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In the absence of PCR testing, infectious disease experts and epidemiologists are anxiously awaiting serology results from the household contact and two healthcare workers who may have been infected with H5N1 bird flu by a patient in Missouri who tested positive for the disease.

The CDC said in an last week that Missouri health officials collected blood samples from the case and that person's household contact, which are being sent to the CDC "for serologic testing to look for antibodies to avian influenza A(H5) virus, which would indicate a previous infection."

The first healthcare worker who developed respiratory symptoms tested negative for influenza; it is unclear if this person will have serology testing. However, CDC said the second healthcare worker, who was not tested for flu, "will be offered" serology testing.

"Not obtaining serology and immune testing at this point would be public health malpractice," James Lawler, MD, MPH, of the University of Nebraska Medical Center's Global Center for Health Security in Omaha, told MedPage Today. "We must investigate this potential cluster to the fullest extent possible."

If H5N1 antibodies are detected on serology, "that essentially confirms that these were related H5N1 cases and very likely from human-to-human transmission," Lawler said. "There is no other reason for a person to have an immune record of H5 infection, and without clear risky exposure to animals or milk, a human cluster is most likely the result of human-to-human transmission."

Lawler said that in addition to antibody testing, tests of T-cell response should be conducted, "because not everyone who is infected with influenza virus develops a robust antibody response."

Amesh Adalja, MD, of the Johns Hopkins Center for Health Security in Baltimore, cautioned that "other respiratory viruses were circulating in high levels at that time, including COVID." The case was hospitalized on August 22.

There's been limited transmission of H5N1 to caregivers in the past, Adalja said, but it would be "helpful to understand if transmission occurred."

Lawler cautioned that while small clusters of H5N1 infection in humans have been observed, "exposure to poultry is often shared among family members, and to my knowledge, investigations have never confirmed human-to-human transmission with this virus."

"If it has occurred in the past, it is quite rare," he said. "So, if we are seeing human-to-human transmission now, it is a big deal."

He added that the "timing and circumstances that have been discussed publicly suggest that human-to-human transmission is certainly possible."

Neither Adalja nor Lawler suspect there is widespread, sustained human-to-human transmission of H5N1 at this time. Rather, Adalja said there is likely cattle-to-human transmission in Missouri: "Given that the strain is very similar to the strain circulating in dairy cattle, I assume that Missouri, even though it denies having any dairy herds positive, likely does have positive dairy herds."

He also criticized Missouri health officials for not inviting CDC officials on site to help with their investigation: "It seems that they would rather evade the fact that their dairy cattle likely harbor the virus than get a handle on what is happening."

Lawler and Adalja said it would be helpful to understand how the Missouri case became infected in the first place.

"Even sporadic cases of human-to-human transmission indicate a big change in the virus and suggest it is exploring new directions in virus evolution that bring it closer to a pandemic virus," Lawler said.

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