Dr  Sampurna Roy  MD

Human malaria is an acute and chronic protozoal disease caused by any one or a combination of four species of plasmodia - Plasmodia, vivex, falciparum, ovale & malariae.  

P. falciparum cause malignant tertian malaria with high fatality rate.  The other three species are 'benign' . Infections with P. ovale and P malariae are now rare.

All forms malaria are transmitted by female anopheles mosquito.

WHO recognizes malaria as the world’s major primary health problem. About 2000 million persons suffer from malaria.

It is endemic in Asia & Africa but due to widespread jet travel, cases are now reported all over the world. Map:click here

Maternal Malaria:

Maternal malaria is a common complication in endemic areas. Plasmodia are found in great numbers in the intervillous spaces of placenta of infected mothers. The parasites sequester along the surface of the placental membrane - trophoblastic villi , extravillous trophoblasts, and syncytial bridges. The sequestration of parasites may obstruct oxygen-nutrient transfer and can cause hemorrhage.

The disparity between the approximate 30% incidence of placental malaria in endemic areas and the rarity of congenital malaria reports is believed to be related to an immunologically dependant placental barrier mechanism.

 In addition to death, maternal malaria is associated with premature delivery, intrauterine growth retardation, perinatal mortality in the infant, and anemia and in the mother.

Malaria associated with other haematological disorders:

The disease has been associated epidemiologically with many hematological disorders. Inherited erythrocyte abnormalities such as sickle hemoglobinopathy and glucose-6-phosphate dehydrogenase deficiency are extremely common in malarial areas.  Studies have shown that sickle hemoglobin restricts both parasite invasion and growth.

The prevalence of Burkitt's lymphoma in malarious areas has led to the proposal that malaria may enhance the oncogenic potential of the Epstein Barr virus.

  Images of blood smears:  Image Link1 ; Image Link2 ; Image Link3

Malignant malaria (Plasmodium falciparum malaria): Image Link

P. falciparum parasites infect liver cells and then red blood cells, cause severe anemia when red blood cell lyse and produce cerebral infarcts when infected red blood cells bind to endothelial cells in the central nervous system.

P. falciparum proteins form unique knobs on the surface of infected red blood cells and parasitised red blood cells adhere to each other and to endothelial cells.

P. falciparum infection initially cause congestion and enlargement of the spleen whereas in chronic malaria infection the spleen becomes increasingly fibrotic and brittle.

Pigmented phagocytic cells may be found dispersed throughout the bone marrow, lymph nodes, subcutaneous tissues and lungs.

At autopsy the spleen and liver and all organs of reticuloendothelial system in falciform malaria are darkened ("slate grey") by malarial pigment. Image Link

The hepatic cells show cloudy swelling and fatty change. Kupffer cells are large and actively phagocytic. They contain parasites, erythrocytes and malarial pigment. Image Link

A disseminated intravascular coagulopathy may occasionally develop in patients with malaria. This has been associated with the adult respiratory distress syndrome seen in some fatal cases of malaria.

An immune complex glomerulonephritis formed by P. falciparum antigen and corresponding antibodies has been documented by electron microscopy and immunofluorescence.

Note:  P. falciparum has 37 antigenic variants. Parasites escape cytocidal  action of antibodies by altering its antigenic form in circulation. Full protective antibody cannot inactivate the new antigenic variant. As antibodies are formed against this new antigen, parasite changes to yet another variant and this continues till antibodies are formed against all 37 antigens, giving full immunity to infection. This explains why in endemic areas children are subjected to repeated attack of malaria for first few years and then become immune to further infection.

Cerebral malaria: Image Link1  ;  Image Link2

In malignant cerebral malaria caused by P. falciparum, brain vessels are plugged with parasitized red cells, causing ring hemorrhage . This may be accompanied by necrosis of surrounding parenchyma.

Development of trophozoite to schizont takes place in the capillaries of cerebral vessels.

Parasitized RBC and are often occluded by microthrombi causing micro-infarct & micro-hemorrhage.

The disease starts suddenly or slowly , but rapidly progress to cause impaired consciousness, high fever, chill, generalized convulsions, shock, coma that persists for 24-72 hours & death within days or weeks. 

The brain is congested with petechiae limited to white matter.

The damage leads to a reactive gliosis with the formation of malarial granulomas ( Durck's granuloma ).

(Evidence of blood–brain barrier dysfunction in human cerebral malaria)

Differential diagnosis:

i) of ring haemorrhages in the brain: Fat embolism ; bacterial and rickettsial septicaemia ; DIC ; trauma.

ii) of pigment containing cells: Formalin pigment.

Blackwater Fever:click here

Diagnosis of Malaria:

Diagnosis depends on the demonstration of malarial parasites on a Giemsa-stained thick or thin blood smear. Erythrocytes containing multiple ring forms and the presence of banana-shaped gametocytes are diagnostic of P. falciparum. Because of fluctuations in degree of parasitemia, multiple periodic blood-smear examinations should be performed. 

The diagnosis can be corroborated by serologic tests. The methods currently available include the indirect hemagglutination antibody (IHA), the ELISA, the indirect fluorescent antibody test (IFA), radioimmunoassay (RIA) and the complement fixation (CF) test.