title: Combined drug therapy in the management of granulomatous amoebic encephalitis due to Acanthamoeba spp., and Balamuthia mandrillaris.
abstract: Granulomatous amoebic encephalitis (GAE) is caused by two protist pathogens, Acanthamoeba spp., and Balamuthia mandrillaris. Although rare, it almost always results in death. In the present study, amoebae were treated with various combinations of clinically-approved drugs, targeting vital cellular receptors and biochemical pathways. The results revealed that among the seven different combinations tested, three proved highly effective against both Acanthamoeba castellanii as well as B. mandrillaris at a concentration of 100μM. These combinations included (i) prochlorperazine plus loperamide; (ii) prochlorperazine plus apomorphine; and (iii) procyclidine plus loperamide. In viability assays, none of the drug-treated amoebae emerged as viable trophozoites, suggesting irreversible amoebicidal effects. Four combinations of drugs tested showed varied potency against A. castellanii and B. mandrillaris at 100μM. The combination of haloperidol and loperamide was highly effective against A. castellanii at 100μM, but potent effects against B. mandrillaris were observed only at 250μM. Digoxin and amlodipine were effective against A. castellanii and B. mandrillaris at 100μM and 250μM, respectively. In contrast, the combination of apomorphine and haloperidol was effective against B. mandrillaris and A. castellanii at 100μM and 250μM, respectively. At 100μM, the combination of procyclidine and amiodarone was effective against neither A. castellanii nor B. mandrillaris. In this case, amoebicidal properties were observed at 750μM for A. castellanii, and 950μM for B. mandrillaris. As these drugs are used clinically against non-communicable diseases, the findings reported here have the potential to be tested in a clinical setting against amoebic encephalitis caused by A. castellanii and B. mandrillaris.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Huma
authors.initials: H
authors.lastname: Kulsoom
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Abdul Mannan
authors.initials: AM
authors.lastname: Baig
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Ruqaiyyah
authors.initials: R
authors.lastname: Siddiqui
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan. Electronic address: Naveed5438@gmail.com.
authors.forename: Naveed Ahmed
authors.initials: NA
authors.lastname: Khan
mesh_terms: D048248:Acanthamoeba castellanii / Q000187:drug effects*; D000562:Amebiasis / Q000188:drug therapy* / Q000469:parasitology; D000563:Amebicides / Q000494:pharmacology*; D000638:Amiodarone / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D059611:Balamuthia mandrillaris / Q000187:drug effects*; D001921:Brain / Q000098:blood supply; D002478:Cells, Cultured; D004077:Digoxin / Q000494:pharmacology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004660:Encephalitis / Q000188:drug therapy* / Q000469:parasitology; D042783:Endothelial Cells / Q000166:cytology; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008139:Loperamide / Q000494:pharmacology; D055806:Microvessels / Q000166:cytology; D011346:Prochlorperazine / Q000494:pharmacology; D011352:Procyclidine / Q000494:pharmacology
chemical_list: D000563:Amebicides; D017311:Amlodipine; D008139:Loperamide; D004077:Digoxin; D011352:Procyclidine; D006220:Haloperidol; D001058:Apomorphine; D000638:Amiodarone; D011346:Prochlorperazine
keywords: Acanthamoeba castellanii; Amoebicidal; Balamuthia mandrillaris; Clinical drugs; Encephalitis; In vitro