SummaryTo investigate the effects of host polymorphisms on malaria morbidity and infection, the frequency distributions of TNF ␣ promotor gene and sickle cell trait were studied in infants in an area highly endemic for Plasmodium falciparum transmission in Tanzania. Differences in parasite prevalence, density, febrile episodes with and without parasitaemia, PCV levels and the frequencies of different MSP-2 parasite infections were assessed by genotype. The frequency of the TNF ␣ promotor allele 2 was 0.09, and the trait was in Hardy-Weinberg equilibrium. There were no differences in malariametric indices between infants with the normal TNF ␣ promoter gene and those who were heterozygous for this trait. Infants heterozygous for the TNF ␣ promotor gene appeared to have fewer febrile episodes when they were free of parasites. The two infants homozygous for the TNF ␣ promoter allele 2 had both a much higher incidence of fever, independently of parasitaemia, than the average for the other genotypes. The frequency of the sickle cell allele S was 0.06 and the trait was also in Hardy-Weinberg equilibrium. Infants heterozygous for the sickle cell trait had significantly lower parasite densities, but similar prevalence, and MSP-2 infections compared to infants with normal haemoglobin. PCV levels, and the incidence of febrile episodes both with and without parasitaemia were also similar. In contrast to the sickle cell trait, the TNF ␣ promotor polymorphism appeared not to have any protective effect on malaria in this study, and its importance in other unspecified fever-causing diseases in this population needs further investigation.keywords Plasmodium falciparum malaria, tumour necrosis factor-␣ promotor polymorphism, sickle-cell trait, infants correspondence Heide A. Stirnadel,

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.

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.