Primary Amoebic

Meningoencephalitis

Our organism first found its way into medical literature in the

1960’s. Around this time there was a series of meningitis cases

in the southern area of Australia.

During the course of this time a series of people contracted and died from a very aggressive form of

meningitis.

However, within blood and CSF samples there was no causative bacteria noted, as would be

expected in your typical case of meningitis. What was noted and dismissed were small

motile amoeba.

In 1965, two Australian physicians M. Carter and R. Fowler take a closer look at three

meningitis deaths that also occurred in the

southern area of Australia. They

examined the nervous tissue of the victims

from gross and histological aspects. As well as isolating what they thought was the causative agent from

all of the victims bodies.

IN THE GROSS ANATOMY

In their post mortem examinations of the patients they note significant hemorrhaging in the cortex

and frontal lobes of the brain.There are also some sulci that are flattened and

misshapen.The brains themselves show swelling , as well as hemorrhaging in areas surrounding the cribiform

plate and cranial nerve I.

MICROSCOPICALLY

Throughout much of the gross investigation a white exudate is noted in between sulci and within the

ventricles of the brain.

Samples of corticle tissue are taken, and smears are made of the white exudate found on the brain.

Within these smears, small Eukaryotic micro-organisms are noted.

Many of these specimens are prepared via Periodic-Acid – Schiff techniques or stained with haematoxylin

and eosin to show morphology.

Their Findings….

Their Conclusion….

From their investigationt they determine that there is an illness that presents identical to bacterial meningitis. It has nearly the same

symptoms, but a very different causative agent. This illness is caused by amoeba that invade the central nervous system, and then eat its functional

cells, the neuron.

They call this illness Primary Amoebic Meningoencephalitis.

Within the histological samples from the brain and exudatesmears, numerous amoeba are noted.

About the caustive organism

It is a single celled eukaryotic organism.

It is a thermophillic organism, and flourishes during the

temperate summer months in select climates, when water

temperatures rise above 30C.

Commonly it is found in stagnant fresh waters. Often it is near the

floor of the body of water that it is in. However, the movement and stirring of the water’s bottom by

limbs of larger animals, often puts this organism into suspension

within the water.

Don’t assume you are safe at home. This organism has been isolated from, air conditioners, city water supplies,

and poorly chlorinated swimming pools.

This organism also comes in three different arrangements for three

different scenarios.

Feeding - TrophozoiteSurviving - Cyst

Motility -Flagellated

Patho-physiology of this organism

This organism infects its host by moving into its nasal passages and using nerves in that area to access

the CNS.

Water is essential to this organisms entrance to the body. The water

containing this organism must “get up your nose”

Once in your nasal passages, this organism moves up the olfactory

sensory nerves, through the cribiform plate and directly to CNI and the frontal lobe of the brain.

Patho-physiology of this organism, continued

Once inside the cranium, this organism causes intense

inflammation and hemorrhage.

The hemorrhage and inflammation causes further

complications for the patient. Inflammation hinders the

function of still living neurons, and blood is actually toxic to

neurons; so surviving neurons can become poisoned by the bleeding in the brain and die.

The brain itself may swell during this illness. Gyri can be flattened. Select vascular structures such as the middle meningeal artery can collapse or form lesions during

this illness as well.

Tests For Diagnoses of this waterborne organism

As part of routine tests a Complete Blood count is usually

ordered.

A lumbar puncture is the best way test for this organism.

Often a direct wet mount of CSF is sufficient to see at least some

of these micro-organisms

Often analysis of CSF fluid obtained contains markers that

indicate the presence of this organism.

The fluid may be slightly cloudyNormal to low glucose levels:

Up to 80 or <40(low)Increased protein values

>60/100mlPresence of RBC’s (should be <0)

Under the Microscope

When viewing the CSF under the microscope this organism may be

seen in its active feeding form.

Known as a trophozoite

Occasionally a motile form of this organism, referred to as

flagellate can be noted.

Chemical stains and other techniques can be used in addition to, or instead of direct wet mount,

including:

Periodic-Acid-Schiff technique (P.A.S.)

Haematoxylin and eosin staining

PCR identification and direct antibody flourescence

Gram Stain : Negative

Signs and symptoms

Severe Headaches

Loss of the sense of smell (Anosmia)

Cranial Nerve Palsy’s

Change in personality

Blurred vision

Stiff neck

Vomiting

Confusion

Positive Kernigs sign

Positive Brudzinskis sign

TreatmentWhile there are many drugs that have been tried against this organism, these are

the three most common utilized.

Amphotericin B - An anti-fungal drug that targets ergo-

sterols of the cell wall

Flucanazole - Another anti-fungal drug that targets ergo-

sterols of the cell wall

Rifampicin - An antibacterial agent that disrupts RNA synthesis within the target cell.

While these are the standard chemotherapeutic agents used to treat infection by this particular micro-organism, they are actually rather

toxic to the host.

Kidney toxicity is one of the major side effects of their use.

Research continues on chemical compounds that may have a greater specificity for the cells of the infectious agent and not the host. However, at this time they are still limited to animal

studies.

Prevention

This organism is an equal opportunity pathogen. It infects an

immunocompetant individual as effectively as it does an

imunocomprimised person.

With a 95% mortality rate and no vaccine available, the best defense

is avoiding exposure.

Avoid swimming in stagnant waters during the temperate months of

the year.

If you do enter these types of water, wear noseplugs and avoid stirring up the lake or creek bottom as much as

possible.

Works Cited

1. Fowler, M., and R. F. Carter. 1965. Acute pyogenic meningitis probably due to Acanthamoeba sp.: a preliminary report. Br. Med. J. 2:740-742. http://search.ebscohost.com/login.aspx?direct=true&db=cmedm&AN=5825411&site=ehost-live.

2. Hara, T., and T. Fukuma. 2005. Diagnosis of the primary amoebic meningoencephalitis due to Naegleria fowleri. Parasitol. Int. 54:219-221. doi: 10.1016/j.parint.2005.06.001.

3. Joseph Martin, A. 2008. Survival of Naegleria fowleri primary amebic meningocephalitis (PAM) could be improved with an intensive multi-route chemo- and biotherapeutic regimen. Med. Hypotheses. 71:969-971. doi: 10.1016/j.mehy.2008.06.037.

4. Kilvington, S., and J. Beeching. 1995. Development of a PCR for identification of Naegleria fowleri from the environment. Appl. Environ. Microbiol. 61:3764-3767.

5. Kilvington, S., and J. Beeching. 1995. Identification and epidemiological typing of Naegleria fowleri with DNA probes. Appl. Environ. Microbiol. 61:2071-2078.

Works Cited

6. Qvarnstrom, Y., G. S. Visvesvara, R. Sriram, and A. J. da Silva. 2006. Multiplex Real-Time PCR Assay for Simultaneous Detection of Acanthamoebaspp., Balamuthia mandrillaris, and Naegleria fowleri. J. Clin. Microbiol. 44:3589-3595. doi: 10.1128/JCM.00875-06.

7. Shakoor, SadiaBeg, Mohammad AsimMahmood, Syed FaisalBandea, RebeccaSriram, RamaNoman, FatimaAli, FarheenVisvesvara,Govinda S.Zafar, Aria. 2011. Primary Amebic Meningoencephalitis Caused by Naegleria fowleri, Karachi, Pakistan. Emerging Infectious Diseases. 17:258-261. doi: 10.3201/eid1702.100442.http://search.ebscohost.com.proxy.consortiumlibrary.org/login.aspx?direct=true&db=mth&AN=59634978&site=ehost-live.

8. Sparagano, O., E. Drouet, R. Brebant, E. Manet, G. A. Denoyel, and P. Pernin. 1993. Use of monoclonal antibodies to distinguish pathogenic Naegleria fowleri (cysts, trophozoites, or flagellate forms) from other Naegleria species. J. Clin. Microbiol. 31:2758-2763.

9. Travis W., H. 2010. Swimming with death: Naegleria fowleri infections in recreational waters. Travel Medicine and Infectious Disease. 8:201-206. doi: 10.1016/j.tmaid.2010.06.001.

Works Cited

10. Vargas-Zepeda, J., A. V. Gómez-Alcalá, J. A. Vázquez-Morales, L. Licea-Amaya, J. F. De Jonckheere, and F. Lares-Villa. 2005. Successful Treatment of Naegleria fowleri Meningoencephalitis by Using Intravenous Amphotericin B, Fluconazole and Rifampicin. Arch. Med. Res. 36:83-86. doi: 10.1016/j.arcmed.2004.11.003.

11. Bauman, R.W. 2011. Antimicrobials against Eukaryotes: Antifungal Drugs. In Microbiology with Diseases by Taxonomy. Benjamin Cummings Publishing Co.. Glenview Il.

Image Credits

Slide 1Artist unknown. Neuron on Black background. Retrieved 11/1/2011, from http://encefalus.com/wp-content/uploads/2008/07/neuron.jpg

Slide 2Jacobs, Bob. Professor, Colorado College. Golgi Stained Neuron. Retrieved 11/1/2011, from http://www.snl.salk.edu/~nikoosh/outreach2006.html

Slide 3Dunn, Greg. Artist. Hippocampal Pyrimidal Neurons. Retrieved 11/1/2011 from, http://gregadunn.com/images/MrTwit-MasterFolderForNewWebsite/comission/zoomifySFNLARGE/hippocampal-pyramidal.html

Slide 4 Artist Unspecified. Work type unspecified. Retrieved 11/1/2011 from http://3.bp.blogspot.com/_gDNe1xZsxX4/TQd1JlvCgqI/AAAAAAAAAEE/vsPpsINhlmc/s1600/Pyramidal_hippocampal_neuron_40x.jpg

Image Credits

Slide 5Schultz, Thomas. Diffusion MRI image (saggital view). Retrieved 11/22/2011 from, http://en.wikipedia.org/wiki/File:DTI-sagittal-fibers.jpg

Slide 6Pearson education, Educational. Work type unknown. Retreived 11/1/2011 from http://science.kennesaw.edu/~jdirnber/Bio2108/Lecture/LecBiodiversity/28_Labeled_Images/28_03lAmoeba-L.jpg

Slide 7Neumeyer, Ron. Proprietor, Micro-Imaging services. Work type unknown. Retreived 11/1/2001 from http://www.microimaging.ca/protozoa/21ameoba.jpg.

Gray’s Anatomy. Lithograph of Cribiform Plate and Olfactory filaments. Retreived 11/1/2011 from http://www.ganfyd.org/images/1/16/Olfactory_Nerve.png

Image Credits

Slide 8Dunn, Greg. Artist. UCSD Mica and Ink Cortex. Retrieved 11/4/2011 from http://gregadunn.com/images/Gallery-GoldLeaf/data/closeUp/UCSD_cortex_closeup.jpg

Artist Unspecified. Photograph. Retreived 11/4/2011 from http://td.rsmjournals.com/content/38/4/25

Slide 9Artist Unknown. Work type unknown. Retrieved 11/1/2011 from http://bloodjournal.hematologylibrary.org/content/117/16/4168

Artist Unspecified. Photograph. Retreived11/1/2011 from http://upload.wikimedia.org/wikipedia/commons/d/d4/Spinal_needles.jpg

Image Credits

Slide 10Origin Unknown. Work type unknown. Retrieved 11/1/2011 from http://bloodjournal.hematologylibrary.org/content/117/16/4168

Centers for Disease Control. Photograph. Retrieved 11/1/2011 from http://aapredbook.aappublications.org/content/images/large/2006/1/004_03.jpeg

Fritz-Laylin, Lillian. UC Berkely. Photograph. Retreived 11/4/2011 from http://newscenter.berkeley.edu/2010/03/04/naegleria/6/F1.large.jpg

Slide 11Dunn, Greg. Artist. Hippocampal Pyrimidal Neurons. Retrieved 11/1/2011 from, http://gregadunn.com/images/MrTwit-MasterFolderForNewWebsite/comission/zoomifySFNLARGE/hippocampal-pyramidal.html

Unspecified Artist. Educational illustration, “Brudzinski’s sign”. Retreived11/4/2011 from, http://www.pennmedicine.org/encyclopedia/em_PrintArticle.aspx?ptid=1&gcid=000680

Image Credits

Unspecified Artist. Educational illustration, “Kernigs Sign”. Retreived11/4/2011 from, http://www.pennmedicine.org/encyclopedia/em_PrintArticle.aspx?ptid=1&gcid=000680

Slide 12Unspecified artist. Photograph. Retrieved 11/4/2011 from, http://pain3.org/medication.php

Fvasconcellos. Chemical Diagram “Amphotericin B”. Retrieved 11/4/2011 from http://en.wikipedia.org/wiki/File:Amphotericin_B_structure.svg

Artist Unspecified. Chemical Diagram “Fluconazole”. Retrieved 11/4/2011 from http://images.rxlist.com/images/rxlist/flucon1.gif

Fvasconcellos. Chemical Diagram “Rifampicin”. Retrieved 11/4/2011 from http://en.wikipedia.org/wiki/File:Rifampicin.svg

Image Credits

Slide 13Unspecified artist. Photograph. Retrieved 11/4/2011 from, http://pain3.org/medication.php

Slide 14Jadwiga Winiecka-Jar Nell, Infectious Diseases Institute. Photograph. Retrieved 11/4/2011 from, http://www.smittskyddsinstitutet.se/upload/Analyser/AcanthamoebaTrofJWK.jpg

Artist Unspecified. Photograph. Retrieved 11/4/2011 from, https://lh4.googleusercontent.com/-LLBY8iEN-2A/TlwwnLSnjQI/AAAAAAAAAPc/B1M5v0n-EfQ/Naegleria%2Bfowleri.jpg

Slides 15 – 17Artist not Specified. Flourescent Neuron stain. Retrieved 11/4/2011 from http://www.incf.org/about/who-we-are/nodes/switzerland/confocal.jpg

Image Credits

Slides 18 –24Artist not Specified. Diffusion MRI image. Retrieved 11/4/2011 from, http://www.popsci.com/files/imagecache/article_image_large/articles/Flow%20state.jpg