The first case of a person to contract bird flu after no known contact with animals is raising questions about the possibility of human-to-human transmission and highlighting the complicated relationship between states and federal agencies in outbreak response.

An extensive investigation into the case of a patient in Missouri who was hospitalized on 22 August has revealed no links to animals, officials at the US Centers for Disease Control and Prevention (CDC) told reporters on Thursday.

Two contacts of the patient also fell ill around the same time, the agency revealed in a report the next day.

A health worker developed mild symptoms but tested negative for the flu. More troublingly, a household member also developed symptoms on the same day as the patient – but that person was not tested for the flu.

There’s a blood test to check for antibodies to H5N1, a highly pathogenic avian influenza, that may be done as soon as 10 days after infection, but antibody testing has not started, CDC officials said on Thursday.

The patient with a confirmed infection responded to lengthy questionnaires on recent activities, such as doing yard work, having a bird feeder, keeping any pets at home, visiting agricultural fairs or petting zoos, eating undercooked meat, or drinking raw milk. Nothing raised alarm bells with officials about potential exposures.

“Thus far, epidemiologists have not found a clear source of exposure,” said Nirav Shah, principal deputy director of the CDC.

“Missouri is working really hard to go deeper into the [epidemiology] to see if there are any unperceived exposures that are possible,” said Demetre Daskalakis, director of the National Center for Immunization and Respiratory Diseases.

Genomic sequencing revealed that the strain is related to the virus that probably began circulating among dairy cows late last year; the bovine-adapted variant has since spilled into other wild and domesticated animals, including birds and mammals.

The patient’s sample showed at least two mutations, including one that might make current vaccine candidates for H5N1 less effective.

Shah told reporters last Thursday there was no evidence of person-to-person transmission, calling the event a likely “one-off” case.

“None of the individuals that this individual came into contact with have developed any signs and symptoms,” Shah said on Thursday.

Yet last Friday, the CDC reported the other two symptomatic contacts, one of which was shared “subsequently” by Missouri.

The CDC has not been invited by Missouri to help with the investigation, although federal officials are in touch with the state via phone and video calls, Shah said.

The CDC has limited authority for state- and local-level compliance, and recent supreme court decisions may have a chilling effect on regulatory action.

Missouri has been in “very close consultation” with the CDC since detecting the case, “but we have not had a need for more extensive on-site assistance at this time as we are still limited to one case with low risk of sustained transmission”, Lisa Cox, communications director for the Missouri department of health and senior services, told the Guardian.

Only 240 people or so have been tested for H5N1 in the 2024 outbreak, according to the CDC. Typically, tests are done only when someone in close contact with infected animals develops symptoms.

In Missouri, that is not what happened. Health workers suspected a respiratory infection such as the seasonal influenza, but the swab was not fast-tracked as a potential H5N1 infection, Shah said. Instead, it was sent to the state laboratory with other flu A samples to be double-checked as part of routine surveillance looking for any types of unusual flu strains.

This kind of monitoring usually happens during the winter flu season, but in May the CDC recommended states continue monitoring flu A through the summer because of ongoing outbreaks on poultry and dairy farms.

This is the first time an H5N1 case has been detected using the national flu surveillance system.

“Our influenza surveillance system is designed to find needles in haystacks, and as this case and others show, it is working,” Shah said. “We found such a needle, but we don’t know how it got there.”

Missouri has not reported any cases of H5N1 in cows, but the state had only tested 17 of about 60,000 dairy cows as of July. The most recent outbreak of bird flu among Missouri poultry was reported in February.

There have not been any unusual levels of flu activity or emergency department visits in this area compared with last year’s levels, Shah said. “But our investigation is not over.”

The patient in Missouri, who has “significant” underlying conditions, experienced “acute” symptoms of chest pain, nausea, vomiting, diarrhea and weakness, Shah said.

“The patient has underlying chronic medical conditions, and respiratory symptoms were not the leading cause for hospitalization on admission,” Cox said. The patient was not severely ill, was hospitalized for three days, and has recovered.

It is possible that the individual’s existing medical conditions made them more vulnerable to illness, Shah said.

As the virus continues to spread among animals, officials remain on alert for more cases among people, Shah said. “As more animal species exhibit and harbor H5, the possibility of animal-human interaction goes up, and thus the possibility of human cases goes up.”