Primary amoebic meningoencephalitis
Encyclopedia
Primary amoebic meningoencephalitis (PAM, or PAME) is a disease of the central nervous system
caused by infection from Naegleria fowleri
.
(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 exceptionally 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
).
This extreme mortality
is largely blamed on the unusually non-suggestive symptom
ology 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.
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".
. In 1970, the species of amoeba was named N. fowleri.
In 2010, a 7-year-old girl in Stillwater, Minnesota
died of the disease.
In August 2011, a 16-year-old girl in Mims, Florida
died after swimming in the St. John's River
a week earlier. Doctors found N. fowleri in her cerebral spinal fluid.
doses of Amphotericin B
, a systemic antifungal
which 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.
Rifampicin
has also been used with amphotericin B in successful treatment. However, there is some evidence that it does not effectively inhibit Naegleria growth.
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.
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
caused by infection from Naegleria fowleri
Naegleria fowleri
Naegleria fowleri is a free-living excavate form of protist typically found in warm bodies of fresh water, such as ponds, lakes, rivers, and hot springs. It is also found in soil, near warm-water discharges of industrial plants, and unchlorinated swimming pools in an amoeboid or temporary...
.
Presentation
Naegleria fowleri propagates in warm, stagnant bodies of freshwaterFreshwater
Fresh water is naturally occurring water on the Earth's surface in ice sheets, ice caps, glaciers, bogs, ponds, lakes, rivers and streams, and underground as groundwater in aquifers and underground streams. Fresh water is generally characterized by having low concentrations of dissolved salts and...
(typically during the summer months), and enters the central nervous system after insufflation
Insufflation (medicine)
Insufflation is the practice of inhaling a substance. Insufflation has limited medical use, but is a common route of administration with many respiratory drugs used to treat conditions in the lungs and paranasal sinus .The technique is common for many recreational drugs and is also used for some...
of infected water by attaching itself to the olfactory nerve
Olfactory nerve
The olfactory nerve, or cranial nerve I, is the first of twelve cranial nerves. It is instrumental in the sense of smell. Derived from the embryonic nasal placode, the olfactory nerve is capable of regeneration.-Anatomy:...
. 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
Parosmia
Parosmia, also known as troposmia or cacosmia, is an olfactory dysfunction that is characterized by the inability of the brain to properly identify an odor’s “natural” smell....
, rapidly progressing to anosmia
Anosmia
Anosmia is a lack of functioning olfaction, or in other words, an inability to perceive odors. Anosmia may be either temporary or permanent. A related term, hyposmia, refers to a decreased ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one...
(with resultant ageusia
Ageusia
Ageusia is the loss of taste functions of the tongue, particularly the inability to detect sweetness, sourness, bitterness, saltiness, and umami . It is sometimes confused with anosmia - a loss of the sense of smell...
) 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
Mitral cell
Mitral cells are neurons that are part of the olfactory system. They are located in the olfactory bulb in the mammalian central nervous system. They receive information from the axons of olfactory receptor neurons, forming synapses in neuropils called glomeruli...
axons to the rest of the cerebrum, resulting in onset of frank encephalitic
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
symptoms, including cephalgia (headache), nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, and rigidity
Rigidity
Rigid or rigidity may refer to:*Stiffness, the property of a solid body to resist deformation, which is sometimes referred to as rigidity*Structural rigidity, a mathematical theory of the stiffness of ensembles of rigid objects connected by hinges...
of the neck muscles, progressing to vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, seizures, and eventually irreversible coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
. Death usually occurs within 14 days of exposure as a result of respiratory failure
Respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
when the infection spreads to the brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
, destroying the autonomic nerve cells of the medulla oblongata
Medulla oblongata
The medulla oblongata is the lower half of the brainstem. In discussions of neurology and similar contexts where no ambiguity will result, it is often referred to as simply the medulla...
.
The disease is both exceptionally rare and exceptionally 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
Survival rate
In biostatistics, survival rate is a part of survival analysis, indicating the percentage of people in a study or treatment group who are alive for a given period of time after diagnosis...
).
This extreme mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
is largely blamed on the unusually non-suggestive symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
ology of the early-stage disease compounded by the necessity of microbial culture of the cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
to effect a positive diagnosis
Diagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
. The parasite also demonstrates a particularly rapid late-stage propagation through the nerves of the olfactory system
Olfactory system
The olfactory system is the sensory system used for olfaction, or the sense of smell. Most mammals and reptiles have two distinct parts to their olfactory system: a main olfactory system and an accessory olfactory system. The main olfactory system detects volatile, airborne substances, while the...
to many parts of the brain simultaneously (including the vulnerable medulla
Medulla oblongata
The medulla oblongata is the lower half of the brainstem. In discussions of neurology and similar contexts where no ambiguity will result, it is often referred to as simply the 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.
Cause
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 only exposed at the extreme vertical terminus of the paranasal sinuses; the contaminated water must actually 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
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
, 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".
Occurrence
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 Hartmanella, was identified as Naegleria. This same year, occurrence of 16 cases over period of two years (1963-1965) was reported in Ústí nad LabemÚstí nad Labem
Ústí nad Labem is a city of the Czech Republic, in the Ústí nad Labem Region. The city is the 7th-most populous in the country.Ústí is situated in a mountainous district at the confluence of the Bílina and the Elbe Rivers, and, besides being an active river port, is an important railway junction...
. In 1970, the species of amoeba was named N. fowleri.
In 2010, a 7-year-old girl in Stillwater, Minnesota
Stillwater, Minnesota
As of the census of 2000, there were 15,143 people, 5,797 households, and 4,115 families residing in the city. The population density was 2,340.0 people per square mile . There were 5,926 housing units at an average density of 915.7 per square mile...
died of the disease.
In August 2011, a 16-year-old girl in Mims, Florida
Mims, Florida
Mims is a census-designated place in Brevard County, Florida, United States. The population was 9,147 at the 2000 census. It is part of the Titusville, Florida Metropolitan Statistical Area.-Geography:Mims is located at ....
died after swimming in the St. John's River
St. Johns River
The St. Johns River is the longest river in the U.S. state of Florida and its most significant for commercial and recreational use. At long, it winds through or borders twelve counties, three of which are the state's largest. The drop in elevation from the headwaters to the mouth is less than ;...
a week earlier. Doctors found N. fowleri in her cerebral spinal fluid.
Treatment
The current standard treatment is prompt intravenous administration of heroicHeroic measure
In medicine, heroic refers to a treatment or course of therapy which possesses a high risk of causing further damage to a patient's health, but is undertaken as a last resort with the understanding that any lesser treatment will surely result in failure....
doses of Amphotericin B
Amphotericin B
Amphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
, a systemic antifungal
Antifungal
* Antifungal medication, a medication used to treat fungal infection s such as athlete's foot , ringworm, candidiasis, etc.* Antifungal protein, a protein family* an adjective referring to a fungicide compound...
which is one of the few effective treatments for systemic infections of protozoan parasitic diseases (such as leishmaniasis
Leishmaniasis
Leishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly...
and toxoplasmosis
Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...
).
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
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
. Even if definitive diagnosis is effected early enough to allow for a course of medication, Amphotericin B also causes significant and permanent nephrotoxicity
Nephrotoxicity
Nephrotoxicity is a poisonous effect of some substances, both toxic chemicals and medication, on the kidneys. There are various forms of toxicity. Nephrotoxicity should not be confused with the fact that some medications have a predominantly renal excretion and need their dose adjusted for the...
in the doses necessary to quickly halt the progress of the amoebae through the brain.
Rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
has also been used with amphotericin B in successful treatment. However, there is some evidence that it does not effectively inhibit Naegleria growth.
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.
See also
- Free-living amebic infectionFree-living amebic infectionFree-living amoebae in the Amoebozoa group are important causes of disease in humans and animals.Naegleria fowleri is sometimes included in the group "free-living amoebae", and it causes a condition traditionally called primary amoebic meningoencephalitis...
- MeningoencephalitisMeningoencephalitisMeningoencephalitis is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain.-Causes:...
- Waterborne diseasesWaterborne diseasesWaterborne diseases are caused by pathogenic microorganisms which are directly transmitted when contaminated fresh water is consumed. Contaminated fresh water, used in the preparation of food, can be the source of foodborne disease through consumption of the same microorganisms...
- AcanthamoebaAcanthamoebaAcanthamoeba is a genus of amoebae, one of the most common protozoa in soil, and also frequently found in fresh water and other habitats. The cells are small, usually 15 to 35 μm in length and oval to triangular in shape when moving. The pseudopods form a clear hemispherical lobe at the anterior,...
External links
- Primary amoebic meningoencephalitis - Centers for Disease Control and PreventionCenters for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
- http://www.dshs.state.tx.us/idcu/disease/primary_amebic_meningoencephalitis/