A Systematic Review on Prototheca spp. Infections in the Human Central Nervous System and Evaluation of Therapeutic Drug Approaches

Background and Aim: Prototheca is a genus of unicellular, non-photosynthetic microalgae found in diverse environments, including water, soil, and the intestinal microbiota of animals and humans. They are the only algae pathogenic to humans. Infections of the Central Nervous System (CNS) by Prototheca spp. are rare but severe. This research aims to systematically review the pathogenic potential of Prototheca spp. as CNS infectious agents in humans, identify underlying conditions that contribute to disease development, and evaluate the most suitable drug therapy alternatives for this clinical condition. Methods: A systematic review was conducted using PubMed, SciELO, and Google Scholar databases. Search terms included "Prototheca," "Central Nervous System," "meningitis," "encephalitis," "meningoencephalitis," and "brain." Manuscripts published in English, Portuguese, Spanish, and Russian from 1981 to 2024 were reviewed. Results: The review identified 15 case reports of CNS infections by Prototheca spp. described in 14 scientific articles. Three species were implicated: Prototheca wickerhamii, Prototheca zopfii, and Prototheca trispora, with Prototheca wickerhamii being the most prevalent (66.6%). Only four patients were immunocompromised. A significant association was found between hydrocephalus in children and vulnerability to CNS protothecosis, accounting for 20% of cases. All fatal cases occurred in immunocompromised patients. Resistance profile analysis showed 88.9% susceptibility to amphotericin B and susceptibility to two triazoles (voriconazole and isavuconazole) that cross the blood-brain barrier. Conclusion: Immunodeficiency is not a prerequisite for susceptibility to CNS infections by Prototheca spp., but it predicts an unfavorable prognosis. The most promising treatments are combinations of amphotericin B with tetracyclines or isavuconazole. Dosage adjustments are necessary due to the toxicity of long-term algicidal antifungal treatments, posing a challenge in managing drug therapy.