| Summary: | Dimorphic and polymorphic regions of <I>MSP-1 </I>and <I>MSP-2 </I>were genotyped by polymerase chain reaction (PCR) in 379 <I>P. falciparum </I>clinical isolates from Malawi. Polymorphisms in the genes were reflected in antigenic diversity of the translated proteins detected by indirect immunofluorescence (IFA) typing. Most <I>MSP-1 </I>alleles were MAD20 dimorphic and K1 block 2 types, whereas <I>MSP-2</I> type A alleles predominated. The effect of <I>P. falciparum</I> genetic polymorphisms on the specificity of immune responses was investigated in children immunised by natural infections typed for <I>MSP-1 </I>and <I>MSP-2.</I> Specific IgG antibodies detected by ELISA were mainly directed to MSP-1 conserved C-terminus fragments (19kDa and 42kDa), whereas antibodies induced by MSP-2 predominantly recognised group-specific regions. Overall, naturally induced human antibody responses to MSP-1 and MSP-2 were short-lived, type-specific, and correlated with PCR typing of the infecting parasites present. The wide spectrum of disease manifestations observed in <I>P. falciparum </I>infections probably reflects a combination of various host and parasite factors. Children with severe malarial anaemia (SMA, n=50) were distinguished by a higher multiplicity of infections than children with uncomplicated malaria (UM, n=92) or cerebral malaria (CM, n=93). SMA patients had higher prevalence of MSP-1 K1/Well and MSP-2 B dimorphic types, whereas block 2 MAD20-type of MSP-1 was more common in UM cases. A differential pattern of antibody responses to defined regions of the proteins was found. Children who developed SMA contained very low levels of antibodies to conserved regions, whereas children with CM had significantly higher levels of antibodies to the conserved regions than children with UM or SMA. CM and SMA differed substantially for all parameters assessed, indicating that they should not be regarded as one severe disease group but as two very distinct syndromes.
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