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Background: Recurrent outbreaks of the highly pathogenic avian influenza (HPAI) A (H5N1) virus in farmed poultry, and reports of infections in dairy cattle herds in the United States since March 2024, have triggered concerns about the spillover threat to human populations and a subsequent influenza pandemic. The increasing threat that H5N1 poses to human health has led to more vigilant public health monitoring of these developments. In addition to intensifying surveillance, preventative strategies—like vaccinating those at higher risk—are being evaluated to help minimize infection and spread. Objective: Efforts to mitigate and respond to such an event will entail broad public health interventions including vaccination. However, analysis of the COVID-19 pandemic suggests that information quality can significantly impact the effectiveness of such measures by influencing public understanding and trust. Misinformation about H5N1 and other viruses circulating online often includes inaccurate information about transmission, prevention, and the severity of the viruses. By systematically analyzing these false narratives, public health authorities can better tailor their pandemic prevention, preparedness, and response strategies. Methods: In light of the emerging threat of H5N1, we analyzed the content of social media posts from Facebook (approximately 350,000) and Instagram (n=69,551) related to HPAI. Using 40 keywords associated with misinformation, we identified over 500 posts explicitly mentioning H5N1 and related terms for further systematic analysis. Posts were coded to identify targets and topics in the social media narratives. The “target” refers to the organization or person mentioned in the post, while the “topic” refers to the primary issue or subject being addressed. Results: Our content analysis identifies 7 main targets of misinformation, including government (149/544, 27%), health authorities (108/544, 20%), and international organizations (74/544, 14%). Also, from the 6 topics that have been identified, we found that the most widespread one was that authority figures purposefully engineer pandemics to achieve multiple political, economic, and other objectives (362/544, 67%) followed by societal destruction (121/544, 22%), and anti-vaccination (84/544, 15%). Other themes include societal destruction and religious allusions and prophecies. Conclusions: Our analysis of online content showed that H5N1 misinformation was primarily aimed at individuals or groups with differing degrees of political or institutional authority, such as government leaders and public health officials. These figures were often the focus due to their involvement in making health policy decisions and implementing public health measures. Decision-making entities and individuals were the target of various misinformation narratives. Results demonstrate the ongoing need for monitoring health misinformation to inform evolving public health responses to HPAI.

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