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The public health threat from Balamuthia Mandrillaris in the southern United States.

Free-living amebae of the genera Acanthamoeba, Naegleria, and Sappinia are rare causes of amebic encephalitis in humans. (1-4) Several species of Acanthamoeba, however, may also cause Acanthamoeba keratitis (AK), reported in over one to two cases per million contact lens wearers in the United States (US) annually, and not associated with amebic encephalitis. (3) Naegleria fowleri can cause a rapidly progressive and typically fatal amebic encephalitis, primary amebic meningoencephalitis (PAM), following warm freshwater exposures, which enable the organism to penetrate the nasal mucosa and invade the brain via the olfactory nerve tracts. (1,2) Sappinia pedata, recently isolated from soil and animal feces, has caused only one case of non-fatal amebic encephalitis in a Texas cattle rancher. (4) Balamuthia mandrillaris, formerly known as leptomyxid ameba (Leptomyxidae), is another opportunistic, free-living ameba, phylogenetically related to Acanthamoeba, and first isolated from soil in 2003 in association with a fatal pediatric case of amebic encephalitis in California. (5) Like Acanthamoeba, Balamuthia mandrillaris infections can cause skin lesions and granulomatous amebic encephalitis (GAE) in individuals with either compromised or competent immune systems. (5-9) Brain infections caused by these ubiquitous organisms remain rare despite expanding world populations with frequent soil and freshwater exposures; but are, nevertheless, increasing today due to a combination of unexplained, untested factors that may include increased recreational and occupational exposures in warming ecosystems, more immunocompromised patients susceptible to opportunistic pathogens, and better neuroimaging and immunodiagnostic technologies. (1-10)

The objectives of this review and meta-analysis are to describe and to analyze laboratory-confirmed cases of Balamuthia mandrillaris amebic encephalitis (BAE) in the US for any consistent behavioral, environmental, genetic, iatrogenic, recreational, or regional risk factors for pathogen exposures and typically fatal infections.

MATERIALS AND METHODS

Initially, Medline, Pub Med, Google[R], and Google Scholar[R] search engines were queried for references using all key words listed as query terms. The only cases of Balamuthia amebic encephalitis (BAE) included in this meta-analysis were published cases with laboratory-confirmed detection of Balamuthia mandrillaris infective life forms (trophozoites) by direct microscopic observation, by immunohistopathological techniques, by isolation in culture, or by species-specific deoxyribonucleic acid (DNA) as detected by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF), brain or skin biopsies, or brain necropsy tissue. (11-13) Significant behavioral, demographic, environmental, ethnic, iatrogenic, occupational, recreational, and regional exposure factors for BAE were identified over the study period, 1980-2010, in order to make recommendations for the early diagnosis, management, and prevention of BAE and to determine any potential regional threats to public health posed by Balamuthia mandrillaris.

The ages of case-patients were stratified by gender and by age 18 and older (adults) versus age less than 18 years (children) and were compared for statistically significant differences by two-tailed, unpaired t-tests. Statistical significance was indicated by p-values less than or equal to 0.05. Selected behavioral, demographic, environmental, ethnic, occupational, recreational, and regional exposure factors previously presumed to be associated with BAE were also stratified by age and gender, described, and compared by proportions (percentages) and rates. Since this investigation was a comparative descriptive and statistical analysis of previously reported cases, institutional review board approval was not required.

RESULTS

Balamuthia mandrillaris caused typically fatal granulomatous encephalitis without many consistent epidemiological patterns in both children and adults, in immunocompetent and immunosuppresssed patients, and in few case-patients with documented environmental exposures to soil or freshwater. Most cases occurred in immunocompetent patients (n = 29, 83%), unlike Acanthamoeba-associated granulomatous encephalitis, which has remained more common in immunosuppressed patients (Table 1). (7, 8) Table 1 contrasts clinical, diagnostic laboratory, and neuroimaging features of primary amebic meningoencephalitis with the only two known causes of granulomatous amebic encephalitis, Acanthamoeba and Balamuthia mandrillaris. (1, 2 6-39)

There were 35 laboratory-confirmed cases of Balamuthia mandrillaris amebic encephalitis (BAE) in the US during the reporting study period, 1980-2010 (Tables 2-3). (13-29) The mean age of the study population of males was 23.49 ([+ or -] 25.01) years, with males (n = 25, 71%) outnumbering females 2.5:1.0 (n = 10, 29%). Tables 2 and 3 display the demographic, epidemiologic, clinical, and diagnostic presenting features of BAE in laboratory-confirmed male (Table 2) and female (Table 3) case-patients. There were no statically significant differences in the mean ages of male and female cases, and there were few survivors of Balamuthia mandrillaris GAE (n = 6, 3 males and 3 females) for an overall case fatality rate of 83%.

The stratified comparative analysis of BAE cases by gender (Table 4) and by age (Table 5) demonstrated the following consistent epidemiological patterns. (1) Most case-patients, especially children (n = 19, 95%), were immunocompetent and not immunosuppressed by medications or congenital immunodeficiencies. (2) Most cases occurred in the southern-most tier of the continental US from Florida to California (FL, MS, TX, AZ, CA; n = 31, 89%). (3) Cases occurred in patients of Hispanic ethnicity more often than anticipated by population demographics, even in the southern-most tier, Mexican border-states (n = 15, 43%), and especially in children (n = 11, 55%) and in California (n = 8, 53%). (4) BAE was almost uniformly fatal in children (case fatality rate = 90%) and adults (case fatality rate = 73%). (5) With the exceptions of male gender, southern tier state of residence, and Hispanic ethnicity, there were few remaining potential, predisposing risk factors for BAE. (6) Soil exposures did indeed occur prior to some cases in all segments of the stratified study population (n = 6), but were inconsistent and ranged from two cases in children (10%) to four cases in adult males (16%). (6) Lastly, recent cases demonstrated that, like Acanthamoeba granulomatous amebic encephalitis (GAE), Balamuthia mandrillaris infections were also transmitted from organ donors with laboratory confirmed BAE to organ transplant recipients with high case fatality rates, even following accurate diagnosis and aggressive treatment of transplant recipients with recommended conventional and experimental drugs (n = 3, 38%).

[FIGURE 1 OMITTED]

DISCUSSION

Balamuthia mandrillaris was first isolated from the brain of a pregnant mandrill baboon that died of acute meningoencephalitis at the San Diego Zoo in 1990. (30) Since then, Balamuthia mandrillaris has been identified, usually by indirect immunofluorescent methods using rabbit Balamuthia antiserum, in about 200 cases of typically fatal human encephalitis throughout the world. (13, 19, 29, 31) Balamuthia amebic encephalitis (BAE) or balamuthiasis is a chronic infection of the brain that may disseminate to other organs hematogenously and occurs in immunocompetent patients, immunosuppressed patients with the acquired immunodeficiency syndrome (AIDS) or organ transplants, and in patients receiving chemotherapy for cancer or tuberculosis. (12-14) The portal of entry for Balamuthia mandrillaris is through the respiratory tract or via ulcerating skin wounds with hematogenous spread to the CNS and, less commonly, with systemic dissemination to other organs in the severely immunocompromised. (5, 11-14) The life cycle of Balamuthia mandrillaris is depicted in Figure 1, and an infective trophozoite of B. mandrillaris in brain biopsy tissue is depicted in Figure 2.

[FIGURE 2 OMITTED]

Besides immunocompromise, other potential risk factors for balamuthiasis may include contact with stagnant freshwater or with contaminated dust or soil, often through agricultural work, desert motorcycling, dirt-biking, or even gardening and yard work. (5, 12) In some cases, BAE has occurred following indolent skin lesions originating in soil-contaminated puncture wounds or presumed insect bites (Table 2, male case numbers 11, 13, 16, 26). In other cases, BAE has occurred following potential inhalational exposures to aerosols of dirt, dust, and potting soils (Table 2, male case numbers 19, 22, 23, 24; Table 3, female case number 9). A genetic predisposition to Balamuthia mandrillaris GAE has now been identified in American Hispanics, who appear less able to produce effective antibodies against some free living amebae, and may be predisposed by more frequent contact with Balamuthia-contaminated soils and aerosols in agricultural and landscaping occupations. (31, 32)

The incubation period for BAE can extend for weeks or months after primary inoculation in the skin, sinuses, or lungs, with subsequent draining ulcers, chronic sinusitis, or pneumonia. (5, 13-29) However, the incubation period typically exhibits a mean of 8.5 days with a range of 1-30 days following primary inoculation. (12) The clinical presentation of BAE may include early behavioral and personality changes, fever, depressed mental status, seizures, photophobia, visual loss, and nonspecific cranial nerve dysfunction, followed by signs of increased intracranial pressure, including headache, nausea, vomiting, and loss of consciousness. (13-29, 33)

The laboratory diagnosis of BAE is usually based on microscopic identification of characteristic trophozoites in CSF, skin, or brain biopsies. Trophozoites are more often identified in fixed and stained skin ulcer biopsies, brain biopsies, and post-mortem brain tissue than in wet or fixed and stained mounts of CSF (Figure 2). (11, 12) Recently, immunodiagnostic tests using indirect immunofluorescent methods, such as indirect immunofluorescent ultraviolet microscopy and indirect immunofluorescent antibody ultraviolet microscopy with specific anti-pathogen antibodies, and new PCR assays for identification of pathogen DNA have been developed for diagnostic specimens. (34)

Neuroimaging studies by axial computerized tomography (CT) and/or magnetic resonance imaging (MRI) in BAE are nonspecific and often include single to multiple space-occupying lesions in the brain from the frontal cortex to the cerebellum with ring--enhancing and other focal effects slightly more common in balamuthiasis than in other free-living amebic infections of the brain, such as acanthamoebiasis and primary amebic meningoencephalitis (PAM). (35, 36) Evidence of cerebral edema will often be present and may include midline shifts, cisternal and ventricular compression, and hydrocephalus, with hydrocephalus more common in children than adults. (35, 36)

Treatment strategies for BAE will include combinations of critical care techniques to reduce increased intracranial pressure, craniotomy for biopsy or excision of mass lesions, and combination pharmacotherapy with antifungals, anti-protozoal agents, synergistic antibiotics, and several experimental therapies that have shown promise in vitro, such as oral and intravenous treatment with phenothiazines. (37-39) Although case fatality rates in BAE are high ([greater than or equal to] 90%), some successful drug treatment combinations in balamuthiasis have included azoles (albendazole, fluconazole, or itraconazole), flucytosine, pentamidine, sulfadiazine; and synergistic anti-protozoal therapy with macrolide antibiotics (azithromycin or clarithromycin), phenothiazines (thioridazine or trifluoperazine), and the experimental anti-Leishmania agent used to treat visceral leishmaniasis, miltefosine. (37-39) The optimum duration of drug therapy for BAE is unknown, but most survivors have been treated for weeks to months. (12, 37-39) Like Acanthamoeba-caused amebic infections of the brain, Balamuthia mandrillaris infections may also be disseminated hematogenously and were recently associated with two case clusters of organ transplant-transmitted infections in southern tier US states (AZ, MS) with three deaths in transplant recipients (Table 2, male case numbers 21, 22; Table 3, female case number 10). (24, 25)

Prevention and control strategies for BAE should include (1) consideration of BAE in organ transplant and immunocompromised patients with encephalitis and skin ulcers not improving with standard therapies, especially in southern tier US states; (2) recognition of genetic risk factors for acanthamoebiasis and balamuthiasis in Hispanics; and (3) recognition of other soil or stagnant freshwater risk factors in both immunocompetent and immunosuppressed patients with skin ulcers, chronic sinusitis, and unexplained meningoencephalitis. (31, 32)

CONCLUSIONS

The results of this study have demonstrated the following public health threats from Balamuthia mandrillaris in the US. (1) BAE occurs sporadically in patients of all ages and affects both immunosuppressed patients and immunocompetent patients with few predisposing factors. (2) The few predisposing factors include male gender, exposure in a southern tier US state, and Hispanic ethnicity. (3) Most cases of BAE will not be diagnosed in time for aggressive medical intervention and will be fatal. (4) BAE can be transmitted from infected organ donors with undiagnosed causes of infectious meningoencephalitis to immunosuppressed transplant recipients.

Clinicians should suspect free-living amebic infections of the CNS in all refractory cases of meningoencephalitis initially managed as aseptic or bacterial infections, especially in patients predisposed to such infections by behavioral practices, environmental or occupational exposures, ethnicity, or immunosuppression by chemotherapy or organ transplant anti-rejection therapy.

REFERENCES

(1.) Ma P, Visvesvara GS, Martinez AJ, et al. Naegleria and Acanthamoeba infections: review. Rev Infect Dis 1990;12:490-510.

(2.) Primary amebic meningoencephalitis-Arizona, Florida, and Texas, 2007. MMWR 2008;57:573-577.

(3.) Acanthamoeba keratitis multiple states, 2005-2007. MMWR 2007; 56:532-534.

(4.) Gelman BR, Rauf SJ, Popov V, et al. Amoebic encephalitis due to Sappinia diploidea. J Am Med Assoc 2010;285:2450-2451.

(5.) Schuster FL, Dunnebacke TH, Booton GC, et al. Environmental isolation of Balamuthia mandrillaris associated with a case of amebic encephalitis. J Clin Microbiol 2003;41:3175-3180.

(6.) Jung S, Schelper RL, Visvesvara GS, Chang HT. Balamuthia mandrillaris meningoencephalitis in an immunocompetent patient: an unusual clinical course and a favorable outcome. Arch Path Lab Med 2004;128:466-468.

(7.) Steinberg JP, Galindo RL, Kraus ES, et al. Disseminated acanthamoebiasis in a renal transplant recipient with osteomyelitis and cutaneous lesions: case report and literature review. Clin Infect Dis 2002;35:43-49.

(8.) Barete S, Combes A, de Jonckheere JF, et al. Fatal disseminated Acanthamoeba lenticulata infection in a heart transplant patient. Emerg Infect Dis 2007;13:736-738.

(9.) Mutreja D, Jalpota Y, Madan R, et al. Disseminated Acanthamoeba infection in a renal transplant recipient. Indian J Path Microbiol 2007;50:346-348.

(10.) Marcogliese DJ. The impact of climate change on the parasites and infectious diseases of aquatic animals. Revue Scientifique et Technique 2008; 27:467-484.

(11.) Martinez AJ, Visvesvara GS. Laboratory diagnosis of pathogenic free-living amoebas: Naegleria, Acanthamoeba, and Leptomyxid. Clin Lab Med 1991;11:861-872.

(12.) Koshy AA, Blackburn BG, Singh U. Free-living amebas. In: Mandell GL, Bennett JE, Dolin R, et al (editors). Principles and Practice of Infectious Diseases, 7th edition. Philadelphia: Churchill Livingstone Elsevier; 2010:3427-3436.

(13.) Balamuthia amebic encephalitis-California, 1999-2007. MMWR 2008;57:768-771.

(14.) Wessel HB, Hubbard J, Martinez AJ, et al. Granulomatous amebic encephalitis (GAE) with prolonged clinical course: CT scan findings, diagnosis by brain biopsy, and effect of treatment. Neurol 1980;30:442.

(15.) Cox EC. Amebic meningoencephalitis caused by Acanthamoeba species in a four month old child. J SC Med Assoc 1980;76:459-462.

(16.) Neafie RC, Marty AM. Unusual infections in humans. Clin Microbial Rev 1993;6:34-56.

(17.) Griesmer DA, Barton LL, Reese CM, et al. Amebic meningoencephalitis caused by Balamuthia mandrillaris. Pediatr Neurol 1994;10:249-254.

(18.) Rowen JL, Doerr CA, Vogel H, et al. Balamuthia mandrillaris: a newly recognized agent for amebic meningoencephalitis. Pediatr Infect Dis J 1995;14:705-710.

(19.) Deol I, Robledo L, Meza A, et al. Encephalitis due to a free-living amoeba (Balamuthia mandrillaris): case report with literature review. Surg Neurol 2000;53:611-616.

(20.) Healy JF. Balamuthia amebic encephalitis: radiographic and pathologic findings. Am J Neuroradiol 2002;23:486-489.

(21.) Deetz TR, Sawyer MH, Billman G, et al. Successful treatment of Balamuthia amoebic encephalitis: presentation of two cases. Clin Infect Dis 2003;37:1304-1312.

(22.) Bakardjiev A, Azimi PH, Ashouri N, et al. Amebic encephalitis caused by Balamuthia mandrillaris: report of four cases. Pediatr Infect Dis J 2003;22:447-452.

(23.) Pritzker AS, Bong KK, Agrawal D, et al. Fatal granulomatous amebic encephalitis caused by Balamuthia mandrillaris presenting as a skin lesion. J Am Acad Derm 2004;50:S38-40.

(24.) Balamuthia mandrillaris transmitted through organ transplantation-Mississippi, 2009. MMWR 2010;59:1165-1170.

(25.) Notes from the field-Transplant transmitted Balamuthia mandrillaris-Arizona, 2010. MMWR 2010;59:1182.

(26.) Matson DO, Rouah E, Lee RT, et al. Acanthamoeba meningoencephalitis masquerading as neurocysticercosis. Pediatr Infect Dis J 1988;7:121-124.

(27.) Popek EJ, Neafie RC. Case Four: granulomatous meningoencephalitis due to leptomyxid ameba. Pediatr Pathol 1992;12:871-881.

(28.) Katz JD, Ropper AH, Adelman L, et al. A case of Balamuthia mandrillaris meningoencephalitis. Arch Neurol 2000;57:1210-1212.

(29.) Jung S, Schelper RL, Visvesvara GS, et al. Balamuthia mandrillaris meningoencephalitis in an immunocompetent patient: an unusual clinical course and a favorable outcome. Arch Path Lab Med 2004;128:466-468.

(30.) Visvesvara GS, Martinez AJ, Schuster FL, et al. Leptomyxid ameba, a new agent of amebic meningoencephalitis in humans and animals. J Clin Microbiol 1990;28:2750-2756.

(31.) Schuster FL, Glaser C, Honarmand S, et al. Balamuthia amebic encephalitis risk, Hispanic Americans. Emerg Infect Dis 2004;10: 1510-1512.

(32.) Maciver SK. The threat from Balamuthia mandrillaris. J Med Microbiol 2007;56:1-3.

(33.) Radhakrishan V, Bhatia R, Panda GS, Bakhshi S. Acanthamebic meningoencephalitis presenting as personality change. Ped Infect Dis J 2009; 28: 555.

(34.) Qvarnstrom Y, Visvesvara GS, Sriram R, da Silva AJ. Multiplex real-time PCR assay for simultaneous detection of Acanthamoebae spp., Balamuthia mandrillaris, and Naegleria fowleri. J Clin Microbial 2006; 44: 3589-95.

(35.) Singh P, Kochhar R, Vashishta RK, et al. Amebic meningoencephalitis. Am J Neuroradiol 2006;27:1217-1221.

(36.) Kidney DD, Kim SH. CNS infections with free-living amebas: neuroimaging findings. Am J Roentgenol 1998;171:809-812.

(37.) Deetz TR, Sawyer MH, Schuster FL, et al. Successful treatment of Balamuthia amoebic encephalitis in an immunocompetent patient. Arch Pathol Lab Med 2004;128:466-468.

(38.) Schuster FL, Visvesvara GS. Opportunistic amoebae: challenges in prophylaxis and treatment. Drug Resist Updates 2004;7:41-51.

(39.) Martinez DY, Seas C, Bravo F, et al. Successful treatment of Balamuthia mandrillaris amoebic infection with extensive neurological and cutaneous involvement. Clin Infect Dis 2010;51: 7-11.

James H. Diaz, MD, MPH&TM, DrPH, FACPM, FCCM

Dr. Diaz is a professor of public health and preventive medicine, program head of the Environmental and Occupational Health Sciences School of Public Health at Louisiana State University Health Sciences Center in New Orleans (LSUHSC-NO), In addition, he is professor of anesthesiology/critical care medicine in the School of Medicine at LSUHSC-NO.
Table 1. Comparison of the clinical features of primary amebic
meningoencephalitis and granulomatous amebic encephalitis.
(1,2,6-39)

Infections          Primary amebic          Granulomatous amebic
                    meningoencephalitis     encephalitis (GAE)
                    (PAM)                   caused by either
                                            Acanthamoeba species
                                            or Balamuthia
                                            mandrillaris)

Pathogens           Naegleria fowleri       Acanthamoeba spp.

Distribution        Worldwide in warm       Worldwide in
                    freshwater, bottom      freshwater and soil
                    sediment, and soil

Cases reported      180-200                 [less than or equal
worldwide                                   to] 200

Seasonal            Summertime or warmest   Year round
occurrence          seasons

High-risk groups    Immunocompetent         Immuncompromised
                    children and young      children and adults
                    adults, especially      (acquired
                    males with histories    immunodeficiency
                    of freshwater           syndrome, cancer or
                    exposures (skiing,      chemo, organ or bone
                    wakeboarding) within    marrow transplant,
                    two weeks               liver or renal
                                            failure); rarely in
                                            the immunocompetent

Pathology           Trophozoites            Hematogenous
                    penetrate nasal         dissemination from
                    mucosa and cribriform   granulomatous skin
                    plate and migrate via   ulcers or lung
                    olfactory nerves to     granulomas, across
                    olfactory bulbs and     blood-brain barrier
                    tracts along basilar    to CNS
                    brain to cerebellum

Incubation period   Mean 5-7 days (range    Weeks to months
                    1-16 days)              following indolent
                                            draining skin ulcers,
                                            sinusitis, or
                                            pneumonia

Clinical features   Fever, headache,        Same as PAM, early
                    stiff neck              mental status
                    (meningismus),          changes, visual loss,
                    nausea, specific CN     photophobia
                    dysfunction (altered
                    senses of smell and
                    taste, anisocoria),
                    seizures,
                    disorientation, coma

Laboratory          Trophozoites in CSF     Both cysts and
studies             wet mounts, stained     trophozoites in
                    CSF sediment or brain   fixed, stained brain
                    tissues enhanced by     tissue enhanced by
                    IIF or IFA; N.          IIF or IFA;
                    fowleri DNA by PCR on   Acanthamoeba DNA by
                    CSF or unfixed brain    PCR on CSF or unfixed
                                            brain

Imaging studies     Nonspecific: basilar    Nonspecific: multiple
by computed         leptomeningeal          space-occupying
tomography or       enhancement,            lesions, with or
magnetic            intraparaenchymal       without ring-
resonance imaging   lesions and-or          enhancing effects
                    hemorrhagic necrosis;
                    evidence of ICP-
                    cerebral edema,
                    midline shift,
                    cisternal and
                    ventricular
                    compression

Treatment           IV and IT:              IV and IT: azoles IV:
                    amphotericin B,         azoles, flucytosine,
                    azoles: fluconazole,    pentamidine,
                    itraconazole,           rifampin,
                    miconazole              trimethoprim-sulfa-
                    Synergistic             methoxazole
                    antibiotics:            Experimental:
                    azithromycin po,        miltefosine
                    rifampin
                    Experimental:
                    chlorpromazine or
                    other phenothiazines

Outcomes (CFRs)     Death within 3-7 days   Usually fatal in
                    (>95%)                  immunocompromised
                                            (90%-94%);
                                            immunocompetent
                                            children most likely
                                            to survive

Infections          Granulomatous amebic encephalitis (GAE)
                    caused by either Acanthamoeba species or
                    Balamuthia mandrillaris)

Pathogens           Balamuthia mandrillaris

Distribution        Worldwide in freshwater and soil; more
                    common in the US South and South America

Cases reported      Approximately 150
worldwide

Seasonal            Year round
occurrence

High-risk groups    Immunocompetent children and adults,
                    most often males with soil exposures
                    (dirt/biking, agriculture) and/or
                    Hispanic origin; less common in
                    immunocompromised with acquired
                    immunodeficiency syndrome or intravenous
                    drug use

Pathology           Hematogenous dissemination from
                    granulomatous skin ulcers, often facial,
                    or lung granulomas across blood-brain
                    barrier to CNS

Incubation period   Mean 8.5 days (Range 1-30 days)
                    following indolent pneumonia or draining
                    granulomas on the face or upper arms

Clinical features   Same as PAM and GAE with early confusion
                    and disorientation, nonspecific CN
                    dysfunction

Laboratory          IFA staining of fixed brain tissue; PCR
studies             for Balmuthia DNA in CSF or brain tissue

Imaging studies     Nonspecific: cerebral edema,
by computed         hydrocephalus, multiple space-occupying
tomography or       and ring-enhancing in cortex and
magnetic            cerebellum
resonance imaging

Treatment           IV: azoles-albendazole, fluconazole,
                    itraconazole, pentamidine, flucytosine,
                    sulfadiazine Synergistic macrolides:
                    azithromycin, clarithromycin
                    Experimental: phenothiazines-
                    thioridazine, trifluoperazine

Outcomes (CFRs)     Usually fatal ([greater than or equal
                    to] 90%)

CFR: case fatality rate; CN: cranial nerve; CSF: cerebrospinal
fluid; PCR: polymerase chain reaction nucleic acid assay; IFA:
immunofluorescent assay; IIF: indirect immunofluorescence; DNA:
deoxyribonucleic acid; ICP: intracranial pressure; IV:
intravenous; IT: intrathecal

Table 2. Selected demographic and presenting clinical features
of 25 male cases of Balamuthia amebic encephalitis in the US,
1980-2010.

                 State
         Age     of
Case     in      Residence,      Race/Ethnicity
Number   years   Year
                 Reported

1        2.5     FL, 1980        Caucasian

2        0.3     SC, 1980        Caucasian

3        1.5     NC, 1993        Caucasian

4        0.75    CA, 1994        Not reported
                                 (NR)

5        2.25    AZ, 1994        NR

6        5       TX, 1993        Caucasian

7        15      TX, 1993        Hispanic

8        38      TX, 2000        Hispanic

9        32      CA, 2002        Caucasian

10       64      CA, 2003        Caucasian

11       7       CA, 2003        Hispanic

12       2.5     TX, 2003        Hispanic

13       89      TX, 2004        Caucasian

14       1.5     CA, 1999-2007   Hispanic

15       7       CA, 1999-2007   Hispanic

16       12      CA, 1999-2007   Hispanic

17       19      CA, 1999-2007   Hispanic

18       35      CA, 1999-2007   Hispanic

19       43      CA, 1999-2007   Caucasian

20       72      CA, 1999-2007   Pacific
                                 Islander

21       4       MS, 2009        Caucasian

22       27      MS, 2009        Not Hispanic,
                                 otherwise NR

23       27      AZ, 2010        Hispanic

24       56      AZ, 2010        Not Hispanic,
                                 otherwise NR

25       24      AZ, 2010        Not Hispanic,
                                 otherwise NR

         Age
Case     in      Immune status            Exposure status
Number   years

1        2.5     Within normal limits     None

2        0.3     Within normal limits     None

3        1.5     Within normal limits     Bathed in lake 1 month
                                          prior

4        0.75    Within normal limits     None

5        2.25    Within normal limits     None

6        5       Within normal limits     None

7        15      Within normal limits     None

8        38      Within normal limits     Puncture wound on
                                          thigh

9        32      Within normal limits     Alcohol-drug abuse

10       64      Steroid therapy          Nodular lesion-rose
                                          thorn, forearm

11       7       +cysticercosis titer,    None
                 otherwise within
                 normal limits

12       2.5     Within normal limits     None

13       89      Within normal limits     Lived on cattle ranch
                                          and had chronic nasal
                                          ulcer

14       1.5     Within normal limits     None

15       7       Steroid therapy          None

16       12      Within normal limits     Frequent desert
                                          motorcycling

17       19      Within normal limits     Former drug abuser

18       35      Within normal limits     None

19       43      Within normal limits     Occupational soil
                                          exposure

20       72      Within normal limits     Garden and yard soil
                                          exposures

21       4       Within normal limits     Outdoor wading pool
                                          and soil exposures

22       27      Kidney transplant        None
                 recipient, anti-
                 rejection therapy

23       27      Within normal limits     Chronic skin ulcer on
                                          back post insect bite

24       56      Liver transplant         None
                 recipient, anti-
                 rejection therapy

25       24      Kidney-pancreas          None
                 transplant recipient,
                 anti-rejection therapy

         Age
Case     in      Confirmed diagnosis      Outcome   Reference
Number   years                                       number

1        2.5     +IFF on brain biopsy     Died      14

2        0.3     Same                     Died      15

3        1.5     Same                     Died      16

4        0.75    Same                     Died      17

5        2.25    Same                     Died      17

6        5       Same                     Died      18

7        15      Same                     Died      18

8        38      Same                     Died      19

9        32      Same                     Died      20

10       64      +serology and brain      Lived     21
                 biopsy by IIF

11       7       +serology by IIF         Died      22

12       2.5     +brain biopsy by         Died      22
                 microscopy and IIF

13       89      +IFF on nasal lesion     Died      23
                 biopsy

14       1.5     +brain biopsy by         Died      13
                 microscopy and IIF

15       7       +serology and brain      Died      13
                 biopsy by IIF and PCR

16       12      +serology by IIF, +      Died      13
                 brain biopsy by IIF
                 and PCR

17       19      +brain biopsy by IIF     Died      13
                 and PCR

18       35      +serology by PCR         Lived     13

19       43      +brain biopsy by IIF     Died      13
                 and PCR

20       72      +brain biopsy by IIF     Died      13
                 and PCR

21       4       +brain biopsy by IIF     Died      24
                 and PCR; organ donor

22       27      +organ donor by IIF      Lived     24
                 and PCR on brain
                 biopsy

23       27      Organ donor; suspected   Died      25
                 by +IIF and PCR on 2
                 organ recipients

24       56      +IIF and PCR on brain    Died      25
                 biopsy

25       24      Same                     Died      25

FL: Florida; SC: South Carolina; AZ: Arizona; TX:
Texas; CA California; MS: Mississippi; IIF: indirect
immunofluorescence; PCR: polymerase chain reaction
nucleic acid assay

Table 3. Selected demographic and presenting clinical features
of 10 female cases of Balamuthia amebic encephalitis in the US,
1988-2009.

                 State
         Age     of
Case     in      Residence,   Race/Ethnicity   Immune status
Number   years   Year
                 Reported

1        11      TX, 1988     Hispanic         +cysticercosis titer,
                                               otherwise within normal
                                               limits

2        0.4     AZ, 1992     Caucasian        Within normal limits

3        13      AZ, 1994     Hispanic         Within normal limits

4        52      MA, 2000     Caucasian        Chronic neutropenia

5        5       CA, 2002     Hispanic         Within normal limits

6        5       CA, 2003     Hispanic         Within normal limits

7        3       CA, 2003     Hispanic         Within normal limits

8        2       CA, 2003     Hispanic         Within normal limits

9        72      NY, 2004     Caucasian        Within normal limits

10       31      MS, 2009     Non-Hispanic,    Kidney recipient from a
                              otherwise not    brain biopsy +donor;
                              reported         anti-rejection therapy

         Age
Case     in      Exposure status        Confirmed diagnosis
Number   years

1        11      None                   +brain biopsy by IIF

2        0.4     None                   Same

3        13      Frequent travel to     Same
                 Mexico

4        52      None                   Same

5        5       None                   Same

6        5       Frequent travel to     Same
                 Mexico

7        3       Contact with potting   +brain biopsy by IIF and
                 soil                   culture

8        2       Frequent travel to     +brain biopsy by IIF
                 Mexico

9        72      Frequent travel to     +brain biopsy by IIF
                 Arizona and Texas

10       31      None                   +brain biopsy by IIF and
                                        PCR

         Age
Case     in      Outcome   Reference number
Number   years

1        11      Died      26

2        0.4     Died      27

3        13      Died      17

4        52      Died      28

5        5       Lived     20

6        5       Lived     21

7        3       Died      22

8        2       Died      22

9        72      Lived     29

10       31      Died      24

TX: Texas; AZ: Arizona; MA: Massachusetts ; CA: California; NY: New
York; MS: Mississippi; IIF: indirect immunofluorescence; PCR:
polymerase chain reaction nucleic acid assay

Table 4. A comparative analysis of US cases of Balamuthia amebic
encephalitis stratified by gender, N=35.

                       Males                  Females

Number                 25                     10

Mean age [+ or -]      23.49 [+ or -] 25.01   19.44 [+ or -] 24.58
standard deviation

Age significance                    t=0.435; p=0.667
test

Age range (years)      0.3-89                 0.4-72

Hispanic ethnicity     10 (40%)               5 (50%)
(%)

Immunocompetent (%)    21 (84%)               8 (80%)

Immunosuppressed (%)   4 (16%)                2 (20%)

Reside in southern     23 (92%)               8 (80%)
tier US state ** (%)

Soil exposures (%)     6 (24%)                2 (20%)

Deaths (case           22 (88%)               7 (70%)
fatality rate [%])

* Immunosuppressed=steroid therapy, organ transplant anti-rejection
therapy, pre-existing immunodeficiency disorder. ** Southern tier US
state=Arizona, California, Florida, Mississippi, and Texas.

Table 5. A comparative analysis of US cases of Balamuthia amebic
encephalitis stratified by age, N=35.

                       Children (< 18 years   Adults (age 18 years
                       of age)                and older)

Number                 20                     10

Mean age [+ or -]      5.035 [+ or -] 4.454   19.44 [+ or -] 24.58
standard deviation

Age significance                   t=8.369; p < 0.0001
test

Age range (years)      0.3-15                 19-89

Hispanic ethnicity     11 (55%)               4 (27%)
(%)

Immunocompetent (%)    19 (95%)               9 (60%)

Immunosuppressed (%)   1 (5%)                 6 (40%)

Reside in southern     18 (90%)               13 (87%)
tier US state ** (%)

Soil exposures (%)     2 (10%)                4 (27%)

Deaths (case           18 (90%)               11 (73%)
fatality rate [%])

* Immunosuppressed=steroid therapy, organ transplant anti-rejection
therapy, pre-existing immunodeficiency disorder. ** Southern tier US
state=Arizona, California, Florida, Mississippi, and Texas.
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Author:Diaz, James H.
Publication:The Journal of the Louisiana State Medical Society
Article Type:Report
Geographic Code:1USA
Date:Jul 1, 2011
Words:4612
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