Epidemiología de la enfermedad meningocócica en República Dominicana 2012-2022: bases para su prevención / Epidemiology of meningococcal disease in Dominican Republic 2012-2022: strategies for its prevention

Objetivo: La Enfermedad Meningocócica Invasiva es una causa frecuente de morbimortalidad mundial. El objetivo de este estudioes describir la epidemiología de la enfermedad meningocócica en República Dominicana desde 2012 a 2022 y proponer las basespara su prevención.Método: En el análisis se calcularon incidencias, tasas de hospitalización por cada 100.000 habitantes, tasas de letalidad y se hizouna comparación entre grupos de edad de los 325 casos de meningococcemia reportados en el Sistema Nacional de VigilanciaEpidemiológica Dominicano durante estos 10 años.Resultados principales: El 33% de los casos (103) tenía menos de 5 años. Este grupo de edad fue el que tuvo la tasa de hospitalizaciónmás alta, la mayor tasa de mortalidad en edad pediátrica la mayor letalidad.Conclusiones: Si la República Dominicana vacunara a su población, debería comenzar con los menores de 5 años, y así se reduciríanlas hospitalizaciones, muertes, complicaciones y secuelas producidas por el meningococo. (AU)

Objective: Invasive meningococcal disease is a frequent cause of morbidity and mortality worldwide. The aim of this study is todescribe the epidemiology of meningococcal disease in the Dominican Republic from 2012 to 2022 and to propose the basis for itsprevention.Methods: Incidences, hospitalization rates per 100,000 population, case fatality rates and a comparison between age groups ofthe 325 cases of meningococcemia reported in the Dominican National Epidemiological Surveillance System during these 10 yearswere calculated in the analysis.Main results: 33% of the cases (103) were less than 5 years old. This age group had the highest hospitalization rate, the highestmortality rate in pediatric age and the highest case fatality rate.Conclusions: If the Dominican Republic were to vaccinate its population, it should start with those under 5 years of age, and thiswould reduce hospitalizations, deaths, complications and sequelae caused by meningococcus. (AU)

Transtentorial herniation syndrome from meningococcal meningitis in a young woman: the case for neurocritical care.

We report a case of a previously healthy early adolescent female who presented with meningococcal meningitis. While in hospital, she had marked neurologic deterioration with clinical herniation from malignant cerebral oedema. She was transferred to a neurocritical care centre where she underwent invasive intracranial pressure (ICP) and brain tissue oxygen (PbtO2) monitoring. Early in her course, she demonstrated a compete absence of autoregulation, with pressure passive cerebral blood flow. As a result, maintaining a mean arterial pressure between 50 mm Hg and 60 mm Hg, which ensured adequate cerebral oxygenation, while avoiding increases in ICP. Although her course was initially complicated by bilateral optic neuropathy, she has subsequently made a full neurologic recovery and is now undertaking postsecondary education. This case highlights that access to specialist neurocritical care, guided by neurophysiologic monitoring of ICP and PbtO2, may help improve outcomes, even among those patients with catastrophic cerebral oedema from bacterial meningitis.

MeningiSSS: A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis.

BACKGROUND: Knowing the individual child's risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors. METHODS: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure. RESULTS: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores' results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson-Todd Scale (AUC = 0.79) was all associated with death. CONCLUSIONS: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.

Multi-component meningococcal serogroup B (MenB)-4C vaccine induces effective opsonophagocytic killing in children with a complement deficiency.

Vaccination against meningococcal serogroup B is recommended for patients with a complement deficiency; however, although immunogenicity in this patient group has been shown, efficacy has not yet been established. In this study, we collected serum from children with a complement deficiency in the alternative pathway or in late terminal pathway before and after vaccination with multi-component meningococcal serogroup B (MenB)-4C. MenB-4C is a multi-component, protein-based vaccine against MenB consisting of factor H-binding protein, Neisserial heparin-binding protein, Neisserial adhesion A and outer membrane vesicles containing Porin A. We assessed the vaccine immunogenicity and vaccine-mediated protection by a whole cell enzyme-linked immunosorbent assay with Neisseria meningitidis serogroup B strains H44/76, 5/99 and NZ98/254, which shows that vaccination induced antibody titers against meningococcus. We show that the classical serum bactericidal activity assay with exogenous serum indicates the presence of vaccine-induced antibodies and capacity to activate complement-mediated pathogen lysis. However, in children with a late terminal pathway deficiency, no complement-mediated pathogen lysis was observed when autologous serum was applied in the serum bactericidal activity assay, demonstrating a lack of serum bactericidal activity in children with complement deficiencies. However, MenB-4C vaccination still induced effective complement-dependent opsonophagocytic killing against N. meningitidis serogroup B in reconstituted whole blood with autologous serum from children with an alternative pathway or late terminal pathway deficiency. These findings support the recommendation to vaccinate all complement-deficient children against MenB.

Community-acquired acute bacterial meningitis in adults: a clinical update.

BACKGROUND: Acute bacterial meningitis (ABM) in adults is associated with a mortality that may exceed 30%. Immunization programs have reduced the global burden; in the UK, declining incidence but persistently high mortality and morbidity mean that clinicians must remain vigilant. SOURCES OF DATA: A systematic electronic literature search of PubMed was performed to identify all ABM literature published within the past 5 years. AREAS OF AGREEMENT AND CONTROVERSY: Clinical features cannot reliably distinguish between ABM and other important infectious and non-infectious aetiologies. Prompt investigation and empirical treatment are imperative. Lumbar puncture (LP) and cerebrospinal fluid microscopy, biochemistry and culture remain the mainstay of diagnosis, but molecular techniques are increasingly useful. The 2016 UK joint specialist societies' guideline provides expert recommendations for the management of ABM, yet published data suggest clinical care delivered in the UK is frequently not adherent. Anxiety regarding risk of cerebral herniation following LP, unnecessary neuroimaging, underutilization of molecular diagnostics and suboptimal uptake of adjunctive corticosteroids compromise management. GROWING POINTS: There is increasing recognition that current antibiotic regimens and adjunctive therapies alone are insufficient to reduce the mortality and morbidity associated with ABM. AREAS TIMELY FOR DEVELOPING RESEARCH: Research should be focused on optimization of vaccines (e.g. pneumococcal conjugate vaccines with extended serotype coverage), targeting groups at risk for disease and reservoirs for transmission; improving adherence to management guidelines; development of new faster, more accurate diagnostic platforms (e.g. novel point-of-care molecular diagnostics); and development of new adjunctive therapies (aimed at the host-inflammatory response and bacterial virulence factors).

Acute Bilateral Oculomotor Nerve Palsy in an Adult Patient with Neisseria meningitidis.

A 69-year-old woman was admitted to our hospital with a fever, dizziness, and headache caused by Neisseria meningitidis. After ceftriaxone was administered, she suddenly developed bilateral oculomotor nerve palsy. Intra-orbital magnetic resonance imaging using appropriate sequences revealed that her bilateral third intracranial nerves were enlarged and enhanced. She achieved complete recovery by two months after additional short-term treatment with intravenous immunoglobulin and methylprednisolone. Although intracranial nerve disorders that result from bacterial meningitis are most frequently reported in children, it is noteworthy that it can also cause focal intracranial nerve inflammation with ophthalmoparesis in N. meningitidis infection in adults.

Pediatric meningococcocal meningitis in the acute phase: how much does it cost?

BACKGROUND: Meningococcal meningitis (MM) is known to be responsible of high cost for the Public Health Administration. Aim of the work is to calculate the costs for the hospitalization of pediatric patients affected by MM. METHODS: We calculate the costs for the hospitalization of pediatric patients affected by MM in the acute phase (HAP) over a nine year period. We performed a MEDLINE search to verify the cost of MM HAP reported in other studies. RESULTS: At Bambino Gesù Children Hospital, the median cost of HAP was of 12,604 euro (range from 9203 to 35,050 euro). Comparing our data with the previous studies, we find out similar results of approximately 16,750 euro (range 12,000-20,000 euro). DISCUSSION: Despite the relative rarety of the disease, MM is associated to direct high cost of HAP. CONCLUSIONS: Hospital costs are an important end-point in health economic evaluation of the disease and may be useful to policy makers and health economists to understand the potential benefit of improving meningococcal vaccination programmes.

Transcranial Doppler in pediatric emergency and intensive care unit: a case series and literature review.

PURPOSE: Transcranial Doppler (TCD) has been used for more than 30 years in clinical practice. Although adult intensive care is relatively well covered, pediatric cases are still underrepresented. We intend to review a series of pediatric cases where TCD was determinant in clinical decisions and a literature review on this topic. METHODS: We describe cases with different pathologies where TCD had an important role in clinical management of the patients. We discuss TCD utility and potential role both in the emergency department and the intensive care unit. RESULTS: Five patients with different neurologic insults are presented. TCD was useful in the identification of intracranial hypertension in traumatic brain injury, hydrocephalus and central nervous system infection; identification of decreased cerebral perfusion pressure in hypovolemic shock and the diagnosis of impending cerebral circulatory arrest in a child with meningococcal septicemia. We discuss how TCD can be used in emergency and intensive care settings, reviewing relevant literature and our own experience. CONCLUSIONS: Non-invasive testing using TCD can aid clinical decisions. More widespread use of this technique will allow for better care of children with neurologic insults.

Immunization with recombinant truncated Neisseria meningitidis-Macrophage Infectivity Potentiator (rT-Nm-MIP) protein induces murine antibodies that are cross-reactive and bactericidal for Neisseria gonorrhoeae.

Neisseria meningitidis (Nm) and N. gonorrhoeae (Ng) express a Macrophage Infectivity Potentiator (MIP, NMB1567/NEIS1487) protein in their outer membrane (OM). In this study, we prepared independent batches of liposomes (n = 3) and liposomes + MonoPhosphoryl Lipid A (MPLA) (n = 3) containing recombinant truncated Nm-MIP protein encoded by Allele 2 (rT-Nm-MIP, amino acids 22-142), and used these to immunize mice. We tested the hypothesis that independent vaccine batches showed similar antigenicity, and that antisera could recognise both meningococcal and gonococcal MIP and induce cross-species bactericidal activity. The different batches of M2 rT-Nm-MIP-liposomes ±â€¯MPLA showed no significant (P > 0.05) batch-to-batch variation in antigenicity. Anti-rT-Nm-MIP sera reacted equally and specifically with Nm-MIP and Ng-MIP in OM and on live bacterial cell surfaces. Specificity was shown by no antiserum reactivity with Δmip bacteria. Using human complement/serum bactericidal assays, anti-M2 rT-Nm-MIP sera killed homologous meningococcal serogroup B (MenB) strains (median titres of 32-64 for anti-rT-Nm-MIP-liposome sera; 128-256 for anti-rT-Nm-MIP-liposome + MPLA sera) and heterologous M1 protein-expressing MenB strains (titres of 64 for anti rT-Nm-MIP-liposome sera; 128-256 for anti-rT-Nm-MIP-liposome + MPLA sera). Low-level killing (P < 0.05) was observed for a MenB isolate expressing M7 protein (titres 4-8), but MenB strains expressing M6 protein were not killed (titre < 4-8). Killing (P < 0.05) was observed against MenC and MenW bacteria expressing homologous M2 protein (titres of 8-16) but not against MenA or MenY bacteria (titres < 4-8). Antisera to M2 rT-Nm-MIP showed significant (P < 0.05) cross-bactericidal activity against gonococcal strain P9-17 (expressing M35 Ng-MIP, titres of 64-512) and strain 12CFX_T_003 (expressing M10 Ng-MIP, titres 8-16) but not against FA1090 (expressing M8 Ng-MIP). As an alternative to producing recombinant protein, we engineered successfully the Nm-OM to express M2 Truncated-Nm-MIP, but lipooligosaccharide-extraction with Na-DOC was contra-indicated. Our data suggest that a multi-component vaccine containing a select number of Nm- and Ng-MIP type proteins would be required to provide broad coverage of both pathogens.

An epidemic of meningococcal disease in children in North Norway in the 1970s and 1980s was dominated by a hypervirulent group B strain.

AIM: We examined children hospitalised for invasive meningococcal disease, a leading cause of paediatric sepsis, in Troms County, North Norway, from 1973 to 2016, including the epidemic in the 1970s and 1980s. METHODS: This study was a retrospective review of children under the age of 15 years who were hospitalised for meningococcal disease at the University Hospital of North Norway and Harstad Hospital. We studied hospital and bacteriological records to determine the incidence rates and phenotypes involved. RESULTS: There were 300 cases under 15 years and an incidence rate of 17 per 100,000 cases for 1973-2016. This was broken down into the following: 1973-1980 (n = 130, 49), 1981-1990 (n = 129, 39), and 1991-2016 (n = 41, 4.7), respectively. There were 21 (7%) deaths. Phenotype B:15:P1.7,16 was more common than the other phenotypes in the epidemic period before 1990 than after 1990 (p = 0.02) and had a significantly lower mortality rate than the other phenotypes (p = 0.04). Later years showed a more heterogenous phenotype distribution. Serogroup B was the dominant serogroup. CONCLUSION: The B:15:P1.7,6 strain was more prevalent during the Norwegian epidemic of invasive meningococcal disease, but had a significantly lower mortality rate. The phenotype distribution was more heterogeneous after 1990. The dominant serogroup was B.

Clinical findings and management of patients with meningitis with an emphasis on Haemophilus influenzae meningitis in rural Tanzania.

INTRODUCTION: The spectrum of meningitis pathogens differs depending on the age of patients and the geographic region, amongst other. Although meningitis vaccination programs have led to the reduction of incidence rates, an imbalance between low- and high-income countries still exists. METHODS: In a hospital-based study in rural northern Tanzania, we consecutively recruited patients with confirmed meningitis and described their clinical and laboratory characteristics. RESULTS: A total of 136 patients with meningitis were included. Fever (85%), meningism (63%) and impairment of consciousness (33%) were the most frequent clinical symptoms/signs. Nearly 10% of all patients tested were positive for malaria. The majority of the patients with bacterial meningitis (39%), especially those under 5years of age, were confirmed to be infected with Haemophilus influenzae (26%), Streptococcus pneumoniae (19%) and Neisseria meningitidis (15%). Haemophilus influenzae represented the dominant causative organism in children under 2years of age. CONCLUSION: Our study emphasizes the importance of recognizing warning symptoms like fever, meningism and impairment of consciousness, implementing laboratory tests to determine responsible pathogens and evaluating differential diagnoses in patients with meningitis in sub-Saharan Africa. It also shows that Haemophilus influenza meningitis is still an important cause for meningitis in the young, most probabaly due to lack of appropriate vaccination coverage.

Meningitis neonatal por Neisseria meningitidis serogrupo B / Neonatal meningitis caused by serogroup B Neisseria meningitides

La meningitis meningocóccica es una infección poco frecuente en el período neonatal internacionalmente, y solo hay una publicación previa en la literatura médica cubana hace 25 años atrás, de recién nacidos con meningitis bacteriana causada por Neisseria meningitidis. Se presenta el caso de un recién nacido febril, con manifestaciones de toxicidad, fontanela abombada, y cuando se realizó punción lumbar, se encontró pleocitosis del líquido cefalorraquídeo y se aisló N. meningitidis serogrupo B, por lo que se diagnostica meningitis meningocóccica neonatal. Tuvo evolución favorable. Se describen algunas características de la infección meningocócica, y se destaca el diagnóstico y tratamiento recomendado para este tipo de infección, así como se hace referencia a reportes de casos publicados en la literatura internacional(AU)

Meningoccocal meningitis is a rare infection in the neonatal period worldwide and there is just one publication in the Cuban medical literature dated 25 years ago, which presented some neonates with bacterial meningitis caused by Neisseria meningitides. This is a febrile neonate with toxicity manifestations and bulging fontanelle; he was performed a lumbar puncture to find spinal fluid pleocytosis and the serogroup B N. meningitides was then isolated, so he was diagnosed with neonatal meningococcal meningitis with favorable progression. Some characteristics of the meningococcal infection, the diagnosis and recommended treatment were described in addition to making reference to case reports published in the international literature(AU)

Meningitis neonatal por Neisseria meningitidis serogrupo B / Neonatal meningitis caused by serogroup B Neisseria meningitides

La meningitis meningocóccica es una infección poco frecuente en el período neonatal internacionalmente, y solo hay una publicación previa en la literatura médica cubana hace 25 años atrás, de recién nacidos con meningitis bacteriana causada por Neisseria meningitidis. Se presenta el caso de un recién nacido febril, con manifestaciones de toxicidad, fontanela abombada, y cuando se realizó punción lumbar, se encontró pleocitosis del líquido cefalorraquídeo y se aisló N. meningitidis serogrupo B, por lo que se diagnostica meningitis meningocóccica neonatal. Tuvo evolución favorable. Se describen algunas características de la infección meningocócica, y se destaca el diagnóstico y tratamiento recomendado para este tipo de infección, así como se hace referencia a reportes de casos publicados en la literatura internacional.

Meningoccocal meningitis is a rare infection in the neonatal period worldwide and there is just one publication in the Cuban medical literature dated 25 years ago, which presented some neonates with bacterial meningitis caused by Neisseria meningitides. This is a febrile neonate with toxicity manifestations and bulging fontanelle; he was performed a lumbar puncture to find spinal fluid pleocytosis and the serogroup B N. meningitides was then isolated, so he was diagnosed with neonatal meningococcal meningitis with favorable progression. Some characteristics of the meningococcal infection, the diagnosis and recommended treatment were described in addition to making reference to case reports published in the international literature.

[Acute care of patients with bacterial meningitis]. / Akutversorgung von Patienten mit bakterieller Meningitis.

BACKGROUND: Bacterial meningitis is a life-threatening emergency that is still associated with high mortality and poor outcome. OBJECTIVE: The purpose of this article is to provide a review of clinical presentation, diagnostic procedure, therapy, and prognosis in bacterial meningitis. Prognostic factors which could be influenced positively are identified and a focused procedure in the emergency setting and for the treatment of complications are provided. MATERIAL AND METHODS: This work is based on a literature search (PubMed, guidelines) and personal experience (standard operating procedures, SOP). RESULTS: Despite improved health care, bacterial meningitis is still associated with high mortality and poor neurological outcome, which has remained largely unaltered during recent decades. Diagnosis and, more importantly, effective therapy of bacterial meningitis are often delayed, having an immediate negative influence on clinical outcome. Neurological and nonneurological complications often necessitate intensive care and may occur rapidly or in the further course of the disease. CONCLUSION: Immediate initiation of effective therapy is crucial to positively influence mortality and neurological outcome. Antibiotics should be administered within 30 min after admission. To achieve this, a focused and well-organized procedure in the emergency setting is necessary. Because of intra- and extracranial complications, patients need to be treated on intensive care units including neurological expertise and interdisciplinary support.

Méningites à méningocoque en milieu pédiatrique sénégalais. A propos de 79 cas

La méningite cérébrospinale constitue un problème majeur de santé publique, du fait de son potentiel épidémique. Objectifs : L'objectif de ce travail était de décrire les caractéristiques cliniques, épidémiologiques, cliniques, bactériologiques et évolutives des méningites à méningocoque au Centre Hospitalier National d'Enfants Albert Royer (CHNEAR). Méthodes : Il s'agit d'une étude rétrospective, descriptive, et analytique. Tous les enfants âgés de 0 à 15 ans, hospitalisés pour méningite à méningocoque au CHNEAR, entre le 1er janvier 2004 et le 31 décembre 2013, étaient inclus dans cette étude. Résultats : Nous avons colligé 79 cas de méningite à méningocoque parmi les 1491 cas de méningites bactériennes pédiatriques (MBP). Ce qui représentait 3,45% des méningites bactériennes et 0,18% de l'ensemble des hospitalisations. Le sex-ratio 1,92 était en faveur des garçons. L'âge moyen était de 53,3 mois. La majorité des cas était survenue durant la saison sèche, soit 72%, avec des pics en mars et avril. La malnutrition a été décrite chez 4 enfants. La symptomatologie clinique était dominée par la fièvre (95%), la raideur méningée (82,3%), les céphalées (34,2%) et les troubles digestifs (34,2%). Le sérogroupe W135 (54 cas) était le plus isolé suivi des sérogroupes B (7 cas), C (7 cas), et A (5 cas). Dans 6 cas, le sérogroupe était indéterminé. La létalité était de 3,8%. Conclusion : L'incidence des méningites à méningocoques est de 0,18% en milieu pédiatrique sénégalais. Le sérogroupe W135 est en responsable de 2/3 des cas, d'où la nécessité de sa prise en compte dans les stratégies vaccinales actuelles au Sénégal

Response Strategies against Meningitis Epidemics after Elimination of Serogroup A Meningococci, Niger.

To inform epidemic response strategies for the African meningitis belt after a meningococcal serogroup A conjugate vaccine was introduced in 2010, we compared the effectiveness and efficiency of meningitis surveillance and vaccine response strategies at district and health area levels using various thresholds of weekly incidence rates. We analyzed reports of suspected cases from 3 regions in Niger during 2002-2012 (154,392 health area weeks), simulating elimination of serogroup A meningitis by excluding health area years with identification of such cases. Effectiveness was highest for health area surveillance and district vaccination (58-366 cases; thresholds 7-20 cases/100,000 doses), whereas efficiency was optimized with health area vaccination (5.6-7.7 cases/100,000 doses). District-level intervention prevented <6 cases (0.2 cases/100,000 doses). Reducing the delay between epidemic signal and vaccine protection by 2 weeks doubled efficiency. Subdistrict surveillance and response might be most appropriate for meningitis epidemic response after elimination of serogroup A meningitis.