Insufficient vaccination coverage in children with severe neurological pathology: causes and consequences

Children with chronic neurological pathology are at risk for the development of severe infectious diseases, but despite this, there is a poor coverage of preventive vaccinations in this category of children worldwide. For modern vaccine preparations, the presence of severe neurological conditions is not a contraindication to administration. There are only two reasons why vaccination should be postponed or the vaccine drug should be replaced. These are contraindications for the administration of live vaccines to children receiving immunosuppressive therapy, and contraindications for whole-cell pertussis vaccines to children with progressive neurological disease and convulsive syndrome. Studies conducted in different countries of the world prove the good tolerability and safety of vaccination in children with severe neurological pathology. But the use of certain drugs in the treatment of the underlying disease may affect the immunogenicity and effectiveness of vaccination. Currently, there is no generally accepted tactic for vaccinating children with various severe neurological conditions. This fact, as well as outdated attitudes in doctors and parents about the connection of vaccination with the onset of diseases of the nervous system, further increases the number of unvaccinated children. Issues related to the optimal vaccination time for children with severe neurological pathology, the frequency and strategy of vaccine administration still need to be addressed. There is a need to create widely recognized vaccination guidelines for children with severe neurological diseases, considering the nature of the disease, its course, and the therapy received.

Contribution:
Galitskaya M.G., Makarova S.G. — concept and design of the study;
Galitskaya M.G., Abdullayeva L.M. — collection and processing of the material, writing the text;
Fisenko A.P., Makarova S.G. — editing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: May 24, 2024
Accepted: June 11, 2024
Published: July 12, 2024

1. Potekhina E.S., Mikhailyuk E.V., Zenenko M.N. Children and teenagers’ neurologic pathology. Analysis of the main nosological forms. Mezhdunarodnyy studencheskiy nauchnyy vestnik. 2016; (6): 65. https://elibrary.ru/xdzgcf (in Russian)

2. Akopyan T.A. Prevalence, medical-social aspects and prognosis of primary disability of infants-residents of large agricultural region due to nervous system diseases. Sibirskiy meditsinskiy zhurnal (g. Tomsk). 2008; 23(1-2): 52–4. https://elibrary.ru/kzldnh (in Russian)

3. Paul S., Nahar A., Bhagawati M., Kunwar A.J. A review on recent advances of cerebral palsy. Oxid. Med. Cell. Longev. 2022; 2022: 2622310. https://doi.org/10.1155/2022/2622310

4. Boel L., Pernet K., Toussaint M., Ides K., Leemans G., Haan J. Respiratory morbidity in children with cerebral palsy: an overview. Dev. Med. Child Neurol. 2019; 61(6): 646–53. https://doi.org/10.1111/dmcn.14060

5. Kostinov M.P. Vaccination of Children with Health Disorders. A Guide for Doctors. [Vaktsinatsiya detey s narusheniyami sostoyaniya zdorov’ya. Rukovodstvo dlya vrachey]. Moscow: Meditsina dlya vsekh; 2002. (in Russian)

6. Zaccara G., Giovannelli F., Giorgi F.S., Franco V., Gasparini S., Mandò F., et al. Do antiepileptic drugs increase the risk of infectious diseases? A meta-analysis of placebo-controlled studies. Clin. Pharmacol. 2017; 83(9): 1873–9. https://doi.org/10.1111/bcp.13296

7. Surana P., Tang S., McDougall M., Tong C.Y., Menson E., Lim M. Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review. Eur. J. Pediatr. 2011; 170(8): 1007–15. https://doi.org/10.1007/s00431-010-1392-3

8. Desforges M., Le Coupanec A., Dubeau P., Bourgouin A., Lajoie L., Dubé M., et al. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses. 2019; 12(1): 14. https://doi.org/10.3390/v12010014

9. Rack A.L., Grote V., Streng A., Belohradsky B.H., Heinen F., von Kries R., et al. Neurologic varicella complications before routine immunization in Germany. Pediatr. Neurol. 2010; 42(1): 40–8. https://doi.org/10.1016/j.pediatrneurol.2009.07.012

10. Bax M., Goldstein M., Rosenbaum P., Leviton A., Paneth N., Dan B., et al. Executive committee for the definition of cerebral palsy. Proposed definition and classification of cerebral palsy, April 2005. Dev. Med. Child Neurol. 2005; 47(8): 571–6. https://doi.org/10.1017/s001216220500112x

11. McIntyre S., Goldsmith Sh., Webb A., Ehlinger V., Hollung S.J., McConnell K., et al. Global prevalence of cerebral palsy: A systematic analysis. Dev. Med. Child Neurol. 2022; 64(12): 1494–506. https://doi.org/10.1111/dmcn.15346

12. Bekteshi S., Monbaliu E., McIntyre S., Saloojee G., Hilberink S.R., Tatishvili N., et al. Towards functional improvement of motor disorders associated with cerebral palsy. Lancet Neurol. 2023; 22(3): 229–43. https://doi.org/10.1016/S1474-4422(23)00004-2

13. Horber V., Fares A., Platt M.J., Arnaud C., Krägeloh-Mann I., Sellier E. Severity of cerebral palsy – the impact of associated impairments. Neuropediatrics. 2020; 51(2): 120–8. https://doi.org/10.1055/s-0040-1701669

14. Bekteshi S., Vanmechelen I., Konings M., Ortibus E., Feys H., Monbaliu E. Clinical presentation of spasticity and passive range of motion deviations in dyskinetic cerebral palsy in relation to dystonia, choreoathetosis, and functional classification systems. Dev. Neurorehabil. 2021; 24(3): 205–13. https://doi.org/10.1080/17518423.2020.1858457

15. Tedroff K., Lidbeck C., Löwing K. Dystonia during hand activity in children with spastic unilateral cerebral palsy, an observational study. Eur. J. Paediatr. Neurol. 2022; 41: 36–40. https://doi.org/10.1016/j.ejpn.2022.06.015

16. Mert G.G., Incecik F., Altunbasak S., Herguner O., Mert M.K., Kiris N., et al. Factors affecting epilepsy development and epilepsy prognosis in cerebral palsy. Pediatr. Neurol. 2011; 45(2): 89–94. https://doi.org/10.1016/j.pediatrneurol.2011.03.001

17. O’Neill J., Newall F., Antolovich G., Lima S., Danchin M. Vaccination in people with disability: a review. Hum. Vaccin. Immunother. 2020; 16(1): 7–15. https://doi.org/10.1080/21645515.2019.1640556

18. Marpole R., Blackmore A.M., Gibson N., Cooper M.S., Langdon K., Wilson A.C. Evaluation and management of respiratory illness in children with cerebral palsy. Front. Pediatr. 2020; 8: 333. https://doi.org/10.3389/fped.2020.00333

19. Dinleyici M., Carman K.B., Kilic O., Gurlevik S.L., Yarar C., Dinleyici E.C. The immunization status of children with chronic neurological disease and serological assessment of vaccine-preventable diseases. Hum. Vaccin. Immunother. 2018; 14(8): 1970-6. https://doi.org/10.1080/21645515.2018.1460986

20. Greenwood V.J., Crawford N.W., Walstab J.E., Reddihough D.S. Immunisation coverage in children with cerebral palsy compared with the general population. J. Paediatr. Child Health. 2013; 49(2): Е137–41. https://doi.org/10.1111/jpc.12097

21. May P., Smithers-Sheedy H., Muhit M., Cumming R., Jones C., Booy R., et al. Immunisation status of children with cerebral palsy in rural Bangladesh: Results from the Bangladesh Cerebral Palsy Register (BCPR). Infect. Disord. Drug Targets. 2020; 20(3): 318–22. https://doi.org/10.2174/1871526518666181024101002

22. Bozkaya Y.S., Oncel E.K., Dundar N.O., Gencpinar P., Sarioglu B., Arican P., et al. Evaluation of immunization status in patients with cerebral palsy: a multicenter CP-VACC study. Eur. J. Pediatr. 2022; 181(1): 383–91. https://doi.org/10.1007/s00431-021-04219-4

23. Yang L., Peng J., Deng J., He F., Chen C., Yin F., et al. Vaccination status of children with epilepsy or cerebral palsy in Hunan rural area and a relative KAP survey of vaccinators. Front. Pediatr. 2019; 7: 84. https://doi.org/10.3389/fped.2019.00084

24. Tanabe T., Tagawa T., Arai H., Imaishi H., Uno R., Tanaka J., et al. Survey of Japanese pediatricians on vaccination of children with neurological disorders. Pediatr. Int. 2011; 53(5): 626–9. https://doi.org/10.1111/j.1442-200X.2011.03339.x

25. Groce N.E., Ayora P., Kaplan L.C. Immunization rates among disabled children in Ecuador: unanticipated findings. J. Pediatr. 2007; 151(2): 218–20. https://doi.org/10.1016/j.jpeds.2007.04.061

26. Mailand M.T., Frederiksen J.L. Vaccines and multiple sclerosis: a systematic review. J. Neurol. 2017; 264(6): 1035–50. https://doi.org/10.1007/s00415-016-8263-4

27. Stratton K., Ford A., Rusch E., Clayton E.W. Committee to Review Adverse Effects of Vaccines. Washington: National Academies Press; 2011. https://doi.org/10.17226/13164

28. Langer-Gould A., Qian L., Tartof S.Y., Brara S.M., Jacobsen S.J., Beaber B.E., et al. Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA Neurol. 2014; 71(12): 1506–13. https://doi.org/10.1001/jamaneurol.2014.2633

29. Frederiksen J.L., Topsøe M.M. Vaccines and multiple sclerosis. Acta Neurol. Scand. 2017; 136(Suppl. 201): 49–51. https://doi.org/10.1111/ane.12837

30. Boyko A.N., Sivertseva S.A., Chemakina D.S., Spirin N.N., Bykova O.V., Guseva M.E. Vaccination and multiple sclerosis at the present stage. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2021; 121(7-2): 44–8. https://doi.org/10.17116/jnevro202112107244 https://elibrary.ru/jqxxlr (in Russian)

31. Winkelmann A., Loebermann M., Reisinger E.C., Hartung H.P., Zettl U.K. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat. Rev. Neurol. 2016; 12(4): 217–33. https://doi.org/10.1038/nrneurol.2016.21

32. Loebermann M., Winkelmann A., Hartung H.P., Hengel H., Reisinger E.C., Zettl U.K. Vaccination against infection in patients with multiple sclerosis. Nat. Rev. Neurol. 2012; 8(3): 143–51. https://doi.org/10.1038/nrneurol.2012.8

33. Zrzavy T., Kollaritsch H., Rommer P.S., Boxberger N., Loebermann M., Wimmer I., et al. Vaccination in multiple sclerosis: friend or foe? Front. Immunol. 2019; 10: 1883. https://doi.org/10.3389/fimmu.2019.01883

34. Wiedermann U., Sitte H.H., Burgmann H., Eser A., Falb P., Holzmann H., et al. Guidelines for vaccination of immunocompromised individuals. Wien. Klin. Wochenschr. 2016;128(4):337–76. https://doi.org/10.1007/s00508-016-1033-6 (in German)

35. Rubin L.G., Levin M.J., Ljungman P., Davies E.G., Avery R., Tomblyn M., et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin. Infect. Dis. 2014; 58(3): 309–18. https://doi.org/10.1093/cid/cit816

36. Heineman T.C., Cunningham A., Levin M. Understanding the immunology of Shingrix, a recombinant glycoprotein E adjuvanted herpes zoster vaccine. Curr. Opin. Immunol. 2019; 59: 42–8. https://doi.org/10.1016/j.coi.2019.02.009

37. Klotz L., Havla J., Schwab N., Hohlfeld R., Barnett M., Reddel S., et al. Risks and risk management in modern multiple sclerosis immunotherapeutic treatment. Ther. Adv. Neurol. Disord. 2019; 12: 175628641983657. https://doi.org/10.1177/1756286419836571

38. Triplett J., Kermode A.G., Corbett A., Reddel S.W. Warts and all: Fingolimod and unusual HPV-associated lesions. Multiple Scler. J. 2019; 25(11): 1547–50. https://doi.org/10.1177/1352458518807088

39. Hauser S.L., Bar-Or A., Comi G., Giovannoni G., Hartung H.P., Hemmer B., et al. Ocrelizumab versus Interferon Beta-1a in relapsing multiple sclerosis. N. Engl. J. Med. 2017; 376(3): 221–34. https://doi.org/10.1056/NEJMoa1601277

40. Aartsma-Rus A., Ginjaar I.B., Bushby K. The importance of genetic diagnosis for Duchenne muscular dystrophy. J. Med. Genet. 2016; 53(3): 145–51. https://doi.org/10.1136/jmedgenet-2015-103387

41. Birnkrant D.J., Bushby K., Bann C.M., Alman B.A., Apkon S.D., Blackwell A., et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: Respiratory, cardiac, bone health, and orthopedic management. Lancet Neurol. 2018; 17(4): 347–61. https://doi.org/10.1016/S1474-4422(18)30025-5

42. Deng J., Zhang J., Shi K., Liu Z. Drug development progress in Duchenne muscular dystrophy. Front. Pharmacol. 2022; 13: 950651. https://doi.org/10.3389/fphar.2022.950651

43. Emery A.E. The muscular dystrophies. Lancet. 2002; 359(9307): 687–95. https://doi.org/10.1016/S0140-6736(02)07815-7

44. Finder J.D., Birnkrant D., Carl J., Farber H.J., Gozal D., Iannaccone S.T., et al. Respiratory care of the patient with Duchenne muscular dystrophy: ATS consensus statement. Am. J. Respir. Crit. Care Med. 2004; 170(4): 456–65. https://doi.org/10.1164/rccm.200307-885ST

45. Lofaso F., Orlikowski D., Raphael J.C. Ventilatory assistance in patients with Duchenne muscular dystrophy. Eur. Respir. J. 2006; 28(3): 468–9. https://doi.org/10.1183/09031936.06.00059906

46. McNally E.M. New approaches in the therapy of cardiomyopathy in muscular dystrophy. Annu. Rev. Med. 2007; 58: 75–88. https://doi.org/10.1146/annurev.med.58.011706.144703

47. Bourke J.P., Guglieri M., Duboc D. Updating management recommendations of cardiac dystrophinopathy Hoofddorp, The Netherlands, 2018. Neuromuscul. Disord. 2019; 29(8): 634–43. https://doi.org/10.1016/j.nmd.2019.06.598

48. Buddhe S., Cripe L., Friedland-Little J., Kertesz N., Eghtesady P., Finder J., et al. Cardiac management of the patient with Duchenne muscular dystrophy. Pediatrics. 2018; 142(2): 72–81. https://doi.org/10.1542/peds.2018-0333I

49. Schram G., Fournier A., Leduc H., Dahdah N., Therien J., Vanasse M., et al. All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy. J. Am. Coll. Cardiol. 2013; 61(9): 948–54. https://doi.org/10.1016/j.jacc.2012.12.008

50. Matthews E., Brassington R., Kuntzer T., Jichi F., Manzur A.Y. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst. Rev. 2016(5): CD003725. https://doi.org/10.1002/14651858.CD003725.pub4

51. McDonald C.M., Henricson E.K., Abresch R.T., Duong T., Joyce N.C., Hu F., et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: A prospective cohort study. Lancet. 2018; 391(10119): 451–61. https://doi.org/10.1016/S0140-6736(17)32160-8

52. Zhang S., Qin D., Wu L., Li M., Song L., Wei C., et al. Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy. Orphanet J. Rare Dis. 2021; 16(1): 188. https://doi.org/10.1186/s13023-021-01837-x

53. Mercuri E., Finkel R.S., Muntoni F., Wirth B., Montes J., Mainet M., et al. SMA Care Group. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul. Disord. 2018; 28(2): 103–15. https://doi.org/10.1016/j.nmd.2017.11.005

54. Dubowitz V. Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. Eur. J. Paediatr. Neurol. 1999; 3(2): 49–51. https://doi.org/10.1053/ejpn.1999.0181

55. Pearn J.H., Wilson J. Acute Werdnig-Hoffmann disease: acute infantile spinal muscular atrophy. Arch. Dis. Child. 1973; 48(6): 425–30. https://doi.org/10.1136/adc.48.6.425

56. Darras B.T., Jones H.R. Jr., Ryan M.M., De Vivo D.C. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. Elsevier; 2014.

57. Prior Th.W., Leach M.E., Finanger E., Adam M.P., Feldman J., Mirzaa Gh.M., et al. Spinal Muscular Atrophy. In: GeneReviews®. Seattle: University of Washington; 1993–2020.

58. Russman B.S. Spinal muscular atrophy: clinical classification and disease heterogeneity. J. Child Neurol. 2007; 22(8): 946–51. https://doi.org/10.1177/0883073807305673

59. Nicolau S., Waldrop M.A., Connolly A.M., Mendell J.R. Spinal muscular atrophy. Semin. Pediatr. Neurol. 2021; 37: 100878. https://doi.org/10.1016/j.spen.2021.100878

60. Muscular Dystrophy Association. Medical Management – Duchenne Muscular Dystrophy (DMD) – Diseases. Available at: https://www.mda.org/disease/duchenne-muscular-dystrophy/medical-management

61. Qu Y.J., Tian Y.L., Song F., Wang J., Bai J.L., Cao Y.Y., et al. Coverage rate and adverse reactions of National Immunization Program vaccines in children with spinal muscular atrophy: a cross-sectional retrospective cohort study. Zhonghua Er Ke Za Zhi. 2020; 58(4): 308–13. https://doi.org/10.3760/cma.j.cn112140-20200108-00016 (in Chinese)

62. Finkel R.S., Mercuri E., Meyer O.H., Simonds A.K., Schroth M.K., Grahamet R.J., et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul. Disord. 2017; 28(3): 197–207. https://doi.org/10.1016/j.nmd.2017.11.004

63. Hwang A., Veira C., Malvolti S., Cherian T., MacDonald N., Steffen C., et al. Global vaccine action plan lessons learned II: Stakeholder perspectives. Vaccine. 2020; 38(33): 5372–8. https://doi.org/10.1016/j.vaccine.2020.05.048

64. Esposito S., Bruno C., Berardinelli A., Filosto M., Mongini T., Morandiet L., et al. Vaccination recommendations for patients with neuromuscular disease. Vaccine. 2014; 32(45): 5893–900. https://doi.org/10.1016/j.vaccine.2014.09.003

65. Kotulska K., Jozwiak S., Jedrzejowska M., Gos M., Ogrodnik M., Wysocki J., et al. Newborn screening and gene therapy in SMA: Challenges related to vaccinations. Front. Neurol. 2022; 13: 890860. https://doi.org/10.3389/fneur.2022.890860

66. Shamsheva O.V. Healthy and Sick Child. Features of Vaccination [Zdorovyy i bol’noy rebenok. Osobennosti vaktsinatsii]. Moscow: GEOTAR-media; 2020. (in Russian)