An Epidemiological Study of Aeromonas spp. Infections in Norway

    

    

    Figure 2: Incidence of Aeromonas infections by age-group and sex, Norway, 2014-2018. 5-year incidence of (A) all infection types (B) gastrointestinal infections (C) wound infections (D) blood infections.
    

Gastrointestinal Infections

GI cases were the most frequently reported Aeromonas infection during the 5-years study period, with an average number of 70 cases and an incidence of 1.4 per 100,000 inhabitants reported per year. GI infections were more frequently reported in females (n=191, 54.4%), with a male to female ratio of 0.8 and the highest number of cases in adults 45-64 years old (n=101, 28.8%). However, the highest incidence was reported in children below 4 years old (13.1 per 100,000) and in elderly more than 80 years old (8.6 per 100,000). Twenty-four cases reported underlying conditions, mostly cancer, gastric bypass surgery and colitis. Infections followed a seasonal distribution peaking during the summer months (n=119, 33.9%). Aeromonas spp. were detected from faecal samples and not subtyped at species level for most of the cases (n=238, 67.8%). When subtyped, the most reported species was A. hydrophila (n=42, 12.0%), followed by A. veronii (n=40, 11.4%). Thirty-six cases reported coinfections mostly associated with Campylobacter, followed by Salmonella, Shigella, Streptococcus, Klebsiella and Clostridium spp. Almost all cases (96.3%) reported information on hospitalisation and about a quarter (24.0%) were hospitalised. The western region reported the highest number of cases (n=204, 60.2%) followed by the centre, southern, eastern, and northern regions (Table 1).

Wound Infections

Wound infections were the second most reported Aeromonas’s type of infection during the 5-years study period with an average number of 8.6 cases and an incidence of 0.2 per 100,000 inhabitants reported per year. Wound infections were more frequently reported in males (n=24, 55.8%), with a male to female ratio of 1.3, and in all age groups except infants and children below 15 years old. The highest number of cases was reported for the age group 45-64 (n=12, 27.9%), however the highest incidence was reported in the 56–79-year-olds (1.6 per 100,000). Eight cases reported underlying conditions such as complications from wound healing, gangrene, chronic wounds and amputations. Infections followed a seasonal distribution with a peak of cases during summer months (n=21, 48.8%). Aeromonas spp. were detected from open wounds, biopsies and exudate samples, and not subtyped at species level for a large number of cases (n=21, 48.8%). When subtyped, the most reported species was A. hydrophila (n=18, 41.9%) and in lower percentage A. veronii and A. caviae (for both n=2, 4.7%). Five cases reported coinfections mostly associated with Proteus and Staphylococcus spp. More than half of the cases (55%) reported information on hospitalisation and 7.5% were hospitalised. The western region reported the highest number of cases (n=17, 43.6%) followed by the eastern, southern, centre and northern regions (Table 1).

Blood Infections

Blood infections were the third most reported type of Aeromonas infection during the 5-years study period with an average number of 7.4 cases and an incidence of 0.1 per 100,000 inhabitants reported per year. Blood infections were equally distributed between males and females. No blood infections were reported in the age groups below the age of 25, while an increasing number of cases was reported by age-group with the highest number of cases in elderly above 80 years old (n=13; 35.1%). Eight cases reported underlying conditions such as cancer and gallbladder infections. Infections did not follow a seasonal pattern, with a low number of cases reported throughout the seasons. Aeromonas spp. were detected from blood samples and subtyped at species level for many cases (n=12, 32.4%) reporting A. caviae as the predominant detected species (n=16, 43.2%). Eight cases reported coinfections mostly associated with Klebsiella spp. and Escherichia coli.

Almost all cases (93.1%) reported information on hospitalisation and 81.1% were hospitalised. The western region reported the highest number of cases (n=14, 43.8%) followed by the eastern, southern, northern, and centre regions (Table 1).

Other Infections

Other Aeromonas infections included ear infections (n=14, 2.8%), urinary tract infections (n=11, 2.2%), respiratory infections (n=9, 1.8%), skin infections (n=8, 1.6%), and other infections such as appendicitis, cholecystitis, eye infections and peritonitis (n=30, 6%). Epidemiological parameters are available in Table 1.

Risk Factors for Developing Severe Aeromonas Gastrointestinal Infections

Our unmatched multi variate analysis comparing the non-hospitalised with the hospitalised cases of Aeromonas GI infections revealed that sex and seasons do not play a significant role in the risk of developing severe infection. While we observed that the proportion of severe cases increased significantly with increasing age, particularly for elderly in the age group 65-79 years old (OR=3.1; 95% CI: 1.39-6.93) and more than 80 years old (OR=17.7, 95% CI: 5.05-61.79), as well as with A. caviae as GI-causing species (OR=3.3, 95% CI: 1.32-8.05) (Table 3).

Discussion

This epidemiological study provides an overview of the occurrence of Aeromonas infections in Norway between 2014-2018. The overall incidence of Aeromonas infections was calculated to 1.9 per 100,000 inhabitants per year. Incidence of Aeromonas infections from different countries is scarcely reported and vary from 0.2 to 9.9 per 100,000 in France and Australia, respectively [4,20]. A similar incidence to Norway, 1.1 per 100,000, was reported from a study in California, USA. [7]. While many factors influence the overall incidence of Aeromonas in any given country, higher incidence may be linked to warmer and tropical climates which present favourable growth conditions for Aeromonas (20-37°C) [22].

The main infection types of Aeromonas observed in Norway were GI, wound and blood infections. GI infections were also reported among the majority of Aeromonas cases in the Californian study [7], however both the French [5] and Australian studies [20] reported a majority of wound infections.

The incidence of Aeromonas causing GI infections in Norway was 1.1 per 100,000 inhabitants per year. The highest incidence rate was observed in children 0-4 years and elderly above 80 years, highlighting that these age groups are more vulnerable for developing GI infections. The reported GI infections followed a seasonal pattern peaking in the summer with an average of 24 cases per year. The annual cases of GI infections, over the study period stayed relatively stable with an average of 70 cases per year (range 54-78), this points towards a continuous exposure. Aeromonas GI infections are associated with the consumption of contaminated food and water. Observations may be a result of the combination of increased Aeromonas concentration and likelihood for exposure during the summer months [20]. Most cases (60%) in Norway have been reported from the Western region with an incidence of 3.1 per 100,000 per year. To contextualise this value, we can compare with other gastrointestinal infections that are mandatorily notifiable in Norway such as Campylobacter and Salmonella reporting an incidence of 73.8 and 21.2 cases per 100,000 per year from the same region over the same time period [23].

Aeromonas spp. infections are not mandatorily notifiable in Norway, however the higher number of cases reported in the Western region suggests that infections with this opportunistic pathogen are relatively common. Cases may also go undetected as Aeromonas spp. are not routinely tested for but rather are detected in the procedure to exclude more commonly tested pathogens. Therefore, the detection of Aeromonas could be influenced by laboratory sensitivity based on their testing methods, algorithms and procedures.

Regarding risk factors associated with GI infection requiring hospitalisation, our multivariate model showed that the odds of developing GI infections that require hospitalisation is 3.1 and 17.7 times higher in the age groups 65-79 and above 80 years old, respectively compared to other age groups. While patients suffering from GI infections caused by A. caviae were 3.3 times more likely to be hospitalised. These findings may be explained with the increased likelihood of underlying diseases with increasing age and point towards a higher pathogenicity of A. caviae compared to other species.

Wound infections were the second most reported Aeromonas-associated infections. These types of infections were more frequently reported in males of all age groups except in infants and children less than 15 years of age. Although the yearly average number of wound infections was relatively low, the reported cases peaked in 2018 with 18 cases. These cases were reported from all regions of Norway. However, most of those cases were reported in the summer months like GI infections, suggesting a common source of infection such as contaminated water. The trend of an increased number of cases reported during the warmer months was also observed in the Australian context [20]. This is also in line with the co-occurrence of an increase in other waterborne pathogens like Vibrio infections in 2018 reported for the Nordic countries and attributed to the exceptionally warm climate [24].

For blood infections, only few cases were reported, and no clear seasonality was observed however cases clustered in summer and winter with an average of 2 cases per year for each season. There were also no significant peaks of cases observed over the study period with an annual average of 7.4 cases (range 5-11). These findings may point towards different risk factors associated with blood infections compared to GI and wound infections in Norway and seem to be mostly correlated with increased age particularly for elderly above 80 years old. This is in line with previous observations highlighting the importance of age as a risk factor for this type of infection [5].

Severe infections often lead to a higher rate of hospitalisation, which in turn is a burden on the health care system. The percentage of hospitalisation with all types of Aeromonas infections over the study period averages around 32.7% (29.6-36.5) per year which shows that Aeromonas infections requires hospital care in almost a third of the reported cases. The number of hospitalised cases increased by age; this could be explained by underlying conditions also increasing by age group in our dataset.

As expected, the percentage of hospitalised cases was highest for Aeromonas causing blood infections (81.1%) followed by wound (51.0%) and GI infections (23.1%). Like the hospitalisation trend, Aeromonas spp. have been more frequently subtyped for blood infections (67.6%) followed by wound (51.2%) and GI infections (32.2%). These results are expected due to prioritization of subtyping for samples from severe cases.

Overall, the most frequently isolated species detected in patient samples were A. hydrophila (n=77, 15.3%), A. veronii (54, 10.7%) and A. caviae (54, 10.7%). However, due to limitations of the identification methods such as MALDI-TOF [25], the percentage of A. hydrophila could be overestimated. The number of reported cases attributed to these species varied between the years and no trend or pattern was identified. A. hydrophila was more frequently detected in GI (12%) and wound infections (41.9%) while A. caviae was the most frequently detected species in blood infection samples (43.2%). This finding, combined with the increased likelihood of hospitalisation in GI infections caused by this species, suggests that A. caviae is likely the most invasive Aeromonas spp. in Norway. Although the Australian and French study [5,20] showed similar results, other countries like Taiwan and Japan reported A. hydrophila as the most common species causing blood infections [26,27]. Coinfections were reported for 66 cases where Campylobacter spp. was the most common detected pathogen, however further research is needed to clarify the role of Aeromonas in coinfections.

The limitations of this study include sampling bias towards severely ill, older, or comorbid individuals. Consequently, the age distribution of cases could be biased for mild infections, and thus underreported. In case of hospital admission, the reasons for hospitalisation were also not reported. Furthermore, Aeromonas infections are not mandatorily notifiable in Norway, therefore the data in this study were provided by the laboratories based on a voluntary survey, resulting in a reporting bias and completeness limitations for some of the collected parameters such as coinfections and underlaying conditions. Also, Aeromonas is not routinely tested for at medical microbiological laboratories in Norway and is typically only identified after excluding more common pathogens. The observed increase in the Western region highlights an important aspect of the laboratory testing performed for Aeromonas. Our investigation revealed that one laboratory had a significantly higher number of Aeromonas cases compared to other laboratories, which may be a result of different internal laboratory procedures, like culture media and testing practices [19,28]. Results of our study rely on a high response rate from the laboratories, with 76% of laboratories providing information on number of cases and epidemiological variables. However, the number of reported cases largely varied between laboratories with a range of 3-202 cases reported per laboratory.

Conclusion

This study has shed light on the epidemiology of Aeromonas infections in Norway and given insight into possible risk factors associated with infections. The study has shown that GI infections are the predominant infection type in Norway. The highest cumulative incidence was reported in infants and the elderly, and the even distribution of cases in space, time and sex suggests a constant and prolonged environmental exposure. The risk of developing severe infections increased by causing species (A. caviae) and increasing age. Future research and source attribution study investigating potential environmental sources of Aeromonas infections, such as water for human consumption and use, would be valuable to understand the transmission’s dynamics.

Author Statements

Financial Support

The project has been financially supported by the European Programme for Public Health Microbiology Training (EUPHEM), ECDC. The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The views and opinions presented in this article are those of the authors and do not represent the opinion of the ECDC.

Data Availability Statement

Only fully anonymized data (i.e., data that are neither directly nor potentially indirectly identifiable) are permitted to be shared publicly. Therefore, legal restrictions prevent the authors from publicly sharing the dataset used in the study.

Acknowledgements

We would like to acknowledge Loredana Ingrosso (EUPHEM ECDC Fellowship

Programme) and Umaer Naseer for revising this manuscript. We thank the Norwegian microbiology laboratories network for their kind collaboration in providing data.

Authors’ Contributions

AR performed the epidemiological analysis and prepared the first draft manuscript. HS provided data from Stavanger area. EA collected the data at national level and supervised the project. EA, SH and HS advised during epidemiological analysis and interpretation. All authors contributed to the manuscript, revised and approved the final version.

Data Availability Statement

Only fully anonymized data (i.e., data that are neither directly nor potentially indirectly identifiable) are permitted to be shared publicly. Therefore, legal restrictions prevent the authors from publicly sharing the dataset used in the study.

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