International Journal of Epidemiology 2000;29:579-586
© International Epidemiological Association 2000
Assessment of different sources of variation in the antibody responses to specific malaria antigens in children in Papua New Guinea
a Swiss Tropical Institute, Basel, Switzerland.
b Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea.
Reprint requests to: Heide A Stirnadel, Swiss Tropical Institute, Department of Public Health and Epidemiology, Socinstrasse 57, CH-4002 Basel, Switzerland. E-mail: heide.stirnadel{at}roche.com
Background A potential problem for malaria vaccine development and testing is between-host variation in antibody responses to specific malaria antigens. Previous work in adults in an area highly endemic for Plasmodium falciparum in Papua New Guinea found that genetic regulation partly explained heterogeneity in responsiveness. We have now assessed the relative contributions of environmental and genetic factors in total IgG responses to specific malaria antigens in children, and quantified temporal variation within individuals of total IgG responses.
Methods Total IgG responses against schizont extract, merozoite surface protein-1, merozoite surface protein-2, ring-infected erythrocyte surface antigen, and SPf66 were measured by ELISA. Variance component analysis was used to estimate the variation explained by genetic and environmental factors in these antibody responses. Intra- and inter-class correlations of antibody responses within relative pairs were estimated. We adjusted for age, P. falciparum density, sex and village differences either within or prior to the analysis.
Results For all malaria antigens, temporal variation in the total IgG response was the predominant source of variation. There was substantial familial aggregation of all IgG responses, but it remained unclear how much this clustering was attributable to genetic factors and how much to a common environment in the household. The remaining variance, which could not be explained by either of the above, was very small for most of the antigens.
Conclusions Temporal variation and clustering of immune responses to specific malaria antigens need to be taken into account when planning, conducting and interpreting immuno-epidemiological and vaccine studies.
Keywords IgG, malaria, variance component analysis, children, Papua New Guinea
Accepted 4 November 1999