Primary amebic meningoencephalitis (PAM) is a necrotizing and hemorrhagic inflammation of the brain and meninges caused by Naegleria fowleri, a free-living thermophilic ameba of freshwater systems. PAM remains a neglected disease that disproportionately affects children in tropical and subtropical climates, with an estimated mortality rate of 95-98%. Due to anthropogenic climate change, the average temperature in the USA has increased by 0.72 to 1.06 °C in the last century, promoting the poleward spread of N. fowleri. PAM is often misdiagnosed as bacterial meningitis or viral encephalitis, which shortens the window for potentially life-saving treatment. Diagnosis relies on the patient\'s history of freshwater exposure and the physician\'s high index of suspicion, supported by cerebrospinal fluid studies. While no experimental trials have been conducted to assess the relative efficacy of treatment regimens, anti-amebic therapy with adjunctive neuroprotection is standard treatment in the USA. We performed a literature review and identified five patients from North America between 1962 and 2022 who survived PAM with various degrees of sequelae.

BACKGROUND: Balamuthia granulomatous amoebic encephalitis (GAE) is a peculiar parasitic infectious disease of the central nervous system, about 39% of the infected Balamuthia GAE patients were found to be immunocompromised and is extremely rare clinically. The presence of trophozoites in diseased tissue is an important basis for pathological diagnosis of GAE. Balamuthia GAE is a rare and highly fatal infection for which there is no effective treatment plan in clinical practice.
METHODS: This paper reports clinical data from a patient with Balamuthia GAE to improve physician understanding of the disease and diagnostic accuracy of imaging and reduce misdiagnosis. A 61-year-old male poultry farmer presented with moderate swelling pain in the right frontoparietal region without obvious inducement three weeks ago. Head computed tomography(CT) and magnetic resonance imaging(MRI) revealed a space-occupying lesion in the right frontal lobe. Intially clinical imaging diagnosed it as a high-grade astrocytoma. The pathological diagnosis of the lesion was inflammatory granulomatous lesions with extensive necrosis, suggesting amoeba infection. The pathogen detected by metagenomic next-generation sequencing (mNGS) is Balamuthia mandrillaris, the final pathological diagnosis was Balamuthia GAE.
CONCLUSIONS: When a head MRI shows irregular or annular enhancement, clinicians should not blindly diagnose common diseases such as brain tumors. Although Balamuthia GAE accounts for only a small proportion of intracranial infections, it should be considered in the differential diagnosis.

Primary amoebic meningoencephalitis (PAM) is a rare but lethal infection of the brain caused by a eukaryote called Naegleria fowleri (N. fowleri). The aim of this review is to consolidate the recently published case reports of N. fowleri infection by describing its epidemiology and clinical features with the goal of ultimately disseminating this information to healthcare personnel.
A comprehensive literature search was carried out using PubMed, Web of Science, Scopus, and OVID databases until 31 December 2022 by two independent reviewers. All studies from the year 2013 were extracted, and quality assessments were carried out meticulously prior to their inclusion in the final analysis.
A total of 21 studies were selected for qualitative analyses out of the 461 studies extracted. The cases were distributed globally, and 72.7% of the cases succumbed to mortality. The youngest case was an 11-day-old boy, while the eldest was a 75-year-old. Significant exposure to freshwater either from recreational activities or from a habit of irrigating the nostrils preceded onset. The symptoms at early presentation included fever, headache, and vomiting, while late sequalae showed neurological manifestation. An accurate diagnosis remains a challenge, as the symptoms mimic bacterial meningitis. Confirmatory tests include the direct visualisation of the amoeba or the use of the polymerase chain reaction method.
N. fowleri infection is rare but leads to PAM. Its occurrence is worldwide with a significant risk of fatality. The suggested probable case definition based on the findings is the acute onset of fever, headache, and vomiting with meningeal symptoms following exposure to freshwater within the previous 14 days. Continuous health promotion and health education activities for the public can help to improve knowledge and awareness prior to engagement in freshwater activities.

Balamuthia mandrillaris encephalitis is a rare disease with high mortality in the children. Due to the lack of specificity in clinical manifestations, laboratory tests, and neuroimaging, the diagnosis of the disease is difficult, especially the diagnosis of etiology. Currently, the evidence shows that the diagnosis of the disease depends on local brain biopsy or autopsy, and it is difficult to detect the pathogens by traditional etiological detection methods in blood and cerebrospinal fluid. We report a 9-year-old Chinese girl with B. mandrillaris encephalitis who was diagnosed with metagenomic next-generation sequencing (mNGS). The technology of mNGS can provide rapid, early etiological diagnosis without the need for a local brain biopsy, which can buy time for the early treatment of patients. We also provide a comprehensive literature review on this disease.

Primary amebic meningoencephalitis (PAM) is a rapidly progressive and often fatal condition caused by the free-living ameba Naegleria fowleri. To estimate the global occurrence, characterize the epidemiology, and describe the clinical features of PAM, we report a series of PAM cases published in the international literature and reported to the Centers for Disease Control and Prevention (CDC).
We performed a literature search of PAM case reports published through 2018. Additionally, we included cases reported through the CDC\'s Free-Living Ameba surveillance or diagnosed via CDC\'s Free-Living and Intestinal Amebas Laboratory. Cases were classified as confirmed, probable, or suspect on the basis of confirmatory testing, presentation, exposure, and disease course.
A total of 381 PAM cases were identified. Seven reported survivors were classified as confirmed. The most commonly reported exposure associated with PAM was swimming/diving, and the most common class of water source was lakes/ponds/reservoirs. Patients were predominantly male (75%), with a median age of 14 years. Confirmed and probable cases were similar in their survival, course of illness, and cerebrospinal fluid (CSF) findings.
PAM is a rare but deadly disease with worldwide occurrence. Improved clinician awareness, resulting in earlier diagnosis and treatment, may contribute to increased survival among PAM patients. The case definition of probable used in this study appears to capture cases of PAM, as evidenced by similarities in outcomes, clinical course, and CSF profile to confirmed cases. In the absence of confirmatory testing, clinicians could use this case definition to identify cases of PAM.

BACKGROUND: Encephalitis is caused by infection, immune mediated diseases, or primary inflammatory diseases. Of all the causative infectious pathogens, 90% are viruses or bacteria. Granulomatous amoebic encephalitis (GAE), caused by Balamuthia mandrillaris, is a rare but life-threatening disease. Diagnosis and therapy are frequently delayed due to the lack of specific clinical manifestations.
METHODS: A healthy 2 year old Chinese male patient initially presented with a nearly 2 month history of irregular fever. We present this case of granulomatous amoebic encephalitis caused by B. mandrillaris. Next generation sequencing of the patient\'s cerebrospinal fluid (CSF) was performed to identify an infectious agent.
RESULTS: The results of next generation sequencing of the CSF showed that most of the mapped reads belonged to Balamuthia mandrillaris.
CONCLUSIONS: Next generation sequencing (NGS) is an unbiased and rapid diagnostic tool. The NGS method can be used for the rapid identification of causative pathogens. The NGS method should be widely applied in clinical practice and help clinicians provide direction for the diagnosis of diseases, especially for rare and difficult cases.

Naegleria fowleri, a thermophilic flagellate amoeba known as a \"brain-eating\" amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as primary amoebic meningoencephalitis (PAM), both in humans as well as in animals. PAM is a rare but fatal disease affecting young adults all around the world, particularly in the developed world but recently reported from developing countries, with 95%-99% mortality rate. Swimmers and divers are at high risk of PAM as the warm water is the most propitious environment adapted by N. fowleri to cause this infection. Infective amoeba in the trophozoite phase enter the victim\'s body through the nose, crossing the cribriform plate to reach the human brain and cause severe destruction of the central nervous system (CNS). The brain damage leads to brain haemorrhage and death occurs within 3-7 days in undiagnosed cases and maltreated cases. Though the exact pathogenesis of N. fowleri is still not known, it has exhibited two primary mechanisms, contact-independent (brain damage through different proteins) and contact-dependent (brain damage through surface structures food cups), that predominantly contribute to the pathogen invading the host CNS. For the management of this life-threatening infection different treatment regimens have been applied but still the survival rate is only 5% which is ascribed to its misdiagnosis, as the PAM symptoms closely resembled bacterial meningitis. The main objectives of this review article are to compile data to explore the sources and routes of N. fowleri infection, its association in causing PAM along with its pathophysiology; latest techniques used for accurate diagnosis, management options along with challenges for Pakistan to control this drastic disorder.

Primary amebic meningoencephalitis is a rare, almost uniformly fatal disease of cerebral invasion by Naegleria fowleri, occurring most commonly after swimming in warm fresh water in summer months. Treatment using the experimental medication miltefosine demonstrated improved survival and favorable neurocognitive outcome in a 2013 North American patient. There is little information about the electroencephalographic findings of such patients, and our understanding of factors predicting survival is limited.
We describe two children, aged four and 14 years, who both presented with seizures and altered mental status after recent fresh water swimming exposures. With evidence of pyogenic meningitis and examination of cerebrospinal fluid demonstrating motile trophozoites on wet mount, N. fowleri meningoencephalitis was diagnosed. Amebicidal antibiotic regimens with miltefosine were administered. Continuous electroencephalography monitoring demonstrated evolution from diffuse slowing to seizures, status epilepticus, and eventually global attenuation and absence of activity. Both patients ultimately died after complications of progressive increasing intracranial pressure and hemodynamic compromise.
Primary amebic meningoencephalitis is a serious, sporadic infection. We describe two fatal pediatric patients, the evolution of their electroencephalography findings, and compare their findings with the 13 reported pediatric survivors.

Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous amoebic encephalitis. We report herein an autopsy case of B. mandrillaris amoebic encephalitis, which was definitely diagnosed by PCR. An 81-year-old man, who had Sjögren\'s syndrome, manifested drowsiness 2 months before his death with progressive deterioration. Neuroimaging demonstrated foci of T2- and fluid-attenuated inversion recovery high and T1 low-intensity with irregular post-contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10-60 μm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin-embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature.

Primary amebic meningoencephalitis (PAM) is a rare but nearly always fatal infection of the central nervous system caused by the thermophilic, free-living ameba Naegleria fowleri. Since its first description in 1965 through 2010, 118 cases have been reported in the U.S.; all cases are related to environmental exposure to warm freshwater; most have occurred in children and adolescents and are associated with recreational water activities, such as swimming, diving, or playing in freshwater lakes, ponds, or rivers. Over one-fourth of all national PAM cases have occurred in Florida. The authors describe here a fatal case of PAM in a resident of northeast Florida and the ensuing environmental and public health investigation; they also provide a review of all cases of PAM in Florida from 1962 to 2010 and discuss public health responses to PAM in Florida, highlighting opportunities for positive collaboration between state and local environmental health specialists, epidemiologists, and the Centers for Disease Control and Prevention.