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Debate - Adjunctive corticosteroids for acute bacterial meningitis in Africa do we need more evidence?
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Dr Senjuti Saha @ MRF's Meningitis and Septicaemia 2019
- Proma, a 13-year-old girl from Bangladesh, was hospitalized with meningitis symptoms and was eventually diagnosed with tuberculosis meningitis. She remains severely disabled two years later.
- The presentation discussed an ongoing meningitis surveillance program in Bangladesh that aims to describe disease burden and identify causative agents. However, over 50% of cases have unknown etiologies.
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This document discusses cryptococcal meningitis, including its treatment, diagnosis, and challenges. It summarizes recent trials that found abbreviated amphotericin B regimens and the addition of flucytosine significantly reduced 10-week mortality compared to standard amphotericin B alone. Liposomal amphotericin B shows promise as a short-course, less toxic alternative. Adjunctive therapies like interferon-gamma and novel antifungal drugs are being studied. Point-of-care cryptococcal antigen screening followed by preemptive treatment could help diagnose more cases earlier. Overall, advances are being made but mortality remains unacceptably high, calling for further research on new drugs and optimized treatment
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1) There is a need for rapid diagnostic tests for meningitis that can distinguish between bacterial and viral infections at the point of care, identify the pathogen causing meningoencephalitis, and identify the causative organism (Neisseria meningitidis serogroup) in the African meningitis belt.
2) Promising biomarkers and host factors have been identified for distinguishing between bacterial and viral meningitis rapidly. A trim assay using lipocalin-2 is being validated in multi-site studies.
3) Lateral flow immunochromatography tests for N. meningitidis from Biospeedia showed good performance in laboratory and field studies in detecting N. meningitidis ser
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1. Healthy adults were randomly assigned to receive an intranasal inoculation with either Neisseria lactamica (Nlac) or a placebo control. 2. Blood samples were collected to assess B cell responses specific to Nlac and the related pathogen Neisseria meningitidis (Nmen). 3. The study found that colonization with Nlac induced plasma cells that produced antibodies cross-reactive between Nlac and Nmen, suggesting Nlac colonization can stimulate immune memory against Nmen.
Prof Joy Lawn @ MRF's Meningitis and Septicaemia 2019
This document summarizes a presentation on neonatal meningitis and sepsis survivors. The key points are:
1. Survivors of neonatal meningitis and sepsis often experience long-term neurological impairments. Studies find moderate to severe impairment in 18-23% of survivors.
2. There are significant gaps in data on the true burden of neonatal infections due to limitations in care access, clinical assessment, laboratory testing, and long-term follow up in low-resource settings. This impacts estimates of impairment rates.
3. Improving data through strengthened health systems, innovative diagnostics, expanded cohort studies, and better impairment measures is needed to close these gaps and better support survivors long-term.
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- Proma, a 13-year-old girl from Bangladesh, was hospitalized with meningitis symptoms and was eventually diagnosed with tuberculosis meningitis. She remains severely disabled two years later.
- The presentation discussed an ongoing meningitis surveillance program in Bangladesh that aims to describe disease burden and identify causative agents. However, over 50% of cases have unknown etiologies.
- An initial study using metagenomic sequencing on stored CSF samples identified diverse pathogens in positive controls and solved several "mystery meningitis" cases, including mumps virus, Bacillus cereus, and Chikungunya virus.
- Follow-up of 10 solved cases found varying outcomes, from
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Dr Olivier Ronveaux @MRF's Meningitis and Septicaemia 2019
1) There is a need for rapid diagnostic tests for meningitis that can distinguish between bacterial and viral infections at the point of care, identify the pathogen causing meningoencephalitis, and identify the causative organism (Neisseria meningitidis serogroup) in the African meningitis belt.
2) Promising biomarkers and host factors have been identified for distinguishing between bacterial and viral meningitis rapidly. A trim assay using lipocalin-2 is being validated in multi-site studies.
3) Lateral flow immunochromatography tests for N. meningitidis from Biospeedia showed good performance in laboratory and field studies in detecting N. meningitidis ser
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The document discusses using whole genome sequencing (WGS) and building a global genome library as powerful research and public health tools. It describes the Global Meningitis Genome Library initiative which aims to create a comprehensive, representative collection of WGS data for four major causes of meningitis. The initiative will integrate this genome library within the PubMLST.org platform for open access data sharing, analysis and visualization to support epidemiological research and surveillance on a global scale.
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1. Healthy adults were randomly assigned to receive an intranasal inoculation with either Neisseria lactamica (Nlac) or a placebo control. 2. Blood samples were collected to assess B cell responses specific to Nlac and the related pathogen Neisseria meningitidis (Nmen). 3. The study found that colonization with Nlac induced plasma cells that produced antibodies cross-reactive between Nlac and Nmen, suggesting Nlac colonization can stimulate immune memory against Nmen.
Prof Joy Lawn @ MRF's Meningitis and Septicaemia 2019
This document summarizes a presentation on neonatal meningitis and sepsis survivors. The key points are:
1. Survivors of neonatal meningitis and sepsis often experience long-term neurological impairments. Studies find moderate to severe impairment in 18-23% of survivors.
2. There are significant gaps in data on the true burden of neonatal infections due to limitations in care access, clinical assessment, laboratory testing, and long-term follow up in low-resource settings. This impacts estimates of impairment rates.
3. Improving data through strengthened health systems, innovative diagnostics, expanded cohort studies, and better impairment measures is needed to close these gaps and better support survivors long-term.
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PCVs have important indirect effects on reducing vaccine-type carriage and invasive pneumococcal disease. A 2+1 dosing schedule of PCVs provides both direct and indirect protection across populations by inducing sustained functional antibody responses after boosting. More evidence comparing the direct and indirect protective effects of 3+0 and 2+1 PCV schedules is forthcoming.
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2. The fetal sex determination test analyzes DNA from the mother's blood to identify Y chromosome sequences and correctly identified sex with high accuracy after 7 weeks of gestation.
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The document provides an overview of acute bacterial meningitis, including:
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- Clinical presentation often includes the classic triad of fever, neck stiffness, and altered mental status. Investigations include lumbar puncture and analysis of CSF.
- Differentiating between bacterial and viral meningitis can be done using factors like CSF white blood cell count, glucose and protein levels, and peripheral blood markers.
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Dr. Sami Gottlieb of the World Health Organization discussed the potential for meningococcal B (MenB) vaccines to help prevent gonococcal infection on a global scale. MenB vaccines have shown preliminary efficacy against gonorrhea in clinical trials and epidemiological data. WHO is working to define priority populations for gonorrhea vaccines and assess how existing MenB programs could be leveraged. Effectiveness may depend on disease epidemiology, vaccine characteristics, target populations, and integration with current immunization systems. Ongoing trials of MenB vaccines against gonorrhea will provide critical data to inform introduction decisions.
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This document discusses considerations for developing human embryonic stem cell (hESC)-based therapies. It outlines how hESCs can be differentiated into various cell types for potential therapeutic use. Key challenges include developing reproducible differentiation methods, characterizing cell populations, and demonstrating safety and efficacy in clinical trials. Nonclinical studies must address issues like final product characterization, pharmacology, toxicology, tumorigenicity, and allogenicity. Clinical trials require careful design and monitoring to minimize risks while assessing outcomes and cell survival over the short and long term.
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The document discusses the Global Meningitis Genome Partnership (GMGP), which aims to address inequities in genomic surveillance capacity for meningitis pathogens between high-income and low-income countries. It outlines what has been achieved so far, including establishing standardized metadata for sequencing and epidemiological data. The GMGP is working to incorporate genome surveillance into regional surveillance strategies, initially focusing on Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus agalactiae in Africa. Open data sharing is encouraged according to clear governance policies. Standardizing metadata and curating sequencing data in a central library are discussed to facilitate consistent analysis and data visualization for public health benefit
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2 Jackson Humans
1) The document discusses various potential therapies for human rabies that have been studied experimentally, including ketamine, ribavirin, interferon, and therapeutic coma.
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Optimizing antimicrobial therapy for hospitalized pneumonia: Focus on PK/PD p...
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Meningococcal vaccination needed in india july 2016
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- There was a significant reduction in cases of invasive bacterial infections like pneumococcal disease, H. influenzae, and meningococcal disease in 2020 coinciding with COVID-19 containment measures across many countries. Vaccination coverage rates have decreased dramatically in Brazil representing a potential risk of rebound in infectious disease rates. Maintaining disease surveillance is important to inform authorities on current disease burden and carriage rates even though some diseases were reduced during the pandemic.
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This document discusses optimal schedules for controlling pneumococcal infection in countries with high and low carriage. It notes that the African Meningitis Belt has seen sub-optimal pneumococcal conjugate vaccine (PCV) coverage due to geopolitical factors and vulnerable populations. Outbreaks in Ghana pre- and post-PCV introduction show that herd protection may be inadequate. Research is needed to better understand pneumococcal biology and prevention. Improving PCV access and coverage, including schedules with boosters and catch-up campaigns targeting 5-29 year olds, may help prevent outbreaks. Strengthening surveillance systems allows rapid response.
Professor Muhamed-Kheir Taha
Professor Muhamed-Kheir TAHA MD, PhD, HDR presented on lessons and impacts for meningitis in the COVID-19 era. Data showed cumulative cases of invasive meningococcal disease (IMD) from 2014-2020 in France as well as distribution of IMD cases from 2011-2020. Vaccine use in France declined during the COVID-19 pandemic in 2020, with reduced doses of the 5-month and 12-month vaccines. Distribution of IMD cases by age group from 2011-2021 showed an immunity gap in childhood due to the pandemic. Conclusions were that reduced pathogen circulation may decrease herd immunity, social distancing was associated with lower vaccine uptake, and countries need plans to promote
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Progress is being made on developing a combined MenABCWY vaccine. Studies are underway evaluating the immunogenicity and safety of combining different meningococcal vaccines that target serogroups A, C, W, Y. Combining the vaccines could simplify immunization schedules, reduce costs by needing fewer doses, and increase vaccination uptake by reducing the number of required injections. However, a combined vaccine may also increase reactogenicity and interfere with the immune response to other concomitant vaccines. Ongoing studies are evaluating different potential MenABCWY vaccine combinations to determine the optimal formulation.
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1) The PSERENADE project analyzed surveillance data from over 50 sites in 34 countries to assess the impact of PCV10 and PCV13 introduction on pneumococcal meningitis incidence globally in children under 5 years old and adults 18 years and older.
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This study examined sequelae in 49 pediatric patients with invasive meningococcal disease (IMD) in Chile between 2009-2019. The researchers found that 59% of patients experienced sequelae at hospital discharge, with neurological disorders being the most common at 59.2%. Risk factors for sequelae included age under 1 year old, shock, and meningeal signs at admission. Sequelae were also associated with a clinical diagnosis of meningitis with meningococcemia. The study concludes that multidisciplinary follow-up is needed to reduce the long-term impacts of IMD in children.
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- 1. Adjunctive corticosteroids for acute bacterial meningitis in Africa – do we need more evidence? Rob Heyderman
- 2. Rationale for Steroids - Pathogenesis of Bacterial Meningitis Apoptosis Necrosis Senescence Immune activation Macrophages Microglia Astrocytes Endothelium Neurons Neutrophils BBBP Thrombosis Blood Flow Bacterial products (PAMPs) Cytokines Chemokines Reactive Oxygen Species Ecosinoids
- 3. Dexamethasone as Adjunctive Therapy in Bacterial Meningitis Matthijs Brouwer, Peter McIntyre, Kameshwar Prasad, Diederik van de Beek The Cochrane Library, Issue 9, 2015; DOI: 10.1002/14651858 • 25 trials in acute bacterial meningitis (4121 participants) • 16 in children • 7 in adults • 2 children and adults • 22 used dexamethasone; 3 used hydrocortisone or prednisone • 9 were performed in low-income countries; 16 in high-income countries
- 4. Dexamethasone as Adjunctive Therapy in Bacterial Meningitis: MORTALITY The Cochrane Library, Issue 9, 2015; DOI: 10.1002/14651858 RR 0.90, 95% CI 0.80-1.01
- 5. Dexamethasone as Adjunctive Therapy in Bacterial Meningitis: sub-group analyses The Cochrane Library, Issue 9, 2015; DOI: 10.1002/14651858 • Reduced mortality in S. pneumoniae meningitis (RR 0.84, 95% CI 0.72 to 0.98) NOT H. influenzae or N. meningitidis meningitis • Overall reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20-0.59) NOT non-Haemophilus meningitis • In high-income countries • Reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73) • Any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) • Short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85) • No beneficial effect in low-income countries
- 6. The High Mortality for Childhood & Adult Meningitis in SSA
- 7. The Survival Road for Bacterial Meningitis Carriage Invasion Clinical Disease Survival No Sequelae Survival Sequelae Death
- 8. • Are we trying to shortcut deficiencies in healthcare seeking, access healthcare and health systems? • Will corticosteroids work in this setting? • Could steroids be harmful (adverse event reporting has been selective)? Is there sufficient equipoise in this highly vulnerable population?
- 9. Adjunctive corticosteroids for acute bacterial meningitis in Africa – do we need more evidence? VOTE NO • Improve community recognition • Improve access • Health Systems interventions • Identify novel targets & interventions