oulu 2012 d 1165 university of oulu p.o.b. 7500 fi-90014...
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ISBN 978-951-42-9899-8 (Paperback)ISBN 978-951-42-9900-1 (PDF)ISSN 0355-3221 (Print)ISSN 1796-2234 (Online)
U N I V E R S I TAT I S O U L U E N S I S
MEDICA
ACTAD
D 1165
ACTA
Sohvi Kinnula
OULU 2012
D 1165
Sohvi Kinnula
HOSPITAL-ASSOCIATED INFECTIONS AND THE SAFETY OF ALCOHOLHAND GELS IN CHILDREN
UNIVERSITY OF OULU GRADUATE SCHOOL;UNIVERSITY OF OULU, FACULTY OF MEDICINE,INSTITUTE OF CLINICAL MEDICINE,DEPARTMENT OF PAEDIATRICS
A C T A U N I V E R S I T A T I S O U L U E N S I SD M e d i c a 1 1 6 5
SOHVI KINNULA
HOSPITAL-ASSOCIATED INFECTIONS AND THE SAFETYOF ALCOHOL HAND GELS IN CHILDREN
Academic dissertation to be presented with the assent ofthe Doctora l Train ing Committee of Health andBiosciences of the University of Oulu for public defence inAuditorium 12 of the Department of Paediatrics, on 14September 2012, at 12 noon
UNIVERSITY OF OULU, OULU 2012
Copyright © 2012Acta Univ. Oul. D 1165, 2012
Supervised byProfessor Matti UhariDocent Marjo Renko
Reviewed byDocent Olli MeurmanDocent Harri Saxén
ISBN 978-951-42-9899-8 (Paperback)ISBN 978-951-42-9900-1 (PDF)
ISSN 0355-3221 (Printed)ISSN 1796-2234 (Online)
Cover DesignRaimo Ahonen
JUVENES PRINTTAMPERE 2012
Kinnula, Sohvi, Hospital-associated infections and the safety of alcohol hand gelsin children University of Oulu Graduate School; University of Oulu, Faculty of Medicine, Institute ofClinical Medicine, Department of Paediatrics, P.O. Box 5000, FI-90014 University of Oulu,FinlandActa Univ. Oul. D 1165, 2012Oulu, Finland
Abstract
Viral infections are common in childhood and a usual cause for hospitalization. Viruses are easilytransmitted among children both in pediatric wards and in other child care facilities, like child day-care centers. Hand hygiene is an important part of prevention of the transmission of viruses. Sincehospitalization times are getting shorter, hospital-associated infections often manifest afterdischarge.
The aim of the study was to evaluate the magnitude of hospital-associated infections during andafter hospitalization in pediatric wards with a focus on the effect of the ward structure. Data werecollected during two periods of two years in the pediatric infectious diseases ward in OuluUniversity Hospital; data collection in the latter period was done using electronic follow-upmethods. A two-year study period was also carried out in University Children’s hospital in Baseland in North Karelia Central Hospital in Joensuu. Paper questionnaires and electronicquestionnaires were compared as methods of doing continuous surveillance of hospital-associatedinfections during and after hospitalization. The safety of alcohol-based hand gels in children’s usewas studied using alcometer measurements after hand rub. Experiences on the use of alcohol-based hand gels in child day-care centers were collected by interviewing the personnel withquestionnaires.
Altogether 5.8 to 17.5% of hospitalized children (N=7046) got a hospital-associated infection;65 to 93% of the infections became evident after discharge. The number of hospital-associatedinfections was lowest in wards where single rooms and cohorting based on infection etiology wereused. Increased risk for hospital-associated infection was associated with young age, longerhospitalization time and a shared room. A higher response rate was achieved with electronicfollow-up compared with questionnaires on paper, 84 vs. 61%. The costs of follow-up were €13.61and €15.07 per patient in electronic and conventional follow-up, respectively. Electronic follow-up decreased annual expenses by 17.1%. Alcohol-based hand gels were found to be safe inchildren’s use, as no absorption was detected despite several contacts between hands and mucousmembranes. Personnel in child day-care centers were active in using hand rubs and found themuseful and easy to use. Earlier, there had been one incident with fire when using matches whilehands were still wet with alcohol.
The majority of hospital-associated infections in children become evident after discharge, andelectronic follow-up is useful in evaluating their magnitude. The number of hospital-associatedinfections can be decreased with single room bedding and careful infection control. Alcohol-basedhand gels are safe in children’s hand hygiene.
Keywords: child day care centers, cross infection, hand hygiene, hospital-associatedinfection, infection control, pediatrics, risk factors, virus diseases
Kinnula, Sohvi, Sairaalainfektiot ja alkoholikäsihuuhteiden turvallisuus lapsilla Oulun yliopiston tutkijakoulu; Oulun yliopisto, Lääketieteellinen tiedekunta, Kliinisenlääketieteen laitos, Lastentaudit, PL 5000, 90014 Oulun yliopistoActa Univ. Oul. D 1165, 2012Oulu
TiivistelmäLapset sairastavat usein virusinfektioita, jotka ovat yleinen sairaalahoidon syy. Virukset leviävätherkästi lasten keskuudessa, lastentautien osastoilla ja lapsiryhmissä, kuten päiväkodeissa.Virusten leviämistä voidaan estää hyvällä käsihygienialla. Lyhyiden hoitoaikojen vuoksi osavirusten aiheuttamista sairaalainfektioista ilmenee vasta kotona.
Tutkimuksen tarkoituksena oli selvittää sairaalainfektioiden määrä hoidon aikana ja kotiu-tuksen jälkeen sekä osastorakenteen vaikutus sairaalainfektioihin lastentautien osastoilla. Sairaa-lainfektioaineisto kerättiin Oulun yliopistollisen sairaalan lasten infektio-osastolla kahtena kah-den vuoden jaksona, joista jälkimmäisessä käytettiin sähköistä seurantajärjestelmää. Lisäksikahden vuoden aineistot kerättiin Pohjois-Karjalan keskussairaalan lastentautien osastolla jaBaselin yliopistollisen sairaalan lastenosastoilla. Paperikyselylomakkeilla ja sähköisesti tehdynsairaalainfektioseurannan toteutusta verrattiin. Lisäksi tutkittiin alkoholikäsihuuhteiden käytönturvallisuutta lapsilla päiväkotiolosuhteissa. Alkoholin imeytymistä tutkittiin poliisin tarkkuusal-kometrillä käsihuuhteen käytön jälkeen. Oulun kaupungin päiväkodeista kysyttiin käsihuuhtei-den käyttökokemuksista kyselylomakkeilla.
Sairaalainfektion sai 5,8-17,1 % sairaalassa hoidetuista lapsista (N=7046). Infektioista 65-93 % tuli oireisiksi kotiutuksen jälkeen. Sairaalainfektioiden määrä oli pienin osastoilla, jossakäytettiin yhden hengen huoneita ja potilaiden kohortointia taudinaiheuttajan mukaan. Sairaa-lainfektion riskiä lisäsivät lapsen nuori ikä, pitkä sairaalahoitoaika ja jaettu potilashuone. Säh-köisessä sairaalainfektioseurannassa oli parempi kotiutuksen jälkeinen vastausprosentti kuinpaperilomakkeilla, 84 % vrt. 61 %. Potilasta kohden kuluja tuli sähköisessä seurannassa 13,61euroa ja paperilomakkeilla tehdyssä seurannassa 15,07 euroa. Sähköisen seurannan käyttö laskivuosikuluja 17,1 %. Alkoholikäsihuuhteiden käyttö todettiin turvalliseksi lapsilla. Useista lima-kalvokontakteista huolimatta käsihuuhteen käytön jälkeen alkoholia ei imeytynyt verenkiertoon.Käsihuuhteiden käyttö päiväkodeissa on aktiivista, ja henkilökunta koki sen helpoksi ja hyödyl-liseksi. Aiemmin oli tapahtunut yksi vaaratilanne tulen kanssa tulitikkua sytytettäessä käsienollessa vielä käsihuuhteesta märät.
Lasten sairaalainfektioista suuri osa ilmenee kotiutuksen jälkeen, ja näiden infektioidenmäärää voidaan arvioida sähköisellä seurantajärjestelmällä. Sairaalainfektioiden määrää voi-daan vähentää käyttämällä yhden hengen huoneita ja huolehtimalla hyvästä hygieniasta. Alkoho-lihuuhteiden käyttö lasten käsihygieniassa on turvallista.
Asiasanat: käsihygienia, lastentaudit, päiväkodit, riskitekijät, sairaalahygienia,sairaalainfektiot, virusinfektiot
7
Acknowledgements
This study was carried out at the Department of Pediatrics in the University of
Oulu, Finland. Part of the data collection was done in collaboration with the
University Children’s Hospital in Basel, Switzerland, and with the North Karelia
Central Hospital in Joensuu, Finland.
I am deeply grateful to the supervisor of this thesis, Professor Matti Uhari,
M.D., Ph.D., for guiding me throughout these years with his great expertise, and
with patience and flexibility. His extensive knowledge in both clinical pediatrics
and science has been of great importance for this work, and they have inspired me
personally during the years of my medical studies and later at the start of my
pediatric training.
I also want to thank wholeheartedly Docent Marjo Renko, M.D., Ph.D., and
Docent Terhi Tapiainen, M.D., Ph.D. Marjo has been an inspiring teacher who has
supported me with her optimistic and caring heart. She has been always available
with her great knowledge and skills to help with my questions. Terhi has been
another wonderful person with whom I have had the great pleasure to work with.
I appreciate her support and willingness to help together with her good and
valuable comments that have been of great importance for this work.
I sincerely thank Tytti Pokka, M.Sc., for making a great effort in helping me
with the statistics in this study. I value her knowledge and help very much.
I am very thankful for the referees of this study, Docent Harri Saxen, M.D.,
Ph.D., and Docent Olli Meurman, M.D., Ph.D., for their valuable and constructive
comments on this thesis.
I also wish to express my thanks to the collaborators in Basel, Professor
Ulrich Heininger, M.D., and Michael Buettcher, M.D., for being part of this work,
both with the data collection and giving their valuable comments in data analysis
and reporting. Similarly, I thank Kaisa Vepsäläinen, M.D., and Risto Lantto,
M.D., for contributing to this study in Joensuu. They were willing to take part in
something new and to give their effort to it.
Many thanks also belong to the personnel in the child day-care centers in the
city of Oulu that participated this study, both by sharing their experiences and
giving us the possibility to study the use of alcohol hand gel in practice. I thank
all the children and their parents for being willing to take part in this study.
I also appreciate and thank the Oulu Police Department for lending their
official equipment to be used in our trial without any hesitation.
8
I am very grateful to my colleagues in the Pediatric Department at Lapland
Central Hospital for supporting me, being flexible and appreciating this work,
especially during the time of finishing this thesis. I also want to thank Sirpa
Kärkkäinen for her kind help in the library of Lapland Central Hospital.
Finally, I am thankful to my family, my dear parents and sisters, for staying
by my side throughout these years, for giving their love and interest in all
circumstances and for always being there for me. Especially I thank my sister
Miina for her help in translation from French. I thank all my friends for the many
moments of joy and happiness during these years. Most of all, I thank my loving
Lord, Jesus Christ, with whom I know all things are possible.
Rovaniemi, June 2012 Sohvi Kinnula
9
Abbreviations
ACIP Advisory Committee on Immunization Practices
AHG alcohol-based hand gel
AIIR airborne infection isolation room
CDC Centers for Disease Control and Prevention
CDCC child day-care center
CI confidence interval
ESBL extended-spectrum β-lactamase
HAI hospital-associated infection
HCW health-care worker
MRSA methicillin-resistant Staphylococcus aureus
NICU neonatal intensive care unit
OR odds ratio
PICU pediatric intensive care unit
RSV respiratory syncytial virus
SD standard deviation
SENIC Study on the Efficacy of Nosocomial Infection Control
sms short message service
SSI surgical-site infection
10
11
List of the original publications
This thesis is based on the following original articles, which are referred to in the
text by their Roman numerals I–IV.
I Kinnula SE, Renko M, Tapiainen T, Knuutinen M & Uhari M (2008). Hospital-associated infections during and after care in a paediatric infectious diseases ward. J Hosp Infect 68: 334–340.
II Kinnula S, Buettcher M, Tapiainen T, Renko M, Vepsäläinen K, Lantto R, Heininger U & Uhari M (2012). Hospital-associated infections in children: a prospective post-discharge follow-up survey in three different paediatric hospitals. J Hosp Infect 80: 17–24.
III Kinnula S, Renko M, Tapiainen T, Pokka T & Uhari M (2012) Post-discharge follow-up of hospital-associated infections in paediatric patients with conventional questionnaires and electronic surveillance. J Hosp Infect 80: 13–16.
IV Kinnula S, Tapiainen T, Renko M & Uhari M (2009). Safety of alcohol hand gel use among children and personnel at a child day care center. Am J Infect Control 37: 318–321.
12
13
Contents
Abstract
Tiivistelmä
Acknowledgements 7 Abbreviations 9 List of the original publications 11 Contents 13 1 Introduction 15 2 Review of the literature 17
2.1 Epidemiology of hospital-associated infections in children .................... 17 2.1.1 Bacterial hospital-associated infections ........................................ 17 2.1.2 Viral hospital-associated infections .............................................. 19 2.1.3 Risk factors for hospital-associated infections in children ........... 29 2.1.4 Surveillance methods for hospital-associated infections .............. 29
2.2 Consequences of hospital-associated infections ..................................... 33 2.2.1 Historical aspects .......................................................................... 33 2.2.2 Economical burden of hospital-associated infections ................... 34
2.3 Prevention of hospital-associated infections ........................................... 35 2.3.1 Isolation practices ......................................................................... 35 2.3.2 Hygienic procedures ..................................................................... 39 2.3.3 Safety of hygienic procedures ...................................................... 46 2.3.4 Current strategies in organizing prevention of hospital-
associated infections ..................................................................... 48 3 Aims of the study 51 4 Subjects and methods 53
4.1 Hospital-associated infections in pediatric infectious diseases
ward (I) .................................................................................................... 53 4.2 Hospital-associated infections in four pediatric wards (II) ..................... 55 4.3 Continuous follow-up for hospital-associated infections (III) ................ 59 4.4 Safety of alcohol hand rubs (IV) ............................................................. 60 4.5 Ethical considerations ............................................................................. 62
5 Results 63 5.1 Hospital-associated infections in pediatric wards during and after
hospitalization (I, II) ............................................................................... 63 5.1.1 Results from the follow-up study in Oulu University
Hospital ........................................................................................ 63
14
5.1.2 Results from the international multicenter follow-up study ......... 67 5.2 Continuous follow-up for hospital-associated infections (III) ................ 73 5.3 Safety of alcohol hand rubs (IV) ............................................................. 76
6 Discussion 79 6.1 Post-discharge follow-up in hospital-associated infection
surveillance ............................................................................................. 79 6.2 Ward structure and the risk of hospital-associated infections ................. 80 6.3 Continuous surveillance for hospital-associated infections..................... 83 6.4 Use of alcohol hand gels among children ............................................... 84
7 Conclusions 87 References 89 Original articles 105
15
1 Introduction
Hospital-associated infections (HAI) have mainly been discussed in the light of
bacterial infections, as bacteria cause most of the HAIs in adult wards. Especially
surgical site infections (SSI) lead to severe and expensive consequences, and
infection control procedures were first designed to reduce the number of surgical
HAIs. Thus, most recommendations on infection control practices in hospitals
have been based on experiences and studies on bacterial infections in adult wards.
However, the situation in pediatric wards is different, as the majority of HAIs are
viral infections (Allen & Ford-Jones 1990). These respiratory and gastrointestinal
infections are spread in pediatric wards, but as they are seldom documented their
actual number is not known, even though they cause significant morbidity among
children. As the hospitalization times in pediatric acute wards are getting shorter,
most of the viral HAIs become evident after hospitalization and remain
unreported.
According to the Centers for Disease Control and Prevention (CDC)
definition, an infection is hospital-associated when there is no evidence that it was
present or incubating at the time of hospital admission. Similarly, an infection that
is acquired in hospital and becomes evident after discharge is regarded as
hospital-associated (Garner et al. 1988). It has been common to set a time limit
for the appearance of the symptoms of HAI at 48 hours counting from the
admission to hospital and from the time of discharge. However, as the incubation
periods for several viruses are longer than 48 hours, HAI in pediatrics is often
defined as new signs of infection after 72 hours after admission to hospital or
within the first 72 hours after discharge from hospital for the infections becoming
evident at home.
Respiratory and gastrointestinal viruses are easily transmitted in child-care
facilities such as pediatric wards in hospitals and child day-care centers (CDCC).
We wanted both to identify risk factors for the transmission of viruses and to
study the safety of hygienic procedures that are used in infection control in child-
care facilities. To evaluate the number of HAIs in pediatric wards we have
conducted continuous HAI surveillance, which covers the immediate time after
hospitalization.
16
17
2 Review of the literature
2.1 Epidemiology of hospital-associated infections in children
The main focus in studies for HAIs is on bacterial HAIs, especially on SSI and
device-related infections, as these infections are difficult to treat and cause major
expenses. In pediatrics the majority of research on HAIs has been done on
neonatal wards with intensive care facilities, where bacteria predominate as
causes of HAIs. However, viruses cause most of the respiratory and
gastrointestinal infections leading to hospitalization in children (Iwane et al. 2004, McIver et al. 2001, Oh et al. 2003), and these viruses transmit easily in
health care facilities causing the majority of HAIs in general pediatric wards
(Gleizes et al. 2006, Raymond & Aujard 2000). As viral infections with longer
incubation periods often manifest themselves after hospitalization, the magnitude
of this problem is not known.
2.1.1 Bacterial hospital-associated infections
Reported frequencies of HAIs in pediatric hospitals vary from 2 to 7% during
hospitalization (Ford-Jones et al. 1989, Muhlemann et al. 2004, Welliver &
McLaughlin 1984). There is variation in HAI rates between different wards in
pediatric hospitals. HAI rates are the highest in neonatal intensive care unit
(NICU) and pediatric intensive care unit (PICU), and the lowest in general
pediatric wards and infectious diseases wards (Ford-Jones et al. 1989). The most
common bacterial HAIs in children are bloodstream infections, SSI and lower
respiratory tract infections (Muhlemann et al. 2004).
Hospital-associated infections in intensive care
The risk of bacterial HAIs in children is related to intensive care where the use of
invasive medical devices is common (Jarvis & Robles 1996). The risk of
bacteremia is increased by the presence of intravascular catheters, especially
central venous catheters that are used for longer periods. On average 5% of
patients get hospital-associated bloodstream infections in PICU (Raymond &
Aujard 2000, Urrea et al. 2003). Hospital-associated bloodstream infections are
mostly caused by gram-positive bacteria; coagulase-negative staphylococci
18
species and Staphylococcus aureus. Staphylococcus aureus and Pseudomonas aerigunosa cause most of the bacterial lower respiratory tract infections, for
which mechanical ventilation and use of intratracheal tube are risk factors. The
rate of hospital-associated lower respiratory tract infections is about 5% (Ford-
Jones et al. 1989, Raymond & Aujard 2000, Sarvikivi et al. 2008, Urrea et al. 2003). Urinary tract infections are related to the use of urinary catheters, and they
are usually caused by gram-negative pathogens. In PICU about 2% of patients get
hospital-associated urinary tract infection (Ford-Jones et al. 1989, Raymond &
Aujard 2000, Urrea et al. 2003).
In addition to the use of invasive devices, patients in NICU are prone to
infections due to prematurity, low birth weight and immunological immaturity. It
is reported that 7 to 13% of the patients in NICU get a HAI (Jarvis & Robles
1996, Orsi et al. 2009, Raymond & Aujard 2000). The most common HAIs in
NICUs are bloodstream infections, the rate of which is about 7%, and
pneumonias, the rate of which is about 4%. Gram-positive bacteria cause most of
the bloodstream infections, coagulase-negative staphylococci being the leading
pathogen. Pneumonias are mostly due to gram-negative bacteria, especially
Klebsiella pneumonia (Jarvis & Robles 1996, Orsi et al. 2009, Raymond &
Aujard 2000, Sarvikivi et al. 2008).
Surgical site infections
SSI is an infection that occurs on the operated site within 30 days after operation.
If a foreign body is left on the operated site, the time limit is extended to one year
(Mangram et al. 1999). The frequency of SSIs is 4.4 to 6.6% in children
according to studies with post-discharge follow-up extended to 30 days after
operation (Horwitz et al. 1998, Uludag et al. 2000). The risk of SSI is increased
in contaminated and dirty wounds, with operations with longer duration,
emergency operations, and operations done on patients with in-patient status. It
seems that in children, factors related to the operation affect the risk of SSI more
than patient characteristics and physiologic status. Staphylococcus aureus,
coagulase-negative staphylococci and gram-negative bacilli cause most of the
SSIs (Raymond & Aujard 2000).
19
2.1.2 Viral hospital-associated infections
There is plenty of variation in the reported number of viral HAIs, due to epidemic
seasons of viruses and different surveillance methods (Table 1). The comparison
shown in Table 1 includes only surveys focusing on viral infections (Muhlemann et al. 2004). In high epidemic season as many as 17% of hospitalized children in a
general pediatric ward may get a hospital-associated respiratory infection caused
by respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus or influenza
viruses (Wenzel et al. 1977). Outbreaks caused by influenza virus, RSV and
rhinovirus have taken place in neonatal units (Cunney et al. 2000, Valenti et al. 1982). In addition, coronavirus may be an important pathogen for HAIs in
neonatal wards (Sizun et al. 1995). Most studies on respiratory HAIs focus on
RSV that transmits easily and carries significant morbidity especially in young
children, and children with history of prematurity, congenital heart disease,
bronchopulmonary dysplasia or immunosuppression (Berner et al. 2001,
Mlinaric-Galinovic & Varda-Brkic 2000). As the incubation periods for
respiratory viruses are rather long, varying from 0.6 days for Influenza B virus to
5.6 days for adenovirus (Table 2), respiratory HAIs often become evident after
discharge from hospital and remain underreported (Lessler et al. 2009).
Altogether 4.5 to 14% of patients get gastrointestinal HAI during
hospitalization (Table 1), and the majority of them are viral infections. Rotavirus
has been the leading cause of hospital-associated gastroenteritis in children before
the introduction of rotavirus vaccine. Other documented pathogens are astrovirus,
norovirus and other caliciviruses, enterovirus and adenovirus. Viral diarrhea
outbreaks in hospitals occur during the winter and spring months, when there is
an epidemic season for viral gastroenteritis in communities. Young age increases
the risk of gastrointestinal HAI (Bennet et al. 1995, Ford-Jones et al. 1990). Viral
causes for hospital-associated gastroenteritis in children are more common than
bacteria. Clostridium difficile is reported to cause HAIs in older children; these
diarrhea episodes occurred throughout the year without seasonality (Langley et al. 2002).
Tabl
e 1.
Rep
orte
d fr
eque
ncie
s of
hos
pita
l-ass
ocia
ted
vira
l inf
ectio
ns in
gen
eral
ped
iatr
ic w
ards
.
Stu
dy re
fere
nce
War
ds u
nder
sur
veill
ance
In
fect
ion
type
H
AI f
requ
ency
D
urat
ion
of s
urve
illan
ce
In
hos
pita
l (tim
e af
ter
adm
issi
on fo
r def
inin
g H
AI)
Afte
r dis
char
ge (t
ime
afte
r dis
char
ge)
(mon
ths)
Ford
-Jon
es e
t al.
1989
A
ll A
ny
6.0%
N
D1
48
Is
olat
ion
war
d A
ny
1.3%
N
D
48
Wel
liver
& M
cLau
ghlin
198
4)
All
Any
4.
1%
ND
12
Gas
troen
terit
is
0.68
% (>
72 h
ours
) N
D
12
Res
pira
tory
0.
97%
N
D
12
Ray
mon
d &
Auj
ard
2000
) 20
ped
iatri
c un
its
Any
2.
5% (2
to 4
day
s)
ND
6
Gas
troen
terit
is
0.4%
(4 d
ays)
N
D
6
G
ener
al p
edia
tric
war
ds
Any
1.
0% (2
to 4
day
s)
ND
6
Gas
troen
terit
is
0.8%
(4 d
ays)
N
D
6
Juso
t et al.
2003
31
pedi
atric
/neo
nata
l war
ds
Gas
troen
terit
is
3.6%
(>48
hou
rs)
Not
kno
wn
3
Gra
ssan
o M
orin
et
al.
2000
A
ll G
astro
ente
ritis
11
.8%
(>72
hou
rs)
5.8%
(<5
days
) 5
Ben
net e
t al.
1995
G
ener
al p
edia
tric,
sur
gica
l G
astro
ente
ritis
14
% (>
72 h
ours
) N
D
26
Ford
-Jon
es e
t al.
1990
3
pedi
atric
war
ds
Gas
troen
terit
is
4.5%
(>72
hou
rs)
ND
7
Wen
zel e
t al.
1977
G
ener
al p
edia
tric
Res
pira
tory
17
% (>
6 da
ys)
Not
kno
wn
3
Mac
artn
ey e
t al.
2000
A
ll R
SV
infe
ctio
n 0.
098a (>
5 da
ys)
ND
4
x 6b
Isaa
cs e
t al.
1991
2
med
ical
war
ds
RS
V in
fect
ion
4.2%
(>5
days
) N
D
4b
Lecl
air e
t al.
1987
M
edic
al w
ard
RS
V in
fect
ion
0.64
a (>5
days
) N
D
1.5
x 6b
1 ND
=not
don
e, a pe
r 100
pat
ient
day
s, b S
urve
illan
ce in
six
-mon
th p
erio
ds c
orre
spon
ding
to R
SV
sea
son
(Nov
embe
r-A
pril)
21
Table 2. Incubation periods for respiratory viruses1.
Virus Median incubation period (days) 95% Confidence interval
Adenovirus 5.6 4.8 to 6.3
Coronavirus 3.2 2.8 to 3.7
Influenza A 1.4 1.3 to 1.5
Influenza B 0.6 0.5 to 0.6
Parainfluenza 2.6 2.1 to 3.1
RSV 4.4 3.9 to 4.9
Rhinovirus 1.9 1.4 to 2.4 1Lessler et al. 2009
Transmission mechanisms of viruses
There are three basic mechanisms relevant to HAIs describing how
microorganisms are transmitted (Siegel et al. 2007). Contact transmission can
occur via direct and indirect routes. In direct contact transmission a pathogen is
transferred via direct physical contact between an infected person and a
susceptible host. In indirect contact transmission a pathogen is transferred through
the hands of a caregiver or through a contaminated, inanimate object to a
susceptible host. Both respiratory and gastrointestinal viruses can survive on a
fomite and be transmitted through hands or directly from objects, such as toys or
medical equipment (Brady 2005, Coffin & Zaoutis 2005). Respiratory tract
infections are also transmitted through large droplets (>10 to 20 μm diameter)
produced by coughing and sneezing (Siegel et al. 2007). Large droplets contain
viral particles and can travel relatively short distances, approximately 1 to 2
meters, inoculating a susceptible host in close proximity. The third mechanism is
airborne transmission, where pathogens spread through small-particle
aerosols/droplet nuclei that can travel long distances remaining infectious under
favorable conditions (Siegel et al. 2007, Tang et al. 2006). Small-particle aerosols
(<5 to 10 μm diameter) are produced by talking, sneezing, coughing and
breathing; they are spread by air currents and transmission occurs when they are
inhaled. Airborne transmission is difficult to control and carries the potential to
cause outbreaks (Tang et al. 2006).
22
Respiratory syncytial virus
RSV is one of the most important respiratory pathogens in infancy and childhood,
causing bronchiolitis and pneumonia in young children, which often lead to
hospitalization. Older children and adults get milder upper respiratory tract
infections. RSV causes the majority of reported pediatric respiratory HAIs
(Forster et al. 2004). The epidemic season for RSV occurs during the
wintermonths in the Northern Hemisphere (Berner et al. 2001). Both in Finland
and in Switzerland, a major RSV epidemic takes place in the wintertime with
two-year periodicity (Duppenthaler et al. 2003, Waris 1991). During the epidemic
season 4.2 to 5.3% of patients get a hospital-associated RSV infection (Isaacs et
al. 1991, Leclair et al. 1987). The median incubation period of RSV is 4.4 days
(Lessler et al. 2009). Young children and those with a history of prematurity are at
risk for hospital-associated RSV infection. In addition, mechanical ventilation and
nasogastric tube increase the risk of hospital-associated RSV infection in NICU
(Valenti et al. 1982).
RSV is an RNA virus that belongs to the paramyxoviridae family. The
structure of RSV consists of a nucleocapsid that is enclosed within a lipid
envelope (Hall 2004). RSV transmits easily, and almost all children get infected
during the first years of life. RSV can remain viable in the environment and be
further transferred to hands (Hall et al. 1980). In a clinical experiment it has been
shown that RSV transmits through inoculation of large droplets in close contact
with a RSV-infected patient and through self-inoculation after touching surfaces
contaminated with secretions (Table 3) (Hall & Douglas 1981). No clinical
infection occurred after being in the same room at a distance of more than 2
meters from the infected person, suggesting that transmission through small-
particle aerosols is unlikely (Hall & Douglas 1981). Later it has been shown that
small-particle aerosols containing RSV are unstable in normal indoor air
humidity, and under normal conditions airborne transmission does not have a
significant role. During acute infection RSV is secreted in large amounts in nasal
secretions, more than 107 virus particles per milliliter. Secreted viruses remain
infectious on countertops for at least 6 hours, and on cloth and paper tissue for 30
minutes (Goldmann 2001, Musher 2003).
23
Influenza virus
Influenza viruses cause acute respiratory illness that often leads to hospitalization
in children and the elderly. Epidemics take place in temperate climates during
winter months, and especially during epidemics influenza also transmits in
hospitals, with possibly severe consequences (Glezen 2004). The median
incubation period is 1.4 days for influenza A and 0.6 days for influenza B (Lessler et al. 2009). During an influenza outbreak in NICU 35% of the neonates were
positive for influenza, most of them asymptomatic. One prematurely born infant
died. Logistic regression analysis showed that need of mechanical ventilation on
admission and twin pregnancy were risk factors for HAI (Cunney et al. 2000).
Influenza viruses belong to orthomyxoviruses, and there are three major types
of influenza viruses, A, B and C. They are RNA viruses, covered by a lipid
envelope with glycoproteins. Influenza A and B have hemagglutinin and
neuraminidase as surface glycoproteins, which are major antigenic determinants
defining the subtype and strain of the virus. Influenza C virus is of minor clinical
importance. It has a structure with a single glycoprotein with hemagglutinin,
esterase and fusion activity (Glezen 2004). Influenza viruses have the ability to
transform these antigens by processes called antigenic drift and shift. Antigenic
drift is continuous antigenic evolution that occurs through mutation in RNA
during the viral replication. Because of antigenic drift there is an influenza
epidemic every year, as prior infection does not protect against transformed virus.
Antigenic shift is a major change that produces a new subtype of influenza virus.
Antigenic shift occurs through transmission of animal virus to humans, or by
reassortment of the genes of two viruses of different subtypes that happen to
cause a concomitant infection in a host. Antigenic shift happens only in influenza
A virus, and produces a novel subtype that has the potential to cause pandemic
influenza (Glezen 2004).
Influenza transmits through large droplets when particles produced by
coughing or sneezing are inhaled, and through direct contact with secretions
(Table 3). At the highest respiratory tract secretions are highly infective
containing 106 or more virus particles per milliliter. Spread of influenza can also
occur through small-particle aerosols and contaminated hands. However, it is not
known what is the main transmission route for influenza virus not known
(Brankston et al. 2007, Killingley et al. 2011, Musher 2003). Both influenza A
and B viruses can survive on inanimate surfaces 1 to 2 days, depending on
temperature and air humidity, and viruses can be transferred from environment to
24
hands and after that they are shown to remain viable for 5 minutes (Bean et al. 1982). After experimental inoculation of known concentration of H1N1 influenza
A virus, it remained culture-detectable in hands at least 60 minutes, which allows
indirect transmission through hands (Grayson et al. 2009). Influenza A virus can
be detected on environmental surfaces and toys in CDCCs (Boone & Gerba
2005).
Influenza can best be prevented by vaccination, which must be given yearly
because of the transformation of viral antigens. Especially children with
pulmonary and cardiac diseases and immunodeficiency are at increased risk of
hospital-associated influenza if they are not vaccinated (Glezen 2004, Maltezou &
Drancourt 2003). As children under six months of age cannot be vaccinated, they
are susceptible to hospital-associated influenza (Cunney et al. 2000).
Rhinoviruses
Rhinoviruses cause upper respiratory tract infections, wheezing bronchitis and
pneumonia. They are probably the most frequent cause of common cold in
humans. The epidemic peaks are in the fall and spring, but infections occur
throughout the year in temperate climates (Hendley & Gwaltney 1988). The
median incubation period for rhinovirus infection is 1.9 days (Lessler et al. 2009).
Rhinovirus has been shown to cause HAIs in pediatric and neonatal wards
(Valenti et al. 1982, Wenzel et al. 1977).
Human rhinoviruses are divided into three genogroups (A-C). Especially
group C rhinovirus is known to cause lower respiratory tract infections and
asthma exacerbation in children (Mak et al. 2011, Piralla et al. 2009).
Rhinoviruses belong to the family of Picornaviridae. They are small, non-
enveloped RNA viruses, with at least 101 serotypes (Atmar 2004). However, the
number of rhinovirustypes is greater than this as the classification of viruses is
nowadays genetic and new virustypes have been found using PCR technique (Lau et al. 2007, Piralla et al. 2009). Rhinovirus can be transmitted between hands and
from an inanimate surface to hands, and further transfer from the hands to
conjunctival or nasal mucosa can cause infection (Table 3) (Hendley et al. 1973).
In an experimental setting of poker playing with infected and non-infected
persons it was shown that rhinovirus transmits through direct contact transmission
and through large droplets. No transmission occurred through cards contaminated
with secretions when infected persons were not present (Dick et al. 1987). It is
25
not known which transmission route is predominant, but it seems that prolonged
and close contact is needed for transmission of rhinovirus. This is may be related
to the rather low viral load, 5 to 2000 infective doses per milliliter, in the nasal
secretion of an infected patient (Goldmann 2001, Hendley & Gwaltney 1988,
Musher 2003).
Rotavirus
Rotavirus causes gastroenteritis, which may lead to dehydration and
hospitalization, especially in young children. The epidemic season for rotavirus is
during the winter and spring months in temperate climates. The incubation period
for rotavirus infection is 2 to 4 days. Before the start of rotavirus vaccination
rotavirus was the most common cause of gastroenteritis that lead to
hospitalization in children (Bernstein & Ward 2004, Vesikari et al. 1999).
Rotavirus transmits easily in hospitals (Chandran et al. 2006, Fruhwirth et al. 2001b, Gleizes et al. 2006, Lam et al. 1989). Especially children under 2 years of
age are afflicted (Pacini et al. 1987). Rotavirus can be transmitted to personnel,
and as some of infections in adults are asymptomatic, they can further transmit
rotavirus in hospital (Anderson & Weber 2004). Rotavirus has been shown to
spread from an outpatient clinic into community causing an outbreak (Li et al. 2011).
Rotavirus belongs to the Reoviridae family, and viral groups A and C are
associated with human diseases (Bernstein & Ward 2004). Rotavirus is a non-
enveloped RNA virus, the core of which is surrounded by three protein shells.
Two outer capsid proteins, glycoprotein (G-protein) and protease-cleavage protein
(P-protein), determine the serotype of the virus. The main transmission route for
rotavirus is fecal-oral, hands often being the vector in indirect contact
transmission (Table 3). In addition, airborne transmission may play some role.
During the infection there is high viral load in stools, 1012 viral particles per gram
of stools (Bernstein & Ward 2004). Rotavirus remains infectious on non-porous
material (glass, stainless steel and plastic) for several days at room temperature
with low to moderate humidity. Survival on cloth is possible for a few days at
room temperature and longer at lower temperature (Sattar et al. 1986). Rotavirus
can survive at least 4 hours on human hands, and infectious virus can be
transferred between hands and between hands and inanimate objects in both
directions (Ansari et al. 1988). Direct contact or indirect contact through hands
with a contaminated object leads to clinical infection (Ward et al. 1991). During a
26
rotavirus outbreak in CDCC, virus has been found in environment, the detection
rate being the highest in toys (Wilde et al. 1992).
Introduction of rotavirus vaccination into national vaccination programs has
reduced the number of severe rotavirus infections. Hospitalization due to
rotavirus infection in children has decreased up to 93%, the greatest decline being
seen in children younger than 12 months. By national vaccination of young
children the number of hospitalizations of older, unvaccinated children has also
been shown to decrease, suggesting that there may be an indirect protective effect
of rotavirus vaccinations on unvaccinated population (Buttery et al. 2011, Yen et al. 2011). After the first rotavirus vaccine was licensed, there has been a
significant decrease in the number of hospital-associated rotavirus infections. The
number of rotaviral HAIs has decreased from 0.53 per 1000 patient-days in 2003–
2007 to 0.10–0.20 per 1000 hospital-days in 2007 to 2009 (Anderson et al. 2011).
Rotavirus vaccination was introduced to Finland in September 2009, after which
there has been a decrease in the number of hospitalization due to rotavirus in
pediatric wards (Puustinen et al. 2011).
Norovirus
Norovirus (previously named Norwalk-like virus and small round-structured
virus) causes acute gastroenteritis both in children and adults, and it is the most
common cause of gastroenteritis outbreaks worldwide. In children it is estimated
that 10 to 15% of severe gastroenteritis is caused by norovirus (Matson 2004).
Norovirus infection does not cause long-lasting immunity and re-infections are
possible with the same virus strain. There is a peak in norovirus infections during
the winter months, but infections occur throughout the year, and some of them
can be traced to contaminated food or water. The incubation period ranges from
12 to 48 hours, the mean being 24 hours (Matson 2004). Norovirus transmits both
in pediatric and adult wards, infecting typically both patients and personnel
(Bennet et al. 1995, Cheng et al. 2006, Ford-Jones et al. 1990, Weber et al. 2005).
Norovirus belongs to Caliciviridae, which are non-enveloped RNA viruses.
By their protein structure noroviruses are divided into genogroups GI-GV, and
further into several genotypes (Koopmans 2009, Matson 2004). GII.4 genotype
has predominated in norovirus outbreaks during the last few decades, and it is
known to have caused the majority of endemic infections in Finnish children in
1994–2007 (Puustinen et al. 2012). Norovirus transmits through fecal-oral contact
27
transmission (Table 3). Norovirus can remain on a fomite and be further
transmitted in indirect contact transmission (Wu et al. 2005). Transmission can
also occur through aerosols from viral particles present in vomit (Hall et al. 2011). The peak in viral shedding into stools is 2 to 5 days after infection, when
the amount of viral copies can at its highest be 1011 per gram of stools (Matson
2004). After the inoculation of norovirus viral antigen can be found in stools for a
median of 7 days (Atmar et al. 2008). Norovirus is highly contagious; it is
estimated that a dose of 18 viral particles is enough to cause an infection (Hall et al. 2011).
Tabl
e 3.
Cha
ract
eris
tics
of v
irus
es c
ausi
ng p
edia
tric
hos
pita
l-ass
ocia
ted
infe
ctio
ns.
Viru
s S
truct
ure
Incu
batio
n
perio
d (d
ays)
1
Per
sist
ence
on
dry
surfa
ces2
Per
sist
ence
on
hand
s3
Tran
smis
sion
rout
es4
Infe
ctio
us d
ose5
Influ
enza
viru
s E
nvel
oped
RN
A v
irus
1.4
(IVA
6 )
0.6
(IVB
6 )
1 to
2 d
ays
At l
east
60
min
utes
(H1N
1)
Dire
ct c
onta
ct, l
arge
drop
lets
, aer
osol
2 to
790
TC
ID50
RS
V
Env
elop
ed R
NA
viru
s 4.
4 U
p to
6 h
ours
30
min
utes
D
irect
con
tact
, lar
ge
drop
lets
, fom
ites
100
to 6
40 T
CID
50
Rhi
novi
rus
Non
-env
elop
ed R
NA
viru
s 1.
9 2
hour
s to
7 d
ays
1 to
3 h
ours
D
irect
con
tact
, lar
ge
drop
lets
, fom
ites
0.03
2 to
10
TCID
50
Nor
oviru
s N
on-e
nvel
oped
RN
A v
irus
0.5
to 2
8
hour
s to
7 d
ays
40 to
60a m
inut
esFe
cal-o
ral,
aero
sol,
fom
ites
10 to
100
vira
l par
ticle
s
Rot
aviru
s N
on-e
nvel
oped
RN
A v
irus
2 to
4
6 to
60
days
O
ver 4
hou
rs
Feca
l-ora
l, fo
mite
s,
aero
sol
10 to
100
TC
ID50
1 Ber
nste
in &
War
d 20
04, B
oone
& G
erba
200
7, H
all e
t al.
2011
, Les
sler
et a
l. 20
09
2 Kra
mer
et a
l. 20
06),
3 Ans
ari e
t al.
1988
, Gra
yson
et a
l. 20
09, H
all e
t al.
1980
, Hen
dley
et a
l. 19
73
4 Bra
dy 2
005,
Bra
nkst
on e
t al.
2007
, Mus
her 2
003
5 For r
espi
rato
ry v
iruse
s w
ith in
trana
sal i
nocu
latio
n B
oone
& G
erba
200
7, C
aul 1
994,
TC
ID50
=tis
sue
cultu
re in
fect
ive
dose
6 IV
A in
fluen
za A
viru
s, IV
B in
fluen
za B
viru
s a Fo
r hum
an n
orov
irus
surr
ogat
es, f
elin
e ca
liciv
irus
and
mur
ine
noro
viru
s, ti
me
coun
ted
afte
r dry
ing
of v
irus
inoc
ulat
ion
29
Other viruses
Also some other viruses have the potential to cause HAIs in pediatric wards.
Astrovirus, adenovirus and enteroviruses are known as causes for hospital-
associated gastroenteritis (Bennet et al. 1995, Ford-Jones et al. 1990, Langley et al. 2002, Rodriguez-Baez et al. 2002), and coronavirus and parainfluenzaviruses
as causes for respiratory HAIs (Ford-Jones et al. 1989, Sizun et al. 1995, Welliver
& McLaughlin 1984, Wenzel et al. 1977). Newer respiratory viruses, such as
human metapneumovirus, and human bocavirus are reported to cause HAIs
among pediatric patients, the clinical significance of which is still unknown
(Durigon et al. 2010, Jartti et al. 2012, Kim et al. 2003). Other potential viral
causes for pediatric HAIs are varicella and measles (Centers for Disease Control
and Prevention (CDC) 2012, Langley & Hanakowski 2000).
2.1.3 Risk factors for hospital-associated infections in children
In children, HAI rates are inversely proportional to age so that young children get
HAIs easier, the highest HAI rates being reported in children less than 24 months
of age (Ford-Jones et al. 1989). HAI risk increases as the length of hospitalization
time increases (Burgner et al. 1996, Jarvis 1987). Comorbidities, particularly
neoplasms and congenital illnesses, make children more susceptible to HAIs.
Compared to community-acquired RSV infection, hospital-associated RSV
infections are more common in children with pre-existing conditions such as
prematurity, immunosuppression, and lung or heart disease (Cavalcante et al. 2006, Ford-Jones et al. 1990, Langley et al. 1997). An increased number of
roommates increases the risk of hospital-associated diarrhea, and rotavirus is
shown to transmit easily to roommates (Ford-Jones et al. 1990, Gaggero et al. 1992, Nakata et al. 1996). On the contrary, roommates are not often documented
to be the source for respiratory HAIs; respiratory viruses are transmitted in wards
through health care workers, parents and visitors (Slinger & Dennis 2002, Wenzel et al. 1977).
2.1.4 Surveillance methods for hospital-associated infections
Surveillance of HAIs is an essential part of infection control in hospitals. A
program with infection control was first shown to be effective in reducing the
number of bacterial hospital-associated infections in the Study on the Efficacy of
30
Nosocomial Infection Control (SENIC) that was initiated by CDC in the 1970s
(Haley et al. 1985). This control program included infection surveillance. The
study was conducted among adult patients in medical and surgical wards focusing
on bacterial HAIs, namely SSIs, urinary tract infections, pneumonias and
bacteremias. According to the infection surveillance, the risk of SSI was reduced
by 35% in patients with high infection risk and by 41% in patients with low
infection risk. Furthermore, the risk of hospital-associated urinary tract infection
was reduced by 31% in high-risk patients and by 41% in low-risk patients, the
risk of hospital-associated pneumonia was reduced by 27% in surgical patients
and by 13% in medical patients, and the risk of hospital-associated bacteremia
was reduced by 35% (Haley et al. 1985). The amount of reduction was related to
the components of the infection control program and the risk status of the patient
for HAI, such as the use of medical devices and surgical wound classification. In
the prevention of SSIs a component that made the program effective was regular
reporting of the SSI rates to operating surgeons. With other types of HAIs it was
shown that adjacent to other surveillance and control procedures at least one full-
time-equivalent infection control nurse per 250 beds increased the effectiveness
of the program in reducing the number of HAIs (Haley et al. 1985).
Surveillance programs for HAIs are drawn up to collect data, to carry out data
management and data analysis, and to communicate the results to the medical and
nursing staff. For the health care institution surveillance provides data to describe
the baseline rates of HAIs to detect changes in HAI rates and to investigate the
reasons for them, and to evaluate the effectiveness of interventions. Data
collection can be done by several methods. The most comprehensive method is
hospital-wide data collection, where infection control personnel gather data on
HAIs prospectively and continuously by using medical records, microbiology and
autopsy reports, and by talking personally with nursing staff and meeting patients
(Pottinger et al. 1997). This method is time consuming and expensive. In
addition, HAI rates from hospital-wide data collection of this kind are not
necessarily valid for comparison between hospitals. Other possibilities to organize
surveillance are periodic or prevalence surveillance, where data are gathered
during specified time intervals or a specified time period (Pottinger et al. 1997).
In pediatrics repeated prevalence surveys are used to collect data on HAIs. They
may be useful in evaluating the frequency of bacterial HAIs, but because of the
seasonality of viral HAIs, their number is probably better evaluated in
longitudinal surveillance (Burgner et al. 1996).
31
Targeted surveillance can be used in HAI studies. In targeted surveillance
selected services, certain populations or other specified areas are followed up for
HAIs, and accurate HAI risk is assessed within that area. In HAI surveillance an
outbreak threshold can be used to automatically recognize sudden peaks in areas
where baseline infection rates are already known. The use of outbreak threshold
helps to recognize the problem and respond to it quickly (Pottinger et al. 1997).
The method of surveillance is chosen so as to be suitable for the selected
population to be followed up and for the outcome of interest. Despite the chosen
surveillance method, in order to obtain reliable results through surveillance it is
important to maintain the intensity of surveillance at the same level throughout
the surveillance period (Lee et al. 1998). The same is true for other elements of
surveillance, such as the definitions used and the methods that are used for
infection rate calculation, which must be consistent over time to obtain HAI rates
that are comparable. External comparison of HAI rates is valid only when the
elements and intensity of HAI surveillance are similar in the locations that
participate in the comparison (Lee et al. 1998).
HAI surveillance during hospitalization can be done prospectively, i.e. during
the time when the patient is under the care of the health care organization.
Prospective data collection allows interaction with the patient and caregivers.
Another way to collect data from the hospitalization period is retrospective
surveillance, where data collection is performed by reviewing patient records
after the patient is discharged from hospital (Lee et al. 1998). In both methods of
data collection administrative databases, patient records, laboratory reports and
other ancillary service reports can be used as a source of information.
Surveillance after discharge from hospital
The sources described above provide data concerning the hospitalization time. As
the definition of HAI includes the time after hospitalization (Garner et al. 1988),
surveillance that covers the time after hospitalization is needed to obtain the true
HAI rate. This is especially true for certain types of HAIs, e.g. viral infections
with longer incubation periods (Lessler et al. 2009) and SSIs, which are defined
to occur within 30 days after operation. There is no single method used for post-
discharge HAI surveillance (Mangram et al. 1999).
A possibility for post-discharge follow-up is self-reporting of symptoms that
can be done for example using questionnaires or phone calls in data collection.
Sands et al. showed that 84% of SSIs in adult patients become evident after
32
hospitalization, and 63% of them were diagnosed and treated in ambulatory
settings. In addition to medical record review to find SSIs, patients filled in a
follow-up questionnaire where they were asked about wound recovery. Only 33%
of patients returned the questionnaire. The sensitivity of positive patient responses
was 68% when unreturned questionnaires were excluded from the analysis. The
false-positive results were most often due to reporting of a minor wound
complication that did not meet the criteria for SSI (Sands et al. 1996). The
accuracy of self-reporting is probably related to the subject and symptoms under
study. The presence and severity of colds was assessed in a double-blind setting
by patients and by trained clinical observer (Macintyre & Pritchard 1989). In that
study there was a high correlation between self-assessment and observer-
assessment both in evaluating the presence of cold and its severity. Two methods
were used in the assessment of colds for patients, a 5-point ordinal scale with
descriptive definitions and a continuous numerical scale. Both showed a
statistically significant association between physician’s observations and self-
reporting of symptoms (Macintyre & Pritchard 1989).
Post-discharge follow-up for pediatric HAIs has seldom been conducted
(Table 1). In a French study, post-discharge follow-up was done with phone calls
in order to evaluate the number of hospital-associated gastroenteritis during the
winter months (Grassano Morin et al. 2000). Gastrointestinal HAI rate was 11.8%
(96 per 817 patients) during the hospitalization. Furthermore, 48 patients got
diarrhea within 5 days after hospitalization at home, and thus 33% of HAIs
became evident after discharge. Follow-up was done with phone calls to parents,
and taking into account those who were re-hospitalized due to diarrhea. Fifty-five
per cent of the families were reached by phone. Only patients whose diagnosis on
admission was other than gastroenteritis were included in the follow-up (Grassano
Morin et al. 2000).
Electronic data collection
A continuous and comprehensive HAI surveillance is expensive to organize,
especially if post-discharge follow-up is included. As electronic patient records
are now in wide use, it is reasonable to develop a surveillance system that uses
computerized databases for surveillance both during hospitalization and after
hospital stay (Palumbo et al. 2012). When Asthma Quality of Life Questionnaire
was filled in both in paper and electronic form by adults, children, and caregivers
33
for children with asthma, the results showed a high correlation. In addition,
respondents found the use of electronic data collection more convenient than
questionnaires on paper. Data were collected using a touch-screen display device
(Bushnell et al. 2003). Similar results of electronic questionnaires and
questionnaires on paper being equivalent in measuring the quality of life and
wellbeing have been found elsewhere (Cook et al. 2004, Kleinman et al. 2001,
Pouwer et al. 1998).
2.2 Consequences of hospital-associated infections
2.2.1 Historical aspects
The role of the hands of health-care workers (HCW) in transmitting infections in
hospitals was noticed for the first time in the 19th century in transmission of
puerperal fever. In 1846, Ignaz Semmelweis observed a mortality rate of 10%
among women whose deliveries were taken care of by medical students and
physicians, whereas the mortality rate was less than 4% among those whose
deliveries were handled by midwives in another clinic (Boyce et al. 2002, Lane et al. 2010). He paid attention to the common practice of physicians and medical
students to go straight from an autopsy suite to the obstetric ward. Hand washing
was done with soap and water, after which a specific odor was still left in their
hands. Semmelweis suspected that puerperal fever was caused by agents that were
transferred by hands from the autopsy suite, and he introduced the use of chloride
of lime in hand hygiene before entering delivery rooms and between patient
contacts. This procedure of introducing hand antisepsis reduced the maternal
mortality rate in that clinic dramatically (Boyce et al. 2002, Lane et al. 2010).
Some years before Semmelweiss’ observations in Austria, Oliver Holmes made
similar conclusions of the role of hand hygiene in transmission of puerperal fever
in Boston. His colleague died one week after performing a post-mortem
examination to a woman who died of puerperal fever, which prompted Holmes to
investigate disease transmission. In 1843 he published a paper arguing that
unwashed hands are responsible for transmitting puerperal fever among patients.
Both Semmelweiss and Holmes got a hostile response to their findings, which
were left without notice at their time (Boyce et al. 2002, Lane et al. 2010).
34
2.2.2 Economical burden of hospital-associated infections
Even today HAIs cause significant morbidity and mortality in both adults and
children. In 2002 there were 1.7 million incidents of HAIs in the USA, and they
caused 99,000 deaths (Klevens et al. 2007). In addition to excess suffering and
deaths, HAIs cause remarkable costs to the health-care system. Additional costs
are caused for example by extended hospital stay, increased use of antibiotics and
a need of re-operations. Bacterial HAIs cause a major share of the total costs of
HAIs in health-care. The mean direct costs of HAI to health-care system per one
HAI case are evaluated to be USD36,000 for bloodstream infection, USD26,000
for SSI, USD10,000 for ventilator-associated pneumonia and USD1000 for
urinary tract infection (Stone et al. 2005). In the UK it is estimated that a HAI
causes 2.9 times higher total costs of hospitalization, and hospitalization time is
2.5 times longer for patients who get a HAI compared with those who do not.
This study was conducted among adults in a hospital with a HAI rate of 7.8%
during the study (Plowman et al. 2001). In NICU the total costs of hospital care
per patient are almost doubled in the case of a HAI, with evaluated extra costs of
€12,000 per patient with a HAI. HAI extends hospitalization time with an average
of 24 days in NICU, which makes up 72% of the extra costs of HAI (Mahieu et al. 2001).
Viral HAIs cause extra costs to the healthcare system by extending
hospitalization time and increasing the need for diagnostic procedures, laboratory
tests and radiological examinations. In addition to these direct costs of HAIs for
healthcare systems, there are additional costs for society, especially as viral HAIs
often become symptomatic after discharge from hospital. These indirect costs
include loss of working days by parents and possible re-visits to healthcare
facilities due to HAI. Hospital-associated rotavirus infection prolongs hospital
stay by 1.7 to 5.9 days. The direct costs of rotavirus HAI for hospitals in Western
Europe are reported to range from €1000 to €2500 per patient (Gleizes et al. 2006). In Austria, the total cost of rotaviral HAI is evaluated to be €2400 per
patient. Most of these costs are direct medical costs (€1500), followed by costs
for the third party payer (€800) and costs for the family (€120) (Fruhwirth et al. 2001a). Costs of hospital-associated lower respiratory tract infection are €2800,
the majority being direct medical costs. HAI of lower respiratory tract extends
hospitalization time by seven days (Ehlken et al. 2005). Earlier, direct medical
costs for hospital-associated RSV infection were evaluated to be USD9400 using
35
case-control comparison (Macartney et al. 2000). During one influenza season 11
hospital-associated influenza infections caused additional costs of USD83,000, on
average USD7500 per one HAI case (Serwint & Miller 1993).
2.3 Prevention of hospital-associated infections
2.3.1 Isolation practices
Isolation procedures to prevent hospital-associated infections
In patient care isolation procedures are discussed in the light of two categories, as
suggested by CDC (Siegel et al. 2007). Standard precautions are used in all
medical care, and they are based on the principle that all body fluids, blood,
secretions (except sweat), excretions, non-intact skin and mucous membranes
may contain infectious agents. Use of gloves is recommended in those contacts.
In addition, hand hygiene is recommended before and after every patient contact.
Other barrier and protective methods are used based on the anticipated exposure.
Transmission-based precautions are used when a patient is known or suspected to
have a contagious disease, and they are used in addition to the principles of
standard precautions (Siegel et al. 2007). Transmission-based precautions are
classified as contact precautions, droplet precautions and airborne precautions,
which are carried out with the use of personal protective equipment and patient
placement (Table 4). Personal protective equipment - gloves, gowns, masks,
goggles and N95 filtering facepiece respirator (N95 respirator, which corresponds
to filtering facepiece 3 (FFP3) mask in Europe ) - are used to protect HCWs from
being infected and contaminated (Siegel et al. 2007). Masks and goggles protect
mucous membranes, and particulate respirators protect reliably against inhalation
of aerosols. Another part of isolation practices concerns patient placement. If
single rooms are not available, cohorting of infected patients to a certain area is
an option to limit the spread of pathogens in the ward. HCWs can further be
cohorted to work in either clean or contaminated parts (Siegel et al. 2007).
36
Table 4. Transmission-based isolation precautions.
Precaution method Contact precaution Droplet precaution Airborne precaution
Gloves2 Recommended - -
Gowns2 Recommended - -
Mask2 - Recommended If respirator is not available
N95 respirator - - Recommended
Single room Preferred; if not possible,
cohorting and >2 m
separation between beds
Preferred; if not possible,
cohorting and >2 m
separation and curtain
between beds
Single bedding in airborne
infection isolation room
(AIIR)3
1Siegel et al. 2007
2Used based on the principles of standard precautions in all patients 3AIIR has monitored negative pressure relative to surrounding area, 6 to 12 air exchanges per hour and
air exhausted directly outside or recirculated through high efficiency particulate air filtration
Efficacy of contact and droplet precautions in preventing pediatric
hospital-associated infections
Hospital-associated RSV infection rates have been shown to decrease with high
compliance to use of gown and gloves by HCWs while caring for RSV infected
patients (Leclair et al. 1987), and by cohorting of patients based on RSV
screening on admission (Krasinski et al. 1990, Leclair et al. 1987). In one study a
combination of these procedures was needed to reduce hospital-associated RSV
infections (Madge et al. 1992). The use of masks and goggles while caring for
RSV infected patients reduces the number of RSV infection among HCWs (Agah et al. 1987). Furthermore, an intervention involving informing HCWs and parents
of the importance of hand washing, increasing the possibilities to use alcohol
containing hand rub, and cohorting of RSV infected patients to a separate unit led
to a reduction of a pre-intervention RSV HAI rate of 4.2% to 0.6% and 1.1% after
intervention (Isaacs et al. 1991). Preventing RSV transmission in pediatric wards
is cost-effective (Macartney et al. 2000). An infection control program with
education of HCWs about disease transmission, use of gowns and gloves,
cohorting RSV positive patients, cohorting nurses, and regular HAI surveillance
reduced the RSV HAI rate by 39% with a cost-benefit ratio of 1:6 (Macartney et al. 2000). Contradictory to these results, it has also been documented that the use
of gowns by HCWs is associated with increased risk of RSV transmission
(Langley et al. 1997). It has been shown that good compliance with hand hygiene
is needed when using gowns, gloves and masks. After removing personal
37
protective equipment hands and clothes are usually contaminated with virus from
this barrier equipment (Casanova et al. 2008).
Single-room bedding is effective in the prevention of hospital-associated
gastroenteritis. The risk of hospital-associated gastroenteritis increases as the
number of roommates in pediatric wards increases (Ford-Jones et al. 1990). By
analyzing rotavirus strains it has been shown that in 81% of hospital-associated
rotavirus infection the same rotavirus strain had caused infection in a roommate
(Gaggero et al. 1992), but rotavirus spreads also between patients located in
different rooms in pediatric wards (Nakata et al. 1996). Keeping the patient room
door closed and restricting the patient from moving out of the room are associated
with lower risk of hospital-associated diarrhea. The risk was also lower in
healthcare units where the number of patients was under 20, compared with units
with more patients (Jusot et al. 2003). The rate of hospital-associated
gastroenteritis is described to be the lowest in infectious diseases ward and
isolation ward in pediatric hospitals (Ford-Jones et al. 1989, Pacini et al. 1987).
Cohorting of nurses, and using gowns and chlorhexidine in hand hygiene are
effective in preventing bacterial gastroenteritis from spreading in pediatric wards,
but rotavirus HAIs were documented despite these precautions (Lam et al. 1989).
There is less evidence on how to effectively prevent norovirus transmission in
healthcare settings. Most of the data are from outbreak studies rather than
randomized trials (Koopmans 2009). Recommended strategies are cohorting of
infected patients, proper hand hygiene and environmental cleaning and
disinfection. In addition, contact precautions and the use of gloves and aprons in
the care of infected patients is recommended (Chadwick et al. 2000, Dancer 2009,
Hall et al. 2011). During a norovirus outbreak restricting infected HCWs from
work until they are 48 to 72 hours symptom-free and preventing the movement of
HCWs between affected and unaffected areas have been recommended
(Chadwick et al. 2000). However, in a recent meta-analysis, which evaluated the
efficacy of infection control procedures started during a norovirus outbreak, there
was no evidence of the efficacy of infection control measures on the length of the
outbreak or attack rates. In the studies that were analyzed intensified hand
hygiene, enhanced environmental cleaning, and restriction of infected staff from
work were used to prevent the spread of disease (Harris et al. 2010). In addition
to other infection control measures, closure of the affected unit may be needed to
stop the outbreak (Weber et al. 2005).
38
Prevention of airborne transmission
Pathogens’ ability to use airborne transmission can be classified as obligate,
preferential or opportunistic, describing the importance of airborne transmission
in the spread of a disease (Roy & Milton 2004). Obligate airborne transmission
refers to diseases that are spread practically only through aerosol, such as
tuberculosis. Diseases with preferential airborne transmission can also use other
transmission routes, but the spread by small-particle aerosol is predominant (e.g.
measles and varicella). Diseases with opportunistic airborne transmission use
naturally some other transmission route but are spread through aerosols under
favorable circumstances. As contamination of air is more difficult to detect than
contamination of hands or environmental surfaces, airborne transmission is often
left without notice in cases involving other than well-known airborne
transmission (Roy & Milton 2004, Siegel et al. 2007). Pathogens that have some
part of their lifecycle in the respiratory tract have the potential for airborne
transmission. Under certain conditions aerosols may have a role in transmission
of many respiratory pathogens, such as influenza, rhinovirus and RSV, which
usually transmit through contact and droplet transmission (Brankston et al. 2007,
Goldmann 2001, Siegel et al. 2007).Viruses causing gastroenteritis transmit
mainly through fecal-oral contact transmission, where the pathogen is often
inoculated through contaminated hands. In addition, gastrointestinal viruses
transmit by indirect contact transmission from contaminated environment.
Airborne transmission is also a possible route, which can explain the high
infectivity of rotavirus and norovirus (Chadwick et al. 2000, Chandran et al. 2006, Goldmann 1992).
There are particular respirators (N95 or higher level) to prevent the inhalation
of aerosol. Aerosol production can be contributed to by medical procedures like
bronchoscopy, tracheostomy and the use of nebulizers, which set HCWs under
greater risk infection (Siegel et al. 2007). In addition to personal protection,
architecture and ventilation impact the spreading of contagious aerosols in
healthcare facilities (Tang et al. 2006). Airflow directions are dependent on air
pressure in neighboring rooms and corridors, which are sensitive to air
temperature, opening of windows and doors and the use of mechanical fans.
Ventilation ensures that inhaled air is safe and free of infectious particles. Mixing
of contaminated air with uncontaminated air reduces the peak concentration of
small-particle aerosols in the air, reducing the risk of infection for a certain
39
amount of time (Tang et al. 2006). Another way to ventilate is to dilute
contaminated air with fresh air. The recommended ventilation flow rate in new
isolation rooms is at least 12 air changes/hour. For isolation rooms constructed
before 2001 ventilation flow rate of 6 air changes/hour is accepted (Siegel et al. 2007). A third aspect in ventilation is to control the airflow to move from HCWs
to patient, which is done by placing patients close to exhaust vents. Rooms with
air isolation have negative air pressure compared to surrounding area to prevent
the contaminated air from flowing out of isolation rooms to clean areas. A
minimum of 2.5 Pa negative pressure in relation to corridors is recommended
(Tang et al. 2006).
2.3.2 Hygienic procedures
Hand hygiene
Hand hygiene has had a leading role in infection control in healthcare (Boyce et al. 2002). Both hand washing with soap and water and antiseptic agents can be
used in hand hygiene. In the late 20th century, non-antimicrobial soap was still
recommended to be used in hand hygiene between patient contacts in routine
patient care, and antiseptic agents were recommended to be used only in certain
circumstances, such as invasive procedures, with patients at high risk for
infection, and if water and soap were not available (Larson 1988, Larson 1995).
However, hand washing with soap and water between every patient contact is
time consuming and leads to skin irritation, and it has now widely been replaced
by the use of antiseptic hand gels in health care settings (Boyce et al. 2002).
Many common viruses, among them rhinovirus, RSV and rotavirus, are able
to survive on human hands and can be further transmitted through them (Sattar et al. 2002). The latest CDC guideline recommends the use of alcohol-based hand
gel (AHG) in routine patient care as the first choice for hand hygiene (Boyce et al. 2002). Hand washing with soap and water is recommended before the use of
AHG when hands are visibly dirty, soiled or contaminated with protein-
containing material. The efficacy of soap and water in hand washing is based on
the detergent properties of soap and the mechanical removal of dirt and organic
substances from hands, but there is minimal antimicrobial activity. AHGs are now
widely used in healthcare facilities as they have been shown to be effective
against both against gram-positive and gram-negative bacteria, fungi and many
40
viruses, especially viruses with lipophilic envelope (Boyce et al. 2002). Besides
products containing alcohol, there are other possibilities for antiseptic agents.
Chlorhexidinegluconate is effective against gram-positive bacteria and enveloped
viruses, but less effective against gram-negative bacteria, non-enveloped viruses
and fungi. It has greater residual activity than AHGs. Iodine and iodophores have
bactericidal activity against bacteria and they are active against viruses and fungi.
In hand hygiene they may cause more problems with skin irritation than other
antiseptics used. In addition, hexachlorophene, alkyl benzalkonium chlorides and
other quaternary ammonium compounds, and triclosan were earlier used in hand
hygiene, but they are no longer recommended because of lack of efficacy or toxic
adverse effects (Boyce et al. 2002). Newer water-based hand disinfectant
containing polyhexamethylene guanidine is shown to have an efficacy against
bacteria that is equal to that of AHGs (Agthe et al. 2009).
The antimicrobial activity of alcohols is based on their ability to cause cell
membrane damage and to denature proteins. Alcohol concentration of 60 to 90%
is optimal for antiseptics, and both ethanol and isopropanol are used. Viruses with
a lipophilic envelope, for example influenza virus and RSV, are more sensitive to
AHGs and other antiseptic agents than non-enveloped viruses, such as
adenovirus, rhinovirus rotavirus and norovirus (Table 5) (Krilov & Harkness
1993, McDonnell & Russell 1999, Platt & Bucknall 1985). Both AHGs
containing ethanol or isopropanol and hand washing with soap and water are
effective in reducing H1N1 influenza A virus concentration from contaminated
hands. After each hand hygiene protocol no culture detectable virus was found.
When assessed by PCR hand washing with soap and water was slightly superior
to AHGs (Grayson et al. 2009). Antiseptic agents containing 70% alcohol caused
the greatest reduction (mean log10 reduction 2.8 to 3.9 in plaque forming units) in
rotavirus titers measured before and after hand rub. Of the other antiseptics
triclosan had the best efficacy against rotavirus, followed by chlorhexidine,
iodine, parachlorometaxylenol and plain soap (Ansari et al. 1989, Bellamy et al. 1993). AHG containing 60% ethanol is effective against non-enveloped viruses,
rotavirus, rhinovirus and adenovirus reducing the infectivity titer by 2.9 to 4.2.
log10 (Sattar et al. 2000).
It is not so well known what is the most effective antiseptic against non-
enveloped norovirus, as norovirus is difficult to cultivate and there is a lack of in vitro studies. Both feline calicivirus and murine norovirus have been used as
surrogates for human norovirus. Murine norovirus is more sensitive to ethanol
41
than feline calicivirus (Table 5) (Park et al. 2010, Sattar et al. 2011). It has been
shown that ethanol has better efficacy than isopropanol against feline calicivirus
(Kampf et al. 2005). Furthermore, AHGs with rather low ethanol concentration
(50 to 70%,) and low pH may have better efficacy reducing the infectivity of
feline calicivirus, but it has been questioned whether feline calicivirus is a good
model for human norovirus (Park et al. 2010, Sattar et al. 2011). A novel hand rub
containing 70% ethanol, polyquaternium polymer and citric acid was reported to
have good efficacy against non-enveloped viruses. The infectivity of feline
calicivirus was reduced 4.8 log10, and that of murine norovirus was 3.7 log10. This
hand rub had good efficacy also against rotavirus and adenovirus (Macinga et al. 2008). GII.4 human norovirus RNA titers were reduced 1.2 and 1.8 log10 PCR
units/mL by the 5 minutes exposure to 90% concentrations of ethanol and
isopropanol, respectively (Park et al. 2010), but the detection of a decrease in
RNA titers may not be a reliable method of studying the efficacy of antiseptics. It
has been reported that AHG with 62% ethanol was less effective against human
norovirus than hand washing with triclosan-containing soap and water when
efficacy was evaluated with PCR detection (Liu et al. 2010). Hand washing with
soap and water together with the use of ethanol containing AHG is currently
recommended for hand antisepsis against norovirus in Finland (Kuusi et al. 2007).
Tabl
e 5.
Act
ivity
of a
ntis
eptic
age
nts
agai
nst v
irus
es.
Viru
s S
truct
ure
of th
e
viru
s
Han
d w
ashi
ng
with
soa
p
Eth
anol
(60
to 9
5%)
Pro
pano
l (70
% p
ropa
n-1-
ol/p
ropa
n-2-
ol
Chl
orhe
xidi
ne
Tric
losa
n (2
,4,4
’ -
trich
loro
-2’-
hydr
oxyd
iphe
nyl
ethe
r)
Influ
enza
viru
s1 Li
pid
enve
lope
d ++
+ ++
+ ++
+ ++
+ N
D
RS
V2
Lipi
d en
velo
ped
ND
++
+ ++
+ ++
+ N
D
Rhi
novi
rus3
Non
-env
elop
ed
ND
++
+ N
D
ND
N
D
Rot
aviru
s4 N
on-e
nvel
oped
+
+++
+++
- ++
Felin
e ca
liciv
irus5
Non
-env
elop
ed
ND
++
(+++
with
pH
2 to
3)
+ -
+++
(pH
3.0
)
Mur
ine
noro
viru
s6 N
on-e
nvel
oped
N
D
+++
++
- +
+++
= >3
.0 lo
g 10 de
crea
se in
infe
ctiv
ity
++=
2.0
to 3
.0 lo
g 10 de
crea
se in
infe
ctiv
ity
+=1.
0 to
2.0
log 1
0 de
crea
se in
infe
ctiv
ity
-=<
1.0
or n
o de
crea
se in
infe
ctiv
ity
ND
= N
o da
ta
1 Blo
omfie
ld e
t al.
2007
, Boy
ce e
t al.
2002
, Gra
yson
et
al.
2009
, McD
onne
ll &
Rus
sell
1999
2 K
rilov
& H
arkn
ess
1993
, Pla
tt &
Buc
knal
l 198
5 3 K
ampf
et al.
2005
, Par
k et al.
2010
, Sat
tar e
t al.
2000
, Sat
tar e
t al.
2011
4 Bel
lam
y et al.
1993
, Kril
ov &
Har
knes
s 19
93, P
latt
& B
uckn
all 1
985,
Sat
tar e
t al.
2000
5 Sat
tar e
t al.
2011
, Kam
pf e
t al.
2005
, Par
k et al.
2010
1,
2,3,
4,5 B
loom
field
et
al.
2007
, Boy
ce e
t al.
2002
, McD
onne
ll &
Rus
sell
1999
43
Improved hand hygiene leads to a decrease in the number of HAIs in pediatric
wards. During a hand hygiene intervention with an introduction of AHGs in a
pediatric hospital rotaviral HAI frequency decreased from 5.9 to 2.2 per 1,000
discharged patients. With the intervention the overall hand hygiene compliance
increased from 62% to 81%, and the use of AHG increased from 4% to 29% of all
occasions when hand hygiene was practiced (Zerr et al. 2005). Improved hand
hygiene with the availability of AHGs together with cohorting of RSV infected
patients is effective in preventing RSV transmission in pediatric wards (Isaacs et al. 1991). Similarly to pediatric wards, viral infections are transmitted in other
childcare facilities, such as CDCCs and schools. It has been shown that children
attending CDCC are at increased risk for respiratory tract infections and diarrhea
(Louhiala et al. 1995, Louhiala et al. 1997). The number of infections among
children and personnel in CDCC can be reduced by introducing AHGs into hand
hygiene among CDCC personnel together with improving hygiene with food
serving, diaper changing and cleaning (Uhari & Mottonen 1999). Use of AHG in
the homes of families where children attend CDCC reduces the transmission of
gastroenteritis among family members. Transmission of respiratory tract
infections can be reduced by active use of AHG in families (Sandora et al. 2005).
In an elementary school the number of influenza A infections decreased after an
intervention with recommendation to use AHG in hand hygiene and teaching
cough etiquette. There was no effect on influenza B infections. The number of
absence episodes from school was lower in the intervention group than in control
schools (Stebbins et al. 2011).
One obstacle in reducing the occurrence of HAI is HCWs’ compliance to
hand hygiene. Better hand hygiene compliance can be achieved with AHGs
compared to hand washing with soap and water, which leads to a decrease in HAI
rates including MRSA infections (Pittet et al. 2000). Hand hygiene compliance is
documented to be 53% in PICU and 61% in NICU, being higher before patient
contact and aseptic tasks than after contact with patient and the surroundings
(Scheithauer et al. 2011), whereas hand hygiene compliance of only 22% was
documented in adult ICU (Kim et al. 2003). Among HCWs nurses have better
compliance to hand hygiene compared to physicians (Costers et al. 2012, Pittet et al. 2000, Scheithauer et al. 2011). To achieve better hand hygiene compliance
educational intervention is needed besides the introduction of AHGs as an option
for hand hygiene (Harbarth et al. 2002). Hand hygiene campaigns with reminders,
HCW education, promotion of AHGs, informing patients and audits with
44
feedback increase the hand hygiene compliance in health-care settings, part of
which is sustained over longer periods (Costers et al. 2012). Better compliance
achieved by AHGs is mostly because by bed-side-placing they are easily
available, and they are quicker to use than soap and water in hand hygiene (Voss
& Widmer 1997). It has been questioned whether commercial alcohol-containing
hand gels have as good antimicrobial efficacy as alcohol-containing rinses
(Kramer et al. 2002). However, it has later been shown that in clinical use the
antimicrobial efficacy of alcohol containing antiseptics is more related to the
concentration and type of the alcohol than the form (gel or rinse) of the product
(Barbut et al. 2007).
Environmental disinfection
Environmental contamination has a role in the transmission of microorganisms in
hospitals, especially in that of bacteria with antimicrobial resistance and viruses
(Cozad & Jones 2003, Dancer 2009, Sattar 2004). Viruses can remain on a fomite
for hours or days, and are further transmitted through contaminated surfaces
(Ansari et al. 1988, Boone & Gerba 2007, Kramer et al. 2006, Sattar et al. 1986,
Ward et al. 1991, Wu et al. 2005). It is suggested that continuous monitoring of
surface contamination to assess cleanliness is beneficial in all healthcare settings
(Dancer 2009). Cleaning can be done using detergents that remove organic
material, disinfectants that inactivate or kill infectious particles, or using
combination of these. Disinfectants are classified as high-level intermediate-level
and low-level disinfectants (Hota 2004). Patient care areas are recommended to
be cleaned using detergent-disinfectants. “Terminal cleaning” is done in patient
rooms after discharge using disinfectant (Hota 2004). Areas in close proximity to
patients and hand-touch sites are to be cleaned regularly and with efficient
disinfectants (Dancer 2009).
Lipid-enveloped and medium-size viruses are in general sensitive to
detergents and they can be inactivated by low-level disinfectants, whereas non-
enveloped viruses are more resistant and require intermediate level disinfection
(Rutala et al. 2008). Ethanol at concentrations of 60 to 80% is a virucidal
disinfectant against enveloped viruses, such as influenza virus and herpes virus,
and against many non-enveloped viruses, e.g. adenovirus, enterovirus, rhinovirus
and rotavirus. Isopropanol is virucidal against enveloped viruses but it has less
efficacy on non-enveloped gastrointestinal viruses (Rutala et al. 2008). Peroxygen
45
compounds are newer, promising disinfectants, which are effective against many
pathogens including viruses and spores (Dettenkofer & Block 2005, Dettenkofer
& Spencer 2007). Among peroxygen compounds monopercitric acid was shown
to have better efficacy against enveloped vaccinia virus and non-enveloped
adenovirus and poliovirus than peracetic acid (Wutzler & Sauerbrei 2004).
Rotavirus, norovirus and rhinovirus are examples of non-enveloped viruses
relevant in pediatric settings. Rotavirus survives several days on environmental
surfaces in a fomite and even longer if it is suspended in feces (Kramer et al. 2006). Phenolic/ethanol-containing spray is more effective in reducing rotavirus
titer from steel disks than sodium hypochlorite or phenol-based products, but all
of these products interrupt transfer of rotavirus from disks to fingers in an
experimental setting (Sattar et al. 1994). Quaternary ammonium compounds do
not have effect greater than water in removing rotavirus (Sattar et al. 1994). Use
of phenol/ethanol spray prevents the transmission of clinical infection from
rotavirus-contaminated surfaces into humans (Ward et al. 1991). Human
norovirus is shown to persist on a contaminated surface up to 7 days (Kramer et al. 2006), and environmental contamination has been found in outbreaks in
healthcare settings (Wu et al. 2005). Feline calicivirus, a norovirus surrogate, can
be inactivated by sodium hypochlorite, glutaraldehyde and iodone-based products
(Sattar 2004, Weber et al. 2010). The efficacy of alcohols against feline
calicivirus has not been consistent in experiments. However, human norovirus is
thought to be more resistant to disinfectants than feline calicivirus. In a study,
where norovirus was detected by PCR after cleaning the contaminated surface,
cleaning with detergent followed by disinfection with sodium hypochlorite
(chlorine concentration 5000ppm) was the most effective method in eliminating
the contamination and preventing further transfer (Barker et al. 2004). Sodium
hypochlorite (chlorine concentration of 1000 to 5000ppm) is currently
recommended to be used as disinfectant on norovirus-contaminated surfaces
(Weber et al. 2010). Phenol/ethanol-containing disinfectant and sodium
hypochlorite are effective against rhinovirus preventing the transmission from
contaminated disks to fingers, whereas quaternary ammonium- and phenol-based
products have significantly less efficacy (Sattar et al. 1993).
It is well documented that certain pathogens, including many viruses, survive
on environmental surfaces (Boone & Gerba 2007). However, there is less
evidence about the connection of environmental contamination to the number of
HAIs (Hota 2004). In few studies done on the effect of routine surface
disinfection on HAI rates, there was no significant difference in HAI rates after
46
the use of disinfectants versus detergents in cleaning (Dettenkofer et al. 2004).
Thus, there is no international consensus on the routine disinfection of non-
critical surfaces in health-care settings (Daschner & Schuster 2004, Rutala &
Weber 2004). An intervention with improved environmental disinfection in a
preschool, including the use of disinfectants for cleaning, disinfection of toys and
surfaces in the school bus, and improved hand hygiene, decreased the number of
respiratory tract and gastrointestinal infections in preschool children (Krilov et al. 1996). Regular washing of toys and cleaning of surfaces together with intensified
hand hygiene with AHG reduced the number of infections among children and
personnel in CDCCs (Uhari & Mottonen 1999).
2.3.3 Safety of hygienic procedures
Disinfectants have the potential of being harmful both to patients and personnel in
health care and to environment. Extensive use of certain disinfectants, (e.g.
quaternary ammonium compounds, chlorhexidine, aldehydes) in low
concentrations may lead to development of resistance bacteria, and disinfectants
cause pollution of water systems (Daschner & Schuster 2004, Dettenkofer &
Block 2005). Many disinfectants, aldehydes, quaternary ammonium compounds,
triclosan and sodium hypochlorite, are reported to cause skin irritation and
allergies (Daschner & Schuster 2004). However, the relevance of these hazards
has been questioned (Rutala & Weber 2004). Peroxygen compounds are probably
safer for consumer and environment (Dettenkofer & Block 2005, Dettenkofer &
Spencer 2007).
Absorption of substances from the skin is different in children than in adults,
which is especially true in the neonatal period. Hexachlorophene and
chlorhexidine were earlier used in bathing of newborn infants to reduce the
number of staphylococcal colonization and infections. This was stopped as these
antiseptic products were shown to absorb from intact skin into circulation both in
term and preterm neonates (Cowen et al. 1979, Curley et al. 1971).
Hexachlorophene is neurotoxic; spongiform changes in myelinated tracts of the
brainstem were found in preterm infants after being bathed with hexachlorophene.
The type of myelinopathy was similar to what had been seen after
hexachlorophene intoxication in animal experiments (Powell et al. 1973). It is not
well known how alcohol is absorbed percutaneously. There are single reports of
toxic absorption of alcohol from skin in children when alcohol was used in
47
antisepsis. The use of methylated ethanol in skin antisepsis in a premature
neonate led to hemorrhagic skin necrosis and a rise in blood ethanol and methanol
levels (Harpin & Rutter 1982). In a two-year old girl pre-operative use of
bandages soaked with ethanol led to skin damage and a rise of blood ethanol level
up to 0.8‰ (Puschel 1981). The introduction of AHGs in public places raised
discussion in the USA of whether the presence of AHGs should be seen as a fire
hazard as alcohol products are flammable (Voss et al. 2003). However, only few
cases of fire incidents have been reported during the time with widespread use of
AHGs. In Germany seven non-severe cases of fire occurred per 25,038 hospital
years of AHG use. Four incidents were related to HCWs’ use of matches or
cigarette lighter while hands were still wet with AHG. Two cases were due to
vandalism and one caused by a suicidal intention (Kramer & Kampf 2007). After
a couple of years of AHG use in healthcare facilities in the USA, no fire incidents
related to AHGs were reported (Boyce & Pearson 2003).
Problems with skin are one of the most commonly reported reasons for low
compliance to hand hygiene among HCWs. Skin irritation and dryness of hands
with the use of AHG and chlorhexidine-containing soap was evaluated in a trial
where these products were used for hand hygiene during two study periods
(Boyce et al. 2000). Both self-assessment and objective visual assessment of skin
irritation and dryness suggested that regular AHG use causes less skin problems
than hand washing with antimicrobial soap and water. When epidermal water
content was assessed by electrical capacitance measurements, it was shown that
hand washing with soap and water decreased the epidermal water content
significantly whereas no significant change was seen after the period with regular
AHG use (Boyce et al. 2000). There are differences between AHG products from
different manufacturers when it comes to skin irritation, which affects HCWs
compliance to AHG use (Barbut et al. 2007, Girard et al. 2006). In a double-
blinded, randomized setting among nurses in ICU, skin tolerability of AHG was
significantly affected by the type of emollient in the AHG; among the AHGs
available HCWs preferred that with glycerol. The type of alcohol, ethanol
compared to isopropanol, did not affect the skin tolerability of AHG. Other
factors that were significantly associated with skin alteration were male sex, fair
skin and skin alterations before the study (Pittet et al. 2007).
48
2.3.4 Current strategies in organizing prevention of hospital-associated infections
Pediatric aspects in organizing prevention
Both isolation policies and hygienic procedures have been shown to have an
effect on the spread of infections in pediatric wards. Gastroenteritis transmits
easily to roommates (Ford-Jones et al. 1990, Gaggero et al. 1992, Nakata et al. 1996). Isolation precautions, gloves and gowns, and cohorting, reduce the number
of HAIs caused by RSV, especially when combined with good compliance with
hand hygiene (Isaacs et al. 1991, Leclair et al. 1987, Macartney et al. 2000,
Ruuskanen 1995). Both respiratory and gastrointestinal viruses can remain viable
on environmental surfaces (Kramer et al. 2006), and unless disinfection is
appropriate they can be transferred through HCWs’ hands to patients, or directly
from surfaces or inanimate objects, such as toys, to patients. As hands can act as
vector for viruses, hand hygiene among HCWs is one of the single most
important precautions to prevent the spread of viruses. In pediatric wards, where
viruses cause most of the HAIs, AHGs are the first choice for hand hygiene
(Boyce et al. 2002). However, hand washing with soap and water may have better
efficacy than alcohol against norovirus and influenza virus (Grayson et al. 2009,
Hall et al. 2011, Liu et al. 2010).
The lowest HAI rates in pediatric hospitals have been reported in isolation
ward and infectious diseases ward (Ford-Jones et al. 1989, Pacini et al. 1987).
Pacini et al. described their infectious diseases ward as two-person rooms, where
the only difference in the ward structure compared to other wards was an
anteroom, a wider space at the entrance to patient room with a sink, hand washing
agents, and gowns and gloves available. The authors thought that the main reason
for the lower number of rotaviral HAIs in the infectious diseases ward was better
compliance with hand hygiene and that isolation policies were better followed, as
HCWs were used to caring for patients with infectious diseases. These data
suggest that separate wards for infectious diseases are preferable in pediatrics in
order to prevent HAIs. Crowding in the ward may be an important risk factor for
HAI. Patient density and nursing hours per patient days are associated with the
number of HAIs in pediatric wards so that there are more HAIs during the times
when patient density is high and there is nurse understaffing (Archibald et al. 1997, Moisiuk et al. 1998, Stegenga et al. 2002). There were a significant
49
correlation between the monthly patient to nurse ratio and the gastrointestinal
HAI rate. During the times that preceded gastrointestinal HAI the mean nursing
hours per patient day was 12.5 compared to 13.0 during the time after which there
were no HAIs (p<0.05). In the periods with low staffing (nursing hours per
patient day less than 10.5) the risk of gastrointestinal HAI was almost three times
higher than during other times (Stegenga et al. 2002).
Rotavirus infection can be asymptomatic, and rotavirus has been found in the
stools of symptom-free children in hospital (Dearlove et al. 1983, Eiden et al. 1988). This asymptomatic shedding of rotavirus may lead to HAIs unless
compliance to infection control procedures is good with all patients. Similarly,
adults can have an asymptomatic rotavirus infection with virus excretion
(Anderson & Weber 2004). It is documented that HCWs often stay at work while
having an upper respiratory tract infection (Cunney et al. 2000). These respiratory
viruses can be transmitted from HCWs to patients, which was the case with
rhinovirus in a neonatal unit (Valenti et al. 1982).
Vaccinations are one possibility to achieve better infection control in pediatric
wards. Introduction of rotavirus vaccination has led to a significant decrease in
the number of hospital-associated rotavirus infections (Anderson et al. 2011). In
Finland there has been a decrease in the number of rotavirus infections that lead
to hospitalization after the introduction of rotavirus vaccine in 2009 (Puustinen et al. 2011). In efficacy studies rotavirus vaccine was 85–98% protective against
severe rotavirus infection, and 74–87% protective against rotavirus infection of
any severity. Routine rotavirus vaccination is recommended by the Advisory
Committee on Immunization Practices (ACIP) starting at the age of 2 months
(Cortese et al. 2009). Annual vaccinations are the most effective method to
prevent influenza infection. ACIP recommends influenza vaccination to all
persons older than 6 months (Fiore et al. 2010). In Finland children from 6 to 35
months of age are recommended to take influenza vaccination. Older children are
vaccinated based on their risk profile (Terveyden ja hyvinvoinnin laitos 2011).
HCWs are recommended to take influenza vaccination as they are at greater risk
of being infected and vaccinating HCWs protects patients against hospital-
associated influenza. Especially children under 6 months of age are at increased
risk for influenza as they cannot be vaccinated themselves (Advisory Committee
on Immunization Practices & Centers for Disease Control and Prevention (CDC)
2011, Maltezou & Drancourt 2003). Still, the coverage for influenza vaccination
remains low among HCWs. The vaccination rate among nursing staff for
influenza A H1N1 was 15% in a NICU where an outbreak with H1N1 influenza
50
took place (Tsagris et al. 2012). Increase in the influenza vaccine coverage among
HCWs is associated with significant reductions in hospital-associated influenza
rate and influenza infections among HCWs (Salgado et al. 2004).
There are some other possibilities to prevent HAIs, especially gastroenteritis.
There is some evidence that prophylactic use of probiotics reduces the risk of
hospital-associated gastroenteritis in children 1 to 36 months of age. In a placebo-
controlled, randomized trial children who got Lactobacillus GG had less diarrhea
during hospital stay than those in control group, 3 per 45 (6.7%) vs. 12 per 36
(33%). There was no difference in rotaviral shedding in stools between the
Lactobacillus GG group (9/45, 20%) and controls (10/36, 28%), but the rate of
symptomatic rotavirus infection was lower in those who were given probiotics,
2.2% vs. 17% in control group (Szajewska et al. 2001). Probiotics intake reduces
the number and length of diarrhea episodes in young infants in CDCCs (Weizman et al. 2005). Being breast-fed protects against hospital-associated rotavirus
infection. During a rotavirus epidemic 10.6% of breast-fed children got rotavirus
during hospitalization; all infections were asymptomatic. At the same time, the
rate of rotavirus infection was 32.4% among non-breast-fed children, of whom
66% were symptomatic (Gianino et al. 2002). It has been suggested that
lactadherin, a glycoprotein in humanmilk, protects against symptoms of rotavirus
infection (Newburg et al. 1998).
New, emerging infectious diseases, such as severe acute respiratory syndrome
(SARS) and novel influenza viruses, have caused wide public concern during the
last decade. Infection control procedures have been re-evaluated in many health-
care settings in order to be prepared for a new pandemic. There are also other
threats that may challenge pediatric infection control practices in becoming years.
Measles has caused epidemics during the last years especially in Western Europe
where vaccine coverage has decreased (Centers for Disease Control and
Prevention (CDC) 2011, Muscat 2011). Being transmitted through aerosols,
measles can spread quickly in healthcare settings if diagnosis is delayed and air
isolation is not practiced. A measles outbreak took place in a pediatric emergency
department with five secondary cases during a four-hour exposure, one being a
HCW (Centers for Disease Control and Prevention (CDC) 2012).
51
3 Aims of the study
The specific objectives of this study were:
1. To evaluate the magnitude of hospital-associated infections during and after
hospitalization in a pediatric ward other than ICU (Study I, Study II).
2. To identify factors that influence infection transmission in pediatric hospitals
(Study II).
3. To evaluate the possibility of continuous surveillance for hospital-associated
infections during hospitalization and after discharge using electronic data
collection (Study III).
4. To evaluate the safety of hygienic procedures (Study IV).
52
53
4 Subjects and methods
4.1 Hospital-associated infections in pediatric infectious diseases ward (I)
The data were collected prospectively for two years, from June 2001 to May
2003, in a ward for pediatric infectious diseases in Oulu University Hospital. All
the patients hospitalized in the ward during the two years were included. The
ward has nine rooms for patients, and they are mostly used as single rooms. Each
room has an isolation system of two doors separating it from the corridor, and
only one of the doors is opened at a time. In the space between the doors there is a
sink with soap and an alcohol hand gel available, and similar facilities are located
in each room as well.
We defined HAIs according to the CDC definition, saying that an infection is
classified as hospital-acquired when there is no evidence that it was present or
incubating at the time of admission (Garner et al. 1988). Similarly, an infection
that is acquired in hospital and becomes evident after discharge is regarded as a
HAI. We used a time limit of 72 hours after admission to hospital or at home after
discharge for HAI based on the incubation periods of acute respiratory and
gastrointestinal viral infections (Lessler et al. 2009).
Data concerning the patient’s stay in hospital were collected from the hospital
records to a separate sheet (Table 6). When the child was discharged a follow-up
questionnaire was given to the parents with a request to fill it in and send it back
after 14 days (Table 6). Parents were asked whether the child had shown any
symptoms of a new infection and when the symptoms had appeared.
54
Table 6. Data gathered in the questionnaires concerning the patient’s stay in hospital and the two-week period after discharge.
Data collected in hospital Data reported by parents after discharge
Patient’s age Time needed for full recovery
Clinical diagnoses Appearance and timing of symptoms of new infection
Etiology of infection -Fever
Duration of hospitalization -Rhinitis
Number of patients in the room -Cough
Treatment with antimicrobials -Diarrhea
HAI in hospital -Vomiting
Condition at the time of discharge -Other symptoms
Medical help sought
Attendance at child day-care center
The diagnoses of HAI during hospitalization were based on symptoms and
clinical findings of respiratory or gastrointestinal infection, the etiology being
examined when this was clinically indicated. The diagnoses of HAI after
discharge were based on the appearance of new symptoms after discharge
reported by parents. Gastroenteritis was defined as the appearance of diarrhea or
vomiting within 72 hours after discharge. Respiratory infection was defined as the
appearance of rhinitis or cough within 72 hours after discharge.
During hospitalization, fecal specimens were taken to detect rotavirus and
adenovirus antigens to identify the etiology of diarrhea. In Finland the annual
epidemic season for rotavirus lasts from January to May, while RSV infections
have a peculiar seasonal distribution in periods of two years. Every second year
(odd numbers: 2001, 2003, etc.) there is first a smaller RSV epidemic in the
spring followed by the main epidemic at the end of the year (Waris 1991),
continuing into the beginning of the next year, whereas in the years between the
epidemics there are practically no cases of RSV in Finland. To cover this variation
we extended the survey over two full years.
The HAI frequency during hospitalization was taken to be the number of
HAIs relative to all children included in the study. The post-discharge HAI
frequency was calculated relative to the number of children who participated in
the follow-up. We assumed that the occurrence of HAIs follows a Poisson
distribution and defined 95% CI on this basis. The mean values for continuous
variables (age in years, length of hospitalization in days) in each subgroup were
calculated and the statistical significances of the differences were tested with one-
way ANOVA. Post hoc comparisons between the groups were tested with Tukey’s
55
test. Proportions were compared using the chi-square and standard deviation tests
(SND). Spearman correlation coefficients were calculated between the monthly
HAI rate and the number of patient days. Logistic regression analysis was used to
find risk factors for HAI. Odds ratios (OR) and their 95% CIs were calculated for
age, number of patients in the room and antimicrobial therapy (yes/no). For the
risk analysis the data were classified by diagnosis on admission, and that variable
was also included in the logistic modeling.
4.2 Hospital-associated infections in four pediatric wards (II)
The survey was performed in three hospitals: Oulu University Hospital, Finland,
University Children’s Hospital, Basel, Switzerland, and North Karelia Central
Hospital in Joensuu, Finland. Data collection was planned together by the authors
prior to the study and similar questionnaires were used in all hospitals (Table 6).
Data were collected prospectively for two years in each hospital between the
years 2004 and 2008 (Table 7). In the hospital in Joensuu active surveillance of
HAIs was started in 2006 when electronic follow-up became available. We
anticipated that the two-year follow-up would cover annual respiratory and
gastrointestinal virus epidemics as well as one major RSV epidemic in both
countries as two-year periodicity of RSV epidemics has been described both in
Finland and in Switzerland (Duppenthaler et al. 2003, Waris 1991). All
hospitalized patients were included in the survey, as there were no exclusion
criteria.
The hospitals in Oulu and Basel offer care up to the tertiary level and the
hospital in Joensuu up to the secondary level. Oulu University Hospital has a
pediatric department with 103 beds. The survey was conducted in the ward for
infectious diseases (Table 7). The University Children’s Hospital in Basel is a
pediatric hospital with 131 beds. The survey was carried out in two general
wards, a pediatric ward for children older than one year and an infant ward for
those younger than one year (Table 7). North Karelia Central Hospital in Joensuu
is a secondary care hospital with 27 beds for pediatric patients. The survey
applied to a ward with six rooms for 2 to 5 general pediatric or surgical patients
each and two isolation rooms (Table 7).
56
Table 7. Characteristics of the hospitals participating in the survey of HAIs.
Ward characteristics University Hospital
Oulu
University Children’s
Hospital, Basel1
North Karelia Central
Hospital, Joensuu
Linguistic background2 Mainly Finnish
speaking
60% German speaking Mainly Finnish
speaking
Type of the ward Infectious diseases General pediatric General pediatric
Patient capacity 9 22 20
Number of single rooms 9a 22a 2
Area (m²) 605 755 724
Area of rooms (% of total) 143 (24) 298 (39) 151 (21)
Average room size (m²) 15.9 13.5 18.9
Doors to patient rooms Two doors One door One door
Toilet in patient rooms Yes No No3
Nurses per shift 1.5 to 4 2 to 7 2 to 6
Use of AHG Yes Yes Yes
Active cohorting according to the
viral etiology
Yes Yes No
Form of follow-up Electronic On paper Electronic
Response rate in follow-up 84% 59% 71%
Survey period 3/2005-10/2007 10/2004-9/2006 5/2006-5/2008 1Two wards: pediatric ward and infant ward 2Denotes the language used in the questionnaires aOccasionally more than one patient per room 3Toilets only in single rooms used as isolation rooms.
Alcohol hand rub is actively used and the nurse-patient ratio is similar in all
wards (Table 7). Type of wards and the number of available single rooms are
different in the three hospitals (Table 7). Active cohorting according to specific
viral etiology is actively performed based on point-of-care tests for influenza
viruses and RSV in Oulu and for rota- and adenovirus in Basel. The results of
antigen detection tests for respiratory viruses and for gastrointestinal viruses are
available during the next office day in Oulu. Results from multiplex PCR for
adenovirus, influenza viruses, metapneumovirus, parainfluenzaviruses, and RSV
are available within 24 hours in Basel. Active cohorting according to viral
etiology is not practiced in Joensuu (Table 7).
We used a HAI definition of CDC (Garner et al. 1988), with a 72-hour time
limit for infections occurring during hospitalization and after discharge. The
diagnosis of a HAI during hospitalization was clinical, performed by the health
care personnel working on the wards. The etiology of a HAI was analyzed as
57
clinically indicated. The data on HAIs during hospitalization were recorded by the
health care personnel except in Oulu, where medical records were reviewed from
patient records in retrospect.
Data concerning the patient’s stay in hospital were obtained from the hospital
records. The patient’s condition at the time of discharge (symptomatic/fully
recovered) was recorded in Oulu and Basel but not in Joensuu. The post-discharge
follow-up was conducted using a standardized questionnaire (Table 6), this being
done electronically in Oulu and Joensuu (e-mail, short message service (sms) or
phone call, according to the parents’choice). An information sheet describing the
post-discharge follow-up and its questions was given to parents at the time of
discharge, and they were asked to return it seven days later. Those who did not
answer were contacted by phone. The follow-up in Basel used a paper
questionnaire form, which was given to the parents at the time of discharge. They
were asked to send it back to the hospital after two weeks, and a reminder letter
was sent to those who did not return it on time.
Our post-discharge follow-up was based on new symptoms of a probable
viral infection as reported by parents. The viral etiology of new infections was not
tested unless the patient was rehospitalized. To avoid counting the continuation of
already existing symptoms of infection as HAIs, we defined respiratory HAI as a
new symptom of respiratory tract infection in those who were not hospitalized for
a respiratory tract infection, unless they had fully recovered and become ill again
(Fig. 1). Similarly, gastroenteritis was recorded as a HAI only in patients who had
not been hospitalized for gastroenteritis, unless they had fully recovered and
become ill again. For patients hospitalized for other infections or non-infectious
diseases, all reported symptoms of infection in the relevant time frames were
regarded as signs of HAIs (Fig. 1).
58
Fig. 1. Study profile and flowchart of patients according to their diagnoses on admission to hospital.
To study possible reporting bias, all families in Basel who had not returned the
questionnaire two weeks after discharge from hospital were contacted by
telephone over a two-month-period. Data on new symptoms of infection were
received from 70 families by letter in this way and from 156 families by a
telephone interview.
All data were combined and analyzed in the Department of Pediatrics at the
University of Oulu. Similar definitions were used for post-discharge HAIs
throughout the analysis. Gastroenteritis was defined as the appearance of diarrhea
or vomiting within 72 hours after discharge. Respiratory infection was defined as
the appearance of rhinitis or cough within 72 hours after discharge. The HAI
frequency during hospitalization was taken to be the number of HAIs relative to
all children included in the study. The post-discharge HAI frequency was
calculated relative to the number of children who participated in the follow-up.
59
Mean values were calculated for continuous variables (age in years, length of
hospitalization in days), and proportions were compared using the chi-square test.
As the hospitals differed in infrastructure and settings, ward-specific risk factors
for HAIs within each ward were searched by using multivariate logistic
regression analysis with the method where all variables were entered to a model
at the same time. ORs and their 95% CIs were calculated for age (per year of
age), hospitalization time (per day of hospitalization time), shared room (yes/no)
and antimicrobial therapy (yes/no). The analyses were performed using SPSS
(Chicago, IL, USA) for Windows, version 12.0.1.
4.3 Continuous follow-up for hospital-associated infections (III)
When we started prospective HAI surveillance in the ward for pediatric infectious
diseases at Oulu University Hospital in 2001, it was done by collecting data
during and after hospitalization with paper questionnaires. Later we were offered
a chance to participate in a project in which mobile phones and e-mail were to be
used to perform HAI surveillance (Coronaria Ltd, Oulu, Finland). This electronic
means of follow-up was used from March 2005 onwards.
In the conventional follow-up, the data were collected using questionnaires
on paper in two phases (Table 6). The first questionnaire concerned the time in
hospital and the second questionnaire covered the time after hospitalization (Table
6). The data were transferred from the questionnaires to a database by a nurse. All
the patients in the ward were included in the surveillance program.
In the electronic follow-up most of the data concerning hospitalization could
be taken directly from the hospital database by means of a record linkage,
reducing the amount of data entry work. For the post-discharge follow-up, parents
were offered the alternatives of sms, e-mail or phone call to be used for answering
in seven days after discharge. At the time of the deadline a reminder with the
questions was sent to the parents by the chosen data collection method, and if
they did not answer in time they were contacted by phone. The questions in the
electronic questionnaire were similar to those in the printed questionnaires used
earlier except that the answers were coded with numbers or letters to ease
management.
We measured the time per patient that HCWs in the ward needed for
collecting the data and informing the parents about the HAI follow-up with both
methods of surveillance. The costs of the follow-up were then calculated from the
time spent on it and the average wages for HCWs in our department. The monthly
60
costs of employing a nurse were estimated to be €4830 and those for a secretary
€2850. Other expenses in the conventional follow-up were two sheets of paper
and one envelope with postage for each patient. The cost of the electronic follow-
up was €600 per month paid to Coronaria Ltd, who took care of the record
linkage and databases. The price also included information sheets for parents,
post-discharge data collection and reminders sent to parents. The costs of
surveillance were calculated both per patient and per year of follow-up. For
comparison, we also calculated the annual costs of a follow-up for 1000
hospitalized patients with both follow-up procedures, this being a figure that came
close to the true number of patients that we had in the conventional follow-up
(964 per year).
The frequency of HAI during hospitalization was taken as the number of HAI
cases relative to all the children monitored, and the post-discharge HAI frequency
was calculated relative to the children who participated in the follow-up, i.e., for
whom data were received. CDC definition for HAI was used (Garner et al. 1988).
Mean values were calculated for continuous variables (age in years, length of
hospitalization in days). Standard deviation test (SND) was used to compare the
response rates.
4.4 Safety of alcohol hand rubs (IV)
The improvement of infection control practices in CDCCs, including the use of an
AHG, was shown to reduce the number of episodes of any infection among
children significantly (Uhari & Mottonen 1999), and based on these results,
AHGs have been recommended for use by both personnel and children at CDCCs
in Oulu. As parents and CDCC personnel have been concerned about children’s
use of AHGs, and there have earlier been cases where the use of alcohol in skin
disinfection lead to toxic effects (Harpin & Rutter 1982, Puschel 1981), we
wanted to make sure that the use of AHGs is safe in children in CDCC
environment. We conducted an experimental trial at two CDCCs in February
2006 to evaluate the safety of AHG use among children, and a questionnaire
survey among all the CDCCs in Oulu to evaluate the use of AHGs.
Theoretically, a subject’s blood alcohol level would increase significantly
after using a hand gel containing 70% ethanol if this were totally absorbed
through the skin. Ethanol is equally distributed in all body fluids (De Martinis et al. 2006). Thus the maximum rise in the blood alcohol level of a child weighing
61
10 kilograms would be about 0.15‰ after using 1.5 mL of AHG and double that
if 3 mL were used. These blood alcohol levels are high enough to be both
measurable and harmful. Correspondingly, the figure would be 0.075‰ with a
1.5 mL dose for a child weighing twenty kilograms and 0.0375‰ for a child
weighing forty kilograms.
Eighty-two children varying in age from 3.5 to 7.2 years (mean 5.7 years,
standard deviation (SD) 1.1), 37 of whom were males, participated in the
experiment in two CDCCs in Oulu. The children were asked to rub their hands
with AHG, and all contacts between the hands and the mucous membranes (eyes,
mouth, nostrils) were observed and counted during the first 15 minutes afterwards
(Fig. 2). Alcohol concentrations in expiratory air, reflecting the absorption of
alcohol through the skin, were measured using an official alcometer as issued to
the police (Alco-sensor III, identification number 1062558) before and 15 and 60
minutes after use of the AHG. The measurement threshold of the alcometer was
0.01‰. The dose of AHG used was 1.5 mL at one day-care center and 3.0 mL at
the other. Each child’s participation in the trial was voluntary and subject to
written consent from the parents.
Fig. 2. Experiment design.
The use of AHGs in CDCCs was evaluated with a questionnaire asking about the
frequency of its use, the occasions on which it took place and possible risk
situations that had happened. The attitudes of the personnel to the use of an AHG
were evaluated using a Likert scale with respect to ease of use (1=easy,
62
5=difficult), convenience and usefulness. Medians were used to describe these
data as they were not normally distributed. One questionnaire was sent to each of
the 70 CDCCs in Oulu and to each member of the staff of six randomly selected
ones, so that in the end we received 128 completed questionnaires representing 68
CDCCs. The working experience of the respondents varied from one month to 26
years (mean 10 years, standard deviation (SD) 7.3 years) and the group size from
8 to 28 children (mean 19 children, SD 5.2). The analyses of the results
concerning the features of AHG use in each CDCC were performed using only
one randomly selected answer from those CDCCs where more than one person
had answered. The attitudes and personal practices of the personnel were
analyzed using all 128 answered questionnaires.
4.5 Ethical considerations
An ethical committee was consulted about the study protocol for HAI follow-up
in pediatric wards during and after hospitalization. All the patients in the wards
under study were followed up for HAIs during the hospitalization as part of
routine care. Participation in the post-discharge follow-up was offered to all
patients, but it was voluntary and participation status did not affect the treatment.
According to the Medical Research Decree (Finnish Acts and Decrees 1999) and
Declaration of Helsinki, Ethical Committee reviewing was not needed due to the
nature of the survey.
We wanted to study the safety of AHGs in children’s use as it is not known
whether alcohol from the hand rub is absorbed through skin and mucous
membranes in children, especially as children often tend to put their hands into
their mouths even though wet with AHG. The use of AHGs in CDCCs is
suggested after it has been shown that their use reduces the number of infections
in children and personnel (Uhari & Mottonen 1999). It was assumed that their use
is safe as AHG is used in small amounts on rather small skin surface, and it
evaporates in 15 to 30 seconds. Participation in the experiment was voluntary, and
an informed written consent for participation was given by parents. The study
protocol for the AHG safety study was approved by the Ethical Committee of
Northern Ostrobothnia Hospital District.
63
5 Results
5.1 Hospital-associated infections in pediatric wards during and after hospitalization (I, II)
5.1.1 Results from the follow-up study in Oulu University Hospital
During the study period from 6/2001 to 5/2003 1927 patients were hospitalized in
the infectious diseases ward in Oulu University Hospital. The mean length of
hospitalization was 3.0 days (standard deviation (SD) 1.8 days), including the
days of admission and discharge as full days. The mean age of patients was 3.0
years (SD 3.5 years). Almost all patients (90%) had a single room. The most
common diagnoses were gastroenteritis, 566 cases (30.6%), and wheezing
bronchitis, 437 cases (23.6%). A total of 709 patients (38.4%) were treated with
antimicrobials.
Twenty-one out of the 1927 patients (1.1%, 95% CI 0.7% to 1.7%) contracted
a HAI during their stay in the ward. All of them were cases of gastroenteritis, and
seven out of the eighteen tested were rotavirus-positive. The parents of 1175
patients (61%) returned the follow-up questionnaires, and 304 of these patients
(26%) were reported as having been taken ill again during the 14 days, including
86 cases (7.3%, 95% CI 5.9% to 9.0%) whose symptoms started within 72 hours
of discharge. Thus the total HAI rate was 8.4%, with 80% of these (86/107)
occurring at home after discharge. Diarrhea was the most common clinical
symptom among those taken ill within the first 72 hours (49%), followed by
vomiting (42%), fever (34%), rhinitis (31%) and cough (16%). Rhinitis was the
most common symptom among those who got ill 4–14 days after discharge
(53%).
The 1927 patients accounted altogether for 5504 patient days during the two-
year follow-up for which monthly HAI occurrences were recorded and HAI rate
was calculated per 100 patient-days for each month. The epidemic seasons for
respiratory and gastroenteric viruses, especially RSV and rotavirus, were reflected
in the number of diagnoses on admission to our ward per month, the peaks in the
HAI rate being found to coincide with high numbers of respiratory infections with
decreases in the rate at times when we had primarily gastroenteric patients (Fig.
3).
64
Fig. 3. Monthly appearance of hospital-acquired infections (HAI) per 100 patient days and the number of patients cared for because of gastrointestinal (GI) and respiratory tract (RTI) infections at the pediatric infectious disease ward during a two-year follow-up.
The rate of HAIs was associated with the number of patient days spent in the
ward, Spearman’s coefficient for the correlation between the monthly HAI rate
and patient-days being 0.42 (P=0.04) (Fig. 4).
65
Fig. 4. Monthly appearance of hospital-acquired infections (HAI) per 100 patient days and the amount of patient days at the pediatric infectious disease ward in a two-year follow-up.
Sixty-one percent of the parents returned adequately filled in follow-up
questionnaires. To evaluate possible reporting bias, i.e., to find out if the rate of
symptoms after discharge was different between respondents and non-
respondents, we pursued an intensified surveillance policy for a three-month
period from November 2002 to January 2003, during which there were 185
patients in the ward and 126 (68%) of the parents returned the questionnaires. The
59 non-respondent parents were interviewed by phone after the two-week follow-
up. Thirty-three (31.0%) out of the 126 patients whose parents returned the
follow-up questionnaire during the intensified surveillance period from November
2002 to January 2003 became ill. Among the patients whose parents were
contacted by phone, 13 out of 59 (22.0%) had become ill. Thus, even though the
difference between the groups was not significant, we had slightly overestimated
the occurrence of HAIs in the data gathered from the respondents during the
routine surveillance.
66
The patients who developed a HAI were younger than those who remained
healthy (Table 8). The mean hospitalization time was longer for those who had
symptoms of a HAI during their stay at hospital when compared with the other
patients (Table 8). Those who developed HAI symptoms on the fourth day or later
during the 14 days after the discharge did not differ in their length of stay in
hospital from those whose symptoms had started within 72 hours.
Table 8. Appearance of signs and symptoms of a new infection during hospitalization and <72 hours or 4 to 14 days after discharge.
Variables In hospital <72 hours after
discharge
4 to 14 days after
discharge
No new symptoms
N=21 N=86 N=218 N=831
Age (years, mean) 1.6 2.4 2.5* 3.4
Length of hospital
stay (days, mean)
6.0** 3.0 3.0 3.0
Shared room in
hospital (N, (%))
4 (20.0) 8 (10.1) 14 (6.8) 70 (9.8)
Attending a CDCC
(N, (%))***
3 (25.0) 15 (18.1) 40 (18.8) 134 (17.1)
When an overall significant result was obtained in the analysis of variance, the comparison was
continued with post hoc analysis.
*4 to 14 days vs. no, P 0.003
**In hospital vs. any other group, P<0.001
***Comparison between proportions with an overall chi-square test, which gave a non-significant result.
In the logistic regression analysis the patient’s age was the only significant
independent variable associated with the risk of contracting a HAI in the whole
data, with older age providing protection against HAI with an OR (per year in
age) of 0.92 (95% CI 0.85 to 0.99, P=0.02). Among the patients with respiratory
infections, a shared room increased the risk of HAI with an OR of 2.3 (95% CI
1.1 to 4.8, P=0.03), as 10 out of the 90 (11.1%) who were in a shared room
developed a HAI as against 38 out of the 789 (5.1%) in a single room. Treatment
with antimicrobials did not significantly affect the HAI frequency.
67
5.1.2 Results from the international multicenter follow-up study
Altogether 5119 patients were hospitalized in the three hospitals during the
periods concerned, 2838 of whom (55%) were males (Table 8). The most
common reasons for hospitalization in Oulu and Basel were gastroenteritis and
respiratory infections, while in Joensuu 60% of the patients had surgical, other
medical or neurological diseases leading to hospitalization. Altogether 1792
patients (35%) received antibiotics (Table 9).
Table 9. Detailed information on the patients included in the survey of hospital-associated infections in four pediatric wards.
Variables Oulu Basel Joensuu
Pediatric ward Infant ward
N=2309 N=961 N=799 N=1050
N (%) N (%) N (%) N (%)
Mean length of hospitalization (days (SD)) 2.7 (1.4) 5.2 (5.6) 7.4 (13.5) 3.3 (6.7)
Mean age (years (SD)) 2.9 (3.2) 5.9 (5.0) 0.6 (0.60) 5.7 (4.7)
Male 1309 (57) 499 (52) 424 (53) 606 (58)
Single room1 2258 (98) 806 (97) 617 (89) 492 (47)
Two-person room1 48 (2.1) 25 (3.0) 74 (11) 256 (24)
Three-person room1 3 (0.1) 1 (0.1) 5 (0.7) 169 (16)
Room for >3 persons1 - 1 (0.1) 1 (0.1) 13 (13)
Main diagnosis on admission
Respiratory infection (RI) 709 (42) 364 (38) 306 (38) 197 (22)
Gastroenteritis 599 (36) 196 (20) 136 (17) 97 (11)
RI and gastroenteritis 19 (1.1) 26 (2.7) 27 (3.4) 0 (0.0)
Other infection 282 (17) 158 (16) 157 (20) 67 (7.4)
Non-infectious diseases 71 (4.2) 217 (23) 172 (22) 547 (60)
Treatment with antibiotics 909 (39) 359 (37) 273 (34) 251 (24) 1Only available data are presented for different room types in Basel, i.e., missing data are not shown
separately.
The overall HAI frequency was 12.2%, with 80% of cases occurring after
discharge from hospital. We found marked differences in HAI frequencies
between the wards, the figure being lowest in the general pediatric ward for older
children in Basel and highest in the general pediatric ward in Joensuu (Fig. 5).
68
Fig. 5. Hospital-associated infections in hospital and within 72 hours of discharge in the four wards.
Altogether 122 out of 5119 patients developed a HAI during hospitalization,
giving a HAI frequency of 2.4% (Table 10). The most common in-hospital HAIs
in Oulu and in Basel were gastroenteritis, 27% of the cases of which were caused
by rotavirus in Oulu and 85% in Basel, the rest being mainly respiratory
infections.
69
Table 10. The number of HAIs in four pediatric wards during hospitalization and within 72 hours of discharge from hospital.
Variables Oulu Basel Joensuu
Pediatric ward Infant ward
HAI in hospital (N/N1, (%))* 18/2309 (0.8) 10/961 (1.0) 35/799 (4.4) 59/1050 (5.6)
HAI after discharge (N/N2, (%))* 218/1941 (11.2) 28/578 (4.8) 37/463 (8.0) 86/748 (11.5)
Gastrointestinal HAI 108 (5.6) 14 (2.4) 19 (4.1) 37 (4.9)
Respiratory HAI 98 (5.0) 14 (2.4) 17 (3.7) 41 (5.5)
Both respiratory and
gastrointestinal HAI
8 (0.4) - 1 (0.2) 8 (1.1)
Other infection 4 (0.2) - - -
Total HAI rate 12.0% 5.8% 12.4% 17.1%
*Significant difference in proportions with the chi-square test (P<0.001)1Number of patients surveyed for HAIs in hospital 2Number of patients surveyed for HAIs after discharge
Post-discharge follow-up data were received on 3729 (73%) patients (Table 6).
Altogether 365 patients (9.8%, 95% CI 8.9% to 10.8%) developed a viral HAI
that manifested after discharge from hospital. The overall frequency of
gastrointestinal HAI after discharge was 4.8% (N=178) (95% CI 4.1% to 5.5%).
Altogether 170 children (4.6%, 95% CI 3.9% to 5.3%) developed a respiratory
HAI and a further 17 (0.5%, 95% CI 0.3% to 0.7%) showed symptoms of both
respiratory and gastrointestinal HAI (Table 10). In total 464 children out of the
3729 (12%) visited a doctor within the first week after discharge, including 67
who were diagnosed as having gastroenteritis and 75 as having upper respiratory
tract infection.
When the cumulative occurrence of hospital-associated gastroenteritis and
respiratory infections during the first seven days after discharge in the case of the
infectious disease ward in Oulu was plotted against time, the occurrence of
gastroenteritis was seen as an accelerated curve after hospitalization, whereas the
occurrence of respiratory infections was as expected, i.e., constant in time (Fig.
6). This indicates that hospitalization increased the rate of gastroenteritis above
the expected linear pattern. In the general pediatric ward in Joensuu both the
occurrence of gastroenteritis and that of respiratory infections exceeded the
expected rate, and a similar phenomenon was found in the two general wards in
Basel, but with less marked differences (Fig. 6).
70
Fig. 6. Timing of the appearance of respiratory infection (RI) and gastroenteritis (GE) in children whose symptoms appeared after discharge. Assuming that the general infection rate in a large population over a short cumulative observation time will remain constant, the infection rate would be seen as a straight line when plotted against time in the case of no HAIs. The dotted line in the figure represents this straight expected line (EL) for infections.
The ward-specific risk factors for HAI were analyzed separately for each ward
(Table 11). Sharing a room significantly increased the risk of HAI in the infant
ward in Basel (OR=5.5, 95% CI 2.4 to 12.2), but this association could not be
analyzed in the pediatric ward in Basel or in the infectious disease ward in Oulu,
where single rooms were used almost exclusively. Among the HAIs that
manifested themselves in hospital a longer hospitalization time was associated
with a higher HAI risk in every ward except the general ward in Joensuu. This
may be related to the fact that more than half of the patients in this ward had been
hospitalized for other than infectious diseases in Joensuu. Treatment with
antibiotics was associated with a higher HAI risk in the infant ward in Basel and
71
in the general ward in Joensuu, while young age increased the risk of HAI after
discharge in Oulu and in Joensuu (Table 11).
Tabl
e 11
. Ris
k fa
ctor
s fo
r ho
spita
l-ass
ocia
ted
infe
ctio
ns (
HA
Is)
occu
rrin
g du
ring
hos
pita
lizat
ion
and
afte
r di
scha
rge.
Odd
s ra
tios
(OR
) and
95%
con
fiden
ce in
terv
als
(CIs
) for
risk
fact
ors
are
pres
ente
d fo
r eac
h w
ard.
Var
iabl
es in
logi
stic
regr
essi
on m
odel
ing
Oul
u B
asel
Jo
ensu
u
Ped
iatri
c w
ard
Infa
nt w
ard
O
R (9
5% C
I), P
O
R (9
5% C
I), P
O
R (9
5% C
I), P
O
R (9
5% C
I), P
HA
I in
hosp
ital
Age
(per
yea
r)
0.72
(0.5
1 to
0.1
0), 0
.048
0.
71 (0
.51
to 0
.98)
, 0.0
4 1.
44 (0
.86
to 2
.41)
, 0.1
7 0.
97 (0
.91
to 1
.03)
, 0.3
0
Tim
e in
hos
pita
l11.
42 (1
.20
to 1
.67)
, <0.
001
1.22
(1.1
1 to
1.3
4), <
0.00
1 1.
05 (1
.03
to 1
.07)
, <0.
001
0.81
(0.6
7 to
0.9
9), 0
.043
Sha
red
room
N
A
NA
5.
45 (2
.44
to 1
2.2)
, <0.
001
0.85
(0.4
9 to
1.4
8), 0
.56
Ant
ibio
tic tr
eatm
ent
2.55
(0.8
8 to
7.3
9), 0
.09
0.93
(0.1
8 to
4.9
7), 0
.93
3.14
(1.4
4 to
6.8
3), 0
.004
2.
22 (1
.27
to 3
.89)
, 0.0
05
HA
I afte
r dis
char
ge
Age
(per
yea
r)
0.93
(0.8
8 to
0.9
8), 0
.010
0.
90 (0
.80
to 1
.01)
, 0.0
76
0.92
(0.5
0 to
1.6
9), 0
.78
0.91
(0.8
6 to
0.9
7), 0
.002
Tim
e in
hos
pita
l11.
11 (1
.02
to1.
21),
0.02
2 1.
05 (0
.97
to 1
.13)
, 0.2
3 1.
02 (0
.98
to 1
.05)
, 0.3
3 1.
00 (0
.97
to 1
.03)
, 0.9
6
Sha
red
room
0.
66 (0
.23
to 1
.85)
, 0.4
3 1.
67 (0
.20
to 1
4.0)
, 0.6
3 0.
16 (0
.02
to 1
.40)
, 0.0
98
0.78
(0.4
9 to
1.2
6), 0
.31
Ant
ibio
tic tr
eatm
ent
0.98
(0.7
3 to
1.3
1), 0
.89
2.01
(0.8
8 to
4.5
9), 0
.098
1.
19 (0
.57
to 2
.48)
, 0.6
5 0.
82 (0
.47
to 1
.43)
, 0.4
8 1 P
er d
ay o
f tim
e in
hos
pita
l
NA
not
app
licab
le d
ue to
a s
mal
l num
ber o
f pat
ient
s tre
ated
in a
sha
red
room
73
When all the families of discharged patients had been contacted over a period of
two months in Basel, the total HAI rate within 72 hours after discharge was 7/79
(8.8%) in the children whose follow-up data were obtained by letter and 15/156
(9.6%) in those whose families were contacted by telephone, given that no
follow-up questionnaire had been received. This difference was not statistically
significant.
5.2 Continuous follow-up for hospital-associated infections (III)
During the follow-up study with paper questionnaires from 6/2001 to 5/2003 in
the infectious diseases ward in Oulu 1927 patients were recruited for the
conventional follow-up, and 1175 (61%) returned the questionnaires adequately
filled in. During the following study period with electronic questionnaires 1940 of
the 2309 recruited patients (84%) sent the post-discharge information to us. The
difference in response rate was statistically significant (P<0.001). In the electronic
follow-up 20% of the parents chose to answer by sms (response rate 74%), 63%
by e-mail (response rate 85%), while 17% wanted us to call them in order to
collect the data (response rate 92%) (Table 12).
74
Table 12. Participation in the post-discharge follow-up of HAI using conventional and electronic procedures. The main results obtained in the two periods are presented in the table.
Variables Paper questionnaire Electronic questionnaire
N=1927 N=2309
Time period 6/2001-5/2003 3/2005-10/2007
Response rate in total (%)* 61 84
Response rate in sms1 follow-up (%) - 74
Response rate in e-mail follow-up (%) - 85
Response rate in phone call follow-up (%) - 92
Time used for data collection by HCWs per patient 33 minutes 13 minutes
Costs of follow-up per patient €15.07 €13.61
Costs of data collection per year (1000 patients2) €15,070 €12,490
HAI at home 86 (7.3%) 214 (11%)
HAI total3 8.4% 12.2%
Mean age of patients (years) 3.0 2.9
Mean length of hospitalization (days) 3.0 2.7
*Statistically significant difference between the response rates, P<0.0001 1short message service 2For comparison, the annual costs were calculated for 1,000 patients per year with both follow-up
procedures, since this figure was close to the average number of patients treated during the conventional
follow-up (964 per year). 3Sum of HAI rates during hospitalization and the post-discharge period
The time spent by the HCWs on the conventional follow-up was 33 minutes per
patient, compared to 13 minutes per patient on the electronic follow-up. Most of
the savings in time arose because no data entry procedure was needed. In the case
of conventional follow-up a nurse used 20 minutes per patient for collecting data
concerning hospitalization and informing parents, and 10 minutes per patient for
data entry. A further 3 minutes per patient were used by a secretary for preparing
the follow-up questionnaires. The other costs in the conventional follow-up were
€0.041 per patient for two sheets of paper and an envelope with postage, making
the total cost €15.07 per patient. As we had 964 patients annually over that period,
the costs of performing the survey were €14,525 per year.
Fig.
7. C
osts
of t
he tw
o fo
llow
-up
met
hods
.
76
The costs of the electronic follow-up included the time spent on it by the HCWs
and the monthly price of €600 paid to Coronaria Ltd for administering it. On the
electronic follow-up 5 minutes per patient were used by a secretary for collecting
data concerning hospitalization and 8 minutes per patient were used by a nurse for
informing parents about the post-discharge follow-up, making the cost of the time
spent by the HCWs €5.29 per patient. As we had an average of 72 patients per
month, the total cost of the follow-up per patient was €13.61 during the period
concerned and €11,783 per year. When the costs of the two follow-up procedures
were calculated for 1000 patients per year, they were €15,070 in the conventional
follow-up and €12,490 in the electronic follow-up, so that the latter gave a saving
of 17.1% in annual expenses (Table 12), or €2.58 per patient given a total of
1,000 patients per year.
5.3 Safety of alcohol hand rubs (IV)
In the experimental trial 47 children rubbed their hands with 1.5 mL of AHG and
35 with 3.0 mL. All the alcometer results remained below the measurement limit
of 0.01‰, suggesting minimal or no alcohol absorption from the hand gel. The
number of contacts between the hands and the mucous membranes varied from 0
to 30 per child during15 minutes (mean 2.4 times, SD 4.3).
According to the questionnaires, AHGs were used in every CDCC, only
among adults in 11 of the 68 CDCCs (16%), and also regularly by the children in
50 of them (74%). In the remaining seven CDCCs the children had only used
AHGs at times of epidemics. The mean time for which an AHG had been used in
the CDCCs was 7.4 years (SD 3.3). The most common occasions for AHG use by
the personnel were before serving food and after cleaning secretions, whereas
hand washing with soap was most common after going to the toilet (Table 13).
The children most often used an AHG before eating, and washed their hands with
soap after going to the toilet (Table 13).
77
Table 13. Use of AHG and hand washing with soap and water in different situations by personnel and children at 68 CDCCs.
Data collected in questionnaires Personnel (N=68) Children (N=68)
AHG Soap1 AHG Soap1
At the start of the shift (n, (%)) 40 (59) 39 (57) 34 (50) 38 (56)
Before serving food2 (n, (%)) 59 (87) 47 (69) 51 (75) 45 (66)
After serving food2 (n, (%)) 10 (15) 25 (37) 1 (1.5) 35 (51)
Before changing diapers3 (n, (%)) 7 (12) 6 (10) 0 (0.0) 2 (3.4)
After changing diapers3(n, (%)) 47 (81) 36 (62) 9 (16) 22 (38)
Before blowing one’s nose (n, (%)) 5 (7.4) 5 (7.4) 0 (0.0) 1 (1.4)
After blowing one’s nose (n, (%)) 53 (78) 33 (49) 22 (32) 22 (32)
After cleaning secretions (n, (%)) 61 (90) 52 (76) - -
After going to the toilet (n, (%)) 49 (72) 59 (87) 29 (43) 60 (88)
At the end of a shift (n, (%)) 26 (38) 31 (46) 4 (5.9) 3 (4.4) 1Washing hands with soap and water or with water only 2The questions for the children were ‘Before eating’ and ‘After eating’. 3There were 58 persons taking care of children who wore diapers.
Forty-three out of the 128 respondents (34%) always washed their hands with
soap before using an AHG, and the majority, 120 out of 128 (94%), used soap
when their hands were visibly dirty. Seventeen (13%) always washed their hands
with soap before using the AHG. The day-care workers used an AHG from zero
to 50 times per day (mean 6.7 times per day, SD 6.8), and the children from zero
to eight times per day (mean 2.4 times per day, SD 1.7).
The personnel found the use of an AHG easy, the median assessment for ease
being 1.2 (interquartile range 1.0 to 1.4) and the median for usefulness 1.2
(interquartile range 1.0 to 1.4), given that a score of one on a Likert scale denoted
either easy or useful. The median for convenience was 2.4 (interquartile range 1.2
to 3.0).
One case of a fire had occurred when a worker had lit a fire while his hands
were still wet with AHG. In addition, 25 of the 128 respondents (20%) reported
consequences of AHG usage which they believed to be dangerous or harmful. The
most common (15 comments) concern was that children put their fingers in their
mouths or eyes after using the AHG. Three people mentioned skin problems due
to the use of an AHG, while other problems mentioned were splattering of the gel
when applying it (6 comments) and children sniffing their hands after using the
gel (one comment). The reasons for using alcohol for hand antisepsis were well
understood by the personnel, as 98 persons (77%) said it was to prevent the
78
spread of infectious diseases or to improve hygiene. Four respondents (3%) did
not know why an AHG was used.
79
6 Discussion
We found out that 5.8 to 17.5% of the patients hospitalized in pediatric infectious
diseases and general pediatric wards got HAI during hospitalization or within 72
hours after the discharge. The majority of these HAIs became evident at home,
the frequency of HAIs during hospitalization varying from 0.8 to 5.6%.
Gastroenteritis was the most common HAI during hospitalization, and it was
often caused by rotavirus. It has earlier been reported that during the epidemic
seasons 3.6 to 14% of children get gastrointestinal HAI and 4.2 to 17% get
respiratory HAI during hospitalization (Isaacs et al. 1991, Macartney et al. 2000).
6.1 Post-discharge follow-up in hospital-associated infection surveillance
According to our results, a large proportion of HAIs become evident after
discharge, including all the hospital-associated respiratory infections, which is
understandable in view of the known incubation period for RSV (4 to 6 days) and
the short mean hospitalization time among our patients (3 days). This emphasizes
the importance of follow-up after discharge from hospital to avoid
underestimating HAIs. Most surveys of HAIs in pediatric settings have not
included a systematic follow-up after discharge. In one survey where the follow-
up was conducted after discharge by means of phone calls, 144 out of 817
(17.6%) hospitalized children contracted hospital-associated gastroenteritis, one
third of which occurred at home, whereas in our study 80% of all HAIs occurred
after discharge (Grassano Morin et al. 2000). In our study the parents reported the
symptoms as they do in real life, without any special facilities or criteria, which
makes it possible to apply the results to an ordinary population. Earlier self-
assessing of symptoms of common cold has been shown to be reliable compared
to a physician’s observations (Macintyre & Pritchard 1989).
In total, the observed rate of HAIs during hospitalization (1.1%) in our study
was rather low as compared to the previously reported frequencies of pediatric
HAIs, which vary from 3.6% to 14%. The possible reason for the low rate of
HAIs in our study may be the frequent use of disinfection of the hands with AHG
by personnel at our ward. Many viruses, including rotavirus, are sensitive to hand
hygiene products containing 60% to 90% ethanol (Ansari et al. 1989, Bellamy et al. 1993, McDonnell & Russell 1999, Sattar et al. 2000). The use of alcohol hand
gel was recommended for routine decontamination of the hands in the CDC
80
guideline in 2002 (Boyce et al. 2002, Larson 1995). Even so, hand washing with
soap and water is still common in many institutions in comparison to the use of
alcohol hand gel, even during a hand hygiene campaign (Zerr et al. 2005).
The use of single rooms for most patients is probably another important part
of preventing HAIs at our ward. When rooms were shared during our study
period, patients with the same symptoms or with the same assumed pathogens
were placed in the same rooms in order to prevent the spread of pathogens. In
previous studies, a shared room has been shown to be a significant risk factor for
the transmission of rotavirus infection (Ford-Jones et al. 1990, Gaggero et al. 1992), but rotavirus also transmits between patient rooms (Nakata et al. 1996).
One of the lowest HAI frequencies during hospitalization alongside the results of
our present study has been reported by Ford-Jones et al., who observed a rate of
1.3% among patients admitted to an isolation ward, compared to 6.0% in the
whole pediatric hospital (Ford-Jones et al. 1989). Similarly, one of the lowest
HAI rates was reported in the infectious diseases ward in a pediatric hospital
(Pacini et al. 1987). We suggest that those results together with ours show that
low HAI rates can be achieved with good compliance to infection control
procedures.
The peaks in the HAI rate were found to coincide with high numbers of
respiratory infections, with decreases in the rate at times when we had primarily
gastroenteric patients. This is in accordance with the findings of Cavalcante et al. and may also reflect the fact that crowding of the ward is one of the most
important risk factor for HAI (Archibald et al. 1997, Cavalcante et al. 2006,
Moisiuk et al. 1998). Transmission of respiratory viruses can be better prevented
with single room bedding than that of enteric viruses. One reason for lower
number of HAIs during the gastroenteritis epidemics maybe reduced recognizion
of new gastrointestinal HAIs in patients who had gastroenteritis on admission. In
them diarrhea and vomiting after the discharge were counted as HAI only if
patient was reported to be symptom-free at the time of discharge.
6.2 Ward structure and the risk of hospital-associated infections
In the multicentre follow-up study we found clear differences in HAI frequencies
between the pediatric wards. In all wards most viral HAIs became evident after
discharge. The highest HAI frequency was found in the general pediatric ward in
Joensuu, where shared rooms were used most often, active cohorting according to
81
viral etiology was not performed, and where more than half of the patients had
been hospitalized for non-infectious diseases. By contrast, the lowest HAI rate
was found in the general pediatric ward in Basel, where the patients were older
and most of them were treated in a single room. Based on these results we suggest
that single room bedding is effective in preventing HAIs. It also seems that
treating patients with infectious diseases in a separate unit with active cohorting
according to viral etiology is advantageous compared with a general ward.
Our findings are in line with previous findings that a general pediatric ward
had a higher rate of gastrointestinal HAIs than specialized non-infectious wards
(Ford-Jones et al. 1990), and that the lowest HAI rate in a pediatric hospital was
documented in an infectious diseases ward, the majority of the HAIs being
gastrointestinal infections (Ford-Jones et al. 1989). Earlier it has been suggested
that better compliance with hygienic procedures explains lower number of HAIs
in infectious diseases wards compared with other pediatric wards (Pacini et al. 1987). It is also known that an increased number of roommates increases the risk
of hospital-associated gastroenteritis (Ford-Jones et al. 1990), whereas cohorting
of patients has been reported to reduce the risk of hospital-associated RSV
infection (Isaacs et al. 1991, Macartney et al. 2000).
The post-discharge cumulative occurrence of gastroenteritis in an infectious
disease ward with isolation rooms in Oulu was seen as exceeding that expected
after discharge, whereas the occurrence of respiratory infections was as expected
in the general population. In the other wards the occurrence of both
gastrointestinal and respiratory HAIs exceeded that expected after hospitalization,
this phenomenon being most pronounced in the general ward in Joensuu. With the
use of single rooms we could prevent well the spread of respiratory viruses, but
gastrointestinal viruses spread despite this precaution. By analyzing rotavirus
strains it has been shown that rotavirus spreads between patients located in
different rooms in pediatric wards (Nakata et al. 1996). However, cohorting
reduces the transmission of RSV (Isaacs et al. 1991, Macartney et al. 2000).
Rotavirus survives well on environmental surfaces, making spread via indirect
contact possible and infection control more demanding. Another challenge is that
asymptomatic children can excrete rotavirus before and after a symptomatic
infection (Goldmann 1992). Our findings are in accordance with these spreading
mechanisms for infections.
When we analyzed ward-specific risk factors for HAI, young age and longer
duration of hospitalization were found to be risk factors in most wards, as seen in
previous studies (Bennet et al. 1995, Cavalcante et al. 2006, Ford-Jones et al.
82
1990). Young children are at increased risk for HAIs as they are still developing
immunity to common pathogens and get viral infections easily. Treatment in a
shared room appeared to be associated with an increased risk of HAI during
hospitalization in the infant ward in Basel. In the wards that used mainly single
rooms, the association was not statistically significant. Another factor associated
with the risk of HAI was the use of antibiotics. This may be partly a matter of
misinterpretation of the symptoms, as it is not always possible to distinguish
gastroenteritis signs and symptoms due to HAI from the side effects of
antibiotics.
Alcohol hand rubs play an important role in hand hygiene in hospitals, and
besides their efficacy against bacteria, they are effective against common viral
pathogens, among them also non-enveloped viruses; adenovirus, rhinovirus and
rotavirus (Ansari et al. 1989, Bellamy et al. 1993, Boyce et al. 2002, McDonnell
& Russell 1999, Sattar et al. 2000). A lower number of gastrointestinal HAIs has
been shown to be associated with the use of alcohol hand rubs (Zerr et al. 2005).
Alcohol hand rubs were actively used in each of the wards studied here. Although
a high patient-to-nurse ratio has been shown to increase the rate of hospital-
associated gastroenteritis (Stegenga et al. 2002), there were no marked
differences in this respect between the wards we studied.
The strength of our study was that the follow-up of viral HAIs was done both
in hospital and for one week after discharge. The post-discharge follow-up
enabled us to observe viral HAIs that were most likely acquired already in
hospital but became evident after an incubation period at home. In addition, we
collected data prospectively by using similar questionnaires in three different
hospitals for two years in order to cover the seasonal variation in infectious
diseases and make data comparable between the wards.
The limitation of our study was that we might have overestimated the overall
occurrence of HAIs appearing after discharge by calculating all infection
symptoms reported by parents within 72 hours after discharge as HAIs. It is
impossible to define accurately what proportion of the infection symptoms
registered after discharge by the parents were HAIs and which were coinciding
viral infections as they occur in the general population. However, we saw an
increase in infection symptoms above the expected line of infections in
population. The response bias may also have affected the results in different ways
in the different wards since those who did not return the questionnaires had more
HAIs (as assessed by active follow-up by telephone) than those who returned
83
them in Basel, whereas we found the opposite earlier in Oulu. In Joensuu, the
child’s condition at the time of discharge was not recorded and we assumed that
all children were still symptomatic when discharged. Therefore we may have
underestimated the occurrence of new symptoms in Joensuu.
Data collection methods were different in the hospitals under study.
Electronic questionnaires were used in the two study centers in Finland whereas
questionnaires on paper were used in Basel. Electronic questionnaire response
rate was higher than those for the paper versions, 81% versus 59%. It has been
found earlier that data collected by electronic means are equivalent in content to
data collected using paper questionnaires but have less missing data (Bushnell et al. 2003, Junker et al. 2008, Ryan et al. 2002).
6.3 Continuous surveillance for hospital-associated infections
We found out that electronic data collection was a convenient way of performing
a continuous post-discharge follow-up for HAIs, as it both yielded a higher
participation rate and lowered the costs. The parents accepted the electronic data
collection methods well, so that 84% of the parents participated in the post-
discharge electronic data collection, whereas the response rate achieved by
conventional methods was 23 percentage points lower. Most of the parents in the
electronic follow-up chose to answer by e-mail, but all the electronic options
showed high participation rates. Electronic follow-up enabled us to send
reminders to parents, which may partly explain the higher participation rate.
Earlier, respondents have found electronic questionnaires convenient, and
there was a high correlation between the data collected by electronic
questionnaires and questionnaires on paper (Bushnell et al. 2003). The use of
computers in answering did not cause anxiety even though many of the
respondents used computers infrequently (Cook et al. 2004). Patients prefer
electronic data collection to paper system when it is done using computers, but
data collection with paper to a telephone or interactive voice response system.
Using electronic data collection reduces the study costs as no data entry is needed,
and electronically collected data are of better quality with fewer lacking answers
(Ryan et al. 2002, Velikova et al. 1999, Welker 2007). In daily symptom
recording data collected using an electronic or telephone diary has been shown to
be more accurate than those in paper diaries, electronic diaries offering the
possibility of recording the time the diaries were filled in (Lauritsen et al. 2004).
84
Data entry was the most laborious part of the conventional data collection
procedure, whereas with electronic questionnaires we could take the data directly
from the hospital database by record linkage. No additional data entry work was
needed for the post-discharge data either, which made the data easily available for
showing trends in HAI rates. It has been shown previously that electronic
methods can reduce the costs of data collection in clinical trials by as much as
55% (Pavlovic et al. 2009), and that a saving of USD0.63 per patient can be
achieved in surgical wound infection surveillance when automated data entry with
optical scanning is used (Smyth et al. 1997). In our study the data collection costs
decreased by 17% a year with electronic follow-up, implying a saving of €2.60
per patient. These calculations naturally included only the costs in terms of health
care facilities. We estimated that the parents spent approximately the same
amount of time answering the electronic questionnaire as they did filling in the
paper questionnaire.
In this case the electronic surveillance was administered by a private
collaborator, and we paid a fixed price of €600 per month for it. In addition,
besides normal patient care, nurses spent some time on data collection and
informing parents about the arrangements for the post-discharge period, which
increased the expenses. The most expensive parts of the electronic data collection
were the phone calls made to some parents in order to collect post-discharge data
and the reminders sent to parents. Both were included in the monthly price,
however, only 17% of the parents chose phone calls as primary method of
answering. As the data were collected in an electronic form, no data entry was
needed by the private company. Our experience was that electronic data collection
is a recommendable way of organizing HAI surveillance. Use of electronic data
collection led to reduced costs even when we used a private collaborator to
organize it. When electronic means are used for HAI surveillance, an automatic
alarm can be used to identify sudden changes in HAI rates to allow quick
responses. It is probable that electronic data collection will become more common
as time goes by, and most of the costs are caused by following up participation
and reminding those who do not answer.
6.4 Use of alcohol hand gels among children
AHGs were shown to be a safe option for hand hygiene in child care facilities.
Ethanol was not absorbed when the children at the CDCCs used an AHG for hand
85
disinfection in the experimental trial, even though there were as many as 30
contacts between the hands and the mucous membranes. There was no sign of any
elevated alcohol concentration in the children’s alcometer measurements,
although theoretically the amount of alcohol used could have caused a measurable
rise in blood alcohol (De Martinis et al. 2006).
Attendance at a CDCC is a significant risk factor for infectious diseases such
as diarrhea, common colds, otitis media and pneumonia (Louhiala et al. 1995,
Louhiala et al. 1997). It is possible to reduce the number of infections at CDCCs
by improving the practices of the personnel in changing diapers, serving food and
especially hand hygiene (Uhari & Mottonen 1999), and the most effective way of
achieving the latter and preventing the spread of viruses is to use AHGs (Boyce et al. 2002). In our study we found this to be safe in CDCC environment.
Two cases of toxic absorption of alcohol in children have been described
earlier, that of a pre-term infant, where this condition may explain the toxic
absorption of alcohol and the resulting skin damage (Harpin & Rutter 1982), and
that of a two-year-old girl in whom a keloidal scar was exposed overnight to a
wrapping containing alcohol (Puschel 1981). Cases of percutaneous absorption of
disinfectants have been documented after skin cleaning with hexachlorophene and
chlorhexidine in newborn and premature babies (Cowen et al. 1979, Curley et al. 1971, Powell et al. 1973), and this issue has recently been re-evaluated in
connection with the wider use of chlorhexidine in obstetrics and neonatal care in
developing countries in order to reduce neonatal mortality (Mullany et al. 2006).
A single case of toxic use of AHG by a child in CDCC has been reported in
Finland (Lukkarinen & Kujari 2009). A four-year-old girl was brought to
emergency room from CDCC because of lowered consciousness and
inappropriate behavior. No other cause for the condition was recovered, but blood
ethanol was found to be elevated up to 1.9‰. It came out that the girl tended to
lick her hands after using AHG, and liked the taste of it. To achieve this high a
level of blood ethanol, an intake of an amount of 30 mL of AHG with 70%
ethanol was needed for her weight. The results from our trial confirm that when
AHG is used with normal dosing (1.5 or 3.0 milliliters), no measurable level of
ethanol is absorbed even when there are several contacts to mucous membranes.
The reasons for using AHGs are well understood among CDCC personnel,
and their use is taken as a significant improvement. It has been shown earlier that
secondary transmission of infections to family members can be reduced by using
an AHG at home if there are children who attend a CDCC (Lee et al. 2005,
Sandora et al. 2005), and a recent review of the role of AHGs in hand hygiene in
86
home and community settings has recommended its active use to prevent the
transmission of infectious diseases (Bloomfield et al. 2007).
Our study confirmed that the use ethanol containing AHGs is safe in children.
There had been one incident of fire in CDCC when matches were used while
hands were still wet with AHG. A few similar cases have been reported in
Germany; some of the fire incidents were due to vandalism (Kramer & Kampf
2007). In the USA no fire incidents were reported after a couple of years of AHG
use in hospitals (Boyce & Pearson 2003). These data suggest that the risk of fire
incidents related to AHGs is minimal. Other ingredients used in the hand gels are
glycerin and often glycerylcocoate. These skin-conditioning agents are commonly
used in cosmetic products and have been found to be safe in animal and clinical
test (Johnson Jr 2004).
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7 Conclusions
We found that a remarkable number of children get a HAI, the HAI rate being the
highest in a mixed pediatric ward where 17% of patients got a new infection. The
majority of these infections become symptomatic after discharge and they remain
unreported unless HAI follow-up is extended to cover the immediate time at
home after hospitalization. Viral HAI frequency was highest in the general
pediatric ward, suggesting that patients with contagious diseases should be treated
separately. In the wards with lowest HAI rates the majority of patients were in
single rooms and active cohorting was done. These isolation practices were
especially beneficial in preventing respiratory HAIs.
Electronic follow-up for HAIs is a feasible way of doing HAI surveillance
both during hospitalization and after discharge. Post-discharge follow-up is
needed to find out the number of viral infections children get after being
hospitalized. Main focus in infection control is still on bacterial infections despite
the known challenges in prevention of transmission of viruses. Documentation of
viral HAIs is important in order to get more focus on the prevention of spread of
viruses in health care settings. Based on the experiences of this study both a better
response rate and lower costs were achieved with HAI follow-up with electronic
questionnaires. With electronic follow-up continuously collected data are easily
available, showing the trends in HAI rates, which helps us to identify unexpected
peaks in HAI rates so that quick responses can be made. To facilitate this, an
automatic alarm can be set to recognize increased HAI rates. Data is also
available to be used in giving feedback to HCWs to maintain the motivation for
infection control. Continuously collected data will facilitate in measuring the
effect of future interventions to reduce HAI rates.
AHGs are important in preventing viruses from spreading both in healthcare
settings and other facilities with a high number of viral infections spreading. Use
of AHGs was found to be a safe and convenient method for hand hygiene at
CDCCs. Based on our results it can be concluded that the use of AHGs at CDCCs
can be recommended for the children as well as the staff, as all the alcometer
results were below the measurement threshold in children after hand rub.
88
89
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Original articles I Kinnula SE, Renko M, Tapiainen T, Knuutinen M & Uhari M (2008). Hospital-
associated infections during and after care in a paediatric infectious diseases ward. J Hosp Infect 68: 334–340.
II Kinnula S, Buettcher M, Tapiainen T, Renko M, Vepsäläinen K, Lantto R, Heininger U & Uhari M (2012). Hospital-associated infections in children: a prospective post-discharge follow-up survey in three different paediatric hospitals. J Hosp Infect 80: 17–24.
III Kinnula S, Renko M, Tapiainen T, Pokka T & Uhari M (2012) Post-discharge follow-up of hospital-associated infections in paediatric patients with conventional questionnaires and electronic surveillance. J Hosp Infect 80: 13–16.
IV Kinnula S, Tapiainen T, Renko M & Uhari M (2009). Safety of alcohol hand gel use among children and personnel at a child day care center. Am J Infect Control 37: 318–321.
Original publications are reprinted with the permission of Elsevier.
They are not included in the electronic version of the dissertation.
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1159. Hyry, Marjo (2012) Lysyl hydroxylases 1 and 2 : Characterization of their in vivoroles in mouse and the molecular level consequences of the lysyl hydroxylase 2mutations found in Bruck syndrome
1160. Laatio, Liisa (2012) In search of new prognostic molecular markers in ovariancancer
1161. Klintrup, Kai (2012) Inflammation and invasive margin in colorectal cancer
1162. Buler, Marcin (2012) Energy sensing factors modulate expression of inflammatorymediators, mitochondria acetylation and drug metabolism in the liver
1163. Salo, Jarmo (2012) Long-term consequences and prevention of urinary tractinfections in childhood
1164. Ronkainen, Veli-Pekka (2012) Effects of chronic hypoxia on myocardial geneexpression and function
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UNIVERS ITY OF OULU P.O.B . 7500 F I -90014 UNIVERS ITY OF OULU F INLAND
A C T A U N I V E R S I T A T I S O U L U E N S I S
S E R I E S E D I T O R S
SCIENTIAE RERUM NATURALIUM
HUMANIORA
TECHNICA
MEDICA
SCIENTIAE RERUM SOCIALIUM
SCRIPTA ACADEMICA
OECONOMICA
EDITOR IN CHIEF
PUBLICATIONS EDITOR
Senior Assistant Jorma Arhippainen
Lecturer Santeri Palviainen
Professor Hannu Heusala
Professor Olli Vuolteenaho
Senior Researcher Eila Estola
Director Sinikka Eskelinen
Professor Jari Juga
Professor Olli Vuolteenaho
Publications Editor Kirsti Nurkkala
ISBN 978-951-42-9899-8 (Paperback)ISBN 978-951-42-9900-1 (PDF)ISSN 0355-3221 (Print)ISSN 1796-2234 (Online)
U N I V E R S I TAT I S O U L U E N S I S
MEDICA
ACTAD
D 1165
ACTA
Sohvi Kinnula
OULU 2012
D 1165
Sohvi Kinnula
HOSPITAL-ASSOCIATED INFECTIONS AND THE SAFETY OF ALCOHOLHAND GELS IN CHILDREN
UNIVERSITY OF OULU GRADUATE SCHOOL;UNIVERSITY OF OULU, FACULTY OF MEDICINE,INSTITUTE OF CLINICAL MEDICINE,DEPARTMENT OF PAEDIATRICS