 2019The free-living amebae Naegleria, Acanthamoeba, and Balamuthia cause rare but life-threatening infections. All three parasites can cause meningoencephalitis....
Identification of plicamycin, TG02, panobinostat, lestaurtinib, and GDC-0084 as promising compounds for the treatment of central nervous system infections caused by the free-living amebae Naegleria, Acanthamoeba and Balamuthia.
The free-living amebae Naegleria, Acanthamoeba, and Balamuthia cause rare but life-threatening infections. All three parasites can cause meningoencephalitis. Acanthamoeba can also cause chronic keratitis and both Balamuthia and Acanthamoeba can cause skin and systemic infections. There are minimal drug development pipelines for these pathogens despite a lack of available treatment regimens and high fatality rates. To identify anti-amebic drugs, we screened 159 compounds from a high-value repurposed library against trophozoites of the three amebae. Our efforts identified 38 compounds with activity against at least one ameba. Multiple drugs that bind the ATP-binding pocket of mTOR and PI3K are active, highlighting these compounds as important inhibitors of these parasites. Importantly, 24 active compounds have progressed at least to phase II clinical studies and overall 15 compounds were active against all three amebae. Based on central nervous system (CNS) penetration or exceptional potency against one amebic species, we identified sixteen priority compounds for the treatment of meningoencephalitis caused by these pathogens. The top five compounds are (i) plicamycin, active against all three free-living amebae and previously U.S. Food and Drug Administration (FDA) approved, (ii) TG02, active against all three amebae, (iii and iv) FDA-approved panobinostat and FDA orphan drug lestaurtinib, both highly potent against Naegleria, and (v) GDC-0084, a CNS penetrant mTOR inhibitor, active against at least two of the three amebae. These results set the stage for further investigation of these clinically advanced compounds for treatment of infections caused by the free-living amebae, including treatment of the highly fatal meningoencephalitis.
Topics: Acanthamoeba; Amebiasis; Amoebozoa; Antiprotozoal Agents; Carbazoles; Cell Culture Techniques; Central Nervous System Protozoal Infections; Culture Media; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Enzyme Inhibitors; Furans; Heterocyclic Compounds, 4 or More Rings; Inhibitory Concentration 50; Naegleria; Oxazines; Panobinostat; Plicamycin; Pyrimidines
PubMed: 31707263
DOI: 10.1016/j.ijpddr.2019.10.003