Community acquired bacterial meningitis and meningococcal septicaemia amongst adults in

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Community acquired bacterial meningitis and
meningococcal septicaemia amongst adults in England
and Wales : epidemiology and clinical management
Thesis
How to cite:
Gjini, Ardiana (2010). Community acquired bacterial meningitis and meningococcal septicaemia amongst adults in
England and Wales : epidemiology and clinical management. PhD thesis The Open University.
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Dr A Gjini. Bacterial meningitis amongst adults. PhD thesis
Community acquired bacterial meningitis and
meningococcal septicaemia amongst adults in
England and Wales: epidemiology and clinical
management
by
Dr Ardiana Gjini
MBBS, MSc, MFPHM
A thesis submitted in fulfilment of the requirements for a PhD
June 2009
Department of Mathematics and Statistics
Faculty of Mathematics, Computing and Technology
The Open University
Sponsoring university
University of Bristol
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Dr A Gjini. Bacterial meningitis amongst adults. PhD thesis
Acknowledgement
I wish to take this opportunity to express my gratitude to all my supervisor. but
specifically Prof Rob Heyderman and Prof James Stuart - for formulating the initial
working hypothesis for a part of this research. giving me the opportunity to work in
this, what was an exciting throughout. project and mostly for good support, advice
and encouragement through all these years.
My thanks to Prof Debbie Lawlor for advise and support, who at the later stages of
this research, in many ways more challenging ones, became my main supervisor and
through acknowledging my difficulties with balancing service and academic work. and
family life, continued to provide the much needed motivation.
I especially thank Prof Paddy Farrington and Dr Kevin McConway, my supervisors at
the Open University, for good advice and intelligence particularly on the areas less
familiar for me.
I acknowledge the listed members of the Expert Panel for assistance in developing
and undertaking a study of high research standards. In particular, Mr Tom Nichols for
helping me appreciate and apply the more advanced statistical methods. My thanks
are for The South West Public Health Training Scheme and my trainers for
acknowledging the commitment needed; the MRF and all of those who were directly
or indirectly involved in assisting me with this project, at the University of Bristol,
HPA, and the hospitals reviewed.
My special thanks are for my parents for their support throughout the years of my
education, providing a lasting motivation and encouragement. My sincere thanks and
my great appreciation goes to my husband for his continuous support and
understanding for the often-compromised family and social life. My apologies go to
my daughter, Rosie Zana - sorry I had to work so much to complete this. I dedicate
this thesis to you - mezi pres tij kompenzoj kohijn qij s'e kam kalu me ty! I
Dr Ardiana Gjini, Bacterial meningitis amongst adults. Submission for a PhD
acknowledge Rosie's grandparents for spending so much time with her when I
should have.
And lastly my appreciation and thanks to the DH for funding the study in reviewing
the clinical management, funding which made it possible for all this research to be
undertaken.
Dr A Gjini. Bacterial meningitis amongst adults. PhD thesis
Abstract
Background: Bacterial meningitis and meningococcal septicaemia are important
causes of morbidity and mortality in the UK and elsewhere. There have been
achievements in paediatric care, including vaccination; however mortality amongst
otherwise healthy young adults remains high.
Objective: I undertook this study to examine the way by which the public health
burden of meningitis in adults can be reduced.
Methods: I used routine surveillance data (laboratory reports, clinical notifications,
hospital activity, mortality data) to examine the epidemiology and determine the
changing trends. I undertook a capture-recapture study to quantify the underreporting
through the routine surveillance. I conducted a retrospective review of clinical
management of adult patients with meningitis in England and Wales using medical
records of patients diagnosed with meningitis or meningococcal septicaemia. I
examined the association of clinical management with the outcome of the disease
(CABM and MS).
Findings: The epidemiology of adult meningitis in England and Wales is changing.
Overall forms of CABM show no significant changing trend, whilst meningococcal
septicaemia shows an increasing trend. Tubercular meningitis is increasing
significantly, whilst pneumococcal, HiB and Listeria meningitis are falling. Mortality
generally remains in a steady trend. There are differences by age-group and
causative organisms. There is considerable (-50%) underreporting of both, incidence
and mortality from all major routine surveillance systems. Hospital management of
meningitis is largely sub-optimal. Main areas of deficiency in clinical care are: timely
diagnosis and consequently administration of antibiotics, assessment of severity, and
record keeping; and these appeared to vary between the hospitals. It is difficult to
examine the association between clinical with the outcome of meningitis primarily
Dr Ardiana Gjini, Bacterial meningitis amongst adults. Submission for a PhD
due to confounding by severity of illness which in my study was further jeopardised
by the lack of recorded data and study power.
Conclusion: This study has identified areas within public health interventions, such
as vaccination policies, and clinical care, such as improved diagnosis and severity
assessment, where there is potential for improvement towards a reduced public
health burden of adult meningitis in England and Wales.
Dr Ardiana Gjini, Bacterial meningitis amongst adults. Submission for a PhD
Table of content
Abbreviations .................................................................................................................. 1
List of tables ............................................................... ····················································· 3
List of figures ................................................................................................................... 6
List of appendicies .......................................................................................................... 8
Preface ............................................................................................................................ 9
Part one -Introduction to my research
Chapter One - Introduction to the thesis ....................................................................... 11
Chapter Two - Background ............................................................................................ 22
Chapter Three - Data and Methods ............................................................................... 80
Part two - Results of my research
Chapter Four - The recent epidemiology of community acquired bacterial meningitis and
meningococcal septicaemia amongst adults in England and Wales, 1991-2002 ........ 130
Chapter Five - Improving estimates of community acquired bacterial meningitis: an
application of a capture-recapture analysis of pneumococcal meningitis in England ... 158
Chapter Six - A review of hospital management of community acquired bacterial meningitis
and meningococcal septicaemia in adults ................................................................... 185
Chapter Seven - Association of clinical management with the outcome of community
acquired bacterial meningitis and meningococcal septicaemia in adults in England and
Wales .......................................................................................................................... 217
Part three - Interpretation of the results In context
Chapter 8 - Discussion ................................................................................................ 231
Dr Ardiana Gjini, Bacterial meningitis amongst adults. Submission for a PhD
Chapter 9 - Conclusion, recommendations and further work ....................................... 258
References 265
Appendices ................................................................................................................. 301
Dr A Gjini. Bacterial meningitis amongst adults. PhD thesis
Abbreviations
ACHA - American College Health Association
BCG - Bacillus Calmette-Guerin
BIS - British Infection Society
CABM - Community Acquired Bacterial Meningitis
CCDC - Consultant in Communicable Disease Control
CDC, US - Centers for Disease Control
CDR - Communicable Disease Report
CDSC - Communicable Disease Surveillance Centre
CFI-Centre for Infection
CFR - Case Fatality Rate
CSF - Cerebro Spinal Fluid
CT -Computerised Tomography
DH - Department of Health
ECDC - European Centre for Disease Control and Surveillance
EP - Expert Panel
FSML - Food Safety Microbiology Laboratory
GAVI - Global Alliance for Vaccines and Immunization
HES - Hospital Episode Statistics
Hib - Haemophilus influenzae type b
HIV - Human Immunodeficiency Virus
HPA - Health Protection Agency
ICD 10 - International Classification of Diseases 10
1
Dr A Gjini. Bacterial meningitis amongst adults. PhD thesis
ICP - Intracranial Pressure
IPD - Invasive Pneumococcal Disease
LEP - Laboratory of Enteric Pathogens
LP - Lumbar Puncture
MD - Meningococcal Disease
Men C - Menigitis Serogroup C
Men RU - Meningococcal Reference Unit
MREC - Multi-Centre Research Ethics Committee,
MS - Meningococcol Septicaemia
NHS - National Health Service
NM - Neisseria Meningitidis
NNT - Number Needed to Treat
NOlO - Notifications of Infectious Diseases
ONS - Office for National Statistics
PCR - Polymerase Chain Reaction
PCV - Pneumococcal Conjugate Vaccine
PHLS - Public Health Laboratory Service
PI - Principal Investigator
PTC - Primary Care Trusts
RLR - Reconciled Laboratory Reports
RSIL - Respiratory and Systemic Infection Laboratory
SE - Standing Error
T8 - Tubercolosis
T8M - tubercolous meningitis
US - United States
VPD - Vaccine Preventable Diseases
2