Malaria: Epidemiology, Pathophysiology and Clinical Management

Malaria is a serious infectious disease caused by Plasmodium parasites and transmitted by infected female Anopheles mosquitoes. Despite advances in prevention and treatment, it remains a major global health problem, with approximately 249 million cases and over 600,000 deaths reported in 2022. The disease mainly affects sub-Saharan Africa, where children under five years of age and pregnant women are the most at risk. Five species infect humans: P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi. P. falciparum causes the most severe cases and deaths, while P. vivax contributes significantly to illness due to its relapsing liver stage and wide geographic distribution. Progress in malaria control has slowed in recent years due to healthcare disruptions and increasing drug and insecticide resistance. Artemisinin partial resistance, linked to Kelch13 mutations, has now spread beyond Southeast Asia into parts of East Africa, raising concerns for global control efforts. Severe malaria develops during the blood stage of infection. After leaving the liver, parasites invade red blood cells and multiply, causing repeated cycles of red cell destruction that lead to fever. In P. falciparum, infected red blood cells adhere to blood vessel walls through PfEMP1, leading to blockage of small vessels, reduced oxygen delivery, and organ damage. This is further worsened by an excessive inflammatory response, contributing to complications such as cerebral malaria, anemia, and hypoglycemia. Immunity develops slowly with repeated exposure and does not eliminate the parasite. It involves both antibody-mediated and cell-mediated responses, while regulatory mechanisms help control inflammation but may also allow long-term parasite survival. Overall, ongoing resistance, changing epidemiology, and complex disease mechanisms highlight the need for better understanding and improved strategies for malaria control and treatment.