Introduction of IgM testing for the diagnosis of acute Lyme borreliosis: a study of the benefits, limitations and costs

Joyner, Greg; Mavin, Sally; Milner, Rachel; Lim, Chin Leng

doi:10.1007/s10096-021-04366-4

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…Diagnosis of Lyme disease is based on the presence of symptomatology, which may, however, be quite diverse and/or atypical, objective physical findings (such as the manifestation of the characteristic erythema migrans (EM) rash, facial palsy, or arthritis), and history of possible exposure to infected ticks in combination with laboratory work-up. The standard two-tier testing technique (an initial screening test, usually enzyme immunoassay—ELISA—followed by a Western blot for reactive, equivocal samples [ 31 ], and testing for immunoglobulin—IgM and/or IgG—of the Borrelia burgdorferi sensu lato complex) may be poor in terms of detecting early localized infection (<50%). However, it is highly sensitive (>99% sensitivity) in the case of late infection [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Aseptic Meningitis Linked to Borrelia afzelii Seroconversion in Northeastern Greece: An Emerging Infectious Disease Contested in the Region

Kouroupis,

Terzaki,

Moscha

et al. 2024

TropicalMed

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Borreliosis (Lyme disease) is a zoonosis, mediated to humans and small mammals through specific vectors (ticks), with increasing global incidence. It is associated with a variety of clinical manifestations and can, if not promptly recognized and left untreated, lead to significant disability. In Europe, the main Borrelia species causing disease in humans are Borrelia burgdorferi s.s., Borrelia afzelii, Borrelia garinii, and Borrelia spielmanii. The Ixodes ricinus tick is their principal vector. Although Lyme disease is considered endemic in the Balkan region and Turkey, and all three main Lyme pathogens have been detected in ticks collected in these countries, autochthonous Lyme disease remains controversial in Greece. We report a case of aseptic meningitis associated with antibody seroconversion against Borrelia afzelii in a young female patient from the prefecture of Thasos without any relevant travel history. The patient presented with fever and severe headache, and the cerebrospinal fluid examination showed lymphocytic pleocytosis. Serum analysis was positive for specific IgG antibodies against Borrelia afzelii. In the absence of typical erythema migrans, serological evidence of infection is required for diagnosis. Although atypical in terms of clinical presentation, the seasonality and geographical location of potential disease transmission in the reported patient should raise awareness among clinicians for a still controversial and potentially underreported emerging infectious disease in Greece.

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Section: Discussionmentioning

confidence: 99%

Aseptic Meningitis Linked to Borrelia afzelii Seroconversion in Northeastern Greece: An Emerging Infectious Disease Contested in the Region

Kouroupis,

Terzaki,

Moscha

et al. 2024

TropicalMed

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“…This observation provides a cross-reactive explanation for the persistence over time of Borrelia OspC-IgM in patients without symptoms. Several studies have argued against testing for IgM in late LB because of the high frequency of false-positive results [ 23 , 25 , 30 , 51 ]. In general, an isotype switch toward IgG responses is expected after several weeks of infection.…”

Section: Discussionmentioning

confidence: 99%

Classical Borrelia Serology Does Not Aid in the Diagnosis of Persistent Symptoms Attributed to Lyme Borreliosis: A Retrospective Cohort Study

Stelma

Berende

Hofstede

et al. 2023

Life

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Objective: The diagnosis of Lyme borreliosis is based on two-tier testing using an ELISA and Western blot. About 5–10% of patients report persistent symptoms of unknown etiology after treatment, resulting in substantial difficulties in further diagnostic workup. This paper presents a study aimed at determining whether serology can differentiate between patients with persistent symptoms attributed to Lyme and other patients with Lyme borreliosis. Methods: A retrospective cohort study included 162 samples from four subgroups: patients with persistent symptoms of Lyme (PSL), early Lyme borreliosis with erythema migrans (EM), patients tested in a general practitioner setting (GP), and healthy controls (HC). ELISA, Western blots, and multiplex assays from different manufacturers were used to determine inter-test variations in PSL and to compare reactivity against Borrelia-specific antigens among the groups. Results: In comparing the IgG and IgM reactivity by Western blot, IgG was more often positive in the PSL group than in the GP group. The individual antigen reactivity was similar between the PSL and EM or GP groups. Inter-test agreement among the manufacturers was variable, and agreement was higher for IgG testing compared to IgM. Conclusions: Serological testing is unable to define the subgroup of patients with persistent symptoms attributed to Lyme borreliosis. Additionally, the current two-tier testing protocol shows a large variance among different manufacturers in these patients.

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“…The utility of serology for the diagnosis of LB has been much studied and it is well-known that the frequent use of the diagnostic measure for EM patients is a problem ( Dessau et al., 2018 ; Strizova et al., 2020 ; Vreugdenhil et al., 2020 ; Hillerdal and Henningsson, 2021 ; Joyner et al., 2022 ). Meta-studies have estimated that the sensitivity is very low, in the range of 29 - 49% ( European Centre for Disease Prevention and Control, 2016 ), due to the fact that seroconversion occurs late in LB and is often preceded by EM.…”

Section: Discussionmentioning

confidence: 99%

“…The basis for the diagnosis of LB is serology and it is routinely performed by use of enzyme immunoassays. Many reference laboratories use a two-tiered strategy, using Western blot analysis for confirmation of specificity ( Smittskyddsinstitutet, 2013 ; Kodym et al., 2018 ; Lager et al., 2019 ; Joyner et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Utility of Borrelia-specific IgM and IgG antibody titer determinations during a 12-year period – results from a clinical laboratory in Northern Sweden

Liu,

Tabibzada,

Lindgren

et al. 2023

Front. Cell. Infect. Microbiol.

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Interpretation of serological findings in suspected Lyme borreliosis (LB) is challenging and IgM reactivities may have low predictive value. Therefore, if used indiscriminately, there is a risk for incorrect diagnosis of LB. To evaluate the usefulness of IgM titer determination, we performed a study of the prevalence of Borrelia-specific antibodies in serological samples from patients with suspected LB analyzed during the period 2010 - 2021 at the University Hospital of Umeå in Sweden. In total, 19,335 samples had been analyzed for the presence of IgG and IgM antibodies. Overall, there were higher percentages of IgM positive or borderline titers, 1,847 (9.6%) and 905 (4.7%), respectively, than IgG positive or borderline titers, 959 (5.0%) and 406 (2.1%), respectively. Peak number of samples were recorded 2012 - 2013, exceeding 1,800, whereas there were around 1,200 during 2020 - 2021. The peak number of positive IgG and/or positive IgM samples were observed during the period 2015 - 2017 with close to, or above 400, and concomitantly, the proportion of IgG positive samples increased markedly. For IgG positive samples, the increase followed a positive linear time trend (P< 0.001). Peak monthly numbers were observed during August, September, and October. This seasonal increase was significant for the IgG positive group (P< 0.05), but not for the IgM positive/IgG negative group. Repeated samples were obtained from 3,188 individuals and of the initial samples 2,817 were (88%) IgG negative and 2,315 (72%) were IgM negative and of these, 130 (4%) showed IgG seroconversion and 300 (9%) IgM seroconversion. Collectively, the data demonstrate that IgG and/or IgM positive samples represented a minority of all samples, even when repeated sampling had occurred, and IgM positive samples were much more common than IgG positive samples. Thus, the accuracy of the clinical suspicion was low and this will lead to a low predictive value of the analysis, in particular of IgM. These findings question the use of IgM titer determination as a routine analysis.

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Introduction of IgM testing for the diagnosis of acute Lyme borreliosis: a study of the benefits, limitations and costs

Cited by 9 publications

References 20 publications

Aseptic Meningitis Linked to Borrelia afzelii Seroconversion in Northeastern Greece: An Emerging Infectious Disease Contested in the Region

Aseptic Meningitis Linked to Borrelia afzelii Seroconversion in Northeastern Greece: An Emerging Infectious Disease Contested in the Region

Classical Borrelia Serology Does Not Aid in the Diagnosis of Persistent Symptoms Attributed to Lyme Borreliosis: A Retrospective Cohort Study

Utility of Borrelia-specific IgM and IgG antibody titer determinations during a 12-year period – results from a clinical laboratory in Northern Sweden

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