Detection of sequelae from acute meningitis during clinical review by a healthcare provider: a systematic review and meta-analysis

Abstract

Background

Neurological sequelae from acute meningitis are estimated to affect more than 30% of survivors worldwide, though often underreported or undetected due to inadequate follow-up, limited access to healthcare services, and diagnostic challenges. The aim of this systematic review and meta-analysis is to assess the time of administered health assessments for the detection of meningitis-related sequelae associated with acute meningitis diagnosis in adult and pediatric populations.

Methods

A literature review was conducted in three databases. Studies documenting the time frame of sequelae detection after an acute episode of all-cause meningitis were included. Descriptive analysis and meta-analysis of pooled prevalence for neurological outcomes were performed, with subgroup analysis per timepoint of healthcare assessment.

Results

A total of 89 studies met inclusion criteria, reporting 9311 adult and 18,658 pediatric meningitis cases. Among adults, 7301 (78.4%) underwent sequelae assessment, with 1339 (18%) diagnosed. The most frequently reported sequelae were hearing loss, followed by focal neurological deficits, psychological after-effects, neurocognitive impairments, seizures, hydrocephalus, speech disorders, vision impairment, and limb loss. While more were assessed before discharge (5270 vs. 2711), the proportion of sequelae diagnoses was higher post-discharge. The pooled prevalence of sequelae was 24.8% (95% CI 20.5–29.2%) at discharge, compared to 41.5% (95% CI 25.7–57.3%) within 3 months and 31.9% (95% CI 18.5–45.3%) beyond 3 months post-discharge. In children, 14,826 (79%) were assessed, and 3484 (24%) had sequelae, with the most common sequelae being hearing loss, followed by focal neurological deficits, seizures, neurocognitive, and neurodevelopmental impairments. More were assessed post-discharge (8298 vs. 7180), with a higher pooled prevalence of sequelae diagnoses post-discharge. At discharge, the pooled prevalence of sequelae was 28.9% (95% CI 20.8–37%), compared to 29.9% (95% CI 19–40.8%) within 3 months and 38.2% (95% CI 30.3–46.1%) beyond 3 months after discharge.

Conclusions

Meningitis-related sequelae significantly impact quality of life. This review highlights variability and critical gaps in their evaluation, detection, and management, underscoring the need for routine monitoring from discharge through consistent follow-up assessments, as recommended by the new WHO guidelines on meningitis diagnosis, treatment, and care.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12916-026-04627-z.

Background

Neurological sequelae are a significant and debilitating consequence of acute meningitis, affecting over 30% of survivors worldwide [1]. These long-term complications include hearing loss, epilepsy, speech and language impairments, neurocognitive deficits, and motor and vision impairments. Sequelae in children are associated with missed educational opportunities and developmental delays, whereas in adults they are linked to mental health disorders and employment challenges.

However, the long-term burden and impact of neurological sequelae remain poorly defined, as the majority of studies do not follow patients longitudinally [1]. This knowledge gap is particularly pronounced in low- and middle-income countries (LMICs), where few studies include sufficient numbers of patients with extended follow-up [2]. Additional challenges in these settings include stigma, limited access to specialized healthcare, lack of standardized methods to assess neurological status, and delays in diagnosis due to nonspecific clinical presentations. Consequently, leading to sequelae underreport and undetection in the long term [2–4].

Given these challenges in long-term outcome assessment, the World Health Organization (WHO) developed the Defeating Meningitis by 2030: A Global Road Map in 2021, aimed at eliminating meningitis by 2030, as a global public health initiative [5]. This roadmap outlines comprehensive guidelines for public health interventions and strategies designed to reduce the impact of sequelae following meningitis from all causes and enhance life expectancy of affected individuals. However, specific guidelines for optimal time of follow-up care have not been delineated thus far. We conducted a systematic review and meta-analysis to determine when adults and children with acute meningitis are evaluated for sequelae, during hospitalization before discharge or at follow-up visits after discharge, to identify the most appropriate timepoints for their detection and to inform strategies for long-term management and outcome optimization.

Methods

Study selection

This systematic review was performed in adherence with the Preferred Reporting Items for Systematic Review and Meta-Analysis [6] (PRISMA) and Meta-Analysis of Observational studies in Epidemiology [7] (MOOSE) guidelines. The literature search followed the PICO (Population, Intervention, Comparator, and Outcome) framework, as outlined in the WHO Handbook on guideline development [8], which directed the Guideline Development Group (GDG) of the WHO guidelines on meningitis diagnosis, treatment, and care [9]: (1) Should adult cases of all-cause acute meningitis be reviewed by a healthcare provider before discharge from the hospital or at follow-up post-discharge to identify sequelae? (2) Should children and adolescents with acute meningitis from any infectious cause be reviewed by a healthcare provider before discharge from the hospital or at follow-up post-discharge to identify sequelae? The PICO question components are outlined in Additional file 1: Table S1.

The literature search was developed by a senior information specialist [K.U.K.] and conducted using the electronic databases Ovid Medline, Elsevier Embase, and the Cochrane Library, limiting articles published from January 2003 to December 2023. This time range was chosen to capture studies reflecting the impact of widespread conjugate vaccine implementation on meningitis epidemiology [10]. Other databases, such as Scopus and Web of Science, were not included as they largely overlap with Ovid Medline and Embase in terms of biomedical content and were therefore unlikely to yield additional records relevant to the research question. Indexed search terms and free text terms were constructed based on concepts of infectious meningitis and sequelae (search strategy detailed in Additional file 1: Tables S2-S4). To ensure comprehensive literature retrieval, the search strategy included a list of pathogens, considering all etiologic categories (bacterial, viral, fungal, and parasitic) and focusing on community-acquired acute meningitis in adults and children over 1 month of age (Additional file 1: Table S5). Search limits were used to filter out animal studies, letters, conference material, editorials, case reports, and notes.

Studies documenting the time frame at which sequelae were detected after the acute episode of meningitis of any cause were included. The types of studies included for analysis were case–control, cohort studies, case series (> 5 cases), cross-sectional studies, and observational studies embedded in randomized controlled trials. Systematic reviews and meta-analyses were evaluated exclusively to capture primary references not previously captured within the search strategy. Studies focusing on subacute or chronic meningitis, hospital-acquired meningitis, relapsing meningitis, or non-infectious meningitis were excluded. Screening was limited to studies published in English.

Using the COVIDENCE online platform [11], studies captured by the search strategy were screened independently by pairs of authors [L.F.A., C.Y.K., A.C.B., J.A.R., L.M., C.H., F.J.V., A.H., B.M., P.B., and K.T.T.] based on the title and abstract, and by a full-text review. Any disagreements between the two reviewers were resolved during periodic group meetings.

Eligibility criteria and diagnostic parameters

Studies with adult and/or pediatric cases were included. Following the WHO mhGAP Intervention Guide, adults were defined as individuals aged older than 18, while pediatric cases were categorized into the following age groups: 1 month–1 year, 1–5 years, and 5–18 years [12]. Neonatal cases (≤ 28 days old) were excluded, as they fall outside the scope of the WHO meningitis guidelines [9], which address this population separately due to distinct clinical features and management approaches [13, 14].

Diagnosis of meningitis was defined by clinical presentation of community-acquired meningitis with confirmatory laboratory results, including cerebrospinal fluid (CSF) and/or blood cultures positive for bacterial or fungal pathogens and CSF analysis findings consistent with infectious meningitis, the presence of Gram stain positive for meningitis-causative bacteria in CSF, or the detection of microorganisms in CSF through antigen testing or gene amplification. Bacterial, viral, fungal, or parasitic etiologies were included. Unknown etiology was considered in the absence of pathogen isolation in CSF culture, polymerase chain reaction (PCR), or antigen testing, or when the causative agent was not reported in the study.

Meningitis-associated sequelae included hearing loss of any degree, speech and/or language impairment, seizures, neurocognitive/neurodevelopmental impairment, psychological after-effects (such as stress, depression, and behavioral issues), hydrocephalus, motor deficits, vision impairment, and limb loss. The timeframe for sequelae detection was categorized as either before or after discharge. The period before discharge was further classified into sequelae detected during hospitalization or at the moment of discharge. The period after discharge encompassed follow-up evaluations within 1 month, 1–3 months, and beyond 3 months post-discharge.

Data extraction

For the included studies, data extraction stored on the Covidence platform [11] was performed by pairs of reviewers [L.F.A., C.Y.K., A.C.B., J.A.R., L.M., C.H., F.J.V., A.H., B.M., K.T.T., and P.B.], with a third evaluator [L.F.A., C.Y.K.] resolving any discrepancies to reach consensus. Data extraction of general variables included the study’s location, period, and design. Disease-specific details were collected and analyzed separately for adult and pediatric populations: the total number of patients diagnosed with meningitis, the number assessed for sequelae, those who developed sequelae, the mortality rate, and the number lost to follow-up, if reported. Additionally, data on the timing of sequelae diagnosis, the types of sequelae identified, and the etiologic microorganisms associated with meningitis were extracted.

Assessment of risk of bias in included studies

To assess the risk of bias for observational studies embedded in randomized control trials (RCTs), the CLARITY tool was used [15]. For the included observational studies, the tools used to assess the risk of bias were as follows: Newcastle–Ottawa Cohort for cohort studies [16]; Newcastle–Ottawa CC for case–control studies [17]; JBI Checklist for case series studies [18]; and AXIS tool for Cross-sectional studies [19].

Pairs of authors [L.F.A., C.Y.K., A.C.B., J.R., L.M., C.H., F.J.V., A.H., B.M., and P.B.] assessed the risk of bias of each study by using the corresponding risk of bias tool. A third independent author performed consensus of each study assessment. If necessary, some cases were further discussed in periodical group meetings.

Statistical analysis

Descriptive analysis was performed by calculating means as continuous data and counts, and proportions for categorical data. Variables included number of meningitis diagnoses, number of patients that underwent healthcare provider assessments, number of patients with any type of neurologic sequelae, number of patients with each type of sequelae, and the etiological infectious microorganisms responsible for meningitis-related sequelae. The proportion of patients diagnosed with any type of sequelae among those with reported assessments administered by healthcare personnel was assessed per time point, before discharge and after discharge, with further subdivisions of analysis in the post-discharge follow-up periods. Additionally, the weighted average time between the acute meningitis episode and sequelae diagnosis was calculated to determine the average timeframe in which post-meningitis sequelae are typically identified. This descriptive analysis was primarily conducted by using Excel and R programming software version 4.3.3.

Meta-analyses were performed if data on the frequency of sequelae detection were available in two or more studies. Pooled prevalence for outcome along with its corresponding 95% confidence interval (CI) was calculated by using a random-effects model. For pooling, prevalence estimates were transformed by using the Freeman-Tukey double arcsine transformation [20] for better approximation to normal distribution as required by the assumption of conventional meta-analytic model. Subgroup analyses were conducted per time point: during hospitalization, at discharge, and within 1 month, 1–3 months, and > 3 months after discharge. The proportion of patients diagnosed with any sequelae over the total number of patients evaluated by a healthcare provider was used for meta-analysis per time point.

GRADE evidence profile

The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was considered to assess the certainty of evidence for each outcome of interest [21]. Typically, GRADE evaluates key domains such as study limitations, inconsistency, imprecision, indirectness, and publication bias and allows certainty to be downgraded or upgraded based on these factors. However, due to the lack of studies with comparator groups in the included literature, formal GRADE evidence profiles could not be constructed. Instead, the review team qualitatively summarized the available evidence and considered these domains when discussing the strength and certainty of findings.

Results

Included studies

A total of 1978 studies were screened by title and abstract, and 496 by full-text review, of which only 89 studies were included in the analysis (Fig. 1 and Table 1). Studies were excluded if they lacked a sequelae detection timeframe, reported outcomes beyond our scope (e.g., meningitis caused by immune mediated causative agents or subacute/chronic meningitis), were published in a language other than English, or did not report sequelae. The distribution of studies across income groups were based on the World Bank Income Categorization: 48 studies (53.9%) were conducted in high-income countries, 25 (28.1%) in upper-middle-income countries, 22 (24.7%) in lower-middle-income countries, 2 (2.2%) in low-income countries, and 1 study (1.1%) was conducted in an unclassified region (Fig. 2).

Fig. 1.

PRISMA flow chart

This diagram outlines the systematic process employed to include the papers captured by our search strategy

Table 1.

Included studies

	Included studies
	Cohort studies
[22]	Ahmed ASMNU, Khan NZ, Hussain M, et al. Follow-up of cases of Haemophilus influenzae type b meningitis to determine its long-term sequelae. 2013;163:S44-49
[23]	Ai J, Xie Z, Liu G, et al. Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study. 2017;17:494
[24]	Al Khorasani A, Banajeh S. Bacterial profile and clinical outcome of childhood meningitis in rural Yemen: a 2-year hospital-based study. 2006;53:228–234
[25]	Alsubaie S, Alrabiaah A. Clinical Characteristics, Acute Complications, and Neurologic Outcomes of Salmonella Meningitis in Saudi Infants and Children. 2020;15:031–038
[26]	Anh DD, Kilgore PE, Kennedy WA, et al. Haemophilus influenzae type B meningitis among children in Hanoi, Vietnam: epidemiologic patterns and estimates of H. Influenzae type B disease burden. 2006;74:509–515
[27]	Arditi M, Mason EO, Jr., Bradley JS, et al. Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 1998;102:1087–1097
[28]	Auburtin M, Wolff M, Charpentier J, et al. Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study. 2006;34:2758–2765
[29]	Basualdo W, Arbo A. Invasive Haemophilus influenzae type b infections in children in Paraguay. 2004;35:126–133
[30]	Bettinger JA, Scheifele DW, Le Saux N, Halperin SA, Vaudry W, Tsang R. The disease burden of invasive meningococcal serogroup B disease in Canada. 2013;32:e20-25
[31]	Biaukula VL, Tikoduadua L, Azzopardi K, et al. Meningitis in children in Fiji: etiology, epidemiology, and neurological sequelae. 2012;16:e289-295
[32]	Blanco BP, Branas PCAA, Yoshioka CRM, Ferronato AE. Pediatric bacterial meningitis and meningococcal disease profile in a Brazilian General Hospital. 2020;24:337–342
[33]	Bodilsen J, Schonheyder HC, Nielsen H. Hydrocephalus is a rare outcome in community-acquired bacterial meningitis in adults: a retrospective analysis. 2013;13:321
[34]	Bor M, Çokuğraş H. Factors associated with early complications in inpatients who were treated in our clinic between 1992 and 2011 with a diagnosis of acute bacterial meningitis. 2020;55:149–156
[35]	Bozzola E, Spina G, Marsella P, et al. Predicting parameters for audiological complications in pediatric patients affected by meningitis. 2021;16:187–193
[36]	Buckingham SC, McCullers JA, Luján-Zilbermann J, Knapp KM, Orman KL, English BK. Early vancomycin therapy and adverse outcomes in children with pneumococcal meningitis. Pediatrics 2006;117:1688–1694
[37]	Burton C, Best E, Broom M, Heffernan H, Briggs S, Webb R. Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004–2020. 2023;29:686–695
[38]	Cabellos C, Pelegrín I, Benavent E, et al. Invasive meningococcal disease: What we should know, before it comes back. 2019;6
[39]	Casella EB, Cypel S, Osmo AA, et al. Sequelae from meningococcal meningitis in children: a critical analysis of dexamethasone therapy. 2004;62:421–428
[40]	Chamkhaleh MA, Noorbakhsh S, Vafaee-Shahi M, et al. The epidemiology and outcomes of meningitis among Iranian children in a period of 10 years. 2021;15:37–42
[41]	Chauhan D, Mokta K, Kanga A, Grover N. Epidemiology, clinical profile and role of rapid tests in the diagnosis of acute bacterial meningitis in children (aged 1–59 months). 2018;66:1045–1049
[42]	Chen T, Liu G. Long-term outcome of acute central nervous system infection in children. 2018;2:155–163
[43]	Deliran SS, Brouwer MC, van de Beek D. Intracerebral haemorrhage in bacterial meningitis. 2022;85:301–305
[44]	Domingo P, Pomar V, Benito N, Coll P. The changing pattern of bacterial meningitis in adult patients at a large tertiary university hospital in Barcelona, Spain (1982–2010). 2013;66:147–154
[45]	Duval X, Taha M–K, Lamaury I, et al. One-Year Sequelae and Quality of Life in Adults with Meningococcal Meningitis: Lessons from the COMBAT Multicentre Prospective Study. 2022;39:3031–3041
[46]	El-Gindy EM, Ali-Eldin FA, Bayoumy I, Abdel-Moneim L, Ibrahim WA. Cognitive and Neurological Complications of Bacterial Meningitis in Adult Patients: A Hospital Based Study. 2015;45:477–484
[47]	Glimaker M, Johansson B, Grindborg O, Bottai M, Lindquist L, Sjolin J. Adult bacterial meningitis: earlier treatment and improved outcome following guideline revision promoting prompt lumbar puncture. 2015;60:1162–1169
[48]	Grindborg O, Naucler P, Sjolin J, Glimaker M. Adult bacterial meningitis-a quality registry study: earlier treatment and favourable outcome if initial management by infectious diseases physicians. 2015;21:560–566
[49]	Heckenberg SGB, de Gans J, Brouwer MC, et al. Clinical features, outcome, and meningococcal genotype in 258 adults with meningococcal meningitis: a prospective cohort study. 2008;87:185–192
[50]	Jensen ES, Cayé-Thomasen P, Bodilsen J, et al. Hearing Loss in Bacterial Meningitis Revisited—Evolution and Recovery. 2023;10
[51]	Kadziszewska A, Gowin E, Kadziszewski RW. Acute bacterial meningitis in Polish children—assessment of risk factors of neurological complications. 2023;98:102–107
[52]	Klobassa DS, Zoehrer B, Paulke-Korinek M, et al. The burden of pneumococcal meningitis in Austrian children between 2001 and 2008. 2014;173:871–878
[53]	Le Bot A, Ballerie A, Pronier C, et al. Characteristics and outcome of varicella-zoster virus central nervous system infections in adults. 2021;40:2437–2442
[54]	Lovera D, Amarilla S, Araya S, et al. Risk Factors for Death and Severe Neurological Sequelae in Childhood Bacterial Meningitis. 2022;38:637–643
[55]	Meng L, Peng X-L, Xu H-Y, Chen D-D, Zhang H, Hu Y. A Nomogram to Predict Bacterial Meningitis-associated Hydrocephalus: A Single-Center Retrospective Study. 2022;41:706–713
[56]	Moon S-Y, Chung DR, Kim S-W, et al. Is adjunctive corticosteroid beneficial in pneumococcal meningitis in a region with high rates of resistance to penicillin and ceftriaxone? 2012;259:1453–1460
[57]	Moon SY, Chung DR, Kim SW, et al. Changing etiology of community-acquired bacterial meningitis in adults: a nationwide multicenter study in Korea. 2010;29:793–800
[58]	Namani S, Kuchar E, Koci R, Dedushi K, Mehmeti M, Krasniqi V. Acute neurologic complications and long term sequelae of bacterial meningitis in children. 2011;9
[59]	Ostergaard C, Konradsen HB, Samuelsson S. Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infection. 2005;5:93
[60]	Pagliano P, Boccia G, De Caro F, Esposito S. Bacterial meningitis complicating the course of liver cirrhosis. 2017;45:795–800
[61]	Pagliano P, Fusco U, Attanasio V, et al. Pneumococcal meningitis in childhood: a longitudinal prospective study. 2007;51:488–495
[62]	Pan J, Xu W, Song W, Zhang T. Bacterial meningitis in children with an abnormal craniocerebral structure. 2023;11
[63]	Paulke-Korinek M, Kollaritsch H, Kundi M, et al. Characteristics of invasive pneumococcal disease in hospitalized children in Austria. 2014;173:469–476
[64]	Pelkonen T, Roine I, Kallio M, Jahnukainen K, Peltola H. Prevalence and significance of anaemia in childhood bacterial meningitis: a secondary analysis of prospectively collected data from clinical trials in Finland, Latin America and Angola. 2022;12:e057285
[65]	Plumb ID, Lecy KD, Singleton R, et al. Invasive Haemophilus influenzae Serotype a Infection in Children: Clinical Description of an Emerging Pathogen-Alaska, 2002–2014. 2018;37:298–303
[66]	Rabbani MA, Khan AA, Ali SS, et al. Spectrum of complications and mortality of bacterial meningitis: an experience from a developing country. 2003;53:580–583
[67]	Raemy S, Casanova C, Baldan R, et al. Penicillin-Susceptible Streptococcus pneumoniae Meningitis in Adults: Does the Ceftriaxone Dosing Matter? 2023;12
[68]	Resti M, Micheli A, Moriondo M, et al. Comparison of the effect of antibiotic treatment on the possibility of diagnosing invasive pneumococcal disease by culture or molecular methods: a prospective, observational study of children and adolescents with proven pneumococcal infection. 2009;31:1266–1273
[69]	Rivero-Calle I, Vilanova-Trillo L, Pardo-Seco J, et al. The burden of pediatric invasive meningococcal disease in Spain (2008–2013). 2016;35:407–413
[70]	Roine I, Pelkonen T, Bernardino L, Leite Cruzeiro M, Peltola H, Pitkaranta A. Ataxia and Its Association with Hearing Impairment in Childhood Bacterial Meningitis. 2015; 34:809–813
[71]	Rugemalira E, Karppinen M, Savonius O, et al. Health-related Quality of Life After Childhood Bacterial Meningitis. 2021;40:987–992
[72]	Saha SK, Khan NZ, Ahmed ASMNU, et al. Neurodevelopmental sequelae in pneumococcal meningitis cases in Bangladesh: a comprehensive follow-up study. 2009;48 Suppl 2:S90-96
[73]	Sakata H, Sato Y, Nonoyama M, et al. Results of a multicenter survey of diagnosis and treatment for bacterial meningitis in Japan. 2010;16:396–406
[74]	Şensoy G, Sel K, Özkaya E, Çuhaci Çakir B, Vidinlisan S, Doganci L. Enteroviral meningitis in children in Turkey. 2009;4:253–258
[75]	Shamsad IA, Begum T. Initiation of early empiric treatment based on clinical features and early obtainable CSF indices can prevent worse prognosis in childhood meningitis. 2009;18:232–238
[76]	Stockmann C, Ampofo K, Byington CL, et al. Pneumococcal meningitis in children: epidemiology, serotypes, and outcomes from 1997–2010 in Utah. 2013;132:421–428
[77]	Teixeira DC, Diniz LMO, Moreira HMAS, et al. Risk Factors for Severe Outcomes in Bacterial Meningitis. 2021;16
[78]	Theodoridou K, Vasilopoulou VA, Katsiaflaka A, et al. Association of treatment for bacterial meningitis with the development of sequelae. 2013; 17:e707-713
[79]	Tubiana S, Varon E, Biron C, et al. Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort. 2020;26:1192–1200
[80]	Tuncer O, Çaksen H, Arslan S, et al. Cranial computed tomography in purulent meningitis of childhood. 2004;114:167–174
[81]	Türel O, Yildirim C, Yilmaz Y, Külekçi S, Akdaş F, Bakir M. Clinical characteristics and prognostic factors in childhood bacterial meningitis: A multicenter study. 2013;30:80–84
[82]	van Soest TM, Chekrouni N, van Sorge NM, Bijlsma MW, Brouwer MC, van de Beek D. Epidemiology, clinical features and outcome of adults with meningococcal meningitis: a 15-year prospective nationwide cohort study. 2023;30
[83]	van Veen KEB, Brouwer MC, van der Ende A, van de Beek D. Bacterial meningitis in hematopoietic stem cell transplant recipients: a population-based prospective study. 2016;51:1490–1495
[84]	Vasilopoulou VA, Karanika M, Theodoridou K, Katsioulis AT, Theodoridou MN, Hadjichristodoulou CS. Prognostic factors related to sequelae in childhood bacterial meningitis: data from a Greek meningitis registry. 2011;11:214
[85]	Viale P, Scudeller L, Pea F, et al. Implementation of a Meningitis Care Bundle in the Emergency Room Reduces Mortality Associated With Acute Bacterial Meningitis. 2015;49:978–985
[86]	Wang C, Xu H, Deng J, et al. Prognostic factors in pediatric pneumococcal meningitis patients in mainland China: A retrospective multicenter study. 2019;12:1501–1512
[87]	Wang W, Han H, Du L, Li Z, Wu Y. Clinical Features and Outcomes of Streptococcus pneumoniae Meningitis in Children: A Retrospective Analysis of 26 Cases in China. 2022;53:32-
[88]	Wee LYJ, Tanugroho RR, Thoon KC, et al. A 15-year retrospective analysis of prognostic factors in childhood bacterial meningitis. 2016;105:e22-29
	Randomized controlled trials
[89]	Duke T, Mokela D, Frank D, et al. Management of meningitis in children with oral fluid restriction or intravenous fluid at maintenance volumes: a randomised trial. 2002;22:145‐157
[90]	Molyneux EM, Kawaza K, Phiri A, et al. Glycerol and acetaminophen as adjuvant therapy did not affect the outcome of bacterial meningitis in Malawian children. 2014;33:214–216
[91]	Molyneux EM, Walsh AL, Forsyth H, et al. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. 2002;360:211‐218
[92]	Sankar J, Singhi P, Bansal A, Ray P, Singhi S. Role of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with bacterial meningitis. 2007;44:649–656
[93]	Tenhu E, Terasjarvi J, Cruzeiro ML, et al. Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children. 2020;11
[94]	Uppal L, Singhi S, Singhi P, Aggarwal R. Role of Rifampin in Reducing Inflammation and Neuronal Damage in Childhood Bacterial Meningitis: A Pilot Randomized Controlled Trial. 2017;36:556–559
[95]	Vaswani ND, Gupta N, Yadav R, Nadda A. Seven versus Ten Days Antibiotics Course for Acute Pyogenic Meningitis in Children: A Randomized Controlled Trial. 2021;88:246–251
[96]	Thomas R, Le Tulzo Y, Bouget J, et al. Trial of dexamethasone treatment for severe bacterial meningitis in adults. Adult Meningitis Steroid Group. 1999;25:475‐480
	Case series (> 5 cases)
[97]	Antony S, Kaushik A, Mauriello C, Chatterjee A. Non-Type b Haemophilus influenzae Invasive Infections in North Dakota and South Dakota, 2013–2015. 2017;6:281–284
[98]	Dueger EL, Asturias EJ, Halsey NA. Culture- and antigen-negative meningitis in Guatemalan children. 2008;24:248–255
[99]	Deng S, Lin B, Weng B, et al. Clinical Characteristics and Follow-up of Cases of Streptococcus suis Meningitis in Patients of Liuzhou, China. 2023;108:477–481
[100]	Díez de los Ríos J, Reynaga E, García-Gonzàlez M, et al. Clinical and Epidemiological Characteristics of Streptococcus suis Infections in Catalonia, Spain. 2021;8
[101]	Navacharoen N, Chantharochavong V, Hanprasertpong C, Kangsanarak J, Lekagul S. Hearing and vestibular loss in Streptococcus suis infection from swine and traditional raw pork exposure in northern Thailand. 2009;123:857–862
	Cross-sectional study
[102]	Arteta-Acosta C, Villena Martinez R, Santolaya de Pablo ME. Sequelae at Hospital Discharge in 61 Children With Invasive Meningococcal Disease, Chile, 2009–2019. 2022;41:607–613
[103]	Epelboin L, Blonde R, Chamouine A, et al. Angiostrongylus cantonensis Infection on Mayotte Island, Indian Ocean, 2007–2012. 2016;10:e0004635
[104]	Pelkonen T, Roine I, Monteiro L, et al. Acute childhood bacterial meningitis in Luanda, Angola. 2008; 40:859–866
[105]	Pelkonen T, Roine I, Monteiro L, et al. Risk factors for death and severe neurological sequelae in childhood bacterial meningitis in sub-Saharan Africa. 2009; 48:1107–1110
[106]	Teräsjärvi J, Tenhu E, Cruzeiro ML, et al. Gene polymorphisms of IL-17A and bacterial meningitis in Angolan children. 2024;118
	Case–control study
[107]	Edmond K, Dieye Y, Griffiths UK, et al. Prospective cohort study of disabling sequelae and quality of life in children with bacterial meningitis in urban Senegal. 2010;29:1023–1029
[108]	Khowaja AR, Mohiuddin S, Cohen AL, et al. Mortality and neurodevelopmental outcomes of acute bacterial meningitis in children aged < 5 years in Pakistan. 2013;163:S86-S91.e81
[109]	Domingo P, Suarez-Lozano I, Torres F, et al. Bacterial meningitis in HIV-1-infected patients in the era of highly active antiretroviral therapy. 2009;51:582–587
[110]	Huong VTL, Long HB, Kinh NV, et al. Long-term outcomes of patients with Streptococcus suis infection in Viet Nam: A case–control study. 2018;76:159–167

Included references and their corresponding study type

Fig. 2.

Global distribution of study sites

Distribution of study sites from included references according to the World Bank income classification. *Countries included in Thomas et al. ^Countries included in Pelkonen et al

Regarding study design, 67 studies (75.3%) were cohort studies, 8 (9.0%) were RCTs, 5 (5.6%) were case series, 5 (5.6%) were cross-sectional studies, and 3 (3.4%) were case–control studies (Table 1). Most of the studies (62, 69.6%) reported data on children, while 30 studies (33.7%) included data on adults. Three studies evaluated meningitis sequelae in both adults and children. In total, there were 9311 confirmed cases of meningitis reported among adults and 18,658 cases among children.

Risk of bias assessment

The risk of bias assessment for the 67 included cohort studies revealed the following quality ratings: 53 studies (79.1%) were rated as good quality, 11 studies (16.4%) as fair quality, and 3 studies (4.5%) as poor quality. Among the 8 RCTs, 4 (50%) showed some concerns for risk of bias, while 4 (50%) were considered to have a low risk of bias. Of the 5 case series, 1 (20%) was rated as fair quality, and 4 (80%) were rated as good quality. Among the 5 cross-sectional studies, 4 (80%) were rated as fair quality, and 1 (20%) was rated as good quality. Lastly, all 6 case–control studies (100%) were evaluated as good quality. For further details, see Additional file 1: Tables S6-S10.

Adult population

Of the 9311 adult cases of confirmed meningitis, 7301 (78.4%) cases were assessed by a healthcare provider to detect sequelae. Among these, 1339 (18%) cases had identified at least one meningitis-related sequelae—this may include individuals with one or multiple sequelae. The predominant infectious etiology was bacterial, responsible for 99.7% (9290/9311) of meningitis cases, and 99.6% (1334/1339) of meningitis-related sequelae cases. The most common isolated pathogen in this review was Streptococcus pneumoniae, the principal cause of meningitis and meningitis-related sequelae (Table 2).

Table 2.

Infectious etiologies of meningitis and meningitis-related sequelae

	Adults	Children
Studies	30*	62*
Etiology
Meningitis patients	9311	18,658
Bacterial	9290 (99.7%)	17,567 (94.3%)
Viral	21 (0.3%)	529 (2.8%)
Fungal	0	78 (0.4%)
Parasitic	0	14 (0.1%)
Unspecified/not reported	0	386 (2.2%)
Patients with meningitis-related sequelae	1339	3484
Bacterial	1334 (99.6%)	3258 (93.5%)
Viral	5 (0.4%)	62 (1.8%)
Fungal	0	9 (0.2%)
Parasitic	0	2 (0.1%)
Unspecified/not reported	0	129 (3.7%)

^*3 studies evaluated both children and adult populations

Of the 30 adult studies reviewed, with different timepoints of administered assessments for sequelae detection, 18 (60%) studies reported cases of hearing loss, with 395 patients affected out of 3382 assessed (11.7%). Focal neurological deficits were reported in 15 studies, affecting 165 patients out of 2134 assessed (7.7%). Hydrocephalus was reported in 8 studies, with 33 patients affected out of 1188 assessed (2.8%). Neurocognitive impairment was identified in 7 studies, with 70 patients affected out of 817 evaluated (8.6%). Seizures were reported in 6 studies, with 42 patients affected out of 851 assessed (4.9%). Psychological after-effects were reported in 3 studies, with 121 patients affected out of 511 evaluated (23.7%). Speech disorders were identified in 3 studies, with 15 patients affected out of 379 assessed (4%). Lastly, vision loss or any degree of visual impairment was reported in 2 studies, affecting 5 patients out of 299 assessed (1.7%). No limb loss cases were reported. Overall, the most frequently reported sequelae were hearing loss, followed by focal neurological deficits, psychological after-effects, neurocognitive impairments, seizures, hydrocephalus, speech disorders, and vision impairment (Table 3).

Table 3.

Adult sequelae analysis

Type of sequelae	Nº Patients diagnosed/assessed (%)	Nº Studies that reported each sequela
Psychological after-effects	121/511 (23.7%)	3
Hearing loss	395/3382 (11.7%)	18
Neurocognitive/neurodevelopmental impairment	70/817 (8.6%)	7
Focal neurological deficits	165/2134 (7.7%)	15
Seizures	42/851 (4.9%)	6
Speech	15/379 (4%)	3
Hydrocephalus	33/1188 (2.8%)	8
Vision loss/impairment	5/299 (1.7%)	2
Limb loss	0/0 (0%)	0
All neurological sequelae	1339/7301 (18%)	30

Of the 5270 patients screened for sequelae by healthcare providers before discharge, 814 (16%) were found to have at least one sequela during their hospitalization and 29% (785/2711) of patients were diagnosed with at least one sequela after discharge during follow-up evaluations. Among the 18 studies that evaluated sequelae before discharge, 24% (67/273) of patients had at least one sequela detected during hospitalization, while 15% (757/4,997) had at least one sequela detected at the time of discharge. In the 18 studies that assessed sequelae post-discharge, 25% (225/883) of patients were diagnosed with at least one sequela within the first 3 months of follow-up, and 32% (588/1,864) after 3 months. The mean timeframes for sequelae diagnosis were 2 weeks at discharge, 47.8 days (1.6 months) for short-term follow-up, and 172.9 days (5.7 months) for long-term follow-up (Table 4).

Table 4.

Time of neurological sequelae diagnosis

	Studies	Adults (diagnosed/assessed)	Mean time to sequelae diagnosis in days (months)
Before discharge	18	814/5270 (15.4%)
During hospitalization	1	67/273 (24.5%)	-
At discharge	18	757/4997 (15.1%)	14 (0.5)
After discharge	18	785/2711 (28.9%)
Short-term follow-up (1–3 months)	12	225/883 (25.5%)	47.8 (1.6)
Within 1 month	6	85/303 (28.1%)	26 (0.9)
Long-term follow-up (> 3 months)	8	588/1864 (31.5%)	172.3 (5.7)
	Studies	Children (diagnosed/assessed)	Mean time to sequelae diagnosis in days (months)
Before discharge	34	2473/7180 (34.4%)
During hospitalization	4	301/885 (34.0%)	-
At discharge	30	2172/6296 (34.5%)	13.5
After discharge	37	1406/8298 (16.9%)
Short-term follow-up (1–3 months)	13	621/5920 (10.5%)	62.7 (2)
Within 1 month	3	240/357 (67.2%)	30 (1)
Long-term follow-up (> 3 months)	28	879/2738 (32.1%)	551.7 (18.4)

Children and adult populations were examined for neurological sequelae at different times after meningitis diagnosis. Timepoints were divided into before and after discharge. Before discharge, sequelae testing was performed during hospitalization, and at the moment of discharge. After discharge, sequelae evaluation was performed within 1, short-term follow-up (≤ 3 months), and more than 3 months of follow-up. In adults, a larger proportion of patients assessed were diagnosed with sequelae after discharge compared to before discharge. In contrast, a higher proportion of pediatric patients were diagnosed with sequelae before discharge than after discharge. Some studies included multiple timepoints and may have followed patients longitudinally

A total of six studies (Sakata et al. [73], Raemy et al. [67], Moon et al. [57], Jensen et al.50, Huong et al. [110], Auburtin et al. [28]) conducted longitudinal evaluations of sequelae development in adults, both before and after discharge. All six studies assessed sequelae at the time of discharge, with five also conducting follow-up evaluations within 30 to 90 days post-discharge [28, 50, 57, 73, 110]. Only three of the studies extended their follow-up to assess long-term sequelae, with evaluations occurring at 9 months and 1 year after discharge [67, 73, 110].

Among the 30 included studies, it was reported that 1297 adults died from meningitis, corresponding to a 13.9% fatality rate from the 9311 total adult meningitis cases. Mortality was more frequently reported before discharge during hospitalization.

Adult population meta-analysis: pooled prevalence of sequelae by timeframe of screening

Among adult patients screened at hospital discharge, the pooled prevalence of sequelae was 24.8% (95% CI 20.5–29.2%, I² = 93.09%, tau-squared = 0.009), with the most common sequelae being sensorineural hearing loss. When studies were stratified by time of sequelae screening, those that screened within 90 days of diagnosis (12 studies) reported a pooled prevalence of 41.5% (95% CI 25.7–57.3%, I² = 97.81%, tau-squared = 0.073), while those that screened beyond 90 days (8 studies) observed a pooled prevalence of 31.9% (95% CI 18.5–45.3%, I² = 97.78%, tau-squared = 0.035) (Fig. 3A–C). Subgroup analyses for logit transformed proportions stratified by risk of bias did not reveal any credible subgroup effects [111]. Moreover, we assessed the observed heterogeneity as not serious as all the study results were on the same side of the decision threshold for screening [112].

Fig. 3.

A Meta-analysis for adults diagnosed with neurological sequelae at discharge. B Meta-analysis of adults diagnosed with neurological sequelae after discharge within short-term follow-up. Forest plot showing the proportion of adult patients diagnosed with sequelae over the total patients tested for sequelae within 3 months of discharge. C Meta-analysis of adults diagnosed with neurological sequelae after discharge within long-term follow-up. Forest plot showing the proportion of adult patients diagnosed with sequelae over the total patients examined for sequelae after > 3 months of discharge

Pediatric population

A total of 18,658 children were diagnosed with acute meningitis, of whom 79% (14,826) were reported to have been assessed by a healthcare provider to detect sequelae. Of these evaluated patients, 3484 (24%) had sequelae detected. The most predominant infectious etiology was bacterial, responsible for 94.3% (17,567/18,658) of the meningitis cases and 93.5% (3258/3484) of sequelae-related meningitis cases. Moreover, 2.8% (529/18,658) of meningitis cases were due to viral etiologies, followed by 2.2% (386/18,658) of unknown etiology, 0.4% (78/18,658) fungal, and 0.1% (14/18,658) parasitic. Of the meningitis-related sequelae, 1.8% (62/3,484) was caused by viral etiologies, followed by 0.2% (9/3,484) fungal, 0.1% (2/3,484) parasitic, and 3.7% (129/3,484) of unknown etiology (Table 2).

Across included studies, the reporting of sequelae varied, as not all studies reported on every type of sequelae. Of the 62 included studies, 46 (74%) reported hearing loss sequelae, with 1257 patients diagnosed out of 12,624 who were evaluated (10%). Focal neurological deficits were reported in 38 studies, involving 1108 patients out of 7288 assessed (15.2%). Hydrocephalus was documented in 30 studies, affecting 256 patients out of 9067 evaluated (2.8%). Seizures were reported in 28 studies, with 653 out of 9553 evaluated patients (6.8%). Neurocognitive impairment was found in 25 studies, affecting 382 patients from 3859 evaluated (9.9%). Vision loss or impairment was reported in 22 studies, with 167 out of 4437 patients evaluated (3.8%). Speech disorders were identified in 9 studies, involving 89 patients out of 1423 assessed (6.2%). Psychological after-effects, such as depression, were reported in 6 studies, affecting 69 out of 930 patients assessed (7.4%). Finally, limb loss was reported in 6 studies, involving 53 patients out of 1114 evaluated after meningitis (4.8%). In children, the most reported sequelae was hearing loss, followed by focal neurological deficits, seizures, neurocognitive and neurodevelopmental impairment, hydrocephalus, vision impairment, speech disorders, psychological after-effects, and limb loss (Table 5).

Table 5.

Children sequelae analysis

Type of sequelae	Nº Patients diagnosed/assessed (%)	Nº Studies that reported each sequelae
Focal neurological deficits	1108/7288 (15.2%)	38
Hearing loss	1257/12624 (10%)	46
Neurocognitive/neurodevelopmental impairment	382/3859 (9.9%)	25
Seizures	653/9553 (6.8%)	28
Psychological after-effects	69/930 (7.4%)	6
Speech	89/1423 (6.2%)	9
Limb loss	53/1114 (4.8%)	6
Vision loss/impairment	167/4437 (3.8%)	22
Hydrocephalus	256/9067 (2.8%)	30
All neurological sequelae	384/14826 (24%)	62

The proportion of pediatric patients diagnosed with sequelae among those assessed by a healthcare provider was 34.4% (2473/7180) before discharge and 16.9% (1406/8298) after discharge. Of the 34 studies assessing sequelae before discharge, 301 (34.0%) patients were diagnosed with sequelae during hospitalization out of 885 screened patients, and 34.5% (2172/6269) at the moment of discharge. Among the 37 studies evaluating sequelae after discharge, 10.5% (621/5,920) patients were diagnosed with sequelae within the first 3 months after discharge, and 32.1% (879/2,738) after 3 months of follow-up. The average time between sequelae detection to discharge, short-term follow-up, and long-term follow-up was 13.5 days, 62.7 days (~ 2 months), and 551.7 days (~ 18.4 months), respectively (Table 4).

Ten out of the 62 pediatric studies (Uppal et al. [94], Sakata et al. [73], Roine et al. [70], Paulke-Korine et al. [63], Molyneux 2002 et al. [91], Molyneux 2014 et al. [90], Namani et al. [58], Klobassa et al. [52], Duke et al. [89], Blanco et al. [32]) reported sequelae evaluation sequentially through time, before and after discharge.

Regarding mortality across the 62 included studies, it was reported that 2396 children died from meningitis corresponding to a 12.8% fatality rate in all pediatric patients. Mortality was more often reported before discharge during hospitalization, a trend also seen in adult patients.

Pediatric population meta-analysis: pooled prevalence of sequelae by timeframe of screening

Pediatric studies that screened for meningitis sequelae during hospitalization reported a pooled prevalence of 45.8% (95% CI 26.5–65.1%, I² = 97.22%), with sensorineural hearing loss as the most commonly reported outcome. Among the studies that screened children at discharge, the pooled prevalence of meningitis sequelae was 28.9% (95% CI 20.8–37%, I² = 99.11%, tau-squared = 0.046). For studies that screened within and beyond 90 days in children, the pooled prevalence was 29.9% (95% CI 19–40.8%, I² = 99.55%, tau-squared = 0.038) and 38.2% (95% CI 30.3–46.1%, I² = 96.29%, tau-squared = 0.04), respectively (Fig. 4A–D). Subgroup analyses for logit transformed proportions stratified by risk of bias did not reveal any credible subgroup effects. Moreover, we assessed the observed heterogeneity as not serious as all the study results were on the same side of the decision threshold for screening [111, 112].

Fig. 4.

A Meta-analysis of children diagnosed with neurological sequelae during hospitalization. Forest plot showing the proportion of pediatric patients diagnosed with sequelae over the total patients examined for sequelae during hospitalization. B Meta-analysis of children diagnosed with neurological sequelae at discharge. Forest plot showing the proportion of pediatric patients diagnosed with sequelae over the total patients examined for sequelae at discharge. C Meta-analysis of children diagnosed with neurological sequelae within short-term follow-up. Forest plot showing the proportion of pediatric patients diagnosed with sequelae over the total patients examined for sequelae within 3 months of discharge. D Meta-Analysis of children diagnosed with neurological sequelae within long-term follow-up. Forest plot showing the proportion of pediatric patients diagnosed with sequelae over the total patients examined for sequelae after > 3 months of discharge

Discussion

A total of 27,969 patients with acute meningitis were included in this systematic review, of whom 33.3% were adults and 66.7% were children, with bacterial etiologies as the most frequently reported cause of meningitis in both populations. Among the adult patients, 21.6% (2010/7301) did not have documented evaluations for sequelae, while 20.5% (3832/14,826) of the pediatric cases did not have documented assessments for sequelae following their meningitis diagnosis. This gap in evaluation was partly due to mortality rates (13.9% in adults and 12.8% in children) and loss to follow-up, which was not consistently reported across studies.

Among adults, while a higher number of patients were reported to have evaluations before discharge compared to after discharge (5270 vs. 2711), the proportion of sequelae diagnoses was higher post-discharge. The pooled prevalence of sequelae was 24.8% (95% CI 20.5–29.2%) during hospitalization before/at discharge, compared to 41.5% (95% CI 25.7–57.3%) within 3 months and 31.9% (95% CI 18.5–45.3%) beyond 3 months post-discharge. Among children with sequelae assessments and recorded evaluation timeframes, more were assessed post-discharge compared to pre-discharge (8298 vs. 7180), with a higher pooled prevalence of sequelae diagnoses seen post-discharge, consistent with trends found in the adult population. At discharge, the pooled prevalence of sequelae was 28.9% (95% CI 20.8–37%), compared to 29.9% (95% CI 19–40.8%) within 3 months and 38.2% (95% CI 30.3–46.1%, I2 = 96.2%) beyond 3 months after discharge.

Variability in assessments and diagnoses before and after discharge may be attributed to patient deaths, loss to follow-up, or as noted in some studies, improvement in sequelae over time. Lucas et al. [113] and Klobassa et al. [52] reported that some sequelae, including focal neurological deficits, can gradually diminish or resolve. As a result, patients who initially presented with sequelae may no longer exhibit them at follow-up assessments.

Additionally, sequelae resulting from meningitis can emerge at different time points due to various underlying processes. Some develop soon after the acute meningitis episode, while others appear later. For instance, focal neurological sequelae are often associated with cerebrovascular events [114] but can also result from other complications directly linked to meningitis, such as subdural empyema [115], cerebral abscess [116], or intracerebral hemorrhage [117]. These conditions may arise at the time of diagnosis, later during the clinical course, or even after initial treatment and improvement [114, 118].

Overall, variability in the proportion of patients diagnosed before and after discharge is expected. However, this systematic review reveals significant inconsistencies in assessment timing, as only 9 of 61 studies in children (14.8%) and 6 of 30 studies in adults (20%) conducted appropriate longitudinal evaluations before and after discharge. The remaining studies assessed patients at only one time point, either before or after discharge. This highlights the lack of standardized assessment protocols for early sequelae detection that is essential for prompt intervention and minimization of morbidity.

Given the variability in sequelae detection timeframes, it is crucial to recognize that while some patients present with sequelae at discharge, others may develop complications later. Therefore, prioritizing assessments both at discharge and during follow-up is essential to ensure early detection and timely management. Early identification of sequelae prior to discharge remains essential for improving patient outcomes, facilitating timely referral to specialist care and rehabilitation, reducing hospital readmissions, and supporting effective long-term follow-up and management. Notably, considering the higher proportions of diagnoses reported after discharge in both children and adults, proper post-discharge follow-up screening facilitates comprehensive care.

In adherence with the WHO’s Defeating Meningitis by 2030 roadmap and considering the substantial burden of meningitis-related sequelae [5], this systematic review reinforces the urgency of implementing standardized guidelines to ensure appropriate assessments, timely identification, and effective management. Several strengths of this review include the scope and heterogeneity of included studies and granularity of analyzed data. We conducted a comprehensive literature search across three major databases with a yield of 89 included studies with different study designs. Adult and pediatric cohorts were separately analyzed to account for age-related differences across patient populations. Time to sequelae detection was not only classified in multiple subcategories in relation to discharge but also analyzed per neurological sequelae associated with meningitis.

Among the limitations of this systematic review is that only a few studies followed patients longitudinally, while most assessed their populations at a single time point. This variability resulted in different populations that were analyzed at each time point, limiting direct comparisons across timeframes. Though the meta-analyses revealed a high I² statistic, we assessed that the assessment of inconsistency in the context of clinical decisions was not serious, since what would matter is whether study results would lead to different inferences for practice [112]. It was observed that all estimates from individual studies were on the same side of the threshold of 10% which was decided as the threshold by consensus. Additionally, in some analyses the total number of patients screened was not reported and in the few studies that evaluated patients sequentially, it was unclear whether the same individuals were assessed at all time points, or if patients who were not screened earlier were included in follow-up assessments. The protocol for this review was not registered in PROSPERO. Although the study followed the WHO methodological framework, we acknowledge that this does not replace prospective protocol registration and that it is a limitation.

Most included studies were conducted in high-income countries, which may limit the generalizability of findings to lower-income settings [119, 120]. Another challenge was differentiating between sequelae and acute complications, as some conditions classified as sequelae were identified early in the acute phase of meningitis, without a clear distinction from the initial presentation.

Conclusions

The impact of meningitis-related sequelae on the quality of life is significant. Healthcare providers need to exercise vigilance and perform routine follow-ups where possible, given that sequelae can develop immediately after to several months after meningitis diagnosis. This systematic review highlights the variability in sequelae detection and the critical gaps in consistent evaluation practices, underscoring the need for standardized guidelines that specify proper time frames for assessment. In response to these gaps, the recently published WHO guidelines on meningitis diagnosis, treatment, and care [9] provide standardized recommendations to improve the identification and management of post-meningitis sequelae. These guidelines support healthcare providers to systematically assess, diagnose, and treat sequelae early, potentially mitigating long-term disability and improving patient outcomes. As recommended by the new WHO guidelines, patients should receive a comprehensive assessment for sequelae by the moment of hospital discharge, along with clearly defined follow-up plans to ensure timely and appropriate care.

Abbreviations

CI

Confidence interval

CSF

Cerebrospinal fluid

GDG

Guideline Development Group

GRADE

Grading of Recommendations, Assessment, Development, and Evaluation

MOOSE

Meta-Analysis of Observational studies in Epidemiology

PCR

Polymerase chain reaction

PICO

Population, Intervention, Comparator, and Outcome

PRISMA

Preferred Reporting Items for Systematic Review and Meta-Analysis

RCTs

Randomized controlled trials

WHO

World Health Organization

Authors’ contributions

LFA participated in all phases of the systematic review, from its inception, including the development of the search strategy and organization of the systematic review software, to data analysis and manuscript writing. LFA was involved in screening, full-text review, data extraction, and consensus performance. CYK provided essential support in data analysis and manuscript writing, and also participated in screening, extraction, and consensus processes. LM, CEH, ACBT, JAR, FJV, SAH, BMG, and PB assisted with screening, data extraction, and manuscript writing. MP performed specific data analyses, including meta-analyses, and contributed to the supervision and writing of the manuscript. KUK and JU contributed to the development of the search strategy and reviewed the manuscript. FV, NS, NB, EB, and TD supported the conceptualization and construction of the article. KTT, as the principal investigator, led the project, oversaw the execution of the systematic review, participated in consensus discussions, and contributed to the supervision, conceptualization, and writing of the manuscript. All authors read and approved the final manuscript.

Funding

This study was supported by the WHO but received no external funding.

Data availability

All data generated and/or analyzed during this study are included in this published article, its tables and figures document, and its supplementary information file.

Declarations

The authors are responsible for the views expressed in this article. Those views do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.