The United States Centers for Disease Control and Prevention response to Highly Pathogenic Avian Influenza A(H5N1): surveillance, diagnostics, risk assessment, and public health preparedness from 1996 to 2026

Avian influenza A(H5N1) remains a major zoonotic and pandemic concern because of its extensive circulation in birds, repeated spillover into mammals, and capacity to cause illness in humans ranging from asymptomatic infection or conjunctivitis to fatal pneumonia. The detection of clade 2.3.4.4b H5N1 in United States dairy cattle in 2024 created a persistent animal-human interface that required coordinated action across public health, animal health, occupational health, agriculture, and food safety. This review critically examines the role of the United States Centers for Disease Control and Prevention (CDC) in H5N1 surveillance, laboratory diagnosis, genomic risk assessment, clinical guidance, occupational protection, communication, and pandemic preparedness. A structured narrative review was conducted using PubMed and authoritative sources from the Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO), World Organisation for Animal Health (WOAH), U.S. Department of Agriculture (USDA), and U.S. Food and Drug Administration (FDA). The search covered January 1996 through 24 July 2026. Sources were screened for direct relevance and synthesized by predefined thematic domains. Table 1 presents a focused evidence map of key H5N1-specific studies and reports. The CDC response uses surveillance systems, monitoring of exposed persons, public-health laboratory testing, rapid H5 subtyping, sequencing, antigenic characterization, and antiviral-susceptibility assessment. Human infections associated with the United States cattle and poultry outbreaks were predominantly mild and commonly involved conjunctivitis or upper-respiratory symptoms, although severe and fatal disease occurred. Preventive measures include occupational PPE guidance, monitoring and testing of exposed persons, infection-control recommendations, risk communication, and antiviral prophylaxis following selected high-risk exposures.” Important limitations include uneven testing, incomplete participation by exposed workers, barriers to personal protective equipment use, rapidly changing surveillance data, and uncertainty regarding the frequency of mild or asymptomatic infection. The reviewed serosurveys also indicated that symptom-based surveillance can miss infections in exposed workers. The CDC-centered response has expanded detection and preparedness, but its effectiveness depends on sustained One Health coordination, timely animal-outbreak control, accessible worker-centered testing, transparent data sharing, and continuous evaluation of viral evolution, diagnostic performance, antiviral susceptibility, and candidate vaccine-virus match and the need for stronger integration of animal and human data.