Background: The complement system is a vital component of the inflammatory response occurring during bacterial meningitis. Blocking the complement system was shown to improve the outcome of experimental pneumococcal meningitis. Complement factor H (FH) is a complement regulatory protein inhibiting alternative pathway activation but is also exploited by the pneumococcus to prevent complement activation on its surface conferring serum resistance.
Methods: In a nationwide prospective cohort study of 1009 episodes with community-acquired bacterial meningitis, we analyzed whether genetic variations in CFH influenced FH cerebrospinal fluid levels and/or disease severity. Subsequently, we analyzed the role of FH in our pneumococcal meningitis mouse model using FH knock-out (Cfh) mice and wild-type (wt) mice. Finally, we tested whether adjuvant treatment with human FH (hFH) improved outcome in a randomized investigator blinded trial in a pneumococcal meningitis mouse model.
Results: We found the major allele (G) of single nucleotide polymorphism in CFH (rs6677604) to be associated with low FH cerebrospinal fluid concentration and increased mortality. In patients and mice with bacterial meningitis, FH concentrations were elevated during disease and Cfh mice with pneumococcal meningitis had increased mortality compared to wild-type mice due to C3 depletion. Adjuvant treatment of wild-type mice with purified human FH led to complement inhibition but also increased bacterial outgrowth which resulted in similar disease outcomes.
Conclusion: Low FH levels contribute to mortality in pneumococcal meningitis but adjuvant treatment with FH at a clinically relevant time point is not beneficial.
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http://dx.doi.org/10.1186/s12974-019-1675-1 | DOI Listing |
Pan Afr Med J
December 2024
Infectious Diseases Department, Ibn Al Jazzar University Hospital, Kairouan, Tunisia.
Pneumococcal meningitis is the most severe bacterial meningitis rarely complicated by acute myelitis. We report a case of a 54-year-old female who presented with pneumococcal meningoencephalitis. After eight days of hospitalization, the patient presented a sudden onset of bilateral lower leg weakness and bladder and bowel sphincter dysfunction.
View Article and Find Full Text PDFLancet Digit Health
December 2024
Nuffield Department of Population Health, University of Oxford, Oxford, UK. Electronic address:
Microbiology reference laboratories perform a crucial role within public health systems. This role was especially evident during the COVID-19 pandemic. In this Viewpoint, we emphasise the importance of microbiology reference laboratories and highlight the types of digital data and expertise they provide, which benefit national and international public health.
View Article and Find Full Text PDFLancet Infect Dis
December 2024
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Background: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages.
Methods: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%.
J Med Econ
December 2024
Merck & Co., Inc., Rahway, NJ, USA.
Introduction: This study analyzed the health and economic impact of the 21-valent pneumococcal conjugate vaccine (V116) and the 20-valent pneumococcal conjugate vaccine (PCV20), as well as their relative cost-effectiveness, in Japanese adults aged 65 years using a delta pricing approach.
Methods: A Markov model was employed to simulate the movement of the Japanese population among 4 health states: healthy, pneumococcal disease (consisting of invasive pneumococcal disease [IPD] with or without meningitis and non-bacteremic pneumococcal pneumonia [NBPP]), post-meningitis sequelae (PMS), and death. The model was populated with publicly available demographic and epidemiologic data, stratified by risk level.
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