- Primary Amebic Meningoencephalitis Associated With Rafting on an Artificial Whitewater River: Case Report and Environmental Investigation. [Journal Article]
- CIClin Infect Dis 2018 Feb 01; 66(4):548-553
- CONCLUSIONS: This investigation documents a novel exposure to an artificial whitewater river as the likely exposure causing PAM in this case. Conditions in the whitewater facility (warm, turbid water with little chlorine and heavy algal growth) rendered the water treatment ineffective and provided an ideal environment for N. fowleri to thrive. The combination of natural and engineered elements at the whitewater facility created a challenging environment to control the growth of N. fowleri.
- CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM). [Journal Article]
- PNPLoS Negl Trop Dis 2017; 11(12):e0006104
- Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality ...
Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51) target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i) systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii) identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii) analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.
- Estimation of Undiagnosed Naegleria fowleri Primary Amebic Meningoencephalitis, United States1. [Journal Article]
- EIEmerg Infect Dis 2018; 24(1):162-164
- Primary amebic meningoencephalitis is an acute, rare, typically fatal disease. We used epidemiologic risk factors and multiple cause-of-death mortality data to estimate the number of deaths that fit ...
Primary amebic meningoencephalitis is an acute, rare, typically fatal disease. We used epidemiologic risk factors and multiple cause-of-death mortality data to estimate the number of deaths that fit the typical pattern for primary amebic meningoencephalitis; we estimated an annual average of 16 deaths (8 male, 8 female) in the United States.
- A delayed diagnosis of X-linked hyper IgM syndrome complicated with toxoplasmic encephalitis in a child: A case report and literature review. [Case Reports]
- MMedicine (Baltimore) 2017; 96(49):e8989
- CONCLUSIONS: A more thorough clinical history and some features like recurrent respiratory infections, protracted diarrhea, and persistent or intermittent neutropenia companioned with oral ulcer could increase clinical suspicion of XHIGM. Cerebral toxoplasmosis is rare in patients with XHIGM, but still should be considered. The present study firstly reported a delayed diagnosed case of XHIGM with CD40L gene c.654C>A (p.C218X) mutant complicated with toxoplasma encephalitis in Chinese population, which highlighted the importance of CD40-CD40L interaction in cell-mediated immunity against T gondii.
- Production and characterization of monoclonal antibodies against cathepsin B and cathepsin B-Like proteins of Naegleria fowleri. [Journal Article]
- EPExp Parasitol 2017; 183:171-177
- Naegleria fowleri causes fatal primary amoebic meningoencephalitis (PAM) in humans and experimental animals. In previous studies, cathepsin B (nfcpb) and cathepsin B-like (nfcpb-L) genes of N. fowler...
Naegleria fowleri causes fatal primary amoebic meningoencephalitis (PAM) in humans and experimental animals. In previous studies, cathepsin B (nfcpb) and cathepsin B-like (nfcpb-L) genes of N. fowleri were cloned, and it was suggested that refolding rNfCPB and rNfCPB-L proteins could play important roles in host tissue invasion, immune response evasion and nutrient uptake. In this study, we produced anti-NfCPB and anti-NfCPB-L monoclonal antibodies (McAb) using a cell fusion technique, and observed their immunological characteristics. Seven hybridoma cells secreting rNfCPB McAbs and three hybridoma cells secreting rNfCPB-L McAbs were produced. Among these, 2C9 (monoclone for rNfCPB) and 1C8 (monoclone for rNfCPB-L) McAb showed high antibody titres and were finally selected for use. As determined by western blotting, 2C9 McAb bound to N. fowleri lysates, specifically the rNfCPB protein, which had bands of 28 kDa and 38.4 kDa. 1C8 McAb reacted with N. fowleri lysates, specifically the rNfCPB-L protein, which had bands of 24 kDa and 34 kDa. 2C9 and 1C8 monoclonal antibodies did not bind to lysates of other amoebae, such as N. gruberi, Acanthamoeba castellanii and A. polyphaga in western blot analyses. Immuno-cytochemistry analysis detected NfCPB and NfCPB-L proteins in the cytoplasm of N. fowleri trophozoites, particularly in the pseudopodia and food-cup. These results suggest that monoclonal antibodies produced against rNfCPB and rNfCPB-L proteins may be useful for further immunological study of PAM.
- A case report: primary amoebic meningoencephalitis in a young Zambian adult. [Case Reports]
- BIBMC Infect Dis 2017 Aug 01; 17(1):532
- CONCLUSIONS: The isolation of N. fowleri in this patient calls for increased awareness among clinical and laboratory staff on suspected PAM cases to promptly diagnose and effectively manage the disease.
- Congenital toxoplasmosis in Austria: Prenatal screening for prevention is cost-saving. [Journal Article]
- PNPLoS Negl Trop Dis 2017; 11(7):e0005648
- CONCLUSIONS: Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants.
- Comparison of apoptosis in human primary pulmonary endothelial cells and a brain microvascular endothelial cell line co-cultured with Plasmodium falciparum field isolates. [Journal Article]
- BIBMC Infect Dis 2017 Jun 27; 17(1):454
- CONCLUSIONS: These results indicate that the brain microvascular cell line was more susceptible to apoptosis triggered by P. falciparum than the primary pulmonary endothelial cells and may have relevance to host-parasite interaction.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Amebic encephalitis is both exceptionally rare and highly lethal central nervous system infection caused by free-living amoebae, found in fresh water, lakes, and rivers. There are two entities of ame...
Amebic encephalitis is both exceptionally rare and highly lethal central nervous system infection caused by free-living amoebae, found in fresh water, lakes, and rivers. There are two entities of amebic encephalitis: PAM (Primary Amebic Meningoencephalitis) and Granulomatous amebic encephalitis (GAE). The initial symptoms of PAM are indistinguishable from bacterial meningitis, while the symptoms of GAM can mimic a brain abscess or meningitis. These infections are almost always fatal. The mortality rate is above 90%, despite the antimicrobial therapy. There are around 300 cases reported of N. Fowleri. The high mortality rate is due to an unusual symptomology in its early stages, also by the necessity of a microbial culture of the cerebrospinal fluid to establish a positive diagnosis. Parasites demonstrate a very rapid late-stage propagation through the nerves of the olfactory system to many parts of the brain simultaneously (including the vulnerable medulla). Admit patients with amebic meningoencephalitis to the intensive care unit (ICU) for intensive monitoring and therapy. Emergent consultations with infectious disease specialists, neurologists, and neurosurgeons are recommended if PAM or GAE is suspected.
New Search Next
- Knowledge and perceptions on toxoplasmosis among pregnant women and nurses who provide prenatal in primary care. [Journal Article]
- RIRev Inst Med Trop Sao Paulo 2017 Jun 01; 59:e31
- CONCLUSIONS: The nurse plays an important role in educational activities regarding pregnant women, contributing to the quality of prenatal care. Pregnant women were shown to have some knowledge about toxoplasmosis, although they said they did not have assurance about prevention.