Journal of Public Health | Vol. 37, No. 1, pp. 64 –69 | doi:10.1093/pubmed/fdu009 | Advance Access Publication 25 February 2014
Prison and community outbreak of severe respiratory infection due to adenovirus type 14p1 in Tayside, UK B.J. Parcell1, P.G. McIntyre1, D.L. Yirrell1, A. Fraser2, M. Quinn3, K. Templeton4, S. Christie5, F. Romanes6 1
Department of Medical Microbiology, Ninewells Hospital and Medical School, NHS Tayside, Dundee DD1 9SY, UK NHS Health Scotland, Lothian EH10 4SG, UK 3 Department of Public Health, Cameron House, NHS Fife, Leven KY8 5RG, UK 4 Edinburgh Specialist Virology Centre, Royal Infirmary Edinburgh, Edinburgh, EH16 4SA, UK 5 Intensive Care, Ninewells Hospital and Medical School, NHS Tayside, Dundee DD1 9SY, UK 6 Directorate of Public Health, Kings Cross, Clepington Road, Dundee, DD3 8EA, UK Address correspondence to Benjamin John Parcell, E-mail: [email protected] 2
Background This report describes the investigation and public health management of a community-based outbreak of severe adenovirus serotype 14p1 respiratory infection affecting the Tayside area during 2011. It is the first report of an adenovirus outbreak involving prisons. Methods An outbreak-based/incident management approach was carried out. Alerts were sent out to local doctors, general practitioners, prison healthcare staff and consultants so that cases could be identified prospectively. Sequencing of hexon, fibre and E1A regions of adenovirus were carried out to genotype the viruses. Results Fifteen cases were identified in total, including 13 confirmed cases and 2 possible cases. There were 3 deaths amongst the 13 confirmed cases, with a case fatality rate of 23%. Eight of the cases had a direct association with one of the two prisons in the area. Conclusions We advise that surveillance measures for adenovirus infection and guidelines for the management of critically ill patients should be developed in order to identify outbreaks at an early stage and allow patients to receive appropriate treatment. Adenovirus infection should be borne in mind as a cause of severe pneumonia in closed settings such as prisons. Keywords adenovirus, outbreak, pneumonia, prison, sequencing
Introduction Human adenoviruses are DNA viruses that cause a wide spectrum of infections. Fatal infection can occur in neonates, immunocompromised individuals, and healthy children and adults. Most infections are, however, self-limiting.1 Adenovirus is categorized into 7 species (A–G) and 52 immunologically distinct serotypes.2 Species B comprises subspecies B1 and B2. Human adenovirus serotype 14 (also known as ‘agent de Wit’) is a subspecies B2 member and was first identified in 1955 in the Netherlands in a military training camp. During the same year it was responsible for respiratory outbreaks in schools in Great Britain.2 A novel genome variant (termed human adenovirus 14p1, formerly known as ‘14a’) was first identified in the USA and reported in 2008.3 Human adenovirus 14p1 is distinct from the strain reported in the 1950s
64
and it is believed that it arose from recombination with adenovirus 11.2 There are important public health implications as this strain has increased virulence causing outbreaks of acute respiratory disease (ARD) across the USA, on Prince of Wales Island off the coast of Alaska and more recently in Ireland.2 – 4
B.J. Parcell, Specialty Registrar in Medical Microbiology P.G. McIntyre, Consultant Virologist D.L. Yirrell, Consultant Clinical Scientist in Virology A. Fraser, Director of Public Health Science M. Quinn, Health Protection Nurse Specialist K. Templeton, Consultant Clinical Scientist in Microbiology S. Christie, Consultant Anaesthetist F. Romanes, Consultant in Public Health Medicine (Health Protection)
# The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: [email protected].
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
A B S T R AC T
PR I S O N A N D CO M M U N I T Y O U T B R E A K O F S E V E R E RE S P I RATO RY I N F E C T I O N
Methods Outbreak investigation
An outbreak-based/incident management approach lead by Public Health physicians was used to identify cases. Case definitions were agreed as described in Table 1. Health Protection Scotland sent alerts to local doctors, general practitioners, prison healthcare staff and prisoners of the two prisons affected in Tayside in order to increase their awareness of patients with severe respiratory infection so that cases could be identified prospectively. Prison governors alerted all prisons in Scotland, requesting that all cases should be notified to Public Health. All symptomatic patients were assessed, investigated and considered for urgent specialist referral. Prison healthcare staff undertook reviews of prisoner records from 1 January 2011 looking for prisoners presenting with chest infections, pyrexia, signs of pneumonia on chest radiograph or antibiotic use, with no other diagnosis. This search identified one further prisoner for inclusion in NHS Tayside Public Health investigation. Prison staff sickness days were reviewed from the same date. This included staff who had absences of 7 days or more with respiratory symptoms. One staff member was identified following this.
Table 1 Case definitions used in investigation Possible case
Onset since 1 January 2011 Clinical syndrome consistent with adenovirus infection severe enough to cause admission to hospital or death An association with an identified ‘high-risk setting’ in Tayside
Probable case
Onset since 1 January 2011 Clinical syndrome consistent with adenovirus infection severe enough to cause admission to hospital or death Positive for adenovirus on laboratory testing Had an association with Tayside in the 2 weeks prior to onset of symptoms
Confirmed
Onset since 1 January 2011
case
Clinical syndrome consistent with adenovirus infection severe enough to cause admission to hospital or death Positive for adenovirus 14p1 on laboratory testing Had an association with Tayside in the 2 weeks prior to onset of symptoms
Clinical syndrome consistent with adenovirus infection was defined as a patient with at least one of the following: pharyngitis, bronchitis, pneumonia, diarrhoea, conjunctivitis, cystitis, rash, fever. High-risk setting was defined as a prison setting in Tayside only.
Virological investigation
A range of clinical specimens including throat swabs, endotracheal aspirates, broncheoalveolar lavages and venous blood were processed. To investigate the cases real-time polymerase chain reaction (PCR) specific for adenovirus 14p1 as described by Lewis et al. 8 was carried out on all those positive for adenovirus on screening PCR. In this outbreak sequencing of partial hexon, fibre and E1A regions of adenovirus were undertaken to genotype the viruses using the 3130xl Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) at the Edinburgh reference laboratory. The E1A and fibre were amplifying the region as described by Kajon et al. 2 and the partial hexon was as described by Casas et al. 9 Overall, we followed the approach taken by Carr et al. 4 In addition to processing samples the Virology Department conducted a case-finding approach through review of all known adenovirus isolates in an attempt to identify any further cases of adenovirus pneumonia in Tayside that may have been missed. Laboratory requests for each of these samples were searched for the term ‘pneumonia’ in the clinical details section on laboratory request forms from 1 January 2008 to 22 June 2011 as the outbreak had no clear starting point and 2008 was the first calendar year in which the virology department exclusively used PCR for respiratory pathogen screening. To gain a greater understanding of the epidemiology of adenovirus in Tayside, which often causes eye infections, and whether there
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
It has affected closed community settings such as military recruitment training bases, coast guard training centres and residential-care facilities.5 – 7 This is the first report of such an outbreak involving a prison setting. This report describes an adenovirus 14p1 infection outbreak in Tayside, an area on the East coast of Scotland with a population of 400 000. There were 15 cases in total including 13 confirmed cases and 2 possible cases. Overall eight cases had contact with one of two prisons in the area. Of these there was one staff member and seven prisoners. Of the two prisons affected, one was a large closed institution drawing remand, short- and long-term prisoners principally from the surrounding area; the other, was an open prison taking offenders from prisons across the country. Both are male-only prisons with female and male staff. Public Health was first notified on 20 June 2011 by the local virology department following the deaths of three patients with severe pneumonia who were found to have adenovirus 14p1 on respiratory specimens. Following notification, the outbreak was identified as a ‘health risk state’ under the Public Health (Scotland) Act 2008, and after a brief initial investigation an Incident Management Team (IMT) meeting was convened on 5 July 2011 to plan further management of the emerging outbreak. The pattern suggested an outbreak focused in prison with links to the wider community. An additional cohort of cases in the community were identified during the outbreak for which no links with prisons could be identified.
65
66
J O U RN A L O F P U B L IC H E A LT H
Results Cases detected through case finding
There were 15 cases in total, consisting of 13 confirmed cases and 2 possible cases. The epidemic curve at the closure of the outbreak is displayed in Fig. 1. This demonstrates a spread of cases over a prolonged period, from the first week of 2011 until the last two cases (confirmed cases in individuals with an association with the Tayside prison environment) in the week of the 25 July 2011. Of the 13 confirmed cases, all were of white Scottish origin, 10 were male and 3 were female. In our study all cases were adults with ages ranging from 23 to 70 years. For the seven cases likely to have been acquired in the non-prison community (i.e. with no prison exposure), there was a spread from Tayside and one case was from neighbouring Fife. We found after investigation that there were no links with prisons in the community cases. Of the 13 confirmed cases there were 6 cases with probable prison-acquired infection (visitors, staff or prisoner physically attending the Tayside prison estate in the 10 days prior to onset of symptoms). Prison residence was a risk factor in the confirmed cases (P , 0.001). Incarceration length before development of symptoms for prisoners ranged from 20 to 91 days. Reviews of known case movements by prison medical staff demonstrated no firm link, known contact or definable pattern of crossovers between cases within the prison environment even when looking at cell locations, work groups assigned, court attendances and recreational activities. We found that there was a weak association with residence in Perth (P ¼ 0.06) but this was most likely due to the prison being located there. We found that the majority of patients were either current- or
Virological results
We processed a range of samples and carried out PCR specific for adenovirus 14p1. The first seven cases whose isolates were sent to Edinburgh for serotyping had sequencing of the hexon, fibre and E1A regions performed, which indicated a human adenovirus 14p1 (Type 14, prototype 1) strain, which is a genetically changed version of the original 1955 serotype 14 strain that caused outbreaks in military recruits in the USA. The Virology Department identified four further cases by retrospectively reviewing all adenovirus isolates since 1 January 2008 in Tayside with clinical details of ‘pneumonia’ on laboratory request forms. This search also demonstrated that the
Epidemic curve at 24/8/2011 Number
22/08/2011
15/08/2011
08/08/2011
01/08/2011
18/07/2011
11/07/2011
04/07/2011
27/06/2011
20/06/2011
13/06/2011
06/06/2011
30/05/2011
23/05/2011
16/05/2011
09/05/2011
25/07/2011
P P
P P 02/05/2011
25/04/2011
18/04/2011
P P 11/04/2011
04/04/2011
28/03/2011
21/03/2011
14/03/2011
07/03/2011
P 28/02/2011
21/02/2011
14/02/2011
D 07/02/2011
24/01/2011
17/01/2011
10/01/2011
03/01/2011
27/12/2010
D = P = = =
31/01/2011
PD
D
Date of onset
Died Prison exposure, physically attended Tayside prison estate in 10 days prior to onset of symptoms (visitor, staff or prisoner) Possible case Confirmed case
Fig. 1 Epidemic curve at the closure of the outbreak .
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
ex-smokers. This was a major factor in severe disease in the outbreak described by Esposito et al. 10 The clinical findings of confirmed cases are listed in Table 2. The majority of confirmed cases presented with community acquired pneumonia and 62% also had a gastroenteritis syndrome. Lymphopenia was a common finding amongst confirmed cases. Cidofovir was used in four of the confirmed cases. Three patients died, giving a case fatality rate of 23% amongst confirmed cases in this outbreak (Table 2). We found injecting drug use to be more common in our confirmed cases which was higher than the prevalence of problem drug use in Tayside (P , 0.001). There was, however, no significant difference in the proportion of confirmed adenovirus cases with prison contact who were intravenous drug users compared with recent data of the Scottish prison population who injected drugs (P ¼ 0.34).11 There was no evidence to support the transmission of adenovirus via shared injecting equipment. The majority of cases had preexisting medical conditions that may have predisposed to severe disease and other risk factors for adenovirus 14 disease. Table 3 provides a summary of risk factors amongst the 13 confirmed cases, stratified by prison exposure status.
had been any changes in the background prevalence of this virus we reviewed previous eye sample laboratory records that had been adenovirus positive by PCR.
PR I S O N A N D CO M M U N I T Y O U T B R E A K O F S E V E R E RE S P I RATO RY I N F E C T I O N
Table 2 Summary of clinical findings of confirmed cases
67
Table 3 Profile of established risk factors for adenovirus 14 disease amongst confirmed cases
Clinical profile, confirmed cases Risk factors, confirmed cases
Diagnosis Community acquired pneumonia Exacerbation of COPD
12 (92%)
Risk factor
1(8%)
Prison
No prison
exposure (n)
exposure (n)
Total
Additional diagnoses Gastroenteritis
8 (62%)
6
7
13 (100%)
Conjunctivitis
1 (8%)
0– 1 risk factors
1
2
3 (23%)
Meningoencephalitis
1 (8%)
2– 3 risk factors
3
2
5 (38%)
4 risk factors
2
3
5 (38%)
Co-infection with other pathogens Amongst survivors
4 (40%)
Amongst fatal cases
3 (100%)
Disseminated type 14 disease
List of risk factors Smoker, current
4
3
7 (54%)
Smoker, ex-smoker
1
2
3 (23%)
10
Injecting drug use
3
1
4 (31%)
Adenovirus serotype 14
6
Chronic pulmonary
5
1
6 (46%)
Adenovirus serotype 14p1
7
3 (23%)
Outcome Survived Died
disease Chronic heart disease
1
2
10 (77%)
Chronic renal disease
0
1
1 (8%)
3 (23%)
Immunosuppression
1
1
2 (15%)
Bone marrow
0
0
0 (0%)
0
0
0 (0%)
3
1
4 (31%)
Lymphopenia Amongst survivors
9 (90%)
Amongst fatal cases
1 (33%)
Treatment
transplantation Solid organ transplantation
Cidofovir used in survivors
2 (20%)
Cidofovir used in fatal cases
2 (66%)
Highest level of care
Chronic neurological disease Diabetes
1
2
3 (23%)
ICU
5
Cancer
0
0
0 (0%)
HDU
1
Pregnancy
0
0
0 (0%)
Ward
7
BMI .30
1
3
4 (31%)
BMI ,18
1
1
2 (15%)
Mean ICU or HDU days
49 (10 –115)
‘Prison exposure’ was defined as physically attended in any capacity the
proportion of adenovirus infections presenting as pneumonia in 2011 had increased, from 0.0% in 2008 to 5.4% in 2011 (P ¼ 0.005). By looking at previous laboratory records of eye sample results that had been adenovirus positive on PCR in Tayside, we identified after typing that adenovirus 14p1 had become more common in the Tayside area. In 2008 there were no eye samples positive for adenovirus 14p1. However, in 2011 we found the proportion of adenovirus 14p1 in eye samples was 41.4% (12 samples). This increase of adenovirus 14p1 was not seen in samples from neighbouring regions of Edinburgh and Lothian.
Discussion Main finding of this study
From 12 January to 30 July 2011, there were 15 cases identified in total, including 13 confirmed cases and 2 possible
Tayside prison estate in the 10 days prior to onset of symptoms (visitor, staff or prisoner).
cases. There were 3 deaths amongst the 13 confirmed cases, a case fatality rate of 23%. Overall, eight cases had a direct association with one or both of the prisons in the area. Throughout 2011, adenovirus 14p1 was more common in Tayside compared with neighbouring regions and the number of infections presenting as pneumonia also increased. What is already known on this topic
Of the 13 confirmed cases, 10 were male and three were female. As there were only male prisoners the ratio is not particularly surprising. In contrast to our study in which all cases were adults, the majority of patients in the Irish outbreak were neonates or infants (5 out of 9 cases).6 In our outbreak there were 3 deaths amongst the 13 confirmed cases, a case fatality rate of 23%. Two patients who died had chronic pulmonary
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
Virology
Total in category
68
J O U RN A L O F P U B L IC H E A LT H
What this study adds
This is the first reported outbreak of adenovirus involving prisons. Prisoners have higher rates of infection principally with blood-borne viruses and higher rates of injecting drug use.14 However, outbreaks of blood-borne viruses are extremely uncommon and the last major outbreak reported occurred in 1993 in Glenochil Prison, Scotland.15 The commonest infections associated with outbreaks in prisons are due to respiratory diseases. Recent data show that single cases of tuberculosis have increased but outbreaks have remained the same. Seasonal influenza outbreaks have decreased.14 Legionella outbreaks are also extremely rare and in the past 10 years the Scottish Prison Service (SPS) has been markedly free from such incidents.16 In this outbreak eight of the cases had a direct association with one or both prisons in Tayside and prison residence was a risk factor for infection in the confirmed cases (P , 0.001). No definitive view was possible on the exact transmission pathways for each case but it was agreed that in view of the excess of cases identified in prisoners and staff within the SPS estate when compared with cases
identified in the general population, there was likely to have been transmission in the prison setting. As the main modes of transmission are by droplets or by autoinoculation with hands we advised staff and prisoners to follow good hand hygiene. Infection prevention and control measures were similar to other outbreaks with advice given on standard, contact and droplet precautions in general. Alcohol gels were not used. Respiratory precautions were employed for case handling by staff at prisons. Adenovirus can persist on environmental surfaces for weeks and so environmental decontamination with attention to cleaning fomites was also undertaken.5,17 Transmission by blood borne route is unlikely, given reported low incidence of infection by hepatitis C in the Scottish prison population.11 In hospital, patients were placed in single rooms to prevent person-to-person transmission.17 These infection control approaches were effective at preventing further transmission in NHS Tayside and the prison healthcare settings. This advice was based on international and national guidance on preventing respiratory tract infections in the healthcare setting and also Health Protection Agency (HPA) advice for infection control in prisons.17,18 The IMT decided that staff and prisoner screening for adenovirus carriage/infection and reintroduction of adenovirus serotype 4 and 7 vaccination to closed settings should not be adopted. The latter was not deemed practical, as there is no longer a licensed vaccine against adenovirus.2 Case finding was via SPS staff awareness, GPs, frontline clinicians and hospital clinicians on admitting wards by writing to them and advising them of the case definition and raising awareness. Adenoviruses are not routinely typed when detected in UK laboratories unless there is an outbreak or research is being carried out. There is also no system of routine surveillance of adenoviruses in Scotland. There has been surveillance of military recruits with ARD since 1996 in America. Following the outbreak in Ireland a surveillance system for HAdV-14p1 was set up.6 We feel that if an enhanced surveillance system for human adenovirus 14 infection had been in place the rise of a new serotype and the potential for more severe illness would have been identified at an earlier stage. This may have allowed infection control precautions to be put in place and earlier treatment to be instigated, with possible improvement in survival. Limitations of this study
Collection of data relied on accurate completion of records by medical and prison staff. As part of our case definitions we specified the ‘high-risk setting’ to be a prison setting in Tayside and we did not name further high-risk settings. The laboratory case-finding strategy only searched for Tayside cases of adenovirus with ‘pneumonia’ since 1 January 2008. One case presented with exacerbation of chronic obstructive
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
disease and one had diabetes. All three had co-infection with other pathogens, including respiratory syncytial virus, cytomegalovirus (CMV) and hepatitis C virus infection. The reported Irish cases had a case fatality rate of 33%.6 The outbreaks affecting 140 patients across Oregon, Washington and Texas during had a mortality rate of 5%.4 There is no specific treatment for adenovirus infections and management is mainly supportive.6,12 There is evidence to support the use of cidofovir infusions for the treatment of adenovirus in oncology and bone marrow transplantation patients through cases series with historical controls, but there is no data from randomized control trials.12,13 It has been suggested that success rates are highest when cidofovir is given soon after diagnosis of infection.12 Unfortunately, at the start of the outbreak it was not clear whether adenovirus was the cause of pneumonia in the first three patients or if it was a co-occurring finding with another pathogen. Identifying patients at highest risk for adenoviral-related mortality and those who would benefit from treatment was difficult as many of our patients had concurrent renal dysfunction. Cidofovir has been associated with serious side effects such as nephrotoxicity, neutropaenia and breakthrough CMV.12 Methods to reduce renal toxicity with cidofovir were used such as reducing the frequency, dose and administering intravenous fluid. In this outbreak four confirmed cases were treated with cidofovir, and it was also used in two possible cases. Our experience was disappointing with three deaths in the six patients treated. Our experience is that viraemia usually clears many days before the respiratory secretions become PCR negative.
PR I S O N A N D CO M M U N I T Y O U T B R E A K O F S E V E R E RE S P I RATO RY I N F E C T I O N
Conclusion Low levels of immunity to adenovirus 14p1 make the general population susceptible to high attack rates of this infection especially amongst closed communities.3,4 This was the first outbreak of adenovirus affecting the community and prison venues. This strain of adenovirus has led to pneumonia and death in young adults, some with no pre-existing conditions.2 We have observed an increase in adenovirus pneumonia cases following the emergence of this pathogen. We recommend that early diagnosis with access to rapid PCR assay and routine typing is vital for detecting the emergence of this virus and it should be considered as a pathogen in the severely ill presenting with pneumonia. Surveillance of infectious diseases affecting the prison population is carried out by the Prison Infection Prevention team based within the HPA. The potential benefits and cost-effectiveness of an enhanced surveillance system for human adenovirus serotype 14 infection for the general population or patients at risk, or surveillance of virology samples, should be explored at a national level. We followed and adhered to advice from the Centres for Disease Control and Prevention (CDC) and HPA regarding the infection control practices in hospitals and prisons and this most likely reduced transmission. There is no specific curative treatment for this infection and cidofovir showed no clear effectiveness in the treatment. Further research on the use of antivirals and guidelines for the management of critically ill patients with adenoviral infections needs to be carried out and developed.
Acknowledgements We thank Ms Arlene Reynolds for work around case reviews and national epidemiology.
References 1 Rhee EG, Barouch DH. Adenoviruses. In: Mandell GL, Bennett JE, Dolin R (eds). Principles and Practice of Infectious Diseases (7th Edition). Philadelphia: Churchill Livingstone, 2010,2027 – 33. 2 Kajon AE, Lu X, Erdman DD et al. Molecular epidemiology and brief history of emerging adenovirus 14-associated respiratory disease in the United States. J Infect Dis 2010;202(1):93– 103. 3 Louie JK, Kajon AE, Holodniy M et al. Severe pneumonia due to adenovirus serotype 14: a new respiratory threat? Clin Infect Dis 2008;46(3):421– 5. 4 Carr MJ, Kajon AE, Lu X et al. Deaths associated with human adenovirus-14p1 infections, Europe, 2009 – 2010. Emerg Infect Dis 2011;17(8):1402– 8. 5 Centers for Disease Control and Prevention. Acute respiratory disease associated with adenovirus serotype 14- four states, 2006 – 2007. Morb Mortal Wkly Rep 2007;56(45):1181 – 4. 6 O’Flanagan D, O’Donnell J, Domegan L et al. First reported cases of human adenovirus serotype 14p1 infection, Ireland, October 2009 to July 2010. Euro Surveill 2011;16(8):1 – 5. 7 Carr MJ, De Gascun CF, Hall WW. Clinical and epidemiological aspects of the emerging adenovirus 14p1, Part I. Clin Microbiol Newsl 2011;33(19):145– 50. 8 Lewis PF, Schmidt MA, Lu X et al. A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14. J Infect Dis 2009;199(10):1427– 34. 9 Casas I, Avellon A, Mosquera M et al. Molecular identification of adenoviruses in clinical samples by analyzing a partial hexon genomic region. J Clin Microbiol 2005;43(12):6176– 82. 10 Esposito DH, Gardner TJ, Schneider E et al. Outbreak of pneumonia associated with emergent human adenovirus serotype 14-Southeast Alaska, 2008. J Infect Dis 2010;202(2):214 –22. 11 Taylor A, Munro A, Allen E et al. Low incidence of hepatitis C virus among prisoners in Scotland. Addiction 2013;108(7):1296– 304. 12 Carr MJ, De Gascun CF, Hall WW. Clinical and epidemiological aspects of the emerging adenovirus 14p1, Part II. Clin Microbiol Newsletter 2011;33(20):153– 8. 13 Williams KM, Agwu AL, Dabb AA et al. A clinical algorithm identifies high risk pediatric oncology and bone marrow transplant patients likely to benefit from treatment of adenoviral infection. J Pediatr Hematol Oncol 2009;31(11):825– 31. 14 Department of Health. Health Protection in Prisons: 2010 – 2011 Report. London: Department of Health, 2012. 15 Gore SM, Bird AG, Burns SM et al. Drug injection and HIV prevalence in inmates of Glenochil prison. BMJ 1995;310(6975):293– 6. 16 Personal communication with Dr Andrew Fraser, formerly Director of Health and Care, Scottish Prison Service, 2013. 17 Guidelines for Preventing Health-care-Associated Pneumonia. 2003 recommendations of the CDC and the Healthcare Infection Control Practices Advisory Committee. Respir Care 2004;49(8):926– 39. 18 Health Protection Agency and Department of Health—Offender Health. Prevention of Infection and Communicable Disease Control in Prisons and Places of Detention. A Manual for Healthcare Workers and Other Staff. London: Department of Health, 2011.
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
pulmonary disease (COPD) and so we may have missed other presentations of adenovirus. The first seven case isolates were serotyped with sequencing of the hexon, fibre and E1A regions indicating human adenovirus 14p1. Subsequent isolates positive for adenovirus by PCR were not fully characterized and an assumption was made that these would be the 14p1 strain as we had not found any other HAd14 in circulation that was not the HAd14p1 strain. Prisoners were not queried as to whether they knew known cases due to confidentiality concerns. A number of cases of adenovirus were co-infected with other pathogens. These results were reviewed by microbiology and virology medical staff and it was felt that adenovirus was the most likely primary cause of clinically significant infection.
69
Prison and community outbreak of severe respiratory infection due to adenovirus type 14p1 in Tayside, UK B.J. Parcell1, P.G. McIntyre1, D.L. Yirrell1, A. Fraser2, M. Quinn3, K. Templeton4, S. Christie5, F. Romanes6 1
Department of Medical Microbiology, Ninewells Hospital and Medical School, NHS Tayside, Dundee DD1 9SY, UK NHS Health Scotland, Lothian EH10 4SG, UK 3 Department of Public Health, Cameron House, NHS Fife, Leven KY8 5RG, UK 4 Edinburgh Specialist Virology Centre, Royal Infirmary Edinburgh, Edinburgh, EH16 4SA, UK 5 Intensive Care, Ninewells Hospital and Medical School, NHS Tayside, Dundee DD1 9SY, UK 6 Directorate of Public Health, Kings Cross, Clepington Road, Dundee, DD3 8EA, UK Address correspondence to Benjamin John Parcell, E-mail: [email protected] 2
Background This report describes the investigation and public health management of a community-based outbreak of severe adenovirus serotype 14p1 respiratory infection affecting the Tayside area during 2011. It is the first report of an adenovirus outbreak involving prisons. Methods An outbreak-based/incident management approach was carried out. Alerts were sent out to local doctors, general practitioners, prison healthcare staff and consultants so that cases could be identified prospectively. Sequencing of hexon, fibre and E1A regions of adenovirus were carried out to genotype the viruses. Results Fifteen cases were identified in total, including 13 confirmed cases and 2 possible cases. There were 3 deaths amongst the 13 confirmed cases, with a case fatality rate of 23%. Eight of the cases had a direct association with one of the two prisons in the area. Conclusions We advise that surveillance measures for adenovirus infection and guidelines for the management of critically ill patients should be developed in order to identify outbreaks at an early stage and allow patients to receive appropriate treatment. Adenovirus infection should be borne in mind as a cause of severe pneumonia in closed settings such as prisons. Keywords adenovirus, outbreak, pneumonia, prison, sequencing
Introduction Human adenoviruses are DNA viruses that cause a wide spectrum of infections. Fatal infection can occur in neonates, immunocompromised individuals, and healthy children and adults. Most infections are, however, self-limiting.1 Adenovirus is categorized into 7 species (A–G) and 52 immunologically distinct serotypes.2 Species B comprises subspecies B1 and B2. Human adenovirus serotype 14 (also known as ‘agent de Wit’) is a subspecies B2 member and was first identified in 1955 in the Netherlands in a military training camp. During the same year it was responsible for respiratory outbreaks in schools in Great Britain.2 A novel genome variant (termed human adenovirus 14p1, formerly known as ‘14a’) was first identified in the USA and reported in 2008.3 Human adenovirus 14p1 is distinct from the strain reported in the 1950s
64
and it is believed that it arose from recombination with adenovirus 11.2 There are important public health implications as this strain has increased virulence causing outbreaks of acute respiratory disease (ARD) across the USA, on Prince of Wales Island off the coast of Alaska and more recently in Ireland.2 – 4
B.J. Parcell, Specialty Registrar in Medical Microbiology P.G. McIntyre, Consultant Virologist D.L. Yirrell, Consultant Clinical Scientist in Virology A. Fraser, Director of Public Health Science M. Quinn, Health Protection Nurse Specialist K. Templeton, Consultant Clinical Scientist in Microbiology S. Christie, Consultant Anaesthetist F. Romanes, Consultant in Public Health Medicine (Health Protection)
# The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: [email protected].
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
A B S T R AC T
PR I S O N A N D CO M M U N I T Y O U T B R E A K O F S E V E R E RE S P I RATO RY I N F E C T I O N
Methods Outbreak investigation
An outbreak-based/incident management approach lead by Public Health physicians was used to identify cases. Case definitions were agreed as described in Table 1. Health Protection Scotland sent alerts to local doctors, general practitioners, prison healthcare staff and prisoners of the two prisons affected in Tayside in order to increase their awareness of patients with severe respiratory infection so that cases could be identified prospectively. Prison governors alerted all prisons in Scotland, requesting that all cases should be notified to Public Health. All symptomatic patients were assessed, investigated and considered for urgent specialist referral. Prison healthcare staff undertook reviews of prisoner records from 1 January 2011 looking for prisoners presenting with chest infections, pyrexia, signs of pneumonia on chest radiograph or antibiotic use, with no other diagnosis. This search identified one further prisoner for inclusion in NHS Tayside Public Health investigation. Prison staff sickness days were reviewed from the same date. This included staff who had absences of 7 days or more with respiratory symptoms. One staff member was identified following this.
Table 1 Case definitions used in investigation Possible case
Onset since 1 January 2011 Clinical syndrome consistent with adenovirus infection severe enough to cause admission to hospital or death An association with an identified ‘high-risk setting’ in Tayside
Probable case
Onset since 1 January 2011 Clinical syndrome consistent with adenovirus infection severe enough to cause admission to hospital or death Positive for adenovirus on laboratory testing Had an association with Tayside in the 2 weeks prior to onset of symptoms
Confirmed
Onset since 1 January 2011
case
Clinical syndrome consistent with adenovirus infection severe enough to cause admission to hospital or death Positive for adenovirus 14p1 on laboratory testing Had an association with Tayside in the 2 weeks prior to onset of symptoms
Clinical syndrome consistent with adenovirus infection was defined as a patient with at least one of the following: pharyngitis, bronchitis, pneumonia, diarrhoea, conjunctivitis, cystitis, rash, fever. High-risk setting was defined as a prison setting in Tayside only.
Virological investigation
A range of clinical specimens including throat swabs, endotracheal aspirates, broncheoalveolar lavages and venous blood were processed. To investigate the cases real-time polymerase chain reaction (PCR) specific for adenovirus 14p1 as described by Lewis et al. 8 was carried out on all those positive for adenovirus on screening PCR. In this outbreak sequencing of partial hexon, fibre and E1A regions of adenovirus were undertaken to genotype the viruses using the 3130xl Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) at the Edinburgh reference laboratory. The E1A and fibre were amplifying the region as described by Kajon et al. 2 and the partial hexon was as described by Casas et al. 9 Overall, we followed the approach taken by Carr et al. 4 In addition to processing samples the Virology Department conducted a case-finding approach through review of all known adenovirus isolates in an attempt to identify any further cases of adenovirus pneumonia in Tayside that may have been missed. Laboratory requests for each of these samples were searched for the term ‘pneumonia’ in the clinical details section on laboratory request forms from 1 January 2008 to 22 June 2011 as the outbreak had no clear starting point and 2008 was the first calendar year in which the virology department exclusively used PCR for respiratory pathogen screening. To gain a greater understanding of the epidemiology of adenovirus in Tayside, which often causes eye infections, and whether there
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
It has affected closed community settings such as military recruitment training bases, coast guard training centres and residential-care facilities.5 – 7 This is the first report of such an outbreak involving a prison setting. This report describes an adenovirus 14p1 infection outbreak in Tayside, an area on the East coast of Scotland with a population of 400 000. There were 15 cases in total including 13 confirmed cases and 2 possible cases. Overall eight cases had contact with one of two prisons in the area. Of these there was one staff member and seven prisoners. Of the two prisons affected, one was a large closed institution drawing remand, short- and long-term prisoners principally from the surrounding area; the other, was an open prison taking offenders from prisons across the country. Both are male-only prisons with female and male staff. Public Health was first notified on 20 June 2011 by the local virology department following the deaths of three patients with severe pneumonia who were found to have adenovirus 14p1 on respiratory specimens. Following notification, the outbreak was identified as a ‘health risk state’ under the Public Health (Scotland) Act 2008, and after a brief initial investigation an Incident Management Team (IMT) meeting was convened on 5 July 2011 to plan further management of the emerging outbreak. The pattern suggested an outbreak focused in prison with links to the wider community. An additional cohort of cases in the community were identified during the outbreak for which no links with prisons could be identified.
65
66
J O U RN A L O F P U B L IC H E A LT H
Results Cases detected through case finding
There were 15 cases in total, consisting of 13 confirmed cases and 2 possible cases. The epidemic curve at the closure of the outbreak is displayed in Fig. 1. This demonstrates a spread of cases over a prolonged period, from the first week of 2011 until the last two cases (confirmed cases in individuals with an association with the Tayside prison environment) in the week of the 25 July 2011. Of the 13 confirmed cases, all were of white Scottish origin, 10 were male and 3 were female. In our study all cases were adults with ages ranging from 23 to 70 years. For the seven cases likely to have been acquired in the non-prison community (i.e. with no prison exposure), there was a spread from Tayside and one case was from neighbouring Fife. We found after investigation that there were no links with prisons in the community cases. Of the 13 confirmed cases there were 6 cases with probable prison-acquired infection (visitors, staff or prisoner physically attending the Tayside prison estate in the 10 days prior to onset of symptoms). Prison residence was a risk factor in the confirmed cases (P , 0.001). Incarceration length before development of symptoms for prisoners ranged from 20 to 91 days. Reviews of known case movements by prison medical staff demonstrated no firm link, known contact or definable pattern of crossovers between cases within the prison environment even when looking at cell locations, work groups assigned, court attendances and recreational activities. We found that there was a weak association with residence in Perth (P ¼ 0.06) but this was most likely due to the prison being located there. We found that the majority of patients were either current- or
Virological results
We processed a range of samples and carried out PCR specific for adenovirus 14p1. The first seven cases whose isolates were sent to Edinburgh for serotyping had sequencing of the hexon, fibre and E1A regions performed, which indicated a human adenovirus 14p1 (Type 14, prototype 1) strain, which is a genetically changed version of the original 1955 serotype 14 strain that caused outbreaks in military recruits in the USA. The Virology Department identified four further cases by retrospectively reviewing all adenovirus isolates since 1 January 2008 in Tayside with clinical details of ‘pneumonia’ on laboratory request forms. This search also demonstrated that the
Epidemic curve at 24/8/2011 Number
22/08/2011
15/08/2011
08/08/2011
01/08/2011
18/07/2011
11/07/2011
04/07/2011
27/06/2011
20/06/2011
13/06/2011
06/06/2011
30/05/2011
23/05/2011
16/05/2011
09/05/2011
25/07/2011
P P
P P 02/05/2011
25/04/2011
18/04/2011
P P 11/04/2011
04/04/2011
28/03/2011
21/03/2011
14/03/2011
07/03/2011
P 28/02/2011
21/02/2011
14/02/2011
D 07/02/2011
24/01/2011
17/01/2011
10/01/2011
03/01/2011
27/12/2010
D = P = = =
31/01/2011
PD
D
Date of onset
Died Prison exposure, physically attended Tayside prison estate in 10 days prior to onset of symptoms (visitor, staff or prisoner) Possible case Confirmed case
Fig. 1 Epidemic curve at the closure of the outbreak .
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
ex-smokers. This was a major factor in severe disease in the outbreak described by Esposito et al. 10 The clinical findings of confirmed cases are listed in Table 2. The majority of confirmed cases presented with community acquired pneumonia and 62% also had a gastroenteritis syndrome. Lymphopenia was a common finding amongst confirmed cases. Cidofovir was used in four of the confirmed cases. Three patients died, giving a case fatality rate of 23% amongst confirmed cases in this outbreak (Table 2). We found injecting drug use to be more common in our confirmed cases which was higher than the prevalence of problem drug use in Tayside (P , 0.001). There was, however, no significant difference in the proportion of confirmed adenovirus cases with prison contact who were intravenous drug users compared with recent data of the Scottish prison population who injected drugs (P ¼ 0.34).11 There was no evidence to support the transmission of adenovirus via shared injecting equipment. The majority of cases had preexisting medical conditions that may have predisposed to severe disease and other risk factors for adenovirus 14 disease. Table 3 provides a summary of risk factors amongst the 13 confirmed cases, stratified by prison exposure status.
had been any changes in the background prevalence of this virus we reviewed previous eye sample laboratory records that had been adenovirus positive by PCR.
PR I S O N A N D CO M M U N I T Y O U T B R E A K O F S E V E R E RE S P I RATO RY I N F E C T I O N
Table 2 Summary of clinical findings of confirmed cases
67
Table 3 Profile of established risk factors for adenovirus 14 disease amongst confirmed cases
Clinical profile, confirmed cases Risk factors, confirmed cases
Diagnosis Community acquired pneumonia Exacerbation of COPD
12 (92%)
Risk factor
1(8%)
Prison
No prison
exposure (n)
exposure (n)
Total
Additional diagnoses Gastroenteritis
8 (62%)
6
7
13 (100%)
Conjunctivitis
1 (8%)
0– 1 risk factors
1
2
3 (23%)
Meningoencephalitis
1 (8%)
2– 3 risk factors
3
2
5 (38%)
4 risk factors
2
3
5 (38%)
Co-infection with other pathogens Amongst survivors
4 (40%)
Amongst fatal cases
3 (100%)
Disseminated type 14 disease
List of risk factors Smoker, current
4
3
7 (54%)
Smoker, ex-smoker
1
2
3 (23%)
10
Injecting drug use
3
1
4 (31%)
Adenovirus serotype 14
6
Chronic pulmonary
5
1
6 (46%)
Adenovirus serotype 14p1
7
3 (23%)
Outcome Survived Died
disease Chronic heart disease
1
2
10 (77%)
Chronic renal disease
0
1
1 (8%)
3 (23%)
Immunosuppression
1
1
2 (15%)
Bone marrow
0
0
0 (0%)
0
0
0 (0%)
3
1
4 (31%)
Lymphopenia Amongst survivors
9 (90%)
Amongst fatal cases
1 (33%)
Treatment
transplantation Solid organ transplantation
Cidofovir used in survivors
2 (20%)
Cidofovir used in fatal cases
2 (66%)
Highest level of care
Chronic neurological disease Diabetes
1
2
3 (23%)
ICU
5
Cancer
0
0
0 (0%)
HDU
1
Pregnancy
0
0
0 (0%)
Ward
7
BMI .30
1
3
4 (31%)
BMI ,18
1
1
2 (15%)
Mean ICU or HDU days
49 (10 –115)
‘Prison exposure’ was defined as physically attended in any capacity the
proportion of adenovirus infections presenting as pneumonia in 2011 had increased, from 0.0% in 2008 to 5.4% in 2011 (P ¼ 0.005). By looking at previous laboratory records of eye sample results that had been adenovirus positive on PCR in Tayside, we identified after typing that adenovirus 14p1 had become more common in the Tayside area. In 2008 there were no eye samples positive for adenovirus 14p1. However, in 2011 we found the proportion of adenovirus 14p1 in eye samples was 41.4% (12 samples). This increase of adenovirus 14p1 was not seen in samples from neighbouring regions of Edinburgh and Lothian.
Discussion Main finding of this study
From 12 January to 30 July 2011, there were 15 cases identified in total, including 13 confirmed cases and 2 possible
Tayside prison estate in the 10 days prior to onset of symptoms (visitor, staff or prisoner).
cases. There were 3 deaths amongst the 13 confirmed cases, a case fatality rate of 23%. Overall, eight cases had a direct association with one or both of the prisons in the area. Throughout 2011, adenovirus 14p1 was more common in Tayside compared with neighbouring regions and the number of infections presenting as pneumonia also increased. What is already known on this topic
Of the 13 confirmed cases, 10 were male and three were female. As there were only male prisoners the ratio is not particularly surprising. In contrast to our study in which all cases were adults, the majority of patients in the Irish outbreak were neonates or infants (5 out of 9 cases).6 In our outbreak there were 3 deaths amongst the 13 confirmed cases, a case fatality rate of 23%. Two patients who died had chronic pulmonary
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
Virology
Total in category
68
J O U RN A L O F P U B L IC H E A LT H
What this study adds
This is the first reported outbreak of adenovirus involving prisons. Prisoners have higher rates of infection principally with blood-borne viruses and higher rates of injecting drug use.14 However, outbreaks of blood-borne viruses are extremely uncommon and the last major outbreak reported occurred in 1993 in Glenochil Prison, Scotland.15 The commonest infections associated with outbreaks in prisons are due to respiratory diseases. Recent data show that single cases of tuberculosis have increased but outbreaks have remained the same. Seasonal influenza outbreaks have decreased.14 Legionella outbreaks are also extremely rare and in the past 10 years the Scottish Prison Service (SPS) has been markedly free from such incidents.16 In this outbreak eight of the cases had a direct association with one or both prisons in Tayside and prison residence was a risk factor for infection in the confirmed cases (P , 0.001). No definitive view was possible on the exact transmission pathways for each case but it was agreed that in view of the excess of cases identified in prisoners and staff within the SPS estate when compared with cases
identified in the general population, there was likely to have been transmission in the prison setting. As the main modes of transmission are by droplets or by autoinoculation with hands we advised staff and prisoners to follow good hand hygiene. Infection prevention and control measures were similar to other outbreaks with advice given on standard, contact and droplet precautions in general. Alcohol gels were not used. Respiratory precautions were employed for case handling by staff at prisons. Adenovirus can persist on environmental surfaces for weeks and so environmental decontamination with attention to cleaning fomites was also undertaken.5,17 Transmission by blood borne route is unlikely, given reported low incidence of infection by hepatitis C in the Scottish prison population.11 In hospital, patients were placed in single rooms to prevent person-to-person transmission.17 These infection control approaches were effective at preventing further transmission in NHS Tayside and the prison healthcare settings. This advice was based on international and national guidance on preventing respiratory tract infections in the healthcare setting and also Health Protection Agency (HPA) advice for infection control in prisons.17,18 The IMT decided that staff and prisoner screening for adenovirus carriage/infection and reintroduction of adenovirus serotype 4 and 7 vaccination to closed settings should not be adopted. The latter was not deemed practical, as there is no longer a licensed vaccine against adenovirus.2 Case finding was via SPS staff awareness, GPs, frontline clinicians and hospital clinicians on admitting wards by writing to them and advising them of the case definition and raising awareness. Adenoviruses are not routinely typed when detected in UK laboratories unless there is an outbreak or research is being carried out. There is also no system of routine surveillance of adenoviruses in Scotland. There has been surveillance of military recruits with ARD since 1996 in America. Following the outbreak in Ireland a surveillance system for HAdV-14p1 was set up.6 We feel that if an enhanced surveillance system for human adenovirus 14 infection had been in place the rise of a new serotype and the potential for more severe illness would have been identified at an earlier stage. This may have allowed infection control precautions to be put in place and earlier treatment to be instigated, with possible improvement in survival. Limitations of this study
Collection of data relied on accurate completion of records by medical and prison staff. As part of our case definitions we specified the ‘high-risk setting’ to be a prison setting in Tayside and we did not name further high-risk settings. The laboratory case-finding strategy only searched for Tayside cases of adenovirus with ‘pneumonia’ since 1 January 2008. One case presented with exacerbation of chronic obstructive
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
disease and one had diabetes. All three had co-infection with other pathogens, including respiratory syncytial virus, cytomegalovirus (CMV) and hepatitis C virus infection. The reported Irish cases had a case fatality rate of 33%.6 The outbreaks affecting 140 patients across Oregon, Washington and Texas during had a mortality rate of 5%.4 There is no specific treatment for adenovirus infections and management is mainly supportive.6,12 There is evidence to support the use of cidofovir infusions for the treatment of adenovirus in oncology and bone marrow transplantation patients through cases series with historical controls, but there is no data from randomized control trials.12,13 It has been suggested that success rates are highest when cidofovir is given soon after diagnosis of infection.12 Unfortunately, at the start of the outbreak it was not clear whether adenovirus was the cause of pneumonia in the first three patients or if it was a co-occurring finding with another pathogen. Identifying patients at highest risk for adenoviral-related mortality and those who would benefit from treatment was difficult as many of our patients had concurrent renal dysfunction. Cidofovir has been associated with serious side effects such as nephrotoxicity, neutropaenia and breakthrough CMV.12 Methods to reduce renal toxicity with cidofovir were used such as reducing the frequency, dose and administering intravenous fluid. In this outbreak four confirmed cases were treated with cidofovir, and it was also used in two possible cases. Our experience was disappointing with three deaths in the six patients treated. Our experience is that viraemia usually clears many days before the respiratory secretions become PCR negative.
PR I S O N A N D CO M M U N I T Y O U T B R E A K O F S E V E R E RE S P I RATO RY I N F E C T I O N
Conclusion Low levels of immunity to adenovirus 14p1 make the general population susceptible to high attack rates of this infection especially amongst closed communities.3,4 This was the first outbreak of adenovirus affecting the community and prison venues. This strain of adenovirus has led to pneumonia and death in young adults, some with no pre-existing conditions.2 We have observed an increase in adenovirus pneumonia cases following the emergence of this pathogen. We recommend that early diagnosis with access to rapid PCR assay and routine typing is vital for detecting the emergence of this virus and it should be considered as a pathogen in the severely ill presenting with pneumonia. Surveillance of infectious diseases affecting the prison population is carried out by the Prison Infection Prevention team based within the HPA. The potential benefits and cost-effectiveness of an enhanced surveillance system for human adenovirus serotype 14 infection for the general population or patients at risk, or surveillance of virology samples, should be explored at a national level. We followed and adhered to advice from the Centres for Disease Control and Prevention (CDC) and HPA regarding the infection control practices in hospitals and prisons and this most likely reduced transmission. There is no specific curative treatment for this infection and cidofovir showed no clear effectiveness in the treatment. Further research on the use of antivirals and guidelines for the management of critically ill patients with adenoviral infections needs to be carried out and developed.
Acknowledgements We thank Ms Arlene Reynolds for work around case reviews and national epidemiology.
References 1 Rhee EG, Barouch DH. Adenoviruses. In: Mandell GL, Bennett JE, Dolin R (eds). Principles and Practice of Infectious Diseases (7th Edition). Philadelphia: Churchill Livingstone, 2010,2027 – 33. 2 Kajon AE, Lu X, Erdman DD et al. Molecular epidemiology and brief history of emerging adenovirus 14-associated respiratory disease in the United States. J Infect Dis 2010;202(1):93– 103. 3 Louie JK, Kajon AE, Holodniy M et al. Severe pneumonia due to adenovirus serotype 14: a new respiratory threat? Clin Infect Dis 2008;46(3):421– 5. 4 Carr MJ, Kajon AE, Lu X et al. Deaths associated with human adenovirus-14p1 infections, Europe, 2009 – 2010. Emerg Infect Dis 2011;17(8):1402– 8. 5 Centers for Disease Control and Prevention. Acute respiratory disease associated with adenovirus serotype 14- four states, 2006 – 2007. Morb Mortal Wkly Rep 2007;56(45):1181 – 4. 6 O’Flanagan D, O’Donnell J, Domegan L et al. First reported cases of human adenovirus serotype 14p1 infection, Ireland, October 2009 to July 2010. Euro Surveill 2011;16(8):1 – 5. 7 Carr MJ, De Gascun CF, Hall WW. Clinical and epidemiological aspects of the emerging adenovirus 14p1, Part I. Clin Microbiol Newsl 2011;33(19):145– 50. 8 Lewis PF, Schmidt MA, Lu X et al. A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14. J Infect Dis 2009;199(10):1427– 34. 9 Casas I, Avellon A, Mosquera M et al. Molecular identification of adenoviruses in clinical samples by analyzing a partial hexon genomic region. J Clin Microbiol 2005;43(12):6176– 82. 10 Esposito DH, Gardner TJ, Schneider E et al. Outbreak of pneumonia associated with emergent human adenovirus serotype 14-Southeast Alaska, 2008. J Infect Dis 2010;202(2):214 –22. 11 Taylor A, Munro A, Allen E et al. Low incidence of hepatitis C virus among prisoners in Scotland. Addiction 2013;108(7):1296– 304. 12 Carr MJ, De Gascun CF, Hall WW. Clinical and epidemiological aspects of the emerging adenovirus 14p1, Part II. Clin Microbiol Newsletter 2011;33(20):153– 8. 13 Williams KM, Agwu AL, Dabb AA et al. A clinical algorithm identifies high risk pediatric oncology and bone marrow transplant patients likely to benefit from treatment of adenoviral infection. J Pediatr Hematol Oncol 2009;31(11):825– 31. 14 Department of Health. Health Protection in Prisons: 2010 – 2011 Report. London: Department of Health, 2012. 15 Gore SM, Bird AG, Burns SM et al. Drug injection and HIV prevalence in inmates of Glenochil prison. BMJ 1995;310(6975):293– 6. 16 Personal communication with Dr Andrew Fraser, formerly Director of Health and Care, Scottish Prison Service, 2013. 17 Guidelines for Preventing Health-care-Associated Pneumonia. 2003 recommendations of the CDC and the Healthcare Infection Control Practices Advisory Committee. Respir Care 2004;49(8):926– 39. 18 Health Protection Agency and Department of Health—Offender Health. Prevention of Infection and Communicable Disease Control in Prisons and Places of Detention. A Manual for Healthcare Workers and Other Staff. London: Department of Health, 2011.
Downloaded from http://jpubhealth.oxfordjournals.org/ at University of Georgia on June 29, 2015
pulmonary disease (COPD) and so we may have missed other presentations of adenovirus. The first seven case isolates were serotyped with sequencing of the hexon, fibre and E1A regions indicating human adenovirus 14p1. Subsequent isolates positive for adenovirus by PCR were not fully characterized and an assumption was made that these would be the 14p1 strain as we had not found any other HAd14 in circulation that was not the HAd14p1 strain. Prisoners were not queried as to whether they knew known cases due to confidentiality concerns. A number of cases of adenovirus were co-infected with other pathogens. These results were reviewed by microbiology and virology medical staff and it was felt that adenovirus was the most likely primary cause of clinically significant infection.
69
