Risk factors for meningococcal disease in children and adolescents: a systematic review and META-analysis.

Invasive meningococcal disease (IMD) remains a major cause of mortality and morbidity in children worldwide. A systemic review in PubMed and Cochrane Controlled Trials Register was performed for articles on risk factors for IMD in children and adolescents published during a 20-year period (19/09/1998 to 19/09/2018). Inclusion and exclusion criteria were established and applied. The data were meta-analyzed using random-effect model and the results were presented on forest plots separately for each risk factor. We identified 12,559 studies (duplicates removed). Titles, abstracts, and full texts were screened and finally, six studies (five case-control and one cohort study) were included in qualitative synthesis, five in meta-analysis. The median age of meningococcal disease (MD) cases was 72.2 months (0-19 years). Household crowding, smoking exposure, close relationships, and recent respiratory tract infections conferred a more than twofold risk for IMD in exposed individuals compared to controls [overcrowded living OR 2.52 (95% CI 1.75-3.63), exposure to smoke OR 2.10 (95% CI 1.00-4.39), kissing OR 2.00 (95% CI: 1.13-3.51), and recent respiratory tract infection OR 3.13 (95% CI 2.02-4.86)]. Attendance of religious events was associated with a decreased risk [0.47 (95% CI, 0.28-0.79)].Conclusion: Our review highlights the importance of individual characteristics as risk factors for IMD in childhood and adolescence. Preventive policies may consider individual as well as social-environmental factors to target individuals at risk.What is Known:• Close relationships, household crowding, and recent respiratory tract infections are major risk factors for IMD.• Passive smoking is a major risk factor for IMD.What is New:• Intimate kissing, household crowding, and passive smoking were found to double the risk of IMD.• Recent respiratory tract infections almost tripled the risk for IMD.

Long-term safety and efficacy of eculizumab in generalized myasthenia gravis.

INTRODUCTION: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy. METHODS: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients. RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001). DISCUSSION: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.

Vaccines in pediatric transplant recipients-Past, present, and future.

Infections significantly impact outcomes for solid organ and hematopoietic stem cell transplantation in children. Vaccine-preventable diseases contribute to morbidity and mortality in both early and late posttransplant time periods. Several infectious diseases and transplantation societies have published recommendations and guidelines that address immunization in adult and pediatric transplant recipients. In many cases, pediatric-specific studies are limited in size or quality, leading to recommendations being based on adult data or mixed adult-pediatric studies. We therefore review the current state of evidence for selected immunizations in pediatric transplant recipients and highlight areas for future investigation. Specific attention is given to studies that enrolled only children.

Meningococcal carriage in high-risk settings: A systematic review.

BACKGROUND: Historically, semi-closed populations have had high rates of meningococcal carriage and have experienced recurrent outbreaks. As such, these high-risk groups are recommended for targeted vaccination in many countries. METHODS: A systematic review of eight databases and Google Scholar forward citations was conducted to characterize serogroup-specific meningococcal carriage in university students, military personnel, and Hajj pilgrims from 2007 to 2016. RESULTS: A total of 7014 records were identified and 22 studies were included. Overall carriage ranged from 0.0% to 27.4% in Hajj pilgrims, from 1.5% to 71.1% in university students, and from 4.2% to 15.2% in military personnel. Among serogroups A, B, C, W, X, and Y, serogroup B was most prevalent in Hajj pilgrims, B and Y in university students, and B, C, and Y in military personnel. 'Other' serogroups were more prevalent in university students than Hajj pilgrims or military personnel. Risk factors for carriage varied by setting. Among Hajj pilgrims, a high endemicity in the country of origin increased the risk of carriage, while smoking, male sex, and frequently attending parties increased the carriage risk for university students. Similarly, smoking increased the carriage risk for professional soldiers. Data gaps remain for many regions. CONCLUSIONS: Preventative vaccination policies for high-risk groups should be based on current disease data in individual countries, supplemented by carriage data. Meningococcal carriage studies and disease surveillance are critical for determining the local epidemiology, populations responsible for disease transmission, and the need for targeted vaccination.

A rare case of septic shock due to Neisseria meningitidis serogroup B infection despite prior vaccination in a young adult with paroxysmal nocturnal haemoglobinuria receiving eculizumab.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired haematopoietic stem cell disease which causes defects in complement inhibiting proteins. The disease presents classically with the triad of haemolytic anaemia, pancytopenia and thrombosis. Eculizumab, a humanized antibody that blocks the cleavage of complement factor 5, was approved for PNH treatment in 2007 and has improved patients' survival since then. However, several cases of invasive meningococcal disease (IMD) have been reported in eculizumab-treated patients, mostly caused by serogroup B infection which was not covered by the previously administered vaccine (MenACWY). We report a rare case of septic shock due to infection with Neisseria meningitis serogroup B despite prior vaccination with 4CMenB in a young PNH patient treated with eculizumab. There are increasing doubts over whether vaccination ensures sufficient immunoprotection against IMD in patients receiving eculizumab. Therefore, besides monitoring the immune response, lifelong chemoprophylaxis should be considered.

Short-term changes in the health state of children with group B meningococcal disease: A prospective, national cohort study.

OBJECTIVES: The short-term impact of childhood invasive meningococcal disease (IMD) on quality-of-life (QoL) remains largely unquantified. This study aimed to quantify QoL loss at the point when illness was at its worst, and assess health state recovery in the months following illness. METHODS: Parents of children aged <16 years with laboratory-confirmed meningococcal group B (MenB) disease in England, with onset dates from November 2012 to May 2013 were asked to complete a short questionnaire, which included EQ-5DY, a version of EQ-5D for 8-15 year-olds. The parents, or child if able, were asked to complete the questionnaires while considering the child's health on the worst day of illness and on the date the questionnaires were completed. RESULTS: The overall response rate was 43% (109/254 children), with no significant differences between respondents and non-respondents. The median time from disease onset to questionnaire completion was 134 days (interquartile range (IQR), 92 to 156 days). After imputation, the median health index was -0.056 (IQR, -0.073 to 0.102) on the worst day of illness, and 1 (IQR 0.866 to 1.000) on the date of questionnaire completion. The respective Visual Analogue Scores (VAS) were 6.5/100.0 (IQR, 0.0 to 20.0) and 95.0/100.0 (IQR, 90.0 to 100.0). The health state of cases with long-term sequelae (n = 41) was significantly worse at follow-up than those who recovered uneventfully (n = 64; 90.0 vs. 98.0; p<0.001), although there was no significant difference on the worst day of illness (5.0 vs. 10.0; p = 0.671). CONCLUSIONS: This work has provided, for the first time, a quantitative estimate of QoL loss at the peak of illness and in the months after MenB disease in children. The magnitude of QoL loss is staggering, with the reported health state being at, or close to, the worst possible outcome imaginable. This study highlights the difficulties in measuring the impact of illness in young children, who often have the highest burden of potentially preventable infectious diseases.

ACG Clinical Guideline: Preventive Care in Inflammatory Bowel Disease.

Recent data suggest that inflammatory bowel disease (IBD) patients do not receive preventive services at the same rate as general medical patients. Patients with IBD often consider their gastroenterologist to be the primary provider of care. To improve the care delivered to IBD patients, health maintenance issues need to be co-managed by both the gastroenterologist and primary care team. Gastroenterologists need to explicitly inform the primary care provider of the unique needs of the IBD patient, especially those on immunomodulators and biologics or being considered for such therapy. In particular, documentation of up to date vaccinations are crucial as IBD patients are often treated with long-term immune-suppressive therapies and may be at increased risk for infections, many of which are preventable with vaccinations. Health maintenance issues addressed in this guideline include identification, safety and appropriate timing of vaccinations, screening for osteoporosis, cervical cancer, melanoma and non-melanoma skin cancer as well as identification of depression and anxiety and smoking cessation. To accomplish these health maintenance goals, coordination between the primary care provider, gastroenterology team and other specialists is necessary.

Nuevo esquema de vacuna antimeningocóccica en niños / New meningococcal vaccine schedule in children

La enfermedad invasiva por meningococo trae aparejada una alta morbimortalidad. Se presenta habitualmente en forma de casos aislados o brotes epidémicos y afecta en la Argentina a 200 a 300 casos por año, principalmente en niños menores de cinco años de edad. Actualmente en nuestro país se encuentran disponibles dos vacunas que cubren los serotipos A, C, Y, W del meningococo (Menactra® y Menveo®). A partir de Marzo de 2015, el Ministerio de Salud de la Nación Argentina incorporó la vacunación universal contra meningococo, estableciendo un esquema con una dosis a los tres y cinco meses y un refuerzo a los 15 meses de vida; y una dosis única para los adolescentes, a los 11 años de edad. (AU)

Invasive meningococcal disease results in high morbidity and mortality. It usually occurs in the form of isolated cases of epidemic outbreaks and affects 200 to 300 cases per year in Argentina, especially in children under five years of age. Vaccines covering meningococcal serotypes A, C, Y, W (Menactra® and Menveo®) are currently available in our country. Since March 2015, the Argentine's Ministry of Health incorporated the universal vaccination against meningococcus, establishing a scheme with two doses at three and five months and a booster at 15 months of life; and a single dose for adolescents, at 11 years of age. (AU)

[Postoperative pulmonary disease associated with haemophilus influenzae and neisseria meningitidis in a diabetic child]. / Pneumopathie postoperatoire à association Haemophilus Influenzae et Neisseria meningitidis chez un enfant diabetique.

Haemophilus influenzae is a saprophyte that colonizes the nasopharynx in nearly two thirds of children and adults. Neisseria meningitidis is a strict human bacterium which lives in the nasopharynx. It can cause benign nasopharyngitis or asymptomatic colonization. We report the case of a diabetic child with postoperative pneumonia associated with Haemophilus influenzae and Neisseria meningitidis. A 3-year old diabetic patient admitted to the Department of Cardiac Surgery due to delayed surgical treatment. The postoperative course was marked by a worsening of respiratory status caused by abundant secretions requiring patient admission to the intensive care unit. An assessment for the detection of infections was performed, including protected distal sampling which revealed the association of Neisseria meningitidis with Haemophilus influenzae. This case study allowed us to highlight bacterial associations in certain high-risk situations. Each of these two species is responsible for various infections. However their presence in the same infected site is rare.

Anticomplement C5 therapy with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

The complement inhibitor eculizumab is a humanized monoclonal antibody against C5. It was developed to specifically target cleavage of C5 thus preventing release of C5a and activation of the terminal pathway. Paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) are 2 diseases with distinctly different underlying molecular mechanisms. In PNH, progeny of hematopoietic stem cells that harbor somatic mutations lead to a population of peripheral blood cells that are deficient in complement regulators resulting in hemolysis and thrombosis. In aHUS, germline mutations in complement proteins or their regulators fail to protect the glomerular endothelium from complement activation resulting in thrombotic microangiopathy and renal failure. Critical to the development of either disease is activation of the terminal complement pathway. Understanding this step has led to the study of eculizumab as a treatment for these diseases. In clinical trials, eculizumab is proven to be effective and safe in PNH and aHUS.

Enfermedad meningocóccica en la Región Metropolitana de Chile y su correlación con factores ambientales / Meningococcal disease in the Metropolitan Region of Chile and its correlation with environmental factors

Introduction: Meningococcal disease (MD) is a public health problem worldwide, due to its high morbidity and mortality. Most cases occur in sub-Saharan Africa, where there is a marked seasonal pattern with predominance during the dry season. Objectives: To describe the morbidity of MD in the Metropolitan Region (MR) of Chile and explore whether there is a correlation between the number of cases with the levels of atmospheric particulate matter PM 10 and PM 2.5, relative humidity (RH), temperature and total environmental pollen. Materials and Methods: Ecological time series study, statistical analysis with R 3.0.1, graphics with Excel 2013. Results: Between 2010 and 2013, 234 MD cases were reported in the MR with an increasing trend. There is a seasonal pattern with an increase of cases from August to October, and a decrease from March to April. There is no correlation with the levels of PM10 and PM2.5. There is a slight positive correlation with RH and a slight negative correlation with temperature. There is a moderate positive correlation with the levels of total environmental pollens. Discussion: Overcrowding and the winter viral infections could explain the increased incidence of MD and the slight correlation with RH and temperature. The moderate correlation with the pollens could be explained by an effect of irritation of the upper airway. Conclusions: More epidemiological studies whose designs allow a greater causal inference are required.

Introducción: La enfermedad meningocóccica (EM) constituye un problema de salud pública mundial debido a su alta morbi-mortalidad. La mayor cantidad de casos ocurre en África subsahariana, donde existe un marcado patrón estacional en la estación seca. Objetivos: Describir la morbilidad de la EM en la Región Metropolitana (RM) de Chile y explorar si existe correlación entre el número de casos con PM 10, PM 2,5 humedad relativa (HR), temperatura y pólenes ambientales totales. Materiales y Métodos: Estudio ecológico tipo series de tiempo, análisis estadístico con R 3.0.1, gráficos con Excel 2013. Resultados: En el período 2010-2013 se notificaron 234 casos de EM en la RM, con una tendencia al alza. Se observa un patrón estacional con aumento de casos entre agosto y octubre y una disminución entre marzo y abril. No existe correlación con los niveles de PM 10 ni de PM 2,5. Se describe una correlación positiva leve con la HR y negativa leve con la temperatura. Existe correlación moderada positiva con los niveles de pólenes totales ambientales. Discusión: El hacinamiento y las infecciones virales de invierno podrían explicar el aumento de casos de EM y la correlación leve con la HR y la temperatura. La correlación moderada con los pólenes podría explicarse por un efecto de irritación de la vía aérea superior. Conclusiones: Se requieren más estudios epidemiológicos cuyos diseños permitan una mayor inferencia causal.

Vacunas frente a la enfermedad meningocócica invarsora / No disponible

No disponible

Muerte súbita por sepsis meningocócica: diagnóstico post mórtem / Sudden death from meningococcal sepsis: postmortem diagnosis

La presentación más común de la enfermedad meningocócica es la meningitis, con una tasa de incidencia de 0,92 por 100.000 habitantes y una letalidad del 40,3% en España. Un cuadro meníngeo puede cursar con síntomas inespecíficos como la cefalea, entre otros, de tal forma que en ocasiones progresa rápidamente en cuestión de horas y provoca la muerte del paciente antes de haber recibido una atención médica adecuada. Además de la meningitis clásica, el meningococo produce una enfermedad sistémica que incluye la sepsis meningocócica y la coagulopatía intravascular diseminada. En pacientes con sepsis meningocócica se ha descrito el síndrome de Waterhouse-Friderichsen, que se caracteriza por hemorragia suprarrenal bilateral, coagulación intravascular diseminada e hígado de shock, y que produce una bacteriemia grave. Esta combinación provoca unshock fulminante y, si no se trata, puede producir muerte súbita. Presentamos el caso de una paciente con odinofagia, fiebre, vómitos y deposiciones diarreicas de 24 horas de evolución, que a pesar de recibir asistencia médica ambulatoria y hospitalaria fallece como consecuencia de una sepsis fulminante por Neisseria meningitidis y síndrome de Waterhouse-Friderichsen no diagnosticado clínicamente (AU)

The most common presentation of meningococcal disease is meningitis, with an incidence rate of 0.92 per 100,000 inhabitants and a mortality rate of 40.3% in Spain. Meningeal disease may present with nonspecific symptoms such as headache, among others, sometimes progressing rapidly to a fatal outcome before the patient receives adequate medical care. Besides classical meningitis, Neisseria meningitis produces a systemic disease that includes meningococcal sepsis and disseminated intravascular coagulopathy. In patients with meningococcal sepsis the Waterhouse-Friderichsen syndrome is described, which is characterized by bilateral adrenal hemorrhage, intravascular coagulation and shock liver, producing a severe bacteremia. This combination causes a fulminant shock and, if untreated, it may cause sudden death. We report the case of a female patient with sore throat, fever, vomiting and diarrhea of 24 hours of evolution. Despite receiving inpatient and outpatient medical care, she died as a result of N. meningitidis fulminant sepsis and clinically undiagnosed Waterhouse-Friderichsen syndrome (AU)

[Meningococcal disease in the Metropolitan Region of Chile and its correlation with environmental factors]. / Enfermedad meningocóccica en la Región Metropolitana de Chile y su correlación con factores ambientales.

INTRODUCTION: Meningococcal disease (MD) is a public health problem worldwide, due to its high morbidity and mortality. Most cases occur in sub-Saharan Africa, where there is a marked seasonal pattern with predominance during the dry season. OBJECTIVES: To describe the morbidity of MD in the Metropolitan Region (MR) of Chile and explore whether there is a correlation between the number of cases with the levels of atmospheric particulate matter PM 10 and PM 2.5, relative humidity (RH), temperature and total environmental pollen. MATERIALS AND METHODS: Ecological time series study, statistical analysis with R 3.0.1, graphics with Excel 2013. RESULTS: Between 2010 and 2013, 234 MD cases were reported in the MR with an increasing trend. There is a seasonal pattern with an increase of cases from August to October, and a decrease from March to April. There is no correlation with the levels of PM10 and PM2.5. There is a slight positive correlation with RH and a slight negative correlation with temperature. There is a moderate positive correlation with the levels of total environmental pollens. DISCUSSION: Overcrowding and the winter viral infections could explain the increased incidence of MD and the slight correlation with RH and temperature. The moderate correlation with the pollens could be explained by an effect of irritation of the upper airway. CONCLUSIONS: More epidemiological studies whose designs allow a greater causal inference are required.

C5 complement deficiency in a Saudi family, molecular characterization of mutation and literature review.

INTRODUCTION: Complement deficiencies are rare primary immunodeficiency disorders, the diagnosis of which is often underestimated. Only a small number of molecular studies have been carried out for the characterization of the underlying genetic defects in these cases. PURPOSE: Reporting the first family from the Arabian Gulf region with multiple members affected by meningococcemia and abscent serum complement 5 (C5). We tried to correlate clinical, biochemical and molecular genetics features of this family. METHODS: Determination of the serum level of all complement proteins including the terminal cascade (C5-9), followed by mutation analysis on DNA extracted from fresh blood samples of each alive family member. RESULTS: Molecular studies showed a homozygous nonsense mutation in exon 1, with the change of cytosine to thymine at position 55 (55C > T) leading to change of the glutamine amino acid at position 19 to a stop codon (Q19X), and serologically absence of C5 in the serum. A similar but compound heterozygous mutation has been reported in one African-American family. previously. CONCLUSION: Characterization of the underlying mutations in C5 deficient families is important, to understand this uncommon complement deficiency, and try to elucidate structure-function relationships in the C5 gene. This report also highlights the importance of complement screening in cases of sporadic meningococcal Infections, especially in communities with high prevalence of consanguineous marriages, which will ensure timely and adequate clinical interventions.