African tick bite fever is caused by Rickettsia africae, an intracellular gram-negative bacillus transmitted to humans by ticks of the Amblyomma genus. African tick bite fever is part of the spotted fever group of rickettsial infections and is common in travelers to Africa. It is the second most frequent cause of fever after malaria in travelers returning from sub-Saharan Africa.

Cattle, sheep, and other animals are the natural hosts, and humans are accidental hosts. Amblyomma ticks are aggressive and can bite people multiple times. African tick bite fever typically occurs in travelers to southern African countries in areas of high rainfall during the rainy season in regions with tall grasses or abundant shade. Visitors most commonly acquire African tick bite fever in South Africa. The major risk factor is outdoor exposure on safaris, game hunting trips, military exercises, field work, and during recreational sports. Dog owners who crush engorged ticks are also at risk for acquiring infection via conjunctival eye splashes.

The disease is characterized by an acute influenza-like illness with myalgias, regional lymphadenopathy, headache, fatigue, nightmares, and fevers. Neck pain and neck stiffness can be prominent. The acute febrile illness develops 5-7 days after tick exposure. An elevated C-reactive protein, elevated liver function tests, thrombocytopenia, and lymphopenia may be seen during this stage.

The febrile illness is typically preceded by eschars forming at the site of the tick bites and a widespread rash seen in about one-third of patients. Eschars, or "taches noires," are not always apparent. The eschar may be under the scalp hair, behind the ears, in the anogenital area, or on other obscured body sites.