Cryptosporidium within-host genetic diversity: systematic bibliographical search and narrative overview

Knowledge of the within-host genetic diversity of a pathogen often has broad implications for disease management. Cryptosporidium protozoan parasites are among the most common causative agents of infectious diarrhoea. Current limitations of in vitro culture impose the use of uncultured isolates obtained directly from the hosts as operational units of Cryptosporidium genotyping. The validity of this practice is centred on the assumption of genetic homogeneity of the parasite within the host, and genetic studies often take little account of the within-host genetic diversity of Cryptosporidium. Yet, theory and experimental evidence contemplate genetic diversity of Cryptosporidium at the within-host scale, but this diversity is not easily identified by genotyping methods ill-suited for the resolution of DNA mixtures. We performed a systematic bibliographical search of the occurrence of within-host genetic diversity of Cryptosporidium parasites in epidemiological samples, between 2005 and 2015. Our results indicate that genetic diversity at the within-host scale, in the form of mixed species or intra-species diversity, has been identified in a large number (n=55) of epidemiological surveys of cryptosporidiosis in variable proportions, but has often been treated as a secondary finding and not analysed. As in malaria, there are indications that the scale of this diversity varies between geographical regions, perhaps depending on the prevailing transmission pathways. These results provide a significant knowledge base from which to draw alternative population genetic structure models, some of which are discussed in this paper.