Long-Term Residual Infection as a Source of Bovine Tuberculosis Reemergence: A Phylogenetic and Epidemiological Investigation of Recurrent Outbreaks

Abstract

Bovine tuberculosis (TB), primarily caused by Mycobacterium bovis, is a chronic infectious disease of cattle with significant public health and economic implications due to its zoonotic potential and impact on livestock productivity. The control of the disease is hindered by complex epidemiological dynamics and the chronic, and often slow-progressing nature of the disease. The recurrent outbreaks of bovine TB in endemic areas are common and threaten the success of eradication programs. To address this issue, long-term reemergent outbreaks in Catalonia (Northeastern Spain) were retrospectively investigated in depth. In 2009, an outbreak caused by M. bovis spoligotype SB0120 was detected in four extensively managed cattle herds. Following intensive eradication measures, all herds recovered the officially TB-free status by 2012. In 2021, 9 years later, a new outbreak involving the same spoligotype was detected in three herds located in the same area, one of which had been affected in the previous outbreak. Extensive sampling of TB-positive slaughtered cattle and hunted wild ungulates was conducted. Whole genome sequencing (WGS) of M. bovis isolates from cattle affected in both outbreaks, as well as from two culture-positive wild boars was performed. Epidemiological and phylogenetic analyses were conducted to elucidate the origin and transmission dynamics of the outbreaks. The results revealed a long-term residual infection in the cattle herd that linked the first and second outbreaks. This herd was also the most likely source of transmission of M. bovis to wild boars. Since residual infections can jeopardize the final stages of the eradication in low-prevalence settings, thorough investigation of reemerging strains is essential for risk assessment and for guiding TB control decisions.