Severe Campylobacter infections in Finland
Year: 2012
Type: dissertation
Abstract: Campylobacter jejuni and C. coli are among the most important bacterial enteropathogens worldwide, and the last decade Campylobacter infections in the European Union (EU) have shown a rising trend in incidence. The most commonly reported zoonosis in the EU, campylobacteriosis, can be transmitted to humans from a wide variety of wild birds, as well as from domestic and pet animals. Eating or handling raw or undercooked meat, particularly poultry, is considered the primary risk factor for Campylobacter infection, followed by other risk factors such as drinking unpasteurized milk or contaminated water, contact with domestic pets, and swimming in natural water sources. The enteric disease caused by C. jejuni or C. coli is characterized by profuse watery diarrhea, fever, abdominal pain, nausea, and sometimes bloody stools. The disease usually lasts from a few days up to one week, and although Campylobacter infection usually resolves spontaneously without antimicrobial treatment, prolonged symptomatic periods and relapses do occur. A complication that commonly follows and is attributed to Campylobacter infection is reactive arthritis, which occurs in approximately 1 to 10% of the patients. Closely associated with C. jejuni infection is also the more rarely encountered serious inflammatory polyneuropathy Guillain-Barré syndrome. Bacteremia due to C. jejuni or C. coli has been estimated to develop in 0.1 to 1% of patients with campylobacteriosis, and hematogenously spread disease is considered more common in older patients and those with severe underlying diseases. The bacterial characteristics of C. jejuni or C. coli which could lead to a more severe course of disease, to bacteremia, or to post-infectious complications are not well understood. Certain putative virulence factors have been suggested to be of importance for either the invasiveness or the colonization potential of C. jejuni, some examples of which are the plasmid pVir, Campylobacter invasion antigen, and γ-glutamyl transpeptidase (GGT). Other examples of putative virulence factors include those suspected to affect the bacterium s iron uptake, survival or metabolism. Moreover, because of the seriousness of Guillain-Barré syndrome, development of post-infectious adverse immune responses has been subject to specific focus, and structural differences in the lipooligosaccharide in the outer membrane of C. jejuni have been under extensive study. The relevance of these bacterial factors to the actual clinical disease outcome has yet to be explained, however, possibly with the exception of the relatively clear association between sialylated lipooligosaccharides and the development of the Guillain-Barré syndrome. The primary goal of this PhD study was therefore to try to define which bacterial factors could lead to a more severe outcome of Campylobacter infection. Two sets of patient data, along with the corresponding bacterial isolates of those patients, were included. The first was questionnaire-based, and collected from the Uusimaa region in southern Finland during July through December, 2006. The 192 patients included had been diagnosed as stool culture-positive for C. jejuni or C. coli, and all returned their questionnaires along with their informed consent. The second set of data was retrospective, nationwide, and register-based, and included 76 patients diagnosed with C. jejuni or C. coli bacteremia during a 10-year period in Finland, 1998-2007. The isolates from patients with enteritis were tested for antimicrobial susceptibility, the presence of putative virulence factor genes, and the production of GGT. Multilocus sequence typing (MLST) as well as determination of susceptibility to normal human serum was performed on the isolates from the patients with bacteremia. All C. jejuni isolates were tested for production of GGT, and in addition, the presence of the following putative virulence factor genes was tested by polymerase chain reaction (PCR) for all isolates; ceuE, ciaB, cj0486, and virB11, and additionally the gene cluster cdtABC and the genes cgtB, pldA, and wlaN for the enteritis isolates. For the bacteremia isolates, PCR analyses allowed determination of the MLST profiles and lipooligosaccharide (LOS) locus classes of the isolates. Results of multivariate analyses revealed bacterial differences based on the origin of infection among the enteritis isolates, as domestically acquired infections were significantly associated with the production of GGT, while imported infections were significantly associated with ceuE and cj0486. Susceptibilities of the bacterial isolates were tested for those antimicrobial agents most commonly used in the treatment of Campylobacter infections, and when these data were compared with the clinical information, some interesting findings emerged. First, among the patients with enteritis, bacterial resistance to ciprofloxacin did not seem to lead to more severe disease outcome. Instead, this was specifically attributed more to those isolates highly susceptible to ciprofloxacin. Second, the majority of the bacteremia isolates were susceptible to all tested antimicrobial agents. Third, among the patients with bacteremia, appropriate and empirical antimicrobial treatment affected neither patients duration of hospitalization nor the mortality attributable to the infection, to any greater extent. The C. jejuni and C. coli bacteremia patients were moderately young (median age, 46 years) and according to the Charlson weighted index of comorbidity, underlying diseases regarded as comorbidities significantly affecting disease outcome affected only 30%. Among the bacteremia isolates, MLST revealed the clonal complexes ST-677, ST-45, and ST-21 to be the most prevalent, accounting for 48%, 16%, and 14%, of the isolates. All the isolates of the ST-677 complex originated from patients diagnosed with C. jejuni bacteremia during the seasonal peak in May through August; these isolates were significantly more serum resistant than were all other isolates, and all isolates of the ST-677 complex had nonsialylated LOS. Isolates of the ST-45 complex were associated with production of GGT and were significantly more serum sensitive than were all other isolates, and all the ST-45 complex isolates had nonsialylated LOS. Isolates of the ST-21 complex were associated with the gene cj0486, and all these isolates had sialylated LOS.
Source: Työväentutkimus Vuosikirja
Author: Benjamin Feodoroff
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1517405200