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

Disclosures

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

In This Article

Discussion

In this study of 52 adult patients who had erythema migrans but had not been treated for Lyme disease, conducted in the Lower Hudson Valley of New York, the only documented B. burgdorferi co-infection was with B. microti. Several prior studies that used PCR have evaluated I. scapularis ticks found in this region for co-infection with B. burgdorferi; these studies found values of up to 30% for co-infection with A. phagocytophilum,[4,5,9,19] up to 24% for B. microti,[4,5,9,19] 1% for B. miyamotoi,[4] and up to 3.9% for POWV.[4,9] In general, lower rates of co-infection were associated with I. scapularis ticks in the nymphal stage than in the adult stage; this finding is relevant to our study because most cases of early Lyme disease in this region result from bites of ticks in the nymphal stage.[20]

Extrapolating data on the rate of co-infections by PCR testing of ticks to human co-infection rates should be done cautiously. Confounding factors are the possible existence of nonpathogenic strains of Anaplasma or Babesia in ticks and whether these organisms may have contributed to a portion of the positive PCR results for A. phagocytophilum[21] or B. microti. For example, B. odocoilei is found in I. scapularis ticks but is not regarded as a human pathogen.[22] In addition, the potential tick exposure locations of participants in our study were not restricted to the Lower Hudson Valley region of New York. Indeed, tick exposure for 4 of the 52 study participants occurred exclusively in Long Island or Connecticut (Table 1), and 1 of these 4 participants was among the 6 participants with laboratory evidence of B. microti co-infection (Table 2). This participant had no clinical evidence of a febrile illness but had acute- and convalescent-phase B. microti IgG titers ≥1,024.

We systematically evaluated adult patients with erythema migrans for co-infection with 4 I. scapularis tick–transmitted pathogens. We used well-defined and highly rigorous criteria for defining co-infection and focused on consecutively enrolled patients with the most certain clinical marker of early Lyme disease; namely, an erythema migrans lesion.[12] Studies using less stringent case definitions may potentially detect higher numbers of putative co-infections but with less certain validity and less clarity for differentiating sequential from simultaneous infections.[13,23] Unlike a previous study of untreated Babesia co-infections in patients considered to have Lyme disease,[24] patients in our study with evidence of Babesia co-infection at baseline evaluation were not more symptomatic than those without this co-infection.

Limitations of our study are the relatively small sample size and the assumption that the convalescent-phase serum samples were obtained at the appropriate time to reliably identify the co-infections assessed (mean time from baseline visit to collection of the convalescent- phase blood sample was 16.7 days [range 7–30 days]). Most (75%) of the 52 patients in our study had received doxycycline, raising the question of whether this treatment may have affected the likelihood of seroconversion for antibodies to A. phagocytophilum. However, patients with culture-confirmed human granulocytic anaplasmosis regularly produce high antibody titers within 2 weeks of symptom onset despite receipt of doxycycline.[17] Thus, the only theoretical concern about whether doxycycline might have reduced the observed frequency of A. phagocytophilum co-infection would have been for cases of incubating infection that might have been prevented from becoming active.

Another possibility, however, is that we excluded patients whose fever or systemic symptoms were primarily caused by human granulocytic anaplasmosis, rather than Lyme disease, and thus had started antimicrobial drug therapy before study entry. To address this question, we separately looked at acute- and convalescent-phase antibody titers to A. phagocytophilum in 38 patients with erythema migrans who were enrolled into the same study but for whom antimicrobial drug therapy had been initiated before enrollment. For 1 (2.6%) of the 38 patients, we found a 4-fold rise in antibody titers to A. phagocytophilum between the acute- and convalescent-phase serum samples. However, this finding did not differ significantly from what we found for the 52 patients with erythema migrans (1/38 vs. 0/52; p = 0.42).

Another study limitation is our use of serologic testing assays that were not approved by the US Food and Drug Administration; consequently, their performance characteristics are uncertain. Last, our results pertain to a particular geographic area over a discrete time frame and may not pertain to other locations or other periods.

In conclusion, we systematically and rigorously evaluated consecutively enrolled adult patients with erythema migrans for co-infection with the 4 other I. scapularis tick–transmitted pathogens found in parts of New York and in other geographic areas in the northeastern United States. Nearly 90% of the patients evaluated had no serologic evidence of co-infection. B. microti was the only co-infection found, further documenting the clinical relevance of this emerging infection. Similar studies in other geographic areas, in addition to testing acute- and convalescent-phase serum, should include direct diagnostic testing by use of reliable PCR assays to detect potential co-infecting pathogens (particularly for A. phagocytophilum, B. microti, and B. miyamotoi) at the baseline visit.

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