title: MAD 20 alleles of merozoite surface protein-1 (msp-1) are associated with severe Plasmodium falciparum malaria in Pakistan.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University, Karachi, Pakistan.
authors.forename: Najia Karim
authors.initials: NK
authors.lastname: Ghanchi
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University, Karachi, Pakistan.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hasan
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University, Karachi, Pakistan.
authors.forename: Muniba
authors.initials: M
authors.lastname: Islam
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University, Karachi, Pakistan. Electronic address: masim.beg@aku.edu.
authors.forename: Mohammad Asim
authors.initials: MA
authors.lastname: Beg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000953:Antigens, Protozoan / Q000235:genetics; D002648:Child; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000473:pathology*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000235:genetics*; D008875:Middle Aged; D010154:Pakistan; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium
keywords: Genotypes; Merozoite surface proteins; Plasmodium falciparum; Severe malaria