Surge in Anaplasmosis Cases in Maine, USA, 2013–2017

Incidence of human granulocytic anaplasmosis is rising in Maine, USA. This increase may be explained in part by adoption of tick panels as a frequent diagnostic test in persons with febrile illness and in part by range expansion of Ixodes scapularis ticks and zoonotic amplification of Anaplasma phagocytophilum.

disease in Maine. Borrelia burgdorferi, the agent of Lyme disease, is transmitted through the bite of infected blacklegged ticks (Ixodes scapularis). Lyme disease cases in Maine increased from a single case in 1986 to 1,844 in 2017, reflecting the northward range expansion of I. scapularis ticks (1). Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA), is also transmitted by I. scapularis ticks and is the second most common tickborne illness in Maine. Only 45 HGA cases were reported during 2000-2008 (2), but case reports rose dramatically during 2013-2017, generating media attention (3,4). The Maine Center for Disease Control and Prevention (MECDC) reported 663 cases of anaplasmosis in 2017, a 605% increase from 94 cases in 2013, in contrast with Lyme disease cases, which increased by only 33% (1,384 in 2013 to 1,844 in 2017) (5).
We sought to determine whether the increase in anaplasmosis cases reflected broader geographic transmission of A. phagocytophilum from ticks to humans through range expansion of I. scapularis ticks, increased testing effort through increased use of tick panels that detect multiple pathogens by PCR, or both. Evidence for increased transmission would include geographic range expansion of HGA incidence and hospitalizations. Evidence of increased testing effort would be increased use of tick panels, which could lead to discovery of mild A. phagocytophilum infections, especially pediatric cases, because HGA in children is generally a mild illness (6).

Surge in Anaplasmosis Cases in Maine, USA, 2013-2017
Incidence of human granulocytic anaplasmosis is rising in Maine, USA. This increase may be explained in part by adoption of tick panels as a frequent diagnostic test in persons with febrile illness and in part by range expansion of Ixodes scapularis ticks and zoonotic amplification of Anaplasma phagocytophilum.
with panels of MML and other laboratories (H. Webber, pers. comm., 2019 Aug 29). The HGA incidence rate, hospitalization rate, complications, and death rate increase with age (8), whereas Lyme incidence has a bimodal distribution, with peaks in young children and older adults (9). We tabulated HGA cases and incidence for 2008-2017 overall and by age class and tabulated HGA hospitalizations 2013-2017 overall and by age class and annual laboratory testing effort. For comparison, we included annual overall Lyme incidence and hospitalizations. We compared percentage changes from 2013 to 2017 in disease incidence and hospitalizations. To visualize geographic expansion of HGA, we plotted side-byside maps of county-level incidence and populationadjusted hospitalization rates for 2013 versus 2017.

Conclusions
We conclude that the surge in anaplasmosis incidence in Maine, an increase of 602% from 2013 to 2017, was a combination of increased transmission and testing effort, although we cannot partition the relative  contribution of each. The 231% rise in hospitalized patients with HGA and the geographic expansion of HGA incidence and hospitalization indicate increased transmission. Range expansion of I. scapularis ticks in Maine likely has contributed to the rise in HGA cases in areas where this tick species is emergent (i.e., a recent colonizer). In addition, zoonotic amplification of A. phagocytophilum is likely occurring where I. scapularis ticks are established. Because of less efficient enzootic transmission, human infection with Babesia microti, the agent of babesiosis, lags behind B. burgdorferi transmission over time and space (11). Less efficient enzootic transmission of A. phagocytophilum also may be the case, but we know of no confirmatory studies. Concurrent to increased transmission was the 1,085% increase in tickborne disease panel testing performed by the 2 major providers of testing results to Maine during 2013-2017. Increased testing effort may reflect increased clinician and patient awareness and ready availability of tickborne disease panels that detect multiple pathogens. These panels may lead to detection of mild A. phagocytophilum infections or coinfections in persons with nonspecific febrile illness, as suggested by increased detection of less severely ill persons, such as children. Thirty-eight of 39 pediatric HGA cases were reported after 2013, but there were no pediatric hospitalizations. Before the use of panels, pediatric HGA cases may have been ascribed to another illness with similar symptoms.
Studies relying on diagnostic tests are subject to test sensitivity and specificity. PCR is the most effective diagnostic test during early-stage A. phagocytophilum infection with high sensitivity and specificity (12,13). In this study, false positive PCR results were unlikely, based on test specificities reported by Mayo and NorDx.
Collaboration among all state health departments and testing laboratories across New England could help extend our findings. Vermont cases increased 1,078%, from 37 in 2013 to 399 in 2017 (14), and New Hampshire cases increased 260%, from 88 in 2013 to 317 in 2017 (15). Correlation between incidence and testing effort at the county level would corroborate a relationship between rising tickborne diseases and testing effort, if panel data included patient county of residence and travel history. Corroborating datasets on density of A. phagocytophilum-infected I. scapularis ticks would also help clarify the risks posed to human health. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 2, February 2020