Francisella tularensis- specific antibody levels in sera from Swedish patients with suspected tularemia during a 13-year period

Abstract

Introduction: For a majority of tularemia patients, serology is the basis for the diagnosis. The aim of this study was to perform an analysis of the samples analyzed at a Swedish reference laboratory for the presence of Francisella tularensis-specific antibody levels in sera from individuals with suspected tularemia. Annual and monthly variations of the total number of samples and proportions of positive samples were analyzed, as well as the influence of age and gender.

Methods: We performed a retrospective analysis of the presence of F. tularensis-specific antibodies in serological samples from patients with suspected tularemia analyzed during the period 2010 - 2022 at the University Hospital of Umeå in Sweden, a national reference laboratory, by use of various statistical methods. In total, some 15,100 serum samples had been analyzed for the presence of IgG and IgM antibodies by ELISA during the 13-year period.

Results: Overall, there were higher number of samples with IgG positive or borderline titers, 2,522 and 921, respectively, than with IgM positive or borderline titers, 1,802 and 409, respectively. Repeated samples were obtained from some 1,930 individuals and approximately a third of the cases, which were initially seronegative, had seroconverted when resampled. Peak number of monthly samples were recorded in August and September, > 3,000. Annual numbers varied greatly and peak numbers were observed in 2015 and 2019, 1,832 and 2,250, respectively, whereas some other years the numbers were 700 - 800. There was also much variation in the annual and monthly percentages of positive samples and they varied between less than 10% to greater than 20%. The highest percentages of positive samples were recorded in September and October. IgG and IgM titers declined with age and these differences were highly significant for IgG titers, with decreasing average titers for each 20-year interval.

Discussion: Collectively, the data demonstrate the marked annual and seasonal variations in tularemia sampling occurring in Sweden. Also, the proportion of positive samples increased during months and years with peak number of samples. Another notable finding was that average antibody titers decreased with increased age.

Keywords: age-related titers; annual distribution; monthly distribution; serological response; tularemia.

Figure 1

Monthly proportion of IgG and IgM positive serum samples (bars) and numbers of serum samples analyzed each month (dot). The serum samples were collected from patients in Sweden with suspected tularemia during the period 2010 to 2022.

Figure 2

Annual proportion of IgG and IgM positive serum samples (bars) and numbers of serum samples analyzed each year (dot). The serum samples were collected from patients in Sweden with suspected tularemia during the period 2010 to 2022.

Figure 3

Analysis of the effect of age on IgG and IgM levels. Patients were divided into age groups with a 20-year interval and levels of IgG (A) and IgM (B) titers compared. One-way ANOVA with Bonferroni correction was used to assess differences in IgG and IgM levels between age groups. Significant differences are indicated by asterisks. *P < 0.05, **P < 0.01 and ***P < 0.001.

Figure 4

Analysis of the effect of gender on IgG and IgM levels. Patients were divided into groups based on gender and levels of IgG and IgM titers compared using two-sided Student`s t-test. Significant differences are indicated by asterisks. *P < 0.05.

Figure 5

Analysis of the effect of gender and age on IgG and IgM levels. Patients were divided into 20-year age intervals and grouped according to gender. Levels of IgG (A) and IgM (B) between males and females in the different age groups were compared using two-sided Student`s t-test. Significant differences are indicated by asterisks. None of the gender differences was significant.