primární amébová meningoencefalitida Dotaz Zobrazit nápovědu
- Klíčová slova
- primární amébová meningoencefalitida,
- MeSH
- amébiáza * diagnóza epidemiologie mortalita MeSH
- dějiny 20. století MeSH
- dějiny lékařství MeSH
- epidemický výskyt choroby MeSH
- lidé MeSH
- meningoencefalitida etiologie patologie MeSH
- mikrobiologie vody MeSH
- Naegleria fowleri * izolace a purifikace patogenita MeSH
- plavecké bazény MeSH
- protozoární infekce centrálního nervového systému * diagnóza epidemiologie mortalita MeSH
- Check Tag
- dějiny 20. století MeSH
- lidé MeSH
- Publikační typ
- historické články MeSH
- Geografické názvy
- Československo MeSH
Primary amoebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living amoeba Naegleria fowleri The amoeba migrates along the olfactory nerve to the brain, resulting in seizures, coma, and, eventually, death. Previous research has shown that Naegleria gruberi, a close relative of N. fowleri, prefers lipids over glucose as an energy source. Therefore, we tested several already-approved inhibitors of fatty acid oxidation alongside the currently used drugs amphotericin B and miltefosine. Our data demonstrate that etomoxir, orlistat, perhexiline, thioridazine, and valproic acid inhibited growth of N. gruberi We then tested these compounds on N. fowleri and found etomoxir, perhexiline, and thioridazine to be effective growth inhibitors. Hence, not only are lipids the preferred food source for N. gruberi, but also oxidation of fatty acids seems to be essential for growth of N. fowleri Inhibition of fatty acid oxidation could result in new treatment options, as thioridazine inhibits N. fowleri growth in concentrations that can be reached at the site of infection. It could also potentiate currently used therapy, as checkerboard assays revealed synergy between miltefosine and etomoxir. Animal testing should be performed to confirm the added value of these inhibitors. Although the development of new drugs and randomized controlled trials for this rare disease are nearly impossible, inhibition of fatty acid oxidation seems a promising strategy as we showed effectivity of several drugs that are or have been in use and that thus could be repurposed to treat PAM in the future.
Primary amoebic meningoencephalitis is a rare but fatal central nervous system (CNS) disease caused by the "brain-eating amoeba" Naegleria fowleri. A major obstacle is the requirement for drugs with the ability to cross the blood-brain barrier, which are used in extremely high doses, cause severe side effects, and are usually ineffective. We discovered that the 4-aminomethylphenoxy-benzoxaborole AN3057 exhibits nanomolar potency against N. fowleri, and experimental treatment of infected mice significantly prolonged survival and demonstrated a 28% relapse-free cure rate.
- MeSH
- amébiáza * farmakoterapie MeSH
- hematoencefalická bariéra MeSH
- meningoencefalitida * MeSH
- myši MeSH
- Naegleria fowleri * MeSH
- protozoární infekce centrálního nervového systému * farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
xi, 324 s. : il., tab., grafy ; 24 cm
Migration of parasitic worms through the host tissues, which may occasionally result in fatal damage to the internal organs, represents one of the major risks associated with helminthoses. In order to track the parasites, traditionally used 2D imaging techniques such as histology or squash preparation do not always provide sufficient data to describe worm location/behavior in the host. On the other hand, 3D imaging methods are widely used in cell biology, medical radiology, osteology or cancer research, but their use in parasitological research is currently occasional. Thus, we aimed at the evaluation of suitability of selected 3D methods to monitor migration of the neuropathogenic avian schistosome Trichobilharzia regenti in extracted spinal cord of experimental vertebrate hosts. All investigated methods, two of them based on tracking of fluorescently stained larvae with or without previous chemical clearing of tissue and one based on X-ray micro-CT, exhibit certain limits for in vivo observation. Nevertheless, our study shows that the tested methods as ultramicroscopy (used for the first time in parasitology) and micro-CT represent promising tool for precise analyzing of parasite larvae in the CNS. Synthesis of these 3D imaging techniques can provide more comprehensive look at the course of infection, host immune response and pathology caused by migrating parasites within entire tissue samples, which would not be possible with traditional approaches.
- MeSH
- infekce červy třídy Trematoda veterinární MeSH
- larva MeSH
- nemoci zvířat diagnóza parazitologie MeSH
- obratlovci MeSH
- protozoární infekce centrálního nervového systému veterinární MeSH
- Schistosomatidae * MeSH
- zobrazování trojrozměrné metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- bakteriální infekce centrálního nervového systému * diagnóza etiologie farmakoterapie MeSH
- encefalitida * diagnóza etiologie farmakoterapie MeSH
- infekce centrálního nervového systému * diagnóza etiologie farmakoterapie MeSH
- lidé MeSH
- management péče o pacienta MeSH
- meningitida * diagnóza etiologie farmakoterapie terapie MeSH
- parazitární infekce centrálního nervového systému * diagnóza etiologie farmakoterapie MeSH
- protozoární infekce centrálního nervového systému * diagnóza etiologie farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Neglerióza alebo primárna amébová meningoencefalitída (PAM) je zriedkavé ochorenie CNS, pôvodcom ktorého je vo¾ne žijúca meòavka Naegleria fowleri. Medzi stovkami vo¾ne žijúcich meòaviek sú známe i ïalšie rody, ktorých zástupcovia sú schopní infikovaś èloveka a vyvolaś u neho ochorenie. Za patogény sú považovaní zástupcovia rodov Acanthamoeba a Naegleria a druhy Balamuthia mandrillaris a Sappinia diploidea. Infekcie spôsobené týmito organizmami vyvolávajú u ¾udí syndrómy v rozsahu od akútnych fatálnych ochorení po chronické, tkanivá napadajúce infekcie s granulomatóznymi prejavmi. Epidemiológia, imunológia, patológia a klinické prejavy týchto infekcií sa vzájomne ve¾mi líšia. Príspevok podáva preh¾ad o pôvodcovi ochorenia PAM, o jeho morfológii, životnom cykle, ekológii ako aj o patogenéze, symptomatike a spôsoboch laboratórnej diagnostiky negleriózy.
Naegleriasis or primary amoebic meningoencephalitis (PAM) is invariably an acute, often fulminant infection of CNS caused by Naegleria fowleri, a small, free-living amoeba. Pathogenic free-living amoebae can cause serious illnesses in humans. The amoebae belonging to the genus Naegleria, Acanthamoeba and Balamuthia mandrillaris and Sappinia diploidea produce syndromes in man ranging from acute fatal disease to chronic tissue invasion with granulomatous manifestation. The purpose of this report is to describe the clinical history, treatment, pathology and methods of laboratory diagnostic of naegleriasis.
