Naegleria Fowleri Diagnosed with Hospital Autopsy in a Toddler: A Case Study

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S81-S82
Author(s):  
R F Palmer ◽  
E Palavecino ◽  
J L McLemore

Abstract Casestudy Naegleria fowleri, an amoeba, is typically found in warm freshwater lakes, ponds, rivers and hot springs. It is responsible for causing the incredibly rare and lethal central nervous system infection called Primary Amoebic Meningoencephalitis (PAM). In the United States, 145 confirmed cases have been documented since 1962. Most cases are associated with freshwater lakes, ponds and reservoirs, while only a handful have been linked to artificial recreational venues such as pools, interactive water play-grounds, and spas. In addition to highlighting a rare amoebic disease, this case illustrates the continued importance of hospital autopsies especially given recent ruling to eliminate the autopsy requirement by the Centers for Medicare and Medicaid Services. Results An otherwise healthy toddler had upper respiratory symptoms and otitis media days after returning from an artificial recreational water venue, becoming increasingly lethargic and febrile over the next few days. At the hospital, cerebrospinal fluid (CSF) abnormalities were suggestive but not consistent with bacterial meningitis. A meningoencephalitis panel, a Computed Tomograph (CT) scan of the head, and chest-x-ray were negative for abnormalities. Appropriate antimicrobial therapy was initiated. Three days after hospital admission, his symptoms worsened including development of dysconjugate gaze and signs of cerebellitis. He became increasingly hemodynamically unstable, suffered an arrest, and passed away days later. Conclusion Since this death did not fall under the state’s statutes mandating medicolegal autopsy, a hospital- requested autopsy was performed. Cerebral edema and a light gray to light green exudate was along the inferior and lateral left temporal lobe, brain stem, and cerebellum. An exuberant lymphoplasmacytic infiltrate with scattered polymorphonuclear leukocytes expanded the meninges. Small histiocyte-like cells with distinct eccentric nuclei and granular, vacuolated cytoplasm, confirmed by Centers for Disease Control and Prevention (CDC) to be Naegleria fowleri, were best visualized in the Virchow-Robin spaces and deeper parenchyma.

2006 ◽  
Vol 51 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Shannon M. Soltow ◽  
George M. Brenner

ABSTRACT Naegleria fowleri is responsible for producing a rapidly fatal central nervous system infection known as primary amebic meningoencephalitis (PAM). To date, amphotericin B, an antifungal agent, is the only agent with established clinical efficacy in the treatment of PAM. However, amphotericin B is not always successful in treating PAM and is associated with severe adverse effects. We previously found azithromycin to be more effective than amphotericin B in a mouse model of PAM. We therefore investigated the combination of amphotericin B and azithromycin in vitro and in a mouse model of PAM. For the in vitro studies, 50% inhibitory concentrations were calculated for each drug alone and for the drugs in fixed combination ratios of 1:1, 3:1, and 1:3. We found amphotericin B and azithromycin to be synergistic at all three of the fixed combination ratios. In our mouse model of PAM, a combination of amphotericin B (2.5 mg/kg of body weight) and azithromycin (25 mg/kg) protected 100% of the mice, whereas amphotericin B alone (2.5 mg/kg) protected only 27% of mice and azithromycin alone (25 mg/kg) protected 40% of mice. This study indicates that amphotericin B and azithromycin are synergistic against the Lee strain of N. fowleri, suggesting that the combined use of these agents may be beneficial in treating PAM.


2003 ◽  
Vol 69 (10) ◽  
pp. 5864-5869 ◽  
Author(s):  
Francine Marciano-Cabral ◽  
Rebecca MacLean ◽  
Alex Mensah ◽  
Laurie LaPat-Polasko

ABSTRACT The free-living amoeboflagellate Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis (PAM), a rapidly fatal disease of the central nervous system. In the United States, the disease is generally acquired while swimming and diving in freshwater lakes and ponds. In addition to swimming, exposure to N. fowleri and the associated disease can occur by total submersion in bathwater or small backyard wading pools. In the present study, swipe samples and residual pipe water from homes in Arizona were examined for N. fowleri by nested PCR due to the death of two previously healthy children from PAM. Since neither child had a history of swimming in a freshwater lake or pond prior to the onset of disease symptoms, the domestic water supply was the suspected source of infection. Of 19 samples collected from bathroom and kitchen pipes and sink traps, 17 samples were positive for N. fowleri by PCR. A sample from a Micro-Wynd II filter was obtained by passing water from bathtubs through the filter. Organisms attached to the filter also tested positive by PCR. The two samples that tested negative for N. fowleri were one that was obtained from a kitchen sink trap and a swipe sample from the garbage disposal of one home.


Author(s):  
Christopher A. Rice ◽  
Beatrice L. Colon ◽  
Emily Chen ◽  
Mitchell V. Hull ◽  
Dennis E. Kyle

AbstractDiseases caused by pathogenic free-living amoebae include primary amoebic meningoencephalitis (Naegleria fowleri), granulomatous amoebic encephalitis (Acanthamoeba spp.), Acanthamoeba keratitis, and Balamuthia amoebic encephalitis (Balamuthia mandrillaris). Each of these are difficult to treat and have high morbidity and mortality rates due to lack of effective therapeutics. In pursuit of repurposing drugs for chemotherapies, we conducted a high throughput phenotypic screen of 12,000 compounds from the Calibr ReFRAME library. We discovered a total of 58 potent inhibitors (IC50 <1 μM) against N. fowleri (n=19), A. castellanii (n=12), and B. mandrillaris (n=27) plus an additional 90 micromolar inhibitors. Of these, 113 inhibitors have never been reported to have activity against Naegleria, Acanthamoeba or Balamuthia. Rapid onset of action is important for new anti-amoeba drugs and we identified 19 compounds that inhibit N. fowleri in vitro within 24 hours (halofuginone, NVP-HSP990, fumagillin, bardoxolone, belaronib, and BPH-942, solithromycin, nitracrine, quisinostat, pabinostat, pracinostat, dacinostat, fimepinostat, sanguinarium, radicicol, acriflavine, REP3132, BC-3205 and PF-4287881). These compounds inhibit N. fowleri in vitro faster than any of the drugs currently used for chemotherapy. The results of these studies demonstrate the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. Given that many of the repurposed drugs have known mechanisms of action, these compounds can be used to validate new targets for structure-based drug design.Author SummaryFree-living amoebae (FLA) are ubiquitous in soil and freshwater and most are non-pathogenic to people; however, three different pathogenic FLA have been found to cause severe, most often fatal diseases in humans. Due to poor detection and inadequate treatment options available for pathogenic FLA, the fatality rates are still > 90% for the diseases caused by Balamuthia mandrillaris, Naegleria fowleri, and Acanthamoeba spp. With hundreds of cases in the United States and many more cases reported worldwide, there is still an urgent clinical need for effective diagnosis and specific treatments discovered against these opportunistic parasites. Drug repurposing is a powerful approach for drug-discovery because it significantly improves the discovery time, reduces the amount of resources, and decreases costs required to advance lead candidate drugs of interest into the clinic. This is extremely helpful for neglected diseases including pathogenic FLA where there is a need for new active therapies with limited budgets. This report addresses the discovery of new active drugs with potential for repurposing, multiple new drug classes that inhibit pathogenic FLA, and numerous putative drug targets that can be used as tools for further investigation and structure-based drug design.


1995 ◽  
Vol 31 (5-6) ◽  
pp. 119-122 ◽  
Author(s):  
J. M. Cassells ◽  
M. T. Yahya ◽  
C. P. Gerba ◽  
J. B. Rose

Electrolytically generated copper and silver ions (400:40 and 800:80 μg/l) were evaluated, separately and combined with 1.0 mg/l free chlorine, for their efficacy in reducing the viable numbers of Naegleria fowleri amoebas in water (pH 7.3 and 23-25°C). Inactivation rates (k = log10 reduction/min) and T99 values (exposure time required to achieve a 99% or a 2 log10 reduction) of the disinfectants were determined. Copper and silver alone, at ratio of 400:40 to 800:80 μg/l caused no significant inactivation of N. fowleri even after 72 hours of exposure (k = 0.00017 and 0.00013, respectively). Addition of 1.0 mg/l free chlorine to water which contained 400:40 or 800:80 μg/l copper and silver resulted in enhanced inactivation rates (k = 0.458 and 0.515, respectively) compared to either chlorine alone (k = 0.33) or the metals alone. Water containing 800:80 μg/l copper and silver with 1.0 mg/l chlorine showed a T99 value of 3.9 minutes, while chlorine alone showed a T99 of 6.1 minutes. Enhanced inactivation of N. fowleri by a combined system of free chlorine and copper and silver may be attributed to the different mechanism that each disinfectant utilizes in inactivating the amoebas, and may suggest a synergistic effect.


2021 ◽  
pp. 109019812110144
Author(s):  
Soon Guan Tan ◽  
Aravind Sesagiri Raamkumar ◽  
Hwee Lin Wee

This study aims to describe Facebook users’ beliefs toward physical distancing measures implemented during the Coronavirus disease (COVID-19) pandemic using the key constructs of the health belief model. A combination of rule-based filtering and manual classification methods was used to classify user comments on COVID-19 Facebook posts of three public health authorities: Centers for Disease Control and Prevention of the United States, Public Health England, and Ministry of Health, Singapore. A total of 104,304 comments were analyzed for posts published between 1 January, 2020, and 31 March, 2020, along with COVID-19 cases and deaths count data from the three countries. Findings indicate that the perceived benefits of physical distancing measures ( n = 3,463; 3.3%) was three times higher than perceived barriers ( n = 1,062; 1.0%). Perceived susceptibility to COVID-19 ( n = 2,934; 2.8%) was higher compared with perceived severity ( n = 2,081; 2.0%). Although susceptibility aspects of physical distancing were discussed more often at the start of the year, mentions on the benefits of intervention emerged stronger toward the end of the analysis period, highlighting the shift in beliefs. The health belief model is useful for understanding Facebook users’ beliefs at a basic level, and it provides a scope for further improvement.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 388
Author(s):  
Hương Giang Lê ◽  
A-Jeong Ham ◽  
Jung-Mi Kang ◽  
Tuấn Cường Võ ◽  
Haung Naw ◽  
...  

Naegleria fowleri is a free-living amoeba that is ubiquitous in diverse natural environments. It causes a fatal brain infection in humans known as primary amoebic meningoencephalitis. Despite the medical importance of the parasitic disease, there is a great lack of knowledge about the biology and pathogenicity of N. fowleri. In this study, we identified and characterized a novel cysteine protease inhibitor of N. fowleri (NfCPI). NfCPI is a typical cysteine protease inhibitor belonging to the cystatin family with a Gln-Val-Val-Ala-Gly (QVVAG) motif, a characteristic motif conserved in the cystatin family of proteins. Bacterially expressed recombinant NfCPI has a dimeric structure and exhibits inhibitory activity against several cysteine proteases including cathespin Bs of N. fowleri at a broad range of pH values. Expression profiles of nfcpi revealed that the gene was highly expressed during encystation and cyst of the amoeba. Western blot and immunofluorescence assays also support its high level of expression in cysts. These findings collectively suggest that NfCPI may play a critical role in encystation or cyst formation of N. fowleri by regulating cysteine proteases that may mediate encystation or mature cyst formation of the amoeba. More comprehensive studies to investigate the roles of NfCPI in encystation and its target proteases are necessary to elucidate the regulatory mechanism and the biological significance of NfCPI.


Biosensors ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 14
Author(s):  
Priya Dave ◽  
Roberto Rojas-Cessa ◽  
Ziqian Dong ◽  
Vatcharapan Umpaichitra

The United States Centers for Disease Control and Prevention considers saliva contact the lead transmission mean of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). Saliva droplets or aerosols expelled by sneezing, coughing, breathing, and talking may carry this virus. People in close distance may be exposed directly to these droplets or indirectly when touching the droplets that fall on surrounding surfaces and ending up contracting COVID-19 after touching the mucosa tissue of their faces. It is of great interest to quickly and effectively detect the presence of SARS-CoV-2 in an environment, but the existing methods only work in laboratory settings, to the best of our knowledge. However, it may be possible to detect the presence of saliva in the environment and proceed with prevention measures. However, detecting saliva itself has not been documented in the literature. On the other hand, many sensors that detect different organic components in saliva to monitor a person’s health and diagnose different diseases, ranging from diabetes to dental health, have been proposed and they may be used to detect the presence of saliva. This paper surveys sensors that detect organic and inorganic components of human saliva. Humidity sensors are also considered in the detection of saliva because a large portion of saliva is water. Moreover, sensors that detect infectious viruses are also included as they may also be embedded into saliva sensors for a confirmation of the presence of the virus. A classification of sensors by their working principles and the substances they detect is presented, including the sensors’ specifications, sample size, and sensitivity. Indications of which sensors are portable and suitable for field application are presented. This paper also discusses future research and challenges that must be resolved to realize practical saliva sensors. Such sensors may help minimize the spread of not only COVID-19 but also other infectious diseases.


2021 ◽  
pp. 192536212110224
Author(s):  
Melissa C. Mercado ◽  
Deborah M. Stone ◽  
Caroline W. Kokubun ◽  
Aimée-Rika T. Trudeau ◽  
Elizabeth Gaylor ◽  
...  

Introduction: It is widely accepted that suicides—which account for more than 47 500 deaths per year in the United States—are undercounted by 10% to 30%, partially due to incomplete death scene investigations (DSI) and varying burden-of-proof standards across jurisdictions. This may result in the misclassification of overdose-related suicides as accidents or undetermined intent. Methods: Virtual and in-person meetings were held with suicidologists and DSI experts from five states (Spring-Summer 2017) to explore how features of a hypothetical electronic DSI tool may help address these challenges. Results: Participants envisioned a mobile DSI application for cell phones, tablets, or laptop computers. Features for systematic information collection, scene description, and guiding key informant interviews were perceived as useful for less-experienced investigators. Discussion: Wide adoption may be challenging due to differences in DSI standards, practices, costs, data privacy and security, and system integration needs. However, technological tools that support consistent and complete DSIs could strengthen the information needed to accurately identify overdose suicides.


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