Invasive meningococcal disease in Italy: from analysis of national data to an evidence-based vaccination strategy.

INTRODUCTION: Invasive meningococcal disease (IMD) is one of the most severe vaccine-preventable disease not yet under control. In Italy, although different anti-meningococcal vaccines are available, their offer among regions is heterogeneous. The aim of this study is to describe the epidemiology of IMD in Italy based on analysis of national surveillance data for 2011-2017 to optimize the vaccination strategy. METHODS: IMD surveillance data from the Italian National Health Institute were analysed. Microsoft Excel was used to present trend analysis, stratifying by age and serogroups. RESULTS: In Italy, during the period 2011-2017, the incidence of IMD increased from 0.25 cases/100,000 inhabitants in 2011 to 0.33 cases/100,000 in 2017. Most cases after 2012 were caused by non-B serogroups. The number of cases in subjects aged 25-64 years increased steadily after 2012 (36 cases in 2011, 79 in 2017), mostly due to non-B serogroups, representing more than 65% of cases in those aged 25+ years. CONCLUSIONS: In the period from 2011 to 2017, the incidence of IMDs increased in Italy. The increase, probably due also to a better surveillance, highlights the importance of the disease in the adult population and the high level of circulation of non-B serogroups in particular after 2012. Our analysis supports an anti-meningococcal vaccination plan in Italy that should include the highest number of preventable serogroups and be aimed at vaccinating a wider population through a multicohort strategy.

Neisseria meningitidis serogroup C causing primary polyarthritis in an octogenarian.

A man in his 80s presented to the hospital with a 36-hour history of fever, myalgia, bilateral shoulder and right knee pain. Joint fluid aspirates from his shoulders and right knee isolated Gram-negative diplococci. After failing to grow on standard and selective media, Neisseria meningitidis was identified by 16s PCR and subsequently typed as serogroup C. He had no clinical features of meningitis or meningococcaemia. Blood cultures were negative and an EDTA blood sample was negative for meningococcal ctrA gene. Urine PCR was negative for Neisseria gonorrhoeae He was treated successfully with two arthroscopic joint washouts of his right knee, aspirates of both shoulders, 40 days of intravenous ceftriaxone and intensive physiotherapy as both an inpatient and outpatient. In the literature, we have not found any previously documented cases of serogroup C meningococcus causing polyarticular primary septic arthritis in this age group or guidance on duration of antibiotic treatment. Literature on the impact of rehabilitation to baseline function was also found to be lacking. Although rare, primary meningococcal arthritis (PMA) should be considered as a differential diagnosis in cases of acute polyarticular septic arthritis. Polyarticular PMA in older adults may require prolonged rehabilitation before one might expect to return to premorbid function.

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia.

Meningococcemia is notorious for evasion of the host immune system and its rapid progression to fulminant disease, and serves as a unique model for pediatric sepsis. Illness severity is determined by complex interplays among host, pathogen, and environment. The inflammatory host response, including proinflammatory and anti-inflammatory responses in innate and adaptive immunity, skews toward a proinflammatory state. This leads to endothelial dysfunction and activation of the hemostatic response, which may lead to disseminated intravascular coagulation. This article reviews the pathogenesis of sepsis, in particular the inflammatory and hemostatic response in meningococcal sepsis.

Multiple Linear Regression Model of Meningococcal Disease in Ukraine: 1992-2015.

Estimating the rates of invasive meningococcal disease (IMD) from epidemiologic data remains critical for making public health decisions. In Ukraine, such estimations have not been performed. We used epidemiological data to develop a national database. These data were used to estimate the population susceptible to IMD and identify the prevalence of asymptomatic carriers of N. meningitidis using simple epidemiological models of meningococcal disease that may be used by the national policy makers. The goal was to create simple, easily understood analysis of patterns of the infection within Ukraine that would capture the major features of the infection dynamics. Studies used nationally reported data during 1992-2015. A logic model identified the prevalence of carriage and the proportion of the population susceptible to IMD as key drivers of IMD incidence. Multiple linear regression models for all ages (total population) and for children ≤14 years old were fit to national-level data. Linear models with the incidence of IMD as an outcome were highly associated with carriage and estimated susceptible population in both total population and children (R 2 = 0.994 and R 2 = 0.978, respectively). The susceptibility rate to IMD in the study total population averaged 0.0034 ± 0.0009% annually. At the national level, IMD can be characterized by the simple interaction between the prevalence of asymptomatic carriage and the proportion of the susceptible population. IMD association with prevalence rates of carriage and the proportion of susceptible population is sufficiently strong for national-level planning of intervention strategies for IMD.

Fifteen-minute consultation: Symptoms and signs of meningococcal disease.

Meningococcal disease remains a leading cause of meningitis, sepsis and death in children worldwide and in the UK. Successful vaccination programmes in the UK have, however, significantly reduced the burden of disease in children. Unfortunately, despite vaccination, a significant number of children are still diagnosed with invasive meningococcal disease each year.As the prevalence of meningococcal disease falls, it is important that we maintain awareness of the symptoms and signs of meningococcal disease because the prompt recognition of this life-threatening infection improves outcomes.In this article we discuss the pathology, epidemiology and recognition of invasive meningococcal disease in children. The aim is to maintain awareness of this rare but life-threatening infection.

Primary Meningococcal Septic Arthritis Case Report and Literature Review of an Unusual Manifestation of Meningococcal Disease.

INTRODUCTION: Primary meningococcal septic arthritis (PMSA) is an unusual manifestation of meningococcal disease. It is defined as the presence of acute septic arthritis without association with meningitis or the classic meningococcemia and isolation of Neisseria meningitidis in synovial fluid and blood culture. Diagnosis and early treatment, combining antibiotic and joint drainage, are fundamental. CASE PRESENTATION: We present the case of a healthy 17-year-old male who presented with history of an acute onset, painful knee accompanied by fever. N. meningitidis was cultured from the synovial fluid. He was treated with arthroscopic lavage and intravenous ceftriaxone for 2 weeks. He was discharged 7 days after admission receiving outpatient intravenous ceftriaxione for 6 days and was ultimately transitioned to oral ciprofloxacin for 2 weeks thereafter. At the final follow-up visit, he had returned to sports activity with a normal knee joint. LITERATURE REVIEW: We have done an exhaustive literature review in PubMed. Forty-four articles were included, with a total of 46 patients, to which we added ours. We collected the available demographic data, analytical values, culture tests, treatment, and evolution. PURPOSES AND CLINICAL RELEVANCE: This case illustrates an unusual presentation of N. meningitidis infection. Diagnostic suspicion is essential. Joint washing and antibiotics are the mainstays of treatment. Early and proper treatment prevents complications and mortality. Our main objective was to evaluate the diagnostics tools and treatment in PMSA. As a secondary objective, we evaluated the cases with negative cultures in order to evaluate the criteria for the diagnostic suspicion of PMSA.

Talk to Patients About: Meningococcal Disease.

Talk to Patients About: Meningococcal Disease.

Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis.

Pediatric meningococcal sepsis often results in morbidity and/or death, especially in young children. Our understanding of the reasons why young children are more susceptible to both the meningococcal infection itself and a more fulminant course of the disease is limited. Immunoglobulin G (IgG) is involved in the adaptive immune response against meningococcal infections, and its effector functions are highly influenced by the glycan structure attached to the fragment crystallizable (Fc) region. It was hypothesized that IgG Fc glycosylation might be related to the susceptibility and severity of meningococcal sepsis. Because of this, the differences in IgG Fc glycosylation between 60 pediatric meningococcal sepsis patients admitted to the pediatric intensive care unit and 46 age-matched healthy controls were investigated, employing liquid chromatography with mass spectrometric detection of tryptic IgG glycopeptides. In addition, Fc glycosylation profiles were compared between patients with a severe outcome (death or the need for amputation) and a nonsevere outcome. Meningococcal sepsis patients under the age of 4 years showed lower IgG1 fucosylation and higher IgG1 bisection than age-matched healthy controls. This might be a direct effect of the disease; however, it can also be a reflection of previous immunologic challenges and/or a higher susceptibility of these children to develop meningococcal sepsis. Within the young patient group, levels of IgG1 hybrid-type glycans and IgG2/3 sialylation per galactose were associated with illness severity and severe outcome. Future studies in larger groups should explore whether IgG Fc glycosylation could be a reliable predictor for meningococcal sepsis outcome.IMPORTANCE Meningococcal sepsis causes significant mortality and morbidity worldwide, especially in young children. Identification of risk factors for a more fulminant infection would help to decide on appropriate treatment strategies for the individual patients. Immunoglobulin G (IgG) plays an essential role in humoral immune responses and is involved in the adaptive immune response against meningococcal infections. Of great influence on the receptor affinity of IgG is the N-glycan on its fragment crystallizable (Fc) portion. In the present study, we analyzed IgG glycosylation during the fast development of meningococcal sepsis in children, and we were able to identify glycosylation features that are different between meningococcal sepsis patients and healthy controls. These features might be indicative of a higher susceptibility to meningococcal sepsis. In addition, we found glycosylation features in the patients that were associated with illness severity and severe disease outcome, having the potential to serve as a disease outcome predictor.

Mutilating Purpura Fulminans in an Adult with Meningococcal Sepsis.

We report a dramatic case of meningococcal sepsis manifesting as purpura fulminans in an elderly diabetic woman. Hemodynamic instability and severe bilateral cutaneous lesions involving her hands and feet developed rapidly. Specific antibiotic therapy and the administration of inotropic and vasopressor drugs were initiated. The severity and extension of the cutaneous lesions (attributed to purpura fulminans) worsened because of the need for vasoconstrictors for the treatment of septic shock. Bilateral transmetatarsal and metacarpal amputations were required to stabilize the patient.

Arthritis secondary to meningococcal disease: A case series of 7 patients.

Arthritis secondary to invasive meningococcemia is rare and has been described as a direct result of bacteremia or as immunoallergic-type arthritis, related to the immune complex. Only a few case series have been reported.This multicenter study aimed to describe the clinical characteristics and therapeutic outcomes of arthritis secondary to meningococcal infection.We performed a 5-year retrospective study. We included all patients with inflammatory joint symptoms and proven meningococcal disease defined by the identification of Neisseria meningitidis in blood, cerebrospinal fluid, or synovial fluid. Septic arthritis was defined by the identification of N meningitidis in joint fluid. Immune-mediated arthritis was considered to be arthritis occurring after at least 1 day of invasive meningococcal disease without positive joint fluid culture.A total of 7 patients (5 males) with joint symptoms and meningococcal disease were identified. The clinical presentation was mainly oligoarticular and the knee was the most frequent joint site. Five patients had septic arthritis and 4 had immune-mediated arthritis; 2 had septic arthritis followed by immune-mediated arthritis. Immune-mediated arthritis occurred 3 to 7 days after meningococcal meningitis, and treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) led to improvement without complications.Physicians must be vigilant to the different clinical presentations in patients with arthritis associated with invasive meningococcal disease. If immune-mediated arthritis is suspected, NSAIDs are usually efficient.

Acute polyarthritis in a young patient caused by meningococcal and parvovirus B19 infections: a case report and review of the literature.

BACKGROUND: Meningococcal infection is a multifaceted disease including acute polyarthritis. This presentation should be known by clinicians in order to prevent delay in treatment. We report what we believe to be the first case of an association of parvovirus B19 and meningococcal polyarthritis in a young adult. CASE PRESENTATION: A 19-year-old Caucasian woman presented to our hospital with fever, intense leg pain, and a transient rash. A physical examination showed asymmetric polyarthritis and no neurological abnormalities. A parvovirus B19 polymerase chain reaction performed using a blood sample and knee fluid aspirate came back positive, but serology was negative for immunoglobulin M and positive for immunoglobulin G. A blood culture was positive for serotype C meningococcus; a polymerase chain reaction performed for Neisseria meningitidis was positive in joint fluid but negative in blood samples (performed after antibiotic treatment had begun). Our patient was treated with ceftriaxone for 15 days, associated with analgesic therapy. Hydroxychloroquine treatment was introduced 5 months after the onset of polyarthritis because of persisting inflammatory arthralgia. CONCLUSIONS: To the best of our knowledge, this is the first case report of polyarthritis caused by concomitant meningococcal and parvovirus B19 infections. This unusual presentation of meningococcal disease may have resulted from the persistent parvovirus B19 infection. Our experience with this case illustrates the need for a systematic approach to the diagnosis of febrile acute polyarthritis. Only long-term follow-up will reveal if this infectious polyarthritis will evolve towards an autoimmune rheumatism.

Increase in Meningococcal Serogroup W Disease, Victoria, Australia, 2013-2015.

In Victoria, Australia, invasive meningococcal disease caused by Neisseria meningitidis serogroup W increased from 4% of all cases in 2013 to 30% in 2015. This increase resulted largely from strains similar to those in the serogroup W sequence type 11 clonal complex, previously described in the United Kingdom and South America.

Deciphering the Burden of Meningococcal Disease: Conventional and Under-recognized Elements.

Invasive meningococcal disease remains a substantial global public health burden despite being vaccine-preventable worldwide. More than one million cases are reported annually, with average fatality rates ranging from 10% to 40% depending on clinical presentation and geographic location. Survivors may suffer debilitating sequelae that reduce the quality of life for the patient and family members responsible for their care. Major financial burdens are associated with acute treatment and follow-up care, and outbreak management often places extensive financial strains on public health resources. Although the clinical and financial aspects of meningococcal disease burden are straightforward to quantify, other burdens such as lifelong cognitive deficits, psychological stress, adaptive measures for reintegration into society, familial impact, and legal costs are systematically overlooked. These and other facets of disease burden are therefore not systematically considered in cost-effectiveness analyses that public health authorities take into consideration when making decisions regarding vaccination programs. Changing the approach for measuring meningococcal disease burden is necessary to accurately understand the societal consequences of this devastating illness. In this article, the conventional and under-recognized burdens of meningococcal disease are presented and discussed.

Treatment of Meningococcal Disease.

Meningococcal disease is a life-threatening infection that may progress rapidly, even after appropriate treatment has commenced. Early suspicion of the diagnosis is vital so that parenteral antibiotic treatment can be administered as soon as possible to reduce the complications of infection. The outcome of meningococcal disease is critically dependent on prompt recognition of two important complications: shock and raised intracranial pressure. Rapid recognition of disease and of these complications, together with appropriate management is crucial to the outcome of affected patients. This article summarizes the clinical features of invasive meningococcal disease, diagnostic tools, treatment modalities, and common post-infection sequelae.

Meningococcal disease in children and teenagers.

Meningococcal disease is a leading cause of death in children and young people. It causes two major disease processes, meningococcal septicaemia and meningococcal meningitis, and often results in long-term health complications. It remains a difficult disease to recognise and treat. This article, part one in a two-part series, discusses the epidemiology of meningococcal disease and explains its pathophysiology as well as signs and symptoms. Part 2, to be published on 19 March, will review diagnosis, management and prevention.

The burden and impact of severe and long-term sequelae of meningococcal disease.

This review describes current knowledge on the severity and long-term sequelae of meningococcal disease (MD) specifically. The literature databases Medline and Embase were used by combining search terms for MD and Neisseria meningitidis with terms for severity, mortality and sequelae. Case fatality for sufferers of MD remains high, typically 5-10%, despite the best medical care. Long-term sequelae in survivors may include physical, neurological, cognitive, behavioral and psychological consequences, such as hearing loss, amputations, skin scarring and neurodevelopmental deficits. A significantly lower quality of life is seen in survivors of MD compared with unaffected controls, with detrimental effects of childhood MD continuing into adulthood. MD carries a substantial risk of long-term sequelae and mortality. This should be recognized by physicians treating patients with this disease and lends support for the implementation of preventative measures such as vaccination.