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Volume 24, Number 1—January 2018
Research Letter

Estimation of Undiagnosed Naegleria fowleri Primary Amebic Meningoencephalitis, United States1

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Almea Matanock, Jason M. Mehal, Lindy Liu, Diana M. Blau, and Jennifer R. CopeComments to Author 
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA

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Abstract

Primary amebic meningoencephalitis is an acute, rare, typically fatal disease. We used epidemiologic risk factors and multiple cause-of-death mortality data to estimate the number of deaths that fit the typical pattern for primary amebic meningoencephalitis; we estimated an annual average of 16 deaths (8 male, 8 female) in the United States.

Naegleria fowleri causes primary amebic meningoencephalitis (PAM); 0–8 laboratory confirmed cases per year are documented in the United States) (1). PAM causes <0.5% of diagnosed encephalitis deaths in the United States (2). Laboratory-confirmed PAM case-patients in the United States are a median age of 12 years and are identified primarily in southern states during July–September, and 79% are male (1,3). Many case-patients are identified postmortem; 4 known survivors have been reported in the United States (1,4). The signs and symptoms of PAM can be mistaken for other more common neuroinfections, such as bacterial meningitis and viral encephalitis (1,4). Because more than half of neuroinfectious deaths are unspecified (2), clinical expertise and diagnostic testing availability are limited, and true PAM incidence is unknown, concern is reasonable that PAM cases might not be diagnosed. In this study, we estimate the magnitude of potentially undiagnosed cases of PAM by applying previously identified epidemiologic risk factors to unspecified neuroinfectious deaths.

We created a list of codes from the International Classification of Disease, 10th revision (ICD-10), for unspecified possible neuroinfectious deaths by using previously published data (2), ICD-10 codes from death certificates of known PAM case-patients, and expert opinion. We selected codes from any location on the death record, not strictly the primary or immediate cause of death (http://www.cdc.gov/nchs/deaths.htm). We chose to start in 1999 when death certificate data were first coded by using ICD-10 and ended in 2010, using the most updated data at the time of this analysis. Persons 2–22 years of age were included (±10 years from the average age of 12 years), excluding infants and older adults, who are more susceptible to bacterial meningitis. We applied known risk factors for PAM: 1) geographic location, i.e., states that reported diagnosed cases as of 2010; 2) summer seasons; and 3) sex (3). Within this narrowed subset of unspecified neuroinfectious deaths, we reviewed associated ICD-10 codes and removed death records that had more definitive diagnoses.

During 1999–2010, there were 1,676 unspecified neuroinfectious disease deaths among persons 2–22 years old; 49% (826/1,676) occurred during July–September of each year studied, and of those, 23% (192/826) were reported from an included state in the southern United States; 52% (100/192) were male and 48% (92/192) female. An average of 16 (8 male, 8 female) unspecified neuroinfectious deaths per year fit the typical pattern of PAM, in addition to the average 3 laboratory-confirmed cases annually during this time period.

Among all unspecified neuroinfectious deaths, the most common unspecified neuroinfectious death code used was G03.9 meningitis unspecified (n = 505) (Table). For the top 5 codes, 8%–16% of cases matched all the risk factors and 2 had a sex ratio of exactly 50%. We did not have access to death certificates for 20 known laboratory-confirmed case-patients to determine what ICD-10 codes were used in these cases.

Our estimate of annual undiagnosed PAM cases shows that unspecified neuroinfectious deaths that fit the epidemiologic pattern of PAM occur infrequently. This estimate likely includes unspecified neuroinfectious death caused by other pathogens. We have no method to differentiate cases that fit the pattern of PAM, but are caused by another pathogen. Bacterial meningitis, which can be mistaken for PAM (1), has decreased over approximately the same time period as this study, but does not have the epidemiologic pattern of PAM (5). Viral causes (i.e., La Crosse and West Nile viruses) have a similar pattern, occurring during July–September (>80% of cases) and more commonly in males (3:2 male:female ratio) (6). An ICD-10 code for West Nile virus, A92.3, was added in 2005. There was only 1 case in our estimate that had the code Mosquito-borne viral encephalitis, unspecified (A83.9). Similar to PAM, cases of arbovirus disease could be included in even less-specific meningitis and encephalitis codes, illustrating that unspecified neuroinfectious deaths are likely caused by several pathogens.

Medical chart review and autopsies, not available for this study, would provide further information about the cause of death. Although this estimate likely captures more than just PAM cases for the reasons we have outlined, it might not capture all potential PAM cases. Reasons for an underestimate include inaccurate ICD-10 coding (7) and PAM cases that are outside the typical epidemiologic pattern (e.g., 2 cases in Minnesota [8] and out of season, such as adult cases linked to ritual nasal rinsing and sinus irrigation [9,10]).

Although all available evidence points to PAM being a low-incidence disease in the United States, PAM remains a devastating and nearly universally fatal infection that erodes public confidence in the safety of everyday activities (swimming, using public drinking water) and increased stress on local public health departments that are already overextended. The reports of recent survivors indicate that timely diagnosis and early initiation of anti-amebic therapy may be instrumental in combating this deadly infection (4). Therefore awareness, evaluation of risk factors, testing, and early anti-amebic therapy provide the best opportunity for survival (1).

Dr. Matanock was an Epidemic Intelligence Service Officer in the Waterborne Disease Prevention Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, at the time of this project and is now an epidemiologist in the Respiratory Diseases Branch, National Center for Immunization and Respiratory Diseases, CDC. Her research interests include disease detection and surveillance.

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Acknowledgment

We thank the many members of the Waterborne Disease Prevention Branch, Infectious Diseases Pathology Branch, and the Division of High-Consequence Pathogens and Pathology who were essential in formulating the questions, providing the context, and developing this project.

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References

  1. Capewell  LG, Harris  AM, Yoder  JS, Cope  JR, Eddy  BA, Roy  SL, et al. Diagnosis, clinical course, and treatment of primary amoebic meningoencephalitis in the United States, 1937–2013. J Pediatric Infect Dis Soc. 2015;4:e6875. DOIPubMed
  2. Tack  DM, Holman  RC, Folkema  AM, Mehal  JM, Blanton  JD, Sejvar  JJ. Trends in encephalitis-associated deaths in the United States, 1999-2008. Neuroepidemiology. 2014;43:18. DOIPubMed
  3. Yoder  JS, Eddy  BA, Visvesvara  GS, Capewell  L, Beach  MJ. The epidemiology of primary amoebic meningoencephalitis in the USA, 1962-2008. Epidemiol Infect. 2010;138:96875. DOIPubMed
  4. Linam  WM, Ahmed  M, Cope  JR, Chu  C, Visvesvara  GS, da Silva  AJ, et al. Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis. Pediatrics. 2015;135:e7448. DOIPubMed
  5. Castelblanco  RL, Lee  M, Hasbun  R. Epidemiology of bacterial meningitis in the USA from 1997 to 2010: a population-based observational study. Lancet Infect Dis. 2014;14:8139. DOIPubMed
  6. Gaensbauer  JT, Lindsey  NP, Messacar  K, Staples  JE, Fischer  M. Neuroinvasive arboviral disease in the United States: 2003 to 2012. Pediatrics. 2014;134:e64250. DOIPubMed
  7. Stickler  DE, Royer  JA, Hardin  JW. Accuracy and usefulness of ICD-10 death certificate coding for the identification of patients with ALS: results from the South Carolina ALS Surveillance Pilot Project. Amyotroph Lateral Scler. 2012;13:6973. DOIPubMed
  8. Kemble  SK, Lynfield  R, DeVries  AS, Drehner  DM, Pomputius  WF III, Beach  MJ, et al. Fatal Naegleria fowleri infection acquired in Minnesota: possible expanded range of a deadly thermophilic organism. Clin Infect Dis. 2012;54:8059. DOIPubMed
  9. Yoder  JS, Straif-Bourgeois  S, Roy  SL, Moore  TA, Visvesvara  GS, Ratard  RC, et al. Primary amebic meningoencephalitis deaths associated with sinus irrigation using contaminated tap water. Clin Infect Dis. 2012;55:e7985. DOIPubMed
  10. Centers for Disease Control and Prevention (CDC). Notes from the field: primary amebic meningoencephalitis associated with ritual nasal rinsing—St. Thomas, U.S. Virgin islands, 2012. MMWR Morb Mortal Wkly Rep. 2013;62:903.PubMed

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Table

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Cite This Article

DOI: 10.3201/eid2401.170545

1Preliminary results of this study were presented at the Infectious Diseases Society of America Conference; October 8–12, 2014, Philadelphia, Pennsylvania, USA.

Table of Contents – Volume 24, Number 1—January 2018

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Jennifer R. Cope, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop C09, Atlanta, GA 30329, USA

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Page created: December 19, 2017
Page updated: December 19, 2017
Page reviewed: December 19, 2017
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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