Co-infections in Persons With Early Lyme Disease, New York, USA

Gary P. Wormser; Donna McKenna; Carol Scavarda; Denise Cooper; Marc Y. El Khoury; John Nowakowski; Praveen Sudhindra; Alexander Ladenheim; Guiqing Wang; Carol L. Karmen; Valerie Demarest; Alan P. Dupuis II; Susan J. Wong


Emerging Infectious Diseases. 2019;25(4):748-752. 

In This Article


At the time of the baseline visit, none of the 52 patients with erythema migrans had received antimicrobial drugs; 31 (59.6%) patients had 1 erythema migrans lesion, and 21 (40.4%) patients had multiple erythema migrans lesions (Table 1). Thirty-four (65.4%) patients were male, mean age ± SD was 50.2 ± 15.7 years (range 20–86 years), and 39 (75.0%) patients had concomitant subjective symptoms such as fatigue. All but 4 patients had been exposed to ticks while in areas that included the Lower Hudson Valley (Table 1).

Convalescent-phase blood samples, which were obtained at a mean of 16.7 days (range 7–30 days) after the baseline visit, were screened for antibodies to the C6 peptide of B. burgdorferi and for antibodies to A. phagocytophilum, B. microti, GlpQ protein of B. miyamotoi, and POWV. A total of 46 (88.5%) patients were seropositive by the C6 Lyme ELISA, 32 (69.6%) on both the baseline and convalescent-phase blood samples, and 14 (30.4%) on the convalescent-phase sample only.

None of the 52 patients had evidence of A. phagocytophilum co-infection, although 4 had an IgG titer of 1:64 on the convalescent-phase blood sample, which is regarded as a nonspecific finding.[13,17,18] Titers <1:64 were considered to be negative by the performing laboratory and thus were not reported.

Of the 52 patients, 4 (7.7%, 95% CI 3%–18%) had convincing evidence of B. microti co-infection (Table 2), and active babesiosis was clinically suspected for 3 of these patients. For 1 of the 3 patients who had clinical evidence of active babesiosis and a single erythema migrans lesion, fever developed on day 4 of amoxicillin therapy. Another of these patients underwent diagnostic testing for babesiosis because of fever before development of a single erythema migrans lesion. The third patient, who was afebrile, was tested for babesiosis 2 days after beginning antimicrobial drug treatment for a single erythema migrans lesion because of thrombocytopenia and anemia that were documented at the time of study entry. These 3 patients were positive for B. microti DNA by PCR, and 1 of the 3 also had a positive blood smear. All 3 patients received a course of treatment for babesiosis.

A fourth patient without a febrile illness had a convalescent-phase IgG titer of 1:512 and an acute-phase titer of <1:64, consistent with co-infection with B. microti. In addition, 2 patients without clinical evidence of a febrile illness had acute- and convalescent-phase IgG titers of ≥1,024 (Table 2). Because the exact titer for these serum specimens was not determined, it was not possible to determine if the convalescent-phase sample demonstrated a 4-fold increase in titer. Although none of these 3 patients received anti-Babesia drug therapy, all recovered fully from Lyme disease during the 1-year follow-up period.

Therefore, up to 6 (11.5%; 95% CI 5%–23%) of the 52 patients may have been co-infected with Babesia; 3 of these patients were known to have had fever, hematologic findings consistent with active Babesia infection, or both. All 6 had ≥1 nonspecific symptoms at study entry; mean ± SD was 3.3 ± 3.4 symptoms (range 1–10 symptoms). In comparison, the mean number of symptoms for the other 46 patients at the baseline visit was 3.1 ± 3.3 (range 0–12 symptoms; p = 0.88). One additional patient had a convalescent-phase IgG titer of 1:128 and an acute-phase IgG titer of 1:256, possibly indicative of a prior Babesia infection antedating the onset of Lyme disease.

None of the 52 patients met criteria for serologic evidence of B. miyamotoi co-infection, although 4 (7.7%) were seropositive for antibodies to GlpQ on acute- and convalescent-phase serum samples but without a discernible increase in values on the convalescent-phase sample. In addition, none of the 52 patients met criteria for serologic evidence for possible or confirmed POWV co-infection; 1 serum sample was positive for IgM to the LB strain of POWV but negative for neutralization antibodies to both the LB strain and a deer tick virus subtype strain of POWV. Therefore, more patients had laboratory evidence of co-infection with Babesia than with A. phagocytophilum, B. miyamotoi, or POWV (possibly as high as 6 [11.5%] for Babesia vs. 0 for the other pathogens tested; p = 0.031).