Coxiella burnetii and Atypical Respiratory Infectious Burden in Stroke

Coxiella burnetii and Atypical Respiratory Infectious Burden in Stroke To the Editor: We have previously reported the seroprevalence of 3 common atypical respiratory pathogens, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila, in casecontrol studies involving an elderly cohort of stroke/transient ischemic attack (TIA) and medical patients.1 We concluded that the risk of stroke/TIA appeared to associate with the aggregate number of chronic infectious burden of these atypical respiratory pathogens.1 We have now determined the seroprevalence (immunoglobulins, IgG and IgM) of Coxiella burnetii, another well-recognized atypical respiratory pathogen in this same cohort of patients. Using commercial enzyme-linked immunosorbent assay (ELISA) kits (PANBIO Ltd), the seropositivity of Coxiella burnetii IgG was found in 2 (2.4%) out of the 85 ischemic stroke/TIA cases, and none in the 84 control subjects. None of the 85 cases and 3 (3.6%) of the 84 control subjects were seropositive for C burnetii IgM. With such sparse data and zero counts (ie, 0/84 and 0/85), we were unable to estimate any meaningful relative risk; therefore, it was impossible to make any conclusion about association between C burnetii infection and stroke. Nevertheless, the current Coxiella burnetii in Elderly Patients with Stroke (C-BEPS) study served as a pilot seroepidemiological survey of C burnetii infection in hospitalized elderly stroke/ medical patients. Previous studies in the United Kingdom reported a C burnetii IgG seroprevalence of 15% to 27% in farm workers, and 4% to 11% in people working in nonfarming sectors.2 We were unable to obtain more detailed occupational/ farming history in our cohort retrospectively. Asymptomatic2,3 infection or false seropositivity was a possibility. According to the manufacturer’s data, C burnetii ELISA had a sensitivity, specificity, and agreement of 72.2%, 100%, and 79.6%, respectively, for IgG, and 97.1%, 84.4%, and 89.8%, respectively, for IgM, when tested against the immunofluorescence reference method. ELISA had been recognized as a useful tool for seroepidemiological studies.1,2 Various microorganisms may contribute to atherogenesis and atherothrombosis through inflammatory/immunological mechanisms.1,4 Among these, C pneumoniae is the one most investigated and implicated in the infectious hypothesis of atherosclerosis, an acknowledged inflammatory disease.1,4 Like C pneumoniae, C burnetii is a Gram-negative, intracellular bacterium that may result in chronic infection and exert a chronic immunological response.1–6 Furthermore, C burnetii, C pneumoniae, M pneumoniae, and L pneumophila are all atypical respiratory pathogens that share similar microbiological and clinical features, including vascular invasion and neurological manifestations.1–3,5,6 Indeed, C burnetii infection was reported to associate with cerebrovascular and ischemic heart diseases.6 If the infectious hypothesis of atherosclerosis holds true, it is likely that a large but specific group of microorganisms (specific infectious burden), rather than a selected few, will be discovered to be involved in atherogenesis and atherothrombosis. This concept has implication in the design of future antimicrobial interventional clinical trials in stroke and other atherosclerotic vascular diseases, because subjects infected with a specific infectious burden may be identified and randomized to receive specific antimicrobial/therapeutic agents or even vaccines. Atypical respiratory pathogens can cause up to 50% of cases of community-acquired pneumonia,1 in addition to other systemic manifestations. The development of effective vaccination program in future is becoming a pressing public health issue that will not only prevent atypical respiratory infection but also may clarify if the infectious burden has a causal relationship with stroke and other atherosclerotic vascular diseases.