Symptomatic and asymptomatic respiratory viral infections in the first year of life: association with acute otitis media development.

BACKGROUND: Sensitive diagnostic assays have increased the detection of viruses in asymptomatic individuals. The clinical significance of asymptomatic respiratory viral infection in infants is unknown. METHODS: High-throughput, quantitative polymerase chain reaction assays were used to detect 13 common respiratory viruses from nasopharyngeal specimens collected during 2028 visits from 362 infants followed from near birth up to 12 months of age. Specimens were collected at monthly interval (months 1-6 and month 9) and during upper respiratory tract infection (URTI) episodes. Subjects were followed closely for acute otitis media (AOM) development. RESULTS: Viruses were detected in 76% of 394 URTI specimens and 27% of asymptomatic monthly specimens. Rhinovirus was detected most often; multiple viruses were detected in 29% of the specimens. Generalized mixed-model analyses associated symptoms with increasing age and female sex; detection of respiratory syncytial virus (RSV), influenza, rhinovirus, metapneumovirus, and adenovirus was highly associated with symptoms. Increasing age was also associated with multiple virus detection. Overall, 403 asymptomatic viral infections in 237 infants were identified. Viral load was significantly higher in URTI specimens than asymptomatic specimens but did not differentiate cases of URTI with and without AOM complication. The rate of AOM complicating URTI was 27%; no AOM occurred following asymptomatic viral infections. AOM development was associated with increasing age and infection with RSV, rhinovirus, enterovirus, adenovirus, and bocavirus. CONCLUSIONS: Compared to symptomatic infection, asymptomatic viral infection in infants is associated with young age, male sex, low viral load, specific viruses, and single virus detection. Asymptomatic viral infection did not result in AOM.

Use of symptoms and risk factors to predict acute otitis media in infants.

OBJECTIVES: Infants and children with upper respiratory tract infection (URI) often have concurrent acute otitis media (AOM). Young infants have fewer specific symptoms than older children. The purpose of this study was to evaluate the usefulness of symptoms and other risk factors in predicting the presence of AOM in infants. METHODS: Healthy infants, age less than four weeks, were enrolled and followed prospectively for up to age one year. Infants were scheduled for a research visit when their parents noted the onset of symptoms. At each URI visit, parents first reported the severity of symptoms. An investigator then diagnosed the presence or absence of concurrent AOM. Risk factors and symptom scores for infants with and without AOM were studied. RESULTS: Infants (N=193, mean age at first URI 3.9±2.5 months) experienced 360 URI episodes and 63 AOM events. Symptoms consisting of fever, earache, poor feeding, restless sleep, and irritability together (ETG-5) were statistically associated with the prediction of AOM (P=0.006). A multiple variable statistical model (J-Score) that included day care attendance, age, severity of cough and earache best predicted AOM (P<0.001), with 95% specificity. Both ETG-5 and J-score yielded relatively low sensitivity for AOM prediction. CONCLUSIONS: In infants with URI in the first year of life, severity of symptoms was significantly associated with concurrent AOM. Daycare attendance, presence and severity of earache and cough added to better correlation. These observations may have clinical application in identification of infants at risk for AOM.

Acute Otitis Media and Other Complications of Viral Respiratory Infection.

BACKGROUND: Viral upper and lower respiratory tract infections (URI, LRI) are common in 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 1-6, 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.

Factors Affecting Staphylococcus aureus Colonization of the Nasopharynx in the First 6 Months of Life.

BACKGROUND: Staphylococcal aureus (SA) colonization in early infancy is common, but the pattern and factors affecting its acquisition and persistence in the first few months of life are not well studied. The aim is to study the rate of SA nasopharyngeal (NP) colonization at monthly intervals in the first 6 months of life and its association with environmental and host factors and other pathogenic NP bacteria. METHODS: Data from a prospective study were analyzed on bacterial cultures of 1765 NP swabs from 367 infants who were followed from birth to 6 months of age. Demographic, breastfeeding, cigarette smoke exposure and day care attendance data were collected at each monthly visit. RESULTS: The rate of infants colonized with SA was highest at age 1 month (25%) and declined to lowest rate by age 6 months (12%). The proportion of SA strains that was methicillin-resistant SA was also highest at age 1 month and declined rapidly by age 4 months (18% vs. 6%, P = 0.05). Colonization with Streptococcus pneumoniae (SP), nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis (MC) increased at different rates up to age 6 months. Univariate analysis showed that SA colonization rate was significantly lower with increasing age, black race, day care attendance, and colonization with NTHI, MC and SP (P < 0.05). Multivariate analysis showed that this effect was independently associated only with increasing age and MC colonization (P < 0.05). Furthermore, the time to first acquisition of SA from one month of age onwards was significantly associated with day care attendance, and NTHI and MC colonization. None of the infants colonized with SA developed SA infections through age 6 months. CONCLUSIONS: SA colonization of NP begins very early in life and declines quickly. Methicillin-resistant SA has lower ability to maintain prolonged colonization status than methicillin-susceptible strains in the first 6 months of life. As the NP is colonized with other respiratory bacterial pathogens, the colonization with SA declines; however, this effect is stronger with Gram-negative bacteria, such as NTHI and MC.

Acute bacterial sinusitis complicating viral upper respiratory tract infection in young children.

BACKGROUND: Acute bacterial sinusitis (ABS) is a common complication of viral upper respiratory tract infections (URI). Clinical characteristics of URIs complicated by ABS in young children have not been well studied. METHODS: We identified ABS episodes in a prospective, longitudinal cohort study of 294 children (6-35 months of age at enrollment), who were followed up for 1 year to capture all URI episodes and complications. At the initial URI visit seen by the study personnel (median day = 4 from symptoms onset), nasopharyngeal samples were obtained for bacterial cultures and viral studies. RESULTS: Of 1295 documented URI episodes, 103 (8%) episodes (in 73 children) were complicated by ABS, 32 of which were concurrent with acute otitis media. The majority (72%) of ABS episodes were diagnosed based on persistent symptoms or a biphasic course. Average age at ABS diagnosis was 18.8 ± 7.2 months; White children were more likely to have ABS episodes than Blacks (P = 0.01). Hispanic/Latino ethnicity (P < 0.0001) was negatively associated, and adequate 7-valent pneumococcal conjugate vaccine immunization status (P = 0.001) appeared to increase the risk of ABS. Girls had more ABS episodes than boys (0.5 ± 0.8 vs. 0.3 ± 0.6 episodes/yr, respectively, P = 0.03). Viruses were detected in 63% during the initial URI visit; rhinovirus detection was positively correlated with ABS risk (P = 0.01). Bacterial cultures were positive in 82/83 (99%) available samples obtained at the initial URI visit; polymicrobial (56%), Moraxella catarrhalis (20%) and Streptococcus pneumoniae (10%) were the most common cultures. Presence of pathogenic bacteria overall and presence of M. catarrhalis during URI were positively correlated with the risk for ABS (P = 0.04 for both). CONCLUSIONS: ABS complicates 8% of URI in young children. Girls have more frequent ABS episodes than boys. Presence of rhinovirus and M. catarrhalis during URI are positively correlated with the risk for ABS complication.

Duration of rhinovirus shedding in the upper respiratory tract in the first year of life.

BACKGROUND: Current molecular diagnostic methods have detected rhinovirus RNA in a high proportion of asymptomatic infants and children, raising the question of the clinical significance of these findings. This study investigates the prevalence of prolonged rhinovirus RNA presence in the upper respiratory tract of infants during the first year of life. METHODS: In a longitudinal study, infants were followed from birth up to 12 months. Nasopharyngeal specimens were collected monthly (months 1-6 and month 9) and during an upper respiratory infection. Rhinoviruses were detected by quantitative reverse-transcription polymerase chain reaction. Presence of repeated rhinovirus RNA was evaluated by nucleotide sequence analysis. RESULTS: A total of 2153 specimens from 362 infants were studied; 341 distinct rhinovirus infections in 216 infants were identified. Follow-up specimens were available within 30 days for 179 infections, creating the sample set to assess prolonged rhinovirus presence. Of the 179 infections, 46 involved the detection of the same rhinovirus strain in repeated specimens, including 8 events of prolonged presence of the same strain (detected in specimens collected >30 days apart), representing 4.5% of the evaluable rhinovirus infections. There were 26 events in which a rhinovirus strain was replaced by a different strain within a 30-day interval, representing 14.5% of the 179 infections. CONCLUSIONS: Although rhinovirus infections are common in healthy infants, prolonged presence of rhinovirus RNA in the respiratory tract after an upper respiratory infection was uncommon (<5%). Detection of rhinovirus RNA in an infant most likely represents an infection within a 30-day period.

Effect of the 2009 influenza A/H1N1 pandemic on viral respiratory infections in the first year of life.

BACKGROUND: The effect of the 2009 H1N1 influenza pandemic on viral epidemiology of upper and lower respiratory tract infections (URI and LRI) in healthy infants in the first year of life has not been well studied. METHODS: A total of 180 healthy infants were enrolled from birth and monitored for occurrences of URI, LRI and acute otitis media complications until the first acute otitis media episode or between 6 and 12 months of age. Nasopharyngeal specimens collected during acute respiratory illnesses were tested for 18 viruses. RESULTS: Between October 2008 and April 2011, 373 URI episodes, including 20 with LRI, in 139 infants were documented. Viral studies were performed on 189 URI episodes; 87% were positive. Throughout the 31-month period (1386 patient-months), rhinovirus was the predominant virus causing URI (55%); respiratory syncytial virus was the major cause of LRI (64%). Although there was a significant increase in parent-initiated visit rate during the 15-month influenza pandemic as compared with prepandemic and postpandemic periods, only 4 cases of influenza were detected (2 cases during and 2 cases prepandemic and postpandemic). CONCLUSIONS: The 2009 influenza A/H1N1 pandemic had no impact on the overall viral epidemiology of respiratory infections in healthy infants in the first year of life but resulted in increased parent-initiated visits due to respiratory symptoms. Maternal antibody and absence of comorbidity may explain the low influenza burden whereas parental anxiety may explain the increased healthcare visit rate during the pandemic.