key: cord-0746732-36wjr7hf authors: Siripurapu, Govinda; Samad, Sameer Abdul; Fatima, Saman; Wig, Naveet; Srivastava, M.V. Padma title: SUCCESSFUL MANAGEMENT OF POST-COVID-19 ACANTHAMOEBIC ENCEPHALITIS date: 2021-07-22 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.07.046 sha: 1c77e40f2f76eb5028e868bc094a7794add2f904 doc_id: 746732 cord_uid: 36wjr7hf Acanthamoebic encephalitis is a rare and highly fatal disease that has no standard management protocol. Coronavirus disease 2019 (COVID-19) causes immune dysfunction and may predispose patients to this infection. The present study describes successful management of acanthamoebic encephalitis in a young male who recently recovered from COVID-19 using a combination of medical and surgical approaches. A combination of miltefosine with other agents with trophicidal and cysticidal activities should be used in the regimen. Surgical excision of the abscess should be undertaken whenever feasible. The present study reports a case of acanthamoebic encephalitis in a patient after recovery from COVID-19 that was successfully managed with a combination of the medical and surgical approaches. A 32-year-old man with no previously known comorbidities was diagnosed with moderate COVID-19 and received a five-day course of methylprednisolone and oxygen supplementation along with other supportive measures; the patient remained asymptomatic for six weeks. One day, the patient nearly got into an accident while driving because he was unable to correctly estimate the distance to a nearby vehicle. Three days after the incident, the patient developed a weakness of the right side of the body and facial deviation to the left, which rapidly progressed to a maximum within four days. Magnetic resonance imaging (MRI) of the brain showed a multifocal variable-sized ring and enhancing nodular lesions in the bilateral hemispheres ( Figure 1A ). Cerebrospinal fluid (CSF) analysis showed 4 lymphocytes per microliter and normal levels of the protein and sugar. The tests for bacterial, fungal, and tubercular infections were negative. The patient had a family history of diabetes mellitus, and HbA1c at admission was 8.61 g/dL. The tests for HIV-1 and -2 were negative. Over the next 15 days, the patient also developed left hemiparesis, followed by severe diffuse headache, vomiting, and a sensorial decline. Urgent decompressive craniectomy was performed. 5 Histopathological examination of the brain biopsy revealed the presence of necrotic tissue with inflammation and numerous amoebic trophozoites ( Figure 1B) . The tests for serum anti-Toxoplasma IgG and anti-herpes simplex virus (HSV) IgM were positive. However, Toxoplasma cysts or tachyzoites were not detected by histopathological examination, and the polymerase chain reaction (PCR) test for HSV in the CSF was negative. Miltefosine was added to the regimen at a dose of 50 mg thrice daily and was continued for four weeks. The patient did not show any further improvement over the next four weeks; contrastenhanced MRI of the brain was repeated, and the images showed an organizing abscess within central necrotic tissue and a surrounding enhancing rim ( Figure 1C) . A surgical procedure was performed to excise the abscess. Another histopathological examination of the brain biopsy revealed multiple acanthamoeba trophozoites, as confirmed by PCR. 7 After debridement, the sensorium of the patient gradually improved, and repeated imaging of the brain revealed a significant decrease in the mass effect ( Figure 1D ). After 15 weeks of hospital stay, the patient was finally discharged in a hemodynamically stable tracheostomized state with a Glasgow coma score of E4VtM6 on five anti-amoebic drugs, including flucytosine, fluconazole, rifampicin, azithromycin, and albendazole. The patient is being followed up by telephone due to the current COVID-19 surge. The patient is doing well at home eight weeks after discharge from the hospital. Amphotericin B is the cornerstone therapy against Naegleria in primary amoebic meningoencephalitis; however, there is little evidence for the use of this drug in acanthamoebic encephalitis. The drug has been discontinued after the presence of the etiological agent in the patient was confirmed by PCR. Considering the changes detected by MRI of the brain before and after the treatment with miltefosine, the drug apparently had the maximum effect in the studied case. Acanthamoeba castellani is highly sensitive to miltefosine in vitro, whereas Acanthamoeba lugdunensis and other species have low sensitivity to the drug even at higher concentrations ([12]Mrva et al., 2011). The concentration of miltefosine achieved in the human brain parenchyma is yet to be determined. The lesions began to organize following the combination medical therapy with miltefosine; however, the patient's sensorium further improved only after surgical excision of the abscess. This approach has been rarely used previously in the survivors but should be considered whenever feasible. 9 Acanthamoebic encephalitis should be considered when patients present with neurological deficits and brain lesions, which rapidly progress and cause mass effects. The best approach to the management involves a combination of medical and surgical interventions. Randomized clinical trials are needed to standardize the treatment for acanthamoebic encephalitis, and the role of COVID-19 in predisposition of the patients to this infection needs to be evaluated. Miltefosine: A Miracle Drug for Meningoencephalitis Caused by Free-Living Amoebas Effect of caspofungin on trophozoites and cysts of three species of Acanthamoeba Acanthamoeba castellanii: High antibody prevalence in racially and ethnically diverse populations Article 827 (2020) Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) Drug discovery against acanthamoeba infections: 11 Present knowledge and unmet needs Pharmacokinetics of 18F-labeled fluconazole in healthy human subjects by positron emission tomography Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living Immunopathogenicity of acanthamoeba spp. In the brain and lungs Amoebas from the genus Acanthamoeba and their pathogenic properties The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway Weak cytotoxic activity of miltefosine against clinical isolates of Acanthamoeba spp The Role of Type I Interferons in the Pathogenesis and Treatment Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment We thank Dr Manish Soneja for his valuable input in medical therapy and Dr Manmohan Singh for skillful surgical intervention. Next of kin of the patient described in the study gave consent to publish the history and images of the investigation anonymously. The authors declare that they have no known competing interests that influenced the work reported in this paper. This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.