Spectrum of disease due to Branhamella catarrhalis in children with particular reference to acute otitis media.

For many years Branhamella catarrhalis was regarded as a non-pathogenic inhabitant of the respiratory tract. This article outlines the spectrum of B. catarrhalis disease in childhood and the extent of the evidence for a pathogenic role of the organism. B. catarrhalis is a rare etiologic agent in septicemia, meningitis, and other systemic illness in both apparently normal and immunocompromised infants and children. It is an unusual cause of ophthalmia neonatorum, but can be confused with Neisseria gonorrhoeae. Whether or not B. catarrhalis is acquired from the birth canal in these cases has not been established. B. catarrhalis is most common as a respiratory tract pathogen in children, including pneumonia, bacterial tracheitis, sinusitis, and otitis media. Since it is difficult to rigorously document pathogenicity of any bacterium in bronchopulmonary infections in children, it is probable that the spectrum of B. catarrhalis disease is wider than that reported to date. The evidence for pathogenicity in acute otitis media is more extensive than for other infections. Otitis media due to B. catarrhalis is clinically similar to that due to other pathogens. B. catarrhalis can be isolated in pure culture from the middle ear exudate and persists if there is no antibacterial treatment. Gram-negative intracellular and extracellular diplococci can be seen on smears of the inflammatory exudate. There is preliminary evidence that there is an antibody response in B. catarrhalis otitis media. B. catarrhalis has emerged as an important and common pathogen in neonates, infants, and children.

Bacterial etiology of conjunctivitis-otitis media syndrome.

Simultaneous cultures of conjunctivae and middle ear exudates were obtained from 20 episodes of the syndrome of purulent conjunctivitis and otitis media. Paired cultures from 18 episodes yielded Haemophilus influenzae at both sites. In two cases with prior topical antibacterial therapy of the conjunctivitis, H influenzae was isolated from the middle ear exudate only. Biotyping and outer membrane protein analysis of H influenzae isolates from five patients demonstrated that: conjunctival and middle ear strains were concordant in all cases, and all five patients had different strains. The conjunctivitis-otitis media syndrome is most often caused by strains of nontypable H influenzae of diverse clonotype.

Persistence of antibody and booster responses to reimmunization with Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children initially immunized at 15 to 24 months of age.

To evaluate the persistence of antibody after Haemophilus influenzae type b polysaccharide vaccine (PRP) and H influenzae type b polysaccharide diphtheria toxoid conjugate vaccine (PRP-D), a group of 141 infants initially immunized between 15 and 24 months of age were studied 1 year later. One month after immunization with PRP, the man anti-PRP antibody level was 0.27 microgram/mL and 1 year later was 0.29 microgram/mL (not significant). In the group immunized with PRP-D, the levels were 1.34 micrograms/mL and 1.20 micrograms/mL (not significant), respectively. To evaluate immunogenicity and safety of a booster immunization 1 year after initial vaccination, subjects were randomly assigned to receive saline, PRP, or PRP-D. In addition, 73 age-matched previously unimmunized subjects were vaccinated with PRP or PRP-D. In all groups, adverse reactions were minor and resolved by 48 hours. Subjects receiving booster immunization with PRP or PRP-D had significantly greater antibody responses than children of the same age receiving their first dose of vaccine. The highest antibody levels were achieved in children initially immunized with PRP-D, regardless of whether the booster vaccine was PRP (112.8 micrograms/mL) or PRP-D (122.0 micrograms/mL) (not significant). Antibody levels after booster vaccine were significantly lower in those initially given PRP compared with those initially given PRP-D but significantly higher than in age-matched previously unimmunized control subjects (PRP booster 3.16 micrograms/mL vs control of 0.62 microgram/mL [P less than .05]; PRP-D booster 12.31 micrograms/mL vs control 2.31 micrograms/mL [P less than .01]).

Serous and recurrent otitis media. Pharmacological or surgical management?

The management of recurrent acute otitis media and serous otitis media is both challenging and controversial. The efficacy of antimicrobial prophylaxis of children at high risk for recurrent acute otitis media is established, but the indications for such therapy are controversial. Tympanostomy tube insertion also decreases the frequency of recurrent otitis media. High-risk children can be successfully managed with chemoprophylaxis from autumn through to spring. If this fails, then tympanostomy tube insertion should be considered. Serous otitis media that follows acute otitis media resolves spontaneously in more than 90% of cases. Serous otitis media of unknown onset also has a strong tendency to resolve without treatment. Antihistamines and decongestants, although popular, have no significant effect on the course of serous otitis media. Antimicrobial therapy has a modest effect on the resolution of serous otitis media. Tympanostomy tubes usually improve the conductive hearing loss associated with serous otitis media and should be used when bilateral serous otitis media fails to resolve spontaneously. If repeated tympanostomy tube insertion fails, then adenoidectomy should be considered. With the course of management outlined, most children will have a successful outcome with conservative therapy and the need for surgery will be minimised.

Efficacy of Haemophilus influenzae type b vaccines in Massachusetts children 18 to 59 months of age.

Since 1987 Haemophilus influenzae b (Hib) conjugate vaccines have been licensed for use in children ages 18 months and older. Before licensure there were no clinical trials of a single dose of any conjugate vaccine in children ages 18 months or older. To fulfill this need we performed an age- and residence-matched case-control study of the efficacy of Hib vaccines. In our study population the protective efficacy (PE) of Hib-diphtheria toxoid conjugate vaccine was 88% (95% confidence interval, 45 to 98%). No vaccine failures were observed with Hib oligosaccharide CRM197 diphtheria protein conjugate vaccine, but usage was not sufficient to establish efficacy: PE = 100% (95% confidence interval, -37 to 100%). The protective efficacy of Hib capsular polysaccharide vaccine was 18% (95% confidence interval -487 to 89%). We conclude that for children ages 18 to 60 months a single dose of the Hib conjugate vaccine, PRP-D, is protective against invasive Hib infections. Consistent with most studies Hib polysaccharide vaccine provided suboptimal protection.

Depression of anticapsular antibody after immunization with Haemophilus influenzae type b polysaccharide-diphtheria conjugate vaccine.

Invasive Haemophilus influenzae type b infections have been observed in the week after immunization with capsular polysaccharide vaccine. We sought to document depression of antibody concentrations after immunization of 18-month-old infants with H. influenzae type b capsular polysaccharide-diphtheria conjugate vaccine. All 9 infants with detectable preimmunization anticapsular antibody had depression of antibody concentrations on the second day after immunization (P = 0.002). By Day 7 all had achieved anticapsular antibody concentrations greater than 0.15 micrograms/ml, a level believed to provide protection to immediate challenge with H. influenzae type b. Of those without detectable preimmunization antibody, 7 of 21 (33%; 95% confidence interval, 11 to 56%) had not achieved concentrations of greater than 0.15 mg/ml 1 week after immunization. We conclude that there is depression of anticapsular antibody concentrations during the first week after immunization with H. influenzae type b capsular polysaccharide-diphtheria conjugate vaccine. We speculate that H. influenzae type b infections after immunization with H. influenzae type b vaccines may be the result of: (1) low antibody concentrations because of either depression of antibody concentrations or failure to develop antibody; and (2) exposure to H. influenzae type b. Depression of antibody concentrations could be explained by binding of in vivo antibody to the vaccine.

Ipsilateral acoustic reflexes in infants.

Ipsilateral acoustic reflex thresholds were studied in otoscopically normal ears of infants 2 weeks to 12 months old. Probe tones of 220 and 660 Hz and pure tone activators were used. Reflex recordings were free of activator artifact and were measured using quantitative standards. Reflexes were detected in 85% to 95% of infant ears for 500, 1,000, and 2,000 Hz activators but were present in only 76% of ears at 4,000 Hz. Median thresholds of 80 to 85 dB hearing level were obtained with all activators and both probe tones. There were no differences in proportions of reflexes obtained with the two probe tones. With a 500-Hz activator, thresholds at 220 Hz were lower than those at 660 Hz, while no threshold differences were demonstrated between probe tones at other activators. No relationship was demonstrated between age in the first year of life and presence or threshold of reflexes. Ipsilateral acoustic reflex measures have potential use in the identification of hearing loss and middle ear disease in infancy.

The Red Ear-drum: To Treat or Not To Treat?

Acute otitis media is typified by the patient with fever, earache, and a "red" ear-drum. Suppurative otitis media, however, often presents without specific symptoms, and redness is the least reliable physical finding. Impaired tympanic membrane mobility on pneumatic otoscopy and bulging and opacification of the ear-drum are more reliable and important physical signs. Review of placebo-controlled trials reveals that antimicrobial therapy produces more rapid relief of fever and earache in patients with the most symptoms. Effects on patients with fewer symptoms are more modest. Amoxicillin remains the standard first-line treatment. Reasonable indications for alternative therapy are reviewed.

Acute phase reactants and risk of bacterial meningitis among febrile infants and children.

STUDY OBJECTIVE: To test the hypothesis that quantitation of either C-reactive protein (CRP) or the total peripheral WBC count can improve clinical detection of underlying bacterial meningitis among young febrile children. DESIGN: Cross-sectional survey of selected symptoms of central nervous system infection, signs of meningeal irritation and/or elevated intracranial pressure, levels of CRP in serum, and total peripheral WBC counts among unselected pediatric patients undergoing lumbar punctures for evaluation of acute febrile illnesses. SETTING: Emergency department and acute care "walk-in" clinic of an urban, university-affiliated general hospital. PARTICIPANTS: 160 previously well, acutely febrile infants and children (median age, 6 months). RESULTS: The prevalence of bacterial meningitis was 6%. Sensitivity of symptoms was 1.00 and specificity was 0.17. Sensitivity of signs was 0.70 and specificity was 0.81. Of the acute phase reactants, sensitivity of a CRP level of more than 1.0 mg/dL was 0.80, while that of a total peripheral WBC count of more than 15,000/mm3 was 0.40. The presence of signs and/or a CRP level of more than 1.0 mg/dL correctly identified all children with bacterial meningitis (sensitivity, 1.00). The absence of signs and a CRP level of 1.0 mg/dL or less correctly identified 71 of 150 children without bacterial meningitis (specificity, 0.47). Of 125 children without meningeal signs, the combination of symptoms and a CRP level of more than 1.0 mg/dL correctly identified all three children with bacterial meningitis (sensitivity, 1.00). The absence of these symptoms and/or a CRP level of 1.0 mg/dL or less correctly identified 80 of 122 children without bacterial meningitis (specificity, 0.66). CONCLUSION: Quantitation of CRP but not the total peripheral WBC count can increase the sensitivity of physical examination findings and the specificity of symptoms for the diagnosis of bacterial meningitis. Measurement of CRP in serum is useful as an adjunct to history and physical examination for the detection of acute bacterial meningitis in the acutely febrile child.

The changing epidemiology of invasive bacterial infections in Massachusetts children, 1984 through 1991.

Coincident with the licensure of Haemophilus influenzae b conjugate vaccines from 1987 to 1990, the incidence of meningitis and other invasive infections caused by H influenzae type b declined in Massachusetts children by 87% and 91%, respectively. By 1991, Neisseria meningitidis had replaced H influenzae b as the leading cause of bacterial meningitis, accounting for 57% of cases. During the period 1984 through 1991, serogroup C displaced sero-group B as the most common cause of N meningitidis disease. Streptococcus pneumoniae caused 92% of nonmeningitis invasive disease, with sero-groups 14, 6, 19, 18, 4, 23, and 9 causing 94.5% of infections. These findings have implications for the development of additional polysaccharide-protein conjugate vaccines for the prevention of childhood infections.

Measuring the comparative efficacy of antibacterial agents for acute otitis media: the "Pollyanna phenomenon".

In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success, (62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media. These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy: (1) tympanocentesis and culture before and during therapy (bacteriologic efficacy), (2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media. For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media. For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media. We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are. The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media.

Ipsilateral and contralateral acoustic reflexes in neonates.

Ipsilateral and contralateral acoustic reflexes were studied in neonates using 220 and 660 Hz probe tones and 500, 1000, 2000, and 4000 Hz activators. Activator sound pressure level was measured in all ears. Ipsilateral and contralateral reflexes were detected three times more frequently with a 660 Hz probe tone than with a 220 Hz probe tone. The maximum detection rate (76%) occurred with 1000 and 2000 Hz ipsilateral activators and the 660 probe tone. There was no significant difference between neonatal and adult ipsilateral thresholds at 500, 1000, and 4000 Hz. Neonatal intrameatal sound pressure levels for ipsilateral activators were found to be significantly higher than would be indicated from the otoadmittance meter manufacturer's specifications.

The 1993 epidemic of pertussis in Cincinnati. Resurgence of disease in a highly immunized population of children.

BACKGROUND: In 1993 there was a resurgence of pertussis in the United States. Altogether, 6335 cases were reported, the most in 26 years. METHODS: Using active microbiologic surveillance, we investigated the epidemic of pertussis in Greater Cincinnati in 1993. The population of 1.7 million in this area is served by a single children's hospital and pertussis laboratory. We prospectively followed patients given a new diagnosis of pertussis in July through September 1993 to determine the characteristics of the epidemic. RESULTS: From 1979 to 1992, there was a cumulative total of 542 cases of pertussis. In 1993, 352 cases were diagnosed, an increase of 259 percent over the 1992 total. Sixty-three percent of the cases had positive cultures for Bordetella pertussis, 18 percent were positive on direct fluorescent-antibody testing only, and 19 percent were diagnosed clinically. The outbreak began in the suburbs during the summer and spread through Greater Cincinnati. Of 255 total cases diagnosed in July through September (195 excess cases over the maximal base-line level of 20 per month in the previous 14 years), 75 percent were in white patients and 67 percent of the patients had private insurance or paid for care out of pocket. In 1993, as compared with 1979 through 1992, there was a shift in incidence from younger infants to older children; the percentages of cases according to age group were as follows: 0 to 6 months, 53 percent from 1979 through 1992 and 35 percent in 1993 (P < 0.001); 7 months to 5 years, 33 percent and 43 percent (P < 0.002); 6 to 12 years, 5 percent and 11 percent (P < 0.001); and more than 12 years, 5 percent and 11 percent (P < 0.003). Immunization records revealed that 74 percent (75 of 101) of the children with pertussis who were 19 months to 12 years old had received four or five doses of the combined diphtheria-pertussis-tetanus (DPT) vaccine, and that 82 percent (103 of 126) of those 7 to 71 months old had received at least three doses of DPT vaccine. The whole-cell vaccines used came from both of the major manufacturers (Connaught Laboratories and Lederle Laboratories). Disease was not severe, but 80 of the 255 children (31 percent) given diagnoses during the three epidemic months were hospitalized. There were no deaths. CONCLUSIONS: Since the 1993 pertussis epidemic in Cincinnati occurred primarily among children who had been appropriately immunized, it is clear that the whole-cell pertussis vaccine failed to give full protection against the disease.

Course and outcome of otitis media in early infancy: a prospective study.

We determined the course of otitis media in a prospective, longitudinal study of infants who were enrolled at birth and followed to age 1 year. Bilateral chronic otitis media with effusion developed in eight of 24 (33%) with onset of otitis media before age 2 months, compared to two of 30 (7%) with later onset (P = 0.012). Infants with bilateral chronic otitis media with effusion could be identified early: eight of 15 (53%) infants with bilateral middle ear effusion at age 2 months subsequently had bilateral chronic otitis media with effusion, compared to two of 55 (4%) infants without bilateral effusions at age 2 months (P = 0.000007). The onset of otitis media was symptomatic in 29 of 54 (54%), and asymptomatic in 25 of 54 (46%). If regular well-child examinations with otoscopy had not been performed in asymptomatic infants, bilateral chronic otitis media with effusion would not have been detected in six of 10 infants. Infants with otitis media in early infancy may be asymptomatic and are at high risk for chronic otitis media with effusion.