Bacterial carriage and respiratory tract infections in subjects ≥ 60 years during an influenza season: Implications for the epidemiology of Community Acquired Pneumonia and influenza vaccine effectiveness

Abstract

During the 2010/11 influenza season an epidemiological prospective cohort active study was organized, to evaluate etiologic role due to the main bacteria and viruses causing Community Acquired Pneumonia (CAP) and Influenza like-illness (ILl) in elderly and to explore the role of the bacterial nose-pharingeal carriage in subjects with respiratory tract infections.
An integrated active surveillance of a cohort of adults aged > or = 60 y based on a double prospective and retrospective mechanisms of capture of ILl and CAP cases was organized. Samples were collected from all ILI and CAP prospectively identified. The samples were be tested by multiplex PCR for detection of the main respiratory bacteria and viruses.
The study population amounted to 2,551 adults. During the 2010/11 influenza season, the ILl cumulative incidence was 4.2%, that was twice higher than that calculated by regional sentinel-based Influenza surveillance system during the 2010/11 season in the elderly (2.2%). Among 45 patients with ILI of which had been collected the swab, 17 (37.8%) were positive for influenza viruses and 2 (4.4%) for RSV, 6 (13.3%) patients carried Streptococcus pn and 6 (13.3%) Haemophilus in. In the same period, 7 CAP cases were observed; 3 cases were prospectively identified and samples were collected, while 4 cases were retrospectively detected. The CAP cumulative incidence was 0,3%. The influenza vaccine effectiveness in prevention of laboratory-confirmed influenza emerged by our study was 61%, in condition of good antigenic matching between vaccine and circulating strains observed during the 2010/11. These data contribute to better defining the epidemiological picture of upper and lower respiratory tract infections, fundamental information in light of the recent introduction of new vaccines for prevention of pneumonia in the elderly, including 13-valent conjugate pneumococcal vaccine.

Full text

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J PREV MED HYG 2012; 53: 94-97
Introduction
Community Acquired Pneumonia (CAP) and Influenza
have a relevant impact in terms of Public Health espe-
cially in elderly and high risk groups. Combined, influ-
enza and pneumonia rank as the sixth leading cause of
death worldwide and as the leading infectious cause of
death [1, 2]. Synergism exists between influenza virus
and bacterial pathogens, in particular Streptococcus pn,
accounting for excess mortality during influenza epidem-
ics. The synergistic interaction between influenza virus
and streptococcus pn is a multifactorial process. What
these factors are and what the relative contribution of
each is to excess morbidity and mortality is poorly under-
stood [3]. Furthermore, other respiratory viral infections
may facilitate secondary bacterial infections through
different mechanisms, largely little known [4]. Further
comprehensive studies of the viral and bacterial etiol-
ogy of upper and lower respiratory tract infections are
required both for estimate the real burden of the different
agents and for setting up a prevention and control strate-
gies for CAP. In order to evaluate etiologic role due to
the main bacteria and viruses causing CAP and Influenza
like-illness (ILI) in elderly and to explore the role of the
bacterial nose-pharingeal carriage in subjects with res-
piratory tract infections, an epidemiological, lab-based,
population-based, prospective cohort active study was
organized during the 2010/11 influenza season. The sec-
ondary aims of the study included the estimation of the
incidence of CAP and ILI in adults older than 60 years,
the evaluation of the role of the potential risk-factors as-
sociated with CAP and ILI and the study of the pattern of
co-infections between respiratory viruses and bacteria.
Methods
Procedures of the Study. Twenty General Practitioners
(estimated surveyed ≥ 60 year adults: > 9,000) invited
eligible subjects aged ≥ 60 years to participate into the
Sh o r t a r t I c l e
Bacterial carriage and respiratory tract infections
in subjects ≥ 60 years during an influenza season:
implications for the epidemiology of Community
Acquired Pneumonia and influenza vaccine
effectiveness
F. ANSALDI , D. DE FLORENTIIS, V. PARODI, E. RAPPAZZO, M. COPPELLI, M. MARTINI,
C. ALICINO, P. DURANDO, G. ICARDI
Department of Health Sciences, University of Genoa, Italy
Key words
Influenza•Pneumococcus•Elderly
Summary
Introduction. During the 2010/11 influenza season an epidemio-
logical prospective cohort active study was organized, to evalu-
ate etiologic role due to the main bacteria and viruses causing
Community Acquired Pneumonia (CAP) and Influenza like-illness
(ILI) in elderly and to explore the role of the bacterial nose-phar-
ingeal carriage in subjects with respiratory tract infections.
Methods. An integrated active surveillance of a cohort of adults
aged ≥ 60 y based on a double prospective and retrospective
mechanisms of capture of ILI and CAP cases was organized. Sam-
ples were collected from all ILI and CAP prospectively identified.
The samples were be tested by multiplex PCR for detection of the
main respiratory bacteria and viruses.
Results and discussion. The study population amounted to 2,551
adults. During the 2010/11 influenza season, the ILI cumulative
incidence was 4.2%, that was twice higher than that calculated
by regional sentinel–based Influenza surveillance system dur-
ing the 2010/11 season in the elderly (2.2%). Among 45 patients
with ILI of which had been collected the swab, 17 (37.8%) were
positive for influenza viruses and 2 (4.4%) for RSV, 6 (13.3%)
patients carried Streptococcus pn and 6 (13.3%) Haemophilus in.
In the same period, 7 CAP cases were observed; 3 cases were
prospectively identified and samples were collected, while 4 cases
were retrospectively detected. The CAP cumulative incidence was
0,3%. The influenza vaccine effectiveness in prevention of lab-
oratory-confirmed influenza emerged by our study was 61%, in
condition of good antigenic matching between vaccine and circu-
lating strains observed during the 2010/11. These data contribute
to better defining the epidemiological picture of upper and lower
respiratory tract infections, fundamental information in light of
the recent introduction of new vaccines for prevention of pneumo-
nia in the elderly, including 13-valent conjugate pneumococcal
vaccine.
The full article is free available on www.jpmh.org

RESPIRATORY TRACT INFECTIONS IN ELDERLY
95
study, coordinated by the Department of Health Sci-
ences, University of Genoa. At this Centre, subjects
received information about aims and procedures of the
study; inclusion and exclusion criteria were checked
by the investigators of the Centre and written informed
consent was obtained for each participants. Inclusion
criteria included age ≥60 years, written informed con-
sent, availability to follow study procedures, vaccination
with 23-valent polysaccharides pneumococcal vaccine
performed not less than 5 years before the study entry,
participation to any other clinical trial, any particular
clinical conditions that could interfere with the study ac-
tivities and aims. Demographic and medical data were
collected by the investigators and the case definitions
of clinically suspected CAP and ILI were illustrated
to the eligible participants (see the following section).
Between November 2010 and April 2011, each partici-
pant who presented a respiratory tract infection episode
should phone to the Department of Health Sciences, us-
ing a dedicated phone-number (on call seven days per
week, between 8 a.m. to 8 p.m.). A health care worker
of the Department of Health Sciences, in agreement with
the general practitioner, went to the patient home or to
hospital to obtain further information about her/his clini-
cal conditions and to collect biological samples for the
virological and microbiological assays: these procedures
included a nase-pharingeal swab, a urine and a blood
(0.5 ml) sample for patients with suspected CAP and a
nase-pharingeal swab for all the patients presenting ILI.
Moreover, an active phone-survey was performed by the
study personnel of the Department of Health Sciences,
to monitor the medical conditions of the enrolled par-
ticipants, and to verify the potential occurrence of any
suspected clinical respiratory syndrome not signaled by
phone by the patient, yet. A risk-assessment analysis of
all the main factors and conditions reported by the pa-
tients presenting CAP and ILI will be performed.
Definitions of CAP and ILI. Suspected CAP was consid-
ered in any patient with an acute illness and symptoms
suggesting lower respiratory tract infection, including a
new cough with high fever or chills, pleuritic chest pain,
dyspnea or prolonged fever.
Confirmed CAP was defined as a new radiological infil-
trate associated with one major criteria (cough, expecto-
ration and fever) or two minor criteria (dyspnea, pleuritic
pain, altered mental status, pulmonary consolidation on
auscultation, and leukocytosis).
ILI was defined by the presence of fever > 38°C and at
least one other symptom (headache, malaise, myalgia,
chills or sweats, asthenia) and one respiratory symptom
(cough, sore throat, nasal congestion or runny nose), ac-
cording Italian surveillance network guideline.
Laboratory assays. Collected biological samples will be
tested by multiplex PCR for detection of the main respi-
ratory bacteria and viruses. The detection of Streptococ-
cus pn, Legionella pn, Chlamidia pn, Haemophilus in,
Mycoplasma pn, Bordetella pertussis and by type A and
B Influenza Virus, Respiratory Syncytial Virus, Parain-
fluenza virus, Adenovirus, Coronavirus, Metapneumov-
irus, Rhinovirus will be performed using molecular tests
of genic amplification multiplex Seeplex PneumoBacter
ACE (Seegene) and Seeplex RV12 ACE (Seegene), re-
spectively [5]. Influenza viruses will be characterized
using HI assay and sequence analysis of genes codifying
surface glycoproteins (HA and NA).
Results
The study population amounted to 2,551 adults aged more
than 59 years (≥ 60 years). Age distribution, risk factors
for influenza complication and pneumonia, and influenza
vaccination coverage in the study population is reported in
Table I. Age group including subjects older than 79 years
was the largest and showed the highest prevalence of pa-
tients with chronic heart failure (8%) and the highest in-
fluenza vaccine coverage (87%). Subjects aged between
75 and 79 years showed the highest prevalence of chronic
heart (13%) and pulmonary chronic (8%) diseases, while
diabetes was more frequent in 70-74 year adults (19%).
The influenza vaccine coverage observed among the
2,551 ≥ 60 year adults (74%) was very close to the 2010
WHO objective for subjects older than 65 years (75%).
The WHO objective was reached in 70-74 (78%), 75-79
(81%) and ≥ 80 (87%) year age groups.
Tab. I. Age distribution, risk factors for influenza complication and pneumonia, and influenza vaccination coverage in the study population.
Age group (yrs)
60-64 65-69 70-74 75-79 ≥80 Unknown All
Enrolled subjects 378
(15%)
438
(17%)
547
(21%)
481
(19%)
628
(25%)
79
(3%)
2,551
(100%)
Risk factors
Chronic heart disease (%) 6 7 10 13 11 10
Chronic heart failure (%) 1 2 1 3 8 3
Pulmonary chronic dis. (%) 2 4 6 8 7 5
Diabetes (%) 14 15 19 16 15 16
Previous Hospital. (%) 17 16 17 17 17 17
Influenza vaccination* (%) 48 67 77 81 87 74
* considering only subjects whose age was known

F. ANSALDI ET AL.
96
During the 2010/11 influenza season, 108 ILI cases were
observed; 45 cases were prospectively identified and
samples were collected, while 63 cases were retrospec-
tively detected by the active phone-survey foreseen by
the protocol. The cumulative incidence of ILI was 4.2%
(95% C.I. 3.5-5.1%). ILI cumulative incidence accord-
ing age groups was shown in Figure 1. Among 45 pa-
tients with ILI of which had been collected the swab, 17
(37.8%) were positive for influenza viruses and 2 (4.4%)
for RSV. Typing and sub-typing of influenza viruses al-
lowed to identify 10 A(H1N1) pdm 09, 3 A(H3N2) and
4 B viruses; molecular characterization of hemaggluti-
nine confirmed the good matching between circulating
strains and vaccine viruses.
The cumulative incidence of laboratory-confirmed influ-
enza was 0.7% (95% C.I. 0.4-1.1%). If the proportion of
samples positive for influenza we observed among patients
with ILI of which had been collected the swab was applied
to all cases of ILI, the incidence of laboratory-confirmed
influenza would rise to 1.6% (95% C.I. 1.2-2.2%).
According influenza vaccination status, 0.5% (95% C.I.
0.2-0.9%) and 1.2% (95% C.I. 0.6-2.2%) among vac-
cinated and non-vaccinated subjects, respectively, had
laboratory-confirmed influenza. The influenza vaccine
effectiveness in prevention of laboratory-confirmed in-
fluenza was 61.3% (95% C.I. 0.1-85%).
Among 45 adults with ILI of which had been collected
the swab, 6 (13.3%) patients carried Streptococcus pn
and 6 (13.3%) Haemophilus in.
Between November 2010 and April 2011, 7 CAP cases
were observed; 3 cases were prospectively identified
and samples were collected, while 4 cases were retro-
spectively detected by the active phone-survey foreseen
by the protocol. The cumulative incidence of CAP was
0.3% (95% C.I. 0.1-0.6%). Among 3 patients with CAP
of which had been collected the swab, 1 was positive for
A(H1N1) pdm 09 influenza virus.
Discussion
By coupling a sentinel-based and active epidemiologi-
cal surveillance for the detection and documentation
of ILI and CAP cases with a virological and bacterio-
logical surveillance for laboratory confirmation of the
etiology, our study precisely defined the impact of up-
per and lower respiratory tract infections in adults aged
≥ 60 years.
Some potential limitations of this investigation should
be mentioned. First, the study focused on only a sin-
gle health care setting (primary care facilities) and dis-
regarded the burden of ILI and CAP on hospitals and
emergency departments. Second, only adults seeking
health care or remembering ILI or CAP events were
identified by surveillance system, resulting in an un-
derestimation of incidence rates and in potential bias
(because study selection may have been influenced by
factors such as the socioeconomic status or the severity
of the disease). Third, the small study population lim-
ited the precision of some estimates, such as vaccine
effectiveness.
Despite these limitations, the design of surveillance sys-
tem allowed a very high sensitivity in detection of ILI
and CAP cases and an estimation both of the role played
by the different etiologic agents and of vaccine effec-
tiveness.
Our estimation of ILI cumulative incidence was 4.2%,
that was twice higher than that calculated by regional
sentinel-based Influenza surveillance system during the
2010/11 season in the elderly (2.2%) and was higher
than the incidence registered by Italian sentinel-based
Influenza surveillance system in this age-group in the
last decade [6]. The incidence of laboratory-confirmed
influenza estimated in the elderly if a swab was avail-
able for every ILI cases (1.6%) was higher than that
observed in England, in Australia and Hong Kong and
similar to that observed in Norway and New Zealand
in serological studies after the first pandemic wave [7].
Although these data should be confirmed by other stud-
ies, they would change the perception of the impact of
ILI and influenza in elderly populations where high
vaccine coverage have been achieved.
The CAP incidence we observed, corresponding to 6.4
cases/1,000 year*person using person time of follow-
up as denominators, was in line with that observed in
Europe and North America: incidence rates varying be-
tween 2-40 cases/1,000 elderly person*year have been
reported during the last two decades [8-12].
As far as the etiologic role played by the different viruses
and bacteria, in our study, the responsibility of influenza
viruses was preeminent: 38% and 33% of ILI and CAP,
respectively, were due to A(H1N1) pdm 09, AH3N2) or
B influenza viruses. Worthy of note and deserving of
further study is the frequent carriage of Streptococcus pn
and Haemophilus in observed in subjects with ILI.
The estimation of effectiveness of the seasonal influenza
vaccine to prevent ILI confirmed as influenza, among the
target population for the influenza vaccine is an ongoing
challenge. Influenza virus is constantly evolving and the
antigenic composition of vaccines requires annual update.
Therefore, vaccine effectiveness estimates from previous
years cannot be used to measure the performance of the cur-
rent year’s vaccine. The influenza vaccine effectiveness in
prevention of laboratory-confirmed influenza emerged by
our study winter was 61%, in condition of good antigenic
matching between vaccine and circulating strains observed
during the 2010/11. I-MOVE (Influenza Monitoring Vac-
cine Effectiveness in Europe), a multicentre case-control
study based on sentinel practitioner surveillance networks
in eight European Union Countries, estimated 2010/11 in-
fluenza vaccine effectiveness against medically-attended
ILI laboratory-confirmed as influenza. In I-MOVE study,
adjusted vaccine effectiveness in adults aged more than 60
years was 60% (95% C.I. 17-81%). Interestingly, although
the approaches, the study design and the population used
in our study and in I-MOVE are different, the estimation of
vaccine effectiveness was overlapping, consolidating the
data published by Kissling [13].
These data contribute to better defining the epidemio-
logical picture of upper and lower respiratory tract in-
fections, fundamental information in light of the recent

RESPIRATORY TRACT INFECTIONS IN ELDERLY
97
introduction of new vaccines for prevention of pneu-
monia in the elderly, including 13-valent conjugate
pneumococcal vaccine. Continued surveillance will
be crucial to further understand the mechanisms of in-
teraction between viruses and bacteria in determining
both upper and lower respiratory tract infections and
the effect of the implementation of pneumococcal vac-
cination.
n Received on January 24, 2012. Accepted on March 5, 2012.
n Correspondence: F. Ansaldi, DiSSal, University of Genoa,
via Pastore 1, 16132 Genoa, Italy - E-mail: filippo.ansaldi@unige.it
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