Skin biopsy in adult patients with meningococcal purpura fulminans: a multicenter retrospective cohort study.

BACKGROUND: Neisseria meningitidis is the leading responsible bacterium of Purpura Fulminans (PF) accounting for two thirds of PF. Skin biopsy is a simple and minimally invasive exam allowing to perform skin culture and polymerase chain reaction (PCR) to detect Neisseria meningitidis. We aimed to assess the sensitivity of skin biopsy in adult patients with meningococcal PF. METHODS: A 17-year multicenter retrospective cohort study including adult patients admitted to the ICU for a meningococcal PF in whom a skin biopsy with conventional and/or meningococcal PCR was performed. RESULTS: Among 306 patients admitted for PF, 195 had a meningococcal PF (64%) with a skin biopsy being performed in 68 (35%) of them. Skin biopsy was performed in median 1 day after the initiation of antibiotic therapy. Standard culture of skin biopsy was performed in 61/68 (90%) patients and grew Neisseria meningitidis in 28 (46%) of them. Neisseria meningitidis PCR on skin biopsy was performed in 51/68 (75%) patients and was positive in 50 (98%) of them. Among these 50 positive meningococcal PCR, five were performed 3 days or more after initiation of antibiotic therapy. Finally, skin biopsy was considered as contributive in 60/68 (88%) patients. Identification of the meningococcal serogroup was obtained with skin biopsy in 48/68 (71%) patients. CONCLUSIONS: Skin biopsy with conventional culture and meningococcal PCR has a global sensitivity of 88% and should be systematically considered in case of suspected meningococcal PF even after the initiation of antimicrobial treatment.

Meningococcal pericarditis caused by the MenW:cc11 strain in an older adult.

INTRODUCTION: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a disease with a high mortality and morbidity rate. Serogroup W meningococci (MenW) used to be associated with sporadic disease worldwide. In recent years, a surge in MenW incidence is being observed. REPORT: An older adult presenting with acute onset shortness of breath, chest pain and fever, was diagnosed with pericarditis with meningococcemia due to MenW:ST11 strain. MenW infections are reported to have a higher case fatality rate and atypical clinical presentations: MenW has been identified in patients presenting with pneumonia, gastro-intestinal symptoms, arthritis, and pericarditis. DISCUSSION: In Belgium, the National Reference Laboratory is also noticing an increase in serogroup Wmeningococcal disease. Recent epidemiological data for Belgium is reported in the article. MenW infections are reported to have a higher case fatality rate and atypical clinical presentations: MenW has been identified in patients presenting with pneumonia, gastro-intestinal symptoms, arthritis, and pericarditis. CONCLUSION: When factors for poor prognosis are present in patients with pericarditi clinicians should be vigilant and search for the underlying aetiology .

Immunoadsorption therapy for a meningococcemia patient with myocarditis, adrenal hemorrhage, and purpura fulminans: a case report

Abstract Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs, it is frequently severe and potentially life-threatening. A ten-year-old female patient developed a purpuric rash with fever. Upon arrival to the pediatric intensive care department, she was unconscious and in a poor general condition. We combined treatment with antibiotics, volume resuscitation, hydrocortisone, and CytoSorb® therapy resulted in a stabilization of hemodynamics, as well as control of hyperinflammation. We observed a significant decrease in vasopressor dosage in this patient.

Meningococcaemia In Children-An Under Recognized Public Health Problem In Pakistan.

Background: Meningococcaemia is a serious bacterial disease caused by Neisseria meningitidis resulting in septicaemia and meningitis in previously well individuals and is associated with serious consequences including mortality. As the data from our region is scarce, the study was conducted with an aim to highlight the disease manifestations and outcomes so that appropriate interventions are devised. Method: A descriptive study was conducted in Paediatrics A Unit from 1st March 2020 to 30th September 2021 after approval of institutional review board. Children admitted with features of meningococcaemia in the form of fever and typical petechial purpuric rash were included in the study. Results: A total of 46 patients with meningococcaemia were included in the study. Of these, 24 (52.2%) were male. Majority of the patients 22 (47.8%) were in the age group of 1 year to five years, Major complications were meningitis in 39 (84.8%), septic shock in 26 (56.5%) and purpura fulminans in 12 (26.1%) patients. Mortality was documented in 6 (13%) patients. Outcome was associated with age. (p= 0.039). There was a significant difference in outcome in patients with prolonged PT/APTT (p=0.031), purpura fulminans (p=0.000) and septic shock (p=0.021). Conclusion: Meningococcaemia is prevalent in our region in paediatric population. The disease has a fulminant course with a myriad of complications and potentially fatal outcomes especially in children under one year of age.

A Double Whammy Pneumonia: The First Reported Case of Concurrent Neisseria meningitidis and SARS-CoV-2 Pneumonia.

Meningococcal pneumonia (MP) is a rare manifestation of meningococcal disease. The MP was first described in 1907 when Neisseria meningitidis (NM) isolates were identified in sputum samples obtained from soldiers with pneumonia. Preceding and concurrent viral infections constitute a major risk for MP. During the 1918-1919 influenza pandemic, a significant increase in MP cases were reported in patients with preceding influenza infection. Despite the end of the last H1N1 influenza pandemic in 2010, seasonal influenza infections still pose a risk for simultaneous MP. History appears to be repeating itself with concomitant bacterial and viral coinfection amid the current SARS-CoV-2 pandemic. Herein presented is a unique case of an elderly woman who presented with, to the best of our knowledge, the first reported case of possible concurrent SARS-CoV-2 and MP infections.

Long-term impact of invasive meningococcal disease in children: SEINE study protocol.

INTRODUCTION: Invasive meningococcal disease (IMD) is still an important cause of mortality in children and survivors can have significant long-term disabling sequelae. There are few prospective studies looking at the long term neuropsychological and developmental consequences of IMD in surviving children, and the rate of sequelae may be underestimated. The SEINE study aims to have a more reliable estimate of the real rate of sequelae by assessing the long-term physical, neuropsychological, learning disorders and sensory sequelae of IMD in children and adolescents and by assessing the post-traumatic stress in parents. METHODS AND ANALYSIS: The SEINE study is a multicentre, prospective, non-randomized, interventional study based on the French bacterial meningitis surveillance network. The study will include 100 children aged from birth to 15 years old, hospitalized in a Paris area paediatric ward for a meningococcal meningitis or a purpura fulminans between 2010 and 2019. The first outcome will assess long-term sequelae (physical, neurological, or sensory) measured by a general clinical and neurological examination, a neurocognitive assessment, learning development, a pure tone audiometry and an ophthalmic examination. The second outcome will assess the long-term post-traumatic stress in parents measured by the Impact of Event Scare Revised questionnaire. PERSPECTIVES: By providing a better estimation of the rate of sequelae in children and offering an adapted follow-up of these children, we believe that the SEINE study will help to improve the management of patients surviving IMD. TRIAL REGISTRATION NUMBER: NCT04685850.

Sequelae at Hospital Discharge in 61 Children With Invasive Meningococcal Disease, Chile, 2009-2019.

BACKGROUND: Invasive meningococcal disease (IMD) is an unpredictable and severe infection caused by Neisseria meningitidis . Its case fatality rate could vary from 9.7% to 26% and up to 36% of survivors may experience long-term sequelae, representing a challenge for public health. AIMED: To describe the sequelae at hospital discharge caused by IMD in children between years 2009-2019. METHODS: Cross-sectional study performed in 2 pediatric hospitals. Patients with microbiologically confirmed diagnosis of IMD from 2009 to 2019 were included. Bivariate and logistic regression analysis were performed. RESULTS: The records of 61 patients were reviewed and included. Sixty-seven percent were male, median age 9 months (interquartile range 4-27), 72% were admitted to intensive care unit. Thirty-seven (60.5%) had at least 1 sequela (75% and 37% in patients with or without meningitis, respectively). The most frequents sequelae were neurological 72%, hearing loss 32%, and osteoarticular 24%. Significant differences were found comparing patients with and without sequelae: drowsiness 67.6% versus 41.7% ( P = 0.04), irritability 67.6% versus 25% ( P = 0.01), meningeal signs 62.2% versus 29.2% ( P = 0.01). In logistic regression analysis, postdischarge follow-up had OR 21.25 (95% confidence intervals [CI]: 4.93-91.44), irritability had OR 8.53 (95% CI: 1.64-44.12), meningeal signs had OR 8.21 (95% CI: 0.71-94.05), invasive mechanical ventilation had OR 8.23 (95% CI: 0.78-85.95), meningitis plus meningococcemia OR 1.70 (95% CI: 0.18-15.67) to have sequelae, while children with meningococcemia and vomiting had a OR 0.04 (95% CI: 0.00-0.36) and OR 0.27 (95% CI: 0.03-2.14), respectively. N. meningitidis serogroup W (MenW) was isolated in 54.1% (33/61), and N. meningitidis serogroup B (MenB) in 31.1% (19/61) of cases. A significant difference was found in osteoarticular sequelae ( P = 0.05) between MenB and MenW. There was a decrease in cases after the meningococcal conjugate vaccine against serogroups A, C, W and Y was implemented (2015-2019). CONCLUSIONS: IMD remains as a public health concern. A high rate of sequelae was found in pediatric patients in our series, even in the clinical manifestations other than meningitis. Neurological sequelae were the most prevalent. Multidisciplinary follow-up protocols to reduce long-term impact must be urgently established to assess all children with IMD.

A database study of clinical and economic burden of invasive meningococcal disease in France.

OBJECTIVE: Invasive meningococcal disease (IMD) is life-threatening and associated with substantial morbidity and mortality. The study aimed to examine the clinical characteristics and hospital-based healthcare resource use and related costs following IMD diagnosis in France. METHODS: Patients admitted to hospitals due to IMD between 2014 and 2016 were selected from the French hospital discharge database (PMSI). Demographics, clinical outcomes and health utilization (HRU) during index hospitalization were described. HRU and costs during the follow-up period were also examined. A generalized linear model was applied to examine 1-year costs after index hospitalization adjusting for age, type of IMD and presence of sequelae at index hospitalization. RESULTS: A total of 1,344 patients were identified. About 30% cases were in children < 5 years old and 25% aged 10-24 years. Majority of patients presented as meningococcal meningitis (59%), 25% as meningococcaemia, and 9% both. The case fatality rate during the index hospitalization was 6%. About 15% of patients had at least one sequela at index hospital discharge. The median length of stay and the median cost of index hospitalization were 9 days and 8,045€, respectively. Patients with at least one sequela, with clinical manifestation as both meningitis and meningococcaemia, or aged 25 years and older were statistically significantly associated with higher costs than others. CONCLUSION: IMD is unpredictable and can occur in all ages. The study highlights the severity and high health and economic burdens associated with the disease. The data underlines the importance of prevention against IMD through vaccination.

Care pathways in invasive meningococcal disease: a retrospective analysis of the French national public health insurance database.

Invasive meningococcal disease (IMD) carries a high burden in terms of mortality, long-term complications, and cost, which can be significantly reduced by vaccination. The objectives of this case-control study were to document the care pathways of patients with IMD before, during, and after hospitalization and to assess in-hospital complications and long-term sequelae. Cases consisted of all people hospitalized for IMD in France between 2012 and 2017. Controls were matched by age, gender, and district of residence. Data were extracted from the French national public health insurance database on demographics, hospitalizations, mortality and potential sequelae of IMD. Overall, 3,532 cases and 10,590 controls were assessed and followed up for 2.8 years (median). During hospitalization, 1,577 cases (44.6%) stayed in an intensive care unit, 1,238 (35.1%) required mechanical ventilation, and 43 (1.2%) underwent amputation; 293 cases (8.3%) died in hospital and a further 163 (4.6%) died following discharge; 823 cases (25.4% of survivors) presented ≥1 sequela and 298 (9.2%) presented multiple sequelae. The most frequently documented sequelae were epilepsy (N = 205; 5.8%), anxiety (N = 196; 5.5%), and severe neurological disorders (N = 193; 5.5%). All individual sequelae were significantly more frequent (p < .0001) in cases than controls. Hearing/visual impairment and communication problems were conditions that presented the highest risk for cases compared to controls (risk ratios >20 in all cases). In conclusion, this study highlights the importance of providing optimal medical care for patients with IMD, of minimizing the delay before hospitalization, and of effective prevention through comprehensive vaccination programs.

Benefits of providing optimal medical care for IMD patients.Importance of minimising the delay before hospitalization.IMD remains challenging to diagnose, and vaccination is the most efficient way to prevent the disease and its complications.

Risk of sequelae after invasive meningococcal disease.

BACKGROUND: Invasive meningococcal disease (IMD) is a rare but severe bacterial infection, of which a high proportion of survivors are affected by sequelae. In Denmark, IMD is a notifiable disease and data collection on sequelae information has been automated, enabling studies of sequelae due to IMD diagnosed after discharge. The aim of this study was to examine possible determinants for sequelae after IMD and to describe the distribution of sequelae by age, serogroup and clinical presentation, for all cases in Denmark from 2005-2020. METHODS: Data from The National Database for Notifiable Infectious Diseases was linked to data from The Danish National Patient Register and the Civil Registration System. Logistic regression models were used to study whether age, serogroup and/or clinical presentation were associated with sequelae. A descriptive analysis of the proportion of different types of sequelae across age groups, serogroups and clinical presentations was performed. RESULTS: In total, 25% of IMD survivors experienced one or more sequelae. We found no significant association between sequelae and age. The five most common sequelae in decreasing order of incidence were hearing loss, epilepsy, learning disabilities, headache and visual defects/loss of vision, with rates ranging from 8.2 to 2.8% of IMD survivors. The proportion of survivors with hearing loss and visual defects/loss of vision was not significantly different between clinical presentations. CONCLUSIONS: We suggest revising IMD treatment guidelines, to include routine referral to hearing and vision tests, irrespective of clinical presentation. Furthermore, it is important to increase the awareness among parents of children who have had IMD of possible future learning disabilities to make sure that necessary measures are taken in a timely manner.

SURGICAL TREATMENT OF VITREORETINAL COMPLICATIONS DURING DISSEMINATED INTRAVASCULAR COAGULATION SECONDARY TO MENINGOCOCCEMIA.

PURPOSE: To report a case of the surgical management of vitreoretinal complications during disseminated intravascular coagulation secondary to meningococcemia. METHODS: A case report. RESULTS: A 25-year-old man presented with loss of vision due to retinal and vitreous hemorrhages during disseminated intravascular coagulation secondary to meningococcemia. Examination revealed the visual acuity to be counting fingers in the right eye and light perception in the left eye. Bilateral vitreous hemorrhages were found on fundus examination. A dome-shaped lesion overlying the macula consistent with a subinternal limiting membrane hemorrhage was seen on optical coherence tomography. Bilateral vitrectomy was performed. Multiple subinternal limiting membrane hemorrhages were evident in the posterior pole. A membrane forceps was used to peel the internal limiting membrane and remove the fibrin under it. The internal limiting membrane and vitreous samples were sent for anatomopathological examination confirming our hypothesis. The peripheral retina revealed bilateral multiple ischemic areas, and argon laser photocoagulation was performed on it. Both eyes were filled with silicone oil. Eight months after surgery, his vision improved to 70 and 65 on the early diabetic retinopathy study scale in the right and left eyes, respectively. CONCLUSION: Published cases of retinal and vitreous hemorrhages during disseminated intravascular coagulation secondary to meningococcemia are few. There is no specific and codified management of these ocular complications. This case is the first reporting positive visual recovery after surgical treatment. Surgical procedure seems to be effective to treat multiple vitreoretinal hemorrhages secondary to meningococcemia.

Comorbidity Increases the Risk of Invasive Meningococcal Disease in Adults.

BACKGROUND: Risk of invasive meningococcal disease (IMD) is increased in patients with complement deficiency and human immunodeficiency virus (HIV) infection. Risk associated with comorbidity is not well described. METHODS: This was a nationwide adult case-control study. Cases for the period 1977-2018 were identified by the national meningococcus reference laboratory. Matched controls were identified by registry linkage. Comorbidities diagnosed prior to IMD were based on the International Classification of Diseases, Eighth or Tenth Revision. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression after adjustment for sex, age, and other comorbidities. RESULTS: We identified 1221 cases (45% male), with a median age of 45 years (interquartile range, 22-64 years). The dominant meningococcal serogroups were B (n = 738) and C (n = 337). Increased risk of IMD was associated with solid organ transplantation (SOT) (OR 40.47 [95% CI: 4.84-337.23]), hemolytic anemia (OR 7.56 [95% CI: 2.63-21.79]), renal disease (OR 2.95 [95% CI: 1.77-4.92]), liver disease (OR 2.54 [95% CI: 1.58-4.08]), cancer (OR 2.31 [95% CI: 1.85-2.89]), diabetes (OR 1.74 [95% CI: 1.27-2.39]), neurological disease (OR 1.72 [95% CI: 1.20-2.46]), and autoimmune disease (OR 1.70 [95% CI: 1.63-2.11]). Having 1, 2, and ≥3 comorbidities was associated with increased risk of IMD (ORs 1.6-3.5). Increased risk was not associated with specific serogroups. CONCLUSIONS: This study of adults with IMD over 4 decades showed increased risk of IMD associated with renal disease, immunological disorders, liver disease, cancer, and SOT ranging from a 2- to 40-fold increased risk. Vaccination may be warranted in these populations.

Excess Invasive Meningococcal Disease Associated With Seasonal Influenza, South Africa, 2003-2018.

BACKGROUND: Invasive meningococcal disease (IMD) is a devastating illness with high mortality rates. Like influenza, endemic IMD is seasonal, peaking in winter. Studies suggest that circulation of influenza virus may influence the timing and magnitude of IMD winter peaks. METHODS: This ecological study used weekly data from 2 nationwide surveillance programs: Viral Watch (proportion of outpatient influenza-positive cases from throat or nasal swab samples) and GERMS-SA (laboratory-confirmed cases of IMD), occurring across South Africa from 2003 through 2018 in all age bands. A bivariate time series analysis using wavelet transform was conducted to determine cocirculation of the diseases and the time lag between the peak seasons. We modeled excess meningococcal disease cases attributable to influenza cocirculation, using univariate regression spline models. Stata and R statistical software packages were used for the analysis. RESULTS: A total of 5256 laboratory-confirmed IMD cases were reported, with an average annual incidence of 0.23 episodes per 100 000 population and a mean seasonal peak during week 32 (±3 weeks). Forty-two percent of swab samples (10 421 of 24 741) were positive for influenza during the study period. The mean peak for all influenza occurred at week 26 (±4 weeks). There was an average lag time of 5 weeks between annual influenza and IMD seasons. Overall, 5% (1%-9%) of IMD cases can be attributable to influenza cocirculation, with, on average, 17 excess IMD cases per year attributable to influenza. CONCLUSIONS: A quantifiable proportion of IMD in South Africa is associated with influenza cocirculation; therefore, seasonal influenza vaccination may have an effect on preventing a small portion of IMD in addition to preventing influenza.

Immunoadsorption therapy for a meningococcemia patient with myocarditis, adrenal hemorrhage, and purpura fulminans: a case report.

Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs, it is frequently severe and potentially life-threatening. A ten-year-old female patient developed a purpuric rash with fever. Upon arrival to the pediatric intensive care department, she was unconscious and in a poor general condition. We combined treatment with antibiotics, volume resuscitation, hydrocortisone, and CytoSorb.½ therapy resulted in a stabilization of hemodynamics, as well as control of hyperinflammation. We observed a significant decrease in vasopressor dosage in this patient.

Primary meningococcal septic arthritis associated with joint calcium oxalate crystals: A case report and review of the literature.

Primary meningococcal septic arthritis (PMSA) is an extremely rare local infection by Neisseria meningitidis in the absence of meningitis or meningococcaemia syndrome. A 30-year-old healthy, immunocompetent man presented with arthralgia, fever, chest rash, and significant swelling of the right knee. On admission, a disseminated maculopapular and purpuric rash, oligoarthritis, neutrophilia, and elevated acute phase reactants were documented. Following arthrocentesis of the right knee, isolation of N. meningitidis and the presence of calcium oxalate crystals in the synovial fluid were reported. The diagnosis of PMSA was made. Histological analysis of the skin lesion showed leucocytoclastic vasculitis. He was treated with intravenous ceftriaxone plus open surgical drainage and ambulatory cefixime with adequate response. After 1 month, he presented resolution of the pathological process. We performed an extensive review of the literature, finding that the key elements supporting the diagnosis of PMSA are prodromal upper respiratory tract symptoms and skin involvement prior to or synchronous with the arthritis. Also, the most frequently involved joint is the knee. This report is the first case of a patient presenting with PMSA associated with calcium oxalate crystals in the synovial fluid. Herein, we discuss the most frequent clinical manifestations, the unusual histological features, the recommended treatment, and the reported prognosis of this rare entity.

[Analysis of fatal outcomes of meningococcal infection in adults].

Clinical characteristics and pathomorphological manifestations in 69 patients aged 18 to 86 years with a fatal outcome of the disease were examined in order to analyze the causes of severe course and high mortality of generalized forms meningococcal infection. It was found that the main clinical form was meningococcemia (90%), in the majority in combination with meningitis (52%). The fulminant course in 77% of patients with meningococcal sepsis manifested itself as a sudden onset, rapid development of typical symptoms. Hemorrhagic exanthema was detected on the first day of meningococcemia. The leading complications and critical conditions were infectious-toxic shock, disseminated intravascular coagulation and acute adrenal insufficiency (Waterhouse-Friederiksen syndrome). The severe course of meningitis (in 10%) led to the development of cerebral coma, the morphological substrate of which was edema - swelling of the brain.

Acute kidney injury in a mouse model of meningococcal disease.

INTRODUCTION: Meningococcal disease is associated with high mortality. When acute kidney injury (AKI) occurs in patients with severe meningococcal disease, it is typically attributable to sepsis, although meningococcal disease and lipopolysaccharide release are rarely investigated. Therefore, we evaluated renal tissue in a mouse model of meningococcal disease. METHODS: Female BALB/c mice were induced to AKI by meningococcal challenge. Markers of renal function were evaluated in infected and control mice. RESULTS: In the infected mice, serum concentrations of tumor necrosis factor alpha, interferon gamma, interleukins (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12), and granulocyte-macrophage colony-stimulating factor were elevated, as was renal interstitial infiltration with lymphocytes and neutrophils (p < 0.01 for the latter). Histological analysis showed meningococcal microcolonies in the renal interstitium, without acute tubular necrosis. Infected mice also showed elevated renal expression of toll-like receptor 2, toll-like receptor 4, and Tamm-Horsfall protein. The expression of factors in the intrinsic pathway of apoptosis was equal to or lower than that observed in the control mice. Urinary sodium and potassium were also lower in infected mice, probably due to a tubular defect. CONCLUSION: Our findings corroborate those of other studies of AKI in sepsis. To our knowledge, this is the first time that meningococci have been identified in renal interstitium and that the resulting apoptosis and inflammation have been evaluated. However, additional studies are needed in order to elucidate the mechanisms involved.