Changing epidemiological patterns in human avian influenza virus infections

Abstract

Explosive geographical expansion of the avian influenza virus (AIV) continues to threaten human and animal health during and after the COVID-19 pandemic. Individuals from 17 countries across five continents have been infected by the five emerging (H5N8, H10N3, H3N8, H10N5, and H5N2) and four re-emerging (H5N1, H5N6, H7N9, and H9N2) subtypes of AIV since 2019 (appendix). H5N1 viruses, especially those of clade 2.3.4.4b, continue to diversify genetically, spread geographically, and infect humans, as illustrated by the first ever human infection in Victoria, Australia,1Department of Health. Victoria AustraliaHuman case of avian influenza (bird flu) detected in returned traveller to Victoria.https://www.health.vic.gov.au/health-advisories/human-case-of-avian-influenza-bird-flu-detected-in-returned-traveller-to-victoriaDate: May 21, 2024Date accessed: May 31, 2024Google Scholar in May, 2024, and a presumed novel transmission from dairy cattle to a dairy worker from Texas, USA,2Cohen J Worries about bird flu in US cattle intensify.Science. 2024; 384: 12-13Crossref PubMed Scopus (0) Google Scholar in April, 2024. Moreover, high viral concentrations have been detected in unpasteurised milk from infected dairy cattle. A comprehensive sequence-based analysis suggested that the viruses isolated from wild birds, cows, cats, and humans in Texas during March, 2024, share the same origin, ie, infected migratory wild birds.3Hu X Saxena A Magstadt DR et al.Highly pathogenic avian influenza A (H5N1) clade 2.3.4.4b virus detected in dairy cattle.bioRxiv. 2024; (published online April 16) (preprint)https://doi.org/10.1101/2024.04.16.588916Google Scholar The ever-growing list of potential sources, such as alpacas,4Cable News NetworkAlpacas test positive for H5N1 bird flu for the first time.https://edition.cnn.com/2024/05/28/health/alpacas-h5n1-bird-flu/index.htmlDate: May 28, 2024Date accessed: June 4, 2024Google Scholar dairy cows, goats,2Cohen J Worries about bird flu in US cattle intensify.Science. 2024; 384: 12-13Crossref PubMed Scopus (0) Google Scholar civets,5He WT Hou X Zhao J et al.Virome characterization of game animals in China reveals a spectrum of emerging pathogens.Cell. 2022; 185: 1117-1129.e8Summary Full Text Full Text PDF PubMed Scopus (110) Google Scholar and minks,6Lu M He WT Pettersson JH-O et al.Zoonotic risk assessment among farmed mammals.Cell. 2023; 186: 2040.e1Summary Full Text Full Text PDF Scopus (9) Google Scholar raises immense concern regarding the consequences of exposure to AIV.See Online for appendix See Online for appendix In humans with AIV infection, extra-pulmonary, beyond-influenza-like conditions and symptoms at the onset of the illness, including conjunctivitis (ocular), diarrhoea (gastrointestinal), and seizures (neurological), warrant special attention.7US Centers for Disease Control and PreventionWhat Causes Bird Flu Virus Infections in Humans. Avian Influenza (Bird Flu).https://www.cdc.gov/bird-flu/virus-transmission/avian-in-humans.htmlDate: May 3, 2024Date accessed: June 14, 2024Google Scholar Reports of two fatal mixed infections in humans—one involving H10N5 and seasonal H3N2,8WHOAvian influenza A (H10N5) and influenza A (H3N2) coinfection - China.https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON504Date: Feb 13, 2024Date accessed: April 25, 2024Google Scholar and the other involving H5N1 and influenza B/Victoria lineage viruses9WHOHuman infection with avian influenza A (H5N1) - India.https://www.who.int/emergencies/disease-outbreak-news/item/human-infection-with-avian-influenza-a(h5n1)-%EF%BD%B0-indiaDate: Aug 16, 2021Date accessed: April 28, 2024Google Scholar—suggest that mixed infections not only increase mortality risk but also reassort with human influenza viruses and potentially adapt the viruses to humans with a risk of triggering a pandemic. Immunisation, particularly of those at high risk of exposure, is recommended to reduce the risk of coinfection of AIV and seasonal influenza viruses. In addition, educating physicians on the risk factors and natural history of human AIV infection can increase awareness and improve diagnostic ability. Understanding the delay between illness onset and pathogen identification and hospital admission can help to tailor early risk assessment and mitigation strategies to improve prognosis and limit the spread of AIV. Compared to a 10·7-day delay during 2003–13,10Cowling BJ Jin L Lau EHY et al.Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population-based study of laboratory-confirmed cases.Lancet. 2013; 382: 129-137Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar the median time-delay from illness onset to laboratory confirmation in human H5N1 cases has been reduced to 8 days since 2019 (appendix). However, the viral identification of emerging AIVs took even longer, such as the first H10N5 human case (53 days)8WHOAvian influenza A (H10N5) and influenza A (H3N2) coinfection - China.https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON504Date: Feb 13, 2024Date accessed: April 25, 2024Google Scholar and the first H5N2 human case (35 days),11WHOHuman infection caused by avian Influenza A(H5N2)- Mexico.https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON520Date: Jun 5, 2024Date accessed: June 5, 2024Google Scholar despite the former case having a clear history of poultry exposure. The time from illness onset to admission varies among inpatients infected by H9N2, H5N1, and H5N6 viruses owing to the differences in the virus genotype, patterns in exposure, disease progression, and health-care services. These delays have contributed to fatal outcomes among inpatients, with half of the fatal cases characterised by a delay of more than 7 days. Collecting and reporting temporal data on pathogen identification and hospital admission in a standardised manner are recommended for better risk assessment. Addressing health inequities and unmet medical needs is also necessary. Given the unpredictable risk posed by AIVs, the implementation of One Health-based prevention and control strategies is essential. The main challenges requiring attention are disease detection and diagnosis. Although the gold standard for the diagnosis of AIV is RT-PCR testing, current resource and capacity limitations in many countries, such as issues with storing and transporting samples, restrict the amount of testing. Thus, enhanced deployment of rapid influenza diagnostic tests in both humans and animals, including neglected mammals that come in close contact with humans, is imperative. To characterise zoonotic AIVs, viral sequencing at different outbreak stages should be encouraged to identify genetic changes that could facilitate adaptation to mammals or humans. Understanding the mechanisms that determine the host range and virulence of AIVs is essential to ensure optimal preparedness. Stricter biosecurity measures are required in all commercial farms where farm workers might be in direct contact with animals. Furthermore, education, training, and support among farm workers might enable better self-protection and disease management. Vaccines for farmed mammals are urgently needed, particularly for species with high economic value, to reduce viral spread and economic losses and provide secondary protection to farm workers. Moreover, given the multiple detections of AIVs in produce such as uncooked meats and milk from farms susceptible to the virus, food safety measures should be strengthened. Considerable collaboration is required to address socioeconomic inequalities; overcome the limitations in access to diagnosis, treatments, and vaccines; and update strategies to combat AIVs. We declare no competing interests. SS and MK are financially supported by the National Key Research and Development Program of China (Grant No. 2022YFC2604203), Program of Shanghai Academic Research Leader (23XD1420700), and Medical Science Data Center of Fudan University. MK acknowledges support from the Shanghai Hospital Development Center “Research physician innovation and translational ability training program” (SHDC2022CRS028). GB acknowledges support from the Research Foundation - Flanders (‘Fonds voor Wetenschappelijk Onderzoek – Vlaanderen’, G0E1420N, and G098321N), from the EU Horizon 2023 RIA project LEAPS (grant agreement no. 101094685), and from the DURABLE EU4Health project 02/2023-01/2027, which is co-funded by the EU (call EU4H-2021-PJ4) under Grant Agreement No. 101102733. We acknowledge support from Wenkai Zhang for the figures in the appendix. Download .pdf (4.73 MB) Help with pdf files Supplementary appendix

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