Spotted Fever Rickettsiae and Rickettsioses in Germany



Fig. 15.1
Phylogenetic relationships between important Rickettsia species



In Germany, only limited data on the prevalence of rickettsiae in ticks have been available so far, and research on rickettsioses in ticks has been started rather recently (Hartelt et al. 2004; Dautel et al. 2006; Wölfel et al. 2006). In the available studies, mainly molecular detection methods are used to detect rickettsial DNA in ticks. All studies we have identified through a literature review together are patchwork, and only spotlights of the spatial distribution of the particular rickettsial species are possible. Neither a framework of systematic sampling of ticks in Germany nor a nationwide screening for pathogens they may harbour is existing at the moment. But based on these data, the rickettsiae of the spotted fever group transmitted by ticks seem to play a major role. A total of six Rickettsia species have been identified in Germany so far. R. helvetica and R. raoultii were detected in Ixodes (I.) ricinus and in Dermacentor (D.) reticulatus, respectively. A very recent study identified DNA of R. felis and R. helvetica in fleas from various animals (Gilles et al. 2008). The detection of R. felis is supported by the description of two human cases of flea-borne spotted fever (Richter et al. 2002). In 2002, a so far unknown rickettsial species was detected in I. ricinus, collected in a city park in Munich, southern Germany, and was named R. monacensis (Simser et al. 2002). Another rickettsial species, R. massiliae or a closely related species was detected in one single Ixodes ricinus tick from south-eastern Germany (Dobler and Wölfel 2009). Already more than 30 years ago, the isolation of a Rickettsia species, later to be identified as Rickettsia slovaca from D. marginatus ticks, was reported (Rehácek et al. 1977). Here, we intend to provide an overview of the current knowledge of each of the Rickettsia species described in Germany thus far (Table 15.1).


Table 15.1
Known Rickettsia species in Germany














































Rickettsia species

Vector (prevalence)

Possible or suggested vertebrate reservoir

Human illness

R. helvetica

Ixodes ricinus (3–10%)

Cattle, game animals, rodents

Aneruptive fever, endocarditis (?)

R. monacensis

Ixodes ricinus (0.5%)

Lizards, other reptiles

Spotted fever

R. massiliae

Ixodes ricinus (1.7%)

Rodents

Spotted fever

R. felis

Ixodes ricinus (?)

Cats

Flea-borne spotted fever

Ctenocephalides felis

R. raoultii

Dermacentor reticulatus (20–50%)

Rodents

TIBOLA (?)

R. slovaca

Dermacentor marginatus

Sheep, goat

TIBOLA


15.1.1 Rickettsia helvetica



15.1.1.1 Prevalence in Ticks


Several studies in different parts of Germany confirm the presence of R. helvetica. In the federal state of Baden-Württemberg in south-western Germany, adjacent to Bavaria in the West, 13% of I. ricinus were found positive for R. helvetica (Hartelt et al. 2004), and in various public parks in Bavaria, an average of about 7% of the I. ricinus ticks carried R. helvetica (Schorn et al. 2011). In eastern Germany, 18.8% of adult I. ricinus were positive in Thuringia (Hildebrandt et al. 2010), in Saxony this percentage was 12.7% (Silaghi et al. 2011), while in Berlin only 14.2% of I. ricinus nymphs were reported positive (Pichon et al. 2006). Assuming that R. helvetica is the rickettsial species most frequently found in I. ricinus, this species would account for the majority of rickettsiae found in studies which do not distinguish between the species because a generic PCR (e.g. targeting the gltA gene, Wölfel et al. 2008) is used; the overall prevalence of R. helvetica is above 10%.


15.1.1.2 Seroprevalence in Animals


No detailed data on the seroprevalence rates of antibodies against R. helvetica in animals are available. In a study in Myodes (M.) glareolus and Apodemus (A.) flavicollis, only 1/110 transudates of M. glareolus and 0/98 transudates of A. flavicollis were found positive for R. helvetica antibodies, while 14/110 sera of M. glareolus and 11/98 transudates of A. flavicollis showed antibodies against R. conorii (Dobler and Wölfel 2009).


15.1.1.3 Natural Transmission Cycle


There is some evidence that larger game animals and larger farm animals may play a role for the transmission of R. helvetica. However, systematic studies are lacking. There is, however, good evidence that transovarial transmission may play a major role for the maintenance of R. helvetica in nature. In a study testing I. ricinus of different developmental stages from eastern Bavaria for R. helvetica, 7/136 unengorged tick larvae were found positive, implicating that the larvae had been infected via transovarial transmission.


15.1.1.4 Seroprevalence in Humans


Seroprevalence data of antibodies against R. helvetica in humans in Germany are missing so far. In a serosurvey in France, 9.2% of tested forest workers in the Alsace region were found positive for IgG against R. helvetica (Fournier et al. 2000). In a seroprevalence study in Poland, none of 129 analysed sera showed clear positive reactivity against R. helvetica (Podsiadly et al. 2011).


15.1.1.5 Medical and Veterinary Importance


R. helvetica seems to play a minor role in human pathogenicity. An earlier report on its role in aetiology of myocarditis has not been confirmed so far (Nilsson et al 1999). However, it seems to play a role as cause of undifferentiated flu-like disease with fever and constitutional symptoms (“aneruptive fever”) during the time of activity of I. ricinus (Fournier et al. 2000). Rather recently, a case of meningitis was traced to R. helvetica in a patient in Sweden (Nilsson et al. 2010). Seroprevalence rates of 5–10% imply that infections of R. helvetica in humans may be more frequent than thought but that, in many cases, symptoms may be lacking or mild. There is no evidence that R. helvetica is causing animal disease.


15.1.2 Rickettsia monacensis


Rickettsia monacensis is a rickettsial species which was detected in ticks (I. ricinus) several years ago in a city park in Munich, southern Germany (Simser et al. 2002). Furthermore, two additional strains of R. monacensis could be isolated from ticks (I. ricinus) in the district of Amberg, north-eastern Bavaria, about 200 km north of the original location of isolation. Further characterization showed that several genes of the two new isolates showed highest homologies with R. monacensis and R. sp. IRS4/IRS3 (Dobler et al. 2009).


15.1.2.1 Prevalence in Ticks


While no data on the prevalence of R. monacensis in ticks of the original isolation are available, additional data on the detection of this rickettsial species in ticks in north-eastern Bavaria resulted in a prevalence of 0.55% (8/1,450) for R. monacensis in I. ricinus. In Thuringia, 12 out of 64 rickettsiae-positive I. ricinus of which the species could be determined (147 out of 1,000 tested I. ricinus were positive for Rickettsia spp.) were R. monacensis (Hildebrandt et al. 2010). The detection in this region constitutes the most northern detection of this rickettsial species so far. Rickettsia monacensis since then has been detected in additional European countries. A recent study found R. monacensis in Hungary with a prevalence rate of 0.9% (Sreter-Lancz et al. 2005). The area where R. monacensis had been detected is close to the former Czechoslovak Republic, where R. sp. IRS4/IRS3 was detected (Sekeyova et al. 2000). Further studies also detected R. monacensis or a very closely related strain in Bulgaria (Christova et al. 2003). Molecular studies comparing the two Bavarian strains of R. monacensis showed that R. monacensis is closely related or identical to R. sp. IRS4/IRS3 (Dobler et al. 2009). These results are supported by similar results from a Hungarian group (Sreter-Lancz et al. 2005). Further studies in humans and molecular comparisons of German and Spanish strains have to show whether R. monacensis could also exhibit pathogenicity in humans in Germany and to determine the genetic homogeneity or plasticity of this rickettsial species over its wide geographical range.


15.1.2.2 Prevalence in Animals


There are no data available on the seroprevalence rates of antibodies against R. monacensis in animals. In this context, it should be stated that antibodies within the spotted fever-group and the typhus-group rickettsiae are cross reacting, but there is currently no species-specific serological test available that would allow the allocation of a particular sero-reactivity to a particular Rickettsia species within any of the two groups. This in turn means that any seroprevalence data can only be judged as group-specific antibodies.


15.1.2.3 Natural Transmission Cycle


There is increasing evidence that R. monacensis is circulating within a transmission cycle of ticks of the genus Ixodes and reptiles, mainly lizards (de Sousa et al. 2010). This host preference may explain the relatively low prevalence rates in ticks which have been found so far. On the other hand, a higher prevalence would be expected in climatic warmer regions, for example, the Mediterranean countries, with a year-round activity and higher abundance of reptiles in comparison to our regions north of the Alps. Further data on transovarial or transstadial transmission are not available. It is also not clear to what extent Ixodes ticks serve as vectors and as reservoirs for R. monacensis.


15.1.2.4 Seroprevalence in Humans


No data on the seroprevalence of antibodies against R. monacensis are available.


15.1.2.5 Medical and Veterinary Importance


More recently, R. monacensis was detected in the blood of two patients in Spain presenting with a non-pruritic macular rash. Both patients did not show any eschars but sought medical attention with a diagnosis of Mediterranean spotted fever (Jado et al. 2007). These two patients are the first patients with R. monacensis as etiologic agent and demonstrate the pathogenic potential of this rickettsial species. So far, however, no human cases with symptoms of spotted fever were described in the area where R. monacensis had been isolated in Germany. No data on the pathogenesis in animals are available.


15.1.3 Rickettsia massiliae


Rickettsia massiliae was detected in a brown dog tick (Rhipicephalus sanguineus) near Marseille in 1992 and finally was characterized as a distinct species (Beati and Raoult 1993). Since that time, it has been detected in southern Europe (Greece, Portugal, Spain) and central Europe (Switzerland) as well as in some African countries (Central African Republic, Mali). Recently, it was also detected on the American continent, in northern Arizona and in Argentina (Babalis et al. 1994; Bacellar et al. 1995; Beati et al. 1996; Fernandez-Soto et al. 2006; Santos-Silva et al. 2006; Bernasconi et al. 2002; Eremeeva et al. 2006).


15.1.3.1 Prevalence in Ticks


Rickettsia massiliae or a closely related (according to the ompB gene) rickettsial species was detected in one I. ricinus tick in an eastern Bavarian district (Dobler et al. 2009). To our knowledge, this constitutes the first and so far only detection of R. massiliae at all in Germany and also in ticks of the species I. ricinus. The medical importance for humans could be demonstrated by isolation of this rickettsial species from a patient with a classical spotted fever in Parma, Italy (Vitale et al. 2006). In Argentina, a patient showed a severe form of spotted fever caused by R. massiliae (García-García et al. 2010). Ticks of the genus Rhipicephalus seem to constitute the main vector and possible reservoir of R. massiliae in the Mediterranean, in Africa and in parts of northern and southern America. Rh. sanguineus is a highly abundant ixodid tick species of the warmer climate zones worldwide. If this tick species indeed serves as the main vector, this would argue for an overlapping distribution of R. massiliae with the corresponding geographical range of Rh. sanguineus. Because of high infestation rates of dogs with this particular tick species in the Mediterranean and the large number of dogs that travel from there, Rh. sanguineus is frequently imported into yet non-endemic countries, for example, Germany. Travelling infested dogs thus might also be carrying R. massiliae into different parts of the world. Due to the non-existence of Rh. sanguineus in Germany, the detection of this rickettsial species in I. ricinus is somewhat surprising. However, a former detection in ticks (Rh. sanguineus) in the Tessin in Switzerland seems to make a distribution north of the Alps at least possible. Furthermore, Czech scientists recently also reported on the detection of rickettsial DNA closely related or identical to R. massiliae in I. ricinus in the Slovak Republic (Derdáková et al. 2011). These results imply that R. massiliae or a closely related Rickettsia species may be distributed in east-central and maybe central Europe. Further studies in ticks will have to show to what extent R. massiliae is circulating in Germany and whether it could be of importance as a human pathogen in the respective area.


15.1.3.2 Prevalence in Animals


Data on prevalence of rickettsiae in animal hosts other than ticks are not available. Also no information on seroprevalence of R. massiliae antibodies in animals is available.


15.1.3.3 Natural Transmission Cycle


No information on the transmission cycle of R. massiliae is yet available. It may, however, be speculated that dogs may play a potential role as vertebrate hosts as they may constitute important vertebrate hosts for the brown dog tick, Rh. sanguineus, which is the main vector of R. massiliae in the Mediterranean and in Africa. In Slovak Republic, R. massiliae was detected in ear biopsies of rodents. However, the potential role of rodents for R. massiliae has not been elucidated so far. As with the R. massiliae sequence detected in I. ricinus from eastern Bavaria, Rh. sanguineus is not present in Slovak Republic. Hence, another tick species than Rh. sanguineus, maybe I. ricinus, has to serve here as a vector and potentially also as reservoir.


15.1.3.4 Seroprevalence in Humans


Few population-based seroprevalence studies on antibodies against R. massiliae are available. In a study on patients with fever and symptoms compatible with spotted fever, a total of 15 patients from Catalonia, Spain, exclusively reacted against R. conorii and R. massiliae with significantly higher titres against R. massiliae than against R. conorii (Cardenosa et al. 2003). In a seroprevalence study in Polish forest workers, however, 15/129 (11.6%) sera reacted against R. massiliae (Podsiadly et al. 2011). These results and the detection of R. massiliae as cause in hitherto presumably diagnosed Mediterranean spotted fever cases imply that R. massiliae might be responsible for a part of those cases in the Mediterranean and possibly in other areas in the world.


15.1.3.5 Medical and Veterinary Importance


Rickettsia massiliae may cause a severe form of spotted fever in humans, including fever, eschar, a maculopapular rash including palms and soles and a mild hepatomegaly. The clinical syndrome cannot be clinically differentiated from classical Mediterranean spotted fever. The incidence of infections with R. massiliae in humans is not known so far, but results in clinical studies show that it may be frequent at least in some areas around the Mediterranean. An important difference to other rickettsial species is the natural resistance against rifampicin (Rolain et al. 1998). This might be of importance as rifampicin constitutes an important antibiotic in the treatment of rickettsioses in childhood.


15.1.4 Rickettsia raoultii


Rickettsia raoultii was detected independently several times in different parts of the world. A strain from Dermacentor (D.) nuttallii from Siberia was provisionally named as strain “DnS14” (Rydkina et al. 1999). Another strain, named “RpA4”, was detected in Astrakhan ticks of the species Rh. pumilio (Shpynov et al. 2001). Molecular studies showed that both strains were genetically closely related or almost identical (Mediannikov et al. 2007). Meanwhile, the wide geographic distribution in ticks of the genus Dermacentor is recognized. Strains or nucleic acid sequences belonging to the species R. raoultii have been detected in D. nuttallii, D. pumilio, D. reticulatus, D. silvarum, D. niveus and D. marginatus through the Eurasian continent from far eastern Russia to France, Spain, Croatia and also central Europe.

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Aug 31, 2016 | Posted by in GENERAL | Comments Off on Spotted Fever Rickettsiae and Rickettsioses in Germany

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