Vol. 21, No. 12
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Tuesday, April 2, 2002
B. The Johns Hopkins Hospital, Department of Pathology, Information
provided by, Jeffrey L. Seibel MD, Ph.D.
Case description: A 52-year old white male physician presented to the Dermatology Clinic with skin lesions, headache and fatigue. The patient had returned from South Africa two weeks ago, where he had visited a game park. Two days after his return he had noticed two pimples on his thigh and abdomen. The skin lesions were accompanied by headache, fatigue, anorexia and fevers to 38.3 degrees Celsius. Physical examination showed approximately thirty slightly indurated papules on the lower back and two small eschars on the abdomen and medial left thigh. There was a papular rash on the face, trunk, hands and legs. No lymphadenopathy or hepatosplenomegaly was present. The hematocrit was 41%, white blood cell count 4900 per cu mm, platelets 224,000 per cu mm and ALT 38 IU/L. Other components of the metabolic panel and a urinalysis were within normal limits. A biopsy of one of the skin ulcers revealed a lymphohistiocytic vasculitis with epidermal necrosis, dermal edema and dermal perivascular and interstitial mononuclear cell infiltrates. Several blood vessels contained fibrin thrombi. Acute phase serology for spotted fever group Rickettsia was negative, however immunohistochemical staining of the tissue with antisera to spotted fever group Rickettsia was positive. The temporal relationship between the illness, travel to South Africa and the presence of Rickettsia in the tissue led to a diagnosis of African tick-bite fever.
Organism: Rickettsia africae is the causative agent of African tick-bite fever, the most common tick-borne rickettsial infection in sub-Saharan Africa. Like other Rickettsia, R. africae is a fastidious bacteria that lives as an obligate intracellular parasite. It is a pleomorphic coccobacillus measuring between 0.3 and 2.0 microns in greatest dimension. The mammalian reservoir is cattle and game, and the transmitting vector is the hard-bodied tick, Amblyomma. African tick-bite fever is highly prevalent in Sub-Saharan Africa. Seroprevalence in Zimbabwe, Tanzania and South Africa is 30-56%. Several cases have also been reported in the Carribean Island of Guadeloupe.
Clinical manifestations: The incubation period for African tick-bite fever is approximately 7 days. It is generally a mild disease and presents with headache, fever, regional lymphadenopathy and ulceration at the site of one or multiple tick bites. Although each tick takes only one blood meal at a time, multiple bites occur in 50% of cases because Amblyomma ticks tend to cluster around their nests and feed together on the same victim. This is in contrast to the single lesion of Mediterranean spotted fever, also found throughout Africa, southern Europe and southern Asia. This disease is caused by R. conorii, whose tick vector Rhipicephalus sanguineus feeds alone. Myalgia is present in roughly 60% of cases of African tick-bite fever. Maculopapular, pruritic or vesicular rash is present in only 50%. Complications of infection are rare.
Diagnosis: A presumptive diagnosis of African tick-fever is usually made clinically. R. africae crossreacts serologically with other spotted fever group Rickettsia, but acute titers are typically negative for 10-14 days after infection. Biopsy of the bite eschar can be an excellent tool in acute infection. The histologic picture described above is typical, but not specific. Indirect immunofluorescence on frozen tissue sections reportedly has a sensitivity of nearly 70% and specificity of 100%, especially if involved blood vessels are present in the section. Immunohistochemical stains, as used in the case above, are research tools that are not widely available. The diagnosis can be confirmed by a four-fold or greater rise in convalescent spotted fever group Rickettsia (e.g. R. rickettsii) serologic titers. Serologic tests specific for R. africae have been described. Culture is not practical since the organism is an obligate intracellular parasite and can only be grown in cell culture, only available in research laboratories. Doxycycline and fluoroquinolones are the most frequently used antibiotics, however antimicrobial sensitivity testing is difficult, again due to the intracellular location of the bacterium. Some in vitro data suggests that R. africae is sensitive to rifampin but resistant to erythromycin. Vaccines consisting of recombinant fragments of two major outer membrane proteins of spotted fever group Rickettsia (rOmpA and rOmpB) are in development.
References:
2. Kelly PJ, et al. Rickettsia africae sp. Nov., the etiological agent of African tick bite fever. Int J Syst Bacteriol (1996); 46:611-614.
3.Rolain JM, et al. In vitro susceptibilities of 27 Rickettsiae to 13 antimicrobials. Antimicrobial Agents and Chemotherapy (1998); 42:1537-1541.
4. Diaz-Montero CM. Identification of protective components
of two major outer membrane proteins of spotted fever group Rickettsia.
Am
J Trop Med Hyg (2001); 65:371-378.
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