SUPPLEMENTARY INFORMATION:

Coxiella burnetti is a select agent that is regulated pursuant to the HHS select agent and toxin regulations (42 CFR part 73). C. burnetii is a gram-negative intracellular bacterium that causes Q Fever. Q Fever is a zoonotic disease that causes flu-like symptoms in humans, including fever, chills, fatigue, and muscle pain. Humans become infected when they are in close contact with infected animal fluids and products.

The HHS select agent regulations (42 CFR part 73) established a process by which an attenuated strain of a select biological agent that does not have the potential to pose a severe threat to public health and safety may be excluded from the requirements of the regulations. On October 15, 2003, C. burnetii Phase II, Nine Mile Strain, plaque purified clone 4 was excluded from HHS select agent regulations as it does not pose a significant threat to public health and safety ( https://selectagents.gov/​sat/​exclusions/​hhs.htm).

As set forth under 42 CFR 73.4(e)(2), if an excluded attenuated strain is subjected to any manipulation that restores or enhances its virulence, the resulting select agent will be subject to the requirements of the regulations. On March 20, 2023, an entity informed CDC of a reversion whereby C. burnetii Phase II, Nine Mile Strain, plaque purified clone 4 spontaneously mutated. The C. burnetii Phase II, Nine Mile Strain, plaque purified clone 4 with reversion to wildtype cbu0533 displayed increased pathogenicity and virulence. The entity stated that after the excluded strain was injected into guinea pigs, a spontaneous reversion occurred that resulted in a mutant strain of the agent and the guinea pigs subsequently exhibited elevated fever and weight loss. The genetic mutation that led to the mutant strain was the reversion and restoration of a deletion in the cbu0533 gene. CDC subject matter experts have determined that this reversion in cbu0533 restored virulence and pathogenicity. Therefore, C. burnetii Phase II, Nine Mile Strain, plaque purified clone 4 with reversion to wildtype cbu0533 is determined to be a select agent and subject to 42 CFR part 73.

88 FR 54247