From the Guidelines
Malaria causes splenomegaly through several mechanisms related to the body's response to Plasmodium parasite infection, including splenic congestion, hyperactive immune function, and extravascular hemolysis, as supported by the highest quality study available 1. The spleen plays a crucial role in filtering infected red blood cells from circulation, leading to increased workload and subsequent congestion and enlargement. Additionally, the spleen becomes hyperactive in its immune function, with increased numbers of macrophages and lymphocytes responding to the infection. The organ also serves as a site for extravascular hemolysis, where damaged red blood cells are destroyed. In chronic malaria infections, repeated cycles of parasite replication and immune response cause persistent inflammation and cellular hyperplasia within the spleen. The resulting fibrosis and structural changes contribute to sustained splenomegaly even after the acute infection resolves. Some key points to consider when evaluating splenomegaly in malaria patients include:
- The presence of splenomegaly is a significant predictor of malaria, with a likelihood ratio (LR+) of 5.1-13.6, as reported in a systematic review and meta-analysis 1.
- The absence of thrombocytopenia can strongly reduce the probability of malaria, with a likelihood ratio (LR-) of 0.2 1.
- Repeated malaria infections can lead to chronic splenomegaly, known as tropical splenomegaly syndrome, characterized by massive splenic enlargement and hypersplenism. It is essential to note that while the provided studies 1 discuss the management and diagnosis of malaria, they do not directly address the mechanisms of splenomegaly caused by the disease. Therefore, the recommendation is based on the most relevant and highest quality study available 1.
From the Research
Malaria and Splenomegaly
- Malaria infection is a common cause of spleen rupture and splenomegaly, albeit variably, a landmark of malaria infection 2.
- The spleen plays a crucial role in filtering and destroying senescent red blood cells, infectious microorganisms, and Plasmodium-parasitized RBCs 2.
- Infection by malaria can lead to splenomegaly, which is usually absent in adult patients who have already suffered from falciparum malaria or who are natives of an endemic falciparum zone 3.
Mechanism of Splenomegaly
- The spleen may contribute to malaria pathogenesis, particularly anemia that is associated with splenomegaly 4.
- Large spleens may also shelter parasites in chronic carriers, allowing the parasite to persist in the body 4.
- The spleen's role in mechanically retaining subsets of infected RBCs may reduce the pace at which the parasite biomass increases before the adaptive immune response operates 4.
Treatment and Splenomegaly
- Treatment with artemisinins can clear circulating parasites by pitting and release 'once-infected' RBCs in circulation, triggering postartesunate delayed hemolysis 4.
- Splenic retention of RBCs also applies to gametocytes, the clearance of which may be enhanced by stiffening them with drugs, a potential way to block malaria transmission 4.
- Comparative clinical trials have shown that artemether-lumefantrine is effective in treating uncomplicated Plasmodium falciparum malaria, with faster fever clearance time and shorter hospitalization time compared to atovaquone-proguanil 5.