Cold agglutinins and their relationship to malaria

Abstract

It is well recognized that cold agglutinins frequently occur in high titre in the sera of Melanesian inhabitants of Papua New Guinea. There have been numerous studies of the specificities of these Melanesian cold agglutinins, but few of their pathogensis. They are known to be a common accompaniment of tropical splenomegaly syndrome in New Guineans, but their prevalence in other coastal New Guineans is less well documented, and their relationship to malarial infection has not been clarified. The present study included 332 New Guineans living in the one malarious area, none of whom had received regular suppressive antimalarial therapy prior to this investigation. Cold agglutinins in a titre of greater than 1:32 were rare in young children, but occurred in 6% of older children and in 28% of adults. The corresponding rates after 12 mth of protection against malaria were 2% and 10% respectively. Treatment of acute attacks of malaria only, without regular prophylaxis, produced no such change in a control group. Cold agglutinin titres showed a significant correlation with serum IgG and IgM concentrations, and with titres of antimalarial antibody as measured by indirect immunofluorescence, both in initial values and in subsequent decreases. Values in subjects with tropical splenomegaly syndrome were no higher than in the rest of the community. These data suggest that in Melanesians the production of cold agglutinins forms part of the normal immune response to recurrent malarial infections experienced over many years. The phenomenon does not occur in other races exposed to a similar pattern of malaria, and this may indicate a genetically determined response to a weak antigen released or exposed in parasitized red cells.