MAD 20 alleles of merozoite surface protein-1 (msp-1) are associated with severe Plasmodium falciparum malaria in Pakistan.

BACKGROUND

Various factors determine the outcome of Plasmodium falciparum infection such as parasite load, sequestration, adhesion molecules, and immune mediators. P. falciparum merozoite surface protein-1 (msp-1) and msp-2 genotypes were also found associated with severe disease. We investigated the association between msp-1 and msp-2 genotypes in patients with uncomplicated malaria (UM) and severe malaria (SM).

METHODS

Twenty-two malaria patients with microscopy-confirmed P. falciparum infection and eight healthy endemic controls were selected for analysis. Nested polymerase chain reaction (PCR) was used to identify P. falciparum genotypes. The plasma concentration of cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ)] and chemokines [chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10] were evaluated using enzyme-linked immunosorbent assay (ELISA).

RESULTS

TNF-α levels were significantly higher in both UM (389 pg/mL, p = 0.020) and SM (771 pg/mL, p = 0.004) compared with healthy controls, while they were greater in SM (p = 0.012) as compared to UM. CXCL9 levels were significantly raised in SM as compared to UM and negative controls (NCs). CXCL10 levels were raised in UM (550 pg/mL, p = 0.001) and SM (1480 pg/mL, p = 0.01) as compared with NCs. Increased levels of IL-6 were found in patients carrying the FC27 allelic type of msp-2. A higher prevalence of MAD 20 and K1 msp-1 alleles was observed in the SM group compared to UM.

CONCLUSION

Overall, a greater prevalence of MAD 20 alleles and increased serum TNF-α and CXCL9 levels were associated with severe outcome in malaria. Understanding the diversity of malaria genotypes is important for predicting disease-related outcomes of P. falciparum infection in endemic areas.