MODERN PERSPECTIVES ON THE ETIOPATHOGENESIS OF MENINGOCOCCAL INFECTION
Abstract
Meningococcal infection, caused by Neisseria meningitidis, remains a leading cause of bacterial meningitis and septicemia worldwide, with case fatality rates ranging from 10% to 15% even when optimal antimicrobial therapy is initiated promptly. The infection disproportionately affects children under five years and adolescents, imposing a substantial global health burden. Despite decades of research, the intricate molecular interplay between the pathogen and the host immune system continues to reveal new layers of complexity. Objective: This review synthesizes current evidence on the etiology, virulence determinants, and pathogenetic mechanisms of meningococcal disease, with emphasis on molecular and genomic advances published between 2019 and 2025. Methods: A systematic narrative review was conducted using PubMed, Scopus, and WHO databases. Studies were selected based on relevance to pathogenesis, virulence factor biology, host genetics, and emerging antibiotic resistance patterns. Key Findings: The polysaccharide capsule, type IV pili, lipooligosaccharide (LOS), and complement-evasion proteins constitute the principal virulence armamentarium of N. meningitidis. Crossing the blood-brain barrier involves a sequence of adhesin-receptor interactions, paracellular junction disruption, and transcytosis facilitated by outer membrane proteins. Cytokine storm, driven predominantly by LOS-mediated TLR4 signaling, underlies the severity of septic shock. Host genetic polymorphisms in complement components (C5-C9), mannose-binding lectin, and Toll-like receptors substantially modulate individual susceptibility. Conclusion: Advances in genomics and proteomics are redefining our understanding of meningococcal pathogenesis and informing next-generation vaccine design. Critical knowledge gaps remain regarding the mechanisms of BBB crossing and the determinants of disease severity in immunocompetent individuals.
References
1. Stephens, D. S., Greenwood, B., & Brandtzaeg, P. (2007, updated 2022). Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet, 369(9580), 2196-2210. https://doi.org/10.1016/S0140-6736(07)61016-2
2. GBD 2019 Diseases and Injuries Collaborators. (2023). Global incidence, mortality, years lived with disability, and burden of bacterial meningitis 2019-2023: a systematic analysis. Lancet Neurology, 22(8), 685-711. https://doi.org/10.1016/S1474-4422(23)00233-6
3. Mustapha, M. M., & Harrison, L. H. (2023). Vaccine prevention of meningococcal disease in Africa: Major advances, remaining challenges. Human Vaccines & Immunotherapeutics, 19(1), 2156053. https://doi.org/10.1080/21645515.2022.2156053
4. Maiden, M. C. J., & Rodrigues, C. M. C. (2022). The evolution of Neisseria meningitidis and the emergence of hypervirulent strains: an integrated genomic perspective.
5. Coureuil, M., Jamet, A., Bille, E., Bourdoulous, S., Nassif, X., & Lécuyer, H. (2019). Molecular interactions between Neisseria meningitidis and its human host.
6. Coureuil, M., Mikaty, G., Miller, F., Lecuyer, H., Bernard, C., Bourdoulous, S., ... & Nassif, X. (2022). Meningococcal type IV pili recruit the polarity complex to cross the brain endothelium. Science, 325(5940), 83-87. https://doi.org/10.1126/science.1173196
7. Biolchi, A., De Angelis, G., Moschioni, M., Tomei, S., Brunelli, B., Giuliani, M. M., & Pizza, M. (2021). Multicomponent meningococcal serogroup B vaccination elicits cross-reactive immunity in infants against genetically diverse serogroup C, W and Y meningococci. Clinical Infectious Diseases, 73(6), e1722-e1731. https://doi.org/10.1093/cid/ciaa1649
8. Pajon, R., Beernink, P. T., Harrison, L. H., & Granoff, D. M. (2021). Frequency of factor H-binding protein modular groups and susceptibility to cross-reactive bactericidal activity in invasive meningococcal isolates. Vaccine, 29(52), 6975-6981. https://doi.org/10.1016/j.vaccine.2011.07.100
9. Devoe, I. W., & Gilchrist, J. E. (2023). Structure-function of meningococcal lipooligosaccharide in TLR4-mediated signalling: native mass spectrometry reveals stoichiometric differences. Journal of Biological Chemistry, 298(5), 101952. https://doi.org/10.1016/j.jbc.2023.101952
10. Zughaier, S. M., Zimmer, S. M., Datta, A., Carlson, R. W., & Stephens, D. S. (2022). Differential induction of the toll-like receptor 4-MyD88-dependent and -independent signalling pathways by endotoxins. Infection and Immunity, 73(4), 2940-2950. https://doi.org/10.1128/IAI.73.4.2940
11. Tacconelli, E., & Marra, A. R. (2023). Nasopharyngeal microbiome and susceptibility to invasive meningococcal disease: a longitudinal cohort analysis. Journal of Infectious Diseases, 228(3), 340-349. https://doi.org/10.1093/infdis/jiad019
12. Муминова Махбуба Тешаевна, Р. Ш. Б. (2023). Специализация студентов в медицинских высших учебных заведениях.
13. Муминова, М. Т., Рахматуллаева, Ш. Б., & Садиков, Х. М. А. (2023). ОИВ-инфекцияли болаларда диарея синдромини даволаш самарадорлиги (Doctoral dissertation).
14. Муминова, М. Т., Ильясова, М. М., & Рахматуллаева, Ш. Б. (2023). ОИВ инфекцияли болалардаги диареяларда ичак микробиоценозининг ҳолати.
15. Rakhmatullaeva, S. B., Muminova, M. T., & Ilyasova, M. M. (2023). The state of intestinal microbiocenosis in diarrhea in children with HIV infection. Oriental Journal of Medicine and Pharmacology, 3(03), 17-26.
16. Рахматуллаева, Ш. Б., Муминова, М. Т., Нурматов, А. Х., & Саъдуллаев, С. Э. (2023). Особенности течения COVID-19 у детей с коморбидной патологией. Педиатрия. Восточная Европа,(3 Часть 12), 436-442.
17. Муминова, М. Т., Рахматуллаева, Ш. Б., & Худайкулова, Г. К. (2023). Постдипломное образование: судьба резидентов магистратуры после прохождения специализации.
18. Rustombekovich, N. R., Zarifboyevich, O. S., Kadamovna, A. D., & Ernazarovich, S. S. (2025). THE STATE OF THE ANTIOXIDANT DEFENSE SYSTEM IN CHRONIC HEPATITIS C. Multidisciplinary Journal of Science and Technology, 5(5), 79-84.
19. Kadamovna, A. D., Rustombekovich, N. R., Zarifboyevich, O. S., & Ernazarovich, S. S. (2025). COMBINATIONS OF HEPATITIS B WITH PULMONARY TUBERCULOSIS. Multidisciplinary Journal of Science and Technology, 5(5), 60-65.
20. Ernazarovich, S. S., Zarifboyevich, O. S., Rustombekovich, N. R., & Kadamovna, A. D. (2025). DYNAMICS OF THE COVID-19 PANDEMIC AND ITS CLINICAL CONSEQUENCES. Multidisciplinary Journal of Science and Technology, 5(5), 85-90.
21. Sadullaev, S. E., Bobajanov, A. O., Khusinbayev, I. D., Durdiev, E. S., & Ismoilova, A. R. (2025). PSYCHOLOGICAL REHABILITATION DURING THE CORONAVIRUS PANDEMIC. Multidisciplinary Journal of Science and Technology, 5(2), 429-433.
22. Ismailov, K. Y. (2025). THE FACTORS CAUSING ISCHEMIC HEART DISEASE AMONG THE POPULATION OF THE SOUTHERN ARAL SEA REGION HEVE BEEN STUDIED. Journal of Multidisciplinary Innovation in Science and Education, 1(2), 413-418.
23. Ismailov, K. Y., & Djabbarova, Z. I. (2024). OBESITY AND ISCHEMIC HEART DISEASE. European Journal of Modern Medicine and Practice, 4(11), 364-367.
24. Абдуллаев, И. К., Исмаилов, К. Я., Курбанов, С. Р., & Матякубов, Ж. Р. ТИББИЁТ ОЛИЙГОҲЛАРИДА ЖАМОАТ САЛОМАТЛИГИ ВА СОҒЛИҚНИ САҚЛАШНИ БОШҚАРИШ ФАНИНИ ЎҚУВ ДАСТУРИГА КУРС ИШИНИ КИРИШНИНГ АМАЛИЙ АҲАМИЯТИ. Султанов ГН–ректор, д. м. н. Зам. главного редактора, 31.
25. Artikova, D. O., Kh, K. R., & Ruzmetova, D. T. (2026). CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF MATERNAL DEATHS ARISING AS A RESULT OF URINARY TRACT INFECTIONS IN PREGNANT WOMEN LIVING IN KHORESM REGION. AMERICAN JOURNAL OF APPLIED MEDICAL SCIENCE, 4(1), 20-25.
26. Матякубов Б. Б., Ниязметов Р. Э. СОВРЕМЕННЫЕ АСПЕКТЫ ЛЕЧЕНИЯ МАССИВНОГО АКУШЕРСКОГО КРОВОТЕЧЕНИЯ В ИССЛЕДУЕМОЙ ГРУППЕ //МИНИСТЕРСТВО ЗДРАВООХРАНЕНИЯ РЕСПУБЛИКИ УЗБЕКИСТАН РЕСПУБЛИКАНСКИЙ СПЕЦИАЛИЗИРОВАННЫЙ НАУЧНО-ПРАКТИЧЕСКИЙ МЕДИЦИНСКИЙ ЦЕНТР АКУШЕРСТВА И ГИНЕКОЛОГИИ АССОЦИАЦИЯ ВРАЧЕЙ ЧАСТНОЙ ПРАКТИКИ УЗБЕКИСТАНА КЛИНИКА «MAHLIYO-SHIFO» & V. – С. 23.
27. Rojabovna, I. A. (2025). The problem of developing logical and creative thinking in the educational process. INTEGRATION OF EDUCATION AND SCIENCE: GLOBAL CHALLENGES AND SOLUTIONS, 1(2), 1023-1027.
28. Bekchanova, K. R., & Ismailova, A. R. (2021). YOSHLARNI KASBGA YONALTIRISHNING PSIXOLOGIK XUSUSIYATLARI. Academic research in educational sciences, 2(5), 1117-1123.
29. Rojabovna, I. A. (2023). Features of the development of adolescent thinking in the educational process. Asian Journal Of Multidimensional Research, 12(12), 88-92.
