To the Editor—We read with interest the article by de Sousa et al. [1] on intraspecies variation in the virulence of Rickettsia conorii. In their study of 140 patients infected with R. conorii including 29 who died, de Sousa et al. demonstrated that those infected with the Israeli spotted fever (ISF) strain had significantly fewer eschars, more nausea and vomiting, greater hepatic involvement, and a higher fatality rate than those infected with the Malish strain. This work confirms previous studies in which serotypic, geographic, and pathogenic differences between these strains were observed despite great genetic homogeneity

The status of rickettsial strains related to R. conorii has long been a matter of debate among rickettsiologists. These bacteria include the prototype strains Malish, Indian tick typhus (ITT), ISF, and Astrakhan spotted fever rickettsia (AFR), which are mostly transmitted to humans by Rhipicephalus ticks. These strains are the causative agents of Mediterranean spotted fever, ITT, ISF, and Astrakhan fever in the Mediterranean basin and in Africa, India, the Middle East, and southern Russia, respectively. The controversy over the status of these 4 strains has been fueled by contradictory clinical and laboratory studies. Some authors, including de Sousa et al. [2], initially considered that most of the clinical features of Mediterranean spotted fever, ITT, ISF, and Astrakhan fever overlapped and that the 4 diseases were, in fact, only different names given to a single illness characterized by a febrile and generalized maculopapular rash. In contrast, others identified distinct features—such as the rare presence of an inoculation eschar in Astrakhan fever and ISF, in comparison with Mediterranean spotted fever—and believed that the 4 strains caused diseases that varied in clinical presentation and severity in addition to geographical distribution, making their denomination useful (table 1)

Table 1

Ecological, epidemiological, and clinical characteristics of diseases associated with rickettsial strains closely related to Rickettsia conorii [3]

Table 1

Ecological, epidemiological, and clinical characteristics of diseases associated with rickettsial strains closely related to Rickettsia conorii [3]

Laboratory data have also been controversial. Early results from mouse serotyping and complement fixation could not distinguish the 4 strains. In contrast, the use of mouse polyclonal [4] and monoclonal [5] antibodies differentiated the ITT strain from the Malish strain; polymerase chain reaction restriction fragment–length polymorphism analysis distinguished the Malish strain from the ISF strain [6]; SDS-PAGE mobility and PFGE profiles [7] discriminated the Malish, ISF, and AFR strains; and all 4 strains were clearly identified on the basis of ompA sequences [8]. Because of these contradictory data, the taxonomic status of strains related to R. conorii have remained unclear, with some authors proposing that they belonged to the R. conorii species [9] and others to a “R. conorii complex” [4, 9] or to distinct species, namely R. conorii, R. sharonii and R. caspii

In 2003, in an effort to clarify the taxonomy of the Malish, ITT, ISF, and AFR strains, we used gene sequence–based criteria developed for the identification of Rickettsia isolates at the genus, group, and species levels [10] and showed that they could not be considered distinct species but belonged to the R. conorii species [10]. Furthermore, using the proposal of the Ad Hoc Committee on Reconciliation of Approaches to Bacterial Systematics that, even if related genetically, bacterial isolates within a given species could be considered distinct subspecies if they differed phenotypically, we proposed the creation of subspecies within the R. conorii species to accommodate both the genetic homogeneity and the phenotypic diversity of the Malish, ITT, ISF, and AFR strains [3]. The validation of the R. conorii subspecies conorii, indica, israelensis and caspia respectively, was approved by a majority of rickettsiologists and is currently being examined by the International Committee for the Systematics of Prokaryotes

The study by de Sousa et al. [1] clearly demonstrates clinical differences between infections caused by Malish and ISF strains and contradicts the findings of their previous study [2], highlighting the need to draw careful conclusions before contradicting previous work, especially when studying limited numbers of patients. The study [1] also supports our proposal to clearly delineate taxonomic entities within the R. conorii species on the basis of phenotypic specificities, despite their genetic similarity

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Potential conflicts of interest: none reported
Financial support: none reported