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 / Lay Summary / Public Health Wales Investigator / Useful Links and Publications
1 / Characterisation of HPV viral integration in DNA obtained from residual cervical smears collected within Baseline HPV
2009 / 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.
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.
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. / Helen Beer (Senior Information Manager and Research Specialist, Screening Division)

2 / KESS Project: Developing an integrated whole genome amplification and next generation sequencing method to characterise Cryptosporidium clinical isolates / Cryptosporidium is a group of protozoan parasites which cause an intestinal disease called 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 is no licensed treatment for cryptosporidiosis. To 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 University. / Professor Rachel Chalmers (Consultant Clinical Scientist/Honorary Professor
Head, Cryptosporidium Reference Unit
Public Health Wales Microbiology)
3 / A survey to investigate the reasons why patients in the ‘standard’ and ‘non-urgent’
triage categories attend the
Emergency Department (ED) and to explore what other options they have considered. / 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 ‘non-urgent’ 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. / Dr Robert Atenstaedt (Consultant in Public Health Medicine, Public Health Wales) / Atenstaedt, R, Gregory, J, Price-Jones, 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 :pp.
4 / Development and assessment of a Nucleic Acid Amplification Test for the detection of Toxoplasma gondii in meat entering the human food chain / 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 mixed meat and ham. The results will provide a guideline for future detection of toxoplasma in meat. / Professor Edward Guy (Consultant Clinical Scientist - Head of Toxoplasma Reference Unit, Public Health Wales)
5 / Evaluation of the Bactec fx system in combination with various novel molecular methods for the detection and identification of Candida species causing Candidaemia / 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 disease and reduce unnecessary therapy and toxicity in other patients, resulting in cost saving for the NHS. / Paula Brookes (Operational Manager Bacteriology, Public Health Wales)

6 / What is the unrecognised UK prevalence of Coxiella Burnetti in patients prior to cardiac
Valve replacement surgery: A pilot study / 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.
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. / Dr Brendan Healy (Consultant in Microbiology and Infectious Diseases, Public Health Wales)
7 / Understanding healthcare utilisation of responders and non-responders
to the bowel screening programme in Wales
before and after invitation to screening in order to improve early detection either through screening or opportunistic
testing / In Wales, bowel screening is currently offered to men and women aged between 60 and 71 years old. Screening programmes require good uptake to be effective. In order to develop a strategy for increasing uptake we first need to find out how non-responders differ from responders. For bowel screening, which is a test undertaken at home, there may be opportunities to promote uptake through contact with categories of health professionals not usually associated with the bowel screening programme. Through understanding healthcare utilisation we hope to find potentially useful intervention points and conversely, and not waste time and resources pursuing strategies unlikely to be successful.
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. / Dr Rosemary Fox (Director of Screening Division, Public Health Wales)
/ http://medicine.cf.ac.uk/primary-care-public-health/research/healthy-ageing/completed-projects/understanding-healthcare-utilisation-responders-and-non-responde/
8 / A prospective study of faecal parasite infections among children in Cambodia / 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 the detection and characterisation of the Cryptosporidium parasite. The DNA will have already been extracted from stools at Liverpool University. / Professor Rachel Chalmers
(Consultant Clinical Scientist/Honorary Professor
Head, Cryptosporidium Reference Unit
Public Health Wales Microbiology)
9 / Sensitivity and specificity of dried blood spot testing for the diagnosis of blood born viral infection / 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. / Dr Rachel Jones
(Consultant Virologist, Wales Specialist Virology Centre, Public Health Wales)

10 / Identification of antibacterial 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. / Eugene Rees
(Technical Head of Bacteriology, Public Health Wales Microbiology Swansea)

11 / A prospective randomised, multicentre trial to assess the impact of laboratory based RAPId Diagnosis on Outcome in patients with Blood Stream Infections (RAPIDO) / Blood stream infections (BSI) are a major problem and about 8% of hospital inpatients have a BSI. Some will be admitted with a BSI and others will develop an infection during their hospital stay. Recent improvements in 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 groups.