Refractory Immune-Mediated Cysticercal Meningitis and Role of B Cell Depleting Therapy.

BACKGROUND: Extraparenchymal neurocysticercosis (NCC) commonly presents with symptoms of raised intracranial pressure such as headache, nausea, vomiting, or delirium. Intraventricular NCC is frequently associated with obstructive hydrocephalus as well as recurrent inflammatory cascade leading to chronic meningitis. OBJECTIVE: The aim of this study was to report the novel use and benefit of B cell depleting therapy in a case of treatment-refractory cysticercal meningoencephalitis. CASE: In this article, we report about a young male with intraventricular NCC, who had recurrent meningitis (with encephalitis) and kept relapsing despite multiple cerebrospinal fluid diversion procedures, cysticidal therapy, and high-dose steroids. He finally showed clinical and radiological resolution with pulsed rituximab therapy. CONCLUSION: This off-label use of a monoclonal antibody against CD20 may be considered as a rescue therapy in steroid-refractory immune-mediated cysticercal meningitis.

Prospective randomized trial comparing relapse rates in dogs with steroid-responsive meningitis-arteritis treated with a 6-week or 6-month prednisolone protocol.

BACKGROUND: Traditionally, 6-month courses of prednisolone are used to treat steroid-responsive meningitis-arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life. HYPOTHESIS/OBJECTIVES: Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6-month prednisolone protocol and a 6-week protocol. ANIMALS: Forty-four hospital cases from multiple referral centers in the United Kingdom (2015-2019). Twenty of 44 were treated with the 6-month protocol and 24/44 with the 6-week protocol. METHODS: Prospective, randomized trial with 12-month follow-up. The same prednisolone protocol reinitiated in the event of relapse. Analysis of relapses with binary logistic and Poisson regression modeling. RESULTS: All cases responded to their treatment protocol. Relapses occurred in 6/20 (30%) of the 6-month protocol and 9/24 (38%) of the 6-week protocol. There was no statistical difference in the incidence risk of at least 1 relapse between the 2 groups (odds ratio = 1.40; 95% confidence interval [CI], 0.40-4.96, P = 0.60). Among the 15 dogs that relapsed, 10/15 (67%) relapsed once, 3/15 (20%) relapsed twice, and 2/15 (13%) relapsed 3 times. No statistical difference was detected in the incidence rate ratio (IRR) of total relapse events between the 2 groups (IRR = 1.46; 95% CI, 0.61-3.48; P = 0.40). CONCLUSIONS AND CLINICAL IMPORTANCE: "Short" 6-week prednisolone protocols could be used to treat SRMA, thereby presumably reducing the duration and severity of prednisolone's adverse effects.

Quercetin Protects Blood-Brain Barrier Integrity via the PI3K/Akt/Erk Signaling Pathway in a Mouse Model of Meningitis Induced by Glaesserella parasuis.

Glaesserella parasuis (G. parasuis) causes serious inflammation and meningitis in piglets. Quercetin has anti-inflammatory and anti-bacterial activities; however, whether quercetin can alleviate brain inflammation and provide protective effects during G. parasuis infection has not been studied. Here, we established a mouse model of G. parasuis infection in vivo and in vitro to investigate transcriptome changes in the mouse cerebrum and determine the protective effects of quercetin on brain inflammation and blood-brain barrier (BBB) integrity during G. parasuis infection. The results showed that G. parasuis induced brain inflammation, destroyed BBB integrity, and suppressed PI3K/Akt/Erk signaling-pathway activation in mice. Quercetin decreased the expression of inflammatory cytokines (Il-18, Il-6, Il-8, and Tnf-α) and BBB-permeability marker genes (Mmp9, Vegf, Ang-2, and Et-1), increased the expression of angiogenetic genes (Sema4D and PlexinB1), reduced G. parasuis-induced tight junction disruption, and reactivated G. parasuis-induced suppression of the PI3K/Akt/Erk signaling pathway in vitro. Thus, we concluded that quercetin may protect BBB integrity via the PI3K/Akt/Erk signaling pathway during G. parasuis infection. This was the first attempt to explore the protective effects of quercetin on brain inflammation and BBB integrity in a G. parasuis-infected mouse model. Our findings indicated that quercetin is a promising natural agent for the prevention and treatment of G. parasuis infection.

Gnathostoma infection after ingestion of raw fish is a probable cause of eosinophilic meningitis in the Brazilian Amazon.

We report a case of eosinophilic meningitis associated with the ingestion of raw fish (Cichla sp.) from the Brazilian Amazon, likely caused by Gnathostoma. A 36-year-old male visited Juruena river on a fishing trip. After 50 days, the patient presented with an intense frontal headache. A cerebrospinal fluid examination revealed 63% eosinophilia. Another individual who ingested raw fish developed linear dermatitis on the abdominal wall. Anti-Gnathostoma serum antibodies were detected, and the patient made a full recovery after treatment with corticosteroids and albendazole. To date, autochthonous Gnathostoma spp. infections in Latin American countries have only caused linear panniculitis. This report raises awareness of gnathostomiasis-causing meningitis.

[Idiopathic hypertrophic pachymeningitis]. / Idiopaticheskii gipertroficheskii pakhimeningit.

The article presents a case of idiopathic hypertrophic pachymeningitis of a 61-year-old male patient with severe cephalgia and progressive neuropathy of the oculomotor nerves. The diagnosis was confirmed by MRI with gadolinium, which revealed thickening of the dura mater with accumulation of paramagnetic in the convexital parts of the frontal and temporal regions, as well as on the base of the skull and tentorium. During the use of pulse therapy with glucocorticosteroids (GCS) the symptoms regressed, but when the therapy was stopped, there was a relapse of ptosis and oculomotor abnormalities on the other side followed by a slower effect of GCS therapy. The article also presents a brief review of current knowledge about this pathology.

[A case of liver abscess with meningitis and endophthalmitis: invasive liver abscess syndrome].

A woman in her 70s was hospitalized and was diagnosed with liver abscess and managed with antibiotics in a previous hospital. However, she experienced altered consciousness and neck stiffness during treatment. She was then referred to our hospital. On investigation, we found that she had meningitis and right endophthalmitis concurrent with a liver abscess. Klebsiella pneumoniae was detected from both cultures of the liver abscess and effusion from the cornea. A string test showed a positive result. Therefore, she was diagnosed with invasive liver abscess syndrome. Although she recovered from the liver abscess and meningitis through empiric antibiotic treatment, her right eye required ophthalmectomy. In cases where a liver abscess presents with extrahepatic complications, such as meningitis and endophthalmitis, the possibility of invasive liver abscess syndrome should be considered, which is caused by a hypervirulent K. pneumoniae.

Presumptive spontaneous hemothorax associated to thymic involution in a dog with steroid responsive meningitis-arteritis (SRMA).

OBJECTIVE: To describe an unusual case of spontaneous hemothorax resulting from thymic involution in a dog with suspected acquired bleeding dyscrasia associated with steroid-responsive meningitis-arteritis (SRMA). CASE DESCRIPTION: A 6-month-old spayed female Golden Retriever was referred due to the sudden onset of lethargy, fever (pyrexia), loss of appetite (anorexia), and moderate neck pain. These symptoms emerged six days after an ovariohysterectomy performed by the primary veterinarian. Upon admission, the patient exhibited pale mucous membranes, tachycardia (180 bpm), bilateral muffled heart sounds and tachypnea. Abdominal and thoracic point-of-care ultrasound (POCUS) were performed and revealed bilateral pleural effusion. Due to the patient's unstable condition, emergent thoracocentesis and transfusion of packed red blood cells was required. The initial work-up performed included a complete blood cell count (CBC), biochemistry profile, venous blood gas and coagulation panel (PT, APTT, fibrinogen). Pleural effusion analysis was compatible with hemothorax. Bloodwork was unremarkable including the initial coagulation panel. Further coagulation test was performed including buccal mucosal bleeding time, viscoelastic-based clot detection tests (TEG) and Von Willebrand factor antigen measurement. TEG revealed marked hyperfibrinolysis. Angiostrongylus vasorum and 4DX snap test were performed and yielded a negative result. Thoracic CT scan revealed the presence of a soft tissue-attenuating mass in the ventral mediastinum, thymic involution, and enlargement of the sternal and mediastinal lymph nodes. Therapy with tranexamic acid and corticosteroids at anti-inflammatory doses was initiated. Marked clinical improvement was observed within 24 hours, and after three days of hospitalization the patient was discharged. One month later, the dog was referred again for acute pyrexia, hyporexia, and neck pain which progressed to non-ambulatory tetraparesis. Neurological examination was compatible with C6-T2 lesion. MRI and cerebrospinal fluid analysis were performed and revealed a final diagnosis of steroid-responsive meningitis-arteritis (SRMA) with associated intramedullary hemorrhage. Corticosteroids were started again, and the patient showed a dramatic improvement over the next 24 hours. Three weeks after the diagnosis, the dog returned to a clinically normal state. The treatment was gradually tapered over the following months, guided by regular neurological and clinical examinations and CRP measurements, without any relapses. NEW OR UNIQUE INFORMATION: To the best of the author's knowledge, this is the first documented case of a dog experiencing spontaneous hemothorax as a result of thymic hemorrhage/involution which, in the absence of other identifiable diseases, was attributed to a hyperfibrinolytic state induced by a severe inflammatory disease such as SRMA.

Neutrophil extracellular traps in CSF and serum of dogs with steroid-responsive meningitis-arteritis.

In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies.

Escherichia coli Meningitis in a 72-year-old Woman.

Spontaneous community-acquired meningitis caused by E. coli is rare in the adult population. It is associated with a high risk of morbidity and mortality. We describe a case of a 72-year-old woman who presented with altered mental status and neck stiffness and was found to have E. coli meningitis. Urine cultures grew E. coli, representing a likely source. The E. coli strain was identified as sequence type 73 (E. coli ST73). Her symptoms and laboratory values improved following antibiotic initiation, and she was discharged from the hospital to a rehabilitation facility.

Early Experiences with Intrathecal Administration of Amphotericin B Liposomal Formulation at a Neurosurgical Center.

BACKGROUND: Intrathecal administration of amphotericin B represents an important adjunctive therapy for management of severe fungal meningitis. Intrathecal preparations have traditionally used amphotericin B deoxycholate. Liposomal amphotericin B is an alternative formulation with good clinical outcomes as systemic therapy, but scant data exist investigating intrathecal use. OBJECTIVE: The aim of this exploratory study was to evaluate outcomes following intrathecal administration of liposomal amphotericin B for treatment of severe fungal meningitis. METHODS: A national shortage of amphotericin B deoxycholate necessitated revision of institutional protocols at a southwestern neurosurgical center in Spring 2023. A starting intrathecal daily dose of 0.125-0.5 mg liposomal amphotericin B was recommended (dependent on insertion device), with 0.125-0.25 mg slow titration every 48 h and up to a 2 mg maximum daily dose. RESULTS: Four cases of fungal meningitis treated with adjunctive intrathecal amphotericin B liposomal formulation were reviewed. This included three cases of coccidioidal meningitis and one case of presumed Fusarium solani meningitis following an outbreak. All patients had initial disease improvement following initiation of intrathecal amphotericin B and were able to tolerate long-term therapy. One coccidioidal meningitis patient expired of neurologic complications shortly after being moved from the intensive care unit (ICU) to a floor unit. All other patients were successfully discharged from the hospital. New headache was the only reported adverse effect, which was managed with dose reduction and did not require therapy discontinuation. CONCLUSIONS: Liposomal amphotericin B may be feasibly administered intrathecally for the adjunctive treatment of severe fungal meningitis.

Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review / Infección del sistema nervioso central por Streptococcus bovis en adultos: reporte de 4 casos y revisión de la literatura

Objectives: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. Methods: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. Results: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). Conclusions: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.(AU)

Introducción: Streptococcus bovis, una causa bien conocida de endocarditis asociada a cáncer colorrectal, es también una causa poco frecuente de infecciones del sistema nervioso central (SNC), incluyendo meningitis, abscesos cerebrales o empiema subdural. El objetivo de este estudio es describir las características clínicas, los antecedentes médicos y la asociación con la enfermedad intestinal en las infecciones por S. bovis en el SNC. Métodos: Describimos 4 infecciones por S. bovis en el SNC en nuestra Unidad y, a continuación, presentamos una revisión bibliográfica de los artículos publicados entre 1975-2021 en PubMed/MEDLINE. Resultados: Se encontraron 52 estudios con 65 casos; 5 se excluyeron por datos incompletos. En total se analizaron 64 casos incluyendo nuestros 4: 55 con meningitis y 9 con infecciones focales intracraneales. Ambas infecciones se asociaron con frecuencia a condiciones subyacentes (70,3%) como la inmunosupresión (32,8%) o el cáncer (10,9%). En 23 casos se identificó un biotipo, siendo el más frecuente el biotipo ii (69,6%), y dentro de ellos, S. pasteurianus. En el 60,9% de los casos se detectaron enfermedades intestinales, siendo las más frecuentes las neoplasias (41,0%) y la infestación por Strongyloides (30,8%). La mortalidad global fue del 17,1%, con una tasa mayor en la infección focal (44,4 frente a 12,7%; p=0,001). Conclusiones: Las infecciones del SNC debidas a S. bovis son poco frecuentes y la forma clínica más común es la meningitis. En comparación con las infecciones focales, la meningitis tiene un curso más agudo, está menos asociada a la endocarditis y tiene una menor mortalidad. La inmunosupresión y la enfermedad intestinal fueron frecuentes en ambas infecciones.(AU)

The early recognition and diagnosis of neoplastic meningitis.

INTRODUCTION: The diagnosis and monitoring of leptomeningeal metastases (LM) from solid tumors are challenging, and the combination of neurological symptoms, MRI findings, and cerebrospinal fluid (CSF) cytology does not always allow to achieve a definitive diagnosis. AREAS COVERED: This review summarizes the studies that have investigated CSF liquid biopsy to improve the initial diagnosis of LM in case the CSF cytology is negative or only suspicious for tumor cells, and monitoring of tumor response following targeted therapies or immunotherapy. In this regard, the early detection of LM recurrence and the development of resistant mutations are critical issues. Moreover, the early identification of subgroups of patients with a higher risk of LM progression, as well as the correlation of LM burden with survival, are discussed. EXPERT OPINION: There is an urgent need of prospective studies to monitor longitudinally LM using CSF liquid biopsy and investigate the role of CTC, ctDNA or novel assays. The optimal setting for the longitudinal CSF and blood collection can be clinical trials focused on the molecular diagnosis of LM as well as the response and monitoring following targeted agents.

Extensive, circumferential, epidural spinal cord compression by IgG4-related pachymeningitis.

A rare case of IgG4-related pachymeningitis is presented. The manuscript describes the multidisciplinary treatment of a rare entity in an exceptional location, prompting emergent surgical treatment. However, the correct intraoperative hypothesis led to a minimal surgical approach with fewer risks and good disease control. Finding a balance between maximising treatment outcome and minimising risks is often difficult for clinicians worldwide who encounter the same clinical dilemma. The known cases are summarised, as are radiological characteristics and common treatments.

Off-label use of eculizumab for neurological symptoms and progressive vision loss.

We describe the results of eculizumab treatment of a patient with pachymeningitis, inflammatory infiltration of the left frontal lobe, and cerebral hematoma, who presented with progressive vision loss, epileptic seizures, and abnormal pattern of the complement system parameters. A 30-year-old female patient, initially diagnosed with hypereosinophilia and a tumour of the left orbit, developed a significant visual impairment in the left eye, progressive vision loss in the right eye, and neurological symptoms in the form of epileptic seizures and behavioural changes. Magnetic resonance imaging (MRI) revealed thickening of the dura mater in the left frontal area, slight oedema of the cortex, and subcortical white matter. Orbit biopsy showed non-specific inflammatory infiltrates. Despite the initial good response, symptoms progressed during treatment with glucocorticoids and immunosuppressants. Increased activity of the alternative complement pathway accompanied by a low level of its main inhibitor, factor H (FH), and the presence of anti-FH autoantibodies, was found. Genetic analysis revealed several missense variants of complement proteins, including two disease-linked mutations in FH (p.H402Y) and FI (T300A). An attempt to apply a complement C5 blocker, eculizumab, has been made. Neurological symptoms subsided, vision loss was inhibited, laboratory parameters improved, and discontinuation of steroid therapy was possible. The case underlines the role of complement system dysregulation in neurological distress.

A clinical approach to hypertrophic pachymeningitis / Abordagem diagnóstica para paquimeningite hipertrófica

ABSTRACT Importance: Hypertrophic pachymeningitis (HP) is a non-usual manifestation of rheumatologic, infectious, and neoplastic diseases. Etiological diagnosis is a challenge, but when made promptly it creates a window of opportunity for treatment, with the possibility of a total reversal of symptoms. Observations: HP is an inflammatory process of the dura mater that can occur as a manifestation of sarcoidosis, granulomatosis with polyangiitis, and IgG4-related disease. The HP case evaluation is extensive and includes central nervous system imaging, cerebrospinal fluid analysis, serology, rheumatologic tests, and systemic survey for other manifestations sites. After systemic investigation, meningeal biopsy might be necessary. Etiology guides HP treatment, and autoimmune disorders are treated with corticosteroids alone or associated with an immunosuppressor. Conclusion: HP is a manifestation of several diseases, and a precise etiological diagnosis is crucial because of the difference among treatments. An extensive investigation of patients with HP helps early diagnosis and correct treatment.

RESUMO Importância: Paquimeningite hipertrófica (PH) é uma manifestação não usual de doenças reumatológicas, infecciosas e neoplásicas. O diagnóstico etiológico por vezes é um desafio, entretanto quando realizado em tempo cria uma janela de tratamento com a possibilidade de reversão total dos sintomas. Observações: A PH é um processo inflamatório da dura-máter que pode ocorrer como manifestação da sarcoidose, granulomatose com poliangeíte e doença relacionada à IgG4. A avaliação dos casos de PH é extensa e inclui imagem do sistema nervoso central, análise de líquor, sorologias, provas reumatológicas e rastreio sistêmico para doença em outros sítios. Por vezes, após toda a investigação sistêmica, a biópsia de meninge é necessária. A etiologia orienta o tratamento da HP, sendo que em doenças autoimunes adota-se o uso de corticosteroides isolados ou associados a um imunossupressor. Conclusão e Relevância: A PH é uma manifestação de várias doenças, e seu diagnóstico etiológico preciso é fundamental, visto a diferença entre os possíveis tratamentos. Uma investigação ampla nos casos de PH ajuda no diagnóstico precoce e tratamento adequado.

Vigilância Nacional de Meningite Procedimento Operacional Padrão para Pessoal Clínico / National Meningitis Surveillance Standard Operating Procedure for Clinical Personnel

A meningite bacteriana é uma condição clínica que acarreta risco de vida, requerendo diagnóstico e tratamento precoces. Estima-se que ocorreram 2,8 milhões de casos de meningite em todo o mundo, em 2016 (Colaboradores GBDM Lancet 2018). Até 70% dos pacientes com meningite morrem sem tratamento (Rosenstein NEJM 2001). Mesmo com diagnóstico e tratamento adequados, cerca de 8 a 15% dos pacientes com meningite acabam por morrer e cerca de 20% dos sobreviventes poderão sofrer de perda de audição permanente e dificuldades de aprendizagem (OMS 2019). As crianças com menos de 5 anos de idade correm um risco maior de contraírem meningite bacteriana, que é causada por três agentes infecciosos principais: Streptococcus pneumoniae, Haemophilus influenzae e Neisseria meningitidis. Estão disponíveis vacinas eficazes contra estes agentes infecciosos. Moçambique, por exemplo, introduziu uma vacina pneumocócica conjugada 10-valente (PCV), em 2013, e dados da vigilância mostram que a prevalência da meningite pneumocócica de tipo PCV10 reduziu de 84,2% (48/57), em 2013, para 0% (0/3), em 2015 (Nhantumbo PLoS One 2017). No entanto, é importante manter uma vigilância robusta e ativa da meningite bacteriana em Moçambique devido a preocupações com o aumento de serotipos não incluídos na fórmula atual da vacina (Martcheva J R Soc Interface 2008) ou o surgimento de serotipos resistentes a múltiplos antibióticos (OMS 2017)...

Vigilância Nacional de Meningite: Procedimento Operacional Padrão para Pontos Focais / National Meningitis Surveillance Standard Operating Procedure for Focal Points

A meningite bacteriana é uma condição clínica que acarreta risco de vida, requerendo diagnóstico e tratamento precoces. Estima-se que ocorreram 2,8 milhões de casos de meningite em todo o mundo, em 2016 (Colaboradores GBDM Lancet 2018). Até 70% dos pacientes com meningite morrem sem tratamento (Rosenstein NEJM 2001). Mesmo com diagnóstico e tratamento adequados, cerca de 8 a 15% dos pacientes com meningite acabam por morrer e cerca de 20% dos sobreviventes poderão sofrer de perda de audição permanente e dificuldades de aprendizagem (OMS 2019). As crianças com menos de 5 anos de idade correm um risco maior de contraírem meningite bacteriana, que é causada por três agentes infecciosos principais: Streptococcus pneumoniae, Haemophilus influenzae e Neisseria meningitidis. Estão disponíveis vacinas eficazes contra estes agentes infecciosos. Moçambique, por exemplo, introduziu uma vacina pneumocócica conjugada 10-valente (PCV), em 2013, e dados da vigilância mostram que a prevalência da meningite pneumocócica de tipo PCV10 reduziu de 84,2% (48/57), em 2013, para 0% (0/3), em 2015 (Nhantumbo PLoS One 2017). No entanto, é importante manter uma vigilância robusta e ativa da meningite bacteriana em Moçambique devido a preocupações com o aumento de serotipos não incluídos na fórmula atual da vacina (Martcheva J R Soc Interface 2008) ou o surgimento de serotipos resistentes a múltiplos antibióticos (OMS 2017)...