DIPHTHERIA AS A SYSTEMIC DISEASE: ANALYSIS OF COMPLICATIONS ASSOCIATED WITH DIPHTHERIA TOXIN
Abstract
Diphtheria is a contagious disease caused by the bacteria Corynebacterium diphtheriae. This disease, although morbidity has significantly decreased in developed nations thanks to immunizations, continues to provide a substantial health risk in areas with low immunization rates. Diphtheria, with the acute inflammatory phase of the upper respiratory tract, can result in severe organ problems, mainly due to the effects of diphtheria toxin. Cardiac involvement, manifested as myocarditis, constitutes the most severe consequence of diphtheria and is the primary cause of mortality in affected persons. Diphtheritic polyneuropathy represents a considerable portion of post-diphtheritic sequelae and has a positive prognosis; therefore, timely diagnosis is crucial for efficient treatment. Renal impairment in diphtheria is less commonly reported than cardiac and neurological sequelae, necessitating greater investigation in this domain. This article reviews the current knowledge on the mechanisms of action of diphtheria toxin, the epidemiology of complications, their clinical manifestations, and possible diagnostic and therapeutic strategies. The significance of prophylaxis and the increasing danger of illness recurrence due to diminishing vaccination rates in some communities was also emphasized.
Aim of the study: This article aims to elucidate the current state of knowledge on organ complications of diphtheria, focusing on the mechanisms of diphtheria toxin, prevalent clinical manifestations, and potential implications in the cardiovascular, neurological, and renal systems. The paper seeks to highlight the significance of early diagnosis and underscore the need for a multidisciplinary approach in the management of respiratory diphtheria.
Materials and methods: A review of the literature available in the PubMed and Google Scholar database was performed, using the key words: „diphtheria”, „cardiac complications”, „neurological complications”, „myocarditis”, „polyneuropathy”, „Corynebacterium diphtheriae”.
References
Arvind, B., Ojha, V., Arava, S. K., Seth, S., & Ramakrishnan, S. (2022). Diphtheritic myocarditis: An unusual and reversible cause of heart failure. Annals of Pediatric Cardiology, 15(3), 311–313. https://doi.org/10.4103/apc.apc_144_21
Chanh, H. Q., Trieu, H. T., Vuong, H. N. T., Hung, T. K., Phan, T. Q., Campbell, J., Pley, C., & Yacoub, S. (2022). Novel Clinical Monitoring Approaches for Reemergence of Diphtheria Myocarditis, Vietnam. Emerging Infectious Diseases, 28(2), 282–290. https://doi.org/10.3201/eid2802.210555
Diphtheria reported cases and incidence. WHO. (2024), Https://Immunizationdata.Who.Int/Pages/Incidence/Diphtheria.Html?CODE=PAK&YEAR= (Access 7.08.2025)
Foo, J. C., Rahmat, K., Mumin, N. A., Koh, M. T., Gan, C. S., Ramli, N., & Fong, C. Y. (2017). Diphtheric encephalitis and brain neuroimaging features. Journal of Clinical Neuroscience, 45, 155–157. https://doi.org/10.1016/j.jocn.2017.08.024
Ilyas, S., Khan, I., Yousafzai, Z. A., Kamran Amin, Q., Rahman, Z., & Bilal, M. (2024). Diphtheria-Associated Myocarditis: Clinical Profiles and Mortality Trends in a Tertiary Care Hospital in Pakistan. Cureus. https://doi.org/10.7759/cureus.56744
Ilyas, S., Yousafzai, Z. A., Khan, I., Amin, Q. K., & Bilal, M. (2024). Diphtheria’s Dual Threat: Amplifying Awareness of Cardiac Complications for Enhanced Intervention. Cureus. https://doi.org/10.7759/cureus.56093
Jain, A., Samdani, S., Meena, V., & Sharma, M. P. (2016). Diphtheria: It is still prevalent!!! International Journal of Pediatric Otorhinolaryngology, 86, 68–71. https://doi.org/10.1016/j.ijporl.2016.04.024
Jammar, S. K., Sharma, S., Agarwal, S., Kataria, T., Jat, P. S., Singh, S. N., Jain, D., Sehra, R., & Gupta, A. (2022). Spectrum of Neurological Outcomes in Diphtheria: A Case Series. Indian Journal of Otolaryngology and Head and Neck Surgery, 74, 5454–5459. https://doi.org/10.1007/s12070-021-02706-6
Loiacono, M. M., Pool, V., & van Aalst, R. (2021). DTaP combination vaccine use and adherence: A retrospective cohort study. Vaccine, 39(7), 1064–1071. https://doi.org/10.1016/j.vaccine.2021.01.009
Maghrabi, K. (2024). Temporary Transvenous Pacemaker for the Treatment of Diphtheria Myocarditis and Progressive Conduction Block: A Case Report. Cureus. https://doi.org/10.7759/cureus.65508
Mahamadou, D., Bara Abdoul-Aziz, A., Mahaman Moustapha, L., Hassane, D., Adoum Fils, S., Hamsatou, B., Thomas Abraham, G., Sahada, M., Idrissa, H., Ousmane, S., Zaratou, A., Abdoul Aziz, G., Abdoulaye, O., Eric, A., & Paul Eholié, S. (2024). The resurgence of diphtheria in Zinder, Niger. Infectious Diseases Now, 54(8). https://doi.org/10.1016/j.idnow.2024.104979
Mangion, J. P., Mancini, S., Bachy, C., de Weggheleire, A., & Zamatto, F. (2023). Diphtheria in Europe. Public Health Action, 13(2), 31–33. https://doi.org/10.5588/pha.23.0011
Manikyamba, D., Satyavani, A., & Deepa, P. (2015). Diphtheritic polyneuropathy in the wake of resurgence of diphtheria. Journal of Pediatric Neurosciences, 10(4), 331–334. https://doi.org/10.4103/1817-1745.174441
Ott, L. (2018). Adhesion properties of toxigenic corynebacteria. In AIMS Microbiology (Vol. 4, Issue 1, pp. 85–103). AIMS Press. https://doi.org/10.3934/MICROBIOL.2018.1.85
Ott, L., Möller, J., & Burkovski, A. (2022). Interactions between the Re-Emerging Pathogen Corynebacterium diphtheriae and Host Cells. In International Journal of Molecular Sciences (Vol. 23, Issue 6). MDPI. https://doi.org/10.3390/ijms23063298
Pérez, L. G., & Brisse, S. (2024a). Diphtheria antitoxin treatment: from pioneer to neglected. In Memorias do Instituto Oswaldo Cruz (Vol. 119). Fundacao Oswaldo Cruz. https://doi.org/10.1590/0074-02760240214
Pérez, L. G., & Brisse, S. (2024b). Diphtheria antitoxin treatment: from pioneer to neglected. In Memorias do Instituto Oswaldo Cruz (Vol. 119). Fundacao Oswaldo Cruz. https://doi.org/10.1590/0074-02760240214
PLEASURE, D., & MESSING, A. (2005). Diphtheritic Polyneuropathy. In Peripheral Neuropathy (pp. 2147–2151). Elsevier. https://doi.org/10.1016/B978-0-7216-9491-7.50098-3
Prasad, P. L., & Rai, P. L. (2018). Prospective study of diphtheria for neurological complications. In Journal of Pediatric Neurosciences (Vol. 13, Issue 3, pp. 313–316). Wolters Kluwer Medknow Publications. https://doi.org/10.4103/JPN.JPN_130_17
Rosana, Y., Inta Prilandari, L., Ajisman, R., Sarry Hartono, T., & Yasmon, A. (2020). Detection of toxin-producing Corynebacterium diphtheriae from throat swabs of diphtheria patients using duplex real-time PCR (Vol. 12, Issue 6). http://ijm.tums.ac.ir
Samdani, S., Jain, A., Meena, V., & Meena, C. B. (2018). Cardiac complications in diphtheria and predictors of outcomes. International Journal of Pediatric Otorhinolaryngology, 104, 76–78. https://doi.org/10.1016/j.ijporl.2017.10.032
Truelove, S. A., Keegan, L. T., Moss, W. J., Chaisson, L. H., Macher, E., Azman, A. S., & Lessler, J. (2020). Clinical and epidemiological aspects of diphtheria: A systematic review and pooled analysis. In Clinical Infectious Diseases (Vol. 71, Issue 1, pp. 89–97). Oxford University Press. https://doi.org/10.1093/cid/ciz808
Weerasekera, D., Möller, J., Kraner, M. E., Antunes, C. A., Mattos-Guaraldi, A. L., & Burkovski, A. (2019). Beyond diphtheria toxin: Cytotoxic proteins of corynebacterium ulcerans and corynebacterium diphtheriae. Microbiology (United Kingdom), 165(8), 876–890. https://doi.org/10.1099/mic.0.000820
Views:
72
Downloads:
60
Copyright (c) 2025 Patrycja Jędrzejewska-Rzezak, Monika Czekalska, Natalia Kulicka, Kinga Knutelska, Aleksandra Winsyk, Paulina Gajniak, Maciej Karwat, Tytus Tyralik, Klaudia Bilińska, Joanna Węgrzecka
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
