What does H5N1 in cattle, humans portend?

Global outbreak of Avian Influenza H5N1 in birds, spreading to cattle and humans, raising concerns for potential evolution and transmission.

The emergence of a new clade of Avian Influenza H5N1 (2.3.4.4b) in late 2020 has led to a swift and widespread global outbreak, carried by migratory birds. Since then, the highly contagious clade has spread quickly across the world causing widespread mortality among birds. The outbreak is estimated to have killed millions of birds and the virus has infected over 200 mammalian species including humans.

A surprising twist occurred in March 2024, when avian influenza was detected in cattle in the U.S. Farmers had noticed a drop in milk production as early as January, but it was not until later that the U.S. Department of Agriculture (USDA) confirmed avian influenza H5N1 as the cause. The initial outbreak, caused by a sublineage that was identified in Texas, spread rapidly, impacting 100 herds by mid-June. It has since expanded to over 330 herds across 14 states. A preprint posted in May, which extensively analysed early genome sequences from the outbreak, suggested that the sublineage of the virus (B3.13) was likely introduced to cattle through poultry, possibly in late last year. It remained undetected for nearly four months before being confirmed by the USDA. Recent studies in experimental settings suggest that the virus can infect cattle when administered through both aerosol and intramammary routes. With its continued spread among mammals, the outbreak shows no signs of slowing down, raising significant concerns. If the virus becomes endemic in mammals, it could create numerous opportunities for the virus to evolve and optimise its transmission.

Human infections from the outbreak in cattle were first noted as early as April 2024 in Texas. Since then, 26 cases have been reported in California, Colorado, Michigan, Missouri, and Texas. Among them, 15 individuals had direct exposure to infected cattle, while 10 had contact with infected poultry. However, a case reported in Missouri in September had no known exposure to infected animals, and this remains a puzzle. The CDC confirmed that the Missouri patient had avian influenza A(H5N1) based on blood test results. Serology tests on close contacts did not indicate further human transmission. A household contact of the patient showed weak signs of potential exposure but did not meet the WHO criteria for confirmed infection. There are concerns that the reported numbers may represent only a small portion of the actual cases, as human testing for the virus is not widespread, and access to tests remains limited. However, early sero-surveillance studies on limited numbers of exposed individuals suggest that while the overall prevalence of H5N1 infections has been low, the risk increases with close and prolonged exposure to infected animals or contaminated environments.

According to the CDC, the risk of infection with avian influenza H5N1 for humans not directly working with cattle or poultry remains low. However, we are still navigating uncharted territory with this virus. So far, there has been no documented human-to-human transmission, and genome sequences do not show any signs of the virus adapting to spread between humans. Despite the current calm, caution is necessary as spillover events in both cattle and humans continue to rise and the virus continues to evolve and adapt.

The wastewater surveillance programme in the US supplements conventional surveillance methods to provide early warnings. Genomic surveillance could enable timely interventions, enhance disease monitoring, and improve preparedness by identifying potential risks early, especially if the virus evolves to allow efficient human-to-human transmission.

(Vinod Scaria is a senior consultant and Bani Jolly is a senior scientist at Karkinos Healthcare)