Lyme Disease (Borrelia burgdorferi)

2021 Case Definition

CSTE Position Statement Number: 21-ID-05

Clinical Criteria

An illness characterized by one of the following early or late-stage manifestations, as reported by a healthcare provider, and in the absence of another known etiology:

Erythema migrans (EM) rash. For purposes of surveillance, EM is defined as a skin lesion (observed by a healthcare provider) that typically begins as a red macule or papule and expands over a period of days to weeks to form a large round lesion, often with partial central clearing. A single primary lesion must reach a size of ≥5 cm in diameter. Note: Secondary lesions also may occur.
Musculoskeletal system. Recurrent, brief attacks (weeks or months) of objective joint swelling in one or a few joints. Note: Objective joint swelling may sometimes be followed by chronic arthritis in one or a few joints.
Nervous system. Any of the following signs that cannot be explained by any other etiology, alone or in combination: lymphocytic meningitis; cranial neuritis, particularly facial palsy (unilateral or bilateral); radiculoneuropathy; or, rarely, encephalomyelitis.
Cardiovascular system. Acute onset of high-grade (2nd-degree or 3rd-degree) atrioventricular conduction defects that resolve in days to weeks. Note: Atrioventricular conduction defects may sometimes be associated with myocarditis.

Laboratory Criteria

For the purposes of surveillance, laboratory evidence includes:

Confirmatory laboratory evidence:

Isolation of B. burgdorferi or B. mayonii in culture, OR
Detection of B. burgdorferi or B. mayonii in a clinical specimen by a B. burgdorferi group-specific NAAT assay, OR
Detection of B. burgdorferi group-specific antigens by immunohistochemical assay on biopsy or autopsy tissues, OR
Positive serologic tests in a two-tier or equivalent format, including:
1. Standard two-tier test (STTT): a positive or equivocal first-tier screening assay, often an enzyme immunoassay [EIA] or immunofluorescence assay [IFA] for IgM, IgG, or a combination of immunoglobulins, followed by a concordant positive IgM¹ or IgG² immunoblot interpreted according to established criteria, OR
2. Modified two-tier test (MTTT): positive or equivocal first-tier screen, followed by a different, sequential positive or equivocal EIA in lieu of an immunoblot as a second-tier test.

Presumptive laboratory evidence:

Positive IgG immunoblot, interpreted according to established criteria, without positive or equivocal first-tier screening assay

¹ IgM WB is considered positive when at least two of the following three bands are present: 24 kDa (OspC)*, 39 kDa (BmpA), and 41 kDa (Fla) in a specimen collected within 30 days of symptom onset.

² IgG WB is considered positive when at least five of the following 10 bands are present: 18 kDa, 24 kDa (OspC)*, 28 kDa, 30 kDa, 39 kDa (BmpA), 41 kDa (Fla), 45 kDa, 58 kDa (not GroEL), 66 kDa, and 93 kDa.

^* Depending upon the assay, OspC could be indicated by a band of 21, 22, 23, 24 or 25 kDA.

Case Classification

Confirmed: A clinically compatible case that meets confirmatory laboratory criteria.

Probable: A clinically compatible case that meets presumptive laboratory criteria.

Suspected:

A case that meets confirmatory or presumptive laboratory criteria, but no clinical information is available, OR
A case of erythema migrans rash with no laboratory evidence of infection.

Note: This CSTE case definition is intended solely for public health surveillance purposes and does not recommend diagnostic criteria for clinical partners to utilize in diagnosing patients with potential Lyme Disease.

Criteria to Distinguish a New Case

A new case is one that has not been reported within the same calendar year (January through December).

Table VII. Classification Table: Criteria for defining a case of Lyme disease.

Criterion	High Incidence States				Low Incidence States
Criterion	Suspect	Probable			Suspect				Probable	Confirmed
Clinical evidence
Erythema migrans rash					N				O	O	O	O
Objective joint swelling									O	O	O	O
Lymphocytic meningitis									O	O	O	O
Cranial neuritis									O	O	O	O
Facial palsy									O	O	O	O
Radiculoneuropathy									O	O	O	O
Encephalomyelitis									O	O	O	O
High-grade atrioventricular conduction defects (2nd-degree or 3rd-degree)									O	O	O	O
No clinical information available						N	N	N
Clinical symptoms reported by healthcare provider									N	N	N	N
Absence of another known etiology									N	N	N	N
Laboratory evidence
Isolation of B. burgdorferi sensu stricto or B. mayonii in culture		S				O				O
Detection of B. burgdorferi sensu stricto or B. mayonii in a clinical specimen by a B. burgdorferi group-specific NAAT assay		S				O				O
Detection of B. burgdorferi group-specific antigens by immunohistochemical assay on biopsy or autopsy tissues		S				O				O
Standard Two-Tier Test (STTT)^{^2}
Positive or equivocal result for serum antibody to B. burgdorferi by EIA or IFA			N				N				N
Positive immunoblot for B. burgdorferi-specific IgM^{^3} or IgG^{^4}			N				N				N
Modified Two-Tier test (MTTT)^{^2,5}
Positive or equivocal result for serum antibody to B. burgdorferi by EIA or IFA				N				N				N
Positive or equivocal result for serum antibody to B. burgdorferi by different, sequential EIA				N				N				N
Positive IgG immunoblot^{^6} (in the absence of a positive or equivocal first-tier screening assay)	S					O			N
No laboratory evidence of infection					N
Criteria to distinguish a new case
Not reported within the same calendar year (January through December)	N	N	N	N	N	N	N	N	N	N	N	N

Notes:
S = This criterion alone is SUFFICIENT to classify a case.
N = All “N” criteria in the same column are NECESSARY to classify a case. A number following an “N” indicates that this criterion is only
required for a specific disease/condition subtype (see below). If the absence of a criterion (i.e., criterion NOT present)
is required for the case to meet the classification criteria, list the absence of criterion as a necessary component.
O = At least one of these “O” (ONE OR MORE) criteria in each category (categories=clinical evidence, laboratory evidence, and epidemiologic evidence)
in the same column—in conjunction with all “N” criteria in the same column—is required to classify a case. A number
following an “O” indicates that this criterion is only required for a specific disease/condition subtype.
^{^2} Currently, there are no serologic tests available for B. mayonii infection, but cross-reactivity with B. burgdorferi testing may occur.
^{^3} IgM WB is considered positive when at least two of the following three bands are present: 24 kDa (OspC)^*, 39 kDa (BmpA), and 41 kDa (Fla).
Low incidence states should disregard IgM results for specimens collected >30 days after symptom onset. *Depending upon the
assay, OspC could be indicated by a band of 21, 22, 23, 24 or 25 kDA.
^{^4} IgG WB is considered positive when at least five of the following 10 bands are present: 18 kDa, 24 kDa (OspC)^*, 28 kDa, 30 kDa,
39 kDa (BmpA), 41 kDa (Fla), 45 kDa, 58 kDa (not GroEL), 66 kDa, and 93 kDa. ^*Depending upon the assay, OspC could
be indicated by a band of 21, 22, 23, 24 or 25 kDA.
^{^5} The MTTT algorithm should be performed using assays specifically cleared by the US Food and Drug Administration (FDA) for this purpose.
(Mead et al, 2019)
^{^6} While a single IgG WB is adequate for surveillance purposes, a two-tier test is still recommended for clinical diagnosis.

Council of State and Territorial Epidemiologists
Technical Supplement: 21-ID-05

Date Updated: September 15, 2023