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Community-Acquired Bacterial Meningitis

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Community-Acquired Bacterial Meningitis PRIMER Community-acquired bacterial meningitis Diederik van de Beek1, Matthijs Brouwer1, Rodrigo Hasbun2, Uwe Koedel3, Cynthia G. Whitney4 and Eelco Wijdicks5 Abstract | Meningitis is an inflammation of the meninges and subarachnoid space that can also involve the brain cortex and parenchyma. It can be acquired spontaneously in the community — community-acquired bacterial meningitis — or in the hospital as a complication of invasive procedures or head trauma (nosocomial bacterial meningitis). Despite advances in treatment and vaccinations, community-acquired bacterial meningitis remains one of the most important infectious diseases worldwide. Streptococcus pneumoniae and Neisseria meningitidis are the most common causative bacteria and are associated with high mortality and morbidity; vaccines targeting these organisms, which have designs similar to the successful vaccine that targets Haemophilus influenzae type b meningitis, are now being used in many routine vaccination programmes. Experimental and genetic association studies have increased our knowledge about the pathogenesis of bacterial meningitis. Early antibiotic treatment improves the outcome, but the growing emergence of drug resistance as well as shifts in the distribution of serotypes and groups are fuelling further development of new vaccines and treatment strategies. Corticosteroids were found to be beneficial in high-income countries depending on the bacterial species. Further improvements in the outcome are likely to come from dampening the host inflammatory response and implementing preventive measures, especially the development of new vaccines. Meningitis is an inflammation of the meninges and sub- Despite the existence of antibiotic therapies, acute bac- arachnoid space that can also involve the brain cortex terial meningitis causes substantial morbidity and mor- and parenchyma owing to the close anatomical relation- tality, both in high-income and low-income countries4,5. ship between the cerebrospinal fluid (CSF) and the brain Bacterial meningitis is an emergency situation and (FIG. 1). Per definition, bacterial meningitis is an infection individuals with suspected disease require immediate of the CSF-filled subarachnoid space. Inflammation of evaluation and treatment. In this Primer, we provide an the meninges and subarachnoid space leads to the classic overview of community-acquired bacterial meningitis, triad of meningitis symptoms — headache, fever and neck focusing on the epidemiology, disease mechanisms, stiffness — and to pleocytosis (an increased cell count, diagnosis, screening, prevention and management. particularly of leukocytes) in the CSF1. Involvement of the brain cortex and parenchyma, because of either direct Epidemiology inflammation or vascular complications, might result in H. influenzae, S. pneumoniae and N. meningitidis behavioural changes, focal neurological abnormalities Bacterial meningitis is associated with high mortality and impairment of consciousness1, which are typically and morbidity worldwide, with an estimated 16 million Correspondence to D.v.d.B. considered symptoms of encephalitis. Acute meningi- cases in 2013, causing 1.6 million years lived with dis- Department of Neurology, 6 Center of Infection and tis can be caused by a wide variety of infectious agents, ability each year . Globally, the pathogens implicated in 2 Immunity Amsterdam but can also be a manifestation of non-infectious diseases . this disease vary somewhat and incidence varies widely (CINIMA), Academic Medical Bacterial meningitis is considered the most severe form between regions. Africa is the region with the highest Center, P.O. BOX 22660, of this disease; the routes of exposure are mainly respir- meningitis disease burden; before the introduction of 1100DD Amsterdam, (BOX 1) The Netherlands. atory, but can be enteric, as is the case in listerial infection. a vaccine , the estimated incidence of invasive [email protected] Meningitis can be acquired spontaneously in the commu- disease due to Haemophilus influenzae type b (Hib) nity — community- acquired bacterial meningitis2 — or infection was 46 per 100,000 population per year among Article number: 16074 doi:10.1038/nrdp.2016.74 in the hospital as a complication of invasive procedures children <5 years of age and Streptococcus pneumoniae Published online 3 Nov 2016 or head trauma (nosocomial bacterial meningitis)3. (pneumo coccus) infection was 38 per 100,000 population NATURE REVIEWS | DISEASE PRIMERS VOLUME 2 | 2016 | 1 ©2016 Mac millan Publishers Li mited, part of Spri nger Nature. All ri ghts reserved. PRIMER Author addresses to intermittent epidemics of meningococcal meningi- tis, with rates reaching nearly 1% of the population in 1 Department of Neurology, Center of Infection and the worst outbreaks4. Epidemics were usually caused Immunity Amsterdam (CINIMA), Academic Medical Center, by serogroup A N. meningitidis, but a vaccination pro- P.O. BOX 22660, 1100DD Amsterdam, The Netherlands. 2 gramme, initiated in 2010, against this bacterium has Department of Internal Medicine, UT Health McGovern 14 Medical School, Houston, Texas, USA. reduced its incidence . Epidemics caused by sero- 3Department of Neurology, Clinic Grosshadern of group X (2006–2010), serogroup W (2010–2011) and 15–17 the Ludwig-Maximilians University of Munich, Munich, serogroup C (2015) have also been reported . Germany. Certain serotypes or serogroups of the leading patho- 4Respiratory Diseases Branch, Division of Bacterial gens that cause bacterial meningitis have been shown to Diseases, National Center for Immunization and have a higher ability to cause severe disease than others.­ Respiratory Diseases, Centers for Disease Control Thirteen serogroups of meningococcus have been and Prevention, Atlanta, Georgia, USA. identi­fied, although six account for the majority of dis- 5 Division of Critical Care Neurology, Department of ease (serogroups A–C and serogroups W–Y). Although Neurology, Mayo Clinic, Rochester, Minnesota, USA. at least 94 pneumococcal serotypes have been identi­ fied, the currently available 10‑valent and 13‑valent per year; Neisseria meningitidis (meningococcus) infec- vaccine formulations cover the serotypes that cause tion was >1,000 per 100,000 per year among all ages dur- ≥70% of cases in most areas of the world18. Serotype 2, ing epidemics4. The overall rates of community-­acquired a non-vaccine serotype, recently emerged as a common bacterial meningitis caused by specific aetiologies in cause of pneumococcal meningitis among children in Africa remain unclear owing to a lack of diagnostic tools. Bangladesh19. Pneumococcal meningitis typically does Incidence rates of community-acquired bacterial menin­ not occur in outbreaks, although periods of hyper­ gitis in high-income areas (such as Europe, the United endemicity (that is, of high and continuous incidence) States and Australia) are 1–3 per 100,000 population per caused by serotype 1 pneumococcus have been observed year4. In the Netherlands, the incidence of adult menin­ in Burkina Faso and Ghana, with high case fatality rates gitis declined from 1.72 to 0.94 per 100,000 per year of >40%20. from 2007 to 2014; S. pneumoniae caused 72% of epi- sodes7. Reported case fatality rates are high and vary with Other pathogens patient age, causative pathogen and country income5,8. Among other aetiologies are group B streptococcus21, Meningitis caused by S. pneumoniae has the highest case a leading cause of meningitis in infants <3 months of age, fatality rates: 20–37% in high-­income countries and up and Listeria monocytogenes22, which is most commonly to 51% in low-income countries­ 8. Case fatality rates for seen in infants8. For group B streptococcus, serotype III meningococcal meningitis are ­distinctly lower, in the is the most likely serotype to cause meningitis in infants23; range of 3–10% worldwide5,9. a nationwide surveillance study in the Netherlands The epidemiology of community-acquired bacterial showed the emergence of a serotype III group B strepto­ meningitis is changing as prevention measures become coccus with a genotype belonging to clonal com- increasingly used4. The most common causes of bac­ plex 17 (REF. 21). Aerobic Gram-negative (for example, terial meningitis are S. pneumoniae and N. meningitidis, Escherichia coli) meningitis occurs especially in neonates, with varying prevalence depending on age group and the elderly and debilitated or diabetic people8,24. region8,10. Pneumococcal meningitis is in general more In pig-farming countries in Asia, Streptococcus suis common than meningococcal meningitis in children (group R haemolytic streptococcus) is the most common <5 years of age and in the elderly (≥65 years of age), cause of meningitis25. Large case series of S. suis sero- whereas meningococcal meningitis is more frequent type 2 meningitis (and rarely infective endocarditis and among older children, adolescents and young adults11. septicaemia) were reported in Hong Kong, Thailand, Pneumococcal conjugate vaccines, which are routinely China and Vietnam25. The precise epidemiology remains used in most high-income countries and increasingly unclear, but S. suis infection is correlated with occupa- in developing countries, have reduced the rates of tional contact with pigs or pork. Splenectomized patients pneumococcal meningitis not only among vaccinated are particularly susceptible to infection by capsulated young children but also among age groups that are not Gram-positive organisms, such as S. suis26. Although targeted for
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