Acanthamoeba Infection and Nasal Rinsing, United States, 1994-2022.

We describe 10 patients with nonkeratitis Acanthamoeba infection who reported performing nasal rinsing before becoming ill. All were immunocompromised, 7 had chronic sinusitis, and many used tap water for nasal rinsing. Immunocompromised persons should be educated about safe nasal rinsing to prevent free-living ameba infections.

Estimates of Incidence and Predictors of Fatiguing Illness after SARS-CoV-2 Infection.

This study aimed to estimate the incidence rates of post-COVID-19 fatigue and chronic fatigue and to quantify the additional incident fatigue caused by COVID-19. We analyzed electronic health records data of 4,589 patients with confirmed COVID-19 during February 2020-February 2021 who were followed for a median of 11.4 (interquartile range 7.8-15.5) months and compared them to data from 9,022 propensity score-matched non-COVID-19 controls. Among COVID-19 patients (15% hospitalized for acute COVID-19), the incidence rate of fatigue was 10.2/100 person-years and the rate of chronic fatigue was 1.8/100 person-years. Compared with non-COVID-19 controls, the hazard ratios were 1.68 (95% CI 1.48-1.92) for fatigue and 4.32 (95% CI 2.90-6.43) for chronic fatigue. The observed association between COVID-19 and the significant increase in the incidence of fatigue and chronic fatigue reinforces the need for public health actions to prevent SARS-CoV-2 infections.

Differences in Report of Post-COVID Conditions Among Adults Tested for SARS-CoV-2 by Race and Ethnicity: 2022 Porter Novelli SummerStyles Survey, U.S.

Introduction: Since March 2020, Hispanic and Black/African American persons have made up a disproportionate number of COVID-19 cases, hospitalizations, and deaths. However, little is known about whether the prevalence of postacute sequelae or post-COVID conditions differs by race/ethnicity. Methods: This study used cross-sectional survey data collected by Porter Novelli Public Services to determine the prevalence of ≥1 ongoing symptom lasting ≥4 weeks by SARS-CoV-2 test status and racial/ethnic groups among 2,890 adults in the U.S. Results: Overall, 57% (95% CI=54%, 60%) of respondents with positive SARS-CoV-2 tests reported ≥1 ongoing symptom, compared with 22% (95% CI=20%, 24%) of respondents who tested negative. Among those with positive SARS-CoV-2 tests, Hispanic respondents had higher AORs of experiencing ≥1 ongoing symptom (AOR=1.79, 95% CI=1.27, 2.53) than non-Hispanic White respondents. In addition, Hispanic respondents had significantly higher ORs of experiencing 2 or more ongoing symptoms (AOR=2.03, 95% CI=1.45, 2.86), respiratory/cardiac symptoms (AOR=1.47, 95% CI=1.03, 2.07), neurologic symptoms (AOR=1.77, 95% CI=1.26, 2.48), and other symptoms (AOR=1.53, 95% CI=1.09, 2.14) than non-Hispanic White respondents. Non-Hispanic other respondents who reported at least 1 positive SARS-CoV-2 test had significantly higher ORs of experiencing gastrointestinal symptoms (AOR=4.06, 95% CI=1.78, 8.89) than non-Hispanic White respondents. Conclusions: These results highlight potential disparities in ongoing symptoms, even after accounting for demographic differences, and reinforce the need for culturally appropriate and targeted strategies to increase access to health care and reduce SARS-CoV-2 infections.

Estimating Waterborne Infectious Disease Burden by Exposure Route, United States, 2014.

More than 7.15 million cases of domestically acquired infectious waterborne illnesses occurred in the United States in 2014, causing 120,000 hospitalizations and 6,600 deaths. We estimated disease incidence for 17 pathogens according to recreational, drinking, and nonrecreational nondrinking (NRND) water exposure routes by using previously published estimates. In 2014, a total of 5.61 million (95% credible interval [CrI] 2.97-9.00 million) illnesses were linked to recreational water, 1.13 million (95% CrI 255,000-3.54 million) to drinking water, and 407,000 (95% CrI 72,800-1.29 million) to NRND water. Recreational water exposure was responsible for 36%, drinking water for 40%, and NRND water for 24% of hospitalizations from waterborne illnesses. Most direct costs were associated with pathogens found in biofilms. Estimating disease burden by water exposure route helps direct prevention activities. For each exposure route, water management programs are needed to control biofilm-associated pathogen growth; public health programs are needed to prevent biofilm-associated diseases.

A Case of Primary Amebic Meningoencephalitis Associated with Surfing at an Artificial Surf Venue: Environmental Investigation.

Naegleria fowleri is a thermophilic ameba found in freshwater that causes primary amebic meningoencephalitis (PAM) when it enters the nose and migrates to the brain. In September 2018, a 29-year-old man died of PAM after traveling to Texas. We conducted an epidemiologic and environmental investigation to identify the water exposure associated with this PAM case. The patient's most probable water exposure occurred while surfing in an artificial surf venue. The surf venue water was not filtered or recirculated; water disinfection and water quality testing were not documented. N. fowleri and thermophilic amebae were detected in recreational water and sediment samples throughout the facility. Codes and standards for treated recreational water venues open to the public could be developed to address these novel venues. Clinicians and public health officials should also consider novel recreational water venues as a potential exposure for this rare amebic infection.

Amebic encephalitis and meningoencephalitis: an update on epidemiology, diagnostic methods, and treatment.

PURPOSE OF REVIEW: Free-living amebae (FLA) including Naegleria fowleri , Balamuthia mandrillaris , and Acanthamoeba species can cause rare, yet severe infections that are nearly always fatal. This review describes recent developments in epidemiology, diagnosis, and treatment of amebic meningoencephalitis. RECENT FINDINGS: Despite similarities among the three pathogenic FLA, there are notable variations in disease presentations, routes of transmission, populations at risk, and outcomes for each. Recently, molecular diagnostic tools have been used to diagnose a greater number of FLA infections. Treatment regimens for FLA have historically relied on survivor reports; more data is needed about novel treatments, including nitroxoline. SUMMARY: Research to identify new drugs and guide treatment regimens for amebic meningoencephalitis is lacking. However, improved diagnostic capabilities may lead to earlier diagnoses, allowing earlier treatment initiation and improved outcomes. Public health practitioners should continue to prioritize increasing awareness and providing education to clinicians, laboratorians, and the public about amebic infections.

Cronobacter sakazakii Infections in Two Infants Linked to Powdered Infant Formula and Breast Pump Equipment - United States, 2021 and 2022.

Cronobacter sakazakii, a species of gram-negative bacteria belonging to the Enterobacteriaceae family, is known to cause severe and often fatal meningitis and sepsis in young infants. C. sakazakii is ubiquitous in the environment, and most reported infant cases have been attributed to contaminated powdered infant formula (powdered formula) or breast milk that was expressed using contaminated breast pump equipment (1-3). Previous investigations of cases and outbreaks have identified C. sakazakii in opened powdered formula, breast pump parts, environmental surfaces in the home, and, rarely, in unopened powdered formula and formula manufacturing facilities (2,4-6). This report describes two infants with C. sakazakii meningitis reported to CDC in September 2021 and February 2022. CDC used whole genome sequencing (WGS) analysis to link one case to contaminated opened powdered formula from the patient's home and the other to contaminated breast pump equipment. These cases highlight the importance of expanding awareness about C. sakazakii infections in infants, safe preparation and storage of powdered formula, proper cleaning and sanitizing of breast pump equipment, and using WGS as a tool for C. sakazakii investigations.

The Epidemiology and Clinical Features of Non-Keratitis Acanthamoeba Infections in the United States, 1956-2020.

Background: Acanthamoeba is a free-living ameba that can cause severe disease affecting the central nervous system, skin, sinuses, and other organs, particularly in immunocompromised individuals. These rare but severe infections are often fatal, yet incompletely described. Methods: Cases included were either reported to the Centers for Disease Control and Prevention (CDC) Free-Living Ameba program or published in scientific literature. Characteristics of all patients in the United States with laboratory-confirmed non-keratitis Acanthamoeba infections were described using descriptive statistics, and associations with survival were determined using χ2 and Fisher exact tests. Results: Of 173 patients identified, 71% were male and the median age was 44 years (range, 0-87 years). Of these, 26 (15%) survived. Most patients (88%) had at least 1 immunocompromising condition, most commonly human immunodeficiency virus (39%), cancer (28%), and solid organ or hematopoietic stem cell transplant (28%). Granulomatous amebic encephalitis (GAE) was the most common disease presentation (71%). Skin (46%), sinuses (29%), lungs (13%), and bone (6%) were also involved. Nearly half of patients (47%) had involvement of >1 organ system. Survival was less frequent among those with GAE (3%, P < .001) compared with cutaneous disease, rhinosinusitis, or multiorgan disease not including GAE. Of 7 who received the currently recommended treatment regimen, 5 (71%) survived. Conclusions: Non-keratitis Acanthamoeba infections occur primarily in immunocompromised individuals and are usually fatal. Survival may be associated with disease presentation and treatment. Providers who care for at-risk patients should be aware of the various disease manifestations to improve early recognition and treatment.

(Mis)perception and Use of Unsterile Water in Home Medical Devices, PN View 360+ Survey, United States, August 20211.

Tap water is not sterile, and its use in home medical devices can result in infections from waterborne pathogens. However, many participants in a recent survey in the United States said tap water could safely be used for home medical devices. These results can inform communication materials to reduce the high consequence of infections.

Prevalence of Select New Symptoms and Conditions Among Persons Aged Younger Than 20 Years and 20 Years or Older at 31 to 150 Days After Testing Positive or Negative for SARS-CoV-2.

Importance: New symptoms and conditions can develop following SARS-CoV-2 infection. Whether they occur more frequently among persons with SARS-CoV-2 infection compared with those without is unclear. Objective: To compare the prevalence of new diagnoses of select symptoms and conditions between 31 and 150 days after testing among persons who tested positive vs negative for SARS-CoV-2. Design, Setting, and Participants: This cohort study analyzed aggregated electronic health record data from 40 health care systems, including 338 024 persons younger than 20 years and 1 790 886 persons aged 20 years or older who were tested for SARS-CoV-2 during March to December 2020 and who had medical encounters between 31 and 150 days after testing. Main Outcomes and Measures: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes were used to capture new symptoms and conditions that were recorded 31 to 150 days after a SARS-CoV-2 test but absent in the 18 months to 7 days prior to testing. The prevalence of new symptoms and conditions was compared between persons with positive and negative SARS-CoV-2 tests stratified by age (20 years or older and young than 20 years) and care setting (nonhospitalized, hospitalized, or hospitalized and ventilated). Results: A total of 168 701 persons aged 20 years or older and 26 665 younger than 20 years tested positive for SARS-CoV-2, and 1 622 185 persons aged 20 years or older and 311 359 younger than 20 years tested negative. Shortness of breath was more common among persons with a positive vs negative test result among hospitalized patients (≥20 years: prevalence ratio [PR], 1.89 [99% CI, 1.79-2.01]; <20 years: PR, 1.72 [99% CI, 1.17-2.51]). Shortness of breath was also more common among nonhospitalized patients aged 20 years or older with a positive vs negative test result (PR, 1.09 [99% CI, 1.05-1.13]). Among hospitalized persons aged 20 years or older, the prevalence of new fatigue (PR, 1.35 [99% CI, 1.27-1.44]) and type 2 diabetes (PR, 2.03 [99% CI, 1.87-2.19]) was higher among those with a positive vs a negative test result. Among hospitalized persons younger than 20 years, the prevalence of type 2 diabetes (PR, 2.14 [99% CI, 1.13-4.06]) was higher among those with a positive vs a negative test result; however, the prevalence difference was less than 1%. Conclusions and Relevance: In this cohort study, among persons hospitalized after a positive SARS-CoV-2 test result, diagnoses of certain symptoms and conditions were higher than among those with a negative test result. Health care professionals should be aware of symptoms and conditions that may develop after SARS-CoV-2 infection, particularly among those hospitalized after diagnosis.

Acanthamoeba castellanii encephalitis in a patient with AIDS: a case report and literature review.

Amoebic encephalitis is a rare cause of CNS infection for which mortality exceeds 90%. We present the case of a 27-year-old man with AIDS who presented to a hospital in Atlanta (Georgia, USA) with tonic-clonic seizures and headache. His clinical condition deteriorated over several days. Brain biopsy revealed lymphohistiocytic inflammation and necrosis with trophozoites and encysted forms of amoebae. Immunohistochemical and PCR testing confirmed Acanthamoeba castellanii encephalitis, typically described as granulomatous amoebic encephalitis (GAE). No proven therapy for GAE is available, although both surgical and multiagent antimicrobial treatment strategies are often used. Most recently, these include the antileishmanial agent miltefosine. Here we review all cases of GAE due to Acanthamoeba spp in people with HIV/AIDS identified in the literature and reported to the Centers for Disease Control and Prevention. We describe this case as a reminder to the clinician to consider protozoal infections, especially free-living amoeba, in the immunocompromised host with a CNS infection refractory to traditional antimicrobial therapy.

Long-Term Symptoms Among Adults Tested for SARS-CoV-2 - United States, January 2020-April 2021.

Long-term symptoms often associated with COVID-19 (post-COVID conditions or long COVID) are an emerging public health concern that is not well understood. Prevalence of post-COVID conditions has been reported among persons who have had COVID-19 (range = 5%-80%), with differences possibly related to different study populations, case definitions, and data sources (1). Few studies of post-COVID conditions have comparisons with the general population of adults with negative test results for SARS-CoV-2, the virus that causes COVID-19, limiting ability to assess background symptom prevalence (1). CDC used a nonprobability-based Internet panel established by Porter Novelli Public Services* to administer a survey to a nationwide sample of U.S. adults aged ≥18 years to compare the prevalence of long-term symptoms (those lasting >4 weeks since onset) among persons who self-reported ever receiving a positive SARS-CoV-2 test result with the prevalence of similar symptoms among persons who reported always receiving a negative test result. The weighted prevalence of ever testing positive for SARS-CoV-2 was 22.2% (95% confidence interval [CI] = 20.6%-23.8%). Approximately two thirds of respondents who had received a positive test result experienced long-term symptoms often associated with SARS-CoV-2 infection. Compared with respondents who received a negative test result, those who received a positive test result reported a significantly higher prevalence of any long-term symptom (65.9% versus 42.9%), fatigue (22.5% versus 12.0%), change in sense of smell or taste (17.3% versus 1.7%), shortness of breath (15.5% versus 5.2%), cough (14.5% versus 4.9%), headache (13.8% versus 9.9%), and persistence (>4 weeks) of at least one initially occurring symptom (76.2% versus 69.6%). Compared with respondents who received a negative test result, a larger proportion of those who received a positive test result reported believing that receiving a COVID-19 vaccine made their long-term symptoms better (28.7% versus 15.7%). Efforts to address post-COVID conditions should include helping health care professionals recognize the most common post-COVID conditions and optimize care for patients with persisting symptoms, including messaging on potential benefits of COVID-19 vaccination.

Death From Primary Amebic Meningoencephalitis After Recreational Water Exposure During Recent Travel to India-Santa Clara County, California, 2020.

BACKGROUND: In February 2020, a man returned to the United States after an 11-day trip to India and died of primary amebic meningoencephalitis (PAM), caused by nasal exposure to the free-living ameba Naegleria fowleri found in warm water. We identified potential exposures, confirmed etiology, and described the molecular epidemiology of the infection. METHODS: We reviewed medical records to describe his clinical course and interviewed his family to determine water exposures. Genotyping was performed on the N. fowleri strain and compared with North American strains through repetitive nonpolymorphic nuclear loci analysis to identify differences. We reviewed N. fowleri strains in the National Center for Biotechnology Information database (GenBank) to determine genotypes present in India. RESULTS: The patient became acutely encephalopathic 3 days after returning; the only known nasal water exposure was at an indoor swimming pool in India 5 days earlier. Cerebrospinal fluid (CSF) testing demonstrated neutrophil-predominant pleocytosis and low glucose, but negative gram stain and culture. CSF microscopy revealed trophozoites; N. fowleri was detected by real-time polymerase chain reaction. Classical genotyping confirmed genotype I, common in the United States and among Indian strains in GenBank. The North American N. fowleri strains and the patient's strain varied at 5 nonpolymorphic loci. CONCLUSIONS: A man died from PAM after likely exposure at a vacation rental pool in India. We recommend including PAM in the differential diagnosis when CSF studies suggest bacterial meningitis but gram stain is negative. Genotyping can advance our understanding of N. fowleri molecular epidemiology and support future investigations.

Comparative Genomic and Transcriptomic Analysis of Naegleria fowleri Clinical and Environmental Isolates.

Out of over 40 species of Naegleria, which are free-living thermophilic amebae found in freshwater and soil worldwide, only Naegleria fowleri infects humans, causing primary amebic meningoencephalitis (PAM), a typically fatal brain disease. To understand the population structure of Naegleria species and the genetic relationships between N. fowleri isolates and to detect pathogenic factors, we characterized 52 novel clinical and environmental N. fowleri genomes and a single Naegleria lovaniensis strain, along with transcriptomic data for a subset of 37 N. fowleri isolates. Whole-genome analysis of 56 isolates from three Naegleria species (N. fowleri, N. lovaniensis, and Naegleria gruberi) identified several genes unique to N. fowleri that have previously been linked to the pathogenicity of N. fowleri, while other unique genes could be associated with novel pathogenicity factors in this highly fatal pathogen. Population structure analysis estimated the presence of 10 populations within the three Naegleria species, of which 7 populations were within N. fowleri. The whole-nuclear-genome (WNG) phylogenetic analysis showed an overall geographical clustering of N. fowleri isolates, with few exceptions, and provided higher resolution in identifying potential clusters of isolates beyond that of the traditional locus typing. There were only 34 genes that showed significant differences in gene expression between the clinical and environmental isolates. Genomic data generated in this study can be used for developing rapid molecular assays and to conduct future population-based global genomic analysis and will also be a valuable addition to genomic reference databases, where shotgun metagenomics data from routine water samples could be searched for the presence of N. fowleri strains. IMPORTANCE N. fowleri, the only known Naegleria species to infect humans, causes fatal brain disease. PAM cases from 1965 to 2016 showed <20 cases per year globally. Out of approximately 150 cases in North America since 1962, only four PAM survivors are known, yielding a >97% case fatality rate, which is critically high. Although the pathogenesis of N. fowleri has been studied for the last 50 years, pathogenetic factors that lead to human infection and breaching the blood-brain barrier remain unknown. In addition, little is known regarding the genomic diversity both within N. fowleri isolates and among Naegleria species. In this study, we generated novel genome sequences and performed comparative genomic and transcriptomic analysis of a set of 52 N. fowleri draft genome sequences from clinical and environmental isolates derived from all over the world in the last 53 years, which will help shape future genome-wide studies and develop sensitive assays for routine surveillance.

Outcomes Among Patients Referred to Outpatient Rehabilitation Clinics After COVID-19 diagnosis - United States, January 2020-March 2021.

As of June 30, 2021, 33.5 million persons in the United States had received a diagnosis of COVID-19 (1). Although most patients infected with SARS-CoV-2, the virus that causes COVID-19, recover within a few weeks, some experience post-COVID-19 conditions. These range from new or returning to ongoing health problems that can continue beyond 4 weeks. Persons who were asymptomatic at the time of infection can also experience post-COVID-19 conditions. Data on post-COVID-19 conditions are emerging and information on rehabilitation needs among persons recovering from COVID-19 is limited. Using data acquired during January 2020-March 2021 from Select Medical* outpatient rehabilitation clinics, CDC compared patient-reported measures of health, physical endurance, and health care use between patients who had recovered from COVID-19 (post-COVID-19 patients) and patients needing rehabilitation because of a current or previous diagnosis of a neoplasm (cancer) who had not experienced COVID-19 (control patients). All patients had been referred to outpatient rehabilitation. Compared with control patients, post-COVID-19 patients had higher age- and sex-adjusted odds of reporting worse physical health (adjusted odds ratio [aOR] = 1.8), pain (aOR = 2.3), and difficulty with physical activities (aOR = 1.6). Post-COVID-19 patients also had worse physical endurance, measured by the 6-minute walk test† (6MWT) (p<0.001) compared with control patients. Among patients referred to outpatient rehabilitation, those recovering from COVID-19 had poorer physical health and functional status than those who had cancer, or were recovering from cancer but not COVID-19. Patients recovering from COVID-19 might need additional clinical support, including tailored physical and mental health rehabilitation services.

A case report of primary amebic meningoencephalitis in North Florida.

Primary amebic meningoencephalitis is a rare, usually fatal disease, caused by Naegleria fowleri. This case highlights the challenging clinicopathologic diagnosis in a 13-year-old boy who swam in freshwater in northern Florida where a previous case had exposure to a body of water on the same property in 2009.

Draft Chromosome Sequences of a Clinical Isolate of the Free-Living Ameba Naegleria fowleri.

We present the chromosome sequences of a Naegleria fowleri isolate from a human primary amebic meningoencephalitis (PAM) case. The genome sequences were assembled from Illumina HiSeq and PacBio sequencing data and verified with the optical mapping data. This led to the identification of 37 contigs representing 37 chromosomes in N. fowleri.

Health Care Utilization and Clinical Characteristics of Nonhospitalized Adults in an Integrated Health Care System 28-180 Days After COVID-19 Diagnosis - Georgia, May 2020-March 2021.

As of April 19, 2021, 21.6 million COVID-19 cases had been reported among U.S. adults, most of whom had mild or moderate disease that did not require hospitalization (1). Health care needs in the months after COVID-19 diagnosis among nonhospitalized adults have not been well studied. To better understand longer-term health care utilization and clinical characteristics of nonhospitalized adults after COVID-19 diagnosis, CDC and Kaiser Permanente Georgia (KPGA) analyzed electronic health record (EHR) data from health care visits in the 28-180 days after a diagnosis of COVID-19 at an integrated health care system. Among 3,171 nonhospitalized adults who had COVID-19, 69% had one or more outpatient visits during the follow-up period of 28-180-days. Compared with patients without an outpatient visit, a higher percentage of those who did have an outpatient visit were aged ≥50 years, were women, were non-Hispanic Black, and had underlying health conditions. Among adults with outpatient visits, 68% had a visit for a new primary diagnosis, and 38% had a new specialist visit. Active COVID-19 diagnoses* (10%) and symptoms potentially related to COVID-19 (3%-7%) were among the top 20 new visit diagnoses; rates of visits for these diagnoses declined from 2-24 visits per 10,000 person-days 28-59 days after COVID-19 diagnosis to 1-4 visits per 10,000 person-days 120-180 days after diagnosis. The presence of diagnoses of COVID-19 and related symptoms in the 28-180 days following acute illness suggests that some nonhospitalized adults, including those with asymptomatic or mild acute illness, likely have continued health care needs months after diagnosis. Clinicians and health systems should be aware of post-COVID conditions among patients who are not initially hospitalized for acute COVID-19 disease.

Granulomatous amoebic encephalitis caused by Acanthamoeba in a patient with AIDS: a challenging diagnosis.

INTRODUCTION: Acanthamoeba spp. is a ubiquitous free-living amoeba that causes human infections affecting predominantly the cornea and central nervous system. The diagnosis and treatment of Acanthamoeba encephalitis is very challenging. CASE SUMMARY: A 53-year-old male with HIV/AIDS was admitted for altered mental status and fever. On initial examination, he had left hemianopia with left-sided weakness and numbness. MRI revealed an inflammatory and enhancing parenchymal mass associated with leptomeningeal enhancement in the occipitoparietal lobe containing multiple punctate hemorrhages. He was treated with empiric antibiotics for presumptive toxoplasmosis, brain abscess, fungal infection and tuberculosis with an unremarkable lymphoma work up. Initial brain biopsy studies were unremarkable except for non-specific granulomas and adjacent necrotic tissue. The patient passed away 2.5 months after initial presentation with no diagnosis. Post-mortem testing by the Centers for Disease Control and Prevention (CDC) confirmed the diagnosis of granulomatous amoebic encephalitis (GAE) by visualization with immunohistochemistry staining and PCR. Recovery is rare from GAE likely due to delay in diagnosis. CONCLUSIONS: This case illustrates the importance of including GAE into the differential diagnosis of brain mass. We advocate early molecular testing of tissue specimen by the CDC to achieve an appropriate diagnosis, and a multidisciplinary approach for the management of this condition.

Epidemiology and Clinical Characteristics of Primary Amebic Meningoencephalitis Caused by Naegleria fowleri: A Global Review.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.