Association of Rickettsia helvetica with chronic perimyocarditis in sudden cardiac death

Background Richettsia helvetica is the only non-imported rickettsia found in Scandinavia. It was first detected in Ixodes ricinus ticks, but has never been linked to human disease. We studied two young Swedish men who died of sudden cardiac failure during exercise, and who showed signs of perimyocarditis similar to those described in rickettsial disease. Methods Samples from the heart and other organs were analysed by PCR and DNA sequencing. May-Grunwald-Giemsa, Grocott, and acridine-orange stains were used for histopathological examinations. Staining of R helvetica grown on shell-vials in vero cells, and the early descriptions of R rickettsii by H T Ricketts and S B Wohlbach served as controls. Immunohistochemistry was done with Proteus OX-19 rabbit antisera as the primary antibody. The structure of rickettsia-like organisms was investigated by transmission electron microscopy. Serological analyses were carried out by indirect immunofluorescence with R helvetica as the antigen. Findings By use of a semi-nested PCR, with primers specific for the 16S rRNA and 17-kDa outer-membrane-protein genes, and sequence analysis of the amplified products, genetic material from R helvetica was detected in the pericardium and in a lymph node from the pulmonary hilum in case 1, and in a coronary artery and the heart muscle in case 2. A serological response in case 1 revealed an endpoint titre for R helvetica of 1/320 (1/256 with R rickettsii as the antigen). Examination of PCR-positive tissue showed chronic interstitial inflammation and the presence of rickettsia-like organisms predominantly located in the endothelium. These organisms reacted with Proteus OX-19 antisera, and their size and form were consistent with rickettsia, Electron microscopy confirmed that the appearance of the organisms was similar to that described for spotted-fever rickettsia. Interpretation R helvetica, transmitted by I ricinus ticks, may be an important pathogen in the aetiology of perimyocarditis, which can result in sudden unexpected cardiac death in young people.