As Bird Flu Spreads, Two New Cases Diagnosed in California

Both patients were dairy workers whose illnesses were mild. Investigators are continuing to evaluate the contacts of a Missouri patient who had no exposure to animals.

Two more people were diagnosed with bird flu this week, even as scientists in Missouri continued to investigate a possible cluster of infections in that state, federal health officials said at a news briefing on Friday.

In California, two farmworkers who were exposed to infected dairy cattle at different farms tested positive for the virus, called H5N1, state health officials said on Thursday. Those cases bring the total this year to 16, not including those under investigation.

The cases do not come as a surprise, because the number of infected herds in California has risen to 56 from 16 two weeks ago, said Dr. Nirav Shah, the principal deputy director at the Centers for Disease Control and Prevention.

“As 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. The risk to the public remains low, he added.

Still, experts said that the appearance of H5N1 in multiple states was worrisome.

Flu viruses are adept at acquiring new abilities by swapping their genes. As the flu season swings in, even one person who becomes infected with both bird flu and the seasonal flu virus could help H5N1 to gain the ability to spread as readily among people as seasonal flu does.

Given the many variables, it’s difficult to gauge the true risk of the virus mutating into a more contagious form, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Center in Seattle.

“The answer could be not at all, or we could have a major human outbreak,” he said. “Both of those are possible.”

Last month, the C.D.C. announced that a patient in Missouri with no known exposure to infected animals had been hospitalized with gastrointestinal symptoms and had tested positive for H5N1. Last week, the agency said that one household member and six health care workers who had been in contact with that patient had all developed symptoms.

C.D.C. officials said on Friday that they did not know whether the symptomatic individuals in Missouri had been tested for other illnesses, and they referred those queries to state health officials.

The workers developed symptoms before the initial patient was diagnosed with H5N1, according to Missouri officials. The single worker who sought testing at that time was negative for multiple respiratory viruses, including flu.

Another worker who had persistent symptoms and sought care long after the exposure window was negative for Covid, mononucleosis and strep.

It is possible that the workers had Covid-19 or some other illness with flulike symptoms. A summer Covid wave is just beginning to abate; although it did not overwhelm hospitals, many people became ill.

Because the hospitalized patient did not carry high amounts of virus when tested, officials have said that it is unlikely that the others were infected with H5N1.

The chances of human transmission or a cluster of illnesses may well be low, said Angela Rasmussen, a virologist at the University of Saskatchewan in Canada.

“But it’s hard to say that with a lot of confidence,” she said, “when you haven’t done the test to rule it out.”

“It seems to me that there’s a big motivation to avoid panic, or avoid fear, and avoid criticism,” she added, referring to the official response.

The C.D.C. and Missouri health officials have repeatedly said that the hospitalized patient and the household contact did not have “typical” symptoms of seasonal flu or H5N1, but rather gastrointestinal symptoms, including vomiting and diarrhea, making a true H5N1 infection unlikely.

In its external communications, the C.D.C. has cited only conjunctivitis, mild flulike upper respiratory symptoms, fever and muscle aches, as possible symptoms of bird flu infection. The agency did not mention gastrointestinal problems.

But even seasonal flu can be accompanied by vomiting and diarrhea. And early studies have found that patients with H5N1 infections often do have gastrointestinal problems, sometimes without any respiratory symptoms.

“H5N1 can present with diarrhea, sometimes, as the predominant symptom,” Dr. Malik Peiris, a virologist at the University of Hong Kong who has studied H5N1 outbreaks, said in an email.

One hypothesis is that infection via ingestion — consuming infected meat or milk, for example — may lead to predominantly gastrointestinal symptoms, Dr. Peiris added.

Dr. Demetre Daskalakis, the director of the National Center for Immunization and Respiratory Diseases at the C.D.C., said that the agency’s website did list vomiting and diarrhea as less common symptoms of H5N1 infection. The evidence “doesn’t change the way we talk about it,” he said.

Missouri’s state epidemiologist has suggested that the hospitalized patient may not have been infected with H5N1 in the usual sense. Instead, the individual may have simply picked up a small amount of the virus, too little to transmit to anyone else but enough to yield a positive test result.

The P.C.R. test “is very sensitive and can amplify extremely small amounts of genetic material,” Lisa Cox, the communications director at the Missouri Department of Health and Senior Services, said in an emailed statement.

“If a person’s hands are contaminated with genetic material and you touch your face/nose, you may transfer enough genetic material to trigger positive PCR test without actually having infection,” she said.

In bacterial infections like strep or meningococcal bacteria, some individuals can carry the pathogens without ever having an immune response or developing symptoms, said Dr. Gregory Gray, an infectious disease epidemiologist at the University of Texas Medical Branch.

But “we haven’t really thought about that with respect to influenza,” Dr. Gray said. And carriers can still pass along the pathogens to others, he noted.

Dr. Rasmussen and other scientists were more critical, saying the distinction between carrying a virus and an asymptomatic infection was semantic. And they noted that the theory wouldn’t explain how an individual with no exposure to infected animals acquired the virus.

“I mean, if you’re around a bunch of chickens that have H5 that you’re culling, there’s going to be virus flying around,” Dr. Rasmussen said. “But if you’re in a hospital bed in an intensive care unit in Missouri, why is there H5 there?”

The patient may have had low amounts of the virus for other reasons, experts said, such as the swabbing technique used or testing that took place too late in the infection.

There is another way to ascertain whether someone is infected with H5N1. Scientists can look for antibodies to the virus in blood samples using a so-called serology test, which would indicate that the patient had developed an immune response to fight the infection.

C.D.C. researchers are testing blood samples from some of the symptomatic patients in Missouri for these signs of infection. But it will take at least two to three weeks for answers to emerge, because scientists must create a new test specifically for the virus taken from the patient, the officials said.

Serology tests might also not provide a clear answer if a person has fewer antibodies than the test can detect, or if it picks up antibodies to related viruses.

“Most people would mount an antibody response to an influenza infection, but the strength of that response can vary somewhat,” Dr. Bloom said. “If the patient was immunocompromised, they might mount a very weak response, and that might be hard to detect in a serology test.”

Some experts took issue with the C.D.C. for not seeking assistance from outside experts who have experience with flu, including H5N1.

“There are probably hundreds or thousands of labs that could help with this serology,” Dr. Rasmussen said.

Emily Anthes contributed reporting.