Rodent-Associated Bartonella Febrile Illness, Southwestern United States

Jonathan Iralu; Ying Bai; Larry Crook; Bruce Tempest; Gary Simpson; Taylor McKenzie; Frederick Koster

Disclosures

Emerging Infectious Diseases. 2006;12(7):1081-1086. 

In This Article

Discussion

This study provides preliminary serologic evidence for a Bartonella or Bartonella cross-reactive species that is causing acute febrile illness in immunocompetent adults in the rural southwestern United States. Five patients who seroconverted to rodent-associated antigen had fever, myalgias, headache, and chills with varying degrees of leukopenia, mild hepatitis, and thrombocytopenia. Four other patients with a single elevated titer 2–5 weeks into their illness had more severe hepatic injury. In the absence of culture- or PCR-positive evidence of Bartonella infection in any of these patients, the interpretation of these serologic observations is related to the cross-reactivity between Bartonella species as well as non-Bartonella species, interpretation of the quantitative IFA titer, variations among pathogens to stimulate antibody responses, timing of serum specimen collection, and the route of exposure.

Although antigens derived from Bartonella isolated from N. albigula were used, this process does not imply that the human infection was caused by a Bartonella strain that naturally infects N. albigula. Serologic cross-reactions among Bartonella species are common,[20] and the IFA is unable to distinguish between infection with B. quintana or B. henselae.[21] The cross-reactivity between rodent-associated and known Bartonella pathogen–associated antigens was expected and found to some degree in nearly all cases. We did not find clear evidence for infection with Bartonella species known to cause disease in humans, including B. henselae, B. quintana, B. vinsonii, and B. elizabethae, in the sense that titers to rodent-associated, particularly NA-AB, antigens were always higher than those for known human Bartonella species. The lack of cross-reactivity in 3 patients is consistent with a rodent-associated Bartonella infection, although infection with a Bartonella associated with a nonrodent animal cannot be ruled out.[22]

Identification of Bartonella infections in humans in the southwestern United States is important because cat-scratch disease is not common in this region, and cat fleas, presumed vectors for B. henselae, do not naturally exist in such arid environments.[23] Cross-reactivity between Bartonella antigens and antigens of C. burnetii and Chlamydia species has been demonstrated.[24,25] Except for the woman in group D who had clear evidence of acute Q fever hepatitis, significant Bartonella titers ≥128 were not associated with detectable antibody to phase I or II Coxiella antigens in the complement fixation test in all 8 patients tested. None of the patients had a condition associated with nonspecific immune stimulation such as HIV infection, injection drug use, or collagen vascular disease that could account for false-positive results.

The IFA was developed at CDC[21] and has been assessed most extensively in the diagnosis of B. henselae and B. quintana infection in the United States.[20] At the National Referral Center of CDC, a titer of 64 is considered positive.[20] When a strict case definition is used for cat-scratch disease, this titer has a sensitivity of ≈80% and a specificity of 93% to 96%.[20,21,26] Other investigators have found greater specificity when titers of 128,[27] 256,[25] or 512[28] were used to diagnose cat-scratch disease. An IFA titer of 512 to B. henselae in adults with no exposure to cats or illness compatible with cat-scratch disease was uncommon (<1%) in 1 study in Germany.[27] We used a conservative threshold IFA titer of 512 to present clinical data on 9 patients based in part on this experience with cat-scratch disease, recognizing that immunogenicity to immunodominant antigens may vary among species of the same genus. The usefulness of a single titer of 1:512 to NA-AB antigens ( Table 3 ) is unknown because IFA titers to B. henselae persist during the first year after infection.[20]

The clinical syndrome associated with seroconversion to NA-AB antigens was characterized by either a brief undifferentiated febrile illness or fever accompanied by hepatic injury. Clinical evidence for inflammation in the lung, heart, kidney, and nervous system was not apparent. Infection with B. henselae, particularly in immunocompromised hosts, has been documented to involve the liver.[2] Moreover, thrombocytopenia and leukopenia, which were common in our small sample of febrile patients, have also been associated with B. quintana infection[29] in immunocompetent adults and with B. henselae infection in immunocompromised adults.[2] No patient had intraerythrocytic bacilli visible on Giemsa-stained blood smear[30] (F. Koster, unpub. data). A clear definition of the syndrome awaits definitive identification based on culture of the pathogenic species from patients. Thus, a concerted effort to identify acute infections with rodent-associated Bartonella should be undertaken with specific serologic assays as well as intensive PCR-based diagnostics and culture techniques specific to the fastidious Bartonella genus.

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