You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Pyogenic Bacterial Meningitis: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Microbiology
Contributor: Tsang Raymond S. W.

Pyogenic bacterial meningitis is a life threatening condition that can progress rapidly leading to death. When the disease happens in infants, children, and young adults, it may instill fear due to the contagious and potentially deadly nature of the disease especially in outbreak situation.

  • bacterial meningitis
  • conjugate vaccines
  • post-vaccine surveillance

1. Introduction

The three most common causes of acute bacterial meningitis are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae [1]. This group of bacterial meningitis agents can cause disease in all ages of life from newborn to the elderly. The global burden of meningitis disease in 2016 was estimated to be 2.82 million cases, and 318,400 deaths were attributed to meningitis. The three most common pathogens (S. pneumoniae, N. meningitidis, and H. influenzae) were responsible for 55.7% and 57.2% of the meningitis cases and deaths, respectively [2]. Besides meningitis, S. pneumoniae, H. influenzae, and N. meningitidis can cause other forms of invasive diseases such as bacteremic pneumonia, septicemia, septic arthritis, pericarditis, etc. The risk of developing a major (such as hearing loss, seizures, motor deficit, cognitive impairment, hydrocephalus, and visual disturbance) or a minor (learning difficulties, language impairment, developmental delay) sequela from bacterial meningitis was estimated to be 12.8% and 8.6%, respectively [3]. Meningitis caused by S. pneumoniae carried the highest risk with a major sequela (24.7%), followed by H. influenzae (9.5%) and N. meningitidis (7.2%) [3]. Using meningococcal disease (which carries the lowest risk of developing a major sequela) as an example, the cost to care for a case who developed a major sequela was estimated to be £160,000 (US$214,096) to £200,000 (US$267,620) for the first year alone; and the corresponding figure over the lifetime of a case may be as high as £590,000 (US$789,479) to £1,090,000 (US$1,458,529) [4]. Since the incidence of meningitis and the risk of developing sequela are much higher in low- and middle-income countries, and the resources to care for those meningitis patients who develop severe sequela are often lacking in these countries, vaccines are probably the most cost-effective strategy for the control and potentially elimination of this devastating and fearful disease.

Although a number of other bacterial agents can cause meningitis, such as Listeria monocytogenes, Escherichia coli, and other enteric bacteria, group B Streptococcus (S. agalactiae) is gaining attention as a frequent cause of either early or late onset of invasive diseases such as pneumonia, sepsis, or meningitis in the newborn [5][6] as well as various forms of invasive diseases in pregnant women and non-pregnant adults [5][7]. The World Health Organization (WHO) has also identified group B Streptococcus together with S. pneumoniae, N. meningitidis, and H. influenzae as the four major bacterial meningitis agents to be included in its work plan and global vision to defeat meningitis by 2030 [8].

Capsule-based protein-conjugate vaccines that target the major serogroups of N. meningitidis and serotypes of H. influenzae and S. pneumoniae causing invasive diseases are now available and implemented in vaccination programs in many countries [9][10][11]. As a result, the epidemiology of bacterial meningitis has changed with the number of cases caused by strains covered by the vaccine decreased dramatically but at the same time disease due to serogroups or serotypes of the pathogens not included in the vaccine has emerged [12]. Disease surveillance has been described by the WHO as one of the five major pillars on the road map to defeat meningitis, comprehensive surveillance would require accurate laboratory diagnosis with strain characterization to complement field epidemiology studies. Some other important steps to control bacterial meningitis include vaccination, antibiotic treatment and chemoprophylaxis. Capsule polysaccharide conjugate vaccines against GBS have been developed and are now in advanced clinical trials [5][13].

2. Chemoprophylaxis, Corticosteroids, and Experimental Immune Modulating Approaches for Prevention and as Adjuvant Therapeutic Agents of Bacterial Meningitis

Although vaccines remain the primary tool to offer active protection against infections, chemoprophylaxis can prevent secondary cases by offering protection to close contacts and household members of index cases. Chemoprophylaxis can also offer protection to those immunized subjects before adequate level of adaptive immunity can be developed. Guidelines that define household members and close contacts of index cases of H. influenzae serotype b (Hib) and invasive meningococcal disease (IMD) as well as the choice and dosage of prophylactic antibiotics have been published [14][15]. For those requiring chemoprophylaxis to prevent IMD, a single dose of ciprofloxacin is recommended, or rifampicin given twice daily for two days as an alternative. Other prophylactic antibiotics may include ceftriaxone, cefixime, and azithromycin. IMD patients treated with benzylpenicillin (which may not eliminate pharyngeal meningococci) are recommended to receive chemoprophylaxis that can eliminate nasopharyngeal carriage of meningococci before hospital discharge to prevent potential transmission to household members. Rifampicin once a day for four days or ciprofloxacin twice a day for five days are recommended prophylactic antibiotics for contacts of index cases of Hib. Other effective antibiotics may include ceftriaxone and azithromycin. Chemoprophylaxis is generally not recommended for close contacts of IPD patients. However, children with increased risk of invasive pneumococcal disease (IPD) such as those with asplenia or sickle cell disease should receive daily prophylaxis with oral penicillin [16]. Public Health England also has guidelines of infection control, vaccination, and chemoprophylaxis (with rifampicin, penicillin, or azithromycin) for high risk individuals living in closed settings when outbreak or cluster of severe pneumococcal disease occur [17]. To prevent early onset of GBS in neonates, pregnant women should be offered screening for GBS and intrapartum antibiotic prophylaxis in indicated situations [18]. Besides chemoprophylaxis, immunization with the recommended vaccines for IMD, Hib, and IPD should be the primary tool for prevention of these vaccine preventable diseases.

Early treatment with dexamethasone reduced mortality and improved the outcome of adult patients with acute meningitis [19]. However, in a Cochrane review to study corticosteroids as an adjuvant therapy of bacterial meningitis, the authors found that corticosteroids did not reduce the overall mortality in meningitis patients but can reduce hearing loss and neurological sequelae [20]. The effect of corticosteroids on meningitis mortality and sequelae varied according to the bacterial agent causing meningitis [20]. Benefits of corticosteroids in treatment of meningitis patients have led to hypothesis and experimental approaches to modulate the immune response in order to decrease the harmful effects of inflammation and to improve the outcome of bacterial meningitis [21]. In one study, the benefit of prophylactic palmitoylethanolamide (a natural fatty acid amide) was demonstrated in a mouse model of E. coli meningitis to prolong survival and reduce symptoms by reducing inflammation and slowing the progression of infection [22]. Despite success as immunomodulation therapy for a number of auto-immune diseases such as arthritis and psoriasis, this approach, other than the use of dexamethasone, as adjuvant therapy of bacterial meningitis remain elusive and at the pre-clinical stages of development.

3. Conclusions

Nowadays, we have powerful conjugate vaccines that target the most common bacterial meningitis agents (at least the most common invasive serotypes or serogroups) to not only prevent infections in the vulnerable age group, but also by eliminating nasopharyngeal carriage, to provide herd immunity to the non-vaccinated individuals. Conjugate vaccines have prevented millions of deaths from bacterial meningitis over the last two decades [2]. We now also have genomic tools that can read the complete coding sequences of bacteria for a never-before-seen gene-by-gene comparison at the nucleotide sequence level to identify and track the movement of strains (including new strains) and infections globally [23][24][25][26] in order to either quickly deploy vaccines or to develop newer vaccines for control. Nevertheless, we cannot be complacent as we have witnessed changes in the three most common type of bacterial meningitis agents after vaccine introduction. The significant increase of invasive H. influenzae disease due to non-encapsulated or non-typeable strains or the increase in  H. influenzae serotype a (Hia) in some population in recent years are of concern [27][28][29][25][30]. The epidemiology of IMD in Africa has changed with much success in the deployment of the monovalent serogroup A vaccine, MenAfriVac leading to dramatic decreases in incidences of serogroup A diseases [31]. However, other vaccine-preventable serorgroups like W and C still continue to cause significant amount of disease when vaccines against these serogroups have not been deployed yet. The most problematic may be related to IPD due to non-vaccine serotypes emerging to cause disease after the sequential introduction of pneumococcal conjugate vaccine (PCV)7, PCV10 and PCV13 [32][33][34][35][36]. Whether this is related to the large number of serotypes of S. pneumoniae in contrast to the much smaller number of serotypes of H. influenzae or serogroups of N. meningitidis is unknown, but mathematical modelling suggested the number of serotypes might have an effect on strain replacement in nasopharyngeal carriage after vaccination [37]. Even though only 10 serotypes of S. agalactiae have been identified, its different ecology (genito-gastrointestinal colonizer versus pharyngeal colonizer) may make the effect of conjugate vaccines on the subsequent epidemiology difficult to predict.

In summary, we are in a much better position to control bacterial meningitis than ever before and surveillance continues to have a key role to play [38][39].

This entry is adapted from the peer-reviewed paper 10.3390/microorganisms9020449

References

  1. Tunkel, A.R.; van der Beek, D.; Scheld, W.M. Acute meningitis. In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th ed.; Mandell, G.L., Bennett, J.E., Dolin, R., Eds.; Churchill Livingstone Elsevier: Philadelphia, PA, USA, 2010.
  2. Kassebaum, N.J.; Zunt, J.R.; for the GBD Meningitis Collaborators. Global, regional and national burden of meningitis 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018, 17, 1061–1082.
  3. Edmond, K.; Clark, A.; Korczak, V.S.; Sanderson, C.; Griffiths, U.K.; Rudan, I. Global and regional risk of disabling sequelae from bacterial meningitis: A systematic review and meta-analysis. Lancet Infect. Dis. 2010, 10, 317–328.
  4. Wright, C.; Wordsworth, R.; Glennie, L. Counting the cost of meningococcal disease, scenarios of severe meningitis and septicemia. Pediatr. Drugs 2013, 15, 49–58.
  5. Song, J.Y.; Lim, J.H.; Lim, S.; Yong, Z.; Seo, S.H. Progress towards a group B streptococcal vaccine. Hum. Vaccines Immunother. 2018, 14, 2669–2681.
  6. Nanduri, S.A.; Petit, S.; Smelser, C.; Apostol, M.; Alden, N.B.; Harrison, L.H.; Lynfield, R.; Vagnone, P.S.; Burzlaff, K.; Spina, N.L.; et al. Epidemiology of invasive early-onset and late-onset group B streptococcal disease in the United States, 2006 to 2015: Multistate laboratory and population-based surveillance. JAMA Pediatr. 2019, 173, 224–233.
  7. Watkins, L.K.F.; McGee, L.; Schrag, S.J.; Beall, B.; Jain, J.H.; Ponda, T.; Farley, M.M.; Harrison, L.H.; Zansky, S.M.; Baumbach, J.; et al. Epidemiology of invasive group B streptococcal infections among non-pregnant adults in the United States, 2008–2016, JAMA Intern. Med. 2019, 179, 479–488.
  8. World Health Organization. Defeating meningitis by 2030: A Global Road Map. 2018. Available online: (accessed on 25 December 2020).
  9. Black, S.; Shinefield, H.; Fireman, B.; Lewis, E.; Ray, P.; Hansen, J.R.; Elvin, L.; Ensor, K.M.; Hackell, J.; Siber, G.; et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr. Infect. Dis. J. 2000, 19, 187–195.
  10. Kelly, D.F.; Moxon, E.R.; Pollard, A.J. Haemophilus influenzae type b conjugate vaccines. Immunology 2004, 113, 163–174.
  11. Harrison, L.H. A multivalent conjugate vaccine for prevention of meningococcal disease in infants. JAMA 2009, 299, 217–219.
  12. McIntyre, P.B.; O’Brien, K.L.; Greenwood, B.; van de Beek, D. Bacterial meningitis: Effect of vaccines on bacterial meningitis worldwide. Lancet 2012, 380, 1703–1711.
  13. Lin, S.M.; Zhi, Y.; Ahn, K.B.; Lim, S.; Seo, H.S. Status of group B streptococcal vaccine development. Clin. Exp. Vaccine Res. 2018, 7, 76–81.
  14. Public Health England. Guidance for Public Health Management of Meningococcal Disease in the UK. August 2019. Available online: (accessed on 5 February 2021).
  15. Public Health England. Revised Recommendations for the Prevention of Secondary Haemophilus influenzae type b (Hib) Disease. July 2013. Available online: (accessed on 5 February 2021).
  16. American Academy of Pediatrics. Red Book: 2018 Report of the Committee on Infectious Diseases, 31st ed.; Kimberlin, D.W., Brady, M.T., Jackson, M.A., Long, S.S., Eds.; American Academy of Pediatrics: Elk Grove Village, IL, USA, 2018.
  17. Public Health England. Guidelines for the Public Health Management of Clusters of Severe Pneumococcal Disease in Closed Settings. Updated January 2020. Available online: (accessed on 5 February 2021).
  18. Hughes, R.G.; Brocklehurst, P.; Steer, P.J.; Heath, P.; Stenson, B.M.; On behalf of the Royal College of Obstetricians and Gynaecologists. Prevention of early-onset neonatal group B streptococcal disease. Green-top guideline No. 36. BJOG 2017, 124, e280–e305.
  19. de Gans, J.; van de Beek, D. For the European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N. Engl. J. Med. 2002, 347, 1549–1556.
  20. Brouwer, M.C.; McIntyre, P.; Prasad, K.; van de Beek, D. Corticosteroids for acute bacterial meningitis (review). Cochrane Database Syst. Rev. 2015, CD004405.
  21. van der Flier, M.; Geelen, S.P.M.; Kimpen, J.L.L.; Hoepelman, I.M.; Tuomanen, E.I. Reprogramming the host response in bacterial meningitis: How best to improve outcome? Clin. Microbiol. Rev. 2003, 16, 415–429.
  22. Heide, E.C.; Bindila, L.; Post, J.M.; Malzahn, D.; Lutz, B.; Seele, J.; Nau, R.; Ribes, S. Prophylactic palmitoylethanolamide prolongs survival and decreases detrimental inflammation in aged mice with bacterial meningitidis. Front. Immunol. 2018, 9, 2671.
  23. Krone, M.; Gray, S.; Abad, R.; Skoczyńska, A.; Stefanelli, P.; van der Ende, A.; Tzanakaki, G.; Mölling, P.; Simões, M.J.; Křížová, P.; et al. Increase of invasive meningococcal serogroup W disease in Europe, 2013 to 2017. Eurosurveill 2019, 24, 1800245.
  24. Agnememel, A.; Hong, E.; Giorgini, D.; Nuñez-Samudio, V.; Deghmane, A.E.; Taha, M.K. Neisseria meningitidis serogroup X in Sub-Saharan Africa. Emerg. Infect. Dis. 2016, 22, 698–702.
  25. Soeters, H.M.; Oliver, S.E.; Plumb, I.D.; Blain, A.E.; Zulz, T.; Simons, B.C.; Barnes, M.; Farley, M.M.; Harrison, L.H.; Lynfield, R.; et al. Epidemiology of invasive Haemophilus influenzae serotype a disease—United States, 2008–2017. Clin. Infect. Dis. 2020, ciaa875.
  26. Jolley, K.A.; Maiden, M.C.J. BIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinform. 2010, 11, 595.
  27. Ulanova, M. Global epidemiology of invasive Haemophilus influenzae type a disease: Do we need a new vaccine? J. Vaccine 2013, 14, 941461.
  28. Tsang, R.S.W.; Ulanova, M. The changing epidemiology of invasive Haemophilus influenzae disease: Emergence and global presence of serotype a strains that may require a new vaccine for control. Vaccine 2017, 35, 4270–4275.
  29. Boisvert, A.A.; Moore, D. Invasive disease due to Haemophilus influenzae type a in Canada’s north: A priority for prevention. Can. J. Infect. Dis. Med. Microbiol. 2015, 26, 291–292.
  30. Bozio, C.H.; Blain, A.; Edge, K.; Farley, M.M.; Harrison, L.H.; Poissant, T.; Schaffner, W.; Scheuer, T.; Torres, S.; Triden, L.; et al. Clinical characteristics and adverse clinical outcomes of invasive Haemophilus influenzae serotype a cases—United States, 2011–2015. Clin. Infect. Dis. 2020, ciaa990.
  31. Trotter, C.L.; Lingani, C.; Fernandez, K.; Cooper, L.V.; Bita, A.; Tevi-Benissan, C.; Ronveaux, O.; Préziosi, M.P.; Stuart, J.M. Impact of MenAfriVac in nine countries of the African meningitis belt, 2010–2015: An analysis of surveillance data. Lancet Infect. Dis. 2017, 17, 867–872.
  32. Weinbergera, D.M.; Malley, R.; Lipsitcha, M. Serotype replacement in disease following pneumococcal vaccination: A discussion of the evidence. Lancet 2011, 378, 1962–1973.
  33. Brueggemann, A.B.; Pai, R.; Crook, D.W.; Beall, B. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States. PLoS Pathog. 2007, 3, e168.
  34. Makarewicz, O.; Lucas, M.; Brandt, C.; Herrmann, L.; Albersmeier, A.; Ruckert, C.; Blom, J.; Goesmann, A.; van der Linden, M.; Kalinowski, J.; et al. Whole genome sequencing of 39 invasive Streptococcus pneumoniae sequence type 199 isolates revealed switches from serotype 19A to 15B. PLoS ONE 2017, 12, e0169370.
  35. Groves, N.; Sheppard, C.L.; Litt, D.; Rose, S.; Silva, A.; Njoku, N.; Rodrigues, S.; Amin-Chowdhury, Z.; Andrews, N.; Ladhani, S.; et al. Evolution of Streptococcus pneumoniae serotype 3 in England and Wales: A major vaccine evader. Genes 2019, 10, 845.
  36. Kandasamy, R.; Voysey, M.; Collins, S.; Berbers, G.; Robinson, H.; Noel, I.; Hughes, H.; Ndimah, S.; Gould, K.; Fry, N.; et al. Persistent circulation of vaccine serotypes and serotype replacement after 5 years of infant immunization with 13-valent pneumococcal conjugate vaccine in the United Kingdom. J. Infect. Dis. 2020, 221, 1361–1370.
  37. Lipstich, M. Bacterial vaccines and serotype replacement: Lessons from Haemophilus influenzae and prospects for Streptococcus pneumoniae. Emerg. Infect. Dis. 1999, 5, 336–345.
  38. Knol, M.J.; van der Ende, A. Continuous surveillance of invasive pneumococcal disease is key. Lancet Infect. Dis. 2021, 21, 13–14.
  39. Klugman, K.P.; Rodgers, G.L. Time for a third-generation pneumococcal vaccine. Lancet Infect. Dis. 2021, 21, 14–16.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Academic Video Service
Feedback