Etiology

• Most cases of malaria occur in tropical Africa (West and Central Africa).

• Transmission also occurs in other tropical and subtropical regions such as South and Southeast Asia, and Central and South America

• Pathogen: Plasmodia

  • Eukaryotic parasites (belonging to the Sporozoa group)

  • Species that affect humans [2][3][4][5]

    • Plasmodium falciparum: most virulent and causes the most severe disease, i.e., falciparum malaria; dominant in Africa

    • Plasmodium vivax: the most common of the less virulent species and causes milder disease; dominant in endemic areas outside Subsaharan Africa (e.g., Southeast Asia)

    • Plasmodium ovale and Plasmodium malariae: less common and cause milder disease [4]

    • Plasmodium knowlesi: found in Southeast Asia and can cause severe malaria; possibly zoonotic and often misidentified as other species due to morphological similarities. [6]

• Vector: the female Anopheles mosquito

• Host: humans

• Carriers of sickle‑cell mutation

• Individuals with either certain Duffy antigens or no Duffy antigens are resistant to P. vivax and P. knowlesi [8]

• Other hemoglobinopathies (e.g., thalassemia, HbC)

• Infection with malaria subsequently leads to the development of specific Plasmodium antibodies that result in partial immunity for a limited amount of time (less than a year)

Asexual development in humans

1. Transmission of Plasmodium sporozoites via Anopheles mosquito bite → sporozoites travel through the bloodstream to the liver of the host

2. Liver: sporozoites enter hepatocytes → sporozoites multiply asexually → schizonts are formed containing thousands of merozoites → release of merozoites into the bloodstream

3. Circulatory system (two possible outcomes)

   • Merozoites enter erythrocytes → maturation to trophozoites → red cell schizonts are formed containing thousands of merozoites → release of merozoites into the bloodstream (which causes fever and other manifestations of malaria) → penetration of erythrocytes recurs

   • Merozoites enter erythrocytes → differentiation into gametocytes (male or female)

Sexual development in female Anopheles mosquito

• A mosquito bites an infected human and ingests gametocytes → gametocytes mature within the mosquito intestines → sporozoites are formed and these migrate to the salivary glands → transmission of sporozoites to humans via mosquito bite

• See also “Developmental stages of Plasmodium in RBCs.”