RESUMEN
Bacterial meningitis is still a significant public health concern, with high morbidity and mortality rates. Despite this, it is still a rare event that requires the bacterial invasion of the meninges. However, some predisposing factors can trigger recurrent episodes of meningitis. This study is aimed at determining the clinical characteristics and the molecular epidemiology of episodes of recurrent community-acquired meningitis with and without predisposing factors. For this purpose, we performed a retrospective study of our laboratory database during the period of 2010 to 2020. Additionally, using molecular tools developed in our previous works, the epidemiology of the pathogens causing these episodes was analyzed using cerebrospinal fluid samples, especially in the absence of isolated strains. We observed a total of 1,779 meningitis cases and 230 were caused by Streptococcus pneumoniae. Of those, 16 were recurrent meningitis episodes (16/1,779; 0.9%) from seven patients. Pneumococcus was the main agent responsible in these recurrent episodes and only two episodes were caused by Haemophilus influenzae. The mean age of these patients was 20 years old and three had predisposing factors which could have led to contracting meningitis. The samples presented different pneumococcal serotypes. Most of them were non-vaccine-covered serotypes and antibiotic susceptible strains. Therefore, it was demonstrated how the practical employment of molecular tools, developed for research, when applied in the routine of diagnosis, can provide important information for epidemiological surveillance. Furthermore, it was shown how pneumococcus was the leading cause of recurrent community-acquired meningitis without predisposing factors, suggesting that pneumococcal vaccination may be necessary, even in those groups of individuals considered to be less susceptible.
Asunto(s)
Infecciones Comunitarias Adquiridas , Meningitis Neumocócica , Recurrencia , Streptococcus pneumoniae , Humanos , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/epidemiología , Meningitis Neumocócica/epidemiología , Meningitis Neumocócica/microbiología , Adulto , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pneumoniae/clasificación , Estudios Retrospectivos , Femenino , Masculino , Adulto Joven , Persona de Mediana Edad , Adolescente , Factores de Riesgo , Serogrupo , Antibacterianos , Haemophilus influenzae/genética , Haemophilus influenzae/aislamiento & purificación , Haemophilus influenzae/clasificaciónRESUMEN
Bacterial meningitis is considered a life-threatening condition with high mortality rates. In response to the infection, signaling cascades, producing pro-inflammatory mediators trigger an exacerbated host immune response. Another inflammatory pathway occurs through the activation of inflammasomes. Studies highlight the role of the NLR family pyrin domain containing 3 (NLRP3) in central nervous system disorders commonly involved in neuroinflammation. We aimed to investigate the role of NLRP3 and its inhibitor MCC950 on neurochemical, immunological, and behavioral parameters in the early and late stages of experimental pneumococcal meningitis. For this, adult male Wistar rats received an intracisternal injection of Streptococcus pneumoniae or artificial cerebrospinal fluid as a placebo. The animals were divided into control/saline, control/MCC950, meningitis/saline, and meningitis/MCC950. Immediately after the meningitis induction, the animals received 140 ng/kg MCC950 via intracisternal injection. For the acute protocol, 24 h after induction, brain structures were collected to evaluate cytokines, NLRP3, and microglia. In the long-term group, the animals were submitted to open field and recognition of new objects tests at ten days after the meningitis induction. After the behavioral tests, the same markers were evaluated. The animals in the meningitis group at 24 h showed increased levels of cytokines, NLRP3, and IBA-1 expression, and the use of the MCC950 significantly reduced those levels. Although free from infection, ten days after meningitis induction, the animals in the meningitis group had elevated cytokine levels and demonstrated behavioral deficits; however, the single dose of NLRP3 inhibitor rescued the behavior deficits and decreased the brain inflammatory profile.
Asunto(s)
Meningitis Neumocócica , Animales , Masculino , Ratas , Citocinas/metabolismo , Inflamasomas/metabolismo , Trastornos de la Memoria , Meningitis Neumocócica/complicaciones , Meningitis Neumocócica/tratamiento farmacológico , Modelos Teóricos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Wistar , Sulfonamidas/farmacología , Sulfonamidas/uso terapéuticoRESUMEN
INTRODUCCIÓN La enfermedad neumocócica (EN) es una infección bacteriana causada por Streptococcus pneumoniae, que afecta principalmente a la población pediátrica, adultos mayores de 65 años y personas con factores de riesgo. La prevención se basa en la vacunación, ya sea con vacunas conjugadas (VCN) o vacunas polisacáridas (VNP). En España se recomienda actualmente la VCN13 para niños y la VNP23 para mayores de 60 o 65 años; a los grupos de riesgo se les administra VNP23 sola o en combinación con VCN13. Las nuevas VCN frente a 15 y 20 serotipos - VCN15 y VCN20 - recientemente autorizadas por la Comisión Europea, han sido desarrolladas para abordar el aumento de casos de EN por serotipos no cubiertos por las vacunas actuales. Han demostrado su no inferioridad en inmunogenicidad respecto a VCN13, pero aún no se dispone de datos de eficacia protectora. Para la posible sustitución de la vacunación actual por las nuevas VCN se precisa de resultados de su coste-efectividad. OBJETIVOS Evaluar el coste-efectividad, describir las consi
INTRODUCTION Pneumococcal disease is a bacterial infection caused by Streptococcus Pneumoniae, which mainly affects children, older adults above 65 years old and people with underlying conditions. Prevention consists of vaccination, with either conjugate vaccines (PCV) or polysaccharide vaccines (PPSV). In Spain, PCV13 is recommended for children and PPSV23 for adults older than 60 or 65 years, while populations with underlying conditions are vaccinated with PPSV23 alone or in combination with PCV13. New PCVs against 15 and 20 serotypes - PCV15 and PCV20 - recently authorized by the European Commission, have been developed in order to address the increase of cases of Pneumococcal disease caused by serotypes not covered by current vaccine options. These new options have proven their non-inferiority regarding immunogenicity of PCV13, but data on their protective efficiency is not available. In order to explore the possibility of substituting current vaccination options for the new PCV options, results on their cost-effectiveness are needed. OBJECTIVES Evaluate cost-effectiveness, describe ethical, legal, organizational, social and environmental considerations, and identify research needs regarding universal vaccination against pneumococcal disease with the new PCV against 15 and 20 serotypes. METHOD Systematic review of economic evaluations A systematic review was conducted in order to identify scientific evidence regarding cost-effectiveness of universal vaccination against Pneumococcal Disease with PCV15 or PCV20 in the paediatric population, population over 65 years old or population with underlying conditions. Studies published until 31/8/2023 were eligible. Methodological quality was valued following the criteria proposed by Drummond et al. Cost-effectiveness analysis A complete economic evaluation was carried out, in which costs and health outcomes for universal vaccination against pneumococcal disease were evaluated for three populations: children younger than 5 years old, immunocompetent population older than 65 years of age and immunocompromised population older than 18 years of age. This analysis was based on a decision model which synthesizes Spain's epidemiologic data (2022 incidence), vaccine efficiency and costs, as well as consequences and/or side effects of the diseases of interest (in terms of costs and quality-adjusted life years (QALY) gained). Three Markov models with annual cycles were developed. A 3% discount rate was applied to both costs and effects. For each vaccination strategy considered the incremental cost-effectiveness ratio (ICER) was calculated and it was compared with the cost-effectiveness threshold of 25 000/QALY. In addition, probabilistic and deterministic sensitivity analyses were carried out. Budget impact analysis A budget impact analysis for a period of 5 years was conducted in order to inform about the cost that the implantation of the new vaccination strategies would have for the Spanish National Health System. RESULTS Systematic review of economic evaluations After conducting a systematic search in four electronic databases, 16 economic evaluations that evaluated at least one of the new PCV were identified. ⢠Children: Six studies evaluated paediatric vaccination, only one of them without conflict of interest. Results were homogeneous, finding the new PCVs cost-effective or dominant compared to PCV13 for different European countries, USA and Japan. In the economic evaluation identified for Spain and funded by PCV15 manufacturer, it is concluded that this new vaccine is cost-effective compared to PCV13, with an ICER of 3582 per QALY. ⢠Elderly: Ten economic evaluations were identified in Europe, USA and Japan, only two of them without conflict of interest. Nine studies concluded that the new PCV is dominant or cost-effective compared to the current strategy of the country. Four studies compared the new PCVs with one another, including one study in Spain, and results allowed the conclusion in favour of the PCV20, regardless of the funding. ⢠Population with underlying conditions: Evaluated in five studies conducted in Europe, all of them being funded by one of the manufacturers. All the studies conclude in favour of the new PCV evaluated, when compared to the current strategy of each country. Comparison between PCV15 and PCV20 benefits PCV20, regardless of the funding. Cost-effectiveness analysis ⢠Paediatric population: New PCVs would avoid more cases of illness caused by Streptococcus Pneumoniae than the current strategy (PCV13). The strategy of replacing PCV13 for the PCV15 would be dominant (more effective and less costly), while its substitution for the PCV20 would not be cost-effective (ICER 169,335 per QALY). Results are sensitive to vaccine coverage (if it decreases, ICER increases) and to vaccine price (PCV20 would be cost-effective if its price would drop by 22%, from 47.2 to 36.6). Lowering PCV13's price, new PCVs become not cost-effective. ⢠Immunocompetent population over 65 years: New vaccines are also more beneficial than the current strategy (PPSV23). Strategies that include PCV20 (combined with PPSV23 or alone) are dominant compared to the current strategy, being the PCV20+PPSV23 dominant when compared to the rest of strategies. PCV15 in sequence with PPSV23 would be cost-effective (ICER 1561 per QALY) and PCV15 alone would not be cost-effective (ICER 36,792 per QALY). These results change if the indirect effects of paediatric vaccination with the new PCVs are taken into consideration (only sequential strategies would be cost-effective), or if the PCV15's price would drop by 13% (from 45 to 39). ⢠Immunocompromised adult population: The two most effective strategies are the new PCVs in combination with PPSV23, being both of them dominant against current strategy (PCV13+PPSV23). The sequential strategy involving PCV20+PPSV23 is dominant over the rest of evaluated alternatives. Budget impact analysis ⢠Paediatric population: Vaccination with PCV15 instead of with PCV13 would save 4.2 million euros in the following 5 years. As for PCV20, the impact would be of 92.2 million euros in the following 5 years. ⢠Immunocompetent population over 65 years: Substituting PPSV23 with PCV20 would have a net budget impact of 53 million euros in 5 years; the strategy involving PCV20+PPSV23 would have an impact of 91.2 million euros in 5 years. Both strategies with PCV15 would have an impact of 56.8 and 93.1 million euros in the following 5 years, respectively. ⢠Immunocompromised adult population: Strategies involving PCV20 (alone or with PPSV23) and PCV15 alone would generate savings for the NHS of 207.8 million, 39.3 million and 154.4 million euros, respectively, while the strategy with PCV15+PPSV23 would have an insignificant impact in the following 5 years. CONCLUSIONS Available evidence in scientific literature is limited and comes from studies developed in Europe, USA and Japan, mainly funded by the new PCVs' manufacturers. Most of the published economic evaluations conclude that the vaccination strategies which include new PCVs are cost-effective or dominant: ⢠In the paediatric population new PCVs are cost-effective or dominant (more effective and less costly) compared to PCV13. Specifically, the economic evaluation identified for Spain concludes that PCV15 is cost-effective. ⢠For the population of older adults (≥65 years old), the majority of studies conclude that the new PCV evaluated (PCV15 or PCV20) is dominant or cost-effective against the current strategy of each country. Comparisons between new PCVs with one another, including the Spanish study, conclude in favour of PCV20, regardless of the funding. ⢠For the population with underlying conditions, all the economic evaluations conclude in favour of the new PCVs compared to the current recommendations for each country, and in favour of the PCV20 when compared with PCV15, regardless of the funding. Results of the cost-effectiveness model developed for this report, suggest that in Spain: ⢠In the paediatric population vaccination with PCV15 is a more effective and less costly strategy (dominant) when compared to the current strategy with PCV13. Vaccination with PCV20, apart from requiring an additional dose, is not cost-effective and it only would be if the vaccine price drops by 22%. ⢠In immunocompetent older adults above 65 years old, vaccination with PCV20 alone or in combination with PPSV23 are dominant strategies. PCV15 is only cost-effective if combined with PPSV23. PCV15 alone could be considered cost-effective if its price drops by 13%. ⢠Regarding immunocompromised adult population, PCV15+PPSV23 and PCV20+PPSV23 strategies are dominant and this last one (PCV20+PPSV23) is dominant compared to the rest of alternatives. ⢠Results are sensitive to variations in some parameters such as vaccine price, effectiveness, vaccination coverage or the indirect effects of paediatric vaccination. The net budget impact in 5 years established: ⢠Savings (4.2 million euros) from vaccination with PCV15 in the paediatric population. ⢠Additional costs (53-91.2 million euros) from vaccination with PCV20, administering only PCV20 or in combination with PPSV23 in populations older than 65 years. ⢠Savings (39.3 million euros) with PCV20+PPSV23 vaccination in immunocompromised population. It would be recommendable to update this report in 5 years because of the epidemiologic changes that can occur, the possibility of serotype replacement as a consequence of vaccination and the publication of new data regarding effectiveness of new vacines.
Asunto(s)
Vacunación , Programas de Inmunización , Meningitis Neumocócica/prevención & control , Análisis de Costo-EfectividadRESUMEN
Background: The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl. Material and methods: Eleven-day-old rats were infected with S. pneumoniae via intracisternal injection and then administered either vitamin B12 or a placebo. After 24 hours of infection, the animals were euthanized, and apoptosis in the hippocampal dentate gyrus, microglia activation, and the inflammatory infiltrate were quantified in one brain hemisphere. The other hemisphere was used for RNA-Seq and RT-qPCR analysis. Results: In this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug. Conclusion: B12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.
Asunto(s)
Meningitis Neumocócica , Fármacos Neuroprotectores , Humanos , Ratas , Animales , Meningitis Neumocócica/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Histonas , Vitamina B 12/uso terapéutico , Modelos Animales de Enfermedad , Streptococcus pneumoniaeRESUMEN
BACKGROUND: Acute bacterial meningitis (ABM) causes excessive activation of N-methyl-D-aspartate receptors (NMDAr), leading to cortical and hippocampal neuron death. As opposite, enteroviral meningitis is more frequently benign. The kynurenine (KYN) pathway is the major catabolic route of tryptophan (TRP) and some of its metabolites are agonists or antagonists of NMDAr. METHODS: In order to investigate the pathogen-specific patterns of KYN pathway modulation in the central nervous system of children with acute meningococcal (MM), pneumococcal (PM) or enteroviral (VM) meningitis, the cerebrospinal fluid (CSF) concentrations of TRP, KYN, kynurenic acid (KYNA) and quinolinic acid (QUINA) were evaluated by ultra-high performance liquid chromatography (uHPLC) coupled to mass spectrometry. In addition, CSF levels of IL-6, IL-10 and TNF-α were quantified by multi-analyte flow assay. The data was mined and integrated using statistical and machine learning methods. RESULTS: The three forms of meningitis investigated herein up-regulated the neurotoxic branch of the KYN pathway within the intrathecal space. However, this response, represented by the concentration of QUINA, was six and nine times higher in PM patients compared to MM or VM, respectively. CSF levels of IL-6, TNF-α, and IL-10 were increased in MM and PM patients when compared to controls. In VM, CSF IL-6 and IL-10, but not TNF-α were increased compared to controls, although not reaching the high levels found in bacterial meningitis. No correlation was found between the concentrations or the ratios of any pair of KYN metabolites and any cytokine or standard cytochemical parameter tested. CONCLUSIONS: CNS infection with meningococci, pneumococci, and enteroviruses intrathecally activate the KYN pathway, favoring its neurotoxic branch. However, in PM, higher CSF levels of QUINA, compared to MM and VM, may contribute to its poorer neurologic outcome.
Asunto(s)
Meningitis Bacterianas , Meningitis Neumocócica , Niño , Humanos , Quinurenina/metabolismo , Interleucina-10 , Interleucina-6 , Triptófano/metabolismo , Sistema Nervioso Central/metabolismoRESUMEN
Pneumococcal meningitis, inflammation of the meninges due to an infection of the Central Nervous System caused by Streptococcus pneumoniae (the pneumococcus), is the most common form of community-acquired bacterial meningitis globally. Aquaporin 4 (AQP4) water channels on astrocytic end feet regulate the solute transport of the glymphatic system, facilitating the exchange of compounds between the brain parenchyma and the cerebrospinal fluid (CSF), which is important for the clearance of waste away from the brain. Wistar rats, subjected to either pneumococcal meningitis or artificial CSF (sham control), received Evans blue-albumin (EBA) intracisternally. Overall, the meningitis group presented a significant impairment of the glymphatic system by retaining the EBA in the CSF compartments compared to the uninfected sham group. Our results clearly showed that during pneumococcal meningitis, the glymphatic system does not function because of a detachment of the astrocytic end feet from the blood-brain barrier (BBB) vascular endothelium, which leads to misplacement of AQP4 with the consequent loss of the AQP4 water channel's functionality. IMPORTANCE The lack of solute drainage due to a dysfunctional glymphatic system leads to an increase of the neurotoxic bacterial material in the CSF compartments of the brain, ultimately leading to brain-wide neuroinflammation and neuronal damage with consequent impairment of neurological functions. The loss of function of the glymphatic system can therefore be a leading cause of the neurological sequelae developing post-bacterial meningitis.
Asunto(s)
Sistema Glinfático , Meningitis Neumocócica , Animales , Ratas , Albúminas/metabolismo , Acuaporina 4/genética , Acuaporina 4/metabolismo , Astrocitos/metabolismo , Encéfalo/metabolismo , Sistema Glinfático/metabolismo , Meningitis Neumocócica/metabolismo , Ratas WistarRESUMEN
A meningite bacteriana é uma inflamação das leptomeninges que envolvem o Sistema Nervoso Central. Essa patologia, que possui diversos agentes etiológicos, apresenta-se na forma de síndrome, com quadro clínico grave. Entre as principais bactérias que causam a meningite, estão a Neisseria meningitis e Streptococcus pneumoniae. A transmissão ocorre através das vias aéreas por meio de gotículas, sendo a corrente sanguínea a principal rota para as bactérias chegarem à barreira hematoencefálica e, a partir dessa, até as meninges. Atualmente existem vários métodos de diagnóstico precisos, onde a cultura de líquido cefalorraquidiano (LCR) é o método padrão ouro. Ademais, a melhora na qualidade do tratamento com beta-lactâmicos e a maior possibilidade de prevenção, devido à elevação do número e da eficácia de vacinas, vem contribuindo para redução dos casos da doença e de sua gravidade. Porém, apesar desses avanços, ainda há um elevado número de mortalidades e sequelas causadas por essa síndrome.
Bacterial meningitis is an inflammation of the leptomeninges that surround the Central Nervous System. This pathology, which has several etiological agents, is presented as a syndrome with a severe clinical scenario. The main bacteria causing meningitis include Neisseria meningitis and Streptococcus pneumoniae. It can be transmitted by droplets through the airways, with the bacteria using the bloodstream as the main route to reach the blood-brain barrier, and from there to the meninges. There are currently several accurate diagnostic methods, with CSF culture being the gold standard. In addition, the improvement in the quality of beta-lactam treatment and the greater possibility of prevention due to the increased number and effectiveness of vaccines have contributed to reducing the number of cases and severity of the disease. Nevertheless, despite these advances, this syndrome still presents a high number of mortalities and sequelae.
Asunto(s)
Embarazo , Preescolar , Niño , Anciano , Líquido Cefalorraquídeo , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/terapia , Streptococcus pneumoniae/patogenicidad , Síndrome , Bacterias/clasificación , Meningitis Bacterianas/tratamiento farmacológico , beta-Lactamas/uso terapéutico , Bacterias Gramnegativas , Bacterias Grampositivas , Meningitis Neumocócica/tratamiento farmacológico , Neisseria/patogenicidadRESUMEN
Disease surveillance data are needed to monitor trends in disease activity, inform decision-making in public health and evaluate disease prevention/control measures. The Sistema Regional de Vacunas (SIREVA) supports laboratory-based surveillance of invasive pneumococcal disease (IPD) in Latin American countries, providing information on identification, distribution, and anti-microbial susceptibility of pneumococcal strains. We estimated the proportion of pneumococcal meningitis and sepsis/bacteremia cases captured by SIREVA, by comparing the number of SIREVA-reported isolates in Argentina, Brazil, Chile, Colombia, Ecuador and Mexico with the estimated expected number of cases based on regional estimates of disease incidence. In all six countries, the number of isolates reported by SIREVA was consistently lower than the number of cases expected, across all years with data available. The proportion of SIREVA-reported isolates was highest in Chile (43-83%) and lowest in Mexico (1.4-3.5%). Passive surveillance systems such as SIREVA are important tools for monitoring circulating strains that could be related to pneumococcal disease, but our results show that SIREVA is likely to underestimate pneumococcal disease incidence. This under-reporting will limit the precision of surveillance data in monitoring changes in the incidence of IPD after vaccine introduction, and this should be considered when assessing the impact of vaccination programs.
PLAIN LANGUAGE SUMMARYWhat is the context?Infectious disease surveillance is an important epidemiological tool to monitor the health of a population.Surveillence can be used to detect trends in disease activity and to trigger disease control measures.In Latin America, the SIREVA surveillance system monitors occurrence of bacterial pneumonia, sepsis/bacteremia and meningitis.However, passive surveillence systems may understimate disease occurrence.What is new?We compared the number of isolates of invasive pneumococcal disease (IPD), specifically meningitis and sepsis/bacteremia, in children aged <5 years reported in SIREVA data in six countries in Latin America with the expected number of cases based on regional estimates of IPD incidence.Our results show that the number of isolates reported by SIREVA was consistently lower than the estimated number of cases, across all six countries and all the years available.The percent difference between SIREVA-reported isolates and estimated number of cases was variable between countries, ranging from 43-83% in chile to 1.4-3.5% in Mexico.What is the impact?Passive surveillance systems such as SIREVA are important tools for monitoring disease incidence, but they are likely to underestimate pneumococcal disease occrruence.This under-reporting will limit the precision of surveillance data in monitoring changes in disease incidence after vaccine introduction, and this needs to be considered when assessing vaccine impact.
Asunto(s)
Meningitis Neumocócica , Infecciones Neumocócicas , Humanos , Incidencia , Lactante , Laboratorios , América Latina/epidemiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , SerotipificaciónRESUMEN
Abstract Objective To evaluate the clinical and epidemiological profile of bacterial meningitis and meningococcal disease in pediatric patients admitted to a Brazilian Secondary Public Hospital. Methods A descriptive observational study was conducted. Microbiologically proven bacterial meningitis or meningococcal disease diagnosed from 2008 to 2018 were included. Results A total of 90 patients were diagnosed with proven bacterial meningitis. There were 64 confirmed cases of meningococcal disease. The prevalence was higher in boys (n=38), median age 30 months (1-185). The main clinical manifestations were: meningococcal meningitis (n=27), meningococcemia without meningitis (n=14), association of meningococcemia with meningitis (n=13), and fever without a known source in infants (n=7).Admissions to intensive care unit were necessary for 45 patients. Three deaths were notified. Serogroup C was the most prevalent (n=32) followed by serogroup B (n=12).Pneumococcal meningitis was identified in 21 cases; out of the total, 10 were younger than two years. The identified serotypes were: 18C, 6B, 15A, 28, 7F, 12F, 15C, 19A and 14. Pneumococcal conjugate 10-valent vaccine covered four of the nine identified serotypes.Haemophilus influenzae meningitis serotype IIa was identified in three patients, median age 4 months (4-7). All of them needed intensive care. No deaths were notified. Conclusion Morbidity and mortality rates from bacterial meningitis and meningococcal disease remain high, requiring hospitalization and leading to sequelae. Our study observed a reduced incidence of bacterial disease over the last decade, possibly reflecting the impact of vaccination.
Asunto(s)
Niño , Humanos , Lactante , Meningitis Bacterianas/epidemiología , Brasil/epidemiología , Vacunas Neumococicas , Hospitales Generales , Meningitis Meningocócica , Meningitis NeumocócicaRESUMEN
OBJECTIVE: To evaluate the clinical and epidemiological profile of bacterial meningitis and meningococcal disease in pediatric patients admitted to a Brazilian Secondary Public Hospital. METHODS: A descriptive observational study was conducted. Microbiologically proven bacterial meningitis or meningococcal disease diagnosed from 2008 to 2018 were included. RESULTS: A total of 90 patients were diagnosed with proven bacterial meningitis. There were 64 confirmed cases of meningococcal disease. The prevalence was higher in boys (nâ¯=â¯38), median age 30 months (1-185). The main clinical manifestations were: meningococcal meningitis (nâ¯=â¯27), meningococcemia without meningitis (nâ¯=â¯14), association of meningococcemia with meningitis (nâ¯=â¯13), and fever without a known source in infants (nâ¯=â¯7). Admissions to intensive care unit were necessary for 45 patients. Three deaths were notified. Serogroup C was the most prevalent (nâ¯=â¯32) followed by serogroup B (nâ¯=â¯12). Pneumococcal meningitis was identified in 21 cases; out of the total, 10 were younger than two years. The identified serotypes were: 18C, 6B, 15A, 28, 7F, 12F, 15C, 19A and 14. Pneumococcal conjugate 10-valent vaccine covered four of the nine identified serotypes. Haemophilus influenzae meningitis serotype IIa was identified in three patients, median age 4 months (4-7). All of them needed intensive care. No deaths were notified. CONCLUSION: Morbidity and mortality rates from bacterial meningitis and meningococcal disease remain high, requiring hospitalization and leading to sequelae. Our study observed a reduced incidence of bacterial disease over the last decade, possibly reflecting the impact of vaccination.
Asunto(s)
Meningitis Bacterianas/epidemiología , Brasil/epidemiología , Niño , Hospitales Generales , Humanos , Lactante , Meningitis Meningocócica , Meningitis Neumocócica , Vacunas NeumococicasRESUMEN
BACKGROUND: Bacterial meningitis (BM) causes apoptotic damage to the hippocampus and homocysteine (Hcy) accumulation to neurotoxic levels in the cerebrospinal fluid of children. The Hcy pathway controls bioavailability of methyl, and its homeostasis can be modulated by vitamin B12, a cofactor of the methionine synthase enzyme. Herein, the neuroprotective potential and the underlying mode of action of vitamin B12 adjuvant therapy were assessed in an infant rat model of BM. METHODS: Eleven-day old rats were intracysternally infected with Streptococcus pneumoniae serotype 3, or saline, treated with B12 or placebo, and, 24 h after infection, their hippocampi were analyzed for apoptosis in the dentate gyrus, sulfur amino acids content, global DNA methylation, transcription, and proximal promoter methylation of candidate genes. Differences between groups were compared using 2-way ANOVA followed by Bonferroni post hoc test. Correlations were tested with Spearman's test. RESULTS: B12 attenuated BM-induced hippocampal apoptosis in a Hcy-dependent manner (r = 0.80, P < 0.05). BM caused global DNA hypomethylation; however, B12 restored this parameter. Accordingly, B12 increased the methylation capacity of hippocampal cells from infected animals, as inferred from the ratio S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) in infected animals. BM upregulated selected pro-inflammatory genes, and this effect was counteracted by B12, which also increased methylation of CpGs at the promoter of Ccl3 of infected animals. CONCLUSION: Hcy is likely to play a central role in hippocampal damage in the infant rat model of BM, and B12 shows an anti-inflammatory and neuroprotective action through methyl-dependent epigenetic mechanisms.
Asunto(s)
Apoptosis/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Hipocampo/efectos de los fármacos , Meningitis Neumocócica/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Vitamina B 12/uso terapéutico , Animales , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Meningitis Neumocócica/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Regiones Promotoras Genéticas/efectos de los fármacos , Ratas , Ratas Wistar , Streptococcus pneumoniae , Vitamina B 12/administración & dosificaciónRESUMEN
Streptococcus pneumoniae sigue siendo una de las causas más importantes de morbilidad y mortalidad en niños y adultos alrededor del mundo. El objetivo del estudio fue describir la frecuencia de aislamiento de S. pneumoniae en enfermedad invasiva, distribución de serotipos y sensibilidad antimicrobiana en Paraguay (2010-2018). Se estudiaron 793 cepas de S. pneumoniae aisladas de pacientes de todas las edades con enfermedad invasiva en Paraguay, provenientes de los diferentes centros centinelas y colaboradores en el marco de la vigilancia de meningitis y neumonías, durante el periodo 2010-2018. La frecuencia general según diagnóstico resultó 74.9% de neumonías (n=594), 18.4% de meningitis (n=146) y 6.7% de sepsis (n=53). El serotipo 14 fue más frecuente con 174 aislamientos (22.0%), seguido del serotipo 19A con 84 aislamientos (10.6%), el serotipo 3 con 66 aislamientos (8.3%) y el 6A con 37 aislamientos (4.7%). En meningitis se registró una frecuencia general de resistencia a penicilina del 32,2% y de ceftriaxona del 1,4%. En los casos de no meningitis la resistencia a penicilina fue del 0,8% y ceftriaxona del 0,3%. Los resultados de serotipos y sensibilidad antimicrobiana proporcionarán información necesaria para la implementación de estrategias de prevención y tratamiento de la enfermedad neumocócica en nuestro país, por lo que es necesaria una vigilancia continua para evaluar la carga de enfermedad, los serotipos circulantes y el aumento de la resistencia a los antibióticos
Streptococcus pneumoniae remains one of the most important causes of morbidity and mortality in children and adults worldwide. The objective of the study was to describe the frequency of isolation of S. pneumoniae in invasive disease, serotype distribution and antimicrobial susceptibility in Paraguay (2010-2018). We studied 793 strains of S. pneumoniae isolated from patients of all ages with invasive disease in Paraguay, from different sentinel centers and collaborators in the framework of meningitis and pneumonia surveillance during the period 2010-2018. The general frequency according to diagnosis was 74.9% of pneumonia (n = 594), 18.4% of meningitis (n = 146) and 6.7% of sepsis (n = 53). Serotype 14 was more frequent with 174 isolates (22.0%), followed by serotype 19A with 84 isolates (10.6%), serotype 3 with 66 isolates (8.3%) and 6A with 37 isolates (4.70%). In meningitis, there was a general frequency of penicillin resistance of 32.2% and ceftriaxone of 1.4%. In cases of non-meningitis, penicillin resistance was 0.8% and ceftriaxone 0.3%. The results of serotypes and antimicrobial sensitivity will provide necessary information for the implementation of prevention strategies and treatment of pneumococcal disease in our country, therefore it is necessary to continue monitoring in order to assess the burden of the disease, circulating serotypes and increased antibiotic resistance
Asunto(s)
Humanos , Masculino , Femenino , Neumonía Neumocócica , Streptococcus pneumoniae , Meningitis NeumocócicaRESUMEN
BACKGROUND: Studies on the impact of pneumococcal conjugate vaccines (PCV) on mortality, especially among preschoolers are scarce. We aimed to assess time trend mortality from lower respiratory infections (LRI), taken as a proxy of pneumonia, from 1990 to 2017. METHODS: This ecological study assessed the mortality rate among Brazilians under-five before and after the national PCV-10 implementation in 2010. Pneumococcal meningitis (PM) and diarrheal diseases (DD) were included as a "positive and negative controls", respectively. Trend analysis was performed through Global Burden of Disease estimates. Joinpoint regression modeling was used to describe trends in mortality and to identify time points of its statistically significant decreases throughout the study period. RESULTS: There was a sustainable reduction in mortality rates for these three diseases, with no relevant changes in the secular trends for LRI and PM after the PCV-10 implementation. For LRI, PM, and DD the higher and statistically significant (p < 0.05) annual percent change reduction occurred between 2000 and 2003, (-8.3%), 1997-2000 (-11.9%), and 1990-1994. (-13.8%), respectively, i.e., several years before the nationwide implementation of PCV-10. Moreover, for LRI the annual percent change (from -5.9 to -8.8) verified from 1990 to 2009, i.e., 20 years before countrywide vaccination, was comparable to that observed during the PCV era, that is, from minus 5.8 to minus 7.8, between 2010 and 2017. CONCLUSION: Mortality from LRI, PM, and DD decreased over time, irrespective of national PCV-10 implementation in Brazil. Other factors such as healthcare delivery, socioeconomic status improvement, and health interventions may have impacted this secular trend.
Asunto(s)
Meningitis Neumocócica , Infecciones Neumocócicas , Vacunas Neumococicas/uso terapéutico , Infecciones del Sistema Respiratorio/mortalidad , Brasil/epidemiología , Preescolar , Humanos , Lactante , Meningitis Neumocócica/epidemiología , Meningitis Neumocócica/prevención & control , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Infecciones del Sistema Respiratorio/prevención & control , Vacunación , Vacunas ConjugadasRESUMEN
Introdução: O Streptococcus pneumoniae, também conhecido como pneumococo, é colonizante das vias aéreas superiores e principal microrganismo envolvido em otites médias agudas, sinusites, traqueobronquites, infecções do trato respiratório inferior e conjuntivites. Está presente como agente causador de doenças em todas as faixas etárias. O pneumococo é capaz de causar a doença pneumocócica invasiva, que caracteriza infecções de maior gravidade como pneumonia, meningite, bacteremia/sepse, piomiosite e endocardite. Os fatores de risco mais associados a gravidade da doença são: etilismo, extremos de idade (crianças abaixo de 5 anos e idosos acima de 60 anos), presença de asplenia funcional ou cirúrgica, imunodeficiências primárias ou adquiridas, pacientes onco-hematológicos, exposição ao tabagismo ou a drogas imunossupressoras. A Síndrome de Austrian, descrita em 1957, é caracterizada pela tríade de pneumonia, meningite e endocardite pelo pneumococo, que ocorre em um mesmo contexto clínico. Objetivo: Verificar presença de tríade de meningite, endocardite e pneumonia em pacientes admitidos no Instituto de Infectologia "Emílio Ribas" (IIER), de origem comunitária, com culturas positivas para S. pneumoniae, em sítio estéril (sangue periférico, líquor, lavado broncoalveolar), juntamente com as comorbidades associadas a cada paciente; exames complementares e seus respectivos resultados, além da mortalidade durante a internação e condições de alta hospitalar. Metodologia: A coleta de dados e histórico médico foi realizada pelo prontuário eletrônico de pacientes do IIER com culturas (sangue periférico, líquor, lavado broncoalveolar) positivas para S. pneumoniae, entre 48 e 72 horas da admissão hospitalar, do período de 01 de janeiro de 2017 a 22 de maio de 2019. Resultados: Foram selecionados 52 prontuários, quarenta e um (78,84%) pacientes apresentaram pneumonia, dois (3,84%) diagnosticaram meningite e apenas 1 paciente apresentou meningite e pneumonia pneumocócica. A mortalidade foi de 15,68%. Conclusão: Não foram evidenciados casos compatíveis com Síndrome de Austrian no período de 29 meses de análise
Asunto(s)
Humanos , Infecciones Neumocócicas , Neumonía Neumocócica/microbiología , Streptococcus pneumoniae/aislamiento & purificación , Endocarditis Bacteriana/microbiología , Meningitis Neumocócica/microbiología , Estudios Retrospectivos , CoinfecciónRESUMEN
Pneumococcal meningitis produces several inflammatory disorders in susceptible subjects. A worsening of meningitis can occur on the fourth day of evolution in relation with the withdrawal of steroids. Other complications include the development of inflammatory signs in the post-acute stage of infection associated with disseminated vasculitis of the cerebral blood vessels and, even later, an autoimmune chronic meningitis. All these inflammatory complications are well controlled with the use of steroids. We report a 53-year-old woman with pneumococcal meningitis that had a good response to treatment with antibiotics and steroids. On the four day, after the steroids were discontinued, she complained of headache, became confused, and had an abnormal cerebrospinal fluid (CSF), report CT angiography showed signs of arteritis. She improved when the steroids were re-started. She was discharged in good condition but after slow tapering of the steroids over a four-month period she had a relapse of all her symptoms and had a gait disturbance. On readmission, she had an inflammatory CSF, there were no signs of infection and the cerebral MRI showed meningeal thickening with ventricular space enlargement. She improved again with steroids and she is now well on high-dose steroids but deteriorates each time the steroids are stopped. She experienced both acute and sub-acute inflammatory responses and finally developed a chronic meningitis responsive, and is dependent on steroids.
Asunto(s)
Enfermedades Autoinmunes/microbiología , Meningitis Neumocócica/complicaciones , Antibacterianos/uso terapéutico , Enfermedades Autoinmunes/diagnóstico por imagen , Enfermedades Autoinmunes/tratamiento farmacológico , Líquido Cefalorraquídeo/microbiología , Enfermedad Crónica , Femenino , Humanos , Imagen por Resonancia Magnética , Meningitis Neumocócica/diagnóstico por imagen , Meningitis Neumocócica/tratamiento farmacológico , Persona de Mediana Edad , Esteroides/uso terapéutico , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Infectious meningitis is a medical emergency. Within the spectrum of infectious agents, the most important is Streptococcus pneumoniae, the most frequent etiological agent of bacterial meningitis. The initiation of empirical antimicrobial treatment bears great importance and considers third-generation cephalosporins as the first alternative. However, cases of ceftriaxone resistance have been reported in several regions of the world. This has become an emerging problem in need of reconsideration of the current empirical antibiotic treatment schemes. We present the case of a 56-year old man with acute infectious meningitis caused by ceftriaxone-resistant Streptococcus pneumoniae, who responded favorably to combined empirical treatment with ceftriaxone and vancomycin and to whom, during his hospital stay, the presence of hypothyroidism and mega cisterna magna was diagnosed.
La meningitis infecciosa es una emergencia médica. Dentro del espectro de agentes infecciosos, el más importante es el Streptococcus pneumoniae, agente etiológico más frecuente de la meningitis bacteriana. El inicio de tratamiento antimicrobiano empírico es de gran importancia y considera a las cefalosporinas de tercera generación como la primera alternativa. Sin embargo, casos de resistencia a ceftriaxona han sido reportados en diversas partes del mundo, siendo un problema emergente, por lo que necesita una reconsideración de los esquemas antibióticos empíricos actuales. Presentamos el caso de un varón de 56 años que presenta meningitis aguda infecciosa por Streptococcus pneumoniae resistente a ceftriaxona, que respondió favorablemente al tratamiento empírico combinado con ceftriaxona y vancomicina y que durante su estadía hospitalaria se detectó la presencia de hipotiroidismo y megacisterna magna.
Asunto(s)
Antibacterianos/administración & dosificación , Ceftriaxona/administración & dosificación , Meningitis Neumocócica/tratamiento farmacológico , Vancomicina/administración & dosificación , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Humanos , Masculino , Meningitis Neumocócica/microbiología , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Streptococcus pneumoniae/aislamiento & purificación , Resultado del TratamientoRESUMEN
La meningitis bacteriana recurrente es un fenómeno muy poco frecuente en los niños. Las fracturas de la base del cráneo y los implantes cocleares son factores predisponentes importantes, y el agente aislado con mayor frecuencia es el Streptococcus pneumoniae. La implementación de la vacuna neumocócica conjugada de 13 serotipos (VNC13) redujo la incidencia de enfermedades neumocócicas invasivas. La incidencia de enfermedades neumocócicas intercurrentes en pacientes vacunados suele estar relacionada con afecciones predisponentes preexistentes. En este artículo, presentamos un caso de meningitis neumocócica recurrente en una paciente con un implante coclear que sufrió un traumatismo craneoencefálico luego de haber recibido la vacunación completa con la VNC13. La paciente tuvo tres episodios de meningitis en el transcurso de un año. Se detectó la presencia de S. pneumoniae en el cultivo de líquido cefalorraquídeo (LCR) en el primer y tercer episodios, y mediante la prueba de reacción en cadena de la polimerasa (PCR, por su sigla en inglés) en el segundo episodio. Se realizó una intervención neuroquirúrgica luego del tercer episodio de meningitis, y la paciente no tuvo problemas de recurrencias durante los siguientes dos años. Hasta donde sabemos, en la bibliografía no se han descrito casos de meningitis de serotipo 1 por S. pneumoniae luego de la inmunización completa con PCV13.
Recurrent bacterial meningitis is a very rare phenomenon in children. Skull base fractures and cochlear implant are the important predisposing factors and, Streptococcus pneumoniae is the most frequently isolated agent. Implementation of 13-valent conjugated pneumococcal vaccine (PCV13) has reduced the occurence of invasive pneumococcal diseases. Vaccination breakthrough is typically related to underlying predisposing conditions. Herein, we reported recurrent pneumococcal meningitis in a patient with a cochlear implant who experienced a head trauma after being fully vaccinated with PCV13. The patient experienced three meningitis episodes within one year. S.pneumoniae was determined on CSF culture in the first and third episodes and detected by PCR at the second episode. Neurosurgical intervention was performed after the third meningitis episode, and the patient had no recurrence problems for the following two years. To our knowledge, breakthrough S.pneumoniae serotype 1 meningitis after full PCV13 immunization has not been reported elsewhere in the literature.
Asunto(s)
Humanos , Femenino , Preescolar , Streptococcus pneumoniae , Meningitis Neumocócica , Implantación Coclear , Vacunas Neumococicas , Lesiones Traumáticas del EncéfaloRESUMEN
Recurrent bacterial meningitis is a very rare phenomenon in children. Skull base fractures and cochlear implant are the important predisposing factors and, Streptococcus pneumoniae is the most frequently isolated agent. Implementation of 13-valent conjugated pneumococcal vaccine (PCV13) has reduced the occurence of invasive pneumococcal diseases. Vaccination breakthrough is typically related to underlying predisposing conditions. Herein, we reported recurrent pneumococcal meningitis in a patient with a cochlear implant who experienced a head trauma after being fully vaccinated with PCV13. The patient experienced three meningitis episodes within one year. S.pneumoniae was determined on CSF culture in the first and third episodes and detected by PCR at the second episode. Neurosurgical intervention was performed after the third meningitis episode, and the patient had no recurrence problems for the following two years. To our knowledge, breakthrough S.pneumoniae serotype 1 meningitis after full PCV13 immunization has not been reported elsewhere in the literature.
La meningitis bacteriana recurrente es un fenómeno muy poco frecuente en los niños. Las fracturas de la base del cráneo y los implantes cocleares son factores predisponentes importantes, y el agente aislado con mayor frecuencia es el Streptococcus pneumoniae. La implementación de la vacuna neumocócica conjugada de 13 serotipos (VNC13) redujo la incidencia de enfermedades neumocócicas invasivas. La incidencia de enfermedades neumocócicas intercurrentes en pacientes vacunados suele estar relacionada con afecciones predisponentes preexistentes. En este artículo, presentamos un caso de meningitis neumocócica recurrente en una paciente con un implante coclear que sufrió un traumatismo craneoencefálico luego de haber recibido la vacunación completa con la VNC13. La paciente tuvo tres episodios de meningitis en el transcurso de un año. Se detectó la presencia de S. pneumoniae en el cultivo de líquido cefalorraquídeo (LCR) en el primer y tercer episodios, y mediante la prueba de reacción en cadena de la polimerasa (PCR, por su sigla en inglés) en el segundo episodio. Se realizó una intervención neuroquirúrgica luego del tercer episodio de meningitis, y la paciente no tuvo problemas de recurrencias durante los siguientes dos años. Hasta donde sabemos, en la bibliografía no se han descrito casos de meningitis de serotipo 1 por S. pneumoniae luego de la inmunización completa con PCV13.
Asunto(s)
Implantación Coclear , Implantes Cocleares , Traumatismos Craneocerebrales/complicaciones , Meningitis Neumocócica/etiología , Vacunas Neumococicas , Complicaciones Posoperatorias/etiología , Preescolar , Femenino , Humanos , RecurrenciaRESUMEN
OBJECTIVE: To analyze the pneumococcal meningitis incidence rates in the State of São Paulo, Brazil, by age group, municipalities and micro-regions, as well as the spatial distribution of pneumococcal meningitis incidence rates among children under 5 years old in the pre- (2005-2009) and post-vaccination (2011-2013) periods and its associations with socioeconomic variables and vaccination coverage. METHODS: The data source was the Brazilian Notifiable Diseases Information System. For the pre- and post-vaccination periods, thematic maps were built for pneumococcal meningitis incidence in under-5 children, by São Paulo state micro-regions, vaccination coverage and socioeconomic variables, using QGIS 2.6.1 software. Scan statistics performed by the SatScan 9.2 software were used to analyze spatial and spatiotemporal clusters in São Paulo municipalities and micro-regions. A Bayesian inference for latent Gaussian model with zero-inflated Poisson model through the integrated nested Laplace approximation was used in the spatial analysis to evaluate associations between pneumococcal meningitis incidence rates and socioeconomic variables of interest in São Paulo micro-regions. RESULTS: From 2005 to 2013, 3,963 pneumococcal meningitis cases were reported in São Paulo. Under-5 children were the most affected in the whole period. In the post-vaccination period, pneumococcal meningitis incidence rates decreased among this population, particularly among infants (from 4.17/100,000 in 2005 to 2.54/100,000 in 2013). Two clusters were found in pre-vaccination - one of low risk for pneumococcal meningitis, in the northwest of the state (OR = 0.45, p = 0.0003); and another of high risk in the southeast (OR = 1.62, p = 0.0000). In the post-vaccination period, only a high-risk cluster remained, in the southeast (RR = 1.97, p = 0.0570). In Bayesian analysis, wealth was the only variable positively associated to pneumococcal meningitis (RR = 1.026, 95%CI 1.002-1.052). CONCLUSIONS: Pneumococcal meningitis is probably underdiagnosed and underreported in São Paulo. Differentiated rates of pneumococcal meningitis diagnosis and reporting in each microregion, according to the São Paulo Index of Social Responsibility, might explain our results.
Asunto(s)
Inmunización/estadística & datos numéricos , Meningitis Neumocócica/epidemiología , Meningitis Neumocócica/prevención & control , Vacunación/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Brasil/epidemiología , Niño , Preescolar , Mapeo Geográfico , Humanos , Incidencia , Lactante , Persona de Mediana Edad , Características de la Residencia , Adulto JovenRESUMEN
Pneumococcal meningitis produces several inflammatory disorders in susceptible subjects. A worsening of meningitis can occur on the fourth day of evolution in relation with the withdrawal of steroids. Other complications include the development of inflammatory signs in the post-acute stage of infection associated with disseminated vasculitis of the cerebral blood vessels and, even later, an autoimmune chronic meningitis. All these inflammatory complications are well controlled with the use of steroids. We report a 53-year-old woman with pneumococcal meningitis that had a good response to treatment with antibiotics and steroids. On the four day, after the steroids were discontinued, she complained of headache, became confused, and had an abnormal cerebrospinal fluid (CSF), report CT angiography showed signs of arteritis. She improved when the steroids were re-started. She was discharged in good condition but after slow tapering of the steroids over a four-month period she had a relapse of all her symptoms and had a gait disturbance. On readmission, she had an inflammatory CSF, there were no signs of infection and the cerebral MRI showed meningeal thickening with ventricular space enlargement. She improved again with steroids and she is now well on high-dose steroids but deteriorates each time the steroids are stopped. She experienced both acute and sub-acute inflammatory responses and finally developed a chronic meningitis responsive, and is dependent on steroids.