[Prevalence and clinical characterization of Coxiella burnetii infection in patients with protracted low-grade fever].

ABSTRACT

We report here a persistent form of Coxiella burnetii infection. There have been no prospective surveys of chronic C. burnetii infection reported in Japan. Until recently, it was not possible to distinguish between previous and current infection with serological tests for antibody to C. burnetii. The nested PCR method, however, allows us to appreciate the current infection by detecting C. burnetii DNA with high sensitivity. Inoculation method using an A/J mouse was performed to confirm the viability of C. burnetii. To obtain an approximation of the prevalence of C. burnetii infection in the general population, we evaluated a random sample of patients with symptoms of continuous low-grade fever for one month or more. Analysis of 54 subjects with protracted debility and fatigue symptoms identified 13 subjects as carriers of C. burnetii (24.1%). There were no significant differences in age, C-reactive protein levels (0.69 +/- 1.19 mg/dl), white blood cell counts (6,089 +/- 2,189/microliter), eosinophil (3.4 +/- 3.6%) between the patients with C. burnetii infection and infection-free subjects. All thirteen patients had experienced protracted low-grade fever (up to 37.5 degrees C) for four months to seven years (30.5 +/- 27.7 months). Transthoracic echocardiography showed no evidence of endocarditis, or echosonography revealed no abnormal findings in the liver or kidneys. Although domestic animals constitute an important reservoir of C. burnetii, only two of the positive subjects had direct contact with them and none of the positive subjects were occupationally exposed to farm animals or common sources of infection. None had a history of hospitalizations for pneumonia or hepatic disease. Interestingly, five of the thirteen patients had a history of consulting a psychiatrist, and furthermore, one had a history of several admissions in a psychiatric hospital due to chronic fatigue symptoms. Ten of the patients had a high IgE titer (> 295 IU/ml), which shows a higher prevalence than in patients without C. burnetii (76.9% 22.0%, P = 0.001). Four of them had markedly elevated IgE levels, in excess of 2,000 IU/ml. The mean value of IgE was higher in the patients with C. burnetii infection than in infection-free subjects (1,388 +/- 1,706 533 +/- 913 IU/ml, p < 0.045). Two subjects were rheumatoid factor positive and another three had autoimmune thyroiditis. Twelve of the 13 subjects provided written informed consent for treatment with minocycline (200 mg/day). One month later, all subject became asymptomatic and apyretic (37.1 +/- 0.43 degrees C to 36.7 +/- 0.56 degrees C; p < 0.025), and nested PCR did not identify C. burnetii DNA in serum samples. It should be noted that persistent symptoms including low-grade fever were observed for two weeks after the start of medication. Furthermore, three patients had persistent symptoms, and DNA detection by the nested PCR method became positive in all three patients within a few months.