Are We Testing Enough for H5N1?

With H5N1 avian influenza causing unprecedented outbreaks in mammals around the world — including U.S. dairy cattle — infectious disease experts are raising concerns that the U.S. isn’t doing enough to get ahead of any potential problems.

“We really need to be moving quickly to get our heads around what’s happening in the animal population and also what’s happening in the human population,” James Lawler, MD, MPH, of the University of Nebraska Medical Center’s Global Center for Health Security, told MedPage Today. “I don’t think we’ve been testing adequately to be able to get a real picture of that.”

Lawler said we should be particularly cautious “when a virus starts doing things that we don’t expect it to do, like circulating widely in a species where we normally haven’t seen infections. We really need to respect the potential danger that exists.”

Federal officials have confirmed that 33 dairy cattle herds in eight U.S. states have tested positive for H5N1.

However, the outbreak is likely much larger than that, and has probably been spreading undetected for much longer than thought, Lawler said. That’s evidenced by the fact that FDA detected H5N1 in samples from the commercial milk supply, and by recently released viral sequences from animal infections supplied by the U.S. Department of Agriculture (USDA), from which virologists concluded the outbreak likely began in December 2023, with a single spillover incident from birds into cows.

Federal officials have been trying to reassure the public, holding a press briefing with officials from a range of agencies — including the HHS Administration for Strategic Preparedness and Response, USDA, FDA, CDC, and NIH — on Wednesday, and providing detailed information at a public symposium led by the Association of State and Territorial Health Officials (ASTHO) on Thursday.

The USDA recently required testing for influenza before cattle are moved between states, but mandated no other testing requirements for livestock, and symptomatic testing is voluntary. The agency did not return a request for comment from MedPage Today as of press time.

Detecting Human Infections

In an email to MedPage Today, a CDC spokesperson said that while the USDA is responsible for livestock testing, the agencies are “working together to characterize virus specimens and monitor for changes that might make these viruses more likely to transmit to or between humans.”

In the current outbreak, at least 44 people have been monitored for symptoms, the spokesperson said, and more are being passively monitored, where they monitor themselves and report if they develop symptoms.

Overall, 23 people have been tested by states, with only one person — a farm worker in Texas whose only symptom was conjunctivitis — tested positive, the spokesperson said.

Since this particular clade (2.3.4.4b) of H5N1 appeared in the U.S. in 2022, CDC has monitored more than 8,400 people in 52 jurisdictions, Sonja Olsen, PhD, associate director of preparedness and response at CDC’s influenza division, said during the ASTHO symposium.

About 200 people reported symptoms and were tested, which turned up just two positive cases in the U.S. — the recent one in the Texas dairy cattle worker, and another in Colorado in 2022 who had contact with infected birds. Both cases were mild and the patients made full recoveries.

However, since the illness caused by H5N1 can go on in cattle for several weeks, workers are at ongoing risk, so the period for monitoring will be longer than the 10 days outlined in 2014 joint guidance from USDA and CDC, Olsen said.

The CDC spokesperson said the agency is “well positioned to detect this virus — down to the individual case levels.” In terms of human influenza, CDC hasn’t seen “any unusual trends at the national, state, or local levels” nor has it identified “any out-of-the-ordinary influenza-related emergency department data.” Nor has there been any concerning activity in terms of foodborne illness, the spokesperson added.

Testing asymptomatic people “is not routinely recommended because most people who are infected with avian influenza A viruses have usually shown symptoms of illness,” the spokesperson said.

In addition, testing people who’ve potentially been exposed but don’t have symptoms may “pick up small amounts of flu viruses … that do not represent actual infections but are likely surface contamination of mucosal membranes. Those people are unlikely to transmit the virus to others or manifest symptoms themselves,” the spokesperson added.

Will Commercial Tests Be Available if Needed?

Should the U.S. be in a position where testing is needed at scale, the CDC is poised to make that happen, Vivien Dugan, PhD, director of the agency’s influenza division, said during the ASTHO briefing.

Based on genetic sequencing from the Texas human case, there’s no impact on current diagnostics, she said.

The human virus sequence is “nearly identical” to samples from infected dairy cattle and birds in Texas, she said. It appears primarily to have avian viral genetic characteristics and lacks any changes that would make it better at infecting mammals, she added.

It did contain one substitution that wasn’t found in Texas cattle or birds, in the polymerase 2 protein at position E627K. This mutation has been identified in other human cases of H5N1 so it’s “not surprising or uncommon” and may have been acquired during this person’s infection, she said.

Even so, this wouldn’t impact CDC’s real-time polymerase chain reaction diagnostic assays that are available at U.S. public health labs across the country, and which are in use year-round to test for influenza, she said.

Commercial tests for influenza A, Dugan said, are widely available “and we expect they will detect H5 as an influenza A virus.”

“We are actively partnering with commercial diagnostic developers and testing companies in case we need to scale up to increase testing if needed,” she said. “We are positioning ourselves to be ready to go should the situation change.”

‘Society-Ending Pandemic’

Highly pathogenic avian influenza A (H5N1) was first identified in domestic waterfowl in China in 1996 and the first human case occurred in 1997, Olsen said.

Since then, a total of 909 cases from 23 countries have been reported — with a mortality rate of 52%.

“That’s just a reminder of why this disease is such a public health concern,” Olsen said.

Lawler noted that the current case fatality rate is likely an overestimate. “There are probably a lot more undetected cases we haven’t counted,” he said.

But even if mortality is 10-fold lower, “a flu virus with a case fatality rate of 5% is catastrophic. That’s a society-ending pandemic.”

The 1918 H1N1 influenza pandemic probably had a case fatality rate of 2%, he noted, “and that was bad enough.”

“We need to get out in front of this quickly, to make sure that … we assess the true scope of this problem,” he said. “The more opportunity we give this virus to circulate in more species of mammals, the more likely we will get mutations that adapt it more effectively to other mammals, including humans.”