Meningococcal Disease in Older Adults: Challenges in Diagnosis and Management

Abstract

Invasive meningococcal disease (IMD) in older adults frequently presents with atypical clinical manifestations, including bacteremic pneumonia, often without classical meningeal signs or sepsis, which presents clinicians with diagnostic challenges, and may delay treatment, which contributes to the high mortality observed in older adults. Within the broader resurgence of IMD observed since relaxation of quarantine measures introduced to mitigate the impact of the COVID-19 pandemic, there has been a notable increase in reporting of such atypical cases. The aim of this review is to summarize epidemiological, diagnostic, and treatment aspects of non-meningeal forms of IMD in older patients, with a focus on meningococcal pneumonia. By convention, laboratory confirmation requires N. meningitidis detection by culture, polymerase chain reaction (PCR), or antigen detection. In most cases, presentation of meningococcal pneumonia is similar to that of other forms of community-acquired pneumonia, and cerebrospinal fluid sampling may be non-informative. This places a premium on early blood culture for N. meningitidis, allied with testing of respiratory samples (e.g., broncho-alveolar washes). Many cases are linked to isolates of serogroups Y and W. When confirmed, treatment with third-generation cephalosporins is generally preferred. Chemoprophylaxis and vaccination of close contacts is essential for controlling onward meningococcal disease transmission and prevention of further cases.

Key Summary Points

The burden of meningococcal disease is increasing among older adults.

Atypical meningococcal infections such as meningococcal pneumonia are more frequent in older adults, accounting for up to 25% of confirmed cases.

Many atypical cases are due to meningococcal serogroups Y and W.

Delays in diagnosis can contribute to the greater mortality evident in older adults.

Greater and earlier awareness of N. meningitidis as the potential pathogen is paramount.

For meningococcal pneumonia, confirm by blood culture and/or polymerase chain reaction (PCR) on ethylenediaminetetraacetic acid (EDTA) blood. If negative, respiratory samples may be used under strict criteria.

Introduction

Invasive meningococcal disease (IMD) due to Neisseria meningitidis is a devastating disease with high mortality rates across all age groups [1]. In most countries across Europe, the Americas, and in Australia, reporting of all cases to national health authorities by physicians and laboratories is mandatory, often through specific surveillance channels [2]. The incidence of IMD varies with age [3]. In Europe, three peaks of incidence are seen: infants < 1 year, adolescent and young adults aged between 16 and 24 years of age, and then adults from 60 years of age [3]. This third peak is less well-recognized, in part as IMD is more frequently considered as a childhood disease. There has been a general decline in the overall incidence of IMD within most western countries, mainly due to successful vaccination strategies reaching high uptake in younger children and adolescents [4–7]. However, the relative frequency as well as absolute numbers of cases involving older adults remains high, with a resultant shift towards a greater proportion involving older individuals [5, 8, 9].

IMD in older adults has the highest case fatality rate, approaching 20% in those aged ≥ 60 years [1, 10]. In France in 2023, the mortality was 29% in those aged ≥ 60 years [11]. In addition, IMD complications and disease sequelae have a substantial negative impact on the quality of life on patients and their caregivers, with a significant financial burden across all age groups [12, 13]. The highest frequency of disease sequelae is reported in older adults [14], and with the highest cost per capita, both for the index hospitalization and also costs during the year following the index hospitalization [15]. Indeed, resource consumption, such as home care, physiotherapy, and rehabilitation, are higher among older adults compared to other age groups [15]. It is worth noting that patient management and follow-up are expected to be worse in low- and middle-income countries, where resources are limited. A greater loss of autonomy after the index hospitalization is also observed among older adults, who have the longest duration of index hospitalization (mean: 14.8 days) versus 10 days for patients under 25 years of age [14]. This loss of autonomy and prolonged hospitalization are an additional cause of high burden for society [16].

IMD is most commonly seen clinically as meningitis, with the classic triad of fever, headache, and neck stiffness, or as bacteremic sepsis, with petechial or purpuric rash, lower limb pain, cold extremities, and with fulminant sepsis in severe cases; meningitis and septicemia can occur together [17]. These are the most frequent clinical forms, especially among children and younger adults [18]. However, other IMD presentations are well described, and are more frequently observed among older adults [18–20]. Notably, this includes meningococcal pneumonia [21–24]. Less common non-meningeal presentations of IMD include gastrointestinal symptoms and septic arthritis and bacteremia-associated epiglottis in older adults [18, 25–28]. In addition, non-invasive meningococcal infections can present in diverse forms, such as urethritis, conjunctivitis, and otitis media [29–31]. This is well illustrated by data on presentation patterns of IMD in France from 2017 to 2023, where almost 25% of all confirmed IMD cases in adults aged ≥ 65 years showed such atypical clinical presentations, with 15.8% being meningococcal pneumonia (Fig. 1) [11, 32]. Here, we should clarify that all these cases, including pneumonia, were reported as IMD cases, biologically confirmed by N. meningitidis detection through culture and/or PCR in sterile sites (blood, CSF, joint fluid, or pericardial fluid) [11, 32]. Data for the full range of typical and atypical meningococcal presentations in older adults from other regions are limited. Note that, while the focus of the present article is on older adults, as illustrated in Fig. 1, atypical presentations are seen in all age groups. Such presentations are often overlooked. For example, in a previous series of 105 cases of predominantly younger adults with early abdominal manifestations in France, 20 patients (20%) were initially misdiagnosed with appendicitis and underwent abdominal surgery [27]. Atypical forms are more frequently associated with meningococcal serogroups Y and W [20, 21, 25, 26, 33, 34]. In addition, non-meningeal presentations are associated with high mortality; in France, for meningococcal pneumonia cases reported between 2015 and 2022, the early mortality rate (within 72 h) was 13.5% [32].

Fig. 1.

IMD cases according to age and clinical forms (France, 2017–2023). Data represent principal clinical presentation of confirmed IMD cases reported to Santé Publique France and characterized at the National Reference Centre for meningococci and Haemophilus influenzae, France [11, 32]. IMD invasive meningococcal disease

One important observation is that the relative frequency of these non-meningeal forms in older adults seems to have increased following the rebound in IMD cases observed in recent years, after easing of non-pharmaceutical measures, including social distancing, introduced to limit the impact of the COVID-19 pandemic [32, 35]. This greater frequency of the non-meningeal forms may be linked to changes in the upper respiratory microbiota that have occurred with the spread of SARS-CoV-2 [36], and a post-pandemic rebound in respiratory viral epidemics (e.g., influenza), which may influence the clinical development of respiratory meningococcal disease such as meningococcal pneumonia and meningococcal epiglottitis [37].

Establishing the diagnosis and clinical management of meningococcal disease among older adults can be challenging, due to both the higher proportion of cases with atypical, non-meningeal forms [32], and, despite data to the contrary, a general under-recognition of IMD as an important disease in this age group [9]. These aspects contribute to potential underreporting of IMD and treatment delay in the older adult population. The aim of this paper is to provide additional context and specific guidance points to clinicians (and indeed all healthcare workers) to also consider atypical non-meningeal presentations of N. meningitidis disease, and in particular meningococcal pneumonia among older adults. In turn, this may help improve patient outcomes as well as strengthening broader disease surveillance and reporting of atypical, non-meningeal IMD. This review is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Risk Factors for IMD

Given the wide range of possible etiologies, it is important to inquire the patient’s past medical and social history. Learning the well-recognized risk factors for IMD can also lead to high suspicion of meningococcal infection. Firstly, older age is a risk factor for IMD, regardless of other underlying comorbidities, as the incidence of IMD increases in adults from 60 years and peaks from 75 years and older, and so, while often overlooked, as previously highlighted, a higher index of suspicion for IMD should be considered in older adults [9].

In adults of all ages, congenital and acquired immunodeficiency such as complement deficiency or use of complement inhibitors (e.g., eculizumab and ravulizumab), asplenia (functional including sickle cell anemia or anatomical), and hematopoietic stem cell and solid organ transplantation all confer increased risk [38–42]. Risk is substantially elevated in people living with HIV [43, 44]. Greater risk also exists in men who have sex with men (MSM) [45], with numerous outbreaks and disease clusters reported [29, 30]. Chronic respiratory conditions and other medical comorbidity also have greater IMD risk [40, 46]. Social factors play an important role. Living within shared residential accommodation (as is well known for young adults in college dormitories) or residential care (for older adults) represents an increased risk [47, 48]. For example, clustered outbreaks are well-recognized amongst students on college campuses [49], and have been reported in older patients in nursing home and hospital settings [50, 51]. Outbreaks and case clusters are also seen during or following attendance at large-scale events, notably in the past, but also more recent Umrah gatherings in Saudi Arabia [52–55]. In addition, greater risk has been associated with socioeconomic deprivation [40, 56]. However, it should be accepted that, while IMD can be linked to risk factors such as people with HIV infection and MSM [43, 57], the great majority of IMD cases in adults occur in individuals without these specific risk factors [40, 58].

Current Diagnostic Paradigm for IMD

Laboratory diagnosis of IMD follows established principles [59]. In Europe, clinical criteria from the European Centre for Disease Prevention and Control (ECDC) include at least one of the following at presentation: meningeal signs, hemorrhagic rash, septic shock, or septic arthritis [60], which indicate a possible IMD case, although such features may not be apparent in atypical cases. This said, the presence of a non-blanching hemorrhagic rash (purpura fulminans) is generally distinctive for and indicative of IMD and should prompt immediate empiric antibiotic treatment [59]. Laboratory confirmation of IMD requires N. meningitidis detection by culture, polymerase chain reaction (PCR), or antigen detection in samples from normally sterile sites, chiefly cerebrospinal fluid (CSF) and/or blood. ECDC criteria require laboratory confirmation via at least one of the following: isolation of N. meningitidis from a normally sterile site or purpuric skin lesions; detection of N. meningitidis DNA from a normally sterile site or purpuric skin lesions; detection of N. meningitidis antigen in CSF; or detection of Gram-negative stained diplococci in CSF [59, 60]. While these are readily understood for most typical IMD cases, i.e., with meningeal and overt meningococcemia presentations, meningeal signs may be absent in atypical presentations, so lumbar puncture for CSF analysis is rarely performed in atypical IMD. Similarly, purpuric skin lesions may be absent in meningococcal pneumonia [22, 23]. Early blood sampling is crucial to establish or rule out meningococcal bacteremia. Moreover, other diagnostic sampling should be performed in accordance with the clinical presentation, regardless of any early empiric antibiotic treatment [61]. As discussed below, the use of PCR can establish timely diagnosis (Table 1).

Table 1.

Characteristics of microbiological diagnosis methods

Method	Timeframe	Identification	Serotyping	Characterization
Culture	> 24 h	Yes	Yes (agglutination)	Antibiogram
MaldiToF	> 24 h	Yes	No	No
PCR	2–3 h	Yes	Yes (serotype-specific PCR)	Yes (amplification of gene of interest)
WGS	Several days	Yes	Yes (schemes to predict serotypes)	Full characterization and relationships between isolates

MaldiToF matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, PCR polymerase chain reaction, WGS whole genome sequencing

Meningococcal Pneumonia

In most cases, meningococcal pneumonia presentation is similar to that of other forms of community-acquired pneumonia (CAP) [22, 23]. As indicated earlier, for CAP presenting in older adults we would argue that greater consideration be given to N. meningitidis as a potential etiology in older adults. Our suggested approach to diagnosis and treatment is summarized in Fig. 2.

Fig. 2.

Suggested approach to diagnosis and management of meningococcal pneumonia. *Local protocols for meningococcal infection should be followed. When IMD is suspected, empiric treatment is usually initiated immediately – pending AST results – most often with third-generation cephalosporins, as per existing guidance [91, 92]. Our recommendations reflect this guidance. AST antimicrobial susceptibility testing, CT computed tomography, PCR polymerase chain reaction

Cardinal features of meningococcal pneumonia are similar to that of other forms of CAP: acute symptoms of lower respiratory tract infection, typically cough, and at least one of the following symptoms; fever, sputum, dyspnea, wheezing, or pleuritic chest pain [62]. Radiological findings are also indistinct from other CAP etiologies. Chest X-ray (postero-anterior, and, if possible, lateral) may show a wide range of findings such as interstitial, segmental or lobar consolidations, lung cavitation, lymphadenopathy, and pleural effusion [63]. In addition, older adults may have underlying comorbidities (chronic respiratory or cardiac disease) that may interfere with the interpretation of radiological findings. As with any respiratory imaging, findings should be interpreted in the context of how symptomatic the patient is. Computed tomography (CT) can also be useful when chest X-ray may be difficult to interpret and in patients unable to stand upright for lateral chest x-ray. Chest X-Ray and CT are superior to ultrasound. Ultrasound of the lung may reveal pleural effusions that may accompany pneumonia, although infiltration may be detected by ultrasound chiefly when located in the superficial parts of the chest. Echocardiography may reveal pericardial effusion.

Confirmation of Meningococcal Pneumonia

The conventional etiological diagnosis of CAP includes a variety of bacterial and viral agents such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila, and influenza, SARS-COV-2, and respiratory syncytial virus infection. We would suggest that, for all older adults, N. meningitidis should be added to this list of potential pathogens, and inclusion of this within conventional respiratory diagnostic panels be considered. It should also be noted that early diagnosis of SARS-COV2 infection cannot discount any concomitant meningococcal pneumonia, as co-infections have been reported [64–67].

For meningococcal pneumonia, detection of N. meningitidis in blood by culture and/or by PCR on ethylenediaminetetraacetic acid (EDTA)-blood samples should be considered. Blood cultures are a critical tool for diagnosis of any atypical IMD presentation in older adults. To this point, we believe it is crucial that blood culture sampling is included as standard in algorithms for the diagnosis and management of CAP in older adults. Although blood cultures are not routinely recommended in current American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) guidelines for CAP, where their use is recommended only in specific circumstances; e.g., severe pneumonia, or if requiring intensive care admission, or with suspected or recent history of infections with multidrug-resistant organisms [68]. This restricted diagnostic approach has been criticized [69]. Greater use of blood cultures is advocated in other established guidance, e.g., from Germany and the United Kingdom [70, 71].

When meningococcal pneumonia is suspected, laboratory confirmation of N. meningitidis can be made via culture, PCR, or antigen detection on blood and respiratory samples. While including meningococcal infection within the diagnostic approach to CAP in older adults has cost and clinical/laboratory resource use implications, we consider that the high mortality of meningococcal disease, in part related to diagnostic delays [8, 32], would warrant timely diagnosis. Delayed diagnosis of IMD in older adults, often owing to atypical clinical presentations, is linked to substantially higher mortality. In France, bacteremic meningococcal pneumonia increased among older adults following the relaxation of COVID-19 non-pharmaceutical interventions, with this presentation associated with a markedly higher early mortality rate of 13.5% [32]. Atypical or non-specific symptoms in this age group contribute significantly to diagnostic delays and adverse outcomes [8].

If confirmed, samples and isolates can then be sent to suitable reference laboratory for further typing and characterizations. Indeed, we would wish to emphasize here the crucial value of both local microbial laboratory services and regional/national specialist reference centers which underpin clinical care, and, of equal importance, their role in disease surveillance which can transform infectious disease policy. Continued financial support to maintain and expand upon the existing infrastructure to improve such services is critical to face the challenge of combating infectious disease [72].

Blood sampling is key; if not possible or available, respiratory samples (sputum, bronchial aspiration and bronchoalveolar lavages) can be used [73]. Such samples are also useful for culture, and for microscopy, where the presence of Gram-negative diplococci, although not always diagnostic per se, should prompt suspicion of N. meningitidis disease, and can guide appropriate empiric antibiotic therapy. However, interpretation should be correlated with clinical presentation as upper respiratory tract colonization has to be considered [73]. Indeed, asymptomatic N. meningitidis nasopharyngeal carriage is frequent in the general population, including older adults, where the carriage rate is approximately 7% among those aged 50 years and older [74], while attending mass gatherings also increases the risk of carriage acquisition [75]. When blood culture or blood-based PCR is unavailable, or when results are negative, the diagnosis of meningococcal pneumonia as IMD should rely on respiratory samples, provided that the following strict criteria are applied. In addition to the clinical and radiological findings consistent with CAP, as outlined above, a number of microbiological criteria in respiratory samples can be used to ensure a pathologic role of N. meningitidis versus a carriage isolate (1) bacterial concentration should exceed a threshold (10⁶ cfu/mL) in protected respiratory specimens such as bronchoalveolar lavage and endotracheal aspiration, where several studies have established this threshold to distinguish colonization from infection [76–78]; (2) a predominance of N. meningitidis in the sample; and (3) the presence of capsulated meningococcal isolates (as carriage isolates are frequently unencapsulated) [79]. PCR enables the timely determination of isolate capsulation, providing results within 2–3 h (Table 1). Metagenomic approaches may be employed for diagnostic purposes on respiratory samples, albeit with longer turnaround times compared to targeted PCR.

While many laboratories routinely use phenotypic methods such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, this may misidentify other commensal Neisseria species (e.g., N. polysaccharea and N. bergeri that also colonize the nasopharynx) as N. meningitidis [80]. As such, species identification should be confirmed by genotypic methods, ideally with whole genome sequencing (WGS) where available, usually within regional/national specialist reference centers using available tools on the PUBMLST database (https://pubmlst.org/). WGS also allows more extensive characterization of respiratory N. meningitidis isolates which can provide valuable information on the genotypes associated with meningococcal pneumonia and their relationship with those associated with the more usual IMD forms (i.e., meningitis and septicemia). As indicated above, N. meningiditis isolates from pneumonia cases are reported to be more frequently serogroups Y and W. Such isolates are often associated with specific genetic lineages and clonal complexes (cc). In France, where there has been an increase in IMD cases due to serogroups W and Y in the most recent years following the COVID-19 pandemic, genetic patterns are shifting [32, 35]. While serogroup W isolates group mainly within two lineages (W cc11 and W cc9316), serogroup Y isolates show greater heterogeneity, falling within a larger number of genetic lineages [32, 35].

Management of Meningococcal Pneumonia

Microbiological data on pathogens in CAP cases are limited, and indeed in most cases no specific pathogen is detected [81]. Such data are necessary for appropriate antibiotic use, and to avoid unnecessary use of extended-spectrum antibiotics in empirical treatment to limit antimicrobial resistance. In meningococcal pneumonia, determining antimicrobial susceptibility of N. meningitidis isolates is critical, in particular in light of the emergence of antimicrobial resistance in isolates from IMD cases or asymptomatic carriers [2, 82, 83]. Historically, beta-lactams have been the mainstay of treatment for IMD [22, 23, 84]. However, reduced susceptibility to penicillins and overt penicillin-resistant strains are now evident in the Americas, Europe, and Asia [84–88]. Reduced susceptibility to beta-lactam antibiotics, associated with modifications in the penicillin-binding protein 2, is reported in as much as 50% of N. meningitidis isolates in several European countries [84, 87]. Non-susceptibility to amoxicillin has been reported in invasive isolates of all serogroups, varying from 25% to 60% [84, 87]. This makes the first choice of amoxicillin or amoxicillin/clavulanic acid inappropriate for meningococcal pneumonia, where third-generation cephalosporins, e.g., cefotaxime are generally preferred [22, 23]. Moreover, alerts on meningococcal resistance to ciprofloxacin, and dual penicillin–ciprofloxacin-resistant strains are also increasingly reported [75, 85, 89, 90]. Such resistance is associated with most important serogroups (principally B, C, W, and Y) and has been observed in isolates from atypical IMD cases [90]. Ciprofloxacin resistance has also been observed in a high proportion of nasopharyngeal carriage isolates in some populations, including individuals attending the Hajj pilgrimage [75], and also within serogroup W isolates from recently reported IMD cases in the United States, France, and the United Kingdom in individuals returning from Umrah-associated pilgrimage in Saudi Arabia [55]. Note, however, that, while reports of isolates with reduced susceptibility or resistance are increasingly common, N. meningitidis generally remains susceptible to the antibiotics currently used for treatment and prophylaxis. Our aim in highlighting the above patterns is to emphasize the importance of antimicrobial susceptibility testing (AST) in detection and characterization of antimicrobial resistance.

Ultimately, treatment is governed by microbial testing and local recommended protocols. In the United States, current guidance from the CDC recommends that empirical therapy for suspected meningococcal disease should include an extended-spectrum cephalosporin, e.g., cefotaxime or ceftriaxone [91]. Similar guidance from the ECDC remains in place in Europe [92]. Treatment is usually initiated immediately, pending AST results. Then, once diagnosis is confirmed and AST results are available, definitive treatment can either be continued with this approach, or alternatively, if susceptibility to penicillin is confirmed, treatment can be switched to penicillin G or ampicillin [91]. Use of corticosteroids is not routinely recommended in CAP [68, 69], and data are limited for any benefit in meningococcal pneumonia, with no recommendations in place [22, 23].

An important contrast to other CAP etiologies is that, as for any IMD case, the need is to provide chemoprophylaxis for all household members (of any age) and other close contacts of patients with meningococcal pneumonia, regardless of their meningococcal vaccination status [91–93]. Local chemoprophylaxis protocols should be followed. In the United States, ciprofloxacin is preferred but rifampin, ceftriaxone, or azithromycin can each be used as an alternative, for example, when ciprofloxacin-resistant disease is evident in the local setting [94]. Similar recommendations are in place in Europe [92]. We should note that concerns exist about adverse effects of fluoroquinolones such as ciprofloxacin in select patient populations, including individuals at risk of aortic aneurysm and those with diabetes [95]. Nevertheless, ciprofloxacin remains a preferred option [94].

In addition to chemoprophylaxis, vaccination of close contacts should be considered, although policies and decision-making on this can vary. In Europe, the ECDC recommends vaccination against the serogroup associated with the IMD case when the index case is due to serogroups A, C, W, or Y (e.g., utilizing a quadrivalent conjugate MenACWY vaccine) [92]. In the United States, vaccination of close contacts of isolated sporadic IMD cases is not routinely recommended, where specific thresholds for outbreak case numbers apply [96]. However, such guidance continues to evolve. The role of vaccination in older patients following recovery from meningococcal pneumonia remains to be determined.

Other Unusual Non-Meningeal Forms of IMD in Older Adults

While our focus has been upon meningococcal pneumonia, other less common forms of IMD confirmed by N. meningiditis detection from other sterile sites, such as synovial joint or pericardial fluid aspirates, are well recognized. The latest data from the ECDC indicate that in Europe the overall frequency of these forms was 7% in 2021 and 9% in 2022 [97, 98]. Some, such as epiglottitis, are repeatedly reported in older adults, typically associated with the W and Y serogroups [25, 26, 99–102]. In France, an increase in epiglottitis cases was observed to increase after easing of the COVID-19 pandemic, with 8 adult cases (age range 52–86 years) which represents 1.7% of all IMD cases reported between October 2022 and June 2023 [28]. Blood cultures indicate that, except for two cases with Y cc23 strains, most isolates belonged to a hyperinvasive serogroup W lineage (W cc11), recognized to induce a strong pro-inflammatory response [28, 103]. Similar serogroup W and Y isolates have also been reported in adult meningococcal epiglottitis cases in the United States and the United Kingdom [99], and, for serogroup W, in Sweden [25]. The pathogenesis of epiglottitis is usually associated with mucosal epithelial and endothelial damage, with an edematous local inflammatory response of the epiglottis and adjacent supraglottic tissues [104]. In meningococcal cases, epithelial penetration by hyperinvasive N. meningiditis isolates and subsequent passage across the underlying vasculature is entirely in agreement with this pathophysiology [105].

Meningococcal pericarditis is uncommon, although long recognized as an important form of IMD [21]. Cases can be considered as primary meningococcal pericarditis, diagnosed chiefly through pericardial fluid or blood culture, without signs of meningococcemia or meningitis, or where pericarditis reflects part of a broader picture of disseminated meningococcal disease [106–109]. Primary meningococcal ventriculitis, presenting without any neck stiffness nor other symptoms of meningism, has also been described in adults as a rare complication of meningococcal meningitis [110, 111]. Diagnosis is challenging, requiring optimal medical imaging such as magnetic resonance imaging demonstrating pertinent diagnostic abnormalities: intraventricular debris, periventricular hyperintensities, and dilatation of the lateral ventricles [111].

As seen for pneumonia, the management of these other non-meningeal forms is also challenging. The same principles of diagnostic and treatment approach as outlined for pneumonia also apply: confirmation of N. meningitidis in diagnostic samples (e.g., synovial aspirates) [112], with appropriate serogroup identification and characterization, and antimicrobial susceptibility testing. In addition to empiric and then targeted antibiotic therapy, and in contrast to meningococcal pneumonia, corticosteroids should be used concomitantly with antimicrobial therapy, to reduce the underlying inflammatory response evident in these non-pulmonary atypical forms [99, 101]. Moreover, the duration of the antibiotic therapy may be longer than usual IMD regimens (e.g., in meningococcal ventriculitis), lasting up to 6–12 weeks [111]. In one recent case of meningococcal ventriculitis, switching from intravenous third-generation cephalosporins given for 2 weeks to an oral fluoroquinolone for a further 2 weeks was successfully used for a faster regain of functional autonomy, so important in the broader care of older adult patients [111].

Chemoprophylaxis of close contacts of patients with other non-meningeal IMD forms is also recommended, following the guidance described above [31].

Conclusions

The overall burden of IMD in older adults is likely underestimated, in part due to a higher proportion of non-meningeal forms which may be unrecognized or not considered in the initial assessment. This is highly relevant, as it is apparent that IMD cases, and these atypical forms, are increasing in prevalence in the post-COVID-19 pandemic era, with a high medical and socioeconomic burden (mortality, sequelae, loss of autonomy, and cost). Additionally, epidemiologic changes in circulating meningococcal isolates, with a large proportion of cases due to serogroups W and Y [32, 35], contribute to the pathogenesis of these non-meningeal forms. The diagnosis of IMD in older adults is challenging and requires systematic testing of blood samples, by culture and PCR, as well as other samples according to the clinical presentations. Criteria for ascertainment are needed when N. meningitidis is detected in non-sterile sites (such as respiratory samples). It is critical that meningococcal infection remains an important differential diagnosis when considering the presentation of clinical diseases in older adults. Earlier consideration of N. meningitidis as a potential infective etiology, and inclusion of laboratory evaluations within diagnostic protocols, can improve timely diagnosis and intervention, leading to improved clinical outcomes, as well as help inform meningococcal disease surveillance activities and reduce underreporting. To this point, greater awareness of such IMD forms among all healthcare professionals is required. The management of IMD cases among older adults requires specific antibiotic treatment and prophylaxis. Ultimately, protection of older adults through vaccination can help reduce IMD, including atypical presentations. At present, there remains an unmet need of adequate vaccination coverage within existing routine vaccination recommendations for healthy older adults [5, 9]. Specific broadening of existing vaccination policy (beyond boosters/extension in place within the childhood/adolescent calendar) is also warranted.

Author Contributions

Muhamed-Kheir Taha, Catherine Weil-Olivier, Sean Leng, Ener Cagri Dinleyici, and Saber Yezli each participated in the workshop discussions that formed the basis of conceptualization and implementation of this review. Muhamed-Kheir Taha prepared the original draft. All authors reviewed and provided comments on subsequent drafts, and approved the final version for submission.

Funding

The logistics for the EWG meetings and subsequent activities associated with developing this manuscript were supported by Sanofi. Sanofi funded this report and all costs related to the development and publication of this manuscript, including the journal’s Rapid Service Fee.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Muhamed-Kheir Taha conducts work contracts funded by GSK, Pfizer, and Sanofi for the Institut Pasteur, Paris. He also reports the patent NZ630133A “Vaccines for serogroup X meningococcus” issued with GSK. Catherine Weil-Olivier declares receiving fees, travel grants, and honoraria from Sanofi for attending scientific meetings and presentations on this topic. Sean Leng declares participation in Sanofi’s International Advisory Board on SARS-CoV-2 vaccine development and engaged in speaking for GSK on Shingrix vaccine. Ener Cagri Dinleyici declares performing contract work (advisory board member, speaker and grant) for Eskisehir Osmangazi University, funded by GSK, Pfizer, MSD, and Sanofi Pasteur. Saber Yezli declares receiving consultation fees, travel grants, and honoraria from Sanofi for attending scientific meetings and presentations.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.