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Infections in the central nervous system with focus on meningococcal disease: clinical and epidemiological aspects
Örebro University, School of Medical Sciences.ORCID iD: 0000-0003-1999-3383
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Infections in the central nervous system (CNS) include meningitis and encephalitis and are associated with high mortality and morbidity. A large number of different pathogens can cause these infections, including Neisseria meningitidis. It’s crucial to find the causative pathogen in order to provide the best treatment to the patient and for disease surveillance. 

In Paper I, molecular methods were used to investigate the microbial etiology in patients presenting with CNS infections at United Mission Hospital in Tansen, Nepal. Although the cerebrospinal fluid samples were analyzed for a large number of microbes using two commercial multiplex PCR panels and additional in-house real-time PCR, the etiology of the infections was still unknown in a large number of patients. This calls for further development of diagnostic methods for CNS infections.

Neisseria meningitidis, the meningococcus, is a strictly human commensal but also capable to cause severe disease, typically in the form of sepsis and meningitis. The aim of Paper II and III was to study the clinical presentation of N. meningitidis serogroup Y and W infections, which increased unexpectedlyin Sweden from 2007 and 2014, respectively. By reviewing medical records of these infection episodes, the conclusion was drawn that atypical presentations with respiratory and gastrointestinal symptoms were common, rather than meningitis and petechiae.

In Paper IV, meningococcal carriage was studied among students at Örebro University. Age ≤22 years, smoking, previous tonsillectomy, frequent partying and male gender were associated with higher carrier rates. The so far longest observation of carriage of the same meningococcal strain was presented, with a duration of at least one year.

In conclusion, the results from these studies highlight the importance of early detection of meningococcal infections with atypical presentations and the need of improved diagnostics for CNS infections

Place, publisher, year, edition, pages
Örebro: Örebro University , 2022. , p. 122
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 256
Keywords [en]
CNS infection, meningitis, encephalitis, Neisseria meningitidis, serogroup Y, serogroup W, meningococcal disease, carriage, PCR
National Category
General Practice
Identifiers
URN: urn:nbn:se:oru:diva-96457ISBN: 9789175294278 (print)OAI: oai:DiVA.org:oru-96457DiVA, id: diva2:1627752
Public defence
2022-03-25, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2022-01-14 Created: 2022-01-14 Last updated: 2023-04-14Bibliographically approved
List of papers
1. Etiology of Central Nervous System Infections in a Rural Area of Nepal Using Molecular Approaches
Open this publication in new window or tab >>Etiology of Central Nervous System Infections in a Rural Area of Nepal Using Molecular Approaches
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2019 (English)In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 101, no 1, p. 253-259Article in journal (Refereed) Published
Abstract [en]

The etiology of infections of the central nervous system (CNS) in Nepal often remains unrecognized because of underdeveloped laboratory facilities. The aim of this study was to investigate the etiology of CNS infections in a rural area of Nepal using molecular methods. From November 2014 to February 2016, cerebrospinal fluid (CSF) was collected from 176 consecutive patients presenting at United Mission Hospital in Tansen, Nepal, with symptoms of possible CNS infection. After the CSF samples were stored and transported frozen, polymerase chain reaction (PCR) was performed in Sweden, targeting a total of 26 pathogens using the FilmArray® ME panel (BioFire, bioMerieux, Salt Lake City, UT), the MeningoFinder® 2SMART (PathoFinder, Maastricht, The Netherlands), and an in-house PCR test for dengue virus (DENV), Japanese encephalitis virus (JEV), and Nipah virus (NiV). The etiology could be determined in 23%. The bacteria detected were Haemophilus influenzae (n = 5), Streptococcus pneumoniae (n = 4), and Neisseria meningitidis (n = 1). The most common virus was enterovirus detected in eight samples, all during the monsoon season. Other viruses detected were cytomegalovirus (n = 6), varicella zoster virus (n = 5), Epstein-Barr virus (n = 3), herpes simplex virus (HSV) type 1 (HSV-1) (n = 3), HSV-2 (n = 3), human herpes virus (HHV) type 6 (HHV-6) (n = 3), and HHV-7 (n = 2). Cryptococcus neoformans/gatti was found in four samples. None of the samples were positive for DENV, JEV, or NiV. Of the patients, 67% had been exposed to antibiotics before lumbar puncture. In conclusion, the etiology could not be found in 77% of the samples, indicating that the commercial PCR panels used are not suitable in this setting. Future studies on the etiology of CNS infections in Nepal could include metagenomic techniques.

Place, publisher, year, edition, pages
HighWire Press, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-74617 (URN)10.4269/ajtmh.18-0434 (DOI)000476680300040 ()31162021 (PubMedID)2-s2.0-85068911912 (Scopus ID)
Funder
Swedish Society of Medicine
Note

Funding Agencies:

Region Örebro County's Research Committe

Örebro University

Folke Nordbring Foundation

Available from: 2019-06-05 Created: 2019-06-05 Last updated: 2022-03-02Bibliographically approved
2. Clinical presentation of invasive disease caused by Neisseria meningitidis serogroup Y in Sweden, 1995 to 2012
Open this publication in new window or tab >>Clinical presentation of invasive disease caused by Neisseria meningitidis serogroup Y in Sweden, 1995 to 2012
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2017 (English)In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 145, no 10, p. 2137-2143Article in journal (Refereed) Published
Abstract [en]

Over the period 1995-2012, the incidence of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y (NmY) increased significantly in Sweden. This is mainly due to the emergence of a predominant cluster named strain type YI subtype 1, belonging to the ST-23 clonal complex (cc). The aim of this study was to examine the clinical picture of patients with invasive disease caused by NmY and to analyse whether the predominant cluster exhibits certain clinical characteristics that might explain the increased incidence. In this retrospective observational study, the medical records available from patients with IMD caused by Nm serogroup Y in Sweden between 1995 and 2012 were systematically reviewed. Patient characteristics, in-hospital findings and outcome were studied and differences between the dominating cluster and other isolates were analysed. Medical records from 175 of 191 patients were retrieved. The median age was 62 years. The all-cause mortality within 30 days of admission was 9% (15/175) in the whole material; 4% (2/54) in the cohort with strain type YI subtype 1 and 11% (12/121) among patients with other isolates. Thirty-three per cent of the patients were diagnosed with meningitis, 19% with pneumonia, 10% with arthritis and 35% were found to have bacteraemia but no apparent organ manifestation. This survey included cases with an aggressive clinical course as well as cases with a relatively mild clinical presentation. There was a trend towards lower mortality and less-severe disease in the cohort with strain type YI subtype 1 compared with the group with other isolates.

Place, publisher, year, edition, pages
Cambridge University Press, 2017
Keywords
Invasive meningococcal disease, meningococcal disease, Neisseria meningitidis, Neisseria meningitidis serogroup Y, Sweden
National Category
Infectious Medicine Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:oru:diva-58934 (URN)10.1017/S0950268817000929 (DOI)000404243900018 ()28478773 (PubMedID)2-s2.0-85018441510 (Scopus ID)
Note

Funding Agency:

Region Örebro County Research Committee 

Available from: 2017-08-21 Created: 2017-08-21 Last updated: 2023-06-29Bibliographically approved
3. Atypical presentation of Neisseria meningitidis serogroup W disease is associated with the introduction of the 2013 strain
Open this publication in new window or tab >>Atypical presentation of Neisseria meningitidis serogroup W disease is associated with the introduction of the 2013 strain
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2021 (English)In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 149, article id e126Article in journal (Refereed) Published
Abstract [en]

Since 2015, the incidence of invasive meningococcal disease (IMD) caused by serogroup W (MenW) has increased in Sweden, due to the introduction of the 2013 strain belonging to clonal complex 11. The aim of this study was to describe the clinical presentation of MenW infections, in particular the 2013 strain, including genetic associations. Medical records of confirmed MenW IMD cases in Sweden during the years 1995-2019 (n = 113) were retrospectively reviewed and the clinical data analysed according to strain. Of all MenW patients, bacteraemia without the focus of infection was seen in 44%, bacteraemic pneumonia in 26%, meningitis in 13% and epiglottitis in 8%, gastrointestinal symptoms in 48% and 4% presented with petechiae. Phylogenetic analysis was used for possible links between genetic relationship and clinical picture. The 2013 strain infections, particularly in one cluster, were associated with more severe disease compared with other MenW infections. The patients with 2013 strain infections (n = 68) were older (52 years vs. 25 years for other strains), presented more often with diarrhoea as an atypical presentation (P = 0.045) and were more frequently admitted for intensive care (P = 0.032). There is a risk that the atypical clinical presentation of MenW infections, with predominantly gastrointestinal or respiratory symptoms rather than neck stiffness or petechiae, may lead to delay in life-saving treatment.

Place, publisher, year, edition, pages
Cambridge University Press, 2021
Keywords
Invasive meningococcal disease, meningococcal disease, Neisseria meningitidis, serogroup W, Sweden
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-91688 (URN)10.1017/S0950268821001035 (DOI)000652182800001 ()33910672 (PubMedID)
Note

Funding Agency:

Swedish state under the ALF  

Available from: 2021-05-10 Created: 2021-05-10 Last updated: 2023-06-30Bibliographically approved
4. Prevalence and persistence of Neisseria meningitidis carriage in Swedish university students
Open this publication in new window or tab >>Prevalence and persistence of Neisseria meningitidis carriage in Swedish university students
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(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-97724 (URN)
Available from: 2022-03-02 Created: 2022-03-02 Last updated: 2022-03-09Bibliographically approved

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