It is also called as big spleen disease. Recently it has been redefined and more appropriately termed as " hyperreactive malarial syndrome" (HMS ).

Etiology: Although malarial parasite is usually not demonstrated in blood smears of patients with HMS, there are convincing evidence linking it to malaria:

Other factors which may play role in development of HMS include genetic susceptibility, malnutrition and pregnancy.

Pathogenesis: Exact mechanism is unknown. Evidence suggests that interaction of repeated malarial infections and unknown host factors leads to production of cytotoxic IgM anti-suppressor lymphocyte (CD8+) antibodies. This leads to exaggerated stimulation of polyclonal B lymphocytes causing excessive and uncontrolled production of IgM (which is polyclonal and not specific for any one particular malaria species) and formation of cryoglobulins (IgM aggregates and immune complexes). These macromolecular aggregates get deposited in Kupffer cells in liver and spleen leading to reticuloendothelial hyperplasia and hepatosplenomegaly (massive and progressive) leading to anemia.

1. It is prevalent only in malaria endemic areas.
2. High levels of malarial antibodies can be demonstrated in patients with HMS.
   
   
3. Anti malarial treatment reduces splenic size suggesting response to treatment.
   
   
4. Discontinuation of treatment prematurely may be associated with relapse of HMS.
   
   
5. Effective malarial chemoprophylaxis has been shown to reduce spleen rates as well as incidence of HMS.
   
   
6. Sickle cell trait patients are relatively protected from HMS as with malaria.
   
   
7. Animal models have been developed to show similar clinical syndrome after malarial infection.

Epidemiological factors:

1. Age: More frequent in young and middle aged adults. Uncommon in children younger than 8 years, suggesting that prolonged chronic antigenic stimulation is an important factor in development of HMS.
   
   
2. Sex: More common in females, male : female = 1:2.