Rickettsialpox in North Carolina

Abstracts & Commentary

Synopsis: This study reports the first case of rickettsialpox in the southern United States caused by infection with R akari. The North American range for rickettsial disease expands even as newer agents are discovered abroad.

Sources: Krusell A, et al. Rickettsialpox in North Carolina: A case report. Emerg Infect Dis. 2002;8(7):727-728; Kelly D, et al. The past and present threat of rickettsial diseases to military medicine and international public health. Clin Infect Dis. 2002;34(Suppl 4):S145-S169.

A 48-year-old man who had worked at a golf course was admitted with fevers, chills, severe headache and a rash. Seven days prior to admission he had felt an insect bite that developed into an ulcerated papule. Two days before admission, red macules appeared over his anterior chest and then became vesicular.

The patient had a pet dog and cat but had not traveled outside North Carolina in the 3 months before admission. He did notice his cat had brought dead mice to his grounds but he never directly touched them. He reported no recent tick exposures or insect bites. On admission the patient appeared ill, was febrile, and had an eschar on his posterior right thigh. A macular vesicular rash was present on his trunk, arms and legs. All lab values were normal except his low platelet count of 85,000/ml. A clinical diagnosis of rickettsialpox was made and he was treated with doxycycline and cefazolin. He defervesced within 48 hours.

Two serum samples were submitted to CDC, Atlanta. Samples were tested by a standard IFA for IgG antibodies reactive with Rickettsia akari and R rickettsii antigens. Because of antibody cross-reactivity among the spotted fever group or organisms, confirmatory cross-adsorption testing was performed and it confirmed R akari (rickettsialpox) infection.

Comment by Michele Barry, MD, FACP

This patient had a classic clinical presentation for R akari infection with an eschar, vesicular rash, thrombocytopenia, and severe headache. Fever and vesicular rash can sometimes cause confusion with chickenpox or other viral exanthems. However, the presence of an eschar at the site of inoculation and the lack of successive crops of vesicles over time should distinguish the rash from varicella and alert clinicians to the possibility of rickettsialpox.

R akari is transmitted from mice to humans by the house mouse mite. Rickettsialpox was first described in humans in 1946 in a group of residents in apartments clustered within a 3-block area of Queens, NY! Most cases to date have occurred in large metropolitan areas of the northeastern United States. Morbidity and mortality caused by rickettsioses have had a major influence on military activities and public health for > 2000 years. The military experience with epidemic rickettsialpox has been recently described in a Clinical Infectious Disease supplement. The diseases caused by these organisms are notoriously difficult to diagnose because they share symptoms with many other febrile diseases with similar epidemiology.

The rickettsioses, historically included the families of Rickettsiaceae, Bartonellaceae and Anaplasmataceae. (see Table.) They were originally defined as obligate intracellular parasites that grew only within eukaryotic host cells. Members of the family Bartonellaceae have been removed from this family as they grow fastidiously on enriched culture media and share different DNA/RNA sequences. In the past, human rickettsial diseases caused by members of the genus Rickettsia were collectively called "typhus fever." Later the typhus fevers were differentiated by a characteristic lesion (eg, the eschar of scrub typhus), causative agent or vector (eg, louse, flea, tick, mite). Although all agents caused somewhat similar clinical syndromes, characterization of the causative agents resulted in 3 distinct groupings: spotted fever rickettsiosis; typhus (louse-borne epidemic typhus, murine or endemic typhus); and scrub typhus group.


Early in the 20th century the nonspecific Weil-Felix serological test using Proteus species bacterial antigens was used to diagnose typhus and spotted fever rickettsial disease and modified for diagnosis of the scrub typhus group. Although lacking specificity (66%) and sensitivity (80%), the Weil-Felix test has been inexpensive and commercially available to developing countries. The IFA test was developed in the 1960s and is used as a reference standard for more developed countries. Recently PCR has become available in advanced clinical labs.

Prevention and Bioterrorism Considerations

As rickettsial agents are inexpensively and easily mass produced, they are considered select agents for a potential bioterrorism threat. The US military currently has limited capability to prevent rickettsial diseases. There are no FDA-licensed vaccines for protection although there is evidence that weekly doxycycline prophylaxis can reduce morbidity. DDT used effectively during WWII to control louse-borne typhus is no longer legal to use in the United States, but DEET and permethrin treated uniforms can effectively reduce the risk of chigger, tick and flea-borne transmission of rickettsial diseases.

Dr. Barry is Professor of Medicine; Co-Director, Tropical Medicine and International Travelers’ Clinic, Yale University School of Medicine, New. Haven Conn.