Life After Invasive Meningococcal Disease: Insights from Survivors and Their Caregivers

Abstract

Introduction

Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness that is preventable via vaccination. Even with treatment, up to 10–15% of cases are fatal, and many survivors may experience severe long-term sequelae. Building upon the acute-phase findings presented in the Part 1 manuscript for this study, we describe the long-term physical, social, psychological, and economic burden of IMD on US survivors and their caregivers in this Part 2 manuscript.

Methods

This was a novel, non-interventional, mixed-methods study among US survivors and their caregivers using a bespoke survey and qualitative interviews.

Results

Ten adult survivors, one adolescent survivor, and three caregivers participated in this study. Survivors described extensive physical, neurological, and systemic sequelae, including difficulty walking (11/11), repeat secondary infections (9/11), and numbness (6/11), among others, which were echoed by caregivers. Survivors shared that IMD had negatively impacted their long-term quality of life, citing long-term impacts including emotional impacts (11/11), social impacts (10/11), memory (7/11) and attention (5/11) problems, and difficulty with functional (10/11), self-care (7/11), and physical (6/11) activities. Caregivers were also impacted, describing emotional trauma (3/3), sleep problems (2/3), and day-to-day challenges (2/3).

Long-term financial challenges related to healthcare resource utilization were substantial, with specialized care and rehabilitation therapy expenses (11/11), insurance challenges (8/11), and high out-of-pocket costs (6/11) for survivors. Productivity losses were also commonly described by survivors (9/11); sequelae hindered ability to attend school (9/11) or work full time (8/11). Caregivers (2/3) described taking leave from their employment, affecting family income.

Conclusions

The humanistic burden of IMD on survivors and their caregivers is substantial and persistent. A comprehensive approach, including preventative measures (e.g., vaccination) and long-term medical, psychological, and financial support for those affected, is needed to mitigate the burden of IMD.

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Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-024-01060-8.

Plain Language Summary

Invasive meningococcal disease (IMD) is an uncommon but life-threatening disease that can lead to serious long-term health problems and impacts on quality of life. We conducted this study to understand the experiences of survivors of IMD and their caregivers in the USA. In a previous paper, we described the experiences of 11 survivors and 3 caregivers during the time of IMD infection and initial recovery (the “short-term”) [1]. Here, we continue to follow the journeys of those survivors and caregivers, and explore the health complications and impacts of IMD that persist long after initial recovery.

Survivors experienced long-term physical, neurological, and systemic health problems due to IMD, such as difficulty walking, repeat infections, and numbness. Many shared that their quality of life had been negatively affected by IMD, describing memory and attention problems, social challenges, emotional trauma, and difficulty with daily activities. Caregivers were also impacted, experiencing sleep problems, distress, and day-to-day challenges. Even with insurance, specialized medical care and therapies were expensive and led to long-term financial challenges. Many survivors also found it difficult to attend school or work full-time because of their health limitations. Caregivers’ ability to work was also limited because of caregiving needs, affecting ability to earn income.

IMD places a heavy, long-term burden on survivors and their caregivers, and understanding the lived experiences of those affected is crucial. In addition to prevention (such as through vaccination), comprehensive, long-term medical, psychological, and financial support is needed to reduce the burden of this disease.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-024-01060-8.

Key Summary Points

Invasive meningococcal disease (IMD) is an uncommon, life-threatening illness that can have severe long-term consequences.

Following the acute-phase findings presented in a separate manuscript, this manuscript describes the long-term humanistic burden of IMD on survivors and their caregivers.

Survivors and their caregivers described severe long-term sequelae and impacts on their physical, social, emotional, functional, and economic quality of life.

Mitigating the substantial humanistic burden of IMD requires both prevention and a comprehensive approach to providing long-term medical, psychological, and financial support for those affected.

The experiences of survivors and caregivers described in this study can also be used to guide future research on the humanistic burden of IMD in the USA.

Digital Features

This article is published with digital features, including a video abstract, to facilitate understanding of the article. To view digital features for this article, go to 10.6084/m9.figshare.27118980.

Introduction

Invasive meningococcal disease (IMD) is a severe condition that often leads to life-threatening outcomes [2]. While the acute phase of IMD often involves debilitating symptoms, and death in up to 10–15% of cases (even with timely and appropriate treatment) [3, 4], consequences for survivors can persist long beyond hospitalization and recovery [5].

While vaccination against IMD is available in the USA and recommended for adolescents, young adults, and high-risk individuals [6, 7], coverage remains suboptimal, with only 59.7% and 32.4% of 17-year-olds having received the meningococcal serogroups A, C, W, and Y (MenACWY) booster dose and ≥ 1 dose of the meningococcal serogroup B (MenB) vaccine, respectively, as of 2023 [8].

IMD sequelae present a considerable and multidimensional long-term burden [9, 10]. Up to 40% of IMD survivors may experience severe, long-term sequelae such as amputations, hearing and vision loss, and organ failure [9, 11, 12]. Previous quantitative research has suggested that these complications often precipitate psychological effects such as anxiety and post-traumatic stress disorder (PTSD), learning difficulties, and emotional and behavioral difficulties [11]. Despite its low incidence, IMD also incurs significant direct and indirect costs and healthcare resource utilization (HCRU) [9, 13].

Particularly in the USA, existing evidence regarding the burden of IMD among survivors remains limited and outdated, and even more so among caregivers [11, 14]. Most importantly, there is a notable lack of qualitative investigations into the humanistic burden [15], emotional needs, socioeconomic implications, and financial repercussions of IMD on survivors and their caregivers. To address this gap in the literature and to provide an improved understanding of the impacts associated with IMD, we conducted a novel, mixed-methods study. Participants in the study were recruited with the assistance of patient advocacy groups (PAGs), including the National Meningitis Association (active from 2002–2022), the American Society for Meningitis Prevention (formerly the Meningitis B [MenB] Action Project), the Emily Stillman Foundation, and the Kimberly Coffey Foundation [16].

Part 1 of this study examined the experiences of survivors and caregivers during the acute phase of IMD (i.e., the period of infection and initial recovery) [1]. This article builds upon these findings with the results of Part 2, following the journeys of survivors and their caregivers into the long-term phase of IMD (following initial recovery and onwards). The primary objective was to describe the long-term sequelae and physical, psychological, and financial consequences associated with IMD for both survivors and their caregivers in the USA.

Methods

Study Design

This was a cross-sectional, non-interventional, mixed-methods, anonymized study among IMD survivors (i.e., individuals who have contracted and survived IMD, also referred to as “survivors” throughout this study) and their caregivers in the USA. Participants were recruited with the assistance of PAGs [16], and data were collected via a bespoke pre-interview survey (PIS) and qualitative interviews, which were developed and delivered to ensure IMD specificity [1]. Institutional review board approval for this study was sought and obtained from the USA-based Western-Copernicus Group (WCG) IRB; full ethical considerations are provided in the Ethics section.

Study Population and Setting

The study eligibility criteria were previously described in the Part 1 manuscript [1]. Included survivors were either adults (≥ 18 years old) or adolescents (11–17 years old) who have had a confirmed IMD episode at any point in their lifetime; confirmation of diagnosis was obtained for eligible, consenting survivors through provision of either a clinician-completed confirmation of diagnosis form or relevant medical record/screenshots. Caregivers were included if they were the parents/legal guardians (or other individual) who had or were taking care of an IMD survivor at the time of the study.

Sources and Data Collection

USA-based survivors and caregivers were recruited with the assistance of PAGs from February 2023 to June 2023 and screened for eligibility.

Following screening and confirmation of diagnosis, a bespoke online PIS was administered to explore the sequelae and long-term impacts of IMD, followed by qualitative, web-based telephonic interviews using a bespoke standardized interview discussion guide (DG). Questions in the PIS and DGs explored the survivor and/or caregiver experiences of IMD within the context of a preliminary conceptual model of IMD, which was developed on the basis of a previous targeted literature review [17]. Study instrument development, participant screening, and data collection methodology were previously described in the Part 1 manuscript [1].

Supplementary Appendix A contains the complete list of interview quotes analyzed in this study that are relevant to the long-term phase results presented in this manuscript.

Data Analysis

Quantitative analysis in this study included descriptive reporting of demographic and clinical information. For the qualitative analyses, a combined deductive and inductive approach was used to identify sequelae and impacts described by survivors and their caregivers (separately) during their interviews. The number of participants who mentioned sequelae and long-term impacts were tabulated, and concept saturation of long-term IMD impacts reported by survivors was evaluated. Full data analysis methodology for this study was previously described in the Part 1 manuscript [1].

Ethical Approval

This study was conducted in accordance with the study protocol, the Guidelines for Good Pharmacoepidemiology Practices published by the International Society of Pharmacoepidemiology, the ethical principles of the Declaration of Helsinki, and IRB requirements. IRB approval was sought and obtained from the USA-based WCG IRB. Participants and the study sponsor were blinded from each other (i.e., participants were not aware of the study sponsor and only directly interacted with the investigators, and the study sponsor was not aware of any participant-identifying information at any point during study conduct). All participants ≥ 18 years old provided informed consent prior to their participation in the research study; participants < 18 years old provided assent, in addition to consent from their caregiver/legal guardian.

Results

Participant Characteristics

A total of 11 survivors (10 adults, 1 adolescent) and 3 caregivers were included in the study. The average age of survivors was 36 years (median 37 years), while the average age of caregivers was 58 years (median 63 years). Among the 11 survivors, 2 were infants, 3 were children, and 6 were adults when they contracted the disease. All survivors had been diagnosed with IMD more than 12 months before participating in the study. Seven survivors had commercial health insurance, 2 had Medicare, and 1 each had Medicaid and Medishare.

All three caregivers were mothers of survivors; two caregivers provided care to adult survivors, while one provided care to an adolescent survivor. Full survivor and caregiver demographic characteristics are described in the Part 1 manuscript [1].

Sequelae Post-IMD Recovery

Survivors and their caregivers described the long-term sequelae, or complications/conditions resulting from IMD, in the PIS and interviews. These included physical, neurological, and systemic sequelae, and are listed quantitatively (and categorized by “spontaneous” or “probed”) in Supplementary Table 1. Changes in sequelae over time (e.g., worsened or improved since the acute phase) were also reported by survivors (Supplementary Table 2). Concept saturation of IMD sequelae was not evaluated because of dissimilarity of survivor reports.

Physical Sequelae

Survivors described the physical sequelae they experienced as a result of IMD; selected quotes from survivor interviews are presented in Fig. 1a. All survivors (11/11) spontaneously mentioned difficulty walking, and many reported balance issues (10/11), long-term fatigue and exhaustion (9/11), difficulty standing (7/11), scarring (7/11), reconstructive surgeries (e.g., skin grafts; 7/11), repeat sores and/or skin infection (7/11), and amputations (6/11). Of the 7 survivors reporting scarring, 6 experienced extensive scarring in various parts of their bodies, especially on the face, stomach, arms, and legs. Survivors who had undergone amputations detailed the extensive associated surgeries, physical therapy, and ongoing medical challenges associated with limb growth following amputation. Survivors also experienced mobility limitations caused by their condition, amputations, and prosthetics, affecting balance and activities such as running and jumping. Other physical sequelae reported by survivors included bone issues (5/11), muscle weakness (3/11), other surgeries (3/11), teeth issues (2/11), neck problems (2/11), difficulty sitting (2/11), and stunted growth (1/11).

Fig. 1.

Reported sequelae post-IMD recovery. a Physical sequelae^a. b Neurological sequelae^a. c Systemic sequelae^b. ^aSequelae most frequently reported by survivors and their caregivers. ^bWhile systemic sequelae related to liver and heart problems were spontaneously reported by survivors in their interviews, these occurred as a result of organ failures at the time of IMD infection (i.e., during the acute phase rather than the long-term phase). Full quantitative results on the IMD sequelae reported by survivors and their caregivers are listed in Supplementary Table 1. COVID coronavirus disease, ICU intensive care unit, IMD invasive meningococcal disease, PICC peripherally inserted central catheter

Neurological Sequelae

Survivors also experienced neurological sequelae (consequences associated with nerve damage, e.g., cognitive, sensory, and motor deficits) due to IMD (Fig. 1b). Numbness (loss of feeling; 6/11), sensitivity to light (4/11), confusion (4/11), and nerve-related pain (3/11) were frequently reported by the 11 participating survivors. During the interviews, survivors reported sensory changes and nerve damage due to the IMD infection and surgeries, often describing altered or loss of sensation in their feet and legs, reduced ability to feel temperature extremes, and/or injuries. Others experienced reduced motor skills (2/11), hearing and vision loss (1/11 each), blackout seizures (1/11), brain fog due to IMD-related kidney loss (1/11), palsy/paralysis (1/11), and tingling (1/11).

Systemic Sequelae

Survivors’ experiences with systemic sequelae (health conditions/disorders affecting one or more organ systems) highlighted the long-term consequences of IMD on various organ systems (Fig. 1c). Most systemic sequelae were reported spontaneously by survivors. Many survivors (9/11) reported experiencing repeat secondary infections and feeling immunocompromised and “medically fragile”, attributing some chronic health issues to the long-term effects of IMD. Survivors also reported musculoskeletal (joint) pain (7/11), kidney issues (5/11), respiratory issues such as breathing difficulties resulting from nose reconstruction surgeries (3/11), and hormonal problems (1/11). Survivors also reported suffering from heart and liver problems (2/11 each) subsequent to organ failures during the time of infection (i.e., during the acute phase).

Long-Term Impacts of IMD

In the PIS, 19 of the 20 listed sequelae were reported to have at least a minor effect on survivors’ quality of life. Amputation appeared to have the greatest impact, reported as having a very severe effect on life by 4 of 11 survivors (Supplementary Table 3). When reporting areas of their lives that were impacted in the past month (at the time of the PIS) due to living with IMD sequelae, most survivors (10/11) reported being moderately to very impacted emotionally, and 7 reported that their normal daily activities were very to extremely impacted (Supplementary Table 4).

While caregivers (N = 3) did not report the same range of problems that survivors (N = 11) did, they were asked about the impacts of the IMD sequalae they did report. For example, caregivers reported that loss of sensation or feeling (3/3), muscle weakness (2/3), and problems maintaining balance (2/3) had a moderate effect on survivors’ lives. Meanwhile, one caregiver each reported that loss of limbs, skin problems, and problems with teeth and bone development had a very severe effect on survivors’ lives (Supplementary Table 5).

In the interviews, all survivors reported suffering from long-term impacts, many of which were diverse and extensive (Fig. 2, Supplementary Table 6). All survivors (N = 11) expressed the burden of care, treatment, and needing assistance. Many survivors (7/11) reported that their overall quality of life had been affected by IMD, describing differences compared to life pre-IMD and due to day-to-day burden of treatment, ongoing health concerns, and emotional impacts.

Fig. 2.

Long-term impacts of IMD on survivors’ and caregivers’ quality of life. Full quantitative results on the long-term impacts reported by survivors and their caregivers are listed in Supplementary Table 6. ADHD attention deficit hyperactivity disorder, IMD invasive meningococcal disease, PTSD post-traumatic stress disorder

The concept saturation of impacts reported by survivors is described in Supplementary Table 7. In total, 30 unique impacts were reported during the interviews. All impacts (100%) emerged during the first wave of interviews. No new impacts appeared during wave 2 and wave 3. These results indicate that concept saturation of impacts was reached within these 11 interviews.

Physical Impacts

The use of prosthetics and assistive devices was widespread (10/11), and headaches/migraines were reported by most survivors (7/11). Sleep disturbances, including nightmares due to PTSD, were reported by multiple survivors (6/11), affecting their sleep quality. These experiences were echoed by caregivers in their interviews, who reported that they also experienced sleep problems (2/3) and fatigue or exhaustion (1/3), describing being woken up by the memory of traumatic events that occurred during the period of infection. Many survivors (6/11) also mentioned the need for daytime naps or rest due to fatigue and cognitive strain. Falling incidences (4/11) also posed a significant risk for survivors and resulted in injuries among two survivors.

Cognitive Impacts

Cognitive difficulties were prevalent, affecting over half of the 11 participating survivors, and spanned memory problems such as recall difficulty and forgetfulness (7/11), attention problems/deficits (5/11), speech problems (3/11), learning difficulties (3/11), non-specified cognitive problems (3/11), and communication problems (2/11).

Emotional Impacts

All survivors (N = 11) reported long-term emotional impacts and described avenues of support from parents, friends, and family. Many survivors also discussed the support, or lack thereof, from healthcare providers (HCPs), which played a significant role in their struggle with the consequences of IMD. Most survivors (7/11) mentioned suffering from trauma/PTSD as a result of their hospitalization or near-death experiences; some (4/11) expressed gratitude that they survived at all. Many reported feelings of worry (9/11), fear (7/11), being different from others (7/11), and anxiety (6/11). Several described shame and embarrassment (5/11), often related to their condition or physical appearance, as well as frustration due to their amputations or scars (5/11). Feelings of loneliness and isolation (4/11) were also often reported, and survivors emphasized the emotional toll of not being able to engage in physical activities (such as playing or running during childhood), and dealing with the reactions of others (4/11). Caregivers themselves were also emotionally impacted over the long term, experiencing continued worry for their child’s health and PTSD from the acute phase (3/3). Table 1 highlights some of the coping mechanisms survivors reported using to manage their circumstances.

Table 1.

Coping mechanisms and community-building among survivors

Coping mechanisms	Survivor quotes
Mindset	So my perspective…wasn’t why me. I felt like, oh, thank God, I survived. At least I have an option. At least I have my life, even if it’s not the same life. It’s not as good. It just isn’t. It’s significantly diminished. But I’m still very much happy to be alive and cherish it It’s just about learning coping skills. I’m still trying to learn coping skills and things that help me calm down and get out of the funk. Because that just keeps me isolated, which is a big problem of mine
Community	Yes. Yeah, with time and talking to people and learning things about the world, I feel a lot less angry. I don’t ask myself ‘why me’ anymore. It’s more like ‘what can I do with this to help other people’. What can other people learn from this? That’s helps me not focus on the anger I talk to other folks that are similar to me, quadruple amputees and medically fragile. I think some folks struggle more than others. I think maybe something that helps is I was involved… the type of work, the non-profit, was homelessness that I was involved and still am involved in. So I feel like maybe my perspective was helped a little bit with that, because I saw people that suffered so horribly
Spirituality	As years pass, the anger subsides and I’m becoming more spiritual and things like that to help me get through it. But there’s still anger there
Physical activity	Yes. Well, I was mono-skiing for a while after I got sick. It’s adaptive skiing. I haven’t been able to do that. I’d love to get back to doing that because it’s the only sport I’ve ever done that makes me feel free and athletic and capable
Living with prostheses	I mean, I pretty much design my own prosthetics for my shoes, and I just move it from shoe to shoe to shoe, and then, so all my boots have a certain one in it. My Peloton shoe I have a special…like the Peloton bike that you clip into I have made my own shoe out of different…

Social Impacts

Survivors also described impacts on their social and romantic relationships, experiencing shifts in friendships and social patterns (10/11) and reporting uneasiness and needing to adapt within their social circles. Physical limitations and susceptibility to illness also affected survivors’ ability to engage in recreational (10/11) and social activities (9/11), or feel understood by others (4/11), leading to uncertainty and isolation. Overall, IMD also affected the family dynamic, especially if survivors’ needs changed significantly post-diagnosis, and levels of support and understanding survivors reported receiving from their families varied. Caregivers also reported social impacts in their own lives (2/3), including experiencing a lack of understanding from others and concerns about effects on the other children in their care.

Daily Activities

Many survivors reported impacts on their daily activities, often due to physical and cognitive limitations, from functional activities (10/11) and self-care/grooming (7/11) to physical/high-intensity activities (6/11). Dietary/eating restrictions were also a significant concern for some survivors (4/11). Survivors often described how simple tasks or activities they previously took for granted were now much more physically demanding, complex, exhausting, time-consuming, and painful (3/11), and also reported problems due to prostheses/catheters (3/11). Loss of sensory functions like hearing made tasks such as crossing streets more dangerous (1/11). Caregivers also described impacts on their daily activities (2/3), often due to management of care, and reported having difficulty finding someone to help care for their child so they could attend other activities, as well as needing to make adjustments in their home for improved accessibility.

Long-Term Economic and Financial Impacts

Overall, financial considerations remained a significant aspect of both survivors’ and caregivers’ lives post-IMD. Both cohorts highlighted ongoing general financial struggles, including managing expenses (current and future, especially regarding treatment), budgeting, saving, and dealing with limited incomes.

Work/Education (Productivity Loss)

Overall, IMD had significant repercussions on survivors’ and caregivers’ work and education. Productivity loss was a common theme (9/11), as survivors often found themselves unable to perform certain roles, reducing potential to earn more income. Most survivors reported missing workdays and reducing their working hours (9/11), and facing career limitations (8/11) due to the impacts of the disease (e.g., physical limitations, memory issues, and brain fog; Fig. 3). One caregiver, who reported having to quit her job, never regained her former employment status, in turn affecting family income.

Fig. 3.

Long-term financial impacts of IMD on survivors and caregivers. IMD invasive meningococcal disease, OOP out-of-pocket, OTC over-the-counter, W-2 Wage and Tax Statement

There were many reports of school impacts among survivors (6 out of the 6 survivors who were in school during and following IMD onset), such as missed study days, alterations in education hours, and effects on performance. Some survivors expressed aspirations to work more and achieve financial independence despite health constraints, describing the need for adaptive learning techniques and therapy to overcome academic and workforce-related anxiety.

HCRU and Long-Term Costs Associated with IMD

Frequent HCRU among participating survivors (N = 11) included visiting medical specialists (7/11) and undergoing related medical tests or procedures (6/11) in the past year, home care (4/11), and physical (11/11), psychological or psychiatric (9/11), and occupational (7/11) therapy (Supplementary Table 8). Rehabilitation services, including physical and occupational therapy, helped survivors regain functionality and independence in several cases.

Survivors and caregivers alike described the various medical expenses of managing their (or their child’s) IMD and sequelae, highlighting direct costs (medical expenses, hospitalization) and indirect costs (stay around hospitals, travel), summarized in Fig. 3. Overall, many participants (8/11 survivors; 2/3 caregivers) expressed worries about insurance coverage, copays, and out-of-pocket (OOP) expenditures, including the financial burden and uncertainty associated with these costs and how they affected both past and present care. Six survivors reported substantial OOP medical costs due to IMD consequences in the past year (at the time of the PIS). In their interviews, survivors cited OOP costs for various medical needs such as hearing aids (US $3000–4000), insurance premiums with BlueCross (US $800/month), and disability benefits, dermal fillers, and physical therapy. Survivors also faced assorted expenses up to thousands of dollars (USD) for essential home modifications to accommodate their disabilities.

All survivors (11/11) had some form of insurance at the time of the study. However, insurance complexity and the struggle to secure different coverage types were consistently highlighted, especially for individuals with disabilities. While one survivor described Medicare as a lifeline, others faced challenges with insurance coverage for surgeries.

Changes in Impacts over Time

A comparison between reported short-term impacts (investigated in Part 1 of this study [1]) and long-term impacts revealed that despite having survived the acute, life-threatening stage of the disease, many areas of survivors’ lives remained affected over the long term. All impacts that were reported in the acute phase were still reported during the long-term phase, and most short-term impacts were reported by a larger proportion of survivors in the long-term period.

Differences in impacts on functional activities were comparable between the short- and long-term phases following IMD onset. Meanwhile, substantial differences were observed for other impacts, with notable increases in the reporting of memory problems (53%), planning/time constraints (49%), sleep disturbances (44%), and work productivity (38%) in the long-term phase. Comparisons also revealed that with time, the burden of disease was manifested by new and diverse impacts on everyday life, which are summarized in Supplementary Table 9.

Discussion

This novel, mixed-methods study was conducted to assess the humanistic burden of IMD on survivors and their caregivers in the USA, from infection and initial recovery (Part 1) to the long-term state of their health and well-being (Part 2).

Building upon the acute phase findings in Part 1 [1], this manuscript presents the results of Part 2, shedding light on the sequelae, impacts, and financial burden of IMD that endure long past disease onset. A key feature of IMD is the onset of physical, neurological, and systemic sequelae, which were associated with a multiplicity of long-term impacts.

Survivors endured significant physical sequelae such as mobility challenges, amputations, and skin scarring, consistent with previous studies including Shen et al. 2022’s systematic literature review of IMD sequelae [12]. One of the most visible and impactful consequences during the acute phase was having to undergo amputation(s) [1], and this carried into the long-term phase with severe impacts such as inability or difficulty walking, work and education limitations, low self-perception and body image, and greater specialist or rehabilitation service use. Loss of autonomy due to inability to perform simple tasks alone, such as showering or other self-care activities, also took a toll on survivors and their caregivers. Many survivors described the loneliness and isolation caused by limitations in their mobility and overall health and well-being.

Neurological sequelae among survivors included cognitive, sensory, and motor deficits, as well as numbness, nerve pain, and sensitivity to light, similar to findings in two systematic literature reviews of IMD sequelae [11, 12], leading to a lifelong need for medical care, rehabilitation, and assistive devices. Motor skills appeared to be impacted in ways that were not elaborately highlighted in any previous research, and memory issues impacted survivors in all phases of their lives, from daily activities to emotional and social aspects.

Survivors consistently highlighted systemic sequelae, including multiple organ failures during the acute phase, leading to lifelong impacts such as dialysis for kidney failure and “medical fragility”, and making survivors dependent on others for various aspects of their day-to-day activities, school, or work commitments.

The emotional burden of IMD was profound in the acute phase as survivors grappled with the trauma of a near-fatal illness, often accompanied by painful and frightening medical interventions, and PTSD and anxiety disorders ensued from these traumatic experiences in the long term. Almost all survivors presented lasting anxiety and worry about their condition and were in a state of constant self-consciousness, also dealing with body image, shame, embarrassment, and low self-esteem. Previous studies have similarly highlighted the PTSD symptoms found in pediatric ICU cases [18], and impacts of long-term mental health, emotional, and behavioral problems on survivors’ school, home, and social lives [19–21]. As identified in previous literature [22], caregivers also experienced emotional distress as they witnessed their child suffer, compelling them to take on caregiving responsibilities that inevitably impacted their lives, careers, and productivity. One previous study found that parents of children with IMD had high and persistent psychological distress after 36-months follow-up [23]. The detailed emotional consequences of IMD from the perspective of those impacted, which have not been sufficiently captured in the existing literature, are therefore a key contribution of this study.

The social impacts of IMD often intertwined with emotional and psychological aspects; many survivors found it challenging to navigate social situations as a result of cognitive and physical changes, often needing to rely on non-verbal cues or body language to fully understand conversations. This led to feelings of inferiority and frustration in social interactions. Survivors experienced feelings of being different, frustration, and disappointment, which further strained their relationships with others.

Previous studies, such as two recent systematic literature reviews of IMD sequelae and impacts [11, 12], have similarly highlighted the high proportion of IMD survivors affected by long-term sequelae and impacts across the above domains.

Survivors and their families experienced significant work and productivity losses, consistent with recent studies [9, 10, 24]. While most survivors (9/11) completed college, many described struggles with achievement. Similarly, a study in England reported that at a median of 19 months post-IMD, approximately half of adolescent survivors’ academic achievements were affected [25]. Survivors used various aids, online and remote opportunities, and coping mechanisms to pursue their studies. For many, work opportunities or pursuing their planned career paths were lost. Survivors who experienced organ failures were further limited in their work or study, having to focus mainly on comfort and survival. The indirect costs of caregiving were also highlighted by caregivers, who were also limited in their capacities to work and pursue full-time jobs, often resulting in lost income. These impacts have also been reported in previous studies reporting impacts on parents and/or caregivers [22, 26].

While HCRU among survivors was high during the acute phase, hospitalizations, specialist visits, and therapy utilization remained notably high over the long term because of IMD sequelae. Nine survivors reported using psychological or psychiatric care services long-term, reflecting the significant psychological impact that the disease had on their lives. Survivors also faced various essential home modification expenses (e.g., access ramps, shower benches, specialized equipment) of up to thousands of dollars to accommodate their disabilities and improve daily life, highlighting the importance of adapting living spaces to their unique needs and the financial toll of these expenses. As during the acute phase (presented in the Part 1 manuscript [1]), survivors also highlighted interactions with physicians and specialists as key components of their healthcare journeys, emphasizing the role of HCPs long after initial hospitalization and recovery.

The diverse therapeutic and medical interventions used by participants collectively demonstrated the wide-ranging and often long-term effects of IMD, extending beyond individuals’ physical and psychological well-being to the disease’s significant financial repercussions. Insurance-related concerns during the acute phase affected survivors and families [1], and the need for specialized care and rehabilitation services continued for years, resulting in significant financial strain both in terms of OOP expenditures and productivity losses. Furthermore, the economic burden of IMD extends beyond the individual level; consistent with the high HCRU observed among survivors with IMD sequelae, in a 2011 study, the presence of IMD sequelae resulted in approximately US $30,000 in additional costs compared to patients without sequelae [13]. While IMD’s low incidence presents a smaller total economic burden than other, more common infectious diseases, IMD presents clinical and economic implications with a considerable financial burden on healthcare systems, especially for IMD cases with long-term sequelae.

Survivors formulated various coping strategies to deal with their situation, such as engaging with other IMD survivors. As all survivors were recruited through PAGs, a sense of community was evident in their testimonies (and those of caregivers) about advocacy and disease awareness. Survivors’ efforts to cope and build community bring an important perspective to the IMD space, especially as a complex and life-long disease.

The multifaceted sequelae of IMD require a comprehensive approach to long-term care. Access to specialized medical services, such as audiology and neurology, is essential to monitor and manage physical and neurological complications. Psychological support is equally crucial; survivors and caregivers should have access to mental health services to address the emotional and psychological consequences of IMD, including therapy and counseling to manage symptoms of anxiety, depression, and PTSD. Support groups and peer networks can also play a vital role in the long-term care of IMD survivors. Sharing experiences and coping strategies with others who have faced similar challenges can provide emotional relief and a sense of community.

Despite the low incidence of IMD, it is imperative that healthcare systems, providers, and communities recognize the comprehensive and long-term nature of this disease’s burden and work together to provide the support and resources needed to enhance the quality of life of those affected. While reducing the long-term burden of IMD among those affected should remain central to strategic healthcare interventions, so too should prevention of the disease through available methods like vaccination, per Centers for Disease Control and Prevention (CDC) and World Health Organization recommendations specifying vaccination as the best approach to controlling IMD [27, 28]. The burden on survivors and their caregivers should be considered in decision-making regarding vaccination recommendations, especially in light of the availability of approved meningococcal vaccines in the USA [7, 29]. Meningococcal vaccination coverage remains suboptimal in the USA, especially for the MenB vaccine (32.4% coverage of ≥ 1 dose among 17-year-olds) [8, 30], and strategies such as simplifying vaccination recommendations may help to improve coverage and mitigate the burden of IMD.

While previous studies have highlighted similar challenges among survivors (and their caregivers) of conditions such as cancer and stroke [31, 32], or individuals living with chronic diseases such as chronic obstructive pulmonary disease [33], such work in the qualitative and mixed-methods context is among the first of its kind for IMD within the USA. Population-level studies have described key medical and economic outcomes associated with IMD, though insights into the broader humanistic burden of the disease on those affected remains limited [11–13]. Owing to the robust methodological approach of this study, in-depth insights have been captured despite the small sample and reflect the meaningful contributions of patients, their families, and the PAGs that facilitated the study [1].

The various IMD concepts (symptoms, sequelae, and impacts) documented in the Part 1 and Part 2 manuscripts of this study can also inform future studies [1], including those taking a more comprehensive approach to quantify short- and long-term sequelae burden in health economic modeling, with the aim of supporting health policy decision-making.

Limitations

Limitations due to small sample size, possible confounding comorbidities, diversity of participants, and adult-only involvement in PAGs have been previously described [1]. IMD’s low incidence and potential for devastating consequences introduced key recruitment challenges. Furthermore, caregivers of children (< 10 years) were difficult to recruit; while unexpected as a result of high IMD incidence in children, in light of the enormous burden faced by caregivers in this study, it became evident that some caregivers are overburdened, reluctant, or emotionally not ready to be involved in such research.

Future research should explore larger, more diverse samples, as well as other recruitment channels to comprehensively document and represent the experiences of IMD survivors. While generalizability of our results could not be confirmed, this was not the goal of the study, which was to provide a rich and contextualized understanding of the long-term IMD experience.

Conclusions

This study illustrates the enduring sequelae of IMD and heavy long-term humanistic burden on survivors and their caregivers, encompassing physical disabilities, emotional trauma, and substantial financial challenges. Addressing this burden necessitates a comprehensive approach, including preventive measures like vaccination, long-term medical and psychological support, and financial assistance programs to help affected individuals and families cope with the multifaceted consequences of this devastating illness. The robust scientific methodology of this study can also be used to inform future studies in the IMD space. Ultimately, in highlighting the experiences of IMD survivors and their caregivers, this study presents a unique and enriching perspective on the burden of IMD.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Substantial contributions to study conception and design: Oscar Herrera-Restrepo, Nuzhat Afroz, Eliazar Sabater Cabrera, Matthew Reaney, Obinna Onwude; substantial contributions to acquisition, analysis, and/or interpretation of the data: Oscar Herrera-Restrepo, Nuzhat Afroz, Eliazar Sabater Cabrera, Matthew Reaney, France Ginchereau Sowell, Ramiya Kumar, Alicia Stillman, Patti Wukovits, Mariana Rodrigues, Sofia B. Pinto, Zeki Kocaata, Obinna Onwude; drafting the article or revising it critically for important intellectual content: Oscar Herrera-Restrepo, Nuzhat Afroz, Eliazar Sabater Cabrera, Matthew Reaney, France Ginchereau Sowell, Ramiya Kumar, Alicia Stillman, Patti Wukovits, Mariana Rodrigues, Sofia B. Pinto, Zeki Kocaata, Obinna Onwude; and final approval of the version of the article to be published: Oscar Herrera-Restrepo, Nuzhat Afroz, Eliazar Sabater Cabrera, Matthew Reaney, France Ginchereau Sowell, Ramiya Kumar, Alicia Stillman, Patti Wukovits, Mariana Rodrigues, Sofia B. Pinto, Zeki Kocaata, Obinna Onwude.

Funding

This study was sponsored by GSK (Study identifier eTrack ETMF-219353), including funding for the Rapid Service fee for this publication. Support for third-party writing assistance for this article, provided by Océane Parker, Costello Medical, USA was funded by GSK in accordance with Good Publication Practice 2022 guidelines (https://www.ismpp.org/gpp-2022).

Data Availability

The datasets generated and/or analyzed during the current study are included in this published article as supplementary information files, and/or are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

Oscar Herrera-Restrepo, Eliazar Sabater Cabrera, and Zeki Kocaata are employees and stockholders of GSK; Sofia B. Pinto is an employee of GSK. Matthew Reaney, France Ginchereau Sowell, Ramiya Kumar, and Obinna Onwude are employees of IQVIA, which was paid by GSK to conduct this study. Nuzhat Afroz is a current employee of Novo Nordisk, and was an employee of IQVIA during the time the study was conducted. Alicia Stillman, Patti Wukovits, and Mariana Rodrigues are affiliated with the American Society for Meningitis Prevention (formerly the Meningitis B Action Project), which receives educational grants from GSK and Pfizer via the Kimberly Coffey Foundation and the Emily Stillman Foundation. Alicia Stillman, Patti Wukovits, and Mariana Rodrigues received no payment for recruitment and were blinded to any identifiable information from recruited participants.

Ethical Approval

This study was conducted in accordance with the study protocol, the Guidelines for Good Pharmacoepidemiology Practices published by the International Society of Pharmacoepidemiology, the ethical principles of the Declaration of Helsinki, and IRB requirements. IRB approval was sought and obtained from the USA-based WCG IRB. Participants and the study sponsor were blinded from each other (i.e., participants were not aware of the study sponsor and only directly interacted with the investigators, and the study sponsor was not aware of any participant identifying information at any point during study conduct). All participants ≥ 18 years old provided informed consent prior to their participation in the research study; participants < 18 years old provided assent, in addition to consent from their caregiver/legal guardian.