FLINT, MI -- The Centers for Disease Control and Prevention has discovered the first genetic links between city water and patients diagnosed with Legionnaires' disease in Genesee County -- something researchers have sought throughout the Flint water crisis.

But instead of closing the book on what caused the outbreak that killed 12 people in 2014 and 2015, the scientific matches instead raise new questions about whether Flint's water system was the source of the outbreak.

Molecular testing by the CDC in late 2016 established the connection between a water sample taken from McLaren-Flint hospital and three sputum samples from patients who were diagnosed with Legionnaires', officials with the Michigan Department of Health and Human Services told MLive-The Flint Journal.

DHHS learned of a genetic match between the water and Legionnaires' patients only last month, and days later, notified McLaren and the Genesee County Health Department that each may be required to turn over additional water samples and other records to the state.

But while the state has focused on McLaren since the genetic links were found, other experts say the three matches, including one victim who was never a patient at McLaren, suggest that Legionella thrived throughout the Flint water system, making it the real culprit in Legionnaires' deaths and illnesses in 2014 and 2015.

Seventy-eight people in the county contracted the disease during those two years, during parts of which the city used the Flint River as its source of water without treating it to make it less corrosive to lead pipes and plumbing.

"The presence of Legionella in Flint was widespread," said Dr. Janet Stout, a research associate professor at the University of Pittsburgh and a national expert on the disease. "The (laboratory) results show that strains (of the bacteria) were throughout the water system."

On Tuesday, Feb. 14, the state ratcheted up pressure on the hospital, ordering McLaren to turn over information related to its Legionnaires' cases and releasing a letter from a hospital contractor that claimed "the supply water coming from the city of Flint is not contributing to the Legionella issues at McLaren and any issues are likely internal to the hospital system."

Stout was hired by McLaren to assist the hospital in defending itself against a $100-million lawsuit and against state claims that its failings caused what the state calls the "largest healthcare-associated Legionnaires' outbreak known" in the United States.

Amy Pruden, a Virginia Tech university professor and one of five authors of a July 2016 peer-reviewed study on Legionella in Flint water, said the three genetic matches could represent how widespread the bacteria was in city water.

Pruden's study found Legionella levels up to 1,000 times higher than normal tap water in Flint, and said finding a patient who's clinical isolates -- or bacteria -- matched the McLaren water sample without having been hospitalized there "suggests that same strain may have been elsewhere."

The state confirmed the CDC testing showed the lack of a connection between one of the three patients and McLaren, but the agency has not previously released details of that case.

In contrast, MDHHS used the genetic matches between the hospital and the infected patients who stayed at McLaren as one reason for an order issued Feb. 14 that claims McLaren-Flint's water system "is a nuisance, unsanitary condition, or cause of illness" in the community.

Angela Minicuci, a spokeswoman for MDHHS, said state medical officials were told of the CDC testing, which matched a clinical sample from from a November 2016 Legionnaires' patient to a water sample taken in August 2016 at McLaren.

Clinical samples from two other Legionnaires' patients, both diagnosed in 2015, "were also highly related to the McLaren water sample," Minicuci said in an email to MLive-The Flint Journal.

The CDC declined to answer questions about its testing, the results of which were turned over to DHHS in January, according to Minicuci.

Dr. Eden Wells, the state's chief medical executive, said DHHS hasn't been able to determine with certainty how the Legionnaires' patient never hospitalized at McLaren was exposed to the same bacteria strain found in hospital water, calling it an open "medical detective case (that) requires a lot of sleuthing."

"Do we know what the linkage is?" Wells asked. "Not at this time."

Among the possible explanations for the genetic match, according to DHHS, are an association that was never identified during the case investigation, such as a visit to McLaren rather than a hospitalization or exposure to the hospital's cooling towers.

"Cooling towers are always high on our list of concerns when trying to identify a potential Legionella exposure source," Minicuci said. "We don't have any indication or environmental samples to show that this strain is elsewhere in the community, though that's not impossible, but we do have two healthcare-associated cases over a two-year period that match the the McLaren sample, as well as this case strain."

Clinical samples from all three patients came from the infected sputum -- their infected phlegm -- that's typically collected by a cough into a cup or obtained by a hospital from the throat or lung, after which it is cultured for routine bacteria with a specialized culture for Legionella, according to DHHS.

A clinical isolate is a bacteria, or other infectious agent such as a virus or a parasite, that is isolated or grown from a patient's specimen.

Pruden said even though the water sample matching the patient isolates was collected months after Flint discontinued use of the Flint River, the same strain of the bacteria can persist in plumbing even after Flint was switched back to Lake Huron water.

The professor said the genetic matches are "very relevant to the continuing conversation of demonstrating whether or not switching to the Flint River water triggered the countywide spike in Legionnaires' and working toward figuring out exactly where and how the patients were likely exposed and infected with the disease."

"Despite the difference in time, it shows that a strain that is native to McLaren plumbing matched the strains found in patients," Pruden said in an email. "It shows the that strains of Legionella living in Flint tap water matched with strains found in patients. However ... we don't know if this same strain is found widely in other parts of Flint."

Pruden's report on Legionella and Flint last year studied both single-story homes and businesses in Flint and Flint Township and at Hurley Medical Center and McLaren, both of which are located in areas of the city where water is more likely to be stagnant.

DHHS says McLaren was associated with 21 Legionella cases in 2014, 29 in 2015, and two in 2016; the vast majority of hospital-related Laegionnaires' cases; and 10 of 12 deaths from the disease.

Although no Legionella was found in Flint Township, which never used Flint River water, the bacteria was found in Flint tap water at various locations, the study says, supporting the theory that interrupted corrosion control in Flint caused a release of iron, nutrients and depleted chlorine residual into the entire distribution system, driving the abundance of Legionella.

Minicuci said the Flint water system should have been assumed to have Legionella, "and high-risk facilities should closely monitor the water coming into their facility and take steps to prevent exposures to their vulnerable patients."

Hospitals and large institutional buildings are known to be particularly susceptible to Legionella colonization, according to Pruden's study.

McLaren said in a statement Feb. 14 that the state "provided absolutely no support in 2014 and 2015" as evidence piled up that Legionella was a problem in Flint water.

Not only was the city being run by a state-appointed emergency manager when the decision was made to change water source, special prosecutors also allege that employees from the state Departments of Environmental Quality and DHHS allowed problems with lead and Legionella to occur and continue by failing to do their jobs in accordance with state law.

"Now that criminal charges have been made against several state and city employees and additional indictments are possible, the state is taking an aggressive role in retroactively casting blame for cases it knew about -- and did nothing about -- for years," McLaren's statement says.

"Despite the fact that dozens of Legionnaires' disease cases have been reported in patients that have had absolutely no contact with our facilities, and despite the growing consensus among public health and infectious disease specialists that the city's use of the Flint River as a water source is the prime contributor to our community's Legionnaires' disease epidemic, the state refuses to broaden its perspective and hold itself and others accountable for the inaction of prior years," the hospital's statement says.

Public health officials identified the Flint River as a potential source of the city's Legionnaires' outbreak as early as 2014, but city, county, state and federal officials never told the public until more than a year later.

Gov. Rick Snyder also claimed he was left in the dark about the possible connection, and his emergency managers continued to use the river as a source of water until connections between spikes in lead levels and in the blood of Flint children were uncovered late in 2015.