RESEARCH PAPER
Preliminary studies of prevalence of Borrelia burgdorferi sensu lato and Toxoplasma gondii infections markers in patients with encephalitis of unknown aetiology
 
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1
Department of Immunopathology of Infectious and Parasitic Diseases, Medical University, Warsaw, Poland
 
2
Department of Adult Infectious Diseases, Medical University, Warsaw, Poland
 
3
Department of Parasitology, Faculty of Biology, University of Warsaw, Poland
 
 
Corresponding author
Agnieszka Pawełczyk   

Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, Pawinskiego 3c, 02-106, Warszawa, Poland
 
 
 
KEYWORDS
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ABSTRACT
Introduction and objective:
The aetiology of encephalitis frequently remains undetermined. Infections of the central nervous system (CNS) with Borrelia burgdorferi sensu lato and Toxoplasma gondii are particularly challenging to confirm due to inconsistent serological findings and low sensitivity of polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). The chemokine CXCL13 has been proposed as a supportive marker for neuroborreliosis. The aim of the study is to investigate the presence of immunological and molecular markers of B. burgdorferi s.l. and T. gondii in patients with encephalitis of unknown origin, and to evaluate their potential association with CNS involvement.

Material and methods:
A retrospective analysis was conducted on serum and CSF samples from 31 patients with a clinical diagnosis of encephalitis of unknown aetiology. Anti-Borrelia and anti-Toxoplasma antibodies and CXCL13 levels were measured using ELISA. Pathogen DNA was assessed by real-time PCR.

Results:
Anti-Borrelia antibodies were detected in 12 (38.7%) serum samples. Elevated CXCL13 levels (>100 pg/mL) were observed in 2 CSF samples. Anti-T. gondii IgG was found in 14 (45.2%) serum samples, with 5 (16.1%) also positive in CSF. High-avidity IgG was present in 9 (29.0%) serum and 3 (9.7%) CSF samples. Low-avidity IgG was found in 3 cases, with variable IgM status. No Borrelia or T. gondii DNA was detected.

Conclusions:
The presence of antibodies against B. burgdorferi s.l. and T. gondii in serum and/or CSF, occasionally accompanied by elevated CSF CXCL13, suggests a potential role of these pathogens in encephalitis of unknown aetiology, even in the absence of detectable DNA, and highlights the diagnostic value of combining serological and molecular testing.
REFERENCES (33)
1.
Baunbæk EG, Ertner G, Langholz KK, et al. Cerebrospinal fluid pleocytosis in infectious and non infectious central nervous system disease. A retrospective cohort study. Medicine. 2017;96(18):e6686. https://doi.org/10.1097/MD.000....
 
2.
Roos KL, Greenlee JE. Meningitis and encephalitis. Continuum (Minneap Minn) (5 Neurologic Consultation in the Hospital). 2011;17:1010–23. https://doi:10.1212/01.CON.000....
 
3.
Halperin JJ. Cerebrospinal fluid pleocytosis in infectious and noninfectious central nervous system disease Lyme neuroborreliosis. Curr Opin Infect Dis. 2019;32(3):259–264. https://doi.org/10.1097/QCO.00....
 
4.
Esam S. Al-Malki A. Toxoplasmosis: stages of the protozoan life cycle and risk assessment in humans and animals for an enhanced awareness and an improved socio-economic status. Saudi J Biol Sci. 2021;28(1):962–969. https://doi:10.1016/j.sjbs.202....
 
5.
Harari RB. Tick transmission of toxoplasmosis. Expert Rev Anti Infect Ther. 2019;17(11):911–917. https://doi.org/10.1080/147872....
 
6.
Ford L, Tufts DM. Lyme neuroborreliosis: Mechanisms of B. burgdorferi infection of the nervous system. Brain Sci. 2021;11:789. https://doi.org/10.3390/brains....
 
7.
Attias M, Teixeira DE, Benchimol M, et al. The life cycle of Toxoplasma gondii reviewed using animations. Parasit Vectors. 2020;13:588. https://doi.org/10.1186/s13071....
 
8.
Knudtzen FC, Andersen NS, Jensen TG, et al. Characteristics and clinical outcome of Lyme neuroborreliosis in a high endemic area, 1995–2014: A retrospective cohort study in Denmark. Clin Infect Dis. 2017;65:1489–1495. 50. https://doi.org/10.1093/cid/ci....
 
9.
Kubiak K, Szczotko M, Dmitryjuk M. Borrelia miyamotoi – an emerging human tick-borne pathogen in Europe. Microorganisms. 2021;(9):154. https://doi.org/10.3390/microo....
 
10.
Sucilathangam G, Palaniappan N, Sreekumar C, et. al. IgG–indirect fluorescent antibody technique to detect seroprevalence of Toxoplasma gondii in immunocompetent and immunodeficient patients in southern districts of Tamil Nadu. Indian J Med Microbiol. 2010;28:354–7. https://doi.org/10.4103/0255-0....
 
11.
Skogman BH, Lager M, Henningsson AJ, et al. The recomBead Borrelia antibody index, CXCL13 and total IgM index for laboratory diagnosis of Lyme neuroborreliosis in children Eur J Clin Microbiol Infect Dis. 2017;36(11):2221–2229. https://doi.org/10.1007/s10096....
 
12.
Petzke M, Schwartz I. Borrelia burgdorferi pathogenesis and the immune response. Clin Lab Med. 2015;35(4):745–764. https://doi.org/10.1016/j.cll.....
 
13.
Marino A, Santos I, Henriques PH, et al. Circulating inflammatory mediators as biomarkers of ocular toxoplasmosis in acute and in chronic infection. J Leuk Biol. 2020;108(4):1253–1264. https://doi-1org-100001ap50778.
 
14.
Switaj K, Master A, Skrzypczak M, et al. Recent trends in molecular diagnostics for Toxoplasma gondii infections. Clin Microbiol Infect. 2005;11:170–6. https://doi.org/10.1111/j.1469....
 
15.
Schwartz AM, Kugeler KJ, Nelson CA. Use of commercial claims data for evaluating trends in Lyme disease diagnoses, United States, 2010–2018. Emerg Infect Dis. 2021;27:499–507. https://doi.org/10.3201/eid270....
 
16.
Pagalavan F, Kan K. Cerebral toxoplasmosis in systemic lupus erythematosus following intravenous methylprednisolone. Med J Malaysia. 2011;66(1):68–70.
 
17.
Garcia-Monco JC, Benach JL. Lyme neuroborreliosis: Clinical outcomes, controversy, pathogenesis, and polymicrobial infections. Ann Neurol. 2019;85:21–31. https://doi.org/10.1002/ana.25....
 
18.
Waddell LA, Greig J, Mascarenhas M, et al. The accuracy of diagnostic tests for Lyme disease in humans, a systematic review and meta-analysis of North American research. PLOS ONE. 2016;11(12):1–23. https://doi.org/10.1371/journa....
 
19.
Knudtzen FC, Nilsson AC, Hovius, JW, et al. The predictive value of CXCL13 in suspected Lyme neuroborreliosis: a retrospective cross-sectional study. Eur J Clin Microbiol Infect Dis. 2020;39:1461–1470. https://doi.org/10.1007/s10096....
 
20.
Leth TA, Dessau RB, Møller JK. Discriminating between Lyme neuro-borreliosis and other central nervous system infections by use of biomarkers CXCL13 and IL-6. Ticks Tick Borne Dis. 2022;13(5):101984. https://doi.org/10.1016/j.ttbd....
 
21.
Markowicz M, Schotta AM, Kundi M, et al. CXCL13 concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other neurological disorders determined by Luminex and ELISA. Ticks Tick Borne Dis. 2018;9:1137–1142. https://doi.org/10.1016/j.ttbd....
 
22.
Ziegler K, Rath A, Schoerner C, et al. Comparative analysis of the Euroimmun CXCL13 EnzymeLinked Immunosorbent Assay and the ReaScan Lateral Flow Immunoassay for Diagnosis of Lyme Neuroborreliosis. J Clin Microbiol. 2020;58:9 e00207–20.
 
23.
Shah A, O’Horo JC, Wilson JW, et al. An unusual cluster of neuroinvasive Lyme disease cases presenting with Bannwarth Syndrome in the Midwest United States. Open Forum Infect. Dis. 2017;5:ofx276. https://doi.org/10.1093/ofid/o....
 
24.
Wohlfert EA, Blader IJ, Wilson EH, et al. Toxoplasma infections of the central nervous system and skeletal muscle. Trends Parasitol. 2017;33(7):519–531. https://doi.org/doi:10.1016/j.....
 
25.
Wang D, Liu HH, Ma ZX, et al. Toxoplasma gondii infection in immunocompromised patients: A systematic review and meta-analysis. Front Microbiol. 2017; 8:389. https://doi.org/10.3389/fmicb.....
 
26.
Pawełczyk A, Bednarska M, Caraballo Cortés K, et al. Seronegative-Infection with Toxoplasma gondii in asymptomatic human immunodeficiency virus type 1 (HIV-1) infected patients and blood donors. J Clin Med. 2022;11(3):638. https://doi.org/10.3390/jcm110....
 
27.
Teimouri A, Mohtasebi S, Kazemirad E, et al. Role of Toxoplasma gondii IgG avidity testing in discriminating between acute and chronic toxoplasmosis in pregnancy. J Clin Microbiol. 2020;58(9):e00505–20. https://doi.org/10.1128/JCM.00....
 
28.
Ybañez RHD, Ybañez AP, Nishikawa Y. Review on the current trends of toxoplasmosis serodiagnosis in humans. Front Cell Infect Microbiol. 2020;8(10):204. https://doi.org/doi.org/10.338....
 
29.
Gras L, Gilbert RE, Wallon M, et al. Duration of the IgM response in women acquiring Toxoplasma gondii during pregnancy: implications for clinical practice and cross-sectional incidence studies. Epidemiol Infect. 2004;132:541–548. https://doi.org/10.1017/S09502....
 
30.
Rodrigues IM, Castro AM, Gomes MB, et al. Congenital toxoplasmosis: evaluation of serological methods for the detection of anti- Toxoplasma gondii IgM and IgA antibodies. Mem Inst Oswaldo Cruz. 2009;104(3):434–40. https://doi.org/10.1590/S0074-....
 
31.
Chen L, Hou X, Zheng R, et al. Detection of toxoplasma tachyzoites in the cerebrospinal fluid of a COVID-19 positive SLE patient: a case study. BMC Infect Dis. 2025;25:325. https://doi:10.1186/s12879-025....
 
32.
Zając V, Pinkas J, Wójcik-Fatla A, et al. Prevalence of serological response to Borrelia burgdorferi in farmers from eastern and central Poland. Eur J Clin Microbiol Infect Dis. 2017;36:437–446. https://doi.org/10.1007/s10096....
 
33.
Wójcik- Fatla A, Sawczyn-Domańska A, Kloc A, et al. Seroprevalence of Borrelia, Bartonella, Toxoplasma, Mycoplasma, Yersinia, and Chlamydia in human population in Poland. Pathogens 2025;14,1:96; https://doi.org/10.3390/pathog....
 
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ISSN:1232-1966
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