Krystal Revai

Viral upper respiratory tract infection and otitis media complication in young children.

Abstract Background. The common cold or upper respiratory infection (URI) is highly prevalent among young children and often results in otitis media (OM). The incidence and characteristics of OM complicating URI due to specific viruses have not been well studied. Methods. We performed a prospective, longitudinal cohort study of 294 healthy children (age range, 6 months to 3 years). Each child was observed for 1 year to assess the occurrence of URI, acute OM (AOM), and OM with effusion (OME) complicating URI due to specific viruses. Results. We documented 1295 URI episodes (5.06 episodes per child-year) and 440 AOM episodes (1.72 episodes per child-year). Virus studies were performed for 864 URI episodes; 63% were virus positive. Rhinovirus and adenovirus were most frequently detected during URI. The overall incidence of OM that complicated URI was 61%, including a 37% incidence of AOM and a 24% incidence of OME. Young age was the most important predictor of AOM that complicated URI. AOM occurred in approximately one-half of children with URI due to adenovirus, respiratory syncytial virus, or coronavirus and in approximately one-third of those with URI due to influenza virus, parainfluenza virus, enterovirus, or rhinovirus. Conclusions. More than 60% of episodes of symptomatic URI among young children were complicated by AOM and/or OME. Young age and specific virus types were predictors of URI complicated by AOM. For young children, the strategy to prevent OM should involve prevention of viral URI. The strategy may be more effective if the priority is given to development of means to prevent URI associated with adenovirus and respiratory syncytial virus.

Microbial interactions during upper respiratory tract infections.

Competitive interactions between bacteria differ by number and species present; thus, vaccination and treatment strategies may alter nasopharyngeal flora and disease susceptibility.

Incidence of Acute Otitis Media and Sinusitis Complicating Upper Respiratory Tract Infection: The Effect of Age

Infants and young children are prone to developing upper respiratory tract infections, which often result in bacterial complications such as acute otitis media and sinusitis. We evaluated 623 upper respiratory tract infection episodes in 112 children (6–35 months of age) to determine the proportion of upper respiratory tract infection episodes that result in acute otitis media or sinusitis. Of all upper respiratory tract infections, 30% were complicated by acute otitis media and 8% were complicated by sinusitis. The rate of acute otitis media after upper respiratory tract infection declined with increasing age, whereas the rate of sinusitis after upper respiratory tract infection peaked in the second year of life. Risk for acute otitis media may be reduced substantially by avoiding frequent exposure to respiratory viruses (eg, avoidance of day care attendance) in the first year of life.

Effect of pneumococcal conjugate vaccine on nasopharyngeal bacterial colonization during acute otitis media

The heptavalent pneumococcal conjugate vaccine (PCV7) has been shown to reduce the incidence of acute otitis media (AOM) caused by Streptococcus pneumoniae by 34% and reduces the overall incidence of AOM by 6% to 8%. More recent studies have shown increases in the proportion of Haemophilus influenzae and Moraxella catarrhalis in the middle-ear fluid of PCV7-immunized children. There has been no report on the effect of PCV7 on all 3 bacterial pathogens combined, either in the middle-ear fluid or nasopharynx of individual children with AOM. We investigated the impact of PCV7 on nasopharyngeal colonization with bacterial pathogens during AOM in the pre-PCV7 and post-PCV7 vaccination eras. Four hundred seventeen children (6 months to 4 years of age) were enrolled onto AOM studies between September 1995 and December 2004. Of these, 200 were enrolled before the vaccine use (historical controls), and 217 were enrolled after the initiation of PCV7 vaccination (101 were underimmunized, and 116 were immunized). Although the nasopharyngeal colonization rate for S pneumoniae was not different between the 3 groups, a significantly higher proportion of PCV7-immunized children with AOM were colonized with M catarrhalis. Overall, the mean number of pathogenic bacteria types isolated from immunized children (1.7) was significantly higher than in controls (1.4). The increase in bacterial colonization of the nasopharynx during AOM could be associated with an increase in AOM pathogens and theoretically can predispose PCV7-immunized children with AOM to a higher rate of antibiotic treatment failure or recurrent AOM.

Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media.

OBJECTIVE. Susceptibility to otitis media results from complex interactions among genetic factors of the host, exposure to pathogens, and environmental influences. The objective of this study was to study the role of single-nucleotide polymorphisms of regulatory elements of proinflammatory cytokine genes tumor necrosis factor-α−308, interleukin-1β+3953, and interleukin-6−174, in susceptibility to recurrent otitis media in childhood. METHODS. A total of 505 children (296 otitis media susceptible, 209 nonsusceptible as control) were enrolled at 2 sites (Texas and Kentucky). DNA of the children was studied for specific single-nucleotide polymorphisms by restriction fragment length polymorphism assay and confirmed by gene sequencing. RESULTS. In the overall study group, tumor necrosis factor-α−308 and interleukin-6−174 heterozygous or homozygous polymorphisms (high cytokine-producing genotypes) were significantly associated with otitis media susceptibility. The same association was found in a match-paired subgroup of 384 subjects. In the overall study group, there was a significant step-wise increase in otitis media susceptibility with increasing number of concomitant polymorphic genotypes. Simultaneous combination of tumor necrosis factor-α−308 and interleukin-6−174 polymorphisms further increased the risk for otitis media susceptibility. These 2 polymorphic genotypes also were associated with the increased risk for tympanostomy tube placement. Children who had tumor necrosis factor-α−308 polymorphism and were breastfed for <1 month or exposed to cigarette smoke were more likely to be otitis media susceptible. CONCLUSIONS. Our data suggest that tumor necrosis factor-α−308 and interleukin-6−174 polymorphisms are associated with increased risk for otitis media susceptibility and placement of tympanostomy tubes. Environmental factors such as breastfeeding may modify the risk for otitis media susceptibility in polymorphic individuals.

Association of Nasopharyngeal Bacterial Colonization during Upper Respiratory Tract Infection and the Development of Acute Otitis Media

Acute otitis media occurs mostly after upper respiratory tract infection; the causative bacteria are those colonized in the nasopharynx. We studied 709 episodes of upper respiratory tract infection and found that children with no bacteria in the nasopharynx were at low risk for acute otitis media, whereas children with 3 pathogenic bacteria were at the greatest risk.

Persistence of adenovirus nucleic acids in nasopharyngeal secretions: a diagnostic conundrum.

Background: Polymerase chain reaction (PCR) assays increase the rate of viral detection in clinical specimens, compared with conventional virologic methods. Studies suggest that PCR may detect virus nucleic acid (NA) that persists in the respiratory tract. Methods: We analyzed virologic data from children having frequent upper respiratory infections (URI), who were followed up in a longitudinal study. Nasopharyngeal secretions were collected at URI onset and when acute otitis media was diagnosed; virus studies were performed using conventional diagnostics and PCR. Repeated presence of adenovirus by PCR was further studied by sequencing and phylogenetic analysis. Results: Of 581 URI episodes in 76 children, 510 viruses were detected. Of the viruses detected by PCR, 15% were those detected previously; repeated positives occurred most frequently with adenovirus. Sequencing results were available in 13 children with repeated adenovirus detection; the following 4 patterns of infection were identified (16 instances): (1) adenovirus of the same serotype and strain detected continuously (n = 8 instances), (2) adenovirus of different serotypes detected during sequential URI episodes (n = 3), (3) adenovirus of the same serotype but different strains detected during sequential URI episodes (n = 3), and (4) adenovirus of the same serotype and strain detected intermittently (n = 2). Conclusions: Among children with frequent URIs, repeated positive PCR results for adenovirus NA may represent a new serotype/strain, or persistence of viral NA. Results must be interpreted with caution; clinical correlation and presence of other viruses are important. Further longitudinal studies of children during and after infection are required for better understanding of the clinical significance of positive PCR tests for adenovirus NA in the respiratory tract.

Association between cytokine gene polymorphisms and risk for upper respiratory tract infection and acute otitis media

BACKGROUND We previously reported an association between tumor necrosis factor alpha (TNFalpha)(-308)and interleukin (IL)-6(-174) polymorphisms and otitis susceptibility by history. Acute otitis media occurs most commonly as a complication of upper respiratory tract infection (URI); it is not clear why some children develop acute otitis media after URI and others do not. Our objective was to prospectively evaluate the association of TNFalpha(-308)and IL-6(-174) polymorphisms with URI and with acute otitis media development after URI. METHODS Children aged 6-35 months were prospectively followed for occurrences of URI and acute otitis media. Blood or buccal mucosa samples were collected for DNA extraction to determine cytokine genotypes. Active and passive surveillance was used to capture all URI episodes during the 1-year follow-up period in order to study the rate of acute otitis media following URI. Data were analyzed using SAS software (SAS Institute) and general estimating equations modeling. RESULTS Two hundred forty-two children were followed over 2689 patient-months and had DNA genotyped; 1235 URI episodes occurred, and 392 (32%) were complicated by acute otitis media. Children who had IL-6(-174) polymorphism had a higher susceptibility to URI during the study period (incidence density ratio, 1.24) and were more likely to meet established otitis susceptibility criteria (P < .01). Presence of TNFalpha(-308) polymorphism was associated with increased risk for acute otitis media after an episode of URI (odds ratio, 1.43). CONCLUSIONS TNFalpha(-308) and IL-6(-174) genotypes are associated with increased risk for symptomatic URI and acute otitis media following URI. Future studies may be designed to carefully look at the interaction of these genetic polymorphisms with modifiable environmental risk factors.

Clinical spectrum of acute otitis media complicating upper respiratory tract viral infection

Background: Acute otitis media (AOM) often occurs as a complication of upper respiratory tract infection (URI). Objective: To describe otoscopic findings during URI, the full clinical spectrum of AOM, and outcome of cases managed with watchful waiting. Methods: In a prospective study of 294 healthy children (6 months–3 years), characteristics of AOM complicating URI were studied. Otoscopic findings were categorized by tympanic membrane (TM) position, color, translucency, and mobility. Otoscopic score was assigned based on McCormick otoscopy scale (OS)-8 scale. Results: During days 1 to 7 of URI, otoscopic findings at 1114 visits were consistent with AOM in 22%; myringitis (inflamed TM, no fluid) was diagnosed in 7%. In AOM episodes diagnosed within 28 days of URI onset, TM position was described as: nonbulging (19%), mild bulging (45%), bulging (29%), and TM perforation occurred in (6%). OS-8 scale showed mild TM inflammation (OS, 2–3) in 6%, moderate (OS, 4–5) in 59%, and severe (OS, 6–8) in 35%. In 54% of 126 bilateral AOM episodes, inflammation of both TMs was at different stages. Of 28 cases of nonsevere AOM managed with watchful waiting, 4 progressed and 3 later required an antibiotic. Conclusions: AOM is a spectrum of infection that may present at various stages, even in the same child with bilateral disease. During URI, otoscopic changes are observed from the first day of onset. Understanding the wide clinical spectrum of AOM is needed to help with future clinical trial design and development of a scoring system to establish treatment criteria that will minimize antibiotic use.

Clinical presentation of tuberculosis in culture-positive children

BACKGROUND Because tuberculosis (TB) in children implies recent infection, children serve as sentinels for disease transmission within a community. Despite the significance of diagnosing tuberculosis in children, most cases are diagnosed on clinical evidence rather than laboratory findings. METHODS We analyzed the demographic and clinical presentation of 156 children with culture proven tuberculosis using Epi-Info Version 6. RESULTS Although the clinical characteristics of this population were generally consistent with those seen in previous studies, several unexpected results were observed. Boys were overrepresented in the group of very young children (72% < 1 year). Many of the children had coexisting diseases not known to predispose to TB (37%). Cavitation, usually observed in older children, was seen in four children < or = 1 year of age. Few children were homeless or HIV-infected, but many (42%) lived in female-headed households. Of the adult contacts at risk for TB, many (49%) were recent immigrants to the US. Overall 34% of the population was either foreign born or the children of recent immigrants. CONCLUSIONS This series of 156 culture-positive children provides an understanding of the risk factors and clinical presentation of pediatric tuberculosis. The data emphasize the impact of the childs environment on the risk for tuberculosis.