"A. phagocytophilum" is transmitted to humans by "Ixodes" ticks. These ticks are found in the US, Europe, and Asia. In the US, "I. scapularis" is the tick vector in the East and Midwest states, and "I. pacificus" in the Pacific Northwest. In Europe, the "I. ricinus" is the main tick vector, and "I. persulcatus" is the currently known tick vector in Asia.

The major mammalian reservoir for "A. phagocytophilum" in the eastern United States is the white-footed mouse, "Peromyscus leucopus". Although white-tailed deer and other small mammals harbor "A. phagocytophilum", evidence suggests that they are not a reservoir for the strains that cause HGA. A tick that has a blood meal from an infected reservoir becomes infected themselves. If an infected tick then latches onto a human the disease is then transmitted to the human host and "A." "phagocytophilum" symptoms can arise.

"Anaplasma phagocytophilum" shares its tick vector with other human pathogens, and about 10% of patients with HGA show serologic evidence of coinfection with Lyme disease, babesiosis, or tick-borne meningoencephalitis.

Currently, there is no vaccine against human granulocytic anaplasmosis, so antibiotics are the only form of treatment. The best way to prevent HGA is to prevent getting tick bites.