Boutonneuse Fever and African Tick-bite Fever

Boutonneuse fever and its agent were first described in North Africa in 1910, and variants of R. conorii have been identified in South Africa, Kenya, Somalia, Israel, Morocco, Ethiopia, Russia, India and Pakistan. In parts of Africa, tick-transmitted diseases caused by R. conorii and R. africae overlap geographically. Although their clinical manifestations also overlap, there are differences sufficient to distinguish two different disease agents. Generally milder than boutonneuse fever, African tick bite fever has a lower incidence of rash, which is more often vesicular and sparse, a higher incidence of eschars that are frequently multiple, and more prominent regional lymphadenopathy. Each of these diseases has been diagnosed in the United States after patients return from vacation abroad, particularly from African safaris.

Rickettsialpox

R. akari has been recognized mainly in the urban United States as an agent of rickettsialpox The organism maintained in a mite-mouse cycle with humans as an accidental host. The organism may, however, have a broader host range and geographic distribution.

A papule appears at the site of mite feeding in the skin during the incubation period, and over 2-7 days, evolves into an eschar. Later fever, chills, malaise, headache, and myalgia develop, followed after 2-6 days by a macular rash that becomes maculopapular and then vesicular before crusting and healing. Fatalities have not been reported.

Cat Flea Typhus

Despite the widespread geographic distribution and prevalence of R. felis in cat fleas, there have been only a handful of clinical investigations of undertaken to diagnose cat flea typhus.

Among eight reported cases of human infection with R. felis (five diagnosed by polymerase chain reaction [PCR] and three by differential antibody titers), all had fever and constitutional symptoms. The majority manifested rash, headache, and central nervous system (CNS) involvement, and variable proportions suffered nausea, vomiting, diarrhea, abdominal pain, myalgia and conjunctivitis. The actual spectrum of illness of this infection requires further clinical studies.

Typhus Fever

Rickettsia prowazekii infections occur in three situations: louse-transmitted epidemics, reactivation of a long-standing latent infection, and zoonotic infection transmitted from flying squirrels by their ectoparasites. Onset of disease is characterized by fever, chills, headache, and myalgia. Macules of 2-6 mm usually appear first on the trunk on day 5 and later spread to the extremities. Rales, conjunctival injection, and delirium are frequent manifestations. Reactivated typhus is a milder version with the same signs and symptoms. Flying squirrel-associated typhus has also been described as less severe; whether this is due to antimicrobial treatment or less virulent strains of rickettsiae is unclear.

Murine Typhus

Flea-borne R. typhi infections cause extreme discomfort but are seldom fatal healthy young individuals. The difficulty in detecting a rash in darkly pigmented skin was evident in a study finding only 20% of experimentally infected African-American volunteers had rashes, compared to 80% of Caucasian volunteers. The infection can follow a mild course in children with as many as half suffering only fever at night, but necessitates intensive care unit support in 10% of hospitalized adult patients. Pneumonitis or meningoencephalitis can be the major manifestation in some patients.

Treatment of Rickettsioses

Doxycycline is the drug of choice for the treatment of infections caused by Rickettsia except in cases of pregnancy and tetracycline hypersensitivity. some studies have shown that doxycycline is superior to chloramphenicol for the treatment of Rocky Mountain spotted fever as it is associated with a lower case fatality rate and a lower hospitalization rate. Several fluoroquinolones, azithromycin, and clarithromycin, have been used successfully to treat boutonneuse fever but are not recommended for more pathogenic rickettsioses. It should be emphasized that rickettsiae are highly resistant to most antibiotics. Most fatal cases of Rocky Mountain spotted fever have received substantial courses of antimicrobial treatment, including beta lactams, aminoglycosides, and erythromycin. Sulfonamide antimicrobials actually appear to exacerbate the severity of rickettsial infections.

Immunity

Rickettsial infection stimulates an early innate immune response with activation of natural killer cells and production of gamma interferon (gamma IFN), which act in concert to dampen rickettsial growth. Acquired immunity develops with clonal expansion of CD4 and CD8 T lymphocytes as well as antibody-producing B cells. Clearance of intraendothelial rickettsiae is achieved by rickettsicidal effects due to cytokine activation of the infected endothelial cells themselves. Cell mediated immunity (CMI) plays an important role as expected in infection by an intracellular parasite, but antibodies (including those directed at epitopes of OmpA and OmpB) also play a role in protective immunity.