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The first two human cases of were confirmed by CDC testing of specimens submitted by the state on Thursday, and a California-led investigation is underway.

At the same time, testing for antibodies that would confirm spread among contacts of an unusual case in Missouri will begin soon, with results expected in mid- to late October. On a press call Friday morning, CDC officials explained why this case is taking time to investigate.

First Human Cases in California

California reported its first H5N1 outbreaks in dairy cows in August. The two infected humans confirmed in the state on Thursday brings the total to 16 cases nationally this year, said Nirav Shah, MD, JD, principal deputy director of the CDC, during a call with reporters on Friday.

Demetre Daskalakis, MD, MPH, the director of the CDC's National Center for Immunization and Respiratory Diseases who was also on the call, explained that six of the 16 cases -- including the two newly reported cases in California -- have been tied to outbreaks in dairy cows. Nine cases linked back to "poultry depopulation activities" in Colorado were reported in July. The Missouri case has an unknown origin.

According to Shah, the California patients were farm workers at two separate dairy farms already known to have outbreaks of avian influenza among their cattle.

The cases were discovered through "active symptom monitoring," which is a strategy California and its local county health departments are continuing for exposed workers where outbreaks have been detected, he added.

Both of the individuals with confirmed H5N1 experienced mild symptoms, including conjunctivitis; neither reported respiratory issues, and neither individual was hospitalized. One individual said they believed they might have had a fever, Shah noted.

"Both individuals were tested, offered antiviral treatment, and are recovering," he added.

In the meantime, a public health investigation is underway. The CDC will work alongside California's public health officials to investigate the two confirmed cases and monitor for other possible cases. Household contacts -- other dairy workers -- have been contacted by public health officials or will be contacted for follow-up interviews, Shah said.

"There is no known epidemiological link between these two cases, and thus, based on what we know right now, these cases are separate instances of animal-to-human spread of the virus," Shah said.

He stressed that the discovery of these two cases was "not unexpected" and that the CDC's risk assessment for the general public "continues to be low."

Two weeks ago, California had 16 positive cattle herds; today it has 56, he said. "If there are more herds that test positive, there are more workers who are exposed. And where there are more workers who are exposed, the chances of human infection increase," he said.

Mystery Case in Missouri

Meanwhile, investigators continue to explore another human case identified in Missouri on September 6, with no known exposure to either an infected animal or animal products.

The public health response included "intensive interviews" of the patient and their household contacts as well as an infection control investigation at the hospital where the patient was admitted. The interviews did not identify a known source of exposure to the H5N1 virus, but did find a household contact who had been sick with similar symptoms to the identified case and experienced symptoms simultaneously, "implying a common exposure rather than human-to-human transmission," Daskalakis said.

Missouri public health officials also conducted a retrospective investigation at the hospital, which identified 112 healthcare workers who interacted with the patient.

Six of the 112 healthcare workers reported respiratory symptoms. One had been given an influenza PCR test, which was negative. The other five had recovered, and didn't have PCR testing.

Missouri obtained blood specimens for each of these individuals to conduct antibody testing by the CDC to investigate "the unlikely possibility that their symptoms were related to H5 infection resulting from their interaction with the patient," Daskalakis said.

Antibody tests for H5 aren't commercially available. For 3 weeks, the CDC has been developing a specific antibody test to match the Missouri virus, which is part of the reason serology testing has required more time, Daskalakis said.

The process is expected to be completed by Monday, at which point serology testing of samples will begin.

Conclusive serology testing results are expected by mid- to late October, Daskalakis said. "CDC is moving at a very accelerated pace, while conducting rigorous science to assure the validity of these results," he said.

CDC is also revising its H5 protocol to address evidence of "cross-reactivity" between seasonal H1 antibodies and H5N1 viruses, which is one more step being taken to ensure the test's accuracy and avoid a false positive result, he said.

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