Friday, December 12, 2014

Summer, Swimming, and Brain-Eating Amoeba


                  Imagine for a moment that you’re a parent. It’s a hot summer day and you’ve brought your child to the beach. The water is warm and shallow and your child swims for a few hours before you return home, tired and satisfied.

                  After a few days, your child begins to complain of a fever and headache. You aren’t worried – it’s probably a cold. Yet, the symptoms continue and your child now complains of abdominal and neck pain. You give them ibuprofen and send them to bed, confident that they will soon break the fever and feel better.

                  This, however, doesn’t happen. During lunch the next day your otherwise healthy child experiences a seizure – a first. Panicked, you bring your child to the hospital where they are subjected to many tests. They, like you, are scared, but you try to hide your fear as you await diagnosis.

                  The doctor returns stating that he believes your child has bacterial meningitis. Your child is given antibiotics and taken to get a CT scan, but there does not appear to be any brain abnormalities as expected.

                  Over the next couple of days your child seizures get more severe and more frequent as their condition worsens. Suddenly, they are struggling to breathe and doctors rush to force a tube down your child’s throat. You fear the worst, and your expectations are soon met as your child slips into a coma.

                   You wonder how just over a week ago your child was healthy and happy. After all, they’d been swimming a few days prior! You wonder what happened and how their condition progressed so quickly.

                  Still desperate for answers, the doctors take your child for yet another CT scan. However, this time they see something and the doctors tell you what you fear. Your child is dying. Their brain is dying. And nothing can be done. Your child is taken off life support and you ask that an autopsy be performed.

                  Over a week too late, your child is finally diagnosed with primary amoebic meningoencephalitis, or PAM. The doctor says that, while swimming, a brain-eating amoeba swam into your child’s nose and made its way to their brain. Once it got there… Well, you can imagine. You blame yourself. Why did you let your child swim at that beach? Why weren’t you warned about the beach’s condition? And why couldn’t your child have been saved?

                  Unfortunately, detection of Naegleria fowleri, the causative agent of PAM, is a difficult task – both in environmental and clinical settings. N. fowleri, also called “brain-eating amoeba,” is ubiquitous in warm aquatic environments, ranging from lakes and ponds to puddles and hot springs around the world. Further, N. fowleri concentrations fluctuate greatly in response to changes in both temperature and weather, as well as changes in bacterial populations, which serve as a food source for the amoeba. N. fowleri levels even vary at different locations within one water source (1). The combination of these factors make it difficult to monitor amoeba levels environmentally because testing would have to be frequent, causing a drain of both time and money.

                  Clinical detection of N. fowleri is also a difficult task, mostly due to the rapid progression of PAM. The amoeba enters the host’s nose via contaminated water, after which it begins to make its way across the nasal mucosal tissues and to its final destination – the brain (3). Phase I symptoms, usually occurring within two weeks of infection by N. fowleri, include fever, headache, sore neck, nausea, and vomiting (1). These symptoms are common and as such are often assumed to be the result of something far less deadly, such as a cold or flu.

PAM then progresses rapidly to Phase II, at which point the amoeba have entered the brain and cause tissue damage via hemorrhaging, inflammation, and necrosis or tissue death (3). Symptoms are more severe at this point, including altered brain function, seizures, and hallucination. It is during Phase II that most patients are brought to the hospital (1). However, when presenting these symptoms patients are often misdiagnosed with bacterial or viral meningitis and, as a result, go untreated. The lack of early, adequate treatment ultimately results in coma and death within a week following the onset of symptoms (1).

                  Diagnosis of PAM is accomplished via observation of cerebral spinal fluid (CSF) or brain tissue resulting in the detection of amoeba or by CT scan of the brain. However, microscopic observation of CSF and tissues takes a long time, so amoeba are usually not detected until the patient has reached the late stages of PAM (2). CT scan is usually able to detect physical changes to the brain, but these neurological effects are usually not visible until the later stages as well (2). Either way, diagnosis of PAM usually progresses far too slowly to allow for treatment, resulting in a fatality rate of over 99% (1). Even so, a couple of cases in the U.S. have been successfully treated due to early diagnosis (2).

                  Clearly the clinical outcome of PAM is very grim, but how common is this disease? The U.S. sees fewer than 10 cases of PAM each year. In fact from 1962-2008, a period of 46 years, there were only 111 confirmed cases of PAM in the U.S., all of which occurred in southern states (1). Of these cases, 62.2% involved children younger than 13 years old and just fewer than 80% of the cases occurred in males (1). Distributing the 111 PAM cases equally throughout the 46 years, the U.S. would see about two cases every year. However the distribution of these cases is not evenly distributed, but rather has been shown to be increasing during recent years (1).

Interestingly, this increase has been attributed to global warming, which plays a role in increased prevalence because climate is an important risk factor for N. fowleri infection. N. fowleri is a thermophile, and thus prefers warm climates. This explains why all previously known cases of PAM in the U.S. were isolated to southern states, only reaching as far north as Missouri (1). However, recent confirmed cases of PAM in Minnesota suggest that the warm temperatures during the summer months are sufficient for N. fowleri growth, even in colder northern U.S. climates (2). As the effects of global warming intensify and northern summers continue to increase in temperature, there is no doubt that the expansion of N. fowleri and PAM to other cooler climates throughout the world will continue (2).

Aside from climate, other important risk factors for N. fowleri infection include the increased use of recreational water sources and the disruption of sediment while taking part in water-related activities (1). As recreational water sources are utilized more and more in the U.S., particularly during the summer months when N. fowleri levels are highest and swimming and boating become common pastimes, humans enter the natural environment in which the amoeba are found (1). As a result of increased interaction between human hosts and amoeba, there is also an increase in PAM prevalence (1). Disruption of sediment occurs with the disruption of water, resulting indirectly via splashing and diving or directly by digging or the dragging of feet (1). Such behaviors cause sediment, and amoeba within, to be dispersed. This ultimately increases the likelihood of amoeba entering the nasal cavity (1).

                  Unfortunately, the prevention of N. fowleri infection and subsequent progression of PAM has been difficult to address. However the amoeba’s life cycle and its ability to survive in the environment allow many points of intervention. First, the environmental levels of N. fowleri must be controlled. As previously discussed, environmental monitoring of this pathogen is not likely to be an effective control method (2). However, by studying ways in which the amoeba interacts within this aquatic niche, we may be able to develop strategies to reduce N. fowleri levels with minimal effects on the rest of the aquatic ecosystem.

                  Following the amoeba’s interaction with aquatic environments is its interaction with the human host. Many strategies can be used to prevent this interaction. We could use recreational water sources less during summer months, or refrain from activities that promote the disruption of sediment (2). These behaviors would prevent interaction between the human host and amoeba when the N. fowleri levels and risk of infection are greatest. However, activities such as swimming and boating have become greatly anticipated summer activities, and as such it is unlikely that people will give them up. This is particularly true because, as it is difficult to recognize the presence of N. fowleri unless recreational water source users bring their own microscopes, and as the optimal concentration of N. fowleri for promoting infection is not currently known, most people will not be willing to give up these activities when their own risk of N. fowleri infection may already be slim. Even so, an easy way to prevent N. fowleri infection on an individual level is through the use of nose clips or plugging one’s nose while swimming (2). Although these behaviors would also reduce risk, nose plugs are uncomfortable, and children, who are most at risk, would not be likely to want to wear them.

                  This leads us to the greatest paradox related to the issue: Why is it that N. fowleri, an amoeba that is so common in the environment, causes PAM, a disease that seems to be so rare? Much of the answer to this question is not known at this time, likely lying within complex host-pathogen interactions. Since little research has been done in this area to date, perhaps the best way to address N. fowleri infection is through a call to scientists to get involved in answering this question.

                  However, the answer is not simply scientific research. Much of the U.S. population has never heard of N. fowleri or PAM, and education will also play an integral role in tackling this disease. By better educating parents and doctors on the symptoms and risk factors of PAM, perhaps those afflicted by this disease can be diagnosed and treated earlier. Although quick diagnosis is important, there is also a need for better treatment methods, and together, these two solutions could help drastically reduce the fatality rate of PAM.

                  Although better clinical methods are necessary for overcoming PAM, there is also a need for better epidemiological data, both within the U.S. and around the world. Although the public health burden of PAM is not huge at this time, it is clearly increasing (1). Internationally, little data has been compiled regarding PAM, particularly in the developing world where due to inadequate sanitation and lack of secure water sources the disease is very likely to have a much greater burden (5). By compiling better data, we would be able to, not only get a better grasp on the real public health burden of N. fowleri and PAM, but we would also be able to make much needed headway on discovering other risk factors of infection and disease progression.

1.     Yoder et al (2010). The epidemiology of primary amoebic meningoencephalitis in the USA, 1962-
2008. Epidemiology & Infection 138 968-975.
2.     Kemble et al (2012). Fatal Naegleria fowleri Infection Acquired in Minnesota: Possible Expanded
Range of a Deadly Thermophilic Organism. Clinical Infectious Diseases 54(6): 805-809.
3.     Cabanes et al (2001). Assessing the Risk of Primary Amoebic Meningoencephalitis from
                  Swimming in the Presence of Environmental Naegleria fowleri. Applied and
                  Environmental Microbiology July 2001 2927-2931.
4.     CDC. QuickStats: Number of Deaths from Lightning Among Males and Females – National Vital
Statistics System, United States, 1968-2010 in Morbidity and Mortality Weekly Report.
5.     Siddiqui & Khan (2014). Primary Amoebic Meningoencephalitis Caused by Naegleria fowleri: An
                  Old Enemy Presenting New Challenges. PLOS Neglected Tropical Diseases. 8:8 Online.

No comments:

Post a Comment