In this population-based controlled study, obesity, diabetes, and coronary artery disease were found to be associated with an increased risk for for S. dysgalactiae subsp. equisimilis bacteremia. This is the first study presenting obesity and coronary artery disease as risk factors for S. dysgalactiae subsp. equisimilis bacteremia. There is one previous study about the association of diabetes and an increased risk for S. dysgalactiae subsp. equisimilis bacteremia .
There are several studies concerning the risk of infections in obese patients. An association with obesity and an increased risk of infections have been previously reported in skin and soft tissue infections and surgical site infections [17, 24]. Kaspersen et al. studied hospital-treated infections and found that male patients had a higher incidence of skin and soft tissue infections and that the risk of skin and soft tissue infections was increased in obese males . Morbid obesity has been reported to be associated with an increased risk for sepsis . In an American study on invasive Streptococcus pyogenes infections, morbid obesity was also associated with an increased risk for invasive S. pyogenes infections . In one non-controlled population-based study of S. dysgalactiae subsp. equisimilis bacteremia by Broyles et al., 30% of the patients were reported obese .
Several mechanisms for how obesity predisposes to infections have been suggested. Obesity weakens the skin barrier and wound healing and decreases respiratory capacity. Adipose tissue participates in the immune system producing several proinflammatory and anti-inflammatory factors called adipokines. Adipokines have several complex effects on different immune cells, mediating cytokine production in immune cells, cell differentiation and proliferation. [25, 26] Likewise in several other European countries and America, the prevalence of obesity has increased dramatically in Finland over the last two decades. In 1997, 15% of the population were obese, and in 2017 the prevalence of obesity had increased to 23% [21, 27].
In our study, diabetes increases the risk of S. dysgalactiae subsp. equisimilis bacteremia 5-times in the full study group. Diabetes has previously been associated with many severe infections including pneumonia, skin and subcutaneous infections, and sepsis [18, 28]. Thomsen et al. studied the role of diabetes in S. pyogenes, S. agalactiae, and S. dysgalactiae subsp. equisimilis bacteremia and found diabetes to be risk factor for bacteremia in S. agalactiae and S. dysgalactiae subsp. equisimilis . In other studies, diabetes has also been associated with increased risk for S. pyogenes bacteremia [20, 29]. In previous case series, 16 to 42% of the patients with S. dysgalactiae subsp. equisimilis bacteremia have had diabetes [2, 3, 7, 14]. Ogura et al. studied the pathogenicity of S. dysgalactiae subsp. equisimilis with diabetic mice and found that the pathogenicity of S. dysgalactiae subsp. equisimilis was higher in T2DM model mice than in nondiabetic mice .
Coronary artery disease was also found to be a risk factor for S. dysgalactiae subsp. equisimilis bacteremia both in males and in females. In previous studies, some evidence for cardiovascular diseases increasing the risk of invasive S. pyogenes infections and other septic infections has been reported [29, 31].
The prevalence of other underlying conditions, including alcohol use, immunosuppression, skin conditions and malignancies, and are in line with previous studies [2, 3, 7, 14].
In the present study, the majority of S. dysgalactiae subsp. equisimilis bacteremia patients were elderly individuals, as in previous studies [2, 7, 14]. The reason for S. dysgalactiae subsp. equisimilis to affect mainly elderly individuals is multifactorial. Ageing predisposes to infections due to a higher prevalence of comorbidities. However, in this study, there were variation in the distributions of different risk factors according to age. The proportion of obese patients was larger in younger patients, diabetes was more common in the middlest age groups and coronary artery disease was emphasized in the oldest patients. Elderly individuals may have several comorbidities, but ageing is also known to increase the risk for infections by weakening the immune system . Furthermore, the epidemiological features and changes concerning age may also be due to the bacteria itself. There is some evidence on horizontal gene transfer from S. pyogenes to S. dysgalactiae subsp. equisimilis that might affect the virulence of S. dysgalactiae subsp. equisimilis . It seems that a few particularly virulent S. dysgalactiae subsp. equisimilis clone comprises increasing amount of the S. dysgalactiae subsp. equisimilis bacteremia cases, causing more invasive disease than earlier [8, 9, 34]. For example in Japan, where S. dysgalactiae subsp. equisimilis bacteremia is known to occur frequently, the emm stG6792 has been the predominant type . In one previous study from Finland from 2010, the three most common emm-types were stG480, stG6 and stG485, comprising 51% of isolates, but more recent data is not available . The genotype stG6792 was not reported in Finland at the time.
Our study has some limitations. We were not able to compare all possible risk factors for S. dysgalactiae subsp. equisimilis bacteremia due to the different methods in collecting data in the Finhealth study compared to the S. dysgalactiae subsp. equisimilis study group. Use of alcohol was determined differently in the Finhealth study, so the data was not comparable with our study group. Data of malignancies, immunosuppression and neurological diseases were not available in the Finhealth study.
Our study has several strengths. Both our study population and the Finhealth study group are population-based and both studies were carried out at the same time. Our study population is from Pirkanmaa health district and the Finhealth study represents the whole Finland. When different regions were compared in the Finhealth study, no significant regional differences were found . In our study population, all records of patients were thoroughly reviewed by the same infectious disease specialist (SR). The BMI data was comprehensively available (87% of the patients).