Ascorbic acid co-administration with artemisinin based combination therapies in falciparum malaria.

Abstract

Malaria infection poses a serious public health problem in endemic countries. As per World Malaria Report 2015, it is estimated that 3.2 billion people in 97 countries are at risk of being infected with malaria; 214 million cases of malaria with 4,38,000 malaria induced deaths are reported during the year1. Clinical consequences of malaria result primarily from parasitic invasion of red blood cells (RBCs). Inside the RBCs, the parasite metabolizes the host haemoglobin in the acidic environment of the parasite's food vacuole. This leads to production of free haem which contains Fe2+ atoms that can catalyze Fenton and Haber-Weiss reactions, generating the radicals which can cause extensive molecular damage2. Haemolysis of infected red cells releases free haem which may be responsible for an external oxidative stress on both infected and non-infected RBCs2 and may be one of the factors contributing to destruction of normal red cells. Presence of pro-oxidants in plasma of patients suffering from acute falciparum malaria has been demonstrated by measurement of the erythrocyte thiobarbituric acid-reactive substance concentrations3. The parasite develops antioxidant mechanisms partly through reducing its own generation of reactive oxygen species and partly through increased synthesis of reduced glutathione and thioredoxin reductase system2. During intraerythrocytic development of Plasmodium falciparum, a large number of parasite proteins move beyond its own plasma membrane and associate with RBC membrane cytoskeletal proteins. Parasite and host red cell cytoskeletal protein interactions lead to formation of large molecular complexes which appear as electron dense “knobs” on the RBC surface. These changes lead to alterations in the rheological properties of infected red cells which become less deformable and more adhesive4.