THT - 12 Acute Otitis Media and Other Complication of Viral Respiratory Infection
THT - 12 Acute Otitis Media and Other Complication of Viral Respiratory Infection
THT - 12 Acute Otitis Media and Other Complication of Viral Respiratory Infection
BACKGROUND: Viral upper and lower respiratory tract infections (URI, LRI) are common in abstract
infants. We determined the prevalence of viral URI and its complications, including acute
otitis media (AOM) and LRI, and assessed the effect of bacterial-viral interactions, and
genetic and environmental risks on AOM development.
METHODS: Healthy infants were enrolled from near birth and followed to the first episode
of AOM up to 12 months of age. Nasopharyngeal specimens were collected at monthly
intervals (months 16, 9) and during viral URI episodes for bacterial culture and viral
polymerase chain reaction studies. Subjects were followed closely for AOM development.
RESULTS: A total of 367 infants were followed for 286 child-years; 887 URI (305 infants) and
180 AOM episodes (143 infants) were documented. Prevalence of URI, LRI, and AOM in the
first year was 3.2, 0.25, and 0.67 per child-year, respectively. Cumulative AOM incidence by
ages 3, 6, and 12 months was 6%, 23%, and 46%. Infants with and without AOM had 4.7 and
2.3 URI episodes per child-year, respectively (P < .002). Pathogenic bacterial colonization
rates by month were significantly higher in infants with AOM (P < .005). Breastfeeding
reduced both URI and AOM risks (P < .05). Significant bacterial-viral interactions occurred
with Moraxella catarrhalis and a variety of respiratory viruses and altered URI and AOM
risks.
CONCLUSIONS: Almost half of infants experienced AOM by age 1. Important AOM risk factors
included frequent viral URI, pathogenic bacterial colonization, and lack of breastfeeding.
Bacterial-viral interactions may play a significant role in AOM pathogenesis and deserve
further investigation.
NIH
Departments of aPediatrics, bPathology, cPreventive Medicine and Community Health, and dMicrobiology and
WHATS KNOWN ON THIS SUBJECT: Viral upper
Immunology, University of Texas Medical Branch, Galveston, Texas
respiratory tract infection is often complicated by
Dr Chonmaitree conceptualized and designed the study, oversaw the study conduct, drafted the bacterial infections. Medical progress has been made
manuscript, and takes responsibility for the integrity of the data; Dr Trujillo coordinated the in the past few decades in pediatric vaccination and
data collection, tabulated clinical data, reviewed the manuscript and approved the manuscript viral diagnostics. Birth cohort studies on respiratory
as submitted; Dr Jennings carried out the statistical analyses, reviewed the manuscript, and infections mostly came from outside the United
approved the manuscript as submitted; Drs Alvarez-Fernandez and Nokso-Koivisto coordinated
States.
the data collection, reviewed the manuscript, and approved the manuscript as submitted; Dr
Patel co-conceptualized and co-designed the study, participated in clinical data collection, WHAT THIS STUDY ADDS: Updated prevalence
reviewed and revised the manuscript, and approved the manuscript as submitted; Dr Loeffelholz of upper respiratory tract infection, acute otitis
co-conceptualized and co-designed the study, participated in microbiological data collection media, and lower respiratory tract infection in
and analyses, reviewed the manuscript, and approved the manuscript as submitted; Dr Matalon American infants in the pneumococcal conjugate
co-conceptualized and co-designed the study, reviewed the manuscript, and approved the
vaccine era. New information on the dynamics of
manuscript as submitted; Dr Pyles conceptualized and supervised molecular virology studies,
pathogenic bacterial colonization, viral and bacterial
reviewed the manuscript, and approved the manuscript as submitted; Mr Miller co-conceptualized
interactions, and acute otitis media risk factors.
To cite: Chonmaitree T, Trujillo R, Jennings K, et al. Acute Otitis Media and Other
Complications of Viral Respiratory Infection. Pediatrics. 2016;137(4):e20153555
TABLE 2 The First Episode of URI, AOM, and LRI in 311 Subjects and Cumulative Incidence by Month
Age at the First Episode URI Episodes AOM Episodes LRI Episodes
n Cumulative Incidence n Cumulative Incidence n Cumulative Incidence
% (CI) % (CI) % (CI)
1st mo of life 44 14 (10.718.5) 0 0.0 4 1 (0.483.4)
2nd mo 60 33 (28.539.0) 5 2 (0.683.8) 3 2 (1.14.7)
3rd mo 50 50 (44.155.2) 15 6 (4.29.8) 6 4 (2.47.1)
4th mo 37 61 (56.066.8) 16 12 (8.511.6) 6 6 (3.99.4)
5th mo 28 70 (65.374.5) 20 18 (14.222.7) 8 9 (6.012.4)
6th mo 21 77 (72.481.7) 14 23 (18.327.6) 6 11 (7.714.6)
>612 mo of age 47 92 (89.094.9) 73 46 (40.751.7) 18 18 (13.923.0)a
No. of subjects 287a 143 51
CI, condence interval. Cumulative incidence = % of subjects with at least 1 episode of URI, AOM, or LRI by specic age.
a Only 203 subjects were followed to 12 mo.
diagnoses are shown in Supplemental evidence to invalidate the diagnosis, overall (P < .005), with Haemophilus
Table 8. The prevalence of LRI in the we did not exclude these cases from influenzae (P < .001), and with
first 6 and 12 months of life was 0.25 further analyses. The cumulative Moraxella catarrhalis (P = .015).
and 0.24 per child-year, respectively. incidence of AOM (percentage of Statistically significant difference
subjects with at least 1 AOM episode) was not detected for Streptococcus
AOM Incidence and Prevalence by specific age is shown in Table 2. pneumoniae (P = .54).
The prevalence of AOM at ages 6 and
Overall, 143 infants (46%) 12 months was 0.56 and 0.67 per Viral URI
experienced 180 AOM episodes, all but patient-year, respectively.
2 within 28 days of a preceding URI. A total of 311 subjects had 859
Two AOM episodes were diagnosed Factors Affecting AOM Occurrences URI episodes. There were 466 URI
without history of preceding URI. The in the First Year of Life episodes in 143 subjects with AOM
rate of AOM after URI was 21% (178 of and 393 episodes in 168 subjects
Nasopharyngeal Bacterial Colonization
859). AOM was diagnosed, on average, without AOM. Subjects with AOM had
5 days after URI onset (median = 3 Bacterial culture results from significantly more frequent URIs than
days). Investigators diagnosed 104 nasopharyngeal swabs collected those without (4.7 vs 2.3 episodes
AOMs (58%); others diagnosed 76, monthly and during URI/AOM per child-year; P < .002). Types of
22 of these with LRI were diagnosed episodes in subjects with (n = 143) viruses and viral load in URI with
by the hospital physicians. Of AOM and without AOM (n = 168) in the or without AOM from cases seen by
episodes diagnosed by others, 93% first year of life are shown in Fig 1. the study group were previously
documented solid evidence of AOM, Colonization rates with 3 pathogenic reported.21 Overall, 2153 specimens
including bulging, purulent fluid/ bacteria increased with age. Infants from 362 subjects were tested21;
otorrhea, and/or opacification; 7% with AOM were colonized more viruses were detected in 76% of URI
lacked documentation. Having no often with pathogenic bacteria samples: 60% with a single virus and
40% with multiple viruses. Viruses in no significant difference detected presence of M catarrhalis, RSV, or
single-virus samples were as follows: between cases with RSV, compared both increased AOM risk, compared
RV (55%), RSV (11%), parainfluenza with M catarrhalis on URI risk in this with neither. Also, RSV, compared
(8%), coronavirus (8%), MPV (7%), subset. For RV and MPV, presence with M catarrhalis, increased AOM
adenovirus (4%), enterovirus (3%), of M catarrhalis, virus, or both risk, but M catarrhalis with RSV
bocavirus (2%), and influenza (2%). significantly increased URI risk, decreased AOM risk, compared with
compared with neither. Also, the RSV without M catarrhalis.
Viral and Bacterial Interactions During presence of RV or MPV increased URI
URI and AOM risk, compared with presence of M Environmental and Genetic Factors
Of 413 URI episodes seen by the catarrhalis without virus. We collected environmental risk
study group, bacterial and viral Table 4 reports AOM risk by presence data at enrollment and during
data, obtained within 7 days of URI of virus and/or bacteria. Of 104 AOM monthly visits, URI and AOM visits,
onset, were available in 395 (96%) episodes diagnosed or confirmed and phone interviews, an average
episodes. Tables 3 and 4 report by the study group, there were of 12 data encounters per subject.
hazard ratios (HRs), comparing viral 83 (80%) episodes with available Environmental and genetic factors
and/or bacterial pathogens, against bacterial and viral data within 7 associated with URI and AOM risks,
reference. Table 3, top, shows HRs days of AOM diagnosis and before modeled through a multivariate
during URI events by presence of antibiotic treatment. The presence logistic mixed model, are shown in
bacteria or viruses. The presence of any virus or S pneumoniae Tables 5 and 6. We analyzed data in
of any virus, M catarrhalis, or S significantly increased the AOM the first 6 months of life because all
pneumoniae was associated with an risk, compared with no pathogens infants were followed until 6 months
increased URI risk. Data from this (Table 4, top). Data also suggested of age (n = 239 infants); available
model also suggested significant interactions of M catarrhalis, but data after 6 months were not
interactions between M catarrhalis not other bacteria, with RSV and RV. uniform, as the subjects completed
(but not other bacteria) and RSV, Therefore, we further analyzed these the study after the first AOM episode
RV, and MPV; therefore, we further specific subsets (Table 4, bottom). was diagnosed. Day care attendance
analyzed these specific interactions The presence of M catarrhalis, RV, or and multiple siblings were associated
within each subset (Table 3, bottom). both increased AOM risk, compared with increased URI risk. Decreased
Presence of RSV, or M catarrhalis, with neither; but the presence of RV URI risk was associated with birth
but not both, increased URI risk did not alter AOM risk, compared after February 2010, exclusive
compared with neither. There was with presence of M catarrhalis. The breastfeeding >6 months, increased
breastfeeding duration, and TABLE 5 Environmental and Genetic Factors Associated With URI in the First 6 Months (n = 239
increased length of time to exclusive Infants)
formula feeding. Factor n HR (95% CI) P
Seventy infants experienced 87 Cigarette exposurea 54 1.15 (0.891.49) .28
AOM episodes before age 6 months. Day care attendanceb 67 1.74 (1.442.11) <.0001
One or more sibling(s) in the homec 86 1.07 (1.011.14) .032
Compared with infants without AOM,
Breastfeeding exclusively for at least 6 mod 22 0.63 (0.400.99) .049
decreased AOM risk was associated Length of breastfeeding, moe 95 0.96 (0.930.99) .0075
with the following: exclusive Length of time to exclusive formula feeding, 268 0.96 (0.930.98) .0009
breastfeeding >3 months, increased mo
duration of breastfeeding, and Length of time to other feeding, mof 271 0.97 (0.931.00) .070
Born after February 2010g 220 0.84 (0.750.93) .0012
increased length of time to exclusive
TNF308 polymorphismh 81 1.19 (0.691.01) .063
formula feeding. We did not detect IL-6174 polymorphismh 127 1.06 (0.891.27) .50
any environmental or genetic factor CI, condence interval
that increased AOM risk in this model. a Any smoking in the household.
b Yes/no, any length of time.
c Linear function, taking into account the number of siblings.
d The length 6 mo was chosen because it optimized the model t to the data (ie, maximized the likelihood).
DISCUSSION e Length of breastfeeding, not necessarily exclusively.
f Other food than breast milk or formula.
In this large American birth cohort g Heptavalent PCV (7) was given before February 2010; all subjects received PCV13 thereafter. Of the subjects completing
study performed during the PCV the study, 73% had received 4 doses of PCV vaccines, 18% received 3 doses, 5% received 2 doses, and 3% received only
and influenza vaccine era, infants 1 dose.
h Homozygous and heterozygous.
experienced 3.2 URIs per child-
year. Birth cohort studies on viral
respiratory infections have been Our study provided close follow-up AOM incidence at age 3 months,
conducted mostly outside the United of subjects for URI and AOM and our 29 30% to 39% at 6 months,12,29,30
States and have focused on LRI and passive surveillance of data from and 60% to 62% at 1 year.12,29 It
childhood asthma2,3,2628; we focused electronic medical records covered is likely that medical interventions
on AOM, the most common URI all pediatric practices in Galveston in the past few decades, such as the
complication. We clearly showed plus review of AOM diagnoses by use of pneumococcal and influenza
that frequent viral infections, others. AOM incidence in our study virus vaccines, higher breastfeeding
bacterial colonization, and lack of was 6%, 23%, and 46% by ages 3, rates,18 and decreased smoking,17
breastfeeding are major AOM risk 6, and 12 months, respectively, an helped reduce AOM incidence.
factors. Our data also suggested that appreciable decrease from incidence More recent reports from population
interactions between M catarrhalis in previous studies with similar birth cohort studies using ques-
and respiratory viruses may alter the design. Data from studies in the late tionnaire or parental interview have
risk for both URI and AOM. 1980s and 1990s reported 18% reported even lower OM incidences
and performed molecular virology studies, reviewed the manuscript, and approved the manuscript as submitted; and Dr McCormick co-conceptualized and co-
designed the study, participated in clinical data collection, drafted parts of the manuscript, and approved the manuscript as submitted.
Dr Trujillos current afliation is San Juan City Hospital, San Juan, Puerto Rico; the current afliation of Dr Alvarez-Fernandez is the University of Puerto Rico, San
Juan, Puerto Rico; and the current afliation of Dr Nokso-Koivisto is the University of Helsinki, Helsinki, Finland.
DOI: 10.1542/peds.2015-3555
Accepted for publication Jan 22, 2016
Address correspondence to Tasnee Chonmaitree, MD, Department of Pediatrics, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555
0371. E-mail: tchonmai@utmb.edu
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose.
FUNDING: This work was supported by the National Institutes of Health research grants R01DC005841 and UL1TR001439. Funded by the National Institutes of
Health (NIH).
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conicts of interest to disclose.
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