Primary Amebic Meningoencephalitis

(See page 1677 for the Photo Quiz.) Diagnosis: Primary Amebic Meningoencephalitis (PAM). There was an increased likelihood of the diagnosis of PAM due to the symptoms of acute meningoencephalitis with a known history of recent freshwater related activities and increased cerebrospinal fluid (CSF) opening pressure with increased neutrophils, high protein, and low glucose, despite a negative Gram stain. Numerous trophozoite forms of Naegleria fowleri in the CSF (Figure ​(Figure1)1) and a polymerase chain reaction (PCR)–positive test for Naegleria fowleri (performed by the Centers for Disease Control and Prevention [CDC]) confirmed the diagnosis of PAM. Unfortunately, twenty hours after admission, the patient had transtentorial and uncal herniation that resulted in brain death. Figure 1. Naegleria fowleri trophozoites (arrows) with neutrophilic exudate; Wright's Giemsa-stained cytospin preparation of the patient's cerebrospinal fluid, day of presentation, ×50. N. fowleri is a free-living, thermophilic ameba that inhabits freshwater ponds, lakes, rivers, hot springs, minimally chlorinated swimming pools, and other water supplies [1–5]. Infection with Naegleria fowleri causes a rapidly progressive, usually fatal primary amebic meningoencephalitis. Symptoms may include changes in taste (dysgeusia) or smell (parosmia), abrupt onset of fever, nausea, vomiting, severe headache, and other meningeal signs. Rapid progression to coma and death occurs within several days to 2 weeks, usually without focal neurological deficit [2, 6]. Among the 111 case reports of PAM that occurred in the US from 1962 to 2008, only 1 survivor was reported [1, 4]. Exposure primarily occurred in untreated, warm, freshwater lakes or rivers in 15 southern tier states (AR, AZ, CA, FL, GA, LA, MO, MS, NC, NM, NV, OK, SC, TX, and VA), [1] with 53% of the infections occurring in TX and FL [1, 4]. In addition, cases have been reported in New York [7], and recently, in Minnesota [8]. Diagnosis can be made by microscopic examination of motile trophozoites in CSF or by demonstrating the characteristic morphology on stained slides (Figure ​(Figure1).1). Unfortunately, amoebae may undergo extensive degeneration in vivo or in vitro. In this case, the CSF specimen obtained on day 2 (at our facility after the initial hospitalization) demonstrated many white blood cells, but the amebae had significantly degenerated and could no longer be definitely identified as amebae (Figure 2). In these cases, PCR is of paramount importance in making a definitive diagnosis [9]. Figure 2. Degenerating N. fowleri with neutrophilic exudate; Wright's Giemsa-stained cytospin preparation of the patient's cerebrospinal fluid, the second day of admission, ×50. The development of a rapid, multiplex, real-time PCR test by the CDC has made it possible to simultaneously detect and distinguish the 3 species of amebae that are free-living— Acanthamoeba species, Balamuthia mandrillaris, and Naegleria fowleri [10]. Limited data regarding the optimal treatment of PAM exists, in part, due to the limited number of survivors. As of February 2012, there have been a total of 12 survivors of well-documented PAM, out of approximately 200 published cases in the English literature [11–21]. All survivors received systemic amphotericin B and 5 also received intrathecal amphotericin B. There is variability in the treatment options and duration reported in the literature that makes it difficult to conclude which antimicrobials (if any) contributed to survival. Since Naegleria fowleri is highly sensitive to amphotericin B, the CDC recommends initiating its use as early as possible in the disease course [10]. Despite various attempts at treatment, the mortality rate of PAM is estimated to be 98% [3]. This case highlights the importance of obtaining a thorough history, especially in warm summer months, to increase suspicion, early recognition, and possible treatment of Naegleria fowleri infections.