Understanding the Impact of Human and Avian Influenza
Influenza—an acute respiratory illness caused by influenza viruses—poses a major public health risk due to its potential for widespread illness and economic impact.1-4 Human influenza typically spreads via respiratory droplets or, less commonly, through contact with contaminated surfaces.5 The severity of infection can range from mild symptoms like fever, muscle aches, and congestion to extreme complications like pneumonia and death.1 The economic impact of human influenza is also significant; in the United States, total annual direct medical costs are estimated at $3.2 billion, whereas indirect costs accounted for $8.0 billion.6-9
In recent years, sporadic incidences of avian influenza in humans have been detected. Avian influenza, also known as bird flu, is naturally found among wild aquatic birds worldwide and can infect domestic poultry and other animal species.2-4,10,11 While rare, human infection with avian influenza can result in mild to severe symptoms or even death. These infections can occur after close contact with infected birds. The virus can also spread through intermediate hosts, leading to new variants capable of infecting humans.
In bird populations, avian influenza is particularly devastating, often resulting in large-scale deaths. Previous outbreaks of avian influenza in the poultry industry have led to significant economic losses for farmers, disruptions in the food supply chain, and potential impacts on international trade due to the need to cull infected flocks. The 2022 avian influenza outbreak in the United States, for instance, resulted in about 40 million animal losses and economic costs ranging from $2.5 to $3 billion.11-13
The recent detection of avian influenza H5N1 in milk samples has also put the dairy industry at risk.14-16 In affected cowherds, the illness impacts nearly 10% of the animals, causing reduced feed consumption and a 10% to 20% decline in milk production.17 The American Association of Bovine Practitioners (AABP) has estimated the economic impact of H5N1 for dairy cattle to be $100 to $200 per cow, which can result in significant economic losses for dairy producers.17
The Importance of Influenza Surveillance
Given the evolving behavior of influenza viruses, surveillance testing remains indispensable for monitoring virus evolution, assessing disease burden, and informing vaccine development. For these tests to reliably detect new or emerging strains of influenza, it is essential that they are developed and routinely applied using authenticated analytical reference materials (ARMs). These authenticated ARMs provide the necessary controls for calibrating tests, verifying performance, and validating results, thereby ensuring test accuracy and reproducibility. Diagnostic tests may produce false results without them, compromising surveillance data and public health responses, and can also lead to challenges when making comparisons across different datasets produced by various testing methods.
How ATCC Can Help
ATCC is at the forefront of developing new and reliable ARMs for accurate diagnostic testing, surveillance, and research for new and emerging influenza strains. Using synthetic biology technology, we have created synthetic RNA ARMs for highly pathogenic avian influenza (HPAI) strains and seasonal influenza viruses with increasing relevance. These ARMs represent the most extensive set of authenticated synthetic influenza RNA products currently available and are a valued complement to our existing portfolio of live influenza viruses and their genomic RNA derivatives, viral NGS standards, antibodies, and antisera.
Our synthetic RNA standards for HPAI include subtypes H5N1, H5N6, H7N7, H7N9, and H9N2, representing the most concerning and relevant avian influenza subtypes. Each of these ARMs consist of two transcripts with five segments, covering approximately 50% of the influenza genome. These segments are key diagnostic targets for nucleic acid-based tests and provide sufficient genomic context for assessing assay specificity. Our synthetic RNA standards for human influenza virus are based on sequences from H1N1, H3N2, H1N1 2009 pandemic, and Influenza B virus strains used in development and 510k clearance of several in vitro diagnostic devices. Our synthetic RNA ARMs are manufactured under ISO 13485 guidance and do not contain any viable material, are available in fixed concentrations, and can be safely used under BSL-1 settings. They are also fully verified via sequencing and quantified by Droplet Digital PCR® (ddPCR®; Bio-Rad Laboratories, Inc.). to ensure the highest level of authenticity and precision.
As health and economic risks from human and avian influenza strains rise, robust surveillance systems are essential. Accurate detection of influenza viruses improves outbreak preparedness and response, reducing their impact on public health and the economy. Continuous surveillance, reliable diagnostic testing, and control measures help mitigate these risks. ATCC provides industry-standard products and solutions to enhance research and public health responses to influenza and other infectious diseases.
Table 1: ATCC Synthetic RNA for Influenzaa,b
ATCC Item | Sequence of origin | Type | Serotype | Isolation source of the original virus |
VR-3436SD™ | A/white-tailed eagle/Japan/OU-1/2022 | A | H5N1 | Avian |
VR-3437SD™ | A/Shanghai/4664T/2013 | A | H7N9 | Avian |
VR-3438SD™ | A/chicken/Wenzhou/334b/2013 | A | H7N7 | Avian |
VR-3439SD™ | A/goose/Guangdong/GS018/2015 | A | H5N6 | Avian |
VR-3440SD™ | A/ostrich/Yunnan/438/2014 | A | H9N2 | Avian |
VR-3386SD™ | A/Brisbane/59/07 | A | H1N1 | Human |
VR-3388SD™ | A/Netherlands/2629/2009 | A | H1N1pdm09c | Human |
VR-3387SD™ | A/Hiroshima/52/2005 | A | H3N2 | Human |
VR-3384SD™ | B/Malaysia/2506/2004 | B, Victoria lineage | Human | |
VR-3385SD™ | B/Brisbane/60/2008 | B, Victoria lineage | Human |
a The synthetic RNA preparation includes two constructs (transcripts). One construct consists of the complete sequences from segments 4 and 5 encoding the HA and NP genes, respectively. The other construct includes complete sequences from segment 6 (encoding the NA gene), segment 7 (encoding M1 and M2 genes), and segment 8 (encoding NS1 and NEP/NS1 genes). In all constructs based on HPAI viruses, the section of the hemagglutinin gene encoding the polybasic cleavage site in the protein has been removed. Altogetehr the constructs cover 50% of the influenza genome. The product content is verified via sequencing, and the concentration of the transcripts is measured via ddPCR® (Bio-Rad Laboratories, Inc). All synthetic products are manufactured under ISO 13485 guidance and can be handled in BSL-1 settings.
b All ATCC synthetic products are stored in a proprietary nucleic acid buffer, enabling a five-year-long shelf life.
c 2009 pandemic isolate.
Did you know?
ATCC provides an extensive array of authenticated and clinically relevant materials for evaluating the limit of detection, inclusivity, and cross-reactivity of respiratory diagnostic assays. We provide these materials in a variety of formats including live strains, genomic and synthetic molecular standards, high-titer viruses, and panels.
Meet the author
Leka Papazisi, DVM, PhD
Principal Scientist, Microbiology R&D, Product Life Cycle, ATCC
Dr. Papazisi joined ATCC in 2019. His main responsibility is product development, from asset inception through lifecycle management. While at ATCC, Dr. Papazisi led the Microbiology R&D team in developing several new products, including a proprietary nucleic acid storage buffer formulation and various diagnostics control materials. In addition to technical leadership, his responsibilities include talent management, new product innovation, and management of internal and external cross-functional activities. Before joining ATCC, Dr. Papazisi worked for OpGen (2018-2019), Canon U.S. Life Sciences (2011-2018), and J. Craig Venter Institute (2003-2011). At OpGen, he directed the implementation of an antimicrobial-resistance surveillance system for the state of New York. While at Canon US Life Sciences, his main responsibility was the development of PCR-based assays and assay controls for detecting human inherited diseases and infectious agents—launching with his team ca. 700 products. At the JCVI, Dr. Papazisi led a variety of comparative genomic projects of several biothreat agents. During his academic career at the U. of Connecticut and Vet Med U. of Vienna, Dr. Papazisi studied genomics, virulence factors, and vaccine design for mycoplasmas as well as molecular profiling of Salmonella.
References
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- World Organization for Animal Health (WOAH). Avian Influenza. Accessed December 2024. https://www.woah.org/en/disease/avian-influenza/
- Richard M, de Graaf M, Herfst, S. Avian Influenza A Viruses: From Zoonosis to Pandemic. Future Virol 9(5): 513–524, 2014. PubMed: 25214882.
- Centers for Disease Control and Prevention (CDC). Influenza (Flu). Accessed December 2024. https://www.cdc.gov/flu/index.html
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- Federici C, et al. Health care costs of influenza-related episodes in high income countries: A systematic review. PLoS ONE 13(9): e0202787, 2018. PubMed: 30192781.
- Putri WCWS, et al. Economic burden of seasonal influenza in the United States. Vaccine 36(27): 3960-3966, 2018. PubMed: 29801998.
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- AbuBakar U, et al. Avian Influenza Virus Tropism in Humans. Viruses 15(4): 833, 2023. PubMed: 37112812.
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- The FAIRR Initiative. Industry Reinfected: Avian Flu Spotlight on the Economic and Public Health Impacts of Avian Flu. Accessed December 2024. https://www.fairr.org/resources/reports/industry-reinfected-avian-flu
- US Food and Drug Administration (FDA). Investigation of Avian Influenza A (H5N1) Virus in Dairy Cattle. Accessed December 4, 2024. https://www.fda.gov/food/alerts-advisories-safety-information/investigation-avian-influenza-h5n1-virus-dairy-cattle
- Yasharoff H. The USDA is testing raw milk for the avian flu. Is raw milk safe? USA TODAY, November 13, 2024. Accessed December 2024. https://www.usatoday.com/story/life/health-wellness/2024/11/13/is-raw-milk-safe/75891475007/
- Douglas L. Exclusive: US to begin bulk milk testing for bird flu after push from industr. Reuters, October 30, 2024. Accessed December 2024. https://www.reuters.com/world/us/us-begin-bulk-milk-testing-bird-flu-after-push-industry-2024-10-30/
- Morgan T. Mystery Illness is Now Affecting Dairy Cows in Texas, New Mexico As Industry Searches for Answers. Bovine News, March 22, 2024. Accessed December 2024. https://www.bovinevetonline.com/news/industry/mystery-illness-now-affecting-dairy-cows-texas-new-mexico-industry-searches-answers
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