Estimating multiplicity of infection, haplotype frequencies, and linkage disequilibria from multi-allelic markers for molecular disease surveillance

The proposed method can be readily applied in practice for malaria disease surveillance as a replacement for heuristic methods. The first benefit is its ability to estimate MOI, which scales with transmission intensities, and, in a temporal context, can be used to evaluate the effectiveness of disease control measures. MOI is best estimated from molecular markers that are not under selection (neutral markers) and exhibit sufficient genetic variation. The second advantage is that it can estimate pairwise LD without deflating sample size as in heuristic methods, thereby limiting uncertainty in the estimates. This is particularly useful when deriving LD maps from data with many ambiguous observations due to MOI. Importantly, the method per se is not restricted to malaria, but applicable to any disease with a similar transmission pattern. The method and several extensions are implemented in an easy-to-use R script.