Environmental resistance development to influenza antivirals: a case exemplifying the need for a multidisciplinary One Health approach including physicians

Josef D. Järhult

A multidisciplinary approach is a prerequisite for One Health. Physicians are important players in the One Health team, yet they are often hard to convince of the benefits of the One Health approach. Here, the case for multidisciplinarity including physicians is made using the example of environmental resistance development to influenza antivirals. Neuraminidase inhibitors are the major class of anti-influenza pharmaceuticals, and extensively stockpiled globally as a cornerstone of pandemic preparedness, especially important in the first phase before vaccines can be mass-produced. The active metabolite of oseltamivir that is excreted from treated patients degrades poorly in conventional sewage treatment processes and has been found in river waters. Dabbling ducks constitute the natural influenza A virus reservoir and often reside near sewage treatment plant outlets, where they may be exposed to neuraminidase inhibitor residues. In vivo experiments using influenza-infected Mallards exposed to neuraminidase inhibitors present in their water have shown resistance development and persistence, demonstrating that resistance may be induced and become established in the influenza strains circulating in natural hosts. Neuraminidase inhibitor resistance genes may become part of a human-adapted influenza virus with pandemic potential through reassortment or direct transmission. A pandemic caused by a neuraminidase inhibitor-resistant influenza virus is a serious threat as the first line defense in pandemic preparedness would be disarmed. To assess the risk for environmental influenza resistance development, a broad multidisciplinary team containing chemists, social scientists, veterinarians, biologists, ecologists, virologists, epidemiologists, and physicians is needed. Information about One Health early in high school and undergraduate training, an active participation of One Health-engaged physicians in the debate, and more One Health-adapted funding and publication possibilities are suggested to increase the possibility to engage physicians.