Malaria, a parasitic disease caused by Plasmodium parasites, is transmitted to humans through the bite of infected female Anopheles mosquitoes. Histology, the microscopic study of tissues, provides detailed insights into how the parasite affects the human body and helps understand disease progression.
The Microscopic World of Malaria in Blood
Microscopic examination of a blood smear from a malaria-infected individual reveals various stages of the Plasmodium parasite within red blood cells. The earliest stage is the ring form trophozoite, appearing as a delicate blue ring with a small red chromatin dot. These develop into larger, irregular trophozoites, and then into schizonts, which are mature forms containing multiple merozoites clustered around a mass of dark pigment. The final developmental stage seen in peripheral blood is the gametocyte, the sexual form of the parasite.
The appearance of infected red blood cells (RBCs) and the parasites themselves differ among the four main Plasmodium species that infect humans: P. falciparum, P. vivax, P. ovale, and P. malariae. P. falciparum infects red blood cells of normal size, and multiple ring forms can be observed within a single red blood cell. Infected cells may also display Maurer’s clefts, which are irregular, comma-shaped structures. The gametocytes of P. falciparum are uniquely crescent or banana-shaped.
In contrast, Plasmodium vivax infects reticulocytes, which are larger, younger red blood cells, leading to their enlargement and distortion. Infected P. vivax red blood cells exhibit Schüffner’s dots, appearing as fine, yellowish-brown stippling, and the trophozoites can appear amoeboid. Plasmodium ovale also infects reticulocytes, causing them to enlarge and become oval or fimbriated (having feathered edges). Schüffner’s dots are characteristic of P. ovale infections, and its gametocytes are round to oval.
Plasmodium malariae infects older, smaller red blood cells, which do not enlarge. Its trophozoites can form characteristic “band forms,” appearing as elongated, compact structures across the red blood cell. The schizonts of P. malariae arrange merozoites in a rosette pattern. Across all species, the parasite digests hemoglobin, releasing a dark, insoluble, crystalline byproduct called hemozoin. This hemozoin can be seen within the parasites in infected red blood cells, and sometimes free in the blood or engulfed by phagocytic cells.
Malaria’s Impact on Organs and Tissues
Beyond circulating blood cells, malaria induces histological changes in various organs. The liver, as the initial site of parasite multiplication in humans, shows early infection of hepatocytes by sporozoites, which develop into exoerythrocytic schizonts. Later in the disease, the liver exhibits hyperplastic Kupffer cells, which are specialized macrophages, laden with brown hemozoin pigment. Sinusoidal congestion and inflammation within the portal tracts, where blood vessels and bile ducts are located, are also found in severe cases.
The spleen, an organ for filtering blood, undergoes changes, often becoming enlarged, a condition known as splenomegaly. Histologically, the spleen’s red pulp becomes congested with both infected and uninfected red blood cells, and contains numerous large macrophages filled with dark brown hemozoin pigment. The white pulp, which is rich in immune cells, may show disorganization. These changes reflect the spleen’s role in removing parasitized red blood cells and mounting an immune response.
Cerebral malaria, a severe complication, involves distinct histological findings in the brain. Sequestration of P. falciparum-infected red blood cells within the cerebral capillaries leads to microvascular obstruction. This sequestration can be accompanied by microhemorrhages, which are tiny bleeds, and the presence of hemozoin pigment within vessels and sometimes free in the brain tissue. Brain swelling is observed, and the brain itself may appear discolored due to the accumulation of malaria pigment.
Kidney involvement can manifest as acute kidney injury, with histological features such as acute tubular necrosis, where kidney tubules are damaged. Glomerulonephritis, an inflammation of the kidney’s filtering units, and interstitial nephritis, inflammation of the tissue surrounding the tubules, may also be observed. Sequestration of infected red blood cells within glomerular capillaries and accumulation of host monocytes are noted. Hemozoin may also be present in proximal tubules.
In pregnant women, placental malaria is characterized by the accumulation of P. falciparum-infected red blood cells and hemozoin pigment within the intervillous space of the placenta. This is the region where maternal blood bathes the fetal villi, facilitating nutrient and waste exchange. The placenta may appear discolored due to the accumulation of malaria pigment. Histological lesions can include syncytial knotting, thickening of the placental barrier, and infiltration of immune cells in the intervillous space.
Histology’s Role in Diagnosing Malaria
Microscopic examination of blood smears remains the established method for malaria diagnosis. This technique involves preparing and staining blood films, and then observing them under a light microscope. Two main types of blood smears are used: thick films and thin films.
Thick blood smears are prepared from a larger volume of blood where red blood cells are lysed, concentrating the parasites. This allows for a more sensitive detection of parasites and provides an estimate of parasite density, even in cases of low parasitemia. Microscopists examine a minimum of 100 fields before declaring a thick smear negative.
Thin blood smears, where blood is spread in a single layer, are fixed to preserve red blood cell morphology. This preparation is useful for identifying the specific Plasmodium species and observing morphological characteristics of the parasites and infected red blood cells. Distinguishing between species and recognizing low parasite numbers can be challenging, requiring skilled microscopists. Quality control measures are important to ensure accurate diagnoses.
Beyond routine clinical diagnosis, histology plays a role in malaria research and post-mortem analysis. In research, microscopic examination of tissue samples helps to understand pathological processes of malaria in various organs, providing insights into disease mechanisms and potential drug targets. Post-mortem histological examinations confirm malaria as a cause of death by identifying sequestered parasites and hemozoin in organs. These examinations contribute to a broader understanding of how malaria affects the body.