Primary amoebic meningoencephalitis with subsequent organ procurement: a case study.
Article Type: Case study
Subject: Anti-infective agents (Health aspects)
CT imaging (Usage)
Meningoencephalitis (Case studies)
Meningoencephalitis (Development and progression)
Meningoencephalitis (Care and treatment)
Meningoencephalitis (Diagnosis)
Author: Tuppeny, Misti
Pub Date: 10/01/2011
Publication: Name: Journal of Neuroscience Nursing Publisher: American Association of Neuroscience Nurses Audience: Professional Format: Magazine/Journal Subject: Health care industry Copyright: COPYRIGHT 2011 American Association of Neuroscience Nurses ISSN: 0888-0395
Issue: Date: Oct, 2011 Source Volume: 43 Source Issue: 5
Product: Product Code: 2834800 Antiinfective Preparations NAICS Code: 325412 Pharmaceutical Preparation Manufacturing SIC Code: 2834 Pharmaceutical preparations
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 269689133
Full Text: ABSTRACT

Primary amoebic meningoencephalitis (PAM) is a rare and rapidly fatal disease caused by the Naegleria fowleri amoeba. It is a diagnosis rarely seen by medical personnel, yet this amoeba is frequently encountered by people who frequent freshwater bodies of water in certain states. The disease primarily affects children and young adults who swim or take part in water sports in the waters in which the amoeba thrive. The disease presents with symptomatology similar to bacterial meningitis: headache, stiff neck, altered mental status, seizures, and coma with a quick progression to death. Rapid diagnosis is imperative to facilitate prompt treatment, although PAM has 95% mortality. There have been only 10 survivors reported in medical literature. This disease is a public-health risk to those living in affected areas of the country. Healthcare providers need to be cognizant of the disease as well, and, although recover is rare, focus on prevention and risk reduction strategies is imperative. It is not completely understood why, of the millions of people are exposed to freshwater with the amoeba, only a few become infected with it. The Centers for Disease Control and Prevention have suggested that all freshwater areas should always assume a level of risk in waters, even when signage is not posted. This case study will review a fatal case of Naegleria fowled infection in a young patient and will include the pathophysiology, diagnosis, treatment, nursing and public health implications, and organ procurement that occurred with the patient.

Case Study

A 22-year-old male college student presented to the emergency department, accompanied by his sister, with a 1-day history of headache, neck pain, and photosensitivity. He had an unremarkable medical history and denied having allergies. He stated that he had been wakeboarding at a local water sports arena 3 days before. The patient stated that his headache started the next day with a low-grade fever, which progressed with increasing neck pain. An initial neurological exam exhibited him to be alert and cooperative (a positive Brudzinski and Kemig sign) and an oral temperature of 102.3[degrees]F. Initial serum laboratory results were WBC = 17.7/[micro]l and H/H = 13.8 g/dl/ 38.6%. Serum electrolytes were all within normal values, with the exception of potassium, which was 3.3 mEq/l, and replacement therapy was started as per the hospital's standing protocol. The test result for influenza A and B was negative. A computed tomography scan of the brain without contrast revealed no acute intracranial abnormalities. A lumbar puncture

was performed, which did not exhibit any bacteria on Gram stain but had an abundant pleocytosis of neutrophils. Cerebral spinal fluid (CSF) protein level was 450, and glucose was 42 with elevated nucleated cells. Serum neutrophils were 84%, lymphocytes were 8%, monocytes were 2%, and atypical lymphocytes were between 8% and 9%. An infectious disease consult was obtained in the emergency department, and the patient was admitted to the intensive care unit for further care. The patient was then started on vancomycin (Vancocin), ceftriaxone (Rocephin), and amipicillin. Further reports from the technician in the microbiology laboratory stated that he did note free moving amoebas in the fresh prep of the CSF. At that time, the physician then added amphotericin B (Ambisome), rifampin (Rifadin), azithromycin (Zithromax), and fluconazole (Diflucan) to the medication regimen. The diagnosis of amoebic meningoencephalitis was then rendered with Naegleria fowleri being the organism identified. A transfer to the tertiary neurosurgical center was then obtained to start intrathecal antibiotic therapy.

The neurological examination indicated that the patient did follow commands but had increasing difficulty in following them exactly and became increasingly combative during the following hours. Deep tendon reflexes were 1+. The patient then developed horizontal nystagmus, and his speech became illogical. His neurological deterioration quickly continued, and he was subsequently intubated. The patient was then flown via the medical helicopter to the tertiary neurocritical care (NCC) unit of the hospital, where a neurosurgeon had been consulted to emergently place an intracranial pressure monitor to administer intrathecal amphotericin B and monitor intracranial pressures.

On arrival to the NCC unit, the intracranial pressure monitor was placed. Invasive lines for hemodynamic monitoring and line access were inserted by the intensivist. Ambisome intrathecal therapy was then begun, using premedication protocol. Acetaminophen (Tylenol), diphenhydramine (Benadryl), and hydrocortisone were given for the prevention of rigors and chills, commonly seen with AmBisome therapy. Meperidine was not used to prevent any further dulling of the patient's neurological status.

The infectious disease physician and neurosurgeon had a lengthy discussion with the parents to educate them on the diagnosis and the likely grave progression of this disease. The patient continued to deteriorate and eventually progressed to brain death. Confirmatory testing was eventually completed, and a referral was made to the local organ procurement agency, as per hospital protocol. At this time, the nursing staff within the NCC unit had obviously questioned the physicians regarding the likelihood of possible organ donation due to the infectious diagnosis. The infectious disease physician educated the staff that, although this diagnosis was due to an amoebic organism, the amoeba was not known to be found outside the central nervous system and donation would be safe for recipients. Further, the organ procurement coordinator provided literature to educate the staff on the diagnosis and that it was an infection thought to be limited to the central nervous system. The staff was aware that the organ procurement medical director was closely involved with this case to provide expert guidance. The medical director had previously consulted the chairperson for the Organ Procurement and Transplantation Network's Disease Transmission Advisory Committee regarding the risk of disease transmission from Naegleria meningoencephalitis.

The organ procurement coordinator subsequently assessed the patient for suitability for organ or tissue donation. The patient's family was approached for possible organ donation. Lengthy discussion with the family by the organ procurement coordinator and the infectious disease physician allayed any concerns to the family about the possibility of infection being transmitted to a new organ recipient. The patient's family agreed to multiple organ donation, and organs were transplanted to various individuals following the Organ Procurement and Transplantation Network/ United Network for Organ Sharing protocol. No disease or infection transmission has occurred in the recipients 6 months following transplantation.

Epidemiology

Primary amoebic meningoencephalitis (PAM) is a usually fatal disease that affects primarily young children and adults who use warm freshwater for outdoor water activities, primarily in the months of July through September. Through vigorous activities such as swimming or diving, water forcibly enters the nasal passages, the amoeba progresses to the brain where it thrives, and the affected individual subsequently dies. It has been diagnosed in more men than women, but this appears to be because of the activities they participate in versus gender preference. PAM is caused by the Naegleria fowleri, a free living amoeba that thrives in warm freshwater, minimally chlorinated pools, or even heated swimming pools (see Centers for Disease Control and Prevention [CDC] fact sheet; CDC, 2009). It is a thermophilic organism that thrives in tropical and subtropical climates and is found with water temperatures of 80[degrees]F or greater. It has not been isolated in saltwater. There are 30 species of Naegleria; however, Naegleria fowleri is the only one that has been isolated in human cases of amoebic meningitis and is specific to the central nervous system (CDC, 2009; da Rocha-Azevedo, Tanowitz, & Marciano-Cabra, 2009). Although most reports of PAM have been associated with freshwater contact, inhalation of contaminated dust that contains the encysted form of the amoeba has been reported (Grate, 2006).

The incubation period between exposure and clinical manifestation varies from 1 day to 1 week (Bennett, Nespral, Rosson, & McEvoy, 2008). Reported cases have been identified in the eastern coast of the United States, from Virginia to Florida, and the western states of California and Arizona. Countries with identified cases of PAM include Australia, Venezuela, Mexico, and African countries. Fowler and Carter (1965) first identified that the free living amoeba caused human disease in Australia in 1965; however, Butt (1966) reported several cases in Florida and thus coined the term "primary amoebic meningoencephalitis." There have been 200 cases of PAM identified because of Naegleria fowleri worldwide (Parija, Bronze, Gibbs, & Johnson, 2007), with six cases reported to the CDC in 2007 (CDC, 2007).

Naegleria fowleri is an amoeba flagellate that has three morphological forms in its life cycle: the amoeba or trophozoite form that feeds and divides and is the infective stage for humans; the flagellate that swims and seeks out a dietary source; and the cyst form that protects the amoeba from adverse environmental conditions (da Rocha-Azevedo et al., 2009). Warm freshwaters, along with a large bacterial food supply, provide the rich environment for the amoeba to flourish. The warm summer months of certain geographical areas within the United States and worldwide also bring forth water activities in which individuals seek out the water to cool off. Vigorous activities such as swimming, diving, and wakeboarding can stir up of the waters in which the amoeba live and cause them to invade the body via the nasal passages when water forcibly enters the passages. Bodies of water identified as habitats have included manmade bodies of water, ponds, lakes, unchlorinated swimming pools, or natural habitats that become disturbed by vigorous human contact. There have not been any cases in which a person contracted the disease from a properly maintained swimming pool nor can the disease be transmitted from human to human. At this time, there have not been any reported cases in areas in which flooding via natural weather phenomenon (hurricane, flash flood, etc.) has occurred. In addition, there has not been any correlation of occupational exposures of Naegleria fowleri; they have been limited to individuals who have had exposure to freshwater for recreational activities.

Pathophysiology

The infection occurs when water containing the amoeba is forced up into the nasal passages, attaches to the olfactory mucosa, and migrates across the cribiform plate into the brain via the olfactory bulbs. The adherence of the amoeba to the nasal membrane is the critical key piece in the first step of the infective process. The cribiform plate is more porous in children than in adults, and this may also account for a higher incidence of PAM in children versus adults. Once inside the host tissue, the amoeba releases enzymes to dissolve the host's tissues and thus access to the brain. The amoeba has surface proteins that allow the amoeba internal access to the neuron. The ability of the amoeba to have an increased rate of locomotion and its chemotactic responses to nerve cell components may be the key in its quick progression within the human brain (Marciano-Cabral & Cabral, 2007).

In addition to the attachment, the locomotion, and the release of cytolytic molecules, the amoeba has successfully developed mechanisms to evade the host's immune system. Naegleria fowleri is resistant to lysis by tumor necrosis factor and membrane attack complex. Thus, the amoeba can prevent the patient's immune system from destroying the amoeba. The proteins on the amoeba's cell surface interfere with complement-mediated lysis by preventing the activation of the complement (Marciano-Cabral & Cabral, 2007). Thus, the amoebas can prevent the attachment of the host's surface proteins, collect them, and then effectively shed the membrane. The cyst form of the amoeba develops for protection when the amoeba is in a hostile environment; the hard outer cyst prevents destruction by external forces. The membrane that is shed acts as a decoy of the human body, attracting more complement proteins that normally would attack the amoeba. Thus, the amoeba attracts the proteins, collects them, and then sheds them, all the while rapidly dividing and causing more cellular injury to the cerebral tissue. The amoeba can easily be mistaken for leukocytes in the CSF. However, a closer inspection of the motion of the amoeba shows that it is a swift-moving organism whereas leukocytes move much more slowly. This difference alone can set the stage for a late diagnosis when studying the CSF prep in the microbiology laboratory, with mortality rising each hour the correct diagnosis is not made. The amoeba quickly proliferates once in the brain tissue, and death ensues within 7-10 days in most cases (da Rocha-Azevedo et al., 2009). The environment of the brain, which houses heat, glucose, and high-oxygen content, provides the rich environment for the amoeba to rapidly proliferate within the cerebral tissue.

Pathological cerebral changes include acute hemorrhagic necrotizing areas with purulent exudates in the cortex, brain stem, and cerebellum (Grate, 2006). It has been reported that patients who develop meningoencephalitis from Naegleria fowleri may have an immunoglobulin IgA deficiency, which would account for weaker defenses at the mucus membrane level (Reilly, Marchaino, Bradley, & Bradley, 1983). Data suggest that innate immunity may play a greater role than acquired immunity in resistance to the Naegleria fowleri infection (Marciano-Cabral & Cabral, 2007).

Blood-Brain Barrier

To understand the ability of certain antibiotics to infiltrate the brain tissue while this amoeba is specific to the brain only, a simple review of the blood--brain barrier (BBB) may help. The BBB is an intricate network of capillaries within the central nervous system that alters the permeability and restricts passage of certain chemicals and organisms from entering the brain tissue. The junctions between the cells are very tight and can prevent a drug's passage. Furthermore, to leave the blood stream and reach sites of action within the brain, a drug must pass through the cells of this capillary wall. To achieve this, a drug must be lipid soluble or use the aid of a transport system to cross the BBB. This ability to allow certain substances enter the brain and others' inability can be a significant obstacle in medication regimens for treatment of disease. In this case, the amoeba has developed specific proteins to break down the patient's neurons and can evade the patient's immune system. The antibiotic AmBisome is a lipid-based medication and thus can easily cross the BBB to attempt to kill the amoeba, if taken in a timely manner.

Signs and Symptoms

The signs and symptoms of Naegleria fowleri are exceedingly similar to bacterial meningitis and include fever, headache, elevated temperature, nucchal rigidity, positive Kernig and Brudzinski sign, changes in levels of consciousness, photophobia, cranial nerve palsies, and seizures with rapid progression to coma and death. Differential diagnosis closely considered for the patient includes viral or bacterial meningoencephalitis, and the history from the patient or his or her family that describes a recent contact with warm water activities is key to the quick diagnosis of PAM.

Diagnosis

Few cases of patients who have survived a Naegleria fowleri infection are identified very early, and survivors have some form of residual physical and cognitive impairment (Parija et al., 2007). The disease is almost always fatal due to the late diagnosis of the condition during hospitalization, as there are no specific distinguishing differences in the diagnosis of PAM from bacterial meningoencephalitis.

Swift diagnostic laboratory testing is key and would include basic serological testing. When tested, elevated serum white counts with a marked increase in neutrophils are seen. A lumbar puncture is essential in the diagnosis to provide information in regard to CSF electrolytes and possible bacteria or viruses. Radiographic testing (computed tomography scan and magnetic resonance imaging) may show nonspecific lesions and some edema.

Evaluation of the CSF shows purulent CSF, low glucose, high protein, and elevated neutrophils. However, direct microscopic visualization of CSF is optimum, demonstrating the motile amoeba (da Rocha-Azevedo et al., 2009). Gram stain is not useful in Naegleria fowleri diagnosis because clear morphology of the amoeba cannot be visualized. Again, the amoeba can be mistaken for macrophages, but microscopic visualization show a large, central nucleolus, which is its distinguishing characteristic (da Rocha-Azevedo et al., 2009).

Polymerase chain reaction assays are mostly used in research laboratories and best served when used for clinical or environmental samples. Polymerase chain reaction assays are in development for real-time diagnosis of this organism. The development of rapid enzyme-linked immunosorbet assay for CSF may expedite the early detection of PAM and increase effectiveness of antimicrobial treatment (Grate, 2006).

Treatment

Medical treatment begins with an aggressive amphotericin therapy using intravenous and intrathecal routes. It has been used in virtually all cases, as the core antimicrobial, where recovery has occurred (Schuster & Visvesvara, 2004). Other antibiotics such as fluconazole and azithromycin have shown promising results (Kaushal et al., 2008). High-dose steroids, mannitol, and acetaminophen are often used as adjuncts in the overall treatment and symptom management of this diagnosis. There may be many variables associated with the possible survival of a patient afflicted with PAM. Intensive care therapies such as ventilator and inotropic support are used in these cases as well. Laboratory values to be followed for the intensive antibiotic therapy, specifically Ambisome, include renal, hepatic, and electrolyte values.

Nursing Implications

The nursing implications in regard to this patient were many. The diagnosis itself was one not previously encountered by the NCC staff nurses. Education was initially centered on understanding what the infectious organism was, as well as how the patient came in contact with the amoeba. In the State of Florida, the community is becoming more aware of this diagnosis because of the local news stories and the health departments erecting signage in areas of freshwater where the amoebas have been found. The information in regard to the possibility of organ donation did take much more on-site education by the infectious disease physician and literature provided by the organ procurement coordinator.

Nursing care was centered on intracranial pressure management, fever control, and family or friend support. Knowledge of the antibiotic therapies and supportive intensive unit care were essential in this case. An accurate and thorough admission history provided vital information. Simple statements as to the patient's activities before admittance provided early clues that can aid in the facilitation of a quick diagnosis. These statements may easily be missed by the nursing staff, and family or friends may not even think of the significance.

It is known that the patient was with close friends when he was engaging in the wakeboarding activity. Many other individuals were at the water park that day, most of whom were probably exposed to the amoeba, and yet he was the only patient who developed this rare diagnosis. Staff, once educated, easily passed on the knowledge to other staff members. Emotional comfort was provided, and the age of the patient made it very difficult for the staff, as he was close to the younger nurses' age or the age of many of the staff nurses' children. Staff members as parents were also concerned: Living in a state where people engage in water activities every day, what should they do differently for their family members? How does it change what their leisure activities are? Early in the summer months, news stations provided stories that the amoeba are possibly present in bodies of freshwater and anyone engaging in water activities within them should take precautions such as the use of nose clips or should avoid immersing their head and nose in water. The reason why certain individuals are afflicted but others are not is not known, and research is ongoing.

The organ donation process was another area in which education was key. The rarity of the diagnosis, coupled with the possibility of organ donation, was an area on which the staff became educated. The staff, by policy, must notify the organ procurement organization of the brain death of every patient, but they easily dismissed the possibility of organ donation because of the organism. This new information regarding this diagnosis solidified the thought processes that an infectious diagnosis alone does not discount one from possible organ donation but that concise information coupled with evidence-based literature provides new learning opportunities for all.

Organ Procurement Information

Because of the infectious nature of this diagnosis, transplantation of organs was thought to be unsuitable. The first organ donation from a Naegleria fowleri patient was done in 1997 with transplantation of kidney and liver (Kramer, Lerner, & Visvesvara, 1997). Although the organ procurement coordinator is notified on every brain death per protocol, the coordinator was unsure of this diagnosis and the sequelae of organ donation in this case. Literature searches were conducted, and the medical director of organ procurement had direct conversations with appropriate expert consultants with regard to possible donation. The concern from the nursing staff was also understandable. The nature of this amoeba is that it does not cross the BBB, making organ donation possible. Following the donation of organs, the CDC and the state's health department coordinated a follow up of all recipients to assess for disease transmission. All recipients were disease-free at 6 months after donation.

Naegleria fowleri Prevention

The only method to prevent a Naegleria fowleri infection is to refrain from warm water-related activities. Local health departments in affected states routinely test the larger bodies of freshwater for amoeba counts. Prominent signage is then displayed in these areas, warning potential individuals who wish to be involved in water activities that the area is closed. However, other bodies of water may not be closed, but individuals are warned that conditions are favorable for the water to be contaminated with the amoeba. Use of nasal clips can prevent contaminated water from forcefully entering the nasal cavity. The stirring up or digging of sediment is also to be avoided.

Conclusion

Although this type of infection is rare, reports of this amoeba infection heighten public concern and present a challenge to state and local health departments that assess and communicate the risk to the public. Rapid diagnosis of this infection is imperative to survival, although the mortality reported is dismal. Research into this diagnosis is ongoing and needed to facilitate quicker and efficient testing methods to identify this organism sooner. Education to physicians will allow a heightened awareness to the timely diagnosis and referral to specialty physicians and facilities. The public health concern is obvious, and education to those who use warm freshwater lakes and bodies of water is paramount to prevent this infection. Research continues to ascertain why certain individuals are afflicted with this infection whereas countless others who are also exposed to the Naegleria fowleri organism are not affected. It is through continuing education and awareness that the public as well as the medical community become familiar in how to prevent exposure. The medical community needs to be cognizant that organ donation should be considered despite the obvious infectious concerns. Continuing dialogue with the local organ procurement agency and research by the CDC will possibly allow many other patients who need an organ transplant the possibility of a positive outcome despite this infectious diagnosis.

PAM Diagnosis by State in 2007 (CDC, 2007)

Arizona: 2 cases

Florida: 3 cases

Texas: 2 cases

Other States Where PAM Has Been Located From 1937 to 2007 (CDC, 2007)

Arkansas

California

Georgia

Louisiana

Mississippi

Missouri

Nevada

New Mexico

North Carolina

Oklahoma

South Carolina

Virginia

Acknowledgments

The author would like to thank Dr. Robert Metzger, Dr. Mary Lou Sole, and Lynn Rowe, MSN RN, for their review of this manuscript.

References

Butt, C. G. (1966). Primary amebic meningioencpehalitis. New England Journal of Medicine, 274, 1473-1476.

Centers for Disease Control and Prevention. (2007). Morbidity and mortality weekly report: Primary amebic meningioencephalitis--Arizona, Florida, and Texas. Journal of the American Medical Association, 300(2), 161-163.

Centers for Disease Control and Prevention. (2009). Free Living Amebic Infections. Retrieved March 3, 2010, from http:// www.cdc.gov/dpdx/hTML/A_F/FreeLivingAmebicInfections

da Rocha-Azevedo, B., Tanowitz, H., & Marciano-Cabral, F. (2009). Diagnosis of infections caused by pathogenic free living amoeba. Interdisciplinary Perspectives on Infectious Disease, 2009, 1-15.

Fowler, M., & Carter, R. F. (1965). Acute pyogenic meningitis probably due to Acanthamoeba sp: A preliminary report. British Medical Journal, 5464, 740-742.

Grate, I. (2006). Primary amebic meningioencephalitis: A silent killer. Canadian Journal of Emergency Medicine, 8(5), 365-369.

Kaushal, V., Chhina, D. K., Ram, S., Singh, G., Kaushal, R. K., & Kumar, R. (2008). Primary amoebic meningioencephalitis due to Naegleria fowleri. Journal of Association of Physicians of India, 56, 459-462.

Kramer, M. H., Lerner, C. J., & Visvesvara, G. S. (1997). Kidney and liver transplants from a donor infected with Naegleria fowleri. Journal of Clinical Microbiology, 35, 1032-1033.

Marciano-Cabral, F., & Cabral, G. (2007). The immune response to Naegleria fowleri amebae and pathogenesis of infection. FEMS Immunology and Medical Microbiology, 51(2), 243-259.

Parija, S., Bronze, M., Gibbs, B., & Johnson, D. (2007). Naegleria infection. Retrieved March 17, 2010, from http:// emedicine.medscape.com/article/223910

Reilly, M. F., Marchaino, F., Bradley, D. W., & Bradley, S. G. (1983). Agglutination of Naegleria fowleri and Naegleria gruberi by antibodies in human serum. Journal of Clinical Microbiology, 17(4), 576-581.

Schuster, F. L., & Visvesvara, G. S. (2004). Free living amoeba as opportunistic and non-opportunistic pathogens of humans and animals. International Journal for Parasitoogy, 34, 1001-1027.

Questions or comments about this article may be directed to Misti Tuppeny, MSN RN CCRN CNRN CCNS, at misti.tuppeny@flhosp.org. She is the neuroscience clinical nurse specialist at Florida Hospital, Orlando, FL.

DOI: 10.1097/JNN.0b013e318227ef6e
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