Both coinfection and superinfection drive complex Anaplasma marginale strain structure in a natural transmission setting

Authors: KOKU, ROBERTA - Washington State University; Herndon, David; AVILLAN, JOHANNESTY - Washington State University; MORRISON, JILLIAN - College Of Wooster; FUTSE, JAMES - University Of Ghana; PALMER, GUY - Washington State University; BRAYTON, KELLY - Washington State University; Noh, Susan

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/15/2021
Publication Date: 8/2/2021
Citation: Koku, R., Herndon, D.R., Avillan, J., Morrison, J., Futse, J.E., Palmer, G.H., Brayton, K.A., Noh, S.M. 2021. Both coinfection and superinfection drive complex Anaplasma marginale strain structure in a natural transmission setting. Infection and Immunity. 89(11). Article e00166-21. https://doi.org/10.1128/IAI.00166-21.
DOI: https://doi.org/10.1128/IAI.00166-21

Interpretive Summary: Complex infections, the presence of at least two genetic variants of a pathogen within a host at a given time, are increasingly recognized as common, particularly in association with high pathogen prevalence. Complex infections have the potential to lead to more virulent or transmissible pathogens. However, many fundamental knowledge gaps remain including how genetic variants accumulate in hosts through time under natural transmission conditions. Anaplasma marginale is endemic in cattle throughout the world, and the entire transmission cycle in the natural hosts can be readily replicated in experimental conditions. Complex infections are well described in both field and laboratory conditions. In this study we track the acquisition of A. marginale strains in naïve animals introduced into an endemically infected herd in Ghana. 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 could be detected in an individual animal following seroconversion. Thus, while complex infections develop via both co-infection and superinfection, co-infection predominates in this setting. These findings will help to inform vaccination strategies designed to reduce the occurrence of complex infections.

Technical Abstract: 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 is unknown how complex infections develop in a natural transmission setting. We addressed this question by introducing naïve animals into a herd in southern Ghana with high infection prevalence and high transmission pressure and tracking 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 could be 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.