What is Primary Amoebic Meningoencephalitis?
Primary amoebic meningoencephalitis (PAM) is a brain infection caused by a single-celled organism called Naegleria fowleri. The organism typically lives in warm freshwater, and it can infect people when it enters the body through the nose. People who swim in warm lakes, rivers, or hot springs may encounter the organism, and infections are more likely when water is forced into the nose during an activity such as diving.
PAM infections are very rare, affecting only about three people each year in the United States. However, the infection is usually fatal.
PAM infections occur when the organism travels from the nose to the brain through the olfactory nerve. Once in the brain, the organism causes inflammation, swelling, and degeneration of brain tissue, resulting in symptoms similar to bacterial meningitis.
Symptoms of PAM
PAM symptoms usually begin about five days after swimming in contaminated water, but initial symptoms can occur 1-9 days after exposure. After that, the infection progresses rapidly through two stages, and death typically occurs within 1-18 days after symptoms start.
Stage 1 Symptoms
Stage 2 Symptoms
- Stiff neck
- Balance difficulties
When Not to Worry About PAM
If you’re concerned about exposure to the infection-causing organism, keep these facts in mind:
- Naegleria fowleri does not live in salt water.
- Drinking contaminated water does not cause infections.
- PAM can’t be passed from person to person.
What Causes Primary Amoebic Meningoencephalitis?
PAM infections occur when a person is exposed to the Naegleria fowleri amoeba and water containing the amoeba enters the person’s nose. The risk of infection increases when you swim in water that is likely to be contaminated and participate in activities (e.g., diving) that are more likely to force water into your nose under pressure.
Naegleria fowleri prefers to live in warm freshwater, so it is more common in the summer months and in water that is heated, either artificially or naturally. Water sources at higher risk of contamination include:
- Warm lakes and rivers
- Hot springs
- Water near power plants or industrial sites
- Geothermal wells
- Water heaters
- Improperly sanitized swimming pools
Naegleria fowleri can occur anywhere in the United States but is more common in southern states. Historically, most PAM infections have occurred in Texas and Florida.
Is Primary Amoebic Meningoencephalitis Hereditary?
External environmental sources cause PAM infections, and family history plays no part in developing the infection.
How Is Primary Amoebic Meningoencephalitis Detected?
PAM can be difficult to diagnose early because its symptoms are similar to more common types of meningitis. It is often not diagnosed until after death.
Seek immediate medical care if you or someone you care for experiences potential PAM symptoms, such as:
- Sudden onset of fever
- Severe, sudden headache
- Unexplained vomiting
- Stiff neck
Let your doctor know if the person has recently been exposed to water that may have been contaminated with Naegleria fowleri.
How Is Primary Amoebic Meningoencephalitis Diagnosed?
Because PAM is so rare, it may be misdiagnosed as a more common form of meningitis. The laboratory tests used to detect the organism’s presence are specialized and not available at all labs in the United States. Consequently, in most cases, PAM is not definitively diagnosed until after the patient’s death.
When your doctor suspects a PAM infection, they may follow a diagnostic procedure that includes:
- Medical history questions. Your doctor will look for signs that you may be at increased risk for the infection.
- Lumbar puncture (spinal tap). This test will look for evidence of the organism in the cerebral spinal fluid (CSF).
- Biopsy of brain lesions. Doctors may remove a sample of the infected tissue using a fine needle. Tests of this sample can identify the source of the infection and allow for more effective treatment.
How Is Primary Amoebic Meningoencephalitis Treated?
All but five cases of PAM in North America have been fatal. Of the five survivors, the most recent was a 16-year-old boy in the United States in 2016. Although no treatment of the infection has proven consistently effective, the survivors were treated with a variety of medications, leading doctors to try these medications in other cases. Drugs that may be used include:
- Amphotericin B
How Does Primary Amoebic Meningoencephalitis Progress?
PAM progresses rapidly, and some cases progress more rapidly than others. In the acute form, progression from early symptoms (such as changes in sense of smell, headache, light sensitivity, stiff neck) to late symptoms (confusion, delirium, coma) is rapid. Ultimately, death can happen as fast as two days. In the subacute form of the infection, the patient may survive up to four weeks or even longer.
How Is Primary Amoebic Meningoencephalitis Prevented?
Aside from avoiding exposure to warm water entirely, there is no sure way to prevent PAM infections. Millions of Americans swim and participate in warm-water activities every year, but Naegleria fowleri infections are extremely rare. In many cases, other people were swimming in the same water as people who became ill, yet the other people showed no sign of infection. This suggests that some people may be at increased risk for infection, but scientists don’t yet know how or why.
Primary Amoebic Meningoencephalitis Caregiver Tips
If you are a caregiver for a loved one with PAM, keep these tips in mind:
- Attend doctor appointments with your loved one so you can understand the diagnosis, the treatment plan, and the expectations for recovery.
- Communicate well with your health care providers so they understand the situation.
- Call upon family and community to help out whenever possible. Don’t try to take sole responsibility for caregiving.
Primary Amoebic Meningoencephalitis Brain Science
Naegleria fowleri enters the brain by a route that begins in the nose. The organism penetrates mucus membranes in the nose and then travels through a network of nerves called the submucosal nervous plexus. From there, it moves through the olfactory nerves, which transmit scent-related information to the brain. Finally, it passes through the cribriform plate, a porous part of the skull through which the olfactory nerves connect to the brain.
Once in the brain, the organisms secrete toxins that cause inflammation and damage to brain cells and the tissues (meninges) surrounding the brain. Fluid also accumulates in and around the brain tissue, resulting in swelling that causes further damage. The affected tissue eventually dies, causing the infection’s symptoms and, usually, death.
Primary Amoebic Meningoencephalitis Research
Title: Rare Disease Patient Registry & Natural History Study – Coordination of Rare Diseases at Sanford (CoRDS)
Principal Investigator: Benjamin Forred, MBA
Sioux Falls, SD
CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as efficiently as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals, and researchers to assist in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.
Title: Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Principal Investigator: Irini Sereti, MD
National Institute of Allergy and Infectious Diseases (NIAID)
Idiopathic CD4+ lymphocytopenia (ICL) is a disorder characterized by decreased numbers of circulating CD4+ T lymphocytes without known causes of CD4+ lymphocytopenia. ICL is defined as an absolute CD4+ T cell count of fewer than 300 cells/microL in a patient with no human immunodeficiency virus infection or known immunodeficiency syndrome. The causes and frequency of the disorder remain unknown. The condition is typically diagnosed when patients present with a serious infection. In this natural history protocol, we will evaluate patients with CD4+ T cell counts below 300 cells/microL. We propose to follow 300 ICL patients for a minimum of 4 and a maximum of 20 years, with a particular focus on the association between ICL and autoimmune disease. In addition to the ICL patients, we will enroll blood relatives and household contacts to better understand the pathogenesis and etiologies of the syndrome. Researchers will collect blood and other tissues for immunologic, rheumatologic, and genetic testing to identify and understand the underlying defects that cause ICL and follow its course in a cohort of patients who will receive the best standard therapy for opportunistic infections.
Title: Modulating ApoE Signalling to Reduce Brain Inflammation, deLirium, and Postoperative Cognitive Dysfunction (MARBLE)
Principal Investigator: Miles Berger, MD, PhD
This research study will evaluate the effectiveness and estimate the feasibility of administering an investigational drug called ‘CN-105’ (the study drug) to prevent postoperative cognitive decline, delirium (serious confusion), and underlying brain inflammatory and brain activity changes in adults 60 years and older undergoing surgery. The word “investigational” means the study drug is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA).
It is hoped that CN-105 will block signaling via a gene known as ApoE4, the most common gene implicated in late-life Alzheimer’s disease.
Depending on when patients enroll in this study, participants will receive either a placebo or a progressively higher dose of CN-105 until the safest and best-tolerated dose is reached. The study drug is given via IV (intravenous, meaning through a vein) infusion in the hospital. Study drug infusions will be administered up to 4 days after surgery.
Participants will also perform memory and thinking tests, as well as complete a survey and functional assessments, both prior to surgery and again 6 weeks after surgery. Each of those research visits will last about 1 hour.
Additionally, the investigators will collect a blood sample and a cerebrospinal fluid (CSF) sample before the participant’s surgery, 24 hours after surgery, and again 6 weeks after surgery. To obtain the CSF (cerebrospinal fluid) sample, investigators will perform a puncture of a lumbar (the lower part of the spinal column). During surgery, investigators will also record participant brain waves from the scalp using an EEG (electroencephalography) monitor. An electroencephalography monitor reads the brain’s electrical activity in different places using a cap with sensors worn on the head.
Although previous studies have not found any associations between the study drug and any serious medical problems, investigators will monitor its effect on wound healing and postoperative infections.
The benefits of this study include fewer problems in thinking and memory after surgery if this study drug works as hoped.
Risks of participation in this study include headache, infection/discomfort from the lumbar puncture, discomfort from the blood draw, and minor skin irritation or redness from the EEG and heart rate monitor procedures.