Seasonality of Bartonella henselae IgM and IgG Antibody Positivity Rates

LETTER

Bartonella henselae, the agent of cat scratch disease (CSD), is transmitted by the inoculation of B. henselae-containing Ctenocephalides felis flea feces into skin abrasions acquired following a cat scratch or bite (1, 2). CSD is seasonal, due to both cat behavior and the C. felis life cycle, with the majority of cases occurring during the fall and winter and peaking in the United States in September and October (3–6). This seasonality was established using positivity rates from molecular detection assays for B. henselae or through mining health care databases using the International Classification of Diseases, 9th revision (ICD-9) code for B. henselae infection (078.3). Laboratory diagnosis of CSD, however, is most frequently established using serologic methods for the detection of anti-B. henselae IgM/IgG class antibodies. Given the high B. henselae seroprevalence rates (up to ∼20% among healthy individuals, but region dependent), alongside prolonged antibody persistence (>1 year in some cases), it is unclear whether seasonality is also observed with anti-B. henselae serologic results (7–10). Here, we evaluated the monthly anti-B. henselae IgM/IgG positivity rates over a 10-year period at Mayo Clinic Laboratories (MCL; Rochester, MN), a commercial reference laboratory.

Monthly test volumes and positivity rates for anti-B. henselae IgM/IgG serologic testing performed between January 2009 and December 2018 at MCL were reviewed. Testing was performed using Bartonella IgM and IgG immunofluorescence assay (IFA) kits from Focus Diagnostics (DiaSorin, Cypress, CA; used January 2009 to September 2017) and Euroimmun US, Inc. (Mountain Lakes, NJ; used September 2017 to December 2018), in accordance with the manufacturers’ instructions. Both IFA methods allow for simultaneous evaluation of antibodies to B. henselae and Bartonella quintana, and the cutoff titer for positivity was identical between the two manufacturers (i.e., ≥1:20 for IgM and ≥1:64 for IgG). Only B. henselae IgG results with titers of ≥1:256, which are considered indicative of acute or recent infection, were considered to be positive for this analysis. B. quintana antibody titers were not evaluated for the included specimens. All data calculations were performed in Microsoft Office Excel 2010, and P values of <0.05, determined by Student’s t test, were considered statistically significant. Patient consent was waived for this retrospective analysis.

A total of 141,721 serum samples were submitted to MCL for Bartonella serologic testing between 2009 and 2018. The average monthly test volumes and antibody positivity rates for B. henselae over the 10-year period are shown in Fig. 1. While the average monthly test volumes did not significantly vary (range, 1,077 in July to 1,376 in October; P = 0.053), anti-B. henselae IgM and IgG positivity rates were notably higher from September through January than from April through July. The largest difference in monthly positivity rates for anti-B. henselae IgM and IgG occurred between October (4.6%) and June (1.4%) (P < 0.0001) and between January (14%) and June (5.7%) (P = 0.002), respectively.

FIG 1.

Average (Avg.) monthly B. henselae IgM and IgG positivity rates and test volumes over 10 years (2009 to 2018). * and ** indicate a significant difference (P < 0.05) between the widest range of monthly positivity rates for anti-B. henselae IgG and IgM, respectively.

These data show significant seasonality for both anti-B. henselae IgM and IgG class antibodies at clinically relevant titers (i.e., IgG ≥ 1:256). Consistent with prior studies using molecular assays and health care database mining, we show that the highest anti-B. henselae seropositivity rates occur annually in January (3, 6). Notably, while test volumes for B. henselae serologic testing remain consistently elevated throughout all months, IgM/IgG positivity rates were significantly lower during late spring and early summer. These data may be used to better tailor B. henselae serologic test utilization, arguing for a higher threshold of suspicion for CSD and serologic test orders between the months of May and July.