Tamaki, R. et al.

Paper:

Comprehensive Etiological and Epidemiological Study on

Acute Respiratory Infections in Children:
Providing Evidence for the Prevention and Control of
Childhood Pneumonia in the Philippines
Raita Tamaki∗,∗∗∗,† , Veronica L. Tallo∗∗ , Alvin G. Tan∗∗ , Mark Donald C. Reñosa∗∗ ,
Portia P. Alday∗∗ , Jhoys M. Landicho∗∗ , Marianette T. Inobaya∗∗ , Mayuko Saito∗ ,
Taro Kamigaki∗, Michiko Okamoto∗ , Mariko Saito∗ , Clyde Dapat∗ ,
Bindongo P. P. Dembele∗ , Mary Lorraine S. Mationg∗∗ ,
Melisa U. Mondoy∗∗ , Socorro P. Lupisan∗∗ , and Hitoshi Oshitani∗
∗ Tohoku University Graduate School of Medicine
2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
† Corresponding author, E-mail: tamaki@med.tohoku.ac.jp
∗∗ Research Institute for Tropical Medicine, Alabang Muntinlupa City, Philippines
∗∗∗ Nagasaki Women’s Junior College, Nagasaki, Japan

[Received March 21, 2018; accepted May 2, 2018]

Childhood pneumonia has been the leading cause of
morbidity and mortality for decades. Although sub-
stantial progress in the understanding of risk factors
and etiology of pneumonia has been made, childhood
pneumonia remains the major cause of death in chil-
dren, accounting for 900,000 of the estimated 6.3 mil-
lion child deaths worldwide in 2013. More than 90%
of all episodes of clinical childhood pneumonia world-
wide occur in low and middle-income countries. More
effective and feasible interventions need to be devel-
oped and made widely available for such countries,
including the Philippines. Comprehensive research,
including etiological and epidemiological studies for
assessments of risk factors and thereby, intervention
studies to reduce the impact of childhood pneumonia
are required in hospital settings, as well as commu-
nity settings, consistently. A research project entitled
“comprehensive etiological and epidemiological study
on acute respiratory infections in children: providing
evidence for the prevention and control of childhood
pneumonia, the Philippines” was conducted under
SATREPS (Science and Technology Research Partner-
ship for Sustainable Development), which is a funding
scheme to promote international joint research focus-
ing on global issues. This project was implemented in
four sentinel hospitals, with some community settings,
in the Philippines between April 2011 and March 2017,
incorporating five sub-components: etiological study,
disease burden study, risk factor analysis, interven-
tion study, and its evaluation. In this paper, we in-
troduce the research project of SATREPS focusing on
the methodologies, progress, and obtained evidence.
Keywords: pediatric pneumonia, acute respiratory in-
fections, Integrated Management of Childhood Illness
(IMCI), low and middle-income countries, Science and
Technology Research Partnership for Sustainable Devel-
opment (SATREPS)
1. Introduction
Of the 6.3 million pediatric deaths in 2013, it is
estimated that 900,000 died from pneumonia world-
wide [1]. More than 90% of all episodes of clinical pneu-
monia in young children worldwide occur in low and
middle-income countries (LMICs), where the incidence
is estimated at 0.22 episodes per child-year, in contrast
to 0.015 episodes per child-year in high-income coun-
tries [2]. In the World Health Organization (WHO) West-
ern Pacific region, 0.11 pneumonia episodes per child-
year with 61,900 pneumonia-related deaths in children
less than 5 years of age were estimated in 2011. The ma-
jority (>75%) of pneumonia deaths occurred in six coun-
tries including the Philippines [3]. To tackle the burden
of childhood pneumonia, reliable information about the
etiology and the epidemiology for childhood pneumonia
is an essential foundation for national and international
health policy [4].
The understanding of the true burden of etiological
factors for childhood pneumonia in the LMICs is lim-
ited because childhood pneumonia are diagnosed with-
out laboratory confirmation [5]. The limited data avail-
able on the causative organisms have identified Strepto-
coccus pneumoniae (S. pneumoniae) and Haemophilus in-
fluenza (H. influenza) as the major bacterial pathogens,
and respiratory syncytial virus (RSV) as the leading viral

740 Journal of Disaster Research Vol.13 No.4, 2018

 Comprehensive Etiological and Epidemiological Study on Acute Respiratory
Infections in Children: Providing Evidence for the Prevention and Control of
cause. RSV has been identified in 15–40% of pneumo-
nia or bronchiolitis cases in children admitted to hospi-
tals in LMICs, followed by influenza A (FLUA) and in-
fluenza B (FLUB), parainfluenza and human adenovirus
(HAdV) [6]. From recent studies among children in
LMICs, several new viruses have been considered as
pathogens for respiratory infections. Human metapneu-
movirus (HMPV) shows similar clinical symptoms as that
of RSV and may cause severe respiratory infection in chil-
dren less than 2 years old [7]. In the Philippines, the
site-limited local studies on etiology and epidemiology of
childhood pneumonia showed S. pneumoniae and H. in-
fluenza as the most common bacterial causes of childhood
pneumonia [8]. However, investigations on the viral eti-
ology of pneumonia in the Philippines are limited.
A better understanding of the underlying risk fac-
tors associated with childhood pneumonia is important.
Risk factors associated with severe pneumonia commonly
identified in LMICs include socioeconomic status, acces-
sibility to care, crowding, and indoor air pollution [9].
Risk factors with high prevalence in the WHO Western
Pacific region include a lack of exclusive breastfeeding,
cigarette smoke and air pollution exposure, malnutrition,
poverty, and co-morbidities [3]. Updating the risk factors
based on reliable incidence data becomes a mainstay for
pragmatic primary prevention strategies to achieve major
reductions in pneumonia-associated morbidity and mor-
tality in children. However, an appropriate surveillance
system for monitoring and evaluation of the impact of
pneumonia is commonly lacking in the LMICs. Lack
of funding for programmatic activities, lack of coordina-
tion with other child survival programs, inadequate train-
ing for community health workers and physicians, lack
of public awareness about seeking timely and appropriate
care, and insufficient planning and support for the pro-
grammatic activities at provincial and district levels are
major hindrances in decreasing the burden of childhood
pneumonia [10].
One of the core components of the Integrated Man-
agement of Childhood Illness (IMCI) by WHO and the
United Nations Children’s Fund (UNICEF), developed in
the 1980s, is pneumonia. It enables community health
workers to make a diagnosis of pneumonia based on clin-
ical signs and symptoms, such as respiratory rate, and
treat pneumonia with antibiotics unless hospitalization is
indicated. Thus, early diagnosis and management, with-
out doctors, are possible even in rural communities in
the LMICs. Implementing the IMCI strategy may reduce
32–70% of under-five mortality due to pneumonia [11–
13], but may have little effect on nutritional status and
vaccine coverage [14]. In 1996, a pilot IMCI was imple-
mented in the Philippines; thereafter more health workers
and hospital staff were trained to implement the strategy at
the frontline level. However, pneumonia remains a major
cause of childhood morbidity and mortality in the Philip-
pines [3]. In 2013, a major revision was made to the sever-
ity classification of pneumonia of IMCI by WHO [15]. In
the previous version of IMCI, patients with lower chest
wall indrawing were classified as having pneumonia and
Journal of Disaster Research Vol.13 No.4, 2018
Childhood Pneumonia in the Philippines
were treated at hospitals, but this was revised to home
therapy with oral dispersible amoxicillin, which would no
longer require hospitalization. Thus, the applicability of
the revised IMCI in the Philippines needs to be assessed.
With these background and rationales, we implemented
an operational research project for acute respiratory in-
fections (ARIs) in children in the Philippines. Our gen-
eral objective was to reduce mortality and morbidity asso-
ciated with childhood pneumonia by comprehensive eti-
ological and epidemiological studies. The specific ob-
jectives were divided into capacity developments and
research outputs. The objectives for the capacity de-
velopments included: a) to strengthen the capability of
the selected regional hospital bacteriology laboratories in
the diagnosis of bacterial infections by training/updating
the medical technologists in the isolation, identification
and susceptibility testing of bacterial pathogens, b) to
strengthen the capability of the national reference labo-
ratory in the updated diagnosis of bacterial and viral in-
fections, in the isolation, identification and drug suscep-
tibility testing of these pathogens, c) to provide the na-
tional reference laboratory and the selected regional hos-
pital bacteriology laboratories with appropriate laboratory
equipment and supplies to perform necessary bacterio-
logical examinations to diagnose respiratory infections,
d) to update the respective physicians on the recognition
and management of childhood pneumonia, and e) to set
up a sustainable laboratory network in the Philippines
for the surveillance of respiratory infections in children
under five. The objectives for the research outputs in-
cluded: a) to determine the bacterial and viral etiology
of childhood pneumonia, requiring hospital admission,
in the identified sentinel regional hospitals, b) to deter-
mine risk factors associated with childhood pneumonia
by a community based study, c) to determine predictors of
death due to childhood pneumonia, d) to determine host
factors associated with severity of childhood pneumonia,
e) to describe health seeking behavior of caregivers of
children with pneumonia to correlate with patient out-
come, and f) to characterize bacterial and viral pathogens
and compare with previous studies. This project was con-
ducted under the scheme of the Science and Technol-
ogy Research Partnership for Sustainable Development
(SATREPS) entitled “The Project for Comprehensive Eti-
ological and Epidemiological Study on Acute Respira-
tory Infections in Children: Providing Evidence for the
Prevention and Control of Childhood Pneumonia in the
Philippines.” It was jointly conducted by the Research
Institute for Tropical Medicine (RITM), a national refer-
ence laboratory, under the Department of Health (DOH)
in the Philippines, and Tohoku University, with joint co-
ordinating committee (JCC) members including the Em-
bassy of Japan, Japan International Cooperation Agency,
Japan Science and Technology Agency, WHO, DOH, and
National Economic and Development Authority (Fig. 1).
The project was initially launched from April 2011 to
March 2016 for the duration of five years and was ex-
tended until March 2017 for another year because of the
devastating super typhoon Haiyan in November 2013 in
741
Tamaki, R. et al.
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the Philippines, which severely damaged the project sites,
especially in the Eastern Visayas region.
2. Materials and Methods
2.1. Project Outline with Sub-Components
This project was composed of five sub-components:
etiological study, disease burden study, risk factor analy-
sis, intervention study, and its evaluation (Fig. 2). The eti-
ological study was conducted in hospital settings and its
catchment primary health facilities and enrolled patients
aged less than five years, with acute respiratory symp-
toms, to identify etiological agents and prognostic factors.
The disease burden study was conducted on an isolated is-
land, called Biliran. The cohort study had been adopted to
calculate the incidence rate of ARIs including pneumonia.
The community-based risk factors for pneumonia were
identified from the household survey with longitudinal
tracking of the cohort children; hence, time-related factors
could be assessed, such as repeated infections and behav-
ioral factors. The identified risk and prognostic factors,
based on etiological study and disease burden study, were
utilized to develop an intervention study. The facility-
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based and community-based intervention study was con-
ducted in Biliran. The evidence obtained from each com-
ponent were published and provided to DOH and project
sites.
2.2. Component 1 (Etiology Study)
We established the laboratory network between four
sentinel hospitals: RITM in Manila, Ospital ng Palawan
(ONP) in Palawan Island, Eastern Visayas Regional Med-
ical Center (EVRMC) in Leyte Island, and Biliran Provin-
cial Hospital (BPH) in Biliran Island. The study periods
in RITM, ONP, EVRMC, and BPH were from Septem-
ber 2012 to March 2015, August 2012 to March 2015,
April 2011 to March 2015, and September 2012 to June
2016, respectively. Patients aged eight days to less than
five years, who were admitted to the Department of Pe-
diatrics with severe pneumonia based on IMCI, were en-
rolled in the study. All cases were screened for the pres-
ence of cough or difficulty of breathing as the initial as-
sessment. For patients between two months to less than
five years old, the entry criteria included chest indraw-
ing, cyanosis, or an inability to drink or suck. In addi-
tion to these symptoms, for patients between eight days
to less than two months old, the entry criteria also in-
Journal of Disaster Research Vol.13 No.4, 2018
 Comprehensive Etiological and Epidemiological Study on Acute Respiratory
Infections in Children: Providing Evidence for the Prevention and Control of
Childhood Pneumonia in the Philippines

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cluded fast breathing (more than 60 breaths/min). The de-
tailed methodology was described in the preceding study
conducted at EVRMC [16]. Briefly, upon admission af-
ter consent, which was obtained from guardians, illness
histories were taken and physical examinations were con-
ducted by project physicians and nurses. Nasopharyn-
geal swabs (NPS) were collected for polymerase chain
reaction (PCR) and viral isolation. Blood samples were
collected for blood cultures to detect bacteria and basic
blood tests, including complete blood count (CBC) and
chemistry. Chest X-rays were performed to assess “pri-
mary end-point pneumonia” which is defined as alveolar
consolidation and/or pleural effusion by WHO [17]. In
the catchment areas of EVRMC and BPH, we collected
samples from pediatric patients with ARIs (including mild
cases) at the five outpatient sites. The sites were Tanauan
Rural Health Unit (RHU), the outpatient department of
Leyte Provincial Hospital and Tacloban City Health Cen-
ter in the EVRMC catchment areas, and Caibiran RHU
and Kawayan RHU in the BPH catchment, in parallel with
the hospital-based study. The RHU is a primary health
care facility providing primary health services, such as
general consultation, maternal and child health care in-
cluding immunizations and deliveries, located in each mu-
nicipality with a doctor in the Philippines. The clinical
samples, including blood and NPS from the sentinel hos-
pitals and NPS from the RHUs and the outpatients, were
transferred to RITM for further analysis. The blood cul-
tures were conducted at the bacteriology laboratories in
each sentinel hospital. Molecular genetic analysis of each
virus was conducted, together with clinical information,
in RITM and Tohoku University.
2.3. Component 2 (Disease Burden Study)
Biliran Island was selected as the cohort study site.
It was suitable for the cohort design because of its geo-
graphic isolation with a stable population and a simple re-
ferral system with only one referral hospital, where metic-
ulous individual cohort tracking was essential. Before the
cohort study, we conducted a cross-sectional survey in
the whole province to obtain the background character-
istics including demographic information and risk factors
for ARIs of children under five years of age [18]. Based
on the cross-sectional survey, we selected two municipal-
ities, i.e. Caibiran and Kawayan for the cohort sites. The
socioeconomic status in both municipalities was generally
low and the members of the community mostly lived in in-
formal housing, made of building materials from coconut
trees. On November 8, 2013, three days before the offi-
cial commencement of the cohort study, typhoon Haiyan
hit and severely damaged the research sites, especially in
the Eastern Visayas region, where two sentinel hospitals
were located. Two weeks after the disaster, two JICA ex-
perts were sent to the affected areas to assess the sites
for the project contingency plan for the etiology study at
EVRMC [19] and the cohort study at BPH and in Bili-
ran. In addition, we had evaluated the needs in the acute
phase of the disaster in the aspect of the public health
in Leyte Island [20]. With the efforts of the concerned
project staff, the cohort study started with re-enrollments
and household surveys in February 2014. We enrolled

Journal of Disaster Research Vol.13 No.4, 2018 743

Tamaki, R. et al.

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Fig. 3. Geographical distributions of the four sentinel sites and the cohort site with target pathogen at each level.

children (< five years) and followed up between February
25, 2014 and June 30, 2016. We obtained data on risk fac-
tors of ARIs, clinical information and a specimen for vi-
ral identification from each patient with respiratory signs
and symptoms, at either the household or any level of the
health facilities. At the household level, we distributed a
calendar (called “disease calendar”) to record the child’s
health including signs/symptoms, medicine administered,
and health seeking activities, respectively after giving an
orientation. Based on the calendar and detection of ARIs
at the household and the health facilities, we calculated
the incidence rate of ARIs. Combined with Components 1
and 2, the geographical distributions of the four sentinel
sites and a cohort site with a target pathogen at each level
are summarized in Fig. 3.
2.4. Component 3 (Risk Factor Analysis)
The baseline information was collected during the en-
rollment process in the cohort study and on admission in
the etiology study. This included: a) household informa-
tion: list of all family members, socioeconomic status,
toilet use and hand washing practice, and smoking status
of the family members, b) maternal factors: educational
background and health seeking practice for the child’s
illnesses, and c) child factors: birth information, immu-
nization status and breastfeeding history. The clinical in-
formation, including illness history, vitals, and physical
examination results, was collected by project physicians
and nurses. The anthropometry measurements, such as
weight, height, and mid-upper arm circumference were
also regularly done.
2.5. Component 4 (Intervention Study)
From the results of the cohort study, specific interven-
tion studies were conducted in Biliran. The objectives in-
cluded: a) to assess the efficiency of the diagnostic pro-
cedures using a digital device incorporated with IMCI,
b) to assess the revised IMCI in pneumonia severity, re-
leased by WHO in 2013, and c) to assess the impact of
risk advocacy on health seeking behavior and nutrition
in response to childhood pneumonia. For the first objec-
tive, we developed a digital device based on IMCI with a
pulse oximeter, which was used by midwives to manage
the patients at the RHUs and the Barangay Health Sta-
tions (BHSs). A barangay is a smallest administrative unit
in the Philippines, and a BHS is a primary health facility
covering some barangays. Some BHSs are organized un-
der a RHU. A qualitative analysis, including focal group
discussions, was conducted. Patient management with a
pulse oximeter to detect a potential hypoxic patient at the
BHS/RHU level was assessed. For the second objective,
we evaluated the WHO revised IMCI guideline, compared
with the previous version of IMCI, in terms of safety and
cost-effectiveness. The patients with lower chest wall in-
drawing treated in hospitals and managed at home after
the RHU/BHS consultations, were compared based on

744 Journal of Disaster Research Vol.13 No.4, 2018

 Comprehensive Etiological and Epidemiological Study on Acute Respiratory
Infections in Children: Providing Evidence for the Prevention and Control of
Childhood Pneumonia in the Philippines

Table 1. Total number of sampling by the sentinel hospitals and its catchment sites.

Sentinel YEAR
Study Level Sampling criteria
hospitals 2011 2012 2013 2014 2015 2016 Total
RITM Admisison IMCI-severe or very severe 18 102 86 3 209
ONP Admisison IMCI-severe or very severe 179 412 282 30 903
Facility Admisison IMCI-severe or very severe 665 417 350 350 25 1,807
based EVRMC
RHU etc. ILI (Influenza Like Illness) 632 655 145 1,432
study
Admission IMCI-severe or very severe 90 424 308 261 48 1,131
OPD ARI (Acute Respiratory Infection) 396 411 21 828
RHU ARI (Acute Respiratory Infection) 533 674 219 1,426
BPH Admission IMCI-severe or very severe 42 57 15 114
Cohort OPD ARI (Acute Respiratory Infection) 64 50 5 119
study RHU ARI (Acute Respiratory Infection) 1,210 1,635 778 3,623
Household ARI with fever 1,132 984 170 2,286
Total 1,297 1,359 1,433 4,403 4,130 1,256 13,878

the outcomes, including treatment failure for safety and
the total cost spent for cost-effectiveness. For the third
objective, we developed educational materials in foldable
A4 paper with basic information on nutrition and proper
health seeking behavior separately, which was translated
to local dialects (Waray-waray for Caibiran, Cebuano for
Kawayan). After training the Barangay Health Workers
(BHWs) on the contents of the educational material, we
assessed their knowledge retention. Thereafter, the edu-
cational materials were distributed to each home by the
BHWs in the community. The outcomes between pre and
post intervention, the incidence rate of pneumonia with-
out seeking action and the nutritional status, were also as-
sessed.
2.6. Component 5 (Results Dissemination and Pub-
lication)
Obtained results were published in peer-reviewed inter-
national journals. Outputs from the project were provided
to the domestic and international stakeholders.
3. Results and Discussions
The overall enrolled patients at each health facility
and household are summarized in Table 1. A total of
13,878 samples were collected from patients with ARIs.
Of these, 7,736 (56%) samples were collected for the
facility-based etiology study. Of these, 4,050 (52%) sam-
ples were from hospitalized episodes and 3,686 (48%)
samples from the outpatient/RHU level. On the other
hand, 6,142 (44%) samples were from the cohort chil-
dren, of which 114 (2%) were from admitted episodes,
3,742 (61%) were from the outpatient/RHU level, and
2,286 (37%) from the households.
3.1. Component 1 (Etiology Study)
There was no significant difference observed on the
patterns of the causative pathogens of pneumonia between
the sentinel sites. Due to several reasons including self-
medication of antibiotics prior to the consultation, the
positive rate of the bacterial detection (1.2%) by blood
culture was as low as the preceding studies. The com-
mon bacterial pathogens of pneumonia, such as S. pneu-
moniae and H. influenza were detected in this study. Of
these, B. pertussis was detected with the highest mortal-
ity rate. The epidemiology and etiological impacts of
B. pertussis in the Philippines were studied. B. pertussis
was detected from 34 (3%) out of 1,152 admitted cases
by PCR. The pertussis-positive cases had a remarkably
higher fatality rate than the pertussis-negative cases. All
of the fatal cases among pertussis-positive cases were less
than six months old [21]. The B. pertussis population
in the Philippines comprised genetically related strains
which are markedly different from those found in patients
from other countries where acellular pertussis vaccines
are used [22]. These results suggest that more attention
should be given to protect young infants from pertussis
with appropriate vaccine strategies. We collected NPS
for viral detection from patients with severe episodes, as
well as from those with mild episodes. Similar patterns
of viruses from a preceding study such as RSV, influenza,
and rhinovirus were detected in this study [16]. There
were two major RSV outbreaks: between June 2008 and
February 2009, and between June and March 2012 in the
Philippines. The majority of RSV strains detected dur-
ing the former outbreak were RSV-A (97.5%, 203/208)
whereas, during the later outbreak, both RSV-A (54/158,
34.2%) and RSV-B (104/158, 65.8%) were detected. All
RSV-A strains were classified as genotype NA1 and all
RSV-B as genotype BA, which had a 60-nucleotide du-
plication in the second hypervariable region of the G
gene [23]. Among the RSV-B positive samples, there
were two distinct clusters with unique amino acid changes

Journal of Disaster Research Vol.13 No.4, 2018 745

Tamaki, R. et al.
and low homology, compared to other strains in BA, sug-
gesting the emergence of a new variant of RSV-B [23]. In
the admitted cases from June 2012 to July 2013, 423 sam-
ples (28.1%) out of 1,505 were positive for RSV. There
is also the emergence and subsequent predominance of
the ON1 genotype and the sporadic detection of the GB2
genotype. Both genotypes were detected for the first time
in the Philippines [24]. Of the RSV positive cases from
the admitted patients from September 2012 to December
2013, the viral load of NA1 was higher than that of ON1
and BA9 in NPS samples. RSV genotypes may be associ-
ated with RSV viral load [25]. RSV is an important cause
of severe ARIs among children in the Philippines. Further
analysis of the RSV specific disease burden and risk fac-
tors are required for vaccine strategies [26]. We have stud-
ied RSV and influenza seasonality with Influenza-like Ill-
ness (ILI) surveillance data from January 2010 to March
2013. The ILI surveillance detected influenza virus as
a leading virus, but seasonality of influenza was unclear
throughout the study period. Influenza virus and RSV
were predominantly detected (both were 25.7%) followed
by human rhinovirus (HRV) (17.5%). Age was an impor-
tant factor that affected the positive rate of influenza and
other respiratory viruses [27]. Combined with other stud-
ies in the Philippines and Japan, annual seasonal peaks
were observed for FLUA and RSV but were less clear for
FLUB. With the wavelet analysis and the dynamic linear
regression model, the annual amplitude and the variation
in climate variables are more important than their abso-
lute values for determining their effect on the seasonality
of RSV and influenza [28]. From November 2009 to De-
cember 2013 in the Philippines, 15 influenza C (FLUC)
viruses were isolated using Madin-Darby canine kidney
cells, from children with severe pneumonia and ILI. The
clusters that included the Philippine and Japanese strains
were shown to have diverged from a common ancestor
around 1993 [29]. These suggest that the FLUC strain had
emerged through different reassortment events. This was
the first isolated FLUC from the Philippines [29]. Further
analysis and monitoring of influenza in LMICs with a re-
silient and sustainable surveillance system are crucial for
early detection of emerging strains which may potentially
cause pandemics. Among the admitted cases in 2011, a
total of 700 patients were enrolled, of which 22 (3.1%)
died. Nine (1.3%) HAdV cases were confirmed, with
seven identified as serotype HAdV7, one was HAdV3,
and one was HAdV5. Among the nine HAdV-positive
cases, four (44%) with HAdV7 died. The molecular anal-
ysis revealed that all HAdV7 isolates were closely related
to genome type h strains. This study demonstrated the sig-
nificance of HAdV7 as an etiological agent of severe pe-
diatric pneumonia with a high fatality rate. Hence, contin-
uous monitoring is required to define the clinical and pub-
lic health significance of HAdV7 infection [30]. The de-
tection of Enterovirus 68 (EV68) has recently increased,
which occasionally manifests in fatal outcomes. We iden-
tified EV68 from admitted cases and ILI in Leyte. All
21 patients we identified had severe illness. Two of whom
died and are possibly the first reported fatal cases associ-
746
ated with EV68 infection in the Philippines [31]. Hence,
further analysis was conducted which included testing of
5,240 patients from admitted cases and ILI from June
2009 to December 2011. Twelve EV68 positive cases
were detected between August and December in 2011
(detection rate: 0.23%). The detection rate was higher
among the inpatients than the outpatients (p < 0.0001).
Combined with our previous report, EV68 occurrences
were observed twice in the Philippines between 2008 and
2011. We also retrospectively tested 28 EV68-positive
NPS samples. Of these, EV68 was detected in serum sam-
ples of 12 (43%) patients aged between 1 and 4 years. The
results suggest that EV68 can cause viremia by which the
virus may exhibit systemic manifestations [32]. We stud-
ied the receptor binding specificities of EV68 strains for
sialyloligosaccharides using glycan array analysis, which
showed an affinity for 2-6-linked sialic acids (2-6 SAs)
compared to 2-3 SAs. Our study suggested that the emer-
gence of strains with different antigenicities was the pos-
sible reason for the increased detections of EV68 in re-
cent years. Additionally, we revealed that EV68 prefer-
ably binds to 2-6 SAs [33]. This is the first report describ-
ing the properties of EV68 receptor binding to the specific
types of sialic acids [33]. The EV68 detections might be
occurring in cyclic patterns, and the viruses might have
been maintained in the community, while some strains
might have been newly introduced, occasionally leading
to fatalities. However, no specific medicines and vaccines
for EV68 are available at present. Therefore, close mon-
itoring and further analysis of EV68 are of public health
importance.
3.2. Components 2 and 3 (Disease Burden Study
and Risk Factor Analysis)
The results of the cross-sectional household survey
prior to the cohort study showed that the impact of pneu-
monia on mortality is rather limited, whereas the inci-
dence of severe pneumonia was high in the Biliran Is-
land. Of 3,327 households visited in total, 3,302 (99.2%)
agreed to participate, and 5,249 children less than
five years of age were included in the study. The incidence
rates of pneumonia-like episodes, severe pneumonia-like
episodes, and pneumonia-associated mortality were 105,
61, and 0.9 per 1,000 person-years, respectively. The
factors, such as history of asthma (hazard ratio (HR):
5.85, 95% confidence interval (CI): 4.83–7.08), low so-
cioeconomic status (SES) (HR: 1.11, 95% CI: 1.02–
1.20), and long travel time to the healthcare facility esti-
mated by cost-distance analysis (HR: 1.32, 95% CI: 1.09–
1.61) were significantly associated with the occurrence of
pneumonia-like episodes by the Cox proportional hazards
model [18]. For severe pneumonia-like episodes, a history
of asthma (HR: 8.39, 95% CI: 6.54–10.77) and low SES
(HR: 1.30, 95% CI: 1.17–1.45) and long travel time to
hospital (Odds ratio (OR): 0.32, 95% CI: 0.19–0.54) were
significant risk factors. An improved access to health-
care facilities is essential for early and effective manage-
ment [18]. Based on the incidence rate of ARIs and iden-
Journal of Disaster Research Vol.13 No.4, 2018
 Comprehensive Etiological and Epidemiological Study on Acute Respiratory
Infections in Children: Providing Evidence for the Prevention and Control of
tified important risk factors in the context of the commu-
nity setting in the Philippines, we developed the cohort
study protocol. In the cohort study, using the disease cal-
endar dataset, we could calculate the person-year for the
denominator of incidence rate of ARIs. Taken together
with episodes detected at each health facility and house-
hold, we could calculate accurate incidence rate. Based
on the incidence rate, the risk factors of pneumonia were
identified. We observed more than 100 deaths in the hos-
pital settings of the four sentinel sites, whereas four fatal
cases were found in the cohort. Hence, the risks for the
mortality of pneumonia were analyzed with the hospital
dataset.
3.3. Components 4 (Intervention Study)
The detailed analysis is ongoing. The preliminary data
of the intervention study suggested important insights
for the revised IMCI guideline, in terms of safety, cost-
effectiveness, and community acceptance.
3.4. Component 5 (Results Dissemination and Pub-
lication)
We have published 18 papers in peer-reviewed inter-
national journals, and some ongoing analyses are yet to
be published. The outputs from the projects were shared
with the domestic and international stakeholders. A pol-
icy paper based on the results of the intervention study
was submitted to and is to be discussed with DOH.
4. Conclusion
The causative pathogens, such as RSV, HAdV, In-
fluenza, EV68, and HRV, were detected in childhood
pneumonia. RSV was one of the most important etiologic
agent causing severe pneumonia. The etiology studies
outlined the importance of laboratory-based surveillance
to monitor transmission and evolution of the causative
viruses of pneumonia, which contributes in strategizing
against emerging pathogens such as pandemic influenza.
In addition, these insights may also be utilized for vac-
cine strategies. The accurate incidence rate of pneumo-
nia will be most valuable information to determine where
health policy-makers can allocate the limited resources
appropriately, particularly in the LMICs like the Philip-
pines. The risk factors identified in the study can be uti-
lized for strategies against pneumonia. The ongoing anal-
ysis of the results of the intervention study may be use-
ful to implement strategies, potentially to be a packaged
health program against childhood pneumonia. We started
to develop the policy paper with DOH for a social imple-
mentation with the findings and evidence of the project.
With the scheme of SATREPS, we could implement the
comprehensive study against pneumonia, that is recog-
nized as “forgotten killer of childhood illness” by WHO
and UNICEF. The objectives of the scheme of SATREPS
are not only aimed at the research findings and evidence
Journal of Disaster Research Vol.13 No.4, 2018
Childhood Pneumonia in the Philippines
we can publish, but also the capacity development of the
LMICs that we can strengthen.
Acknowledgements
This work was supported by the Science and Technology Research
Partnership for Sustainable Development (SATREPS), Japan
Agency of Medical Research and Development (AMED)/Japan
International Cooperation Agency (JICA). The funding source
had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
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Address:
enterovirus 68,” J. of Virology, Vol.88, No.5, pp. 2374-2384, 2014. 9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
1781, Philippines

Name:
Alvin G. Tan

Affiliation:
Department of Epidemiology and Biostatistics, Research Institute for
Tropical Medicine
Address:
9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
1781, Philippines

Name:
Mark Donald C. Reñosa

Affiliation:
Department of Epidemiology and Biostatistics, Research Institute for
Tropical Medicine
Address:
9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
1781, Philippinese

748 Journal of Disaster Research Vol.13 No.4, 2018

 Comprehensive Etiological and Epidemiological Study on Acute Respiratory
Infections in Children: Providing Evidence for the Prevention and Control of
Childhood Pneumonia in the Philippines

Name: Name:
Portia P. Alday Michiko Okamoto

Affiliation: Affiliation:
Department of Epidemiology and Biostatistics, Research Institute for Department of Virology, Tohoku University Graduate School of Medicine
Tropical Medicine Address:
Address: 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
1781, Philippines

Name:
Mariko Saito
Name:
Jhoys M. Landicho Affiliation:
Department of Virology, Tohoku University Graduate School of Medicine
Affiliation: Address:
Department of Epidemiology and Biostatistics, Research Institute for 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
Tropical Medicine
Address:
9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
1781, Philippines
Name:
Clyde Dapat

Name: Affiliation:
Department of Virology, Tohoku University Graduate School of Medicine
Marianette T. Inobaya
Address:
2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
Affiliation:
Department of Epidemiology and Biostatistics, Research Institute for
Tropical Medicine
Address:
9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
Name:
1781, Philippine
Bindongo P. P. Dembele

Affiliation:
Department of Virology, Tohoku University Graduate School of Medicine
Name: Address:
2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
Mayuko Saito

Affiliation:
Department of Virology, Tohoku University Graduate School of Medicine
Address: Name:
2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
Mary Lorraine S. Mationg

Affiliation:
Department of Epidemiology and Biostatistics, Research Institute for
Name: Tropical Medicine
Taro Kamigaki
Address:
9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
1781, Philippines
Affiliation:
Department of Virology, Tohoku University Graduate School of Medicine
Address:
2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
Name:
Melisa U. Mondoy

Affiliation:
Department of Microbiology, Research Institute for Tropical Medicine
Address:
9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
1781, Philippines

Journal of Disaster Research Vol.13 No.4, 2018 749

Tamaki, R. et al.

Name:
Socorro P. Lupisan

Affiliation:
Director’s Office, Research Institute for Tropical Medicine
Address:
9002 Research Drive, Filinvest Corporate City, Alabang Muntinlupa City
1781, Philippines

Name:
Hitoshi Oshitani

Affiliation:
Department of Virology, Tohoku University Graduate School of Medicine
Address:
2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan

750 Journal of Disaster Research Vol.13 No.4, 2018