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Table 1 Published studies/conference presentations included in the review

From: Invasive meningococcal disease in older adults in North America and Europe: is this the time for action? A review of the literature

Publication Study Dates Country Population Meningitis confirmation Key results
Global Burden of Disease Study 2018 [41] 1990–2016 Worldwide All Varies by country Death rate and incidence increased, as did years of life lived with disability (YLD), in the oldest age groups (age groups up to > 95 years), with other meningitis and meningococcal meningitis causing most of the burden in those aged ≥ 80 years. Meningococcus was the leading cause of meningitis mortality in 1990 (192,833 deaths [95% UI 153,358–221,503] globally), Globally in 2016, 1.48 million (1.04–1.96) YLDs were due to meningitis compared with 21.87 million (18.20–28.28) disability-adjusted life-years (DALYs)
Gray et al. 2019 [42] 1998–2019 UK 525–2573 cases per annum Notified cases to PHE. Mix of PCR test, culture test and PCR/culture testing The age profile of meningococcal disease cases altered in 2017/18, with an increased proportion of cases in those aged ≥ 45 years. This was subsequent to increases in serogroup W and Y cases, together with the decrease in serogroup B disease
Stefanelli et al. 2015 [43] 1994–2014 Italy 174 IMD cases, out of 4,263 nationally reported (www.iss.mabi), occurred in Puglia PCR or antisera Since 2013, 52% of the IMD cases occurred among patients aged ≥ 45 years. The CFR in those aged ≥ 65 was 19%
Säll et al. 2017 [44] 1995–2012 Sweden A total of 191 patients with serogroup Y IMD were identified in Sweden during the 1995–2012 study period. Of the 191 known episodes of serogroup Y IMD during the study period, medical records for 175 (92%) patients were retrospectively and systematically reviewed. For technical reasons, 16 medical records could not be found, the majority from 1995 to 1999. The median age of the 175 patients in the study was 62 years, and two distinct age groups, 11–20 years and patients > 60 years, together represented the majority of cases (73% of all patients). Four patients were < 5 years of age and only one was < 1 year. Meningitis was diagnosed in 33% and pneumonia in 19% of all patients Lab confirmed Two distinct age groups, 11–20 years and > 60 years, together represented the majority of cases (73% of all patients). This age distribution reflects the change in meningococcal epidemiology in Sweden where IMD now largely affects the elderly, with serogroup Y predominating
Folaranmi et al. 2017 [45] Evaluation of data from January 2012-June 2015 USA Incidence of MSM in the USA Meningococcal disease data from the National Notifiable Disease Surveillance System Within the oldest age group (56–64 years) there was just 1 case out of a total of 527 total cases
  Edge et al. 2016 [46] 2007–2011 UK IMD cases confirmed by PHE were linked with national hospital records and death registries Clinical presentation by interrogation of ICD-10 codes Atypical clinical presentations, including pneumonia and septic arthritis, mainly occurred among those aged ≥ 65 years, caused mainly by serogroups W and Y
  Campbell et al. 2020 [47] 2014 UK 340 laboratory-confirmed IMD cases caused by serogroups: B (179 cases), W (95 cases) and Y (66 cases) in individuals aged ≥ 5 years There were 184 (54%) cases confirmed by culture only, 110 (32%) by PCR only and 46 (14%) by both methods CFR varied by serogroup and increased with age group, but no significant associations were identified in the multivariable logistic regression models. However, older adults and those with serogroup Y disease were significantly and independently more likely to develop meningococcal pneumonia
  Ortiz de Zárate et al. 2016 [48] 1995–2014 Spain 675 invasive N. meningitidis isolates were analysed during the study period Lab confirmed isolates Serogroup Y isolates were the most frequent among the elderly aged ≥ 65 years
  Parisi et al. 2019 [49] 2011–2017 Italy IMDs surveillance data from the Italian National Health Institute Presumably notified cases but not explicitly stated The overall IMDs incidence increased from 0.25 cases/100,000 inhabitants in 2011 to 0.33 in 2017. The increased number of cases in adults and elderly was mostly due to serogroups C, W and Y
  Stoof et al. 2015 [50] 1999–2011 The Netherlands A retrospective study using Dutch surveillance data on IMD from June 1999 to June 2011. Clinical information was retrieved from hospital records. Between June 1999 and June 2011, the NRLBM received 939 isolates from the nine sentinel laboratories. Hospital records were retrieved from 879 (94%) of these IMD cases Lab confirmed The overall CFR in this study was 8% and higher for adults compared with children with a clear peak in patients aged ≥ 65 years
  Loenenbach et al. 2019[51] 2015–2018 The Netherlands A total of 565 IMD cases were reported Lab confirmed In patients aged ≥ 65 years, CFR overall for this age group was 8.2% (12/146). In patients aged 20–64 years, the CFR overall was 10.2 (18/176)
  Eriksson et al. 2018[52] January 1995-June 2017 Sweden N = 89 IMD cases at the National Reference Laboratory for Neisseria meningitidis Whole genome sequencing In recent years, a significant increase in the incidence of serogroup W has been noted in Sweden, to an average incidence of 0.15 case/100,000 population in 2015 to 2016. In 2017 (1 January to 30 June), 33% of IMD cases (7/21 cases) were caused by serogroup W
  Bennett et al. 2019 [53] 1996/1997 and 2015/2016 Ireland 3,707 cases were reported National surveillance data on laboratory-confirmed cases CFR was highest in patients aged > 65 years (15.7%; RR 3.73, 95% CI 2.25–6.19; P < 0.0001), although the incidence of IMD was one of the lowest in that age group
  Bijlsma et al. 2014 [54] 1998–2002 compared with 2002–2012 The Netherlands A total of 814 patients were included for analysis Patients from NRLBM A figure within the publication breaks out the only data for patients 55 years old and above (data presented for reported cases over the whole study period) and presents an overall incidence rate of approximately 0.2 in those aged 55 years rising to approximately 0.7 in those aged ≥ 90 years
  Clarke & Mallonee. 2009 [55] 1988–2004 USA Cases from the state-wide passive reporting system with disease onset between 1988 and 2004 were included Passive surveillance In the ≥ 65-year-old age group, 545 cases of IMD occurred in Oklahoma; 71 (13.0%) died. In those aged > 40 years, serogroup Y was most common (54.6%) followed by B, C and W-135
  Peruski et al. 2014 [56] 1988–2011 USA 1,258 cases of IMD were reported to MDPH Lab confirmed Throughout the 24-year time period between 1988 and 2011, serogroup Y became increasingly predominant in IMD cases in those aged ≥ 60 years, accounting for over 50% of all serogroup isolates in this age group after 1995
  Baccarini et al.2013 [57] 1945–2010 United States and Canada Review of different studies over the last half century Varies by study The distribution of IMD by age was similar in both the USA and Canada. Serogroup Y was proportionally more frequent in adults aged > 65 years in both countries, accounting for over 50% of IMD cases in this age group
  Perea-Milla et al. 2009 [27] 1995–2000 Spain 848 patients diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain ICD code and some PCR confirmed A total of 323 patients (38.1%) had sepsis, 336 (39.6%) meningitis and the rest a mixed clinical form, with mortality rates of 10.7%, 2.1% and 4.2%, respectively (P < 0.001). Sepsis vs. the other clinical forms had an OR for death of 4. The results showed that that the older the patient, the greater the mortality, with 4.9% deaths in patients aged under 11 years vs. 25% deaths in those aged > 65 years
  Gil-Prieto et al. 2011 [58] 1997–2008 Spain Total of n = 6,131 cases 036.0 meningococcal meningitis code The CFR increased dramatically with age in meningococcal infection, meningococcal meningitis and meningococcemia (P < 0.001) reaching the highest values in the > 85-year-old group with 37.66% (95% CI: 26.84–48.49), 42.42% (95% CI: 25.56–59.29) and 37.14% (95% CI: 21.13–53.15) for meningococcal infection, meningococcal meningitis and meningococcemia, respectively
  Cabellos et al. 2009 [59] 1977–2006 Spain Prospective study at a 1,000 bed teaching hospital in Barcelona, Spain. Since 1997, all episodes of community-acquired bacterial meningitis were recorded for cases occurring in patients ≥ 65 years old and these were compared with community-acquired bacterial meningitis occurring in those aged < 65 years Lab confirmed There were 675 episodes of meningitis in adults (aged ≥ 18 years) recorded. Of these, 185 (27%) were aged ≥ 65 years (range, 65–93 years). In general, bacterial meningitis in those aged ≥ 65 years was more difficult to diagnose because of the absence of meningeal signs, but the disease had greater neurologic severity and higher rates of complications and mortality
  Goldacre & Maisonneuve. 2013 [60] 1999–2010 UK 19,113 people admitted to hospital for meningococcal disease all people with a discharge diagnosis in HES of meningococcal disease (code A39 in the 10th revision of the ICD, code 036 in the 9th revision) from 1999 to 30 September 2010 OR of CFR by age group 55–59 years5.66
60–64 years5.11
65–69 years8.98
70–74 years6.75
75–79 years8.08
 > 80 years6.92
  Parent du Chatelet et al. 2017 [61] 2011–2015 France 5,690 cases were biologically confirmed. For 85 (1.5%) cases, the confirmation technique was not reported despite an available group result Lab confirmed The CFR was higher in adults ≥ 60 years olds (20%) than in the other age groups (9.9% in infants, 8.9% in 1–4 year-olds, 5.9% in 5–14 year-olds, 9.3% in 25–59 year-olds
  Bai et al. 2019 [62] 2019 Eastern Europe but relevant age-specific data for Poland Findings from Global Round Table Initiative in East Europe In the Eastern European countries participating in the meeting, the predominant serogroups were serogroup B (accounting for approximately 60–90% of cases) and serogroup C (re-emerging in a number of countries and accounting for up to 30% of cases), followed by serogroup A CFRs ranged from approximately 3% to 30% both within and across the Eastern European countries represented. In Poland, the greatest CFR (44%) was noted in individuals aged > 65 years
  Skoczyńska et al. 2013 [63] 2013 paper analysing data from 2002–2011 Poland Invasive meningococcal data collected between 2002 and 2011 in the National Reference Centre for Bacterial Meningitis The isolates were re-identified and characterised by susceptibility testing, MLST analysis, porA and fetA sequencing. A PCR technique was used for meningococcal identification directly from clinical materials The general CFR was 10.0% for cases with known outcome only, and was highest in patients aged > 65 years (46.2%, P = 0.001), although the incidence of IMD was lowest in that age group. Although not broken down by age, the highest CFR was found in patients with sepsis (22.4%), as compared with patients with meningitis and sepsis (7.0%, P = 0.0007) and with meningitis alone (3.1%, P < 0.0001)
  Beebeejaun et al. 2020 [64] 2020 paper based on 2008–2015 data England Analysis of surveillance data of laboratory-confirmed IMD cases diagnosed 2008–2015 matched to death registrations Lab confirmed In older adults aged ≥ 65 years, all 114 and 134 deaths within one and seven days after diagnosis were IMD-related, as were 96% (146/152) of deaths within 30 days of diagnosis. More than half of the IMD-related fatalities amongst serogroup W cases (44/84, 52%) were in those aged ≥ 65 years and 47/70 (67%) of the IMD-related fatalities amongst serogroup Y cases were in those aged ≥ 65 years
  Knol et al. 2017 [65] 2017 paper using surveillance data from 1992–93 to 2015–16 The Netherlands and England Observational cohort study using surveillance data for the Netherlands and England Lab confirmed In the Netherlands, the incidence of meningococcal serogroup W disease increased substantially in 2015–16 compared with 2014–15, with an incidence rate ratio of 5·2 (95% CI: 2·0–13·5) and 11% case fatality. In England, the incidence increased substantially in 2012–13 compared with 2011–12, with an incidence rate ratio of 1·8 (95% CI: 1·2–2·8)
  Masson-Behar et al. 2017 [66] 2011–2016 France A 5-year retrospective study. Included all patients with inflammatory joint symptoms and proven meningococcal disease. A total of 7 patients (5 males) with joint symptoms and meningococcal disease were identified. Of these, 2 had meningitis Identification of Neisseria meningitidis in blood, cerebrospinal fluid, or synovial fluid Patients presented initially with arthritis
  Cikirikcioglu, et al. 2017. [67] 2017 Switzerland A 55-year-old woman with a history of high fever was admitted to the centre and hospitalized with the diagnosis of bronchopneumonia. Transthoracic echocardiography showed severe aortic valve regurgitation with a mobile vegetation and abscess cavity underneath the left main stem PCR test Patient presented with endocarditis
  Bajaj et al. 2019 [68] Not explicitly stated. Year of publication was 2019 USA A 61-year-old woman with past medical history of diabetes and hypertension presented with fever, chills and headache of 1 day duration Lab confirmed This was the fourth case of intraventricular empyema reported secondary to Neisseria meningitidis
  Keeley et al. 2018 [69] 2018 UK A 74-year-old Caucasian woman with no history of immunosuppression or rheumatological disease, but with a history of paroxysmal atrial fibrillation for which she was taking flecainide but no anticoagulation, was admitted following a Baltic cruise holiday PCR confirmed Patient presented as myopericarditis
  Walayat et al. 2018 [70] 2018 USA The case of a 72-year-old man with a past medical history of severe COPD, obstructive sleep apnoea, and stage I lung cancer status post-stereotactic body radiation therapy 1 year ago PCR confirmed Patient presented with a 6-day history of productive cough with yellowish sputum, shortness of breath, extreme myalgia, and fatigue
  Romero-Gomez et al. 2012 [71] 2011 Spain A 94-year-old man sought medical care for left-sided chest pain and difficulty in breathing that began 1 day before admission. He had been healthy until 4 days before admission, when he had sore throat, rhinorrhoea, mild cough, and muscle pain. He had a medical history of ischemic cardiopathy By the VITEK NHI Identification card and by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry Patient presented with bacteraemic pneumonia
  Singh & Swann. 2013 [72] 2013 UK A 55-year-old female nonsmoker with meningococcal septicaemia was treated in an intensive care unit for 11 days, requiring assisted ventilation and renal dialysis. She developed several lesions of necrosis affecting the skin on her arms and legs, as well as ischemic necrosis to her fingers and feet Not specified in paper Patient recovered with no requirement for amputation following antibiotic treatment of IMD
  Arnáiz-García, et al. 2017 [73] 2017 Spain A 78-year-old diabetic woman was admitted to the institution presenting fever, diarrhoea, vomiting, and abdominal pain. The patient reported the appearance of red and purplish macules over her lower extremities within the last 4 h Gram-negative diplococcic, later reported as Neisseria meningitidis, was isolated from blood and cerebrospinal fluid cultures She presented leucocytosis, thrombocytopenia, renal insufficiency, acidosis, and hypoxia cutaneous lesions evolved to haemorrhages and ecchymosis in both hands and feet
  Zimmermann & Chmiel 2018 [74] 2018 Switzerland A 78-year-old woman with a known history of hypertensive cardiomyopathy and paroxysmal benign positional vertigo presented to the emergency department with a 5-day history of throat pain and hoarseness, as well as a progressive and dolorous swelling in the submandibular area Confirmed by lab test Patient presented with acute epiglottitis
  Rosenfield et al. 2017 [75] Not explicitly stated. Year of publication was 2017 Canada A 56-year-old Caucasian woman with past history of severe Neisseria meningitides meningitis and bacteraemia at age 42 years, presented with a 2-day history of feeling unwell with vomiting and loose stools Lab confirmed Patient presented with terminal complement deficiency
  Lesourd et al. 2018 [76] 2018 France A 85-year-old man was allocated to the emergency department based on an initial fever at home. His previous history included atrial fibrillation, renal lithiasis and benign prostatic hyperplasia Lab confirmed Patient presented with primary bacterial ventriculitis
  Lawler et al. 2019 [77] 2015 UK In 2015, two cases of serogroup W IMD occurred in residents aged > 85 years at a 46-bed elderly care home in North East England over a 7-month period; both cases had single bedrooms N. meningitidis was isolated from blood cultures collected on admission Case 1 was admitted to hospital with acute respiratory distress and fever (temperature 41 °C). Case 2 was admitted to hospital with acute onset of fever, tachycardia and hypotension and was treated for respiratory sepsis unsuccessfully
  Puleston et al. 2012 [78] 2012 England 5 people involved in an outbreak in a healthcare setting Lab confirmed The 3 confirmed cases all presented with respiratory symptoms
  Russcher et al. 2017 [79] 2017 The Netherlands A man in his early 60 s consulted his general practitioner (GP) because of a painful, red and swollen ankle Confirmed by tissue culture Patient presented with necrotising fasciitis
  Ladhani et al. 2012 [80] 2007–2009 England and Wales 34 cases in 2007 to 44 in 2008 and 65 in 2009 Lab confirmed There were 162 laboratory-confirmed W-135 cases reported during 2006–2012 (of which about 44% occurred in those aged > 45 years). Most serogroup W-135 infections in older adults presented as pneumonia (usually in the presence of comorbidities). Fatalities occurred in 5.5% of these cases, all in adults older than 45 years. Based on the graph presented, the CFR would appear to be > 0.1 in those aged 45–64 and < 0.2 in those aged ≥ 65 years
  Ristic et al. 2012 [81] 2000–2009 Serbia There were 94 registered cases Laboratory confirmed in 34% (32/94) persons The CFR in this period was 13.8% (septicaemia 26.1%; meningitis 2.1%). The data for meningitis was only reported by two age groups (< 14 years of age and ≥ 15). Of the 48 cases of meningitis, only 12 were in the older group but the age range was not stated. There was one fatality in those aged ≥ 15 years for a CFR of 8.3% (compared with an overall CFR in meningitis of 2.1% for all ages combined)
Clinical burden
  Pellegrino et al. 2014 [82] 1993–2011 USA Two large inpatient databases Estimated the number of cases of meningococcal meningitis and other bacterial meningitides The incidence of hospitalisations for meningococcal meningitis (estimated from the publication) were approximately 5 per 100,000 in the 45–64-year age group; 8 in the 65–84-year age group, and 12 in the ≥ 85-years age group
  1. CFR Case Fatality Rate, CI Confidence Interval, COPD Chronic Obstructive Pulmonary Disease, DALY Disability-Adjusted Life Years, HES Hospital Episode Statistics, ICD International Classification of Diseases, IMD Invasive Meningococcal Disease, IQR Interquartile Range, MDPH Massachusetts Department of Public Health, MLST Multilocus Sequence Typing, MSM Men who have Sex with Men, NRLBM Netherlands Reference Laboratory for Bacterial Meningitis, OR Odds Ratio, PCR Polymerase Chain Reaction, PHE Public Health England, RR Risk Ratio, UI Uncertainty Intervals, YLD Years Lived with Disability