Rickettsia Slovaca Tickborne Lymphadenopathy And Dermacentorbornenecrosiserythemalymphadenopathy

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A novel SFG rickettsia was isolated in 1968 from D. marginatus ticks collected in Slovakia (104). Based on serological studies and C + G content, two strains were found to be close but not identical to R. sibirica and R. conorii (105). Another serologically similar strain was isolated in the former U.S.S.R., present-day Armenia, in 1974 (106). Thorough studies revealed that these strains differed from all prototype strains known by that time and a new species of SFG rickettsia, R. slovaca, have been proposed (107). Subsequently, it has been detected or isolated from ticks in many European countries where D. marginatus and D. reticulatus have been studied for rickettsiae, including France, Switzerland, Slovakia, Russia, Ukraine, Armenia, Yugoslavia, Spain, and Portugal (Figs. 11 and 12) (108,109). Infection prevalence in ticks varies from 1% to 17% (109). These tick species are generally common throughout Europe and central Asia, but D. marginatus is not prevalent in northern Europe. They are active during early spring, autumn, and winter in southern Europe. Adult ticks inhabit forests and pastures and frequently bite people entering these biotopes, particularly on the scalp. These ticks may act as vectors but also as reservoirs of R. slovaca, which is maintained in ticks through trans-stadial and transovarial transmission (104). Eastern limits of R. slovaca distribution should be extended to the Ural Mountains. Anopol isolate from this area was indeed recently identified as R. slovaca (46).

R. slovaca is an example of a human disease-causing rickettsia that has been being considered a "nonpathogenic rickettsia" for more than 20 years following its

Rickettsia
FIGURE 12 Distribution of Rickettsia spp. in Asia, Australia, and North and South Americas recognized (by 2006) as human pathogens, except R. rickettsiiand R. africae (see corresponding chapters for these two rickettsiae).

discovery. However, in 1997, the first documented case of human infection with R. slovaca was reported in a woman who presented with a single eschar of the scalp and enlarged cervical lymph nodes following the bite of a Dermacentor sp. tick in France (Fig. 10). This case was documented by seroconversion and molecular detection of R. slovaca in the eschar's biopsy, and by isolation of the bacterium from the tick (110). Clinically similar but undocumented cases had been seen previously in France, Slovakia, and Hungary, where this clinical syndrome had been named TIBOLA (111).

The number of R. slovaca infections in Europe is still, probably, under-evaluated. From January 1996 to April 2000, its role in this syndrome was evaluated in 67 patients from France and Hungary presenting with TIBOLA (112). A total of 17 cases of R. slovaca infection were confirmed in this cohort by molecular methods. Recently, 14 patients were reported from southern France. It has been suggested that R. slovaca may be responsible for as much as 25% of SFG rick-ettsioses in this region (113). Infections were most likely to occur in children and in patients bitten by a tick during the colder months of the year. Fever and rash were uncommon and sequelae included localized alopecia at the bite site and chronic fatigue. Similar cases have also recently been reported in Bulgaria (114) and Spain (115). Finally, the isolation of R. slovaca from a patient has been recently reported, providing definitive evidence that R. slovaca is a human pathogen (116).

The clinical syndrome called Dermacentor-borne-necrosis-erythema-lymphadenopathy (DEBONEL) has been recently reported in Spain (115). In half of the cases, patients were bitten by D. marginatus, which contributed to the name of the syndrome. Most cases occurred between October and April, with a peak in November. The incubation period was approximately four days (range one to eight days). All patients had an eschar at the tick-bite site (86% on the scalp) associated with regional painful lymphadenopathy, and all but one complained of headache. Low-grade fever was reported in 45% of patients. After antibiotic treatment—doxycycline, except for a child who received josamycin—all patients recovered but the eschar resulted in alopecia lasting for several months for several patients. In this series, the infection was not definitely confirmed to be due to R. slovaca. A weak and late serological response against this rickettsia was observed in 25% of the cases analyzed. Another study from Spain showed that 16.9% of Dermacentor-bitten patients develop seroconversion when tested with R. slovaca antigen (117). All available ticks collected from patients in this study were positive for R. slovaca.

It is also interesting to note that in addition to R. slovaca, another presumably pathogenic rickettsia belonging to R. massiliae genogroup, R. raoultii, has been detected in D. marginatus ticks in Spain (115,118), as previously in other European countries. As R. slovaca seems to be involved in most cases, but not all of DEBONEL or TIBOLA, one should pay attention to other rickettsiae associated with Dermacentor ticks (see "R. raoultii").

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