Metanalysis of the Diagnostic Performance of Western Blot for the Early Diagnosis of Congenital Toxoplasmosis
DOI:
https://doi.org/10.5195/ijms.2023.2388Keywords:
Congenital Toxoplasmosis, Western BlotAbstract
BACKGROUND: Congenital toxoplasmosis is an infection caused by the Toxoplasma gondii a protozoa obligate intracellular parasite that appears after a mother´s primary infection occurs during pregnancy. The congenital infection can cause severe symptoms such as: hydrocephalus, intracranial calcifications, seizures, hepatosplenomegaly, and chorioretinitis, leading to irreversible neurological and ocular lesions. Its early diagnosis is critical to obtain good outcomes after treatment where the western blot is considered as the gold standard. Western blot discriminate antibodies for specific proteins of the microorganism enabling differentiation between antibodies transmitted by mother from those elaborated by the newborn (compared immunological profiles) and can be obtained commercially or be elaborated by the clinical laboratory test (“house made”). However, there is not metanalysis about the diagnostic properties of the test that can support evidence-based recommendations for its use.
METHODS: The research terms used were: “congenital toxoplasmosis” and “western blot”. Databases for bibliographic searches were PubMed and Scopus, without restriction of date or language. Selection criteria were studies of evaluation of the diagnostic performance of western blot assay that included newborn with a definitive diagnosis of congenital infection by Toxoplasma according to the European network case definition (IgG anti-Toxoplasma persistent at 10 months of age) and controls that were defined by IgG antibodies that disappears in the serum of children in absence of treatment before six months of age. Screening and literature selection was done by the four researchers and disagreement were settled by reaching a consensus by discussion with mentor to avoid the erroneous exclusion of eligible articles. The PRISMA statement (http://www.prisma-statement.org/) was followed for quality assessment of the manuscript. The data were organized in an evidence table matrix, and sensitivity, specificity, and diagnostic odds ratio (DOR) index were calculated.
RESULTS: Of 44 articles related to the search terms were found in literature databases, 10 fulfill criteria to be included in the metanalysis. The sensitivity obtained was 93.8 (95 CI: 79.2-98.4) and the specificity of 96.6% (95 CI: 89.8-98.9). However, heterogeneity was observed between the studies. Causes for heterogeneity were the different methods to elaborate the western blot assay. Commercial methods showed better performance that homemade methods. The results suggest that better accuracy can be obtained by using standardized commercial test.
CONCLUSION: In conclusion, the meta-analysis supports the use of the Western Blot test as an effective method for the diagnosis of congenital toxoplasmosis in terms of sensitivity and specificity. However, further research is needed to establish more accuracy regarding sensitivity and specificity in the diagnosis in different settings by using well standardized assays.
Metrics
References
Stajner T, Bobic B, Klun I, Nikolic A, Srbljanovic J, Uzelac A, et al. Diagnóstico prenatal y posnatal temprano de toxoplasmosis congénita en un entorno sin detección sistemática en el embarazo. Medicina (Baltimore) [Internet]. 2016;95(9):e2979. Disponible en: http://dx.doi.org/10.1097/md.0000000000002979
Rilling V, Dietz K, Krczal D, Knotek F, Enders G. Evaluación de un ensayo de transferencia Western IgG/IgM comercial para el diagnóstico postnatal temprano de toxoplasmosis congénita. Eur J Clin Microbiol Infect Dis [Internet]. 2003;22(3):174–80. Disponible en: http://dx.doi.org/10.1007/s10096-003-0906-6
Tissot Dupont D, Fricker-Hidalgo H, Brenier-Pinchart MP, Bost-Bru C, Ambroise-Thomas P, Pelloux H. Utilidad del Western blot en el seguimiento serológico de recién nacidos con sospecha de toxoplasmosis congénita. Eur J Clin Microbiol Infect Dis [Internet]. 2003;22(2):122–5. Disponible en: http://dx.doi.org/10.1007/s10096-003-0887-5
Franck J, Garin YJ, Dumon H. LDBio-Toxo II immunoglobulin G Western blot confirmatory test for anti-toxoplasma antibody detection. J Clin Microbiol. 2008 Jul;46(7):2334-8. Epub 2008 May 14. https://journals.asm.org/doi/10.1128/JCM.00182-08?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
L'Ollivier C, Wallon M, Faucher B, Piarroux R, Peyron F, Franck J. Comparison of mother and child antibodies that target high-molecular-mass Toxoplasma gondii antigens by immunoblotting improves neonatal diagnosis of congenital toxoplasmosis. Clin Vaccine Immunol. 2012 Aug;19(8):1326-8.Epub 2012 Jun 13. https://journals.asm.org/doi/10.1128/CVI.00060-12?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Gallego-Marín C, Henao AC, Gómez-Marín JE. Clinical validation of a western blot assay for congenital toxoplasmosis and newborn screening in a hospital in Armenia (Quindio) Colombia. J Trop Pediatr. 2006 Apr;52(2):107-12. Epub 2005 Jul 13. Disponible en: https://pubmed.ncbi.nlm.nih.gov/16014760/
Machado AS, Andrade GM, Januário JN, Fernandes MD, Carneiro AC, Carneiro M, Carellos EV, Romanelli RM, Vasconcelos-Santos DV, Vitor RW. IgG and IgM western blot assay for diagnosis of congenital toxoplasmosis. Mem Inst Oswaldo Cruz. 2010 Sep;105(6):757-61. Disponible en: https://doi.org/10.1590/s0074-02762010000600005
Jaqueline Dario Capobiango, ThaÃs Cabral Monica, Fernanda Pinto Ferreira, Regina Mitsuka-Breganó, Italmar Teodorico Navarro, João Luis Garcia, Edna Maria Vissoci Reiche. Evaluation of the Western blotting method for the diagnosis of congenital toxoplasmosis. Jornal Pediatra. Volume 92, Issue 6, 2016, Pages 616-623. Estudio retrospectivo. Disponible en: https://pubmed.ncbi.nlm.nih.gov/27504975/
Pinon JM, Dumon H, Chemla C, Franck J, Petersen E, Lebech M, et al. [Strategy for diagnosis of congenital toxoplasmosis: evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies. J Clin Microbiol [Internet].2001:2267–71. Estudio restrospectivo. Disponible en: https://doi.org/10.1128%2FJCM.39.6.2267-2271.2001
Guy EC. Toxoplasmosis. Medicine (Abingdon) [Internet]. 2014 [citado el 9 de abril de 2023];42(1):31–3. Disponible en: https://www.cun.es/enfermedades-tratamientos/enfermedades/toxoplasmosis
Pereira Á, Pérez M. Toxoplasmosis. Offarm [Internet]. 2002 [citado el 9 de abril de 2023];21(4):123–8. Disponible en: https://www.elsevier.es/es-revista-offarm-4-articulo-toxoplasmosis-1302895
Kota AS, Shabbir N. Congenital Toxoplasmosis. StatPearls Publishing; 2022.[citado el 9 de abril de 2023]. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK545228/Edu.co. [citado el 9 de abril de 2023]. Disponible en: https://repository.urosario.edu.co/server/api/core/bitstreams/d1a68022-d6b2-447d-a2b6-c5d6f580cb4d/content#:~:text=La%20prevalencia%20mundial%20de%20toxoplasmosis,1.000%20nacidos%20vivos(22).
Capobiango JD, Monica TC, Ferreira FP, Mitsuka-Breganó R, Navarro IT, Garcia JL, et al. Evaluación del método Western blotting para el diagnóstico de toxoplasmosis congénita. J Pediatr (Río J) [Internet]. 2016;92(6):616–23. Disponible en: https://www.sciencedirect.com/science/article/pii/S0021755716300973
Machado AS, Andrade GMQ, Januário JN, Fernandes MD, Carneiro ACAV, Carneiro M, et al. Ensayo de western blot de IgG e IgM para el diagnóstico de toxoplasmosis congénita. Mem Inst Oswaldo Cruz [Internet]. 2010 [citado el 10 de abril de 2023];105(6):757–61. Disponible en: https://www.scielo.br/j/mioc/a/by3g7f6j5Vcd7bQjcBNCcHg/?lang=es
Pinon JM, Dumon H, Chemla C, Franck J, Petersen E, Lebech M, et al. [Strategy for diagnosis of congenital toxoplasmosis: evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies. J Clin Microbiol [Internet].2001:2267–71. Estudio restrospectivo. Disponible en: https://doi.org/10.1128%2FJCM.39.6.2267-2271.2001
Machado AS, Andrade GM, Januário JN, Fernandes MD, Carneiro AC, Carneiro M, Carellos EV, Romanelli RM, Vasconcelos-Santos DV, Vitor RW. IgG and IgM western blot assay for diagnosis of congenital toxoplasmosis. Mem Inst Oswaldo Cruz. 2010 Sep;105(6):757-61. Disponible en: https://doi.org/10.1590/s0074-02762010000600005
Stajner T, Bobic B, Klun I, Nikolic A, Srbljanovic J, Uzelac A, et al. Diagnóstico prenatal y posnatal temprano de toxoplasmosis congénita en un entorno sin detección sistemática en el embarazo. Medicina (Baltimore) [Internet]. 2016;95(9):e2979. Disponible en: http://dx.doi.org/10.1097/md.0000000000002979
Rilling V, Dietz K, Krczal D, Knotek F, Enders G. Evaluación de un ensayo de transferencia Western IgG/IgM comercial para el diagnóstico postnatal temprano de toxoplasmosis congénita. Eur J Clin Microbiol Infect Dis [Internet]. 2003;22(3):174–80. Disponible en: http://dx.doi.org/10.1007/s10096-003-0906-6
Tissot Dupont D, Fricker-Hidalgo H, Brenier-Pinchart MP, Bost-Bru C, Ambroise-Thomas P, Pelloux H. Utilidad del Western blot en el seguimiento serológico de recién nacidos con sospecha de toxoplasmosis congénita. Eur J Clin Microbiol Infect Dis [Internet]. 2003;22(2):122–5. Disponible en: http://dx.doi.org/10.1007/s10096-003-0887-5
Magi B, Migliorini L. Western blotting for the diagnosis of congenital toxoplasmosis. New Microbiol [Internet]. 2011;34(1):93–5
Franck J, Garin YJ, Dumon H. LDBio-Toxo II immunoglobulin G Western blot confirmatory test for anti-toxoplasma antibody detection. J Clin Microbiol. 2008 Jul;46(7):2334-8. Epub 2008 May 14. https://journals.asm.org/doi/10.1128/JCM.00182-08?
Downloads
Published
How to Cite
License
Copyright (c) 2023 Sebastián Serna Rivera, María Antonia Restrepo Duque, Jocelyn Alexandra Arredondo Torres, Juan David Fandiño López, Luis Felipe Mosquera Solano, Jorge E. Gómez M
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
- Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
- The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
- Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site; with the understanding that the above condition can be waived with permission from the Author and that where the Work or any of its elements is in the public domain under applicable law, that status is in no way affected by the license.
- The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
- Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
- The Author represents and warrants that:
- the Work is the Author’s original work;
- the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
- the Work is not pending review or under consideration by another publisher;
- the Work has not previously been published;
- the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
- the Work contains no libel, invasion of privacy, or other unlawful matter.
- The Author agrees to indemnify and hold Publisher harmless from the Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
Enforcement of copyright
The IJMS takes the protection of copyright very seriously.
If the IJMS discovers that you have used its copyright materials in contravention of the license above, the IJMS may bring legal proceedings against you seeking reparation and an injunction to stop you using those materials. You could also be ordered to pay legal costs.
If you become aware of any use of the IJMS' copyright materials that contravenes or may contravene the license above, please report this by email to contact@ijms.org
Infringing material
If you become aware of any material on the website that you believe infringes your or any other person's copyright, please report this by email to contact@ijms.org