Primary amoebic meningoencephalitis
|Primary amoebic meningoencephalitis|
|Classification and external resources|
Histopathology of amebic meningoencephalitis due to Naegleria fowleri. Direct fluorescent antibody stain. (CDC)
Naegleria fowleri propagates in warm, stagnant bodies of freshwater (typically during the summer months), and enters the central nervous system after insufflation of infected water by attaching itself to the olfactory nerve. It then migrates through the cribiform plate and into the olfactory bulbs of the forebrain, where it multiplies itself greatly by feeding on nerve tissue. During this stage, occurring approximately 3–7 days post-infection, the typical symptoms are parosmia, rapidly progressing to anosmia (with resultant ageusia) as the nerve cells of the olfactory bulbs are consumed and replaced with necrotic lesions.
After the organisms have multiplied and largely consumed the olfactory bulbs, the infection rapidly spreads through the mitral cell axons to the rest of the cerebrum, resulting in onset of frank encephalitic symptoms, including cephalgia (headache), nausea, and rigidity of the neck muscles, progressing to vomiting, delirium, seizures, and eventually irreversible coma. Death usually occurs within 14 days of exposure as a result of respiratory failure when the infection spreads to the brain stem, destroying the autonomic nerve cells of the medulla oblongata.
The disease is both exceptionally rare and highly lethal: there had been fewer than 200 confirmed cases in recorded medical history as of 2004, 300 cases as of 2008, with an in-hospital case fatality rate of ~97% (3% patient survival rate).
The high mortality rate of this disease is largely blamed on the unusually non-suggestive symptomology of the early-stage disease compounded by the necessity of microbial culture of the cerebrospinal fluid to effect a positive diagnosis. The parasite also demonstrates a particularly rapid late-stage propagation through the nerves of the olfactory system to many parts of the brain simultaneously (including the vulnerable medulla).
For those reasons, it has been suggested that physicians should give an array of antimicrobial drugs, including the drugs used to treat amoebic encephalitis, before the disease is actually confirmed in order to increase the number of survivors. However, administering several of those drugs at once (or even some of them known to treat the condition) is often very dangerous and unpleasant for the patient.
Naegleria fowleri is commonly referred to as an amoeba but is actually a unicellular parasite that is ubiquitous in soils and warm waters. Infection typically occurs during the summer months and patients typically have a history of exposure to a natural body of water. The organism specifically prefers temperatures above 32 °C, as might be found in a tropical climate or in water heated by geothermal activity. The organism is extremely sensitive to chlorine (<0.5 ppm). Exposure to the organism is extremely common due to its wide distribution in nature, but thus far lacks the ability to infect the body through any method other than direct contact with the olfactory nerve, which is exposed only at the extreme vertical terminus of the paranasal sinuses; the contaminated water must be deeply insufflated into the sinus cavities for transmission to occur.
Michael Beach, a recreational waterborne illness specialist for the Centers for Disease Control and Prevention, stated in remarks to the Associated Press that the wearing of nose-clips to prevent insufflation of contaminated water would be an effective protection against contracting PAM, noting that "You'd have to have water going way up in your nose to begin with".
This form of nervous system infection by amoeba was first documented in Australia in 1965. In 1966, four cases were reported in the USA. By 1968 the causative organism, previously thought to be a species of Acanthamoeba or Hartmannella, was identified as Naegleria. This same year, occurrence of 16 cases over period of two years (1963–1965) was reported in Ústí nad Labem. In 1970, the species of amoeba was named N. fowleri.
In October 1978, a young girl swimming with the Bath Dolphins, a local swimming club, in the restored Roman bath in Bath, Somerset, contracted meningitis and died, leading to the closure of the bath for several years. Tests showed that N. fowleri was in the water.
In August 2010, 7-year-old Kyle Lewis died after contracting the protist from swimming in Lake Granbury and warm water near Glen Rose, Texas. Texas authorities say this is the tenth case since 2000.
In August 2012, Jack Ariola Erenberg, a 9 year old boy from Stillwater, Minnesota, died after swimming in Lily Lake near his home.
On 7 August 2012, Waylon Abel, 30, of Loogootee IN died after swimming in West Boggs Lake near his home.
The current standard treatment is prompt intravenous administration of heroic doses of Amphotericin B, a systemic antifungal that is one of the few effective treatments for systemic infections of protozoan parasitic diseases (such as leishmaniasis and toxoplasmosis).
The success rate in treating PAM is usually quite poor, since by the time of definitive diagnosis most patients have already manifested signs of terminal cerebral necrosis. Even if definitive diagnosis is effected early enough to allow for a course of medication, Amphotericin B also causes significant and permanent nephrotoxicity in the doses necessary to quickly halt the progress of the amoebae through the brain.
Two cases of similar amoebic infections (caused by Balamuthia mandrillaris) were successfully treated for amoebic encephalitis and recovered, including a 5-year-old girl and a 64-year-old man. The successful use of a combination regimen that includes one amebicidal drug (miltefosine) along with two amebistatic drugs capable of crossing the brain-blood barrier (fluconazole and albendazole) provides hope for attaining clinical cure for an otherwise lethal condition.
There is preclinical evidence that the relatively safe, inexpensive, and widely available phenothiazine antipsychotic chlorpromazine is a highly efficacious amebicide against N. fowleri, with laboratory animal survival rates nearly double those receiving treatment with amphotericin B. The mechanism of action is possibly the inhibition of the nfa1 and Mp2CL5 genes, found only in pathogenic strains of N. fowleri, which are involved in amoebic phagocytosis and regulation of cellular growth, respectively.
See also 
- Cabanes PA, Wallet F, Pringuez E, Pernin P (July 2001). "Assessing the risk of primary amoebic meningoencephalitis from swimming in the presence of environmental Naegleria fowleri". Appl. Environ. Microbiol. 67 (7): 2927–31. doi:10.1128/AEM.67.7.2927-2931.2001. PMC 92963. PMID 11425704.
- Sarica, F. B.; Tufan; Cekinmez; Erdoğan; Altinörs (2009). "A rare but fatal case of granulomatous amebic encephalitis with brain abscess: the first case reported from Turkey". Turkish neurosurgery 19 (3): 256–259. PMID 19621290.
- Centers for Disease Control and Prevention (CDC) (May 2008). "Primary amebic meningoencephalitis—Arizona, Florida, and Texas, 2007". MMWR Morb. Mortal. Wkly. Rep. 57 (21): 573–7. PMID 18509301.
- Cervantes-Sandoval I, Serrano-Luna Jde J, García-Latorre E, Tsutsumi V, Shibayama M (September 2008). "Characterization of brain inflammation during primary amoebic meningoencephalitis". Parasitol. Int. 57 (3): 307–13. doi:10.1016/j.parint.2008.01.006. PMID 18374627.
- Wiwanitkit V (2004). "Review of clinical presentations in Thai patients with primary amoebic meningoencephalitis". MedGenMed 6 (1): 2. PMC 1140726. PMID 15208515.
- Caruzo G, Cardozo J (October 2008). "Primary amoebic meningoencephalitis: a new case from Venezuela". Trop Doct 38 (4): 256–7. doi:10.1258/td.2008.070426. PMID 18820207.
- "Amebic Meningoencephalitis". Retrieved 16 July 2010.
- "Geothermal activity". Retrieved 9 January 2008.[dead link]
- "6 die from brain-eating amoeba in lakes", Chris Kahn/Associated Press, 9/28/07
- Fowler, M.; Carter, R. F. (September 1965). "Acute pyogenic meningitis probably due to Acanthamoeba sp.: a preliminary report". British Medical Journal 2 (5464): 740–2. doi:10.1136/bmj.2.5464.734-a. PMC 1846173. PMID 5825411.
- Symmers, W. S. C. (November 1969). "Primary amoebic meningoencephalitis in Britain". British Medical Journal 4 (5681): 449–54. doi:10.1136/bmj.4.5681.449. PMC 1630535. PMID 5354833.
- Červa, L.; Novák, K. (April 1968). "Ameobic meningoencephalitis: sixteen fatalities". Science 160 (3823): 92. doi:10.1126/science.160.3823.92. PMID 5642317.
- Gutierrez, Yezid (15). "Chapter 6: Free Living Amebae". Diagnostic Pathology of Parasitic Infections with Clinical Correlations (2 ed.). USA: Oxford University Press. pp. 114–115. ISBN 0-19-512143-0.
- "History of Bath's Spa". Bath Tourism. Retrieved 9 January 2013.
- Crowther, Nigel B. (2007). Sport in Ancient Times. Greenwood Publishing Group. p. 98. ISBN 9780275987398. Retrieved 9 January 2013.
- Kilvington, Simon; Beeching, John (June 1995). "Identification and epidemiological typing of Naegleria fowleri with DNA probes". Applied and Environmental Microbiology 61 (6): 2071–2078. PMC 167479. PMID 7793928. Retrieved 9 January 2013.
- Giles, Kevin (26 August 2010). "Stillwater girl died from water organism". Star Tribune. Retrieved 9 January 2013.
- "Tarrant County resident dies from amoeba infection". Pegasus News. 31 August 2010. Retrieved 9 January 2013.
- Caulfield, Philip (14 August 2011). "Florida teen, Courtney Nash, dies from rare brain parasite after swimming in river near her home". New York Daily News. Retrieved 9 January 2013.
- Wolchover, Natalie (16 December 2011). "Neti pots linked to brain-eating amoeba deaths". LiveScience. Retrieved 9 January 2013.
- Davis, Kelly (19 July 2012). "Sumter boy dies of rare brain infection". The State. Retrieved 9 January 2013.
- Abbasi, Shahid (19 July 2012). "Eight die in Karachi due to Naegleria". The News Tribe. Retrieved 9 January 2013.
- "Heartbreak as boy, age 9, is killed by extremely rare brain-eating amoeba he caught swimming in lake". Daily Mail. 9 August 2012. Retrieved 9 January 2013.
- Smith, Nate (1 September 2012). "Beach closed: Autopsy confirms rare parasite". Washington Times-Herald. Retrieved 9 January 2013.
- Poungvarin N, Jariya P (February 1991). "The fifth nonlethal case of primary amoebic meningoencephalitis". J Med Assoc Thai 74 (2): 112–5. PMID 2056258.
- Jain R, Prabhakar S, Modi M, Bhatia R, Sehgal R (December 2002). "Naegleria meningitis: a rare survival". Neurol India 50 (4): 470–2. PMID 12577098.
- Vargas-Zepeda J, Gómez-Alcalá AV, Vásquez-Morales JA, Licea-Amaya L, De Jonckheere JF, Lares-Villa F (2005). "Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin". Arch. Med. Res. 36 (1): 83–6. doi:10.1016/j.arcmed.2004.11.003. PMID 15900627.
- "Proceedings of the Oklahoma Academy of Science". Retrieved 2 January 2009.
- Deetz TR, Sawyer MH, Billman G, Schuster FL, Visvesvara GS (200). "Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases". Clin Infect Dis 37 (10): 1304–12. doi:10.1086/379020. PMID 14583863.
- Kim, JH; Jung, SY, Lee, YJ, Song, KJ, Kwon, D, Kim, K, Park, S, Im, KI, Shin, HJ (November 2008). "Effect of therapeutic chemical agents in vitro and on experimental meningoencephalitis due to Naegleria fowleri.". Antimicrobial agents and chemotherapy 52 (11): 4010–6. doi:10.1128/AAC.00197-08. PMC 2573150. PMID 18765686. Retrieved 22 April 2012.
- Tiewcharoen, Supathra (1 January 2011). "Activity of chlorpromazine on nfa1 and Mp2CL5 genes of Naegleria fowleri trophozoites". Health 03 (03): 166–171. doi:10.4236/health.2011.33032. Retrieved 22 April 2012.
- Primary amoebic meningoencephalitis – Centers for Disease Control and Prevention