Public Health Wales Research and Development 2014/15

Public Health Wales Research and Development 2014/15
The following table contains all research and development projects which concluded in the 2014/15 financial year.
Project Title
Characterisation of
HPV viral integration
in DNA obtained
from residual
cervical smears
collected within
Baseline HPV
Lay Summary
Human Papillomavirus (HPV) is a very common viral
infection and most women will be infected at some
point in their lives. This is a study to see if carrying out
new tests for HPV status on cervical screening samples
could identify women at a higher risk of cervical disease
development. Occasionally, HPV can cause abnormal
cell growth by interfering with the normal cell controls.
Public Health Wales Investigator
Helen Beer (Senior Information
Manager and Research Specialist,
Screening Division)
[email protected]
The tests will start to look for possible changes in the
virus status that could be the cause of this loss of
control. This study will be performed on stored residual
smear material (80°C) that has been previously
collected as part of a pseudoanonymous study and will
not affect patient treatment and will not require
additional samples.
KESS Project:
Developing an
integrated whole
amplification and
next generation
High risk (HR) HPV positive samples will be tested
further with for viral integration status. The results of
these tests will be compared with available smear and
biopsy results collected pseudo-anonymously over 2
rounds of screening (up to 6 years) as part of the
original Baseline HPV 2009 study.
Cryptosporidium is a group of protozoan parasites
Cryptosporidiosis. Infected people develop symptoms
such as diarrhoea and intestinal pain but usually get
better within a few weeks. However, in patients with
weak immune systems the infection can be fatal. There
Professor Rachel Chalmers
(Consultant Clinical
Scientist/Honorary Professor
Head, Cryptosporidium Reference
Public Health Wales Microbiology)
Useful Links and Publications
sequencing method
to characterise
clinical isolates
is no licensed treatment for cryptosporidiosis. To [email protected]
develop better treatments, understand how the disease
spreads and how it can be prevented researchers are
studying the DNA of the parasite by so-called “next
generation sequencing” (NGS) techniques. For
NGS to be successful, enough parasite DNA needs to be
extracted from patient stool samples. However, often
only small amounts of parasite DNA can be extracted,
and NGS is not possible. To be able to analyse samples
containing small amounts of parasite DNA, we want to
use a method called “whole genome amplification”
(WGA). This is a way to make many copies of a DNA
sample and will hopefully make enough copies of the
parasite DNA in samples with amounts to allow us to
analyse the sequence by NGS.
The first aim of the project then is to test whether WGA
and NGS, in combination with other preparation
techniques, works by analysing human clinical samples.
The second aim of the project is to use the method to
analyse the DNA sequences of further clinical isolates to
investigate the Cryptosporidium species causing
outbreaks and sporadic disease in Wales and the UK
and to help develop better methods for identifying
outbreaks of cryptosporidiosis.
The stool samples used in the study will be selected
from those received at the Cryptosporidium Reference
Unit (CRU), Public Health Wales Microbiology, Singleton
Hospital, Swansea for DNA analysis by routine DNA
typing methods and anonymised before testing. The
study will be undertaken at the CRU and Aberystwyth
A survey to
investigate the
reasons why
patients in the
‘standard’ and ‘nonurgent’
triage categories
attend the
Department (ED)
and to explore what
other options they
have considered.
Development and
assessment of a
Nucleic Acid
Amplification Test
for the detection of
Toxoplasma gondii
in meat entering the
human food chain
The ultimate aim of the research is to investigate the
reasons why patients in the ‘standard’ and ‘non-urgent’
triage categories attend ED and to explore what other
options they have considered before attending the ED.
An anonymous self-completion questionnaire will be
designed, pre-piloted and then produced in both
English and Welsh. This will be in a format to allow
electronic analysis, working closely with Bangor
University. The survey will also collect basic
demographic information on patients (age, sex and
postcode). The setting will be the 3 EDs in North Wales
and the survey will be conducted in February and
March of 2014. The survey instrument will be
administered by Betsi Cadwaladr University Health
Board (BCU HB) Emergency Department staff in the 3
EDs to patients and/or their carers (aged 16 years+)
post-triage; this will be limited to patients who have
been flagged up as being in the ‘standard’ and ‘nonurgent’ triage categories (Manchester triage categories
green and blue). Those patients who are incapable
through alcohol or drugs to complete a questionnaire
will be excluded from the survey, as well as those who
are in emotional distress, or those who have been
referred to the ED formally by letter from their GP.
Toxoplasma gondii is a parasite which affects humans
and can cause ocular toxoplasmosis, congenital
toxoplasmosis and miscarriage/stillbirth. The parasite is
transmitted via ingestion of the oocysts through the
consumption of undercooked meat, ingestion
contaminated water or from mother to foetus. The
purpose of this study is to develop and assess a Nucleic
Acid Amplification Test for the detection of oocysts in
Dr Robert Atenstaedt (Consultant
in Public Health Medicine, Public
Health Wales)
[email protected]
Professor Edward Guy (Consultant
Clinical Scientist - Head of
Toxoplasma Reference Unit, Public
Health Wales)
[email protected]
Atenstaedt, R, Gregory, J, PriceJones, C, Newman, J, Roberts, L,
and Turner, J. (2014). Why do
patients with nonurgent
conditions present to the
Emergency Department despite
the availability of alternative
services? Epub ahead of print 17
November. In: Eur J Emerg Med
Evaluation of the
Bactec fx system in
combination with
various novel
molecular methods
for the detection
and identification of
Candida species
mixed meat and ham. The results will provide a
guideline for future detection of toxoplasma in meat.
This project will focus on determining the threshold of
BACTEC fx to detect candidaemia, the most common
infestation of invasive candidiasis. Currently the
sensitivity is 50% and is due to the low organism
numbers in circulation and consequently, collecting
blood samples, resulting in a necessity for a higher
frequency of testing to increase the chances of
detection. Growth also regularly takes a number of days
in blood cultures, with extra time then required for
conventional phenotypic identification. Identification is
required for effective treatment as certain species are
Azole resistant.
A range of Candida species will be inoculated at
different CFU/ml levels into different BACTEC bottle
types and the time for a bottle to become positive will
be monitored and extended if the culture remains
negative after 5 days with end plating of all broth being
done to determine the threshold of the BACTEC fx.
Detection and identification methods ranging from
chromogenic agar, matrix-assisted laser desorption
ionization-time of flight (MALDI TOF) mass
spectrometry, real-time polymerase chain reaction
(PCR) and Raman spectroscopy will be used directly on
blood cultures and cultured isolates to determine the ID
of the various Candida species. The use of rapid and
sensitive techniques, if shown to be reliable, could
hopefully speed up the diagnostic process, reduce
mortality rates and allow appropriate antifungal
treatment to be given to those individuals with invasive
Paula Brookes (Operational
Manager Bacteriology, Public
Health Wales)
[email protected]
What is the
unrecognised UK
prevalence of
Coxiella Burnetti in
patients prior to
Valve replacement
surgery: A pilot
disease and reduce unnecessary therapy and toxicity in
other patients, resulting in cost saving for the NHS.
Q fever is an uncommon disease that in some cases can
cause chronic damage to the valves of the heart. This
often happens with very few symptoms and is often
difficult to differentiate from age related change to the
heart valves. There has not been a study before in the
UK of how many people who need new heart valves
may have Q fever without knowing it.
Dr Brendan Healy (Consultant in
Microbiology and Infectious
Diseases, Public Health Wales)
[email protected]
We aim to study a group of people undergoing routine
heart valve replacement and to test them for
serological (blood) evidence of Q fever and to test the
valve that is removed during their operation for Q fever.
All these tests will happen while the patient is asleep
during their operation.
We aim to use the results to estimate the number of
people undergoing routine valve replacement that have
evidence of Q fever infection and then see how that
may affect the lifespan of their new valve.
In Wales, bowel screening is currently offered to men
and women aged between 60 and 71 years old.
utilisation of
Screening programmes require good uptake to be
responders and non- effective. In order to develop a strategy for increasing
uptake we first need to find out how non-responders
to the bowel
differ from responders. For bowel screening, which is a
test undertaken at home, there may be opportunities to
programme in Wales promote uptake through contact with categories of
before and after
health professionals not usually associated with the
invitation to
bowel screening programme. Through understanding
screening in order to healthcare utilisation we hope to find potentially useful
improve early
intervention points and conversely, and not waste time
Dr Rosemary Fox (Director of
Screening Division, Public Health
[email protected]
detection either
through screening or
A prospective study
of faecal parasite
infections among
children in
and resources pursuing strategies unlikely to be
This study aims to compare the engagement of
responders and non-responders to the bowel screening
programme with health care services in the year before
and the year following invitation. We will explore the
engagement with primary and secondary care before
and after the screening invitation in order to compare
responders and non-responders and to identify possible
strategies for encouraging participation.
We plan to link information from several sources to
compare morbidity, measured by GP consultations,
hospital outpatient, elective and emergency
admissions, both before and after invitation to the
screening programmes.
Cambodia has some of the poorest health indicators in
Southeast Asia, with high rates of malnutrition. Just
under a third of the population have access to improved
sanitation facilities, and rainwater is the main source of
water for most homes. It is therefore not surprising that
infection with gut parasites is a common problem in
children, causing detrimental effects on nutrition,
growth and cognitive development and contributing
substantially to childhood anaemia. The primary
purpose of this study is to define the incidence and
range of faecal parasites causing infections in
Cambodian children presenting to hospitals; the R&D
approval sought here is specifically for the work that
will be undertaken at the national Cryptosporidium
Reference Unit in Public Health Wales Microbiology
Swansea: the analysis of DNA extracted from stools for
Professor Rachel Chalmers
(Consultant Clinical
Scientist/Honorary Professor
Head, Cryptosporidium Reference
Public Health Wales Microbiology)
[email protected]
the detection and characterisation of the
Cryptosporidium parasite. The DNA will have already
been extracted from stools at Liverpool University.
The National Public Health service for Wales will shortly
be rolling out a new form of test (called a dried blood
spot test) for hepatitis B, hepatitis C and HIV infection
amongst individuals at high risk of infection. The dried
blood spot test involves few drops of blood being taken
by a safe and simple finger prick device. The dried blood
spot test samples will be taken by substance misuse
services and specialist nurses and tested by the Welsh
specialist virology unit. The study aims to see how good
the new test is when compared to the previously used
test (a blood sample taken with a needle and syringe)
for detecting hepatitis B, hepatitis C and HIV infection.
This potentially allows the test in future to be offered as
a first line diagnostic tool rather than at present as a
‘pre test’ requiring further confirmation. Individuals
coming forward for routine diagnostic blood borne virus
testing by a blood sample taken with a needle and
syringe will be asked to provide a dried blood spot
sample as well. The results of the two tests will be
compared allowing an assessment of the quality of the
dried blood spot test to accurately detect an infection.
Sensitivity and
specificity of dried
blood spot testing
for the diagnosis of
blood born viral
Identification of
components of oils
and herbs previously
found to have
antibacterial activity
In a previous study it was shown that oils and herbs
showed antibiotic like properties against certain gut
bacteria. The purpose of this study is to look at the oils
and herbs constituent components to see if there are
specific constituents of these compounds that confer
the antibiotic activity.
A prospective
Blood stream infections (BSI) are a major problem and Dr Robin Howe (Consultant
about 8% of hospital inpatients have a BSI. Some will be Microbiologist, Public Health
Dr Rachel Jones
(Consultant Virologist, Wales
Specialist Virology Centre, Public
Health Wales)
[email protected]
Eugene Rees
(Technical Head of Bacteriology,
Public Health Wales Microbiology
[email protected]
multicentre trial to
assess the impact of
laboratory based
RAPId Diagnosis on
Outcome in patients
with Blood Stream
Infections (RAPIDO)
admitted with a BSI and others will develop an infection Wales)
during their hospital stay. Recent improvements in [email protected]
infection control have reduced the number of patients
that acquire an infection during their hospital stay, but
BSI still occur and there are currently around 90100,000
cases a year. In certain infections the death rate can be
as high as 50% and every patient that contracts an
infection has a longer hospital stay. BSI is diagnosed by
taking a blood sample from patients with suspected
infection. Antibiotic treatment is commenced within
hours, but processing of blood cultures takes several
days to reach a definitive diagnosis and identify the
correct antibiotic. The initial antibiotic selected will be a
broad spectrum antibiotic, based on the clinician's
judgment of the clinical picture. However, until
definitive bacterial analysis is performed it is unknown
if the correct antibiotic has been selected and there can
be a time lag of up to 35 days before patients receive
appropriate antibiotic therapy for their BSI.
Administration of the correct antibiotics has been
shown to reduce death by up to 50% in some patient
This study will assess the impact of new technology
designed to speed up laboratory diagnosis. The new
technique should produce information within ½ hr of
commencing laboratory processing of positive
A five centre, randomised controlled trial design will be
used and all patients with BSI will be randomised into
two groups, one which will be subjected to the current
diagnostic approach and the other group will have the
integration analysis
in liquid based
cytology samples as
a biomarker for
cervical disease
A pilot study on the
current diagnostic approach plus the new rapid
diagnostic technology as well. Outcome will be assessed
by collecting the same set of clinical information on
each patient in the study.
This is a study to see if carrying out new tests on
cervical screening samples could safely reduce the
number of women referred to hospital following an
abnormal smear result. Taking part in the study will
involve having one additional smear taken but will not
affect patient treatment. Identifiable personal details
will be removed from the samples before they are
tested. The result of the tests will only be used by the
study team to evaluate the new tests for viral
integration and host biology markers. The result will not
be included in the women’s hospital or screening
records. The women will be invited to take part if they
have been referred to the colposcopy clinic following an
abnormal smear. If they consent to being included in
the study, a smear will be taken and tested for human
Papillomavirus (HPV) before colposcopy.
Helen Beer (Senior Information
Manager and Research Specialist,
Screening Division)
[email protected]
HPV is a very common virus that is responsible for
cervical cancer. HPV types 16 and 18 are considered to
be high risk and, together with type 45, are the three
commonest HPV types in cervical cancer, causing about
80% of cervical cancers. HPV 16, HPV 18 and HPV
45positive samples will be tested further to examine
how far the virus has integrated into the cervix. The
results of these tests will be compared with available
smear and biopsy results from consenting women at
subsequent visits (up to 4 years). These results will be
provided by Screening Services Wales
Toxoplasma is a common single-celled parasite that Professor Edward Guy (Consultant
risk factors for
Toxoplasma Gondii
infection in England
and Wales
infects about 5 in 1000 of the UK population each year.
Once an individual is infected, the parasite forms cysts
in heart and CNS tissues and can remain there for life.
In otherwise healthy individuals Toxoplasma infection
often passes unnoticed or causes only mild to moderate
flu- or glandular fever-like symptoms that require no
If the infection is acquired during
pregnancy, however, this can be severe or lifethreatening for the unborn child.
Clinical Scientist - Head of
Toxoplasma Reference Unit, Public
Health Wales)
[email protected]
Toxoplasma is acquired either by eating raw or
undercooked meat from animals that are infected, or by
inadvertently ingesting oocysts (microscopic parasite
eggs) from the environment. Thus, infection may be
food borne or may be associated with a wide range of
occupational or social activities involving exposure to
the environment. In the UK it is not known which of
these routes is the most important and this information
is critical in ensuring health protection advice is
targeted towards the highest risk activities. The
findings will also inform national strategy and policy on
food safety.
Role of chronic
urinary infection in
the pathophysiology
of overactive
bladder syndrome
This study involves finding out, through a 30 minute
telephone interview and questionnaire, what exposure
to risk factors has been encountered by individuals
recently infected with Toxoplasma.
Overactive bladder (OAB) is characterised by urgency (a
sudden compelling desire to pass urine which is difficult
to defer), with or without urge incontinence (complaint
of involuntary leakage accompanied by or immediately
preceded by urgency), usually with frequency and
nocturia (complaint that the individual has to wake at
Eugene Rees
(Technical Head of Bacteriology,
Public Health Wales Microbiology
[email protected]
night one or more times to void).It effects 13% of the
population and the incidence rises with age. It has
significant adverse effect on quality of life; sleep quality
and emotional wellbeing. OAB has been proposed to
have a greater negative effect on the health related
quality of life (HRQoL) than diabetes mellitus,
hypertension, asthma or depression. Various
hypotheses have explained the pathophysiology of OAB
symptoms but no concrete evidence exists which
supports these hypotheses. In recent years, subclinical
urinary infection has been explored as an etiological
factor for OAB symptoms, but robust data is still lacking.
The comparison of
agar dilution, broth
micro dilution and
Etest for
susceptibility testing
of Bacteroides
species and the
detection of genes
The aim of our study is to investigate whether women
with OAB symptoms (and no evidence of overt clinical
infection by conventional Mid Stream Urine for culture)
have significant markers of subclinical infection when
compared to individuals with no OAB symptoms. We
aim to compare the urine samples of patients with OAB
with healthy controls. We will be looking for the
following markers of infection 1) microscopy of fresh
urine for pus cells 2) culture of urine for bacterial
growth 3) Detection of inflammatory biomarkers in the
urine. 4) Molecular testing for bacterial DNA in the
fourth sample.
Metronidazole resistance is still considered rare in
anaerobic isolates from clinical specimens; however,
since January 2013 the Anaerobic Reference Unit in
Cardiff has received had an increase in the number of
referrals of metronidazole resistant Gram negative
rods, mainly of the genus Bacteroides. As metronidazole
remains the basis of treatment for anaerobic infections,
the development of resistance may have an effect on
Mr Trefor Morris
(Lead Biomedical Scientist,
Anaerobe Reference Laboratory,
Public Health Wales)
[email protected]
conferring antibiotic
resistance in these
Models for Access to
Maternal Smoking
cessation Support:
An evaluation of the
effectiveness of new
models of service
delivery to increase
engagement of
pregnant smokers in
stop smoking
patient management and outcome.
Antimicrobial susceptibility for minimum inhibitory
concentration (MIC), to show if the antibiotic will be
effective or not to the bacteria of Meropenem,
Pipercillin/tazobactam and metronidazole will be
conducted using agar dilution, gradient strip and Trek
plates which are presently only validated for B. Fragilis
to see the sensitivity of the organisms to the different
antibiotics and to see if they all confer the same results.
PCR will be used for detecting resistance genes an
individual gene basis to see if the sensitivity patterns
shown by the three different antimicrobial testing
methods are as expected for the resistance genes
present within the organism. There is currently no
multiplex Polymerase Chain Reaction (PCR) available to
screen several genes in a single transaction but with the
potential to develop one.
The study aims to compare the effectiveness of new
models of service delivery for specialist smoking
cessation services for pregnant women with existing
services delivered by Stop Smoking Wales. The new
models of service delivery (pilots) will be implemented
over a maximum 12 month period in selected sites
across four health boards in Wales using an integrated
approach between maternity services, local public
health teams and stop smoking Wales. Core
recommendations from NICE guidance will be
implemented across pilot and usual care sites within
the participating Health Boards (National Institute of
Health and Clinical Excellence 2010). In usual care sites,
stop smoking support for pregnant women will be
Siobhan Jones (Consultant in Public
Health/Associate Director of Public
Health, Public Health Wales)
[email protected]
Bennett, L, Grant, A, Jones, S,
Bowley, M, Heathcote-Elliott, C,
Ford, C, Jones, A, Lewis, R,
Munkley, M, Owen, C, Petherick,
A, and Paranjothy, S. (2014).
Models for Access to Maternal
Smoking cessation Support
(MAMSS): a study protocol of a
quasi-experiment to increase the
engagement of pregnant women
who smoke in NHS Stop Smoking
Services. BMC Public Health 14
delivered by the existing Stop Smoking Wales service. In
pilot sites, support will be provided by a maternity
support worker, a midwife or a dedicated Stop Smoking
Wales advisor and will be delivered more flexibly than
in usual care sites. Each health board has identified pilot
and usual care sites based on geographical areas or
community midwife teams depending on how
maternity care is organised in the Health Boards.
Routine data collected by Health Board maternity
teams and Stop Smoking Wales for a cohort of women
who participate in either a pilot or usual care service
across the four Health Board areas will be extracted,
linked and analysed for a maximum 12 month period.
Examining the effect
of antifungal
treatment and
prophylaxis on the
detection of
molecular markers
of invasive
The primary outcome is engagement with specialist
smoking cessation services defined by having at least
one face to face therapeutic contact. Secondary
outcomes are pregnant smokers who set a quit date;
pregnant smokers who quit at 4 weeks follow up (CO
verified); smoking status of pregnant smokers during
third trimester and birth outcomes (birth weight,
gestational age). Process measures will assess fidelity to
protocols, feasibility acceptability, maintenance and
sustainability should the pilots be rolled out on a wider
This project is led by the University Hospital of Dr Lewis White (Principal Clinical
Wuerzburg in Germany with an overall aim to Scientist, Public Health Wales)
determine the effect of antifungal drugs on the [email protected]
detection of molecular markers for invasive aspergillosis
(IA) in patient samples.
The major focus of this project is a clinical study of the
effects of antifungal treatment on PCR-based
Grant, A, Lewis, R, Jones, S, and
Paranjothy, S. (2014). Who
should support pregnant women
to quit smoking? Early findings
from a quasi-experiment building
upon NICE guidance: Models for
Access to Maternal Smoking
cessation Support (MAMSS)
(PMM58). [Poster presentation].
In:Perinatal Medicine 9 June
2014 - 11 June 2014, Harrogate.
Arch Dis Child Fetal Neonatal Ed
99 (Suppl 1):pp.A142.
aspergillosis (IA)
with the aim of
improving PCRbased detection to
compensate for any
deleterious effects
from treatment
(Polymerase chain reaction) diagnostic methods.
Specifically, the project will examine the effect of
antifungal drugs on the in vitro release of DNA and
galactomannan (GM) which is measured to determine
the magnitude of drug effects on relevant biomarker
detection. A murine model of IA is used to validate the
in vitro results and to allow optimisation of the
detection methods. The final objective is to see if the
observations from in vitro and in vivo models can be
used to improve detection of fungal DNA and GM in
patient plasma and whole blood samples, and this is the
only involvement Cardiff will have in the study.
As part of the diagnostic service provided by Public
Health Wales and Cardiff University laboratory services)
EDTA blood and serum are routinely collected and
tested by PCR and GM ELISA. PCR is performed on
plasma and GM ELISA is performed on serum.
Remaining samples (serum, plasma and blood cells) are
prospectively stored according to local laboratory
procedures for quality assurance and performance
assessment purposes.
Can we use
polymerase chain
It is proposed to test these stored blood cells and serum
specimens by PCR and stored plasma by GM ELISA. The
aim is to test 1000 blood samples (5ml EDTA anticoagulated blood) from 50 patients who are undergoing
HSC (haematopoietic stem cell transplant) until day
+100 post transplantation, over a 6 month period. All
eligible specimens will be shipped to University Hospital
Wuerzburg for subsequent anonymous PCR analyses.
Aims: The aim of this study is to determine whether
Professor Rosemary Barnes
non-invasive samples such as blood, sputum or
(Honorary Consultant Medical
reaction (PCR) on
specimens to
jirovecii pneumonia?
nasopharyngeal swabs could be used as an alternative
to invasive specimens to diagnose Pneumocytis
pneumonia (PCP).
Methods: For each bronchoalveolar lavage (BAL)
sample that is found to be PCP PCR positive, our aim is
to check for alternative sputum, serum or
nasopharyngeal swabs sent to the microbiology
laboratory for the same patient within the same time
period (+/- 2 days) that were initially sent for alternate
tests. By also performing the same PCP PCR on these
non-invasive specimens and comparing this data with
that obtained from the corresponding BAL, we can work
out the sensitivity and specificity of PCP PCR in these
non-invasive specimens.
Primary outcome measure: To determine whether PCR
can be used on non-invasive samples for the diagnosis
of PCP pneumonia.
Microbiology, Public Health Wales)
[email protected]
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