Standwell C. NkhomaShalini NairIan H. CheesemanCherise Rohr-AllegriniSittaporn SinglamFrançois NostenTim J.C. AndersonTexas Biomedical Research InstituteUniversity of Malawi College of MedicineTexas Department of State Health ServicesShoklo Malaria Research UnitMahidol University2018-06-112018-06-112012-07-07Proceedings of the Royal Society B: Biological Sciences. Vol.279, No.1738 (2012), 2589-259814712954096284522-s2.0-84987722638https://repository.li.mahidol.ac.th/handle/123456789/13431© 2012 The Royal Society. Malaria infections containing multiple parasite genotypes are ubiquitous in nature, and play a central role in models of recombination, intra-host dynamics, virulence, sex ratio, immun ity and drug resistance evolution in Plasmodium. While these multiple infections (MIs) are often assumed to result from superinfection (bites from multiple infected mosquitoes), we know remarkably little about their composition or generation. We isolated 336 parasite clones from eight patients from Malawi (high transmission) and six from Thailand (low transmission) by dilution cloning. These were genotyped using 384 single-nucleotide polymorphisms, revealing 22 independent haplotypes in Malawi (2–6 per MI) and 15 in Thailand (2–5 per MI). Surprisingly, all six patients from Thailand and six of eight from Malawi contained related haplotypes, and haplotypes were more similar within- than between-infections. These results argue against a simple superinfection model. Instead, the observed kinship patterns may be explained by inoculation of multiple related haploid sporozoites from single mosquito bites, by immune suppression of parasite subpopulations within infections, and serial transmission of related parasites between people. That relatedness is maintained in endemic areas in the face of repeated bites from infected mosquitoes has profound implications for understanding malaria transmission, immunity and intra-host dynamics of co-infecting parasite genotypes.Mahidol UniversityAgricultural and Biological SciencesBiochemistry, Genetics and Molecular BiologyEnvironmental ScienceImmunology and MicrobiologyArticleSCOPUS10.1098/rspb.2012.0113