Malaria is a parasitic disease caused by protozoa of the genus Plasmodium and transmitted to humans through the bite of infected female Anopheles mosquitoes. The disease’s physiological effects range from a recurring, debilitating fever to severe, life-threatening multi-organ failure. The consequences of malaria on the human body are rooted in the parasite’s life cycle, which targets and destroys red blood cells, triggering a cascade of inflammatory and mechanical damage throughout the host’s circulatory system.
Acute Clinical Manifestations
The initial symptoms of malaria often resemble a flu-like illness, including headache, muscle aches, and fatigue. Symptoms typically begin 10 to 15 days after the infective mosquito bite, though this incubation period can vary depending on the specific Plasmodium species. These initial manifestations can be easily mistaken for other common viral or bacterial infections, making early diagnosis challenging.
The established infection is characterized by the classic malarial paroxysm, a cyclical occurrence of extreme symptoms linked to the parasite’s reproductive cycle in the blood. This paroxysm involves three distinct stages: the cold stage, the hot stage, and the sweating stage. The cold stage begins suddenly with intense shivering and a feeling of coldness.
This is followed by the hot stage, where the body temperature rapidly rises. During this phase, the skin is flushed and dry, and the patient often experiences a worsening headache and nausea. The cycle concludes with the sweating stage, marked by a profuse sweat that leads to a drop in body temperature and exhaustion. The frequency of this cycle depends on the parasite species, with some causing symptoms every 48 hours and others every 72 hours.
Underlying Pathophysiology: Red Blood Cell Damage and Anemia
The core mechanism of malaria’s damage begins with the parasite’s erythrocytic cycle, the stage where the Plasmodium parasite invades and multiplies within red blood cells (RBCs). After maturing in the liver, the parasites, now called merozoites, burst into the bloodstream and rapidly infect RBCs. Inside the red blood cell, the parasite consumes hemoglobin and grows, eventually causing the cell to rupture and release a new generation of merozoites.
This rupture of red blood cells is directly responsible for the cyclical fever and chills that characterize the malarial paroxysm. The sudden release of parasitic waste products and cellular debris into the bloodstream triggers a powerful inflammatory response. This systemic inflammation involves the release of immune signaling molecules, such as cytokines, which act on the body’s thermoregulatory center to induce fever.
The continuous destruction of red blood cells is the direct cause of severe anemia, a common complication of malaria. Anemia develops not only from the direct lysis of infected RBCs but also from the premature destruction of uninfected red blood cells and the body’s impaired ability to produce new ones. Furthermore, the most dangerous species, Plasmodium falciparum, causes infected RBCs to become stiff and sticky, a process known as cytoadherence.
Cytoadherence is mediated by parasite-derived proteins which are displayed on the surface of the infected RBC. These sticky cells adhere to the endothelial lining of small blood vessels, particularly in deep organs, allowing the parasite to hide from the spleen, which would otherwise filter out and destroy the rigid, infected cells. This sequestration mechanism contributes to microvascular obstruction and localized inflammation, profoundly disrupting blood flow and oxygen delivery to tissues.
Life-Threatening Complications and Severe Malaria
When the parasite burden and systemic inflammation overwhelm the body, the condition progresses to severe malaria, which involves specific organ failure.
Cerebral Malaria
Cerebral malaria is a neurological complication resulting from the sequestration of infected red blood cells in the microvasculature of the brain. The obstruction of blood flow and associated inflammation can cause swelling and damage to the brain tissue, leading to symptoms like impaired consciousness, convulsions, and coma.
Acute Kidney Injury (AKI)
The kidneys are also highly susceptible to damage, resulting in acute kidney injury (AKI). The mechanisms behind AKI involve impaired microcirculation due to sequestered cells, systemic inflammation, and oxidative stress from cell-free hemoglobin released during RBC destruction. This damage can lead to a significant reduction in urine output and a rapid accumulation of waste products in the blood.
Respiratory and Metabolic Complications
Severe malaria can also affect the respiratory system, causing Acute Respiratory Distress Syndrome (ARDS) or pulmonary edema, a condition where fluid builds up in the lungs. The systemic inflammatory response increases the permeability of the capillaries in the lungs, allowing fluid to leak into the air sacs, which severely compromises the body’s ability to exchange oxygen. Metabolic complications, such as hypoglycemia (low blood sugar), are also frequent, particularly in children and pregnant women. This occurs because the parasite rapidly consumes glucose while the host’s metabolic processes are impaired by systemic illness.