Mediterranean spotted fever in the Trakya region of Turkey

Abstract

Mediterranean spotted fever (MSF) is caused by a tick-borne pathogen, Rickettsia conorii subsp. conorii, belonging to the spotted fever group (SFG) rickettsiae. The aim of the present study was to evaluate the cases with confirmed diagnosis of MSF from 2003 to 2009 in the Trakya region of Turkey. Patients with high fever, maculopapular rash (involving the palms or soles) and/or a black inoculation eschar at the site of the tick bite (tache noire) were included in the study. Before doxycycline treatment, skin biopsy specimens, preferably from the eschar or from the maculopapular rash, were obtained for DNA extraction. Immunofluorescence assay (IFA) was performed to detect IgM and IgG antibodies against R. conorii in acute and convalescent sera. Afterwards, a standard PCR reaction using primers suitable for hybridisation within the conserved region of genes coding for outer membrane protein A (ompA) and citrate synthase (gltA) and DNA sequencing were performed. There were 128 patients with confirmed MSF diagnosis. Using IFA, seroconversion or a fourfold or greater rise in titre was observed in 97 (77%) patients, whereas a single high titre was demonstrated in 16 (12.7%) patients. According to PCR analysis, 77 (72.6%) of 106 biopsy samples showed positive results. Of these, 58 (73%) of 79 biopsy specimens were from the eschar and 19 (70%) of 27 specimens were from the maculopapular rash. No significant difference was found between the rate of positive skin biopsies taken from the eschar and the maculopapular rash. DNA sequence analysis was performed to all PCR-positive cases, and R. conorii conorii (type strain: Malish, ATCC VR-613) was detected in each of them. MSF is prevalent, but has been underdiagnosed and underreported so far in Turkey. It is a potentially severe and even fatal disease resembling viral haemorrhagic fevers that has to be included in the differential diagnosis of febrile illness associated with thrombocytopenia, even in the absence of an eschar or a tick bite. While IFA allows for retrospective diagnosis in MSF, advanced molecular techniques provide the rapid detection of rickettsia in all skin samples, including eschar and maculopapular rash.