Acanthamoeba Enhanced Heterogeneously Or in a Ringlike Manner

Acanthamoeba Enhanced Heterogeneously Or in a Ringlike Manner

and Coccidioides spp. Severe immunosuppression with a Successful CD4+ lymphocyte count of 182 cells/μL made HIV infec- tion probable, but HIV testing results were negative. Crani- Treatment of al CT showed multiple small enhancing lesions in cerebral cortex and underlying white matter, pons, midbrain, and Disseminated around most of the cisterns. On magnetic resonance imag- ing (MRI), the lesions appeared as high T2 signal areas that Acanthamoeba enhanced heterogeneously or in a ringlike manner. These sp. Infection with fi ndings were compatible with the diagnosis of meningoen- cephalitis with intracerebellar abscess formation. Miltefosine Cerebrospinal fl uid (CSF) obtained through lumbar puncture was negative for Toxoplasma gondii, Encephali- Alexander C. Aichelburg, Julia Walochnik, tozoon cuniculi, and Enterocytozoon bieneusi by PCR and Ojan Assadian, Helmut Prosch, Andrea Steuer, for Trypanosoma gambiense by indirect hemagglutination Gedeon Perneczky, Govinda S. Visvesvara, assay. Staining and antigen testing (enzyme immunoas- Horst Aspöck, and Norbert Vetter say) for Cryptococcus neoformans was negative, as was We report on an HIV-negative but immunocompromised Treponema pallidum antibody testing. No viruses (herpes patient with disseminated acanthamoebiasis, granuloma- simplex 1 and 2, varicella zoster, enterovirus) could be tous, amoebic encephalitis, and underlying miliary tuber- detected by PCR. Cultures were negative for aerobic/ culosis and tuberculous meningitis. The patient responded anaerobic bacteria and fungi. ZN staining detected acid-fast favorably to treatment with miltefosine, an alkylphospho- bacilli that were confi rmed to be nonresistant M. tubercu- choline. The patient remained well with no signs of infection losis after culture for 38 days. PCR for M. tuberculosis was 2 years after treatment cessation. positive. An Acanthamoeba–specifi c PCR (1) and DNA sequencing of the PCR product showed Acanthamoeba 25-year-old man from India, who had been living in genotype T2 (corresponding to group III). High immu- A Austria for 7 years and had no previous history of ma- noglobulin (Ig) G (2,000) and IgM (1,000) titers against jor illnesses, was brought by ambulance to the hospital for Acanthamoeba spp. could be demonstrated serologically. dyspnea, cough, fever, and weight loss. During neurologic The organism could not be grown in culture (2). examination, a hearing impairment was suspected. The Two skin-biopsy specimens were obtained; they patient was unable to walk because of severe ataxia. Skin showed necrotizing granulomatous infl ammation affect- examination showed several necrotic ulcers with purulent ing the entire dermal thickness and subcutis. Stains and discharge and black eschars, measuring 0.5 cm to 3 cm, culture were negative for Mycobacterium spp., fungi, and located on the skull, back, neck, and arms (Figure 1, pan- Acanthamoeba spp. but the specimens tested positive for els A and B). Miliary tuberculosis (TB) of the lungs, liver, acanthamoebae by PCR. In addition to a standard tuber- spleen, and kidneys was suspected on the basis of chest ra- culostatic 5-drug regimen including intravenous strep- diography and computed tomography (CT) of chest and ab- tomycin, empiric anti-amoebic treatment based on data domen. Ziehl-Nielsen (ZN) staining for acid-fast bacilli in retrieved from the few case reports of successful treat- sputum, bronchial secretions, and lavage obtained through ment of systemic Acanthamoeba infections (3–5) was ini- bronchoscopy was negative. PCR for Mycobacterium tu- tiated. The regimen included a combination of parenteral berculosis in bronchial secretions and serum was positive. trimethoprim/sulfamethoxazole (later changed to oral sul- Culture on Loewenstein agar resulted in growth of nonre- fadiazine) and parenteral fl uconazole. CSF samples drawn sistant M. tuberculosis after 31 days. Blood cultures were 2 and 8 weeks after initiation of therapy tested negative negative for aerobic/anaerobic bacteria, mycobacteria, and for mycobacteria by ZN staining, PCR, and culture but fungi. Results of serologic tests were negative for Asper- remained positive for Acanthamoeba sp. by PCR. gillus, Candida, Cryptococcus, Histoplasma, Blastomyces, Transbronchial lung biopsy specimens from a second bronchoscopy performed 1 month after admission tested Author affi liations: Otto Wagner Hospital, Vienna, Austria (A.C. negative for mycobacteria by ZN staining, PCR, and culture Aichelburg, A. Steuer, N. Vetter, H. Prosch); Medical University of but positive for Acanthamoeba sp. by PCR. Acanthamoe- Vienna, Vienna (J. Walochnik, O. Assadian, H. Aspöck); Kranke- bae could not be cultivated from bronchial secretions or bi- nanstalt Rudolfstiftung, Vienna (G. Perneczky); and Centers for opsy sample; immunostaining that used a polyclonal rabbit Disease Control and Prevention, Atlanta, Georgia, USA (G.S. Vis- anti–A. castellanii (genotype T4) serum was negative. vesvara) Within 12 weeks after initiation of tuberculostatic ther- DOI: 10.3201/eid1411.070854 apy, complete clinical and radiologic resolution of miliary Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 11, November 2008 1743 DISPATCHES Figure 1. Ulcer with purulent discharge located on the skull (A) and on the back at fi rst examination (B) and 17 days after topical treatment with miltefosine was initiated (C). TB of lungs, liver, spleen, and kidneys could be achieved, On MRI scan, performed 8 weeks after admission, and the CD4+ lymphocyte count increased to 421 cells/μL. the brain abscess located in the right cerebellopontine Nevertheless, the neurologic status of the patient deterio- angle had reached a size of 4 cm, leading to a rise of in- rated, even after liposomal amphotericin B and fl ucytosine tracranial pressure that could not be controlled by intra- had been added to the regimen. Consecutive cranial CT and venous administration of mannitol and dexamethasone. cranial MRI scans demonstrated progression of the lesions, Nine weeks after admission, an Ommaya Reservoir was with the biggest lesion (1.8 cm in diameter) located in the implanted, and up to 100 mL of CSF was drained daily right cerebellopontine angle and cerebellum (Figure 2, pan- to control intracranial pressure. Amikacin, the only other els A and B). drug that seemed to have some effi cacy against Acan- As skin lesions were also gaining size, treatment with thamoeba spp. in vitro (2), was given intrathecally and miltefosine, a phosphocholine analog that has proven suc- intravenously (20 mg/2 mL intrathecally + 1,000 mg/d cessful in treating visceral leishmaniasis (6) and is highly intravenously) in place of the streptomycin originally in- effective against acanthamoebae in vitro (7,8), was initi- cluded in the 5-drug regimen, under continuous monitor- ated topically as a solution, 60 mg/mL, 1 drop applied ing of peak and trough levels in CSF and blood. A surgi- directly to each skin lesion 2 times a day. After dramatic cal excision of the abscess was performed 3 weeks later. improvements of the skin lesions were observed within The histologic specimen of this lesion was again positive only 3 weeks (Figure 1, panel C), our patient began pero- for Acanthamoeba sp. by PCR but negative by immunos- ral miltefosine 100 mg/day (2.5 mg/kg); all other drugs taining. Neither acanthamoebae nor mycobacteria could except the tuberculostatic 5-drug regimen were stopped. be grown in culture, despite positive ZN staining of the specimen (Table). Under ongoing therapy with miltefosine, amikacin, and 4 more tuberculostatic drugs, the patient improved. The remaining cerebral lesions regressed in size. Healing of the dermal lesions was achieved within 6 weeks; topical miltefosine treatment was stopped after 8 weeks. Intrathe- cal amikacin and oral miltefosine therapy was halted 6 and 12 weeks, respectively, after initiation. A 2-drug tuberculostatic therapy was maintained for 1 year after the patient had been discharged from hospi- tal. Two more lumbar punctures were performed 23 and 29 weeks after the patient was initially evaluated. For the fi rst time neither mycobacteria nor acanthamoebae could Figure 2. Axial brain magnetic resonance imaging at the level of the be detected. CT scan and MR imaging of the brain showed cerebellum performed 6 weeks after initial consultation. A) Contrast- no major pathology. Serologic titers, which had gradually enhanced T1 weighted image showing several ring-enhancing declined after initiation of miltefosine therapy, reached lesions in the right cerebellar hemisphere and the right cerebellar peduncle. B) The corresponding fl uid attenuation inversion recovery normal levels. The patient was transferred to a specialized image illustrates the extensive perifocal edema exerting a severe neurologic institution for rehabilitation. Ataxia and hearing mass effect through compression and displacement of the fourth impairment did not improve. During the next 24 months, ventricle with consecutive enlargement of the lateral ventricle. the patient was regularly seen in our outpatient clinic. No 1744 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 11, November 2008 Treatment of Disseminated Acanthamoeba sp. Infection Table. Diagnosis of Acanthamoeba sp. and mycobacterial infection* Organism, patient specimen Microscopy PCR Culture Immunostaining Serology Acanthamoeba sp. Cerebrospinal fluid Negative Positive Negative NA NA Brain biopsy Negative Positive Negative Negative NA Bronchial secretions Negative Positive Negative NA NA Lung biopsy Negative Positive

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