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Among the different existing types of bacterial meningitis, the one caused by Neisseria meningitidis is the main presentation of invasive meningococcal disease (IMD). IMD is a significant public health concern and has a reported incidence rate in Argentina of 0.44 cases per 100 000 inhabitants in 2015. However, the actual incidence is thought to be higher as passive surveillance systems neither report nor identify 100% of all cases. The aim of this study is to develop an estimation of the burden of IMD in Argentina closer to reality by adjusting/correcting several limitations observed in the surveillance data available. A retrospective observational study has been performed using four Argentinean national databases recording the number of IMD cases and deaths, serogroups of N. meningitidis and ages, between 2007 to 2016. The reported data were adjusted to account for underreporting and to also integrate the cases missed due to well-known limitations associated with the diagnosis of N. meningitidis detection methods. Data were further analysed by serogroups of N. meningitidis and by age groups. After these adjustments, the potential numbers of IMD cases and IMD-related deaths are estimated to be 3.1 and 1.9 higher than reported, respectively. The study corrects the previous underestimation of the disease burden and provides expectedly more robust estimates aligned with international evidence and highlights the importance of active surveillance, with high-quality methods, for a better definition of preventive strategies against IMD in Argentina.
Based on a wide range of historical sources, including published scientific literature and archives (Institut Mérieux, WHO and IMTSSA), this article examines the history of the development of the meningococcal A vaccine between 1969 and 1973. It explores the social factors of vaccine development including various collaborations, informal discussions, the circulation of products and materials, formal meetings, trials and setbacks to highlight the complex reality of the development, production and use of the vaccine. Inscribed in a ‘Golden Age’ of vaccine development and production, this episode not only adds to the scholarship on the history of vaccines, which has tended to focus on a narrative of progress, but also considers the sharing of knowledge through collaborations, and the risks involved in the development of a vaccine. Finally, this perspective reveals the uncertainties and difficulties underlying the production of an effective vaccine.
Meningococcal carriage dynamics drive patterns of invasive disease. The distribution of carriage by age has been well described in Europe, but not in the African meningitis belt, a region characterised by frequent epidemics of meningitis. We aimed to estimate the age-specific prevalence of meningococcal carriage by season in the African meningitis belt. We searched PubMed, Web of Science, the Cochrane Library and grey literature for papers reporting carriage of Neisseria meningitidis in defined age groups in the African meningitis belt. We used a mixed-effects logistic regression to model meningococcal carriage prevalence as a function of age, adjusting for season, location and year. Carriage prevalence increased from low prevalence in infants (0.595% in the rainy season, 95% CI 0.482–0.852%) to a broad peak at age 10 (1.94%, 95% CI 1.87–2.47%), then decreased in adolescence. The odds of carriage were significantly increased during the dry season (OR 1.5 95% CI 1.4–1.7) and during outbreaks (OR 6.7 95% CI 1.6–29). Meningococcal carriage in the African meningitis belt peaks at a younger age compared to Europe. This is consistent with contact studies in Africa, which show that children 10–14 years have the highest frequency of contacts. Targeting older children in Africa for conjugate vaccination may be effective in reducing meningococcal transmission.
Central nervous system (CNS) may be infected by several agents, resulting in different presentations and outcomes. Analysis of cerebrospinal fluid (CSF) markers could be helpful to differentiate specific conditions and setting an appropriate therapy.
Patients presenting with signs and symptoms were enrolled if, before receiving a diagnostic lumbar puncture, signed a written informed consent. We analyzed CSF indexes of blood–brain barrier permeability (CSF to serum albumin ratio or CSAR), inflammation (CSF to serum IgG ratio, neopterin), amyloid deposition (1–42 β-amyloid), neuronal damage (Total tau (T-tau), Phosphorylated tau (P-tau), and 14.3.3 protein) and astrocyte damage (S-100β).
Two hundred and eighty-one patients were included: they were mainly affected by herpesvirus encephalitis, enterovirus meningoencephalitis, bacterial meningitis (Neisseria meningitidis and Streptococcus pneumoniae), and infection by other etiological agents or unknown pathogen. Their CSF features were compared with HIV-negative patients and native HIV-positive individuals without CNS involvement. 14.3.3 protein was found in bacterial and HSV infections while T-tau and neopterin were abnormally high in the herpesvirus group. P-tau, instead, was elevated in enterovirus meningitis. S-100β was found to be high in patients with HSV-1 and HSV-2 infections but not in those with Varicella Zoster Virus (VZV). Thirty-day mortality was unexpectedly low (2.7%): patients who died had higher levels of T-tau and, significantly, lower levels of Aβ1–42.
This work demonstrates that CSF biomarkers of neuronal damage or inflammation may vary during CNS infections according to different causative agents. The prognostic value of these biomarkers needs to be assessed in prospective studies.
Gender inequality has severe consequences on public health in terms of delay in diagnosis of pulmonary tuberculosis (PTB). In order to explore gender-related differences in diagnosis delay, a cross-sectional study of 10 686 patients diagnosed with PTB in Yulin from 1 January 2009 to 31 December 2014 was conducted. Diagnosis delay was categorised into ‘short delay’ and ‘long delay’ by four commonly used cut-off points of 14, 30, 60 and 90 days. Logistic regression analysis was used to analyse gender differences in diagnostic delay. Stratified analyses by smear results, age, urban/rural were performed to examine whether the effect persisted across the strata. The median delay was 31 days (interquartile range 13–65). Diagnostic delay in females at cut-off points of 14, 30, 60 and 90 days had odds ratios (OR) of 0.99 (95% CI 0.91–1.09), 1.09 (95% CI 1.01–1.18), 1.15 (95% CI 1.05–1.26) and 1.18 (95% CI 1.06–1.31), respectively, compared with males. Stratified analysis showed that females were associated with increased risk of longer delay among those aged 30–60 years, smear positive and living in the rural areas (P < 0.05). The female-to-male OR increased along with increased delay time. Further inquiry into the underlying reasons for gender differences should be urgently addressed to improve the current situation.
To recount experience with cerebrospinal fluid otorrhoea and temporal bone meningoencephalocele repair in a tertiary care hospital.
A retrospective review was conducted of 16 cerebrospinal fluid otorrhoea and meningoencephalic herniation patients managed surgically from 1991 to 2016.
Aetiology was: congenital (n = 3), post-traumatic (n = 2), spontaneous (n = 1) or post-mastoidectomy (n = 10). Surgical repair was undertaken by combined middle cranial fossa and transmastoid approach in 3 patients, transmastoid approach in 2, oval window plugging in 1, and subtotal petrosectomy with middle-ear obliteration in 10. All patients had successful long-term outcomes, except one, who experienced recurrence after primary stage oval window plugging, but has been recurrence-free after second-stage subtotal petrosectomy with middle-ear obliteration.
Dural injury or exposure in mastoidectomy may lead to cerebrospinal fluid otorrhoea or meningoencephalic herniation years later. Congenital, spontaneous and traumatic temporal bone defects may present similarly. Middle cranial fossa dural repair, transmastoid multilayer closure and subtotal petrosectomy with middle-ear obliteration were successful procedures. Subtotal petrosectomy with middle-ear obliteration offers advantages over middle cranial fossa dural repair alone; soft tissue closure is more robust and is preferred in situations where hearing preservation is not a priority.
The pathophysiological mechanisms underlying the seasonal dynamic and epidemic occurrence of bacterial meningitis in the African meningitis belt remain unknown. Regular seasonality (seasonal hyperendemicity) is observed for both meningococcal and pneumococcal meningitis and understanding this is critical for better prevention and modelling. The two principal hypotheses for hyperendemicity during the dry season imply (1) an increased risk of invasive disease given asymptomatic carriage of meningococci and pneumococci; or (2) an increased transmission of these bacteria from carriers and ill individuals. In this study, we formulated three compartmental deterministic models of seasonal hyperendemicity, featuring one (model1-‘inv’ or model2-‘transm’), or a combination (model3-‘inv-transm’) of the two hypotheses. We parameterised the models based on current knowledge on meningococcal and pneumococcal biology and pathophysiology. We compared the three models' performance in reproducing weekly incidences of suspected cases of acute bacterial meningitis reported by health centres in Burkina Faso during 2004–2010, through the meningitis surveillance system. The three models performed well (coefficient of determination R2, 0.72, 0.86 and 0.87, respectively). Model2-‘transm’ and model3-‘inv-transm’ better captured the amplitude of the seasonal incidence. However, model2-‘transm’ required a higher constant invasion rate for a similar average baseline transmission rate. The results suggest that a combination of seasonal changes of the risk of invasive disease and carriage transmission is involved in the hyperendemic seasonality of bacterial meningitis in the African meningitis belt. Consequently, both interventions reducing the risk of nasopharyngeal invasion and the bacteria transmission, especially during the dry season are believed to be needed to limit the recurrent seasonality of bacterial meningitis in the meningitis belt.
Six cases of serogroup C invasive meningococcal disease were identified in Treviso district, Veneto region, Italy between December 13 and 15, 2007. The afflicted patients were found to have attended the same Latin-dance clubs on the same nights, and chemoprophylaxis was provided to potentially exposed individuals. Despite these efforts, 2 cases caused by the same meningococcal strain subsequently occurred in the same area, without any apparent epidemiological correlation to the initial cases. This may have resulted from a failure to neutralize the meningococcal carrier/s. The root cause analysis method applied to public health emergency preparedness was used to analyze the response to this critical incident. The root cause analysis revealed a need to develop regional guidelines for the classification and management of a meningococcal outbreak and for developing risk-communication strategies that include the identification of appropriate channels of communication for differing segments of the population. (Disaster Med Public Health Preparedness. 2019;13:368–371)
Toll-like receptor 2 (TLR2) is a key member of TLRs, which is crucial in the initial inflammatory response against bacteria. TLR2, is also the initial barrier against bacterial infection and plays an important role in recognising a variety of bacterial lipoproteins. Several studies have been performed to investigate the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility. Unfortunately, the results of previous studies were controversial. Therefore, we performed a meta-analysis to derive a more precise estimation of the association. The association between the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility was assessed by odds ratios together with their 95% confidence intervals (CI). Six studies were enrolled in the present meta-analysis. Overall, no significant association between TLR2 + 2477G/A polymorphism and bacterial meningitis risk were found under allele contrast (A vs. G: OR = 1.15, 95% CI = 0.93–1.43, P = 0.202), recessive genetic model (AA vs. AG/GG: OR = 1.12, 95% CI = 0.90–1.41, P = 0.313). The significant association was found between TLR2 + 2477G/A polymorphism and pneumococcal meningitis risk under allele contrast (A vs. G: OR = 1.54, 95% CI = 1.01–2.36, P = 0.046), recessive genetic model (AA vs. AG/GG: OR = 1.63, 95% CI = 1.03–2.57, P = 0.035). We conclude that TLR2 + 2477G/A polymorphism is not associated with meningococcal meningitis risk but contributes an increased risk of pneumococcal meningitis.
Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.
We evaluated the effectiveness and cost of a fungal meningitis outbreak response in the New River Valley of Virginia during 2012-2013 from the perspective of the local public health department and clinical facilities. The fungal meningitis outbreak affected 23 states in the United States with 751 cases and 64 deaths in 20 states; there were 56 cases and 5 deaths in Virginia.
We conducted a partial economic evaluation of the fungal meningitis outbreak response in New River Valley. We collected costs associated with the local health department and clinical facilities in the outbreak response and estimated the epidemiological effectiveness by using disability-adjusted life years (DALYs) averted.
We estimated the epidemiological effectiveness of this outbreak response to be 153 DALYs averted among the patients, and the costs incurred by the local health department and clinical facilities to be $30,413 and $39,580, respectively.
We estimated the incremental cost-effectiveness ratio of $198 per DALY averted and $258 per DALY averted from the local health department and clinical perspectives, respectively, thereby assisting in impact evaluation of the outbreak response by the local health department and clinical facilities. (Disaster Med Public Health Preparedness. 2018;12:38–46)
Subtotal petrosectomy combined with cochlear implantation is a procedure required in specific situations.
A retrospective review of all cases of subtotal petrosectomy in cochlear implant surgery over a five-year period was performed. The indications, complications and outcomes for this procedure are outlined.
Sixteen patients underwent cochlear implantation in combination with subtotal petrosectomy and blind sac closure of the external auditory meatus from 2008 to 2013. Seventy-five per cent of these were completed as a two-stage procedure and 25 per cent as a single-stage procedure. The most common indications for the procedure were chronic otitis media, previous radical cavity, and for surgical access in challenging anatomy or in drill-out procedures. Mastoids were obliterated with fat or musculoperiosteal flaps. The complication rate relating to blind sac closure was 6 per cent. Cochlear implants were successfully placed in all cases and there was no incidence of device failure.
For patients with chronic suppurative otitis media or existing mastoid cavities, subtotal petrosectomy with blind sac closure of the external auditory canal, closure of the eustachian tube, and cavity obliteration is an effective technique to facilitate safe cochlear implantation.
The Global Meningococcal Initiative (GMI) is an international group of scientists and clinicians with recognized expertise in meningococcal disease including microbiology, immunology, epidemiology, public health and vaccinology. The GMI was established to promote the global prevention of meningococcal disease through education, research and international cooperation. The GMI held its second summit meeting in 2013 to discuss the different aspects of existing meningococcal immunization programmes and surveillance systems. Laboratory confirmation and characterization were identified as essential for informing evidence-based vaccine implementation decisions. The relative merits of different confirmatory methodologies and their applications in different resource settings were a key component of the discussions. This paper summarizes the salient issues discussed, with special emphasis on the recommendations made and any deficiencies that were identified.
Leptomeningeal metastasis (LM) is a neurooncological complication of advanced cancer that has a poor prognosis. The incidence of LM is increasing due to advances in neuroimaging. At the same time, the development of new systemic treatments with poor central nervous system penetration has improved outcomes and survival. However, diagnosis of LM remains quite difficult due to clinical polymorphism, inconsistent imaging abnormalities, and the inconsistent presence of neoplastic cells in cerebrospinal fluid. Psychiatric manifestations can blur the neurological frame and confound management of this complication.
To illustrate these difficulties, we report the case of a patient with no past psychiatric history who presented with a manic episode that was attributed to a recurrence of leptomeningeal metastasis.
With this case report, we highlight the importance of referring the patient to a psychiatrist or a member of the psychooncology unit when new behavioral disorders present.
Significance of results:
Leptomeningeal metastases can elicit psychiatric consequences. A hypothesis of this diagnosis should be considered for cancer patients who present with sudden or recent profound mental changes during the course of their disease. Oncologists and neurooncologists should be aware of this possibility. Collaboration with a psychooncologist is recommended to better manage this neuropsychiatric pathology.