Global seroprevalence and sociodemographic characteristics of Borrelia burgdorferi sensu lato in human populations: a systematic review and meta-analysis
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  • Published on:
    Caution advised when comparing or pooling seropositivity proportions
    • Max J. Hassenstein, Research fellow Helmholtz Centre for Infection Research
    • Other Contributors:
      • Manuela Harries, Research fellow
      • Stefanie Castell, Deputy Head of Department, Department for Epidemiology; Research fellow

    We read the systematic review by Dong et al. [1] with great interest. The authors aimed to describe global seroprevalence estimates for B. burgdorferi s.l., the causal agent of Lyme disease.

    First, estimating seropositivity for a target population (here, the global population) has two challenges we would like to address:
    1) The age and sex distribution of the population providing sample(s) and the target population should correspond. The simple reason is that advancing age and male sex are well-established risk factors for a positive IgG antibody serostatus [2]. Therefore, one may not conclude the general population seropositivity from an aged sample with a large share of males if not corrected accordingly, e.g., by applying weights; otherwise, seropositivity may be overestimated. Unfortunately, the age and sex profiles of the individual studies were seemingly not considered or discussed for their final seropositivity estimates.
    2) Then, as already stated in the first reply to this manuscript by A. Semper et al., the studies containing subjects with medical conditions or even patients with suspected or confirmed Lyme disease symptomatology are of little use for general population estimates of seropositivity (e.g., [3, 4], included by Dong et al.), as these populations do not correspond to the global population. Also, pooling seropositivity proportions for high-risk populations to obtain global estimates potentially introduces bias and, hence, should be a...

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    Conflict of Interest:
    None declared.
  • Published on:
    Response to Dong et al: Global seroprevalence and sociodemographic characteristics of Borrelia burgdorferi sensu lato in human populations: a systematic review and meta-analysis
    • Amanda Semper, Principal Scientist and Scientific Programme Manager UK Health Security Agency - Porton (Rare & Imported Pathogens Laboratory)
    • Other Contributors:
      • Eilish Hart, PhD Student
      • Jennifer Warner, Knowledge Discovery Scientist
      • Matthew Dryden, Consultant in Infection
      • Tim Brooks, Clinical Services Director
      • Zoë Gibney, Principal Scientist (Zoonoses)
      • Wendi Shepherd, Consultant in Emerging Infections and Zoonoses
      • Katherine Russell, Consultant Medical Epidemiologist
      • Sally Mavin, Director
      • Dominic Mellor, Consultant in Veterinary Public Health

    Through a systematic review and meta-analysis, Dong et al (1) have calculated a global B. burgdorferi sensu lato (Bbsl) seroprevalence estimate of 14.5% (95% CI 12.8% to 16.3%). We question the accuracy and appropriateness of such an estimate.

    As the authors demonstrate, seroprevalence estimates based on orthogonal 2-tier serological testing with a confirmatory Western-blot assay decrease the risk of false-positive results and are more reliable than those using single assays. Yet the pooled 14.5% estimate includes studies that used single assays, apparently without adjusting for the decreased reliability of single-tier testing. When studies using single-tier assays were excluded, the pooled estimate was reduced to 11.6% (95% CI 9.5% to 14.0%). The 14.5% estimate is based on studies spanning four population categories general, high-risk, tick-bitten and having Lyme-like symptoms. When these sub-groups were compared, the general population had a pooled seropositivity rate of 5.7% (95% CI 4.3% to 7.3%). We argue that only the general population category is relevant when estimating an unbiased population seroprevalence.

    Irrespective of accuracy, using a headline global seroprevalence estimate may be misleading, implying homogeneity when, as the authors report, there is wide variation in B. burgdorferi seroprevalence between countries and regions. Furthermore, the authors suggest that analysis of seropositivity to anti-Bbsl antibodies enhances understanding of th...

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    Conflict of Interest:
    None declared.