Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis.

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.

Ototoxicity resulting from intracochlear perfusion of Streptococcus pneumoniae in the guinea pig is modified by cefotaxime or amoxycillin pretreatment.

Acute changes in the electrophysiology and ultrastructure of the organ of Corti were studied after microperfusion of c. 5 x 10(6) CFU of serotype 2 Streptococcus pneumoniae D39 or Escherichia coli K-12 directly into the scala tympani of guinea pigs. Hearing loss was assessed by recording the auditory nerve compound action potential response to a 10 kHz tone pip. Mean hearing loss 3 h after pneumococcal perfusion (n = 4) was 44 dB, compared to 6 dB after E. coli perfusion (n = 4) (P<0.001). After pneumococcal perfusion, scanning electron microscopy revealed damage to hair cell stereocilia and cratering of the apical surface of supporting cells. Intraperitoneal injection of 100 mg/kg cefotaxime (n = 4) or 100 mg/kg amoxycillin (n = 4) 30 min before perfusion of pneumococci significantly reduced mean hearing loss to 23 dB (P=0.01) or 20 dB (P=0.01), respectively, and diminished ultrastructural damage. The data suggest that if pneumococci invade the inner ear during meningitis, cochlear deafness may rapidly ensue.

Chickenpox in childhood. A review prepared for the UK Advisory Group on Chickenpox on behalf of the British Society for the Study of Infection.

Chickenpox in childhood is a milder condition than in older patients, but serious and even fatal complications may occur. These occur especially in immunosuppressed individuals, but can also be seen in normal children. The commonest of these is secondary bacterial infection with staphylococci or streptococci. Reye's syndrome is now rare in chickenpox, since aspirin no longer used in treatment. Aciclovir and VZIG (varicella zoster immune globulin) have a role in the management of chickenpox in the immunosuppressed or immunodeficient child, and aciclovir may be valuable in managing some normal children. Chickenpox should not always be considered a trivial illness.

Imported infections in east Birmingham children.

This 15-month prospective study of admissions to a children's ward found imported infections in 58 children (1.3% of admissions), aged between two months and 15 years. Most had visited the Indian subcontinent 14 (1-341) days earlier. Few had taken preventative measures. The commonest infection was malaria (n = 23).

A role for pneumolysin but not neuraminidase in the hearing loss and cochlear damage induced by experimental pneumococcal meningitis in guinea pigs.

We investigated the roles of pneumolysin and neuraminidase in the pathogenesis of deafness and cochlear damage during experimental pneumococcal meningitis. Anesthetized guinea pigs were inoculated intracranially with 7.5 log10 CFU of either (i) wild-type Streptococcus pneumoniae D39 (n = 8), (ii) PLN-A, a defined isogenic derivative of D39 deficient in pneumolysin (n = 5), or (iii) deltaNA1, a new derivative of D39 deficient in neuraminidase constructed by insertion-duplication mutagenesis of the nanA gene (n = 5). To quantify hearing loss, the auditory nerve compound action potential evoked by a tone pulse was recorded from the round window membrane of the cochlea every 3 h for 12 h. The organ of Corti was intravitally fixed for subsequent examination by high-resolution scanning and transmission electron microscopy. All animals sustained similar meningeal inflammatory responses. PLN-A induced significantly less hearing loss than D39 over the frequency range of 3 to 10 kHz. Levels of mean hearing loss at 10 kHz 12 h postinoculation were as follows: D39, 50 dB; deltaNA1, 52 dB (P = 0.76 versus D39), and PLN-A, 12 dB (P < 0.0001 versus D39). The mean rates of hearing loss at 10 kHz were 4.4 dB/h for D39, 4.3 dB/h for deltaNA1, and just 1.0 dB/h for PLN-A (P < 0.0001 versus D39). Suppurative labyrinthitis was universal. PLN-A induced the accumulation of less protein in the cerebrospinal fluid (P = 0.04 versus D39). Infection with D39 and deltaNA1 induced significant damage to the reticular lamina, the sensory hair cells, and supporting cells of the organ of Corti. By contrast, after infection with PLN-A, the organ of Corti appeared virtually intact. Pneumolysin seems to be the principal cause of cochlear damage in this model of meningogenic deafness. No clear pathogenic role was demonstrated for neuraminidase.

Possible involvement of nitric oxide in the sensorineural hearing loss of bacterial meningitis.

Microperfusion of scala tympani with the NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), produced marked depression of the compound action potential (CAP) and cochlear microphonic (CM) together with severe and widespread morphological damage to hair cells and supporting cells in the organ of Corti. In addition, direct perfusion of N-methyl-D-aspartate (NMDA) into scala tympani, which probably induces excess stimulation of NMDA receptors within the cochlea and which is known to lead to the release of NO, was found to elicit similar electrophysiological and structural lesions in the cochlea. Pre-perfusion of scala tympani with L-methyl arginine (L-MA), which inhibits the release of NO, or superoxide dismutase (SOD), an O2-scavenger, conferred marked protection upon the cochlea from the lesions caused by NO donors. These observations indicate that enhanced NO production is likely to be an important factor responsible for pathological insult of the cochlea. The possibility is discussed that this factor is involved in the chain of events leading to hearing loss caused by bacterial meningitis. Such hearing loss is a major sequela of bacterial meningitis in children.

Macrolides in the management of streptococcal pharyngitis/tonsillitis.

The most frequent bacterial cause of pharyngitis/tonsillitis, a common infection in children, is group A beta-hemolytic streptococci. Prevention of acute rheumatic fever is the principal goal of treatment, although antibiotic therapy may also relieve the signs and symptoms of infection, shorten the infective period and prevent suppurative complications. Penicillin is the drug of choice. Alternatives are required, however, for patients allergic to penicillin and may be needed if the rate of bacteriologic failure with penicillin observed during the past decade continues. Erythromycin is generally effective in this infection, but its use, especially in children, is complicated by the need for multiple daily doses, a lengthy treatment period and a high rate of gastrointestinal side effects. The newer macrolides clarithromycin and azithromycin offer lower rates of gastrointestinal complaints and more convenient dosing. Clarithromycin is recommended for twice daily and azithromycin for once daily administration. Because of its prolonged tissue half-life, the recommended duration of azithromycin therapy is 5 days, compared with 10 days for penicillin, erythromycin and clarithromycin. Newer macrolides are rational alternatives to erythromycin for streptococcal pharyngitis/tonsillitis in penicillin-allergic patients.

Future indications for macrolides.

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.

Hearing loss during bacterial meningitis.

OBJECTIVE: To determine the natural history and pathogenesis of hearing loss in children with acute bacterial meningitis. DESIGN: Multicentre prospective study. SETTING: 21 hospitals in the south and west of England and South Wales. SUBJECTS: 124 children between the ages of 4 weeks and 16 years with newly diagnosed bacterial meningitis. METHODS: Children underwent repeated audiological assessment with the first tests being performed within six hours of diagnosis. By using a combination of otoacoustic emissions, auditory brainstem responses, and tympanometry the differences between cochlear, neural, and conductive defects were distinguished. RESULTS: Ninety two children (74%) had meningococcal and 18 (15%) had pneumococcal meningitis. All cases of hearing loss were apparent at the time of the first assessment. Three children (2.4%, 95% confidence interval (CI) 0.5 to 6.9%) had permanent sensorineural hearing loss. Thirteen children (10.5%) had reversible hearing loss of whom nine had an impairment that resolved within 48 hours of diagnosis. It is believed that this "fleeting' hearing loss has not been reported previously. The cochlea was identified as the site of the lesion in both the permanent sensorineural and reversible impairments. Hearing loss was more common in children who had been ill for more than 24 hours (relative risk 2.72; 95% CI 0.93 to 7.98). CONCLUSIONS: Sensorineural hearing loss developed during the earliest stages of meningitis. Permanent deafness was rare but 10% of the patients had a rapidly reversible cochlear dysfunction. This may have progressed to permanent deafness if the patients had not been treated promptly.

Acute otitis media and otitis media with effusion in children with bacterial meningitis.

Acute otitis media and otitis media with effusion (OME) have often been observed in children with bacterial meningitis. OME has also been proposed as the mechanism of reversible hearing loss after meningitis. In this controlled study, children with acute bacterial meningitis were studied using auditory brainstem responses (ABR), otoacoustic emissions, tympanometry and otoscopy. An age- and sex-matched control was recruited for each patient and the incidence of acute otitis media and OME was compared between the two groups. One hundred and twenty-four children with meningitis were studied. Ninety-two children (74 per cent) had meningococcal meningitis. Five patients (4 per cent) had conductive hearing loss (ABR threshold > or = 30 dB HL) at the time of discharge from hospital. None of the patients or controls had acute otitis media. Patients and controls were well matched for risk factors for OME and the prevalence of middle ear effusion in patients and controls was 7.2 per cent and 11.3 per cent respectively. The relative risk of OME in the children with meningitis was 0.64 (95 per cent confidence interval 0.29 to 1.42). After nine months, three of the five children with meningitis and conductive hearing loss had regained normal hearing. In contrast to previous reports, there was no relationship between bacterial meningitis and acute otitis media or OME in this study. Nevertheless, coincidental conductive hearing defects were identified as the cause of reversible hearing loss in three patients.

The cochlear lesion in experimental bacterial meningitis of the rabbit.

Sensorineural hearing loss was studied in a rabbit model of experimental bacterial meningitis using electrophysiological and ultrastructural techniques. Hearing impairment was monitored by auditory brain-stem evoked responses (ABERs) and concomitant structural lesions were identified by both transmission (TEM) and scanning (SEM) electron microscopy. Meningitis was induced by intra-cerebrospinal fluid injection of either Escherichia coli (strain 2073 and type K-12) or Haemophilus influenzae type b. Auditory loss of approximately equal to 10 dB occurred in all rabbits by about 10 hours post infection and progressed in severity until by 20 h following infection, hearing losses up to and > 60 dB were obtained. At levels of hearing loss < 20 dB ultrastructural damage to the organ of Corti was barely detectable. With greater levels of hearing loss, patchy structural damage to hair cells, synaptic nerve terminals, supporting cells and inner spiral sulcus cells and cells of the stria vascularis was clearly evident. Bacteria were found in scala tympani, the basilar membrane, the organ of Corti, scala media, the spiral ligament and at the margin of the stria vascularis. Evidence of bleeding was found in some cochleas; erythrocytes were found in scala tympani, scala media, amongst hair cells and beneath the tectorial membrane. The results show that hearing loss is associated with bacterial invasion and damage to the organ of Corti and that the cause of hearing loss is likely to result from multiple lesions within the cochlea. Lesions to sensory cells almost certainly will produce permanent hearing loss. Lesions to supporting cells, nerve terminals and to stria vascularis may well produce only temporary hearing loss.

Primary Sjogren's syndrome and rampant dental caries in a 5-year-old child.

A 5-year-old boy of Pakistani parents first presented with rampant dental caries and later developed bilateral parotid gland enlargement accompanied by intermittent nocturnal fever, anorexia, lethargy and weight loss. Investigations revealed anaemia, hypergammaglobulinaemia, elevated non-specific indices of inflammation, a reduced Schirmer's test value, lymphocytic infiltration and some atrophy of the parotid gland. The parotid gland enlargement, low Schirmer's test value and salivary gland biopsy showing non-focal lymphocytic infiltration led to the diagnosis of primary Sjogren's syndrome. The present case report highlights the need for health professionals to be aware that Sjogren's syndrome is a possible, if rare, predisposing cause of rampant dental caries in children.

Otoacoustic emissions as a screening test for hearing impairment in children.

Transient evoked otoacoustic emissions (TEOAEs) are low amplitude sound waves produced by the healthy cochlea. They can be recorded with a microphone in the external ear. TEOAEs are abolished by hearing losses of 30 dB or more. The feasibility of using TEOAEs as a screening test for hearing loss in children was studied. TEOAE recordings were attempted in 56 children attending an audiology clinic. Recordings were possible from both ears in 52 children; of these 104 ears, 32 had hearing deficits of 30 dB or more. Hearing status was compared with the results of six TEOAE screening criteria. All criteria had a sensitivity of 1.00. Four standard TEOAE criteria yielded specificities of 0.46-0.58. Two new criteria derived from analysis of limited frequencies from the TEOAE waveform gave specificities of 0.76 and 0.82. It can be concluded that, when appropriate pass/fail criteria are employed, TEOAEs are a feasible screening test in children.

Epidemiology of neonatal infections.

Neonatal infections can be considered in three groups, those acquired antenatally, perinatally and nosocomially. For many years it has been recognized that antenatal infections may cause death or serious fetal damage, but only recently have the more subtle features of antenatal infection been recognized. These include particularly the ability of some (such as toxoplasmosis) to produce disease many years later. Perinatal infection is often the result of maternal carriage of organisms, usually asymptomatically, and a variety of treatment approaches including immunotherapy (for hepatitis B) and antibacterial prophylaxis (for chlamydia) are being used to reduce the short- and long-term morbidity associated with this route of neonatal infection. Nosocomial infection in the neonatal nursery, and particularly in the neonatal intensive care unit may again lead to longer term problems in the infant, and organisms such as staphylococci or salmonella acquired during neonatal life may cause invasive disease weeks or even months later. The prevention of nosocomial infection will depend on the synthesis of a variety of approaches to reduce the number and spread of organisms in the environment of the vulnerable neonate.

Current trends in the management of bacterial meningitis.

The relevance of the host inflammatory response in the pathophysiology of bacterial meningitis is an important new concept. Modulation of this process by steroids may significantly affect the prognosis. We examine current trends in the clinical management of bacterial meningitis.

Ependymal cells of the choroid plexus express tumour necrosis factor-alpha.

Tumour necrosis factor-alpha (TNF alpha) is a major proinflammatory cytokine which appears in the cerebrospinal fluid very early after endotoxin challenge, and is likely to be produced locally. Following in vivo and in vitro challenge with endotoxin, we have demonstrated immunocytochemically and by in situ hybridization that pig and guinea-pig choroid plexus ependymal cells can produce TNF alpha. Immuno-electron microscopy shows that this protein is localized within ependymal cells to the cytoplasm and microvilli. We suggest that this TNF alpha may be important in the initiation of the inflammatory response in bacterial meningitis.

Cytotoxic effects on hair cells of guinea pig cochlea produced by pneumolysin, the thiol activated toxin of Streptococcus pneumoniae.

The cytolytic toxin, pneumolysin, from the gram positive bacterium, Streptococcus pneumoniae, when perfused through the scala tympani of the guinea pig cochlea reduced the amplitude of both the compound action potential and the cochlear microphonic potential. When the surface of the organ of Corti was examined by scanning electron microscopy, both inner and outer hair cells and supporting cells were found to be damaged. Inner hair cells and outer hair cells of row 3 were the most susceptible to damage by pneumolysin, followed by row 2 and then by row 1 of the outer hair cells. Damage to hair cells included disruption and splaying of stereocilia, loss of stereocilia and complete dissolution of hair bundles. Apical surfaces of hair cells and supporting cells were torn, pitted and cratered with shrinkage and tearing of cell boundaries. Within the dose range perfused (0.05-1 micrograms/microliters in a 10 microliters aliquot), the magnitude of the physiological and anatomical lesions was concentration dependent. The cytotoxic effects of pneumolysin reported here may be clinically significant factors in deafness caused by meningitis and otitis media in humans.

Experimental reovirus type 3-induced murine biliary tract disease.

The aims of this experiment were: (1) to establish a reovirus type 3-induced murine model of biliary atresia/neonatal hepatitis that as far as possible corresponds to the human disease; (2) to demonstrate that the disease is histologically similar to the human disease, and to investigate the natural history of reovirus type 3 infection in this model; (3) to study the host-virus interrelationships at a molecular level; and (4) to develop sensitive assays that could be translated to the human disease. In this study we were unable to produce an exact model for extrahepatic biliary atresia (EHBA) in the laboratory mouse following a perinatal reovirus type 3 infection. However, the ability of reovirus type 3 to persist in the murine liver and the effects produced in the offspring of infected pregnant mice indicate that this preparation may provide the basis for the eventual development of the experimental model of EHBA.