• View in gallery
    Figure 1.

    Brain CT scan findings of the patient infected with Balamuthia mandrillaris.

  • View in gallery
    Figure 2.

    Brain magnetic resonance imaging from the patient infected with Balamuthia mandrillaris. (A) FLAIR image shows hyperintensity in right parieto-occipital, left occipital, and left frontal lobes suggestive of edema. (B) T1-weighted image shows foci of T1 hyperintensity suggestive of hemorrhagic component.

  • View in gallery
    Figure 3.

    Touch preparation smear of fresh brain lesion that had been extracted intraoperatively from a patient with encephalitis. Large amoeboid structures are seen in the background of mixed inflammatory cells (hematoxylin and eosin stain, magnification ×200).

  • View in gallery
    Figure 4.

    Formalin-fixed tissue section from the patient infected with Balamuthia mandrillaris. (A) High magnification of histologic sections depicted amoebae with large nuclei with prominent central nucleoli (hematoxylin and eosin stain, magnification ×1,000). (B) Brain tissue histologic section showed amoebic infiltration in the parenchyma with adjacent necrosis and mixed inflammatory cells infiltration (hematoxylin and eosin stain, magnification ×100).

  • View in gallery
    Figure 5.

    Agarose gel electrophoresis of conventional PCR products of the extracted DNA from brain tissue of the patient with free-living amoebic encephalitis. Lane 1: no product was detected using Naegleria fowleri–specific primer (negative), lane 2: a 171-bp product was detected using Balamuthia mandrillaris–specific primer (positive), lane 3: no product was detected using Acanthamoeba spp.–specific primer (negative).

  • 1.

    Fowler M, Carter RF, 1965. Acute pyogenic meningitis probably due to Acanthamoeba sp.: a preliminary report. Br Med J 2: 740742.

  • 2.

    Apley J, Clarke S, Roome A, Sandry S, Saygi G, Silk B, Wirhurst G, 1970. Primary amoebic meningoencephalitis in Britain. Br Med J 1: 596599.

  • 3.

    Mungroo MR, Khan NA, Siddiqui R, 2020. Balamuthia mandrillaris: pathogenesis, diagnosis, and treatment. Expert Opin Orphan Drugs 8: 111119.

  • 4.

    Schuster FL, Visvesvara GS, 2004. Opportunistic amoebae: challenges in prophylaxis and treatment. Drug Resist Updat 7: 4151.

  • 5.

    da Rocha-Azevedo B, Tanowitz HB, Marciano-Cabral F, 2009. Diagnosis of infections caused by pathogenic free-living amoebae. Interdiscip Perspect Infec Dis 2009: 251406.

    • Search Google Scholar
    • Export Citation
  • 6.

    Capewell LG, Harris AM, Yoder JS, Cope JR, Eddy BA, Roy SL, Visvesvara GS, Fox LM, Beach MJ, 2014. Diagnosis, clinical course, and treatment of primary amoebic meningoencephalitis in the United States, 1937–2013. J Pediatr Infect Dis Soc 4: e68e75.

    • Search Google Scholar
    • Export Citation
  • 7.

    Qvarnstrom Y, Visvesvara GS, Sriram R, da Silva AJ, 2006. Multiplex real-time PCR assay for simultaneous detection of Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri. J Clin Microbiol 44: 35893595.

    • Search Google Scholar
    • Export Citation
  • 8.

    Jayasekera S, Sissons J, Tucker J, Rogers C, Nolder D, Warhurst D, Alsam S, White JML, Higgins EM, Khan NA, 2004. Post-mortem culture of Balamuthia mandrillaris from the brain and cerebrospinal fluid of a case of granulomatous amoebic meningoencephalitis, using human brain microvascular endothelial cells. J Med Microbiol 53: 10071012.

    • Search Google Scholar
    • Export Citation
  • 9.

    Visvesvara GS, Martinez AJ, Schuster FL, Leitch GJ, Wallace SV, Sawyer TK, Anderson M, 1990. Leptomyxid ameba, a new agent of amebic meningoencephalitis in humans and animals. J Clin Microbiol 28: 27502756.

    • Search Google Scholar
    • Export Citation
  • 10.

    Khurana S, Hallur V, Goyal M, Sehgal R, Radotra B, 2015. Emergence of Balamuthia mandrillaris meningoencephalitis in India. Indian J Med Microbiol 33: 298.

    • Search Google Scholar
    • Export Citation
  • 11.

    Gompf SG, Garcia C, 2019. Lethal encounters: the evolving spectrum of amoebic meningoencephalitis. IDCases 15: e00524.

  • 12.

    Yamanouchi K, Arima H, Sakamoto Y, Kanto K, Kasai K, Ito K, Inaba T, 2018. First report of the isolation of Balamuthia mandrillaris in the northern region of Japan. Parasitol Res 117: 28952900.

    • Search Google Scholar
    • Export Citation
  • 13.

    Siddiqui R, Khan NA, 2015. Balamuthia mandrillaris: morphology, biology, and virulence. Trop Parasitol 5: 1522.

  • 14.

    Lorenzo-Morales J, Cabello-Vílchez AM, Martín-Navarro CM, Martínez-Carretero E, Piñero JE, Valladares B, 2013. Is Balamuthia mandrillaris a public health concern worldwide? Trends Parasitol 29: 483488.

    • Search Google Scholar
    • Export Citation
  • 15.

    Botterill E, Yip G, 2011. A rare survivor of Balamuthia granulomatous encephalitis. Clin Neurol Neurosurg 113: 499502.

  • 16.

    Kum SJ, Lee HW, Jung HR, Choe M, Kim SP, 2019. Amoebic encephalitis caused by Balamuthia mandrillaris. J Pathol Transl Med 53: 327331.

  • 17.

    Niyyati M, Karamati SA, Lorenzo Morales J, Lasjerdi Z, 2016. Isolation of Balamuthia mandrillaris from soil samples in north-western Iran. Parasitol Res 115: 541545.

    • Search Google Scholar
    • Export Citation
  • 18.

    Latifi AR, Niyyati M, Lorenzo-Morales J, Haghighi A, Seyyed Tabaei SJ, Lasjerdi Z, 2016. Presence of Balamuthia mandrillaris in hot springs from Mazandaran province, northern Iran. Epidemiol Infect 144: 24562461.

    • Search Google Scholar
    • Export Citation
  • 19.

    Kiderlen AF, Laube U, 2004. Balamuthia mandrillaris, an opportunistic agent of granulomatous amebic encephalitis, infects the brain via the olfactory nerve pathway. Parasitol Res 94: 4952.

    • Search Google Scholar
    • Export Citation
  • 20.

    Schafer KR, Shah N, Almira-Suarez MI, Reese JM, Hoke GM, Mandell JW, Roy SL, Visvesvara G, 2015. Disseminated Balamuthia mandrillaris infection. J Clin Microbiol 53: 30723076.

    • Search Google Scholar
    • Export Citation
  • 21.

    Visvesvara GS, Moura H, Schuster FL, 2007. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol 50: 126.

    • Search Google Scholar
    • Export Citation
  • 22.

    Schuster FL, Visvesvara GS, 2004. Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals. Int J Parasitol 34: 10011027.

    • Search Google Scholar
    • Export Citation
  • 23.

    Visvesvara GS, Schuster FL, Martinez AJ, 1993. Balamuthia mandrillaris, N. G., N. Sp., agent of amebic meningoencephalitis in humans and other animals. J Eukaryotic Microbiol 40: 504514.

    • Search Google Scholar
    • Export Citation
  • 24.

    Singh P, Kochhar R, Vashishta R, Khandelwal N, Prabhakar S, Mohindra S, Singhi P, 2006. Amebic meningoencephalitis: spectrum of imaging findings. Am J Neuroradiol 27: 12171221.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 857 210 0
Full Text Views 215 108 28
PDF Downloads 152 48 5
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Case Report: Encephalitis Caused by Balamuthia mandrillaris in a 3-Year-Old Iranian Girl

Moeinadin SafaviPathology Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Moeinadin Safavi in
Current site
Google Scholar
PubMed
Close
,
Vahid MehrtashPathology Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Vahid Mehrtash in
Current site
Google Scholar
PubMed
Close
,
Zohreh HabibiNeurosurgery Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Zohreh Habibi in
Current site
Google Scholar
PubMed
Close
,
Masoud MohammadpourPediatric Intensive Care Division, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

Search for other papers by Masoud Mohammadpour in
Current site
Google Scholar
PubMed
Close
,
Mohammad Taghi Haghi AshtianiPathology Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Mohammad Taghi Haghi Ashtiani in
Current site
Google Scholar
PubMed
Close
,
Maryam Sotoudeh AnvariPathology Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Maryam Sotoudeh Anvari in
Current site
Google Scholar
PubMed
Close
,
Nooshin ZaresharifiPathology Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Nooshin Zaresharifi in
Current site
Google Scholar
PubMed
Close
,
Milad ShafizadehNeurosurgery Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Milad Shafizadeh in
Current site
Google Scholar
PubMed
Close
, and
Bita JafarzadehPathology Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Bita Jafarzadeh in
Current site
Google Scholar
PubMed
Close

ABSTRACT

It is about half a century since free-living amoebae were recognized as pathogenic organisms, but there is still much we should learn about these rare fatal human infectious agents. A recently introduced causative agent of granulomatous amoebic encephalitis, Balamuthia mandrillaris, has been reported in a limited number of countries around the world. A 3-year-old girl was referred to our tertiary hospital because of inability to establish a proper diagnosis. She had been experiencing neurologic complaints including ataxia, altered level of consciousness, dizziness, seizure, and left-sided hemiparesis. The patient's history, physical examination results, and laboratory investigations had led to a wide differential diagnosis. Computed tomography (CT) scan and magnetic resonance imaging analyses revealed multiple mass lesions. As a result, the patient underwent an intraoperative frozen section biopsy of the brain lesion. The frozen section study showed numerous cells with amoeba-like appearances in the background of mixed inflammatory cells. Medications for free-living amoebic meningoencephalitis were administered. PCR assay demonstrated B. mandrillaris as the pathogenic amoeba. Unfortunately, the patient died 14 days after her admission. To our knowledge, this is the first report of B. mandrillaris meningoencephalitis in the Middle East and the first time we have captured the organism during a frozen-section study.

INTRODUCTION

It has been 50 years since the first cases of meningoencephalitis caused by free-living amoebae were reported.1,2 However, an effective cure for these amoeba-caused brain infections is yet to be found; cases of cerebral amoebiasis and death are still being reported all over the world.3 Timely diagnosis and a prompt treatment procedure can lead to a more favorable prognosis and a better chance of survival in patients.4 In addition to newer diagnostic approaches such as biochemical, immunological, and molecular methods that are not readily available in all medical centers, a more direct mode of identification can be adopted by examining cerebrospinal fluid and tissue biopsy samples, a common procedure all over the world.5 Pathologists may have the opportunity to detect these amoebae when examining samples that have been sent to the laboratory for a frozen-section procedure. In instances of amoebic brain infections, where the clinical and imaging symptoms are not exclusive, frozen samples might be sent to a pathology laboratory, although in many cases clinical physicians might have failed to include amoebic meningoencephalitis in their differential diagnoses.6 On these occasions, the ability to identify amoebae in frozen samples could be of great help in establishing an accurate diagnosis. We aim to introduce a patient infected with Balamuthia mandrillaris (B. mandrillaris) whose frozen-section sample was sent to our laboratory for intraoperative consultation.

CASE REPORT

A 3-year-old female toddler was referred to our center. At the time of admission, the patient was presented with a progressive loss of consciousness that had begun 3 days before her admission that followed vomiting, dizziness, and progressive ataxia that had begun 2 weeks before the admission. Furthermore, an episode of seizure was reported on the day of admission that was managed by rectal diazepam. She had no history of trauma or medication use.

The patient’s past medical history was unremarkable, and her immunization records were up-to-date. She lived in an urban area but she had occasional contact with freshwater and soil when she visited her grandfather house in a rural area.

In physical examination, she was febrile (38°C) with a heart rate of 135 beats/minute, a respiratory rate of 26 breaths/minute, and a blood pressure of 70/50 mmHg. She was unconscious with a Glasgow Coma Scale score of eight from 15. She had left-sided hemiparesis.

The laboratory data at the time of the admission and during the hospitalization are presented in Table 1.

Table 1

Laboratory data of a patient with amoebic encephalitis

Admission dateRangeMeanDate of passingLaboratory reference value
Complete blood countWBC (103/μL)6.996.5–10.538.38.224–10
Neutrophil, %6651.3–71687150–70
Lymphocyte, %2621–40.8332120–40
Monocyte, %7.62.2–9.25.14.43–8
Eosinophil, %0.40.4–9.44.93.60.5–5
Hemoglobin (g/dL)13.310.7–13.411.811.511–16
Platelet (103/μL)527290–527342388150–450
ESR-1 hour (mm/h)3624–98510–10
BiochemistryBlood glucose (mg/dL)14097–14012270–105
C-reactive protein (mg/L)33–5021< 6
Calcium (mg/dL)9.98.1–10.79.79.88.6–10.3
Magnesium (mg/dL)2.21.7–2.21.81.81.5–2.3
Phosphorus (mg/dL)3.73.2–5.24.15.23.1–6.0
Potassium (meq/L)3.82.8–4.93.92.83.7–5.9
Sodium (meq/L)131131–156142145135–145
Serum osmolality (mOsm/kg)268266–296276275–295
Blood urea nitrogen (mg/dL)124–126.255–20
Creatinine (mg/dL)0.60.3–0.70.450.50.3–0.7
Aspartate transaminase (U/L)3333–807310–31
Alanine transaminase (U/L)1111–423210–31
Alkaline phosphatase (U/L)378225–378301.5180–1,200
Ammonia (micromol/L)1311–51
Lactate (mg/dL)1414–22182–20
UrineSpecific gravity1.0131.005–1.0261.0161.025
Random urine sodium236.462–280273.5
Random urine osmolality (mOsm/kg)638188–70954350–1,400
Venous blood gasPH7.4607.325–7.5047.457.487
pCO222.822.8–60.140.530.1
PO2104.041.7–273153.5144.5
SO298.571.4–99.988.999.0
HCO3 (mmoL/L)16.216.2–31.623.522.322–26
Coagulation testsProthrombin time13.312.5–1413.312.5 (control time)
INR1.11.05–1.21.1
Partial thromboplastin time (sec)3232–3835Up to 65 (newborn)
Cerebrospinal fluid biochemistryGlucose77
Protein80
Cerebrospinal fluid microscopic examinationWBC3 (lymphocytes)
RBC0

WBC = white blood cell; RBC = red blood cell.

Her brain CT scan, which was conducted without contrast, demonstrated diffuse parenchymal hypodensity in the right temporoparietal lobe and scattered areas of white matter hypodensity in other areas of both cerebral hemispheres. These findings were indicative of mass lesion with peripheral edema (Figure 1).

Figure 1.
Figure 1.

Brain CT scan findings of the patient infected with Balamuthia mandrillaris.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 5; 10.4269/ajtmh.20-1257

Cerebrospinal fluid microscopic examination and chemical analysis showed normal cell count and an elevated protein level with a normal glucose level.

Anticonvulsant medication, broad-spectrum antibiotics (vancomycin, ceftriaxone, and ganciclovir), and supportive care such as mechanical ventilation were administered to the patient.

Magnetic resonance imaging of the brain showed large ill-defined infiltrative hyperintense lesions with hemorrhagic components, vasogenic edema in the right temporoparietal lobe with a restriction in diffusion-weighted sequence, and leptomeningeal enhancement after contrast injection. Similar lesions were detected in the left frontal and parietal cortex; periaqueductal, tectal plate; and middle cerebellar peduncle (Figure 2). Infectious lesions were suggested as the first diagnosis, and infiltrating malignancy, lymphoma, and glioma were suggested as other differential diagnoses.

Figure 2.
Figure 2.

Brain magnetic resonance imaging from the patient infected with Balamuthia mandrillaris. (A) FLAIR image shows hyperintensity in right parieto-occipital, left occipital, and left frontal lobes suggestive of edema. (B) T1-weighted image shows foci of T1 hyperintensity suggestive of hemorrhagic component.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 5; 10.4269/ajtmh.20-1257

The bone marrow aspiration and biopsy were unremarkable. The flow cytometry was unremarkable as well, and primary evaluations of the immune system were not suggestive of immune deficiency; however, total IgG and IgM levels were higher than normal. The serum level of IgG was 1,515 mg/dL, with a reference range of 295–1,156 mg/dL, and the serum level of IgM was 300 mg/dL, with a reference range of 37–184 mg/dL.

A small piece of brain white matter was extracted from the right temporoparietal brain lesion through biopsy. Touch preparation smear of fresh brain lesion that had been extracted intraoperatively revealed numerous amoeboid structures in the background of mixed inflammatory cells (Figure 3). The frozen-section procedure showed severe infiltration of mixed inflammatory cells, consisting of neutrophils, eosinophils, lymphocytes, and histiocytes, with an extension of inflammation through perivascular Virchow–Robin spaces.

Figure 3.
Figure 3.

Touch preparation smear of fresh brain lesion that had been extracted intraoperatively from a patient with encephalitis. Large amoeboid structures are seen in the background of mixed inflammatory cells (hematoxylin and eosin stain, magnification ×200).

Citation: The American Journal of Tropical Medicine and Hygiene 104, 5; 10.4269/ajtmh.20-1257

After immersing the sample in 10% neutral buffered formalin as fixative for 24 hours, hematoxylin and eosin stained slides were examined. Examination showed amoebic infiltration in the brain parenchyma as well as adjacent necrosis and mixed inflammatory cell infiltration (Figure 4).

Figure 4.
Figure 4.

Formalin-fixed tissue section from the patient infected with Balamuthia mandrillaris. (A) High magnification of histologic sections depicted amoebae with large nuclei with prominent central nucleoli (hematoxylin and eosin stain, magnification ×1,000). (B) Brain tissue histologic section showed amoebic infiltration in the parenchyma with adjacent necrosis and mixed inflammatory cells infiltration (hematoxylin and eosin stain, magnification ×100).

Citation: The American Journal of Tropical Medicine and Hygiene 104, 5; 10.4269/ajtmh.20-1257

Molecular analysis was conducted on the extracted DNA from brain tissue by a conventional PCR using previously designed primers for free-living pathogenic amoebae including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris (product sizes of 153, 180, and 171 bp were expected as positive results, respectively).7 Subsequently, the PCR product was run on 2% agarose gel, and only a 171-bp product was identified after transillumination, which confirmed the diagnosis of B. mandrillaris infection (Figure 5).

Figure 5.
Figure 5.

Agarose gel electrophoresis of conventional PCR products of the extracted DNA from brain tissue of the patient with free-living amoebic encephalitis. Lane 1: no product was detected using Naegleria fowleri–specific primer (negative), lane 2: a 171-bp product was detected using Balamuthia mandrillaris–specific primer (positive), lane 3: no product was detected using Acanthamoeba spp.–specific primer (negative).

Citation: The American Journal of Tropical Medicine and Hygiene 104, 5; 10.4269/ajtmh.20-1257

After confirming the diagnosis of amoebic encephalitis, treatment with rifampin and metronidazole in addition to miltefosine was initiated. Although treatment began immediately following the confirmation of the diagnosis, the patient, unfortunately, succumbed to her fulminant infection 14 days after her admission.

This case was considered for publication after receiving written consent from the patient’s legal guardian and approval of the Research Ethics Committee of Tehran University of Medical Sciences.

CASE DISCUSSION

Balamuthia mandrillaris is a pathogenic free-living amoeba that causes fatal meningoencephalitis in humans.8 It was first detected as a pathogen during the postmortem sampling from the brain of a dead mandrill baboon at the San Diego Zoo Wild Animal Park in the United States.9 Until now, about 200 cases of B. mandrillaris infection have been reported in humans, most of whom resided in the United States and Latin America, with some reports from Southeast Asia, India,10 Australia, Japan, and the Republic of Korea.1116

In the following report, we present the first case of a patient suffering from an infection caused by B. mandrillaris in Iran and in the Middle East. Environmental isolation of B. mandrillaris was documented in soil and hot springs in Iran; however, human infection by the pathogen has never been reported before in the region.17,18

Brain infection caused by B. mandrillaris, similar to Acanthamoeba spp. cases, manifests through chronic granulomatous infection. It attacks the body through skin inoculations or through respiratory tracts.19 In addition to brain involvement, dermatological and pulmonary manifestations are observed in these patients.20 Granulomatous amoebic encephalitis following B. mandrillaris infection is a chronic disease with slow progression, which can take anywhere between several weeks to several months.21 Neck stiffness, headache, fever, consciousness level decrease, nausea, and seizure are among its symptoms.8 Our patient complained of symptoms such as ataxia, vomiting, progressive decrease in the level of consciousness, and seizure.

Although B. mandrillaris has been observed in patients with healthy immune systems who suffered from no underlying diseases—such as the patient under discussion here—it is much more prevalent among HIV-infected patients, alcoholics, injection drug abusers, organ transplantation recipients, and patients under treatment by immunosuppressive drugs and radiotherapy.22

Clinical symptoms and microscopic findings are similar in B. mandrillaris and Acanthamoeba spp. infected patients; so much so that distinguishing these organisms by light microscopy is next to impossible, and to determine the amoeba type, molecular methods such as PCR or immunofluorescence antibody testing are necessary.21

Examining the cerebrospinal fluid seldom leads to a diagnosis. Our patient’s cerebrospinal fluid results were inconclusive as well, and only showed an increase in the protein level. Microscopic examinations in these patients usually exhibit a minimal opacity, an increase in white cell count with a high ratio of lymphocytes, a small decrease in glucose levels, and an increase in protein levels.3

A timely diagnosis depends on a strong suspicion on the part of the medical practitioner as well as the pathologist’s awareness of the organism’s morphology in a patient’s tissue samples. In many cases, the disease is only identified in postmortem examinations because of a lack of sufficient clinical knowledge in addition to a range of nonexclusive clinical and imaging symptoms.3,23,24 We had the opportunity to capture the B. Mandrillaris through the frozen-section procedure of the patient. She underwent intraoperative frozen-section examination of the brain lesion due to uncertainty of the diagnosis according to clinical, laboratory, and imaging findings. Despite determining the presence of amoeba-like cells, it was extremely challenging to establish the diagnosis.

Our case is a reminder of the fact that in instances where a conclusive diagnosis cannot be reached according to the available clinical and imaging evidence, clinical physicians and pathologists should not exclude rare differential diagnoses they have never encountered before.

ACKNOWLEDGMENTS

We would like to extend our gratitude to the personnel of the Pathology Laboratory of children’s medical center, Tehran, Iran, for their contribution. The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses.

REFERENCES

  • 1.

    Fowler M, Carter RF, 1965. Acute pyogenic meningitis probably due to Acanthamoeba sp.: a preliminary report. Br Med J 2: 740742.

  • 2.

    Apley J, Clarke S, Roome A, Sandry S, Saygi G, Silk B, Wirhurst G, 1970. Primary amoebic meningoencephalitis in Britain. Br Med J 1: 596599.

  • 3.

    Mungroo MR, Khan NA, Siddiqui R, 2020. Balamuthia mandrillaris: pathogenesis, diagnosis, and treatment. Expert Opin Orphan Drugs 8: 111119.

  • 4.

    Schuster FL, Visvesvara GS, 2004. Opportunistic amoebae: challenges in prophylaxis and treatment. Drug Resist Updat 7: 4151.

  • 5.

    da Rocha-Azevedo B, Tanowitz HB, Marciano-Cabral F, 2009. Diagnosis of infections caused by pathogenic free-living amoebae. Interdiscip Perspect Infec Dis 2009: 251406.

    • Search Google Scholar
    • Export Citation
  • 6.

    Capewell LG, Harris AM, Yoder JS, Cope JR, Eddy BA, Roy SL, Visvesvara GS, Fox LM, Beach MJ, 2014. Diagnosis, clinical course, and treatment of primary amoebic meningoencephalitis in the United States, 1937–2013. J Pediatr Infect Dis Soc 4: e68e75.

    • Search Google Scholar
    • Export Citation
  • 7.

    Qvarnstrom Y, Visvesvara GS, Sriram R, da Silva AJ, 2006. Multiplex real-time PCR assay for simultaneous detection of Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri. J Clin Microbiol 44: 35893595.

    • Search Google Scholar
    • Export Citation
  • 8.

    Jayasekera S, Sissons J, Tucker J, Rogers C, Nolder D, Warhurst D, Alsam S, White JML, Higgins EM, Khan NA, 2004. Post-mortem culture of Balamuthia mandrillaris from the brain and cerebrospinal fluid of a case of granulomatous amoebic meningoencephalitis, using human brain microvascular endothelial cells. J Med Microbiol 53: 10071012.

    • Search Google Scholar
    • Export Citation
  • 9.

    Visvesvara GS, Martinez AJ, Schuster FL, Leitch GJ, Wallace SV, Sawyer TK, Anderson M, 1990. Leptomyxid ameba, a new agent of amebic meningoencephalitis in humans and animals. J Clin Microbiol 28: 27502756.

    • Search Google Scholar
    • Export Citation
  • 10.

    Khurana S, Hallur V, Goyal M, Sehgal R, Radotra B, 2015. Emergence of Balamuthia mandrillaris meningoencephalitis in India. Indian J Med Microbiol 33: 298.

    • Search Google Scholar
    • Export Citation
  • 11.

    Gompf SG, Garcia C, 2019. Lethal encounters: the evolving spectrum of amoebic meningoencephalitis. IDCases 15: e00524.

  • 12.

    Yamanouchi K, Arima H, Sakamoto Y, Kanto K, Kasai K, Ito K, Inaba T, 2018. First report of the isolation of Balamuthia mandrillaris in the northern region of Japan. Parasitol Res 117: 28952900.

    • Search Google Scholar
    • Export Citation
  • 13.

    Siddiqui R, Khan NA, 2015. Balamuthia mandrillaris: morphology, biology, and virulence. Trop Parasitol 5: 1522.

  • 14.

    Lorenzo-Morales J, Cabello-Vílchez AM, Martín-Navarro CM, Martínez-Carretero E, Piñero JE, Valladares B, 2013. Is Balamuthia mandrillaris a public health concern worldwide? Trends Parasitol 29: 483488.

    • Search Google Scholar
    • Export Citation
  • 15.

    Botterill E, Yip G, 2011. A rare survivor of Balamuthia granulomatous encephalitis. Clin Neurol Neurosurg 113: 499502.

  • 16.

    Kum SJ, Lee HW, Jung HR, Choe M, Kim SP, 2019. Amoebic encephalitis caused by Balamuthia mandrillaris. J Pathol Transl Med 53: 327331.

  • 17.

    Niyyati M, Karamati SA, Lorenzo Morales J, Lasjerdi Z, 2016. Isolation of Balamuthia mandrillaris from soil samples in north-western Iran. Parasitol Res 115: 541545.

    • Search Google Scholar
    • Export Citation
  • 18.

    Latifi AR, Niyyati M, Lorenzo-Morales J, Haghighi A, Seyyed Tabaei SJ, Lasjerdi Z, 2016. Presence of Balamuthia mandrillaris in hot springs from Mazandaran province, northern Iran. Epidemiol Infect 144: 24562461.

    • Search Google Scholar
    • Export Citation
  • 19.

    Kiderlen AF, Laube U, 2004. Balamuthia mandrillaris, an opportunistic agent of granulomatous amebic encephalitis, infects the brain via the olfactory nerve pathway. Parasitol Res 94: 4952.

    • Search Google Scholar
    • Export Citation
  • 20.

    Schafer KR, Shah N, Almira-Suarez MI, Reese JM, Hoke GM, Mandell JW, Roy SL, Visvesvara G, 2015. Disseminated Balamuthia mandrillaris infection. J Clin Microbiol 53: 30723076.

    • Search Google Scholar
    • Export Citation
  • 21.

    Visvesvara GS, Moura H, Schuster FL, 2007. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol 50: 126.

    • Search Google Scholar
    • Export Citation
  • 22.

    Schuster FL, Visvesvara GS, 2004. Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals. Int J Parasitol 34: 10011027.

    • Search Google Scholar
    • Export Citation
  • 23.

    Visvesvara GS, Schuster FL, Martinez AJ, 1993. Balamuthia mandrillaris, N. G., N. Sp., agent of amebic meningoencephalitis in humans and other animals. J Eukaryotic Microbiol 40: 504514.

    • Search Google Scholar
    • Export Citation
  • 24.

    Singh P, Kochhar R, Vashishta R, Khandelwal N, Prabhakar S, Mohindra S, Singhi P, 2006. Amebic meningoencephalitis: spectrum of imaging findings. Am J Neuroradiol 27: 12171221.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Moeinadin Safavi or Vahid Mehrtash, Pathology Department, Children’s Medical Center, No. 62, Dr Gharib St., Tehran 1419733151, Iran. E-mails: moein.safavi@gmail.com or vahid.mehrtash68@gmail.com

Authors’ addresses: Moeinadin Safavi, Vahid Mehrtash, Mohammad Taghi Haghi Ashtiani, Maryam Sotoudeh Anvari, Nooshin Zaresharifi, and Bita Jafarzadeh, Pathology Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran, E-mails: moein.safavi@gmail.com, vahid.mehrtash68@gmail.com, ashtiani20@yahoo.com, maryamsotoudeh2006@gmail.com, nooshin_zaresharifi@yahoo.com, and bta_jafa@yahoo.com. Zohreh Habibi and Milad shafizadeh, Neurosurgery Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran, E-mails: zohreh_h56@yahoo.com and milad_shafizadeh@yahoo.com. Masoud Mohammadpour, Pediatric Intensive Care Division, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran, E-mail: mmpour@tums.ac.ir.

Save