Malaria is caused by parasites of the Plasmodium genus, transmitted to humans through the bite of infected female Anopheles mosquitoes. The infection cycle involves several key stages:
- Sporozoite Injection – During a mosquito bite, sporozoites are introduced into the bloodstream.
- Liver Stage – Sporozoites migrate to the liver, invade hepatocytes, and multiply.
- Erythrocytic Stage – Merozoites released from the liver infect red blood cells, triggering clinical symptoms such as fever, chills, and anemia.
- Gametocyte Formation – Some parasites differentiate into gametocytes, which are taken up by another mosquito, continuing the transmission cycle.
In some cases, Plasmodium infections occur without any apparent clinical symptoms—this is known as asymptomatic malaria.
Asymptomatic carriers show no signs of illness but harbor the parasite in their blood, enabling mosquitoes to become reinfected and sustain transmission, particularly during the rainy season. These silent infections can persist for months or even years. Asymptomatic malaria is common in highly endemic regions, where individuals often develop partial immunity and become chronic carriers. However, those who leave endemic areas for extended periods may lose this natural immunity and become susceptible again.
These silent infections complicate detection and targeted treatment. They require proactive screening strategies and enhanced epidemiological surveillance, even in the absence of visible symptoms. Community-wide screening campaigns are essential to identify asymptomatic carriers and break the transmission chain. A major challenge is that such infections often go undetected by rapid diagnostic tests (RDTs), which are antigen-based. Only quantitative PCR can reliably identify them—an approach that is often impractical in fragile healthcare systems.
Asymptomatic Plasmodium infections thus pose a significant obstacle to malaria eradication, as these carriers act as reservoirs in endemic areas. The liver harbors dormant forms (hypnozoites) responsible for relapses, while red blood cells contain the asexual forms that cause symptoms. Meanwhile, the Anopheles mosquito serves as a temporary host for the sexual forms (gametocytes).
During the erythrocytic phase, red blood cells infected by Plasmodium falciparum express various versions of the Pfemp1 protein. These proteins are:
- Encoded by approximately 60 var genes, enabling antigenic variation to evade immune detection.
- Central to cytoadhesion, allowing infected red blood cells to bind to endothelial cells and avoid clearance by the spleen.
- Responsible for severe malaria symptoms through sequestration and rosetting, which obstruct microvasculature.
Pfemp1’s structural domains (e.g., DBL and CIDR) mediate binding to host receptors such as ICAM-1 and CD36, making them prime targets for vaccine and therapeutic development.
Numerous studies suggest that asymptomatic infections may be explained by the antigenic variation mechanism employed by P. falciparum as a survival strategy. By encoding different versions of Pfemp1 through its var genes, the parasite enables infected red blood cells to evade immune detection and destruction by the spleen for extended periods. By continuously altering the antigens on the surface of infected red blood cells, the parasite avoids immune recognition, thereby sustaining a chronic, asymptomatic infection.
