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Letter
Balamuthia
Amebic Encephalitis Risk, Hispanic Americans
Frederick L. Schuster,*
Carol Glaser,* Somayeh Honarmand,* James H. Maguire,† and Govinda S. Visvesvara†
*California Department of Health Services, Richmond, California, USA;
and †Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Suggested citation
for this article:
Schuster FL, Glaser C, Honarmand S, Maguire JH, Visvesvara GS. Balamuthia
amebic encephalitis risk, Hispanic Americans [letter]. Emerg Infect
Dis [serial on the Internet]. 2004 Aug [date cited]. Available
from: http://www.cdc.gov/ncidod/EID/vol10no8/04-0139.htm
To the Editor: Balamuthia mandrillaris, a free-living soil
ameba, can cause granulomatous amebic encephalitis as well as nasopharyngeal,
cutaneous, and disseminated infections in humans, nonhuman primates, and
other animals. Approximately 100 published and unpublished cases of Balamuthia
amebic encephalitis (BAE) have been reported; most were fatal. Diagnosis
of BAE is usually made at autopsy, and rarely by biopsy, in part because
the amebas can be overlooked in histopathologic preparations. In recognizing
BAE as a type of encephalitis that might otherwise be undiagnosed, the
California Encephalitis Project (1) has been screening
selected serum samples from patients with encephalitis for evidence of
antibodies to Balamuthia.
We describe cases of BAE in California and compare data with national
data collected on Balamuthia infections since the discovery of
the organism in 1990. Since 1998, serum and other samples (cerebrospinal
fluid [CSF], throat and rectal swabs, brain tissue) from patients with
encephalitis have been submitted to the California Encephalitis Project
by participating physicians throughout California. The goal of the California
Encephalitis Project is to provide enhanced diagnostic testing for etiologic
agents of encephalitis through an intensive testing algorithm. The case
definition of encephalitis is encephalopathy, plus one or more of the
following: fever, seizures, focal neurologic findings, CSF pleocytosis,
or electroencephalographic or neuroimaging findings consistent with encephalitis
(1). Persons with HIV/AIDS, severely immunocompromised
patients, and patients <6 months of age are excluded from the
project.
Serum samples were selected for screening for Balamuthia antibodies
if the patient had clinical or laboratory features suggestive of Balamuthia
encephalitis (elevated CSF protein and leukocyte counts or compatible
findings on neuroimaging) and a history of outdoor occupational (agriculture
or construction work) or recreational (camping or swimming) activities
during which they may have been exposed to pathogenic or opportunistic
free-living amebas. During the study, 215 (approximately 25%) of the >850
serum samples collected in California were tested for Balamuthia
infection by indirect immunofluorescence assay (2). Testing
was conducted on acute-phase serum and a follow-up sample, when available.
Serum samples were tested at dilutions from 1:2 to 1:4,096. Positive and
negative control samples were run in parallel, with titers from 1:128
to 1:256 for the former and negative to 1:32 for the latter. Serum samples
from patients with Balamuthia encephalitis did not cross-react
with Acanthamoeba or Naegleria, two other amebas associated
with amebic encephalitis (3).
Three (1.4%) of 215 samples tested were positive for antibodies to Balamuthia
with titers of 1:128, 1:128, and 1:256. In the course of the study period,
serum samples from four additional persons, including serum from one person
who had been diagnosed by the Centers for Disease Control and Prevention
(CDC), who were not part of California Encephalitis Project were positive.
The diagnosis of Balamuthia encephalitis was confirmed histologically
or by indirect immunofluorescence staining of tissue sections in all seven
cases; in one case amebas also were isolated in culture from necrotic
brain tissue at autopsy (4). All patients were immunocompetent
and of Hispanic American ethnicity, and all died. Case-patients included
two adults and three children who were native Californians, a child who
had arrived from Mexico the previous year, and a child who was a native
of Texas who had been diagnosed by the California Department of Health
Services (5). The observation that all were of Hispanic
American ethnicity prompted a search through CDC's records (N = 104) to
confirm the ethnicity of BAE patients throughout the world (G.S. Visvesvara,
unpub. data). Patients were considered to be of Hispanic American ethnicity
if they were identified as such in case histories or if they had traditional
Hispanic surnames. Specific confirmation of ethnicity was not available
in the CDC records, and reliance on surnames to determine ethnicity might
be a source of error; some Hispanic American persons may have surnames
that are not considered to be ethnically Hispanic, and vice versa. According
to the records, approximately 50% of the 50 North American patients, which
were confirmed by direct immunofluorescence, histopathology, or both,
were Hispanic American. Thirty-six percent of all the BAE cases occurred
in Latin America. Eleven cases have occurred in California since the early
1990s, including those described above, and all but two were fatal (6).
Eight (73%) of these 11 cases occurred in Hispanic Americans.
BAE is not an insignificant disease in California, with 11 cases and
9 deaths reported in the state in the last decade. By comparison, five
deaths from indigenous rabies have been reported in the state since approximately
1990 (7). Furthermore, BAE is likely underdiagnosed because
of unfamiliarity with appearance of amebas in tissue sections and nonspecific
symptoms. Unless there is a high degree of suspicion, it is unlikely that
testing for Balamuthia would be conducted. Most cases are diagnosed
on autopsy, which is often not allowed by families. Also, BAE develops
in a disproportionate number of Hispanic Americans. Hispanic Americans
make up 12.5% of the U. S. population (United States Census Bureau statistics
for 2000) but represent approximately 50% of the cases of BAE. In California,
where Hispanic Americans make up 32% of the state's population, they have
73% of BAE cases (p = 0.001, Fisher exact test). In the California Encephalitis
Project, Hispanic Americans accounted for approximately 25% of all cases
of encephalitis, 26% of serum samples examined for Balamuthia antibody,
and 21% of cases of viral and bacterial encephalitis, but all BAE patients
(n = 3) were in Hispanic Americans (Figure).
Balamuthia lives in soil (4) and can enter through
the respiratory tract or breaks in the skin. Hispanic Americans may be
more likely to reside in agrarian settings with increased exposure to
soil and opportunities for contamination of cuts and other injuries. Whether
caused by environmental factors, genetic predisposition, access to medical
care, or other socioeconomic factors and pressures, the reasons for the
higher incidence of BAE in Hispanic Americans warrant further study.
This study was supported
by the Emerging Infections Program of the CDC.
References
- Glaser CA, Gilliam S, Schnurr D, Forghani B, Honarmand
S, Khetsuriani N, et al. In
search of encephalitis etiologies: diagnostic challenges in the California
Encephalitis Project, 1998–2000. Clin Infect Dis. 2003;36:731–42.
- Visvesvara GS, Schuster FL, Martinez AJ. Balamuthia
mandrillaris N. G., N. Sp., agent of amebic meningoencephalitis
in humans and other animals. J Eukaryot Microbiol. 1993;40:504–14.
- Schuster FL, Glaser C, Honarmand S, Visvesvara GS. Testing for Balamuthia
encephalitis by indirect immunofluorescence. In: Lares-Villa F. Booton
GC, Marciano-Cabral F, editors. Proceedings of the Xth International
Meeting on the Biology and Pathogenicity of Free-Living Amoebae; 2003
Oct 5–10; Ciudad Obregón, Mexico: ITSON-DIEP; 2003. p. 173–8.
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C, et al. Environmental
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FL, et al. Amebic
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treatment of Balamuthia amoebic encephalitis: presentation of
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