Utilização de um fragmento variável de cadeia simples (scFv) anti-Glicosilfosfatidilinusitol (GPI) como potencial tratamento para malária cerebral em modelo murino

Abstract

Malaria is an infectious disease caused by a protozoa of the Plasmodium genus, responsible for the deaths of hundreds of thousands of people every year. Cerebral malaria mainly affects children and is the reason for most deaths and sequelae of the disease. Currently, some treatment protocols are available which act mostly on parasite replication, however, for neurological cases, there is still a need for treatments with higher efficiency, requiring studies of new drugs. Based on that, our goal was to determine the potential therapeutic effect of a single-chain variable (scFv) anti-Glycosylphosphatidylinusitol (GPI) in Plasmodium berghei infection in a preclinical trial. For this, C57BL/6 mice were infected with Plasmodium berghei-ANKA (P. berghei - ANKA) and treated with scFv anti-GPI on days 0, 3 and 6 post infection, the infected controls were treated with saline solution (PBS ) and uninfected controls treated with scFv or PBS. The animals were evaluated for morbidity and mortality scores, body weight, parasitemia and blood count. Our results demonstrate that treatment with anti-GPI scFv in animals infected with P. berghei - ANKA rescued 70% of the challenged mice, promoted recovery from initial weight loss caused by the infection, completely eliminated neurological signs of cerebral malaria (CM), as well as the systemic signs of the disease, reduced parasitemia and improved blood parameters in these animals, showing an important therapeutic effect in the pathology of experimental cerebral malaria (ECM).