Both co-infection and superinfection drive complex Anaplasma marginale strain structure in a natural transmission setting

Vector-borne pathogens commonly establish multi-strain infections, also called complex infections. How complex infections are established, either prior to or after the development of an adaptive immune response, termed co-infection or superinfection, respectively, has broad implications for the maintenance of genetic diversity, pathogen phenotype, epidemiology, and disease control strategies. Anaplasma marginale , a genetically diverse, obligate, intracellular tick-borne bacterial pathogen of cattle commonly establishes complex infections, particularly in regions with high transmission rates. Both co-infection and superinfection can be established experimentally, however it is unknown how complex infections develop in a natural transmission setting. To address this question, we introduced naïve animals into a herd in southern Ghana with high infection prevalence and high transmission pressure and tracked strain acquisition of A. marginale through time using multi-locus sequence typing. As expected, genetic diversity among strains was high and 97% of animals in the herd harboured multiple strains. All the introduced, naïve animals became infected, and three to four strains were typically detected in an individual animal prior to seroconversion, while one to two new strains were detected in an individual animal following seroconversion. On average, the number of strains acquired via superinfection was 16% less than those acquired via co-infection. Thus, while complex infections develop via both co-infection and superinfection, co-infection predominates in this setting. These findings have broad implications for the development of control strategies in high transmission settings.