pVir and bloody diarrhea in Campylobacter jejuni enteritis

Emerging Infectious Diseases, June, 2005 by Dobryan M. Tracz, Monika Keelan, Jasmine Ahmed-Bentley, Amera Gibreel, Kinga Kowalewska-Grochowska, Diane E. Taylor

Bloody stool in C. jejuni gastroenteritis indicates the progression of the infection into the tissues of the colon and rectum (3). This invasion of the intestinal epithelium is responsible for the mucosal damage and inflammatory lesions seen in C. jejuni infections and is a major component of pathogenesis, although the mechanism is currently unknown (11). pVir was previously found to be important for the in vitro invasion of intestinal epithelial cell lines (15,16). The association of pVir in C. jejuni with bloody diarrhea in a clinical setting supports the role of pVir for in vivo epithelial cell invasion and stresses its potential as a marker for the risk of developing a more severe clinical infection.

The lack of association of pVir with bloody stool in a small proportion of patients suggests that other virulence determinants are likely to be involved in severe C. jejuni infections, as are several other host factors that determine the clinical expression of the disease (3). Further studies are necessary to clarify these aspects of clinical C. jejuni infection.

Large variations in invasion frequency have been observed among strains of C. jejuni (4). Fearnely et al. (31) found that C. jejuni strains can either invade cell cultures at high frequencies (hyperinvasive) or have low invasive potential. Subsets of the C. jejuni strains may exist that use different mechanisms to produce disease (15,32). Whether or not the pVir virulence plasmid is the defining feature of a hyperinvasive subset of (2 jejuni strains remains to be determined.

The finding that the pVir virulence plasmid is present in C. jejuni isolates containing a tetracycline-resistance plasmid is of considerable interest. One potential explanation for this association is the impact on the invasive ability of the strain. Variation in the invasion frequencies of C. jejuni 81-176 pVir gene mutants has been observed (33) and may be due to the functional redundancy of T4SS genes found on pVir and a tetracycline-resistance plasmid (16). This finding may, in part, explain the dependence of pVir on the tetracycline-resistance plasmid observed in this study.

The prevalence of tetracycline resistance in C. jejuni in our study (60%) represents a significant increase from 8.6% in 1981 (p<0.0001) (22), but the frequency of resistance to erythromycin or ciprofloxacin has remained low. These results confirm those of other Canadian studies that have identified increasing levels of tetracycline resistance and low levels of erythromycin resistance (20,34,35). Considering that erythromycin is the drug of choice for treating C. jejuni gastroenteritis, that its efficacy has not been compromised by the emergence of resistance is surprising. In our study, a low level of resistance to ciprofloxacin, commonly prescribed to prevent travelers' diarrhea, is also a surprising finding. A temporal link between veterinary use of fluoroquinolones and the emergence of fluoroquinolone resistance in human isolates of C. jejuni coincided with the licensing of fluoroquinolones, such as enrofloxacin, in the late 1980s and early 1990s in the Netherlands, Spain, United Kingdom, the United States, and Canada (36). In the eastern Canadian province of Quebec, resistance to ciprofloxacin increased from 13% in 1995 to 47% in 2001 (20,37). Approval for fluoroquinolone as a therapeutic agent for use in agriculture in Canada was withdrawn in 1997 (38) and may explain the low prevalence of ciprofloxacin-resistant C. jejuni isolated from human specimens in the western Canadian province of Alberta.