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  • Case report
  • Open Access
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Lethal outcome of granulomatous acanthamoebic encephalitis in a man who was human immunodeficiency virus-positive: a case report

Journal of Medical Case Reports201812:201

https://doi.org/10.1186/s13256-018-1734-8

  • Received: 4 December 2017
  • Accepted: 3 June 2018
  • Published:
Open Peer Review reports

Abstract

Background

Acanthamoeba species can cause disseminating infections in immunocompromised individuals.

Case presentation

Here, we report a case of granulomatous acanthamoebic encephalitis with a lethal outcome in a 54-year-old German man who was human immunodeficiency virus-positive. The diagnosis was based on symptoms of progressive neurological deficits, including sensorimotor paralysis of his right leg and deteriorating alertness. Due to the rapid course and rather late diagnosis of the infection, effective treatment could not be applied and he died 12 days after hospital admission.

Conclusions

To the best of our knowledge, this is the second case of granulomatous acanthamoebic encephalitis reported within Germany. Our case highlights the importance of early diagnosis of granulomatous acanthamoebic encephalitis to prevent fatal outcome.

Keywords

  • Acanthamoeba species
  • GAE
  • HIV
  • Miltefosine treatment

Background

Acanthamoeba species are free-living amoeboid single-cell organisms that naturally occur in water and soil, but can also be found in human-made habitats all over the world [15]. Acanthamoeba species are known as causal agents of disseminating infections in immunocompromised individuals (for example, human immunodeficiency virus (HIV) positive, immunosuppressive therapy), including granulomatous acanthamoebic encephalitis (GAE) [68]. GAE is a rare but mostly fatal disease [6, 9]. Furthermore, Acanthamoeba species can cause so-called Acanthamoeba keratitis; Acanthamoeba keratitis mainly occurs in contact lens wearers and increasing casualties have been reported in the past decades [10, 11].

Case presentation

In December 2010, a 54-year-old German man presented to our hospital with suspected cerebral toxoplasmosis. HIV infection had been diagnosed in 1995. He had received a triple-combination highly active antiretroviral therapy (HAART) of lopinavir, lamivudine, and tenofovir, which was stopped in 2009 due to intolerable side effects (diarrhea, nausea).

Over a period of 5 days, progressive neurological deficits including sensorimotor paresis of his right leg and deterioration of alertness occurred.

On clinical and neurological examination, he showed high-grade flaccid paralysis of his right lower limb with preserved muscle proprioceptive reflexes and positive Babinski sign.

Magnetic resonance imaging (MRI) on day 1 revealed a periventricular hyperintense lesion with perifocal edema in the left parieto-occipital region which continued to progress as shown in imaging on day 6 (Fig. 1).
Fig. 1
Fig. 1

Magnetic resonance imaging on day 6 with pronounced perifocal edema in the left parieto-occipital region

Table 1

Results of diagnostics in cerebrospinal fluid, blood, serum, and bronchoalveolar lavage

Disease/Pathogen

Test

Result

Human immunodeficiency virus

Liquor, PCR

Serum, PCR

Positive (670,000 copies/mL)

Positive (2,200,000 copies/mL)

Toxoplasmosis

Immunohistochemistry

Negative

Measles

Liquor,

Serum, IgG

Serum, IgM

Negative

Positive (IgG 1900 U/L)

Negative

Borrelia

Liquor, IgG

Negative

Syphilis

Liquor, TPPA

Negative

FSME

Liquor, IgG

Serum, IgG/IgM

Negative

Both negative

Cryptococcus

Liquor, antigen screen

Negative

HSV 1/2

Liquor, DNA

BAL, DNA

Negative

Positive

VZV (herpes zoster)

Liquor, PCR

Negative

CMV

Liquor, PCR

BAL, PCR

Negative

Negative

EBV

Liquor, PCR

Negative

JCV (human polyomavirus)

Liquor, PCR

BAL, PCR

Negative

Negative

HCV

Serum, PCR

Negative

Enterococcus

BAL

Positive

BAL bronchoalveolar lavage, CMV cytomegalovirus, EBV Epstein–Barr virus, FSME tick-borne encephalitis, HCV hepatitis C virus, HSV herpes simplex virus, JCV John Cunningham virus, PCR polymerase chain reaction, TPPA Treponema pallidum particle agglutination assay, VZV varicella zoster virus

Blood laboratory values on day 1 revealed leukopenia (3.4/nL) and thrombocytopenia (101/nL).

No fungi, viruses (except HIV-1), or bacteria were detected in blood and cerebrospinal fluid cultures nor in serologic tests and polymerase chain reaction (PCR; Table 1). Prophylactic antibiotic treatment (antifungal, antiviral, antibacterial, and antiprotozoal) was administered as listed in Table 2. Immunocytology of cerebrospinal fluid on day 5 showed a reduced absolute lymphocyte count (640/μL), reduced T-helper cells (CD3, 365/μL), and a pathologic CD4/CD8 ratio.
Table 2

Initial antibiotic treatment

Medication

Daily dose

Route of administration

Pyrimethamine

37.5 mg

Orally

Fluconazole

2 × 100 mg

Intravenously

Clindamycin

1800 mg

Intravenously

Ceftriaxone

2 g

Intravenously

Aciclovir

3 × 750 mg

Intravenously

Meropenem

3 × 1 g

Intravenously

Due to pathologic MRI findings, a stereotactic biopsy was performed on day 9. Histopathological results obtained on day 12 showed extensive tissue necrosis with mixed inflammatory infiltrates. Cysts of Acanthamoeba species were detected in periodic acid–Schiff (PAS) and Grocott stainings of brain specimens. Mononuclear trophozoites could be identified in hematoxylin and eosin (HE) and PAS stainings (Fig. 2). Furthermore, additional immunohistochemical staining was performed using an antibody specific to Acanthamoeba species (from rabbits immunized with Acanthamoeba genotype 4; Fig. 3).
Fig. 2
Fig. 2

Acanthamoeba species. a Cyst with periodic acid–Schiff staining and b rounded trophozoite with hematoxylin and eosin staining (× 1000)

Fig. 3
Fig. 3

Immunostained Acanthamoeba trophozoite with characteristic nucleus and prominent contractile vacuole (Multichannel × 400)

Electroencephalography (EEG) on day 6 showed a lesion located in his left frontotemporal region with epileptic patterns in the left parietal lobe. He developed relapsing tonic-clonic seizures which normalized by day 8 following anticonvulsive therapy with valproic acid, methohexital, levetiracetam, and clonazepam.

MRI on day 11 revealed a new and massive ubiquitous subarachnoid hemorrhage, a beginning compression, a generalized cerebral swelling, and, an expanding left parietal periventricular lesion.

Due to the unfavorable prognosis, we, in agreement with his relatives, took no further intensive care measures. He died on day 12 after hospital admission.

Since histopathology did not reveal GAE before day 12, a specific treatment against GAE (for example, miltefosine-based combination therapy) had not been initiated.

Discussion and conclusions

Infections with Acanthamoeba species are rare; hence, clinicians, pathologists, and clinical microbiologists are generally unfamiliar with these diseases. The vast majority of cases of GAE reported in the literature have been diagnosed postmortem [12, 13]. To the best of our knowledge, this is the second case of GAE reported within Germany.

The current case emphasizes the importance of early diagnosis of GAE. Microscopy of centrifuged fresh cerebrospinal fluid is recommended to diagnose Acanthamoeba trophozoites, yet these may be misdiagnosed as macrophages. Histological staining enables a clear differentiation of trophozoites from other cells [13]. Today, PCR is the method of choice for rapid, specific, and sensitive detection of Acanthamoeba species in clinical samples and also allows genotype identification [14] as well as diagnosis from formaldehyde-fixed samples [15, 16]. Early diagnosis and specific treatment is only possible if an infection with Acanthamoeba species is suspected early [13].

Today, there is no standard regimen for the treatment of GAE, but several successfully treated cases have been reported. For example: a patient with acquired immunodeficiency syndrome (AIDS) was treated with a combination of fluconazole and sulfadiazine [17]; two immunocompetent children received trimethoprim-sulfamethoxazole, rifampicin, and ketoconazole [18]; another immunocompetent woman was treated with fluconazole, rifampicin, and metronidazole [13]; a young immunocompromised man with underlying tuberculosis was treated with miltefosine, amikacin, and tuberculostatic drugs [8]; and, another young immunocompetent man was treated with rifampicin, moxifloxacin, and fluconazole [19]. The Centers for Disease Control and Prevention (CDC) recommends administration of miltefosine based on 26 reported cases in which a miltefosine-including regimen seemed to offer a survival advantage [20].

Our patient was prophylactically treated with antibiotics, covering antifungal, antiviral, antibacterial, and antiprotozoal activity. He did not receive a miltefosine-based combination therapy. As pointed out earlier, most reported cases of GAE have been diagnosed postmortem [12] and all successfully treated cases were detected early and mainly by chance. Therefore, both awareness and an early and specific diagnosis followed by an immediate start of a miltefosine-based treatment seem of crucial importance for the successful treatment of GAE. Acanthamoeba species should be considered in patients with unclear encephalitis, particularly in immunocompromised patients.

Abbreviations

AIDS : 

Acquired immunodeficiency syndrome

CDC: 

Centers for Disease Control and Prevention

EEG: 

Electroencephalography

GAE: 

Granulomatous amoebic encephalitis

HAART: 

Highly active antiretroviral therapy

HE: 

Hematoxylin and eosin

MRI: 

Magnetic resonance imaging

PAS: 

Periodic acid–Schiff

PCR: 

Polymerase chain reaction

Declarations

Availability of data and materials

All data (pictures) generated or analyzed during this study are included in this published article.

Authors’ contributions

SG treated the patient, collected the data, and wrote the manuscript. JW performed histological staining and took Multichannel pictures. FP provided PAS-stained and HE-stained pictures. SS treated the patient and contributed with analysis and interpretation of data. FE made substantial contributions to the interpretation of data and manuscript review. All authors read and approved the final manuscript.

Ethics approval and consent to participate

No ethics approval, but patient’s relatives consented (see below).

Consent for publication

Written informed consent was obtained from the patient’s next of kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

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Authors’ Affiliations

(1)
Division of Clinical Toxicology & Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany
(2)
Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Specific Prophylaxis and Tropical Medicine, Kinderspitalgasse 15, 1090 Vienna, Austria
(3)
Institute of Pathology, Academic Clinic Munich-Schwabing, Kölner Platz 1, 80804 Munich, Germany
(4)
Department of Cardiology, Pneumology and Internal Intensive Medicine, Academic Clinic Munich-Schwabing, Kölner Platz 1, 80804 Munich, Germany

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Copyright

© The Author(s). 2018

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