Estimation of numbers of malaria clones in blood samples

Methods are derived for estimating the mean number of clones of the haploid malaria parasite Plasmodium falciparum from samples of blood of infected hosts which have been tested for the presence of alleles at marker loci. For example, at a locus with three alleles the sample might contain only A1, or A1 and A2, or A1, A2 and A3, with multiple allele classes being more common at high infection rates. Assuming either a Poisson or negative binomial distribution of numbers of infections per host, formulae are derived for the frequency of different classes of blood samples, and maximum likelihood methods are used to estimate the mean number of clones and allele frequencies. Two data sets, each on two loci, are analysed. One data set was from the same locality in Tanzania from which oocysts of the parasite in mosquito vectors were tested for clonality (i.e. diploid unions of gametes from the same clone) using genetic markers. Good agreement was obtained between the observed clonality in oocysts and that expected from the number of infections per host (mean approximately three).