Infections Cause Hearing Loss

Otitis Media

A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion. FW Henderson, AM Collier, MA Sanyal, JM Watkins, DL Fairclough, WA Clyde Jr, FW Denny. N Engl J Med 1982 Jun 10;306(23):1377-1383. 14-year longitudinal study. "The incidence of this disorder was increased in children with viral respiratory infections (average relative risk, 3.2; P less than 0.0001). Infection with respiratory syncytial virus, influenza virus (type A or B), and adenovirus conferred a greater risk of otitis media than did infection with parainfluenza virus, enterovirus, or rhinovirus. Colonization of the nasopharynx with Str. pneumoniae or H. influenzae had a lesser effect on the incidence of the disease (average relative risk; 1.5; P less than 0.01). Infections with the viruses more closely associated with acute otitis media (respiratory syncytial virus, adenovirus, and influenza A or B) were correlated with an increased risk of recurrent disease."

Acute otitis media and respiratory virus infections. O Ruuskanen, M Arola, A Putto-Laurila, J Mertsola, O Meurman, MK Viljanen, P Halonen. Pediatr Infect Dis J 1989 Feb;8(2):94-99. 4524 cases of acute otitis media. "Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media."

Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae. A Håkansson, A Kidd, G Wadell, H Sabharwal, C Svanborg. Infect Immun 1994 Jul;62(7):2707-2714. In A549 cells. "Adenovirus (types 1, 2, 3, and 5) commonly causing respiratory tract infections increased the binding of adherent S. pneumoniae strains to the cells. This effect was not seen for other adenovirus types. Adenovirus infection did not change the adherence of cells of poorly adhering strains of S. pneumoniae or H. influenzae. The increase in adherence of S. pneumoniae could be inhibited by the DNA synthesis inhibitor cytosine arabinofuranoside, which is known to block the late phase of the adenovirus infection. When electron microscopy was used, there was no evidence that virus particles bound directly to bacteria. Adherence was not affected by pretreatment of the cells with virus particles or viral proteins. This suggested that adenovirus infection upregulated receptors for S. pneumoniae."

Increasing prevalence of recurrent otitis media among children in the United States. BP Lanphear, RS Byrd, P Auinger, CB Hall. Pediatrics 1997 Mar;99(3):E1. "BACKGROUND: The number of visits for otitis media, the most common diagnosis among preschool children, has increased during the past decade. This study was undertaken to determine whether there has been a concurrent increase in the prevalence of recurrent otitis media among children in the United States and to identify risk factors or demographic changes to explain the increase. METHODS: Secondary analyses of cross-sectional data from the Child Health Supplement to the 1981 and 1988 National Health Interview Surveys (n = 5189 [1981] and n = 6209 [1988]) were done to identify temporal changes in the prevalence and any associated risk factors of recurrent otitis media among children <6 years of age. RESULTS: Recurrent otitis among preschool children increased from 18.7% in 1981 to 26% in 1988 (odds ratio [OR] = 1.6, 95% confidence interval [CI] = 1.4, 1.7). Although the prevalence of recurrent otitis increased with age, the greatest increase in recurrent otitis media occurred in infants (OR = 1.9, CI = 1.3, 2.9)." "These data indicate that there has been a 44% increase in the prevalence of recurrent otitis media among preschool children in the United States from 1981 to 1988; an excess of 1.8 million children with recurrent otitis media."

Epidemiology of otitis media onset by six months of age. KA Daly, JE Brown, BR Lindgren, MH Meland, CT Le, GS Giebink. Pediatrics 1999 Jun;103(6 Pt 1):1158-1166. 596 infants from a health maintenance organization. 39% had an episode and 20% had recurrent otitis media. "[R]espiratory tract infection (relative risk [RR] 7.5), day care (RR 1. 7), >1 sibling (RR 1.4), maternal, paternal, and sibling OM history (RR 1.6, 1.5, and 1.7, respectively) were significantly related to early OM onset. ROM was related to respiratory tract infection (RR 9. 5), day care (RR 1.9), conjunctivitis (RR 2.0), maternal OM history (RR 1.9), and birth in the fall (RR 2.6)."

Importance of respiratory viruses in acute otitis media. T Heikkinen, T Chonmaitree. Clin Microbiol Rev 2003 Apr;16(2):230-241. Review. "[A]mple evidence derived from studies ranging from animal experiments to extensive clinical trials supports a crucial role for respiratory viruses in the etiology and pathogenesis of acute otitis media. Viral infection of the upper respiratory mucosa initiates the whole cascade of events that finally leads to the development of acute otitis media as a complication." "The relatively low rates of viral detection in nasopharyngeal specimens from children with AOM have raised doubts about the extent of viral involvement in the development of this disease. With the increasing availability of PCR-based assays, however, it has become obvious that the low rates have been caused by underdetection of existing viruses in studies where viral detection has been based only on viral culture and/or antigen detection methods. PCR has proved especially valuable in diagnosing rhinovirus infections, for which other methods have been suboptimal."

Trends in otitis media among children in the United States. P Auinger, BP Lanphear, HJ Kalkwarf, ME Mansour. Pediatrics 2003 Sep;112(3 Pt 1):514-520. From the Third National Health and Nutrition Examination Survey, 1988-1991 and 1991-1994. "After controlling for risk factors for OM, the prevalence of OM from phase I to phase II increased from 66.7% to 69.7% (odds ratio [OR] = 1.1; 95% confidence interval [CI] =.99, 1.1), early-onset OM increased from 41.1% to 45.8% (OR = 1.1; 95% CI = 1.03, 1.2), and repeated OM increased from 34.8% to 41.1% (OR = 1.2; 95% CI = 1.1, 1.4). This observed increase corresponds to 561,000 and 720,000 more children having early-onset OM and repeated OM, respectively."

Toll-like receptor 2-dependent NF{kappa}B activation is involved in nontypeable Haemophilus influenzae-induced MCP-1 up-regulation in the spiral ligament fibrocytes of the inner ear. SK Moon, JI Woo, HY Lee, R Park, J Shimada, H Pan, R Gellibolian, DJ Lim. Infection and Immunity 2007 Jul;75(7):3361-3372. Spiral ligament fibrocytes recognize pathogens and secrete cytokines, causing high-frequency hearing loss and labyrinthitis.

Immunopathogenesis of polymicrobial otitis media. LO Bakaletz. J Leukoc Biol 2010 Feb;87(2):213-222. Review. "One mechanism for the commonly observed association between a concurrent URT virus infection and subsequent bacterial superinfection is a result of the fact that cells infected with certain viruses are more permissive to bacterial adherence, ultimately leading to secondary infection and disease. The relevance of this hypothesis to pathogenesis of OM has been demonstrated as a result of the fact that many URT viruses do indeed augment adherence by specific bacterial pathogens of OM. For example, influenza A virus increases the adherence of S. pneumoniae to mouse tracheal epithelial cells but not of NTHI to chinchilla tracheal epithelium in organ culture. Infection with AV types 1, 2, 3, and 5 significantly enhances the binding of adherent strains of S. pneumoniae, which had been isolated from the NP of children with frequent episodes of AOM, to human lung epithelial cells in vitro. Similarly, RSV infection of A549 cells significantly enhances attachment by NTHI that specifically express one of several known adhesins. By flow cytometry, El Ahmer et al. showed that viral infection significantly increased adherence by all three groups of microorganisms most commonly associated with AOM and chronic OM to influenza A virus-infected Hep-2 cells. Through the use of a panel of mAb directed against specific cell-surface antigens, these latter investigators found that infection of Hep-2 cells with influenza A virus resulted in a significant increase in expression of known receptors for adherence used by several Gram-negative bacteria. More recently, it was shown that URT viruses can induce up-regulated expression of carcinoembryonic antigen-related cell adhesion molecule 1, ICAM1, and platelet-activating receptor, additional eukaryotic receptors known to be used for adherence by multiple human mucosal pathogens. Thus, virus-induced up-regulation of host cell-surface antigens that serve as bacterial receptor sites appears to be a common theme in the pathogenesis of OM as well as other diseases of the respiratory tract.... Even in the absence of a concurrent viral URT infection, children are colonized with the organisms that induce OM soon after birth. At 6 months of age, 26% of infants are colonized already with M. catarrhalis, 24% with S. pneumoniae, and 9% with NTHI. By 1 year of age, these percentages increased to 72%, 54%, and 33%, respectively. Early colonization is associated with early, initial episodes of AOM, and colonization with S. pneumoniae or H. influenzae in the first year of life increases the risk of becoming otitis-prone fourfold.... There is an additional, direct relationship between how frequently children are colonized by the pathogens of OM and the frequency of occurrence of AOM.... Among the viruses, influenza virus, parainfluenza virus, rhinovirus, coronavirus, RSV, and AV are those most commonly linked with AOM [70, 87, 88]; however, of these, rhinovirus and RSV are often more commonly identified than others [89]. Whereas rhinoviruses are typically more frequently identified by culture and other molecular mechanisms, RSV is more commonly associated with concurrent AOM. This strong association between RSV and concurrent AOM has been reported by many laboratories [66, 68, 90,91,92,93,94,95,96]." Amoxicillin concentrations in middle ear fluid are lower when a viral infection is also present.

Racial/ethnic and socioeconomic disparities in the prevalence and treatment of otitis media in children in the United States. DF Smith, EF Boss. Laryngoscope 2010 Nov;120(11):2306-2312. "Of 428 abstracts identified, 15 met inclusion criteria. Articles addressed OM prevalence (12 of 15), risk factors (9 of 15), and tympanostomy tube insertion (4 of 15). Minority racial/ethnic groups studied were Black (11 of 15), Hispanic (6 of 15), American Indian/Alaska Native (2 of 15), and Asian (1 of 15). Predominant findings showed: 1) the most common identified risk factor for OM is socioeconomic status; 2) considerable variability exists concerning racial/ethnic disparities in disease prevalence; and 3) White children are more likely to undergo tympanostomy tube insertion compared to Black or Hispanic children."

Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection. MM Pettigrew, JF Gent, RB Pyles, AL Miller, J Nokso-Koivisto, T Chonmaitree. J Clin Microbiol 2011 Sep 7 [Epub ahead of print]. "In unadjusted analyses of data from 194 children, adenovirus, bocavirus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were significantly associated with AOM (χ(2) p-values<0.05). Children with high respiratory syncytial virus load (≥3.16 × 10(7) copies/ml) experienced increased acute otitis media risk. Higher viral loads of bocavirus and metapneumovirus were not significantly associated with acute otitis media. In adjusted models controlling for the presence of key viruses, bacteria, and acute otitis media risk factors, acute otitis media risk was independently associated with: high RSV viral load with Streptococcus pneumoniae [OR 4.40, 95% CI (1.90, 10.19)]; Haemophilus influenzae [OR 2.04 95% CI (1.38, 3.02)]; risk was higher for presence of bocavirus and H. influenzae together [OR 3.61, 95% CI (1.90, 6.86)]. Acute otitis media risk differs by the specific viruses and bacteria involved. Acute otitis media prevention efforts should consider methods for reducing infections caused by respiratory syncytial virus, bocavirus, and adenovirus in addition to acute otitis media bacterial pathogens."

Sudden Sensorineural Hearing Loss

Are enterovirus infections a co-factor in sudden hearing loss? R Mentel, Kaftan H, U Wegner, A Reissmann, L Gürtler. J Med Virol 2004 Apr;72(4):625-629. 55 patients. "Serological screening of these patients for HSV and VZV failed to reveal significant differences between the patient group and the controls. In contrast, enterovirus sequences were detected by RT-PCR in 40% of the patient group, but in none of the controls, suggesting that enterovirus infections may be associated with sudden hearing loss."

Assessment of variation throughout the year in the incidence of idiopathic sudden sensorineural hearing loss. DN Jourdy, LA Donatelli, JD Victor, SH Selesnick. Otol Neurotol 2010 Jan;31(1):53-57. 97 patients. "Overall, no evidence was found for an uneven distribution or for a peak either by chi2 (p > 0.1), which assesses for any uneven distribution, or by the circular mean (p > 0.1), which assesses for a pattern of seasonal variation. In the subset of patients (24 of 97; 24.7%) who reported experiencing an upper respiratory infection before or concurrent with the onset of ISSHL, no evidence was found for an uneven distribution of hearing loss onset throughout the year either by chi2 (p > 0.1) or by the circular mean (p > 0.1)."

Systematic review of the evidence for the etiology of adult sudden sensorineural hearing loss. JK Chau, JR Lin, S Atashband, RA Irvine, BD Westerberg. Laryngoscope 2010 May;120(5):1011-1021. 23 articles with "Randomized controlled trials, prospective cohort studies, and retrospective reviews of consecutive patients in which a clear definition of SSNHL was stated and data from consecutive patients were reported with respect to etiology of hearing loss." "The suspected etiologies for patients suffering sudden sensorineural hearing loss included idiopathic (71.0%), infectious disease (12.8%), otologic disease (4.7%), trauma (4.2%), vascular or hematologic (2.8%), neoplastic (2.3%), and other causes (2.2%)."

Sudden Sensorineural Hearing Loss: Subclinical Viral and Toxoplasmosis Infections as Aetiology and How They Alter the Clinical Course. D Kikidis, TP Nikolopoulos, G Kampessis, G Stamatiou, A Chrysovergis. ORL J Otorhinolaryngol Relat Spec 2011 Mar 8;73(2):110-115. 84 consecutive patients. "All patients were assessed for specific IgM antibodies against cytomegalovirus, herpes simplex virus, toxoplasma and Epstein-Barr virus. All were treated with intravenous steroids and assigned to two groups: 76 IgM negative (NV group) and 8 IgM positive (no history of acute infection - V group). Results: The mean hearing level at presentation was 86.5 dB HL (median, 100) in the V group and 60.7 dB HL (median, 61) in the NV group. The difference was statistically significant (p = 0.003). The mean hearing level following treatment was 81.8 dB HL (median, 88) in the V group and 48.7 dB HL (median, 39) in the NV group. The difference was statistically significant (p = 0.004). There was a considerable improvement in hearing after treatment only in the NV group (p < 0.000001). Conclusions: Recent subclinical viral or toxoplasmosis infections may be involved in the pathogenesis of SSHL (in approx. 10% of cases), suggesting that SSHL is not a single disease. When certain viruses or toxoplasmoses are involved, the hearing is much worse in comparison to patients with no such indication of infection."

CMV is a Leading Cause of Deafness and Mental Impairment in Children

Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection. WD Williamson, GJ Demmler, AK Percy, FI Catlin. Pediatrics 1992 Dec;90(6):862-866. 59 infants with asymptomatic congenital CMV infection compared with 26 control infants. "Eight of 59 infected infants had congenital sensorineural hearing loss (SNHL) but none of the control subjects did. Longitudinal audiologic assessments revealed that 5 of the 8 infants had further deterioration of their SNHL; a ninth infant with initially normal hearing experienced a unilateral SNHL during the first year of life, with further deterioration subsequently. The frequency of SNHL was similar for infected infants born to mothers with recurrent CMV infections during pregnancy (2 of 9) and for those born to mothers who experienced primary CMV infections (5 of 26). There was a significant difference between the occurrence of hearing loss in infected infants with normal computed tomographic scans (2 of 40) compared with those with either periventricular radiolucencies (4 of 13) or calcifications (1 of 3)."

Report and Recommendations: NIDCD Workshop on Congenital Cytomegalovirus Infection and Hearing Loss. National Institute on Deafness and Other Communication Disorders, March 19-20, 2002. Summaries of work at the University of Alabama, Birmingham; Baylor College of Medicine; and the Collaborative Antiviral Study Group. "In limited population-based studies of hearing loss in infants, which have included virologic ascertainment of congenital infection, the results have suggested that CMV infection is a leading cause of sensorineural hearing loss and perhaps the leading cause in children."

Etiology of severe sensorineural hearing loss in children: independent impact of congenital cytomegalovirus infection and GJB2 mutations. H Ogawa, T Suzutani, Y Baba, S Koyano, N Nozawa, K Ishibashi, K Fujieda, N Inoue, K Omori. J Infect Dis 2007 Mar 15;195(6):782-788. 67 Japanese children with severe sensorineural hearing loss. "Congenital CMV infection and GJB2 mutations were identified in 15% and 24% of the patients, respectively. HHV-6 was not detected. All children with CMV-associated cases developed SNHL before they were 2 years old. Most children with CMV-associated SNHL had no obvious clinical abnormality at birth, and their viral loads were lower than those of symptomatic children."

GJB2 and GJB6 mutations in children with congenital cytomegalovirus infection. SA Ross, Z Novak, RA Kumbla, K Zhang, KB Fowler, S Boppana. Pediatr Res 2007 Jun;61(6):687-691. 149 children with congenital CMV infection and 380 uninfected neonates. "The study population was predominantly African American, and 4.3% of the subjects were carriers of a connexin 26 mutation. The overall frequency of GJB2 mutations was significantly higher in the group of children with CMV infection and hearing loss (21%) compared with those with CMV infection and normal hearing (3%, p = 0.017) and the group of uninfected newborns (3.9%, p = 0.016). Eight previously reported mutations (M34T, V27I, R127H, F83L, R143W, V37I, V84L, G160S), and four novel mutations (V167M, G4D, A40T, and R160Q) were detected. None of the study children had the 342-kb deletion (delGJB6-D13S1830) in GJB6, which suggests that this mutation does not play a role in hereditary deafness in the African American population. Although GJB2 mutations were detected in children with and without CMV-related hearing loss, those with hearing loss had a higher frequency of GJB2 mutations."

Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. A Kenneson, MJ Cannon. Rev Med Virol 2007 Jul-Aug;17(4):253-276. "The overall birth prevalence of congenital CMV infection was 0.64%, but varied considerably among different study populations. About 11% of live-born infants with congenital CMV infection were symptomatic, but the inter-study differences in definitions of symptomatic cases limit the interpretation of these data. Non-white race, low socioeconomic status (SES), premature birth, and neonatal intensive care unit admittance were risk factors for congenital CMV infection. Birth prevalence increased with maternal CMV seroprevalence. Maternal seroprevalence accounted for 29% of the variance in birth prevalence between study populations. Maternal seroprevalence and birth prevalence were both higher in study populations that were ascertained at birth rather than in the prenatal period. Thus, timing of ascertainment should be considered when interpreting birth prevalence estimates. Birth prevalence was inversely correlated with mean maternal age, but this relationship was not significant when controlling for maternal seroprevalence. The rate of transmission to infants born to mothers who had a primary infection or a recurrent infection during pregnancy was 32% and 1.4%, respectively. Possible maternal primary infections (i.e. seropositive mother with CMV IgM) resulted in congenital infections about 20% of the time, but are likely to represent a mixture of primary and recurrent infections."

Human cytomegalovirus (HCMV) and hearing impairment: infection of fibroblast cells with HCMV induces chromosome breaks at 1q23.3, between loci DFNA7 and DFNA49 -- both involved in dominantly inherited, sensorineural, hearing impairment. M Nystad, T Fagerheim, V Brox, EA Fortunato, Ø Nilssen. Mutat Res 2008 Jan 1;637(1-2):56-65. "In this work we demonstrate, using fine mapping techniques, that HCMV infection in S-phase fibroblast cells induces genetic damage at 1q23.3, within a maximal region of 37 kb, containing five low copy repeat (LCR) elements. The breakpoint is situated between two hearing impairment (HI) loci, DFNA49 and DFNA7, and in close proximity to the MPZ gene previously shown to be involved in autosomal dominant Charcot-Marie-Tooth syndrome (CMT1B) with auditory neuropathy."

Polymorphisms within human cytomegalovirus chemokine (UL146/UL147) and cytokine receptor genes (UL144) are not predictive of sequelae in congenitally infected children. J Heo, S Petheram, G Demmler, JR Murph, SP Adler, J Bale, TE Sparer. Virology 2008 Aug 15;378(1):86-96. 51 HCMV isolates from congenitally infected children and 13 isolates from children in childcare. "There was no statistically significant correlation between UL146 and UL144 genotypes and HCMV disease and/or sequelae. However, there were some groups that had a relatively large proportion of asymptomatic outcomes. These included UL146 group 8 (7/8 asymptomatic) and UL146 group 10 (3/3 asymptomatic). UL144 group B had 11/15 (73%) asymptomatic. UL146 and UL144 genes remained stable in serial isolates from children in daycare for intervals up to three years."

Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe. A Ludwig, H Hengel. Euro Surveill 2009 Mar 5;14(9):26-32. Review. "In Europe, congenital cytomegalovirus (CMV) infection is the leading cause of neurological disabilities in children, causing severe sequelae such as sensorineural hearing loss, neurodevelopmental delay or blindness." "The prevalence of CMV infection at birth is related to the CMV seroprevalence in women of childbearing age, with a reported increase of 10% in maternal seroprevalence correspondending to a 0.26% increase in CMV birth prevalence. Multiple studies have shown that the overall CMV seroprevalence in women of childbearing age depends on age, parity, ethnicity and social status, and differs between countries and regions. A low socioeconomic status is a risk factor for CMV seroprevalence and congenital CMV infection."

Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells. MH Luo, H Hannemann, AS Kulkarni, PH Schwartz, JM O'Dowd, EA Fortunato. J Virol 2010 Apr;84(7):3528-3541. "Quantitative PCR, Western blot, and immunofluorescence assays confirmed that the mRNA and protein levels of four hallmark NPC proteins (nestin, doublecortin, sex-determining homeobox 2, and glial fibrillary acidic protein) were decreased by HCMV infection. The decreases required active viral replication and were due, at least in part, to proteasomal degradation."

Sensorineural hearing loss in a pediatric population: association of congenital cytomegalovirus infection with intracranial abnormalities. JW Kimani, CA Buchman, JK Booker, BY Huang, M Castillo, CM Powell, KE Weck. Arch Otolaryngol Head Neck Surg 2010 Oct;136(10):999-1004. In children with sensorineural hearing loss. "Of 109 patients, 11 (10%) had positive results for CMV DNA; 10 of the 11 had normal GJB2 sequence and had negative test results for the mtDNA 1555A>G mutation. Brain MRI scans for 97 patients demonstrated a higher proportion of abnormalities in patients with positive CMV test results (80%) compared with those with no detectable CMV DNA (33%) (P = .006). GJB2 mutations and the mtDNA 1555A>G mutation were seen in 10 of 88 patients (11%) and 1 of 97 patients (1%) with SNHL, respectively... The presence of brain abnormalities in most patients with congenital CMV infection suggests that neurological damage in otherwise asymptomatic patients may not be limited to SNHL. Congenital CMV infection accounted for a significant proportion of patients with SNHL, with an incidence rate comparable with that of GJB2-related SNHL"

Congenital cytomegalovirus infection in pediatric hearing loss. S Misono, KC Sie, NS Weiss, ML Huang, M Boeckh, SJ Norton, B Yueh. Arch Otolaryngol Head Neck Surg 2011 Jan;137(1):47-53. 222 children 4 years and older with hearing loss born in Washington State, and 222 matched controls. "Congenital CMV infection was detected in 1.4% of controls and in 9.9% of cases (odds ratio, 10.5; 95% confidence interval, 2.6-92.4). An estimated 8.9% of HL in children in Washington can be attributed to CMV infection. After inclusion of an additional 132 children with HL (for a total of 354 cases in the case cohort), we observed that children with congenital CMV had more severe HL (P < .001) and higher proportions of progressive (P = .02) and unilateral (P = .002) HL compared with children without congenital CMV infection. In the 35 children with congenital CMV infection, there was no relationship between neonatal CMV load and severity of HL."

Association between the cytomegalovirus seroprevalence and hearing loss in early childhood. T Devdariani, K Gogberashvili, N Manjavidze, G Kamkamidze. Georgian Med News 2011 Jun;(195):61-65. 15 children with SNHL, 30 healthy controls. "CMV specific IgG antibodies were positive in 14 (93,3%) of 15 patients from the study group and in 14 (46.7%) of 30 children from the control group (p=0.003)."

Congenital cytomegalovirus - time to diagnosis, management and clinical sequelae in Australia: opportunities for earlier identification. BJ McMullan, P Palasanthiran, CA Jones, BM Hall, PW Robertson, J Howard, WD Rawlinson. Med J Aust 2011 Jun 20;194(12):625-629. 195 infants with cCMV, including 126 definite and 69 probable cases. "During the period of study, neonatal hearing screening was introduced for most Australian infants. Detection of hearing loss increased from 19% of cCMV cases in 1999-2003 to 31% in 2004-2009."

Late-onset sensorineural hearing loss due to asymptomatic congenital cytomegalovirus infection retrospectively diagnosed by polymerase chain reaction using preserved umbilical cord. M Ikeno, A Okumura, Y Ito, S Abe, M Saito, T Shimizu. Clin Pediatr (Phila) 2011 Jul;50(7):666-668. No abstract.

See Also:

EBV Can Cause Mental Impairment in Children

Primary Epstein-Barr virus infections in children have traditionally been considered asymptomatic, or causing merely temporary malaise. However, a new study has implicated EBV in neurological deficits in children, finding five cases within a year just in the small state of Rhode Island. And, there are probably a much greater number of less serious cases. EBV is known to occur much earlier in life in lower socioeconomic groups. None of the anti-smoker studies blaming parental smoking for children's impulsivity, inappropriate behavior, lack of cognitive skills and judgment, etc., has ever considered the role of this or any other infection. They pass out lifestyle questionnaires, and falsely pretend that this is sufficient to control for confounding. Therefore, this claim should be considered yet another example of confounding by infection, and thrown on the junk heap with the rest.

Persistent preceding focal neurological deficits in children with chronic Epstein-Barr encephalitis. JM Caruso, GA Tung, GC Gascon, J Rogg, I Davis, WD Brown. J Child Neurol 2000 Dec;15(12):791-796. "Also, Dr. Caruso told Reuters Health, 'serum tests may come back negative, and physicians would think the patient doesn't have that disorder. Just like in varicella, it can show up negative in serum but positive in CSF polymerase chain reaction testing." (Reuters Health 2001. http://id.medscape.com/34020.rhtml link died)

Neurological complications of acute and persistent Epstein-Barr virus infection in paediatric patients. M. Hausler, VT Ramaekers, M Doenges, K Schweizer, K Ritter, L Schaade. J Med Virol 2002 Oct;68(2):253-263. "Neurological complications of Epstein-Barr virus (EBV) have been reported almost exclusively in the course of acute primary infections. The role of EBV in paediatric neurological disease was investigated prospectively over a 2-year period, searching for acute primary, chronic, and reactivated EBV infections. Active EBV infections were diagnosed in 10/48 patients, including two with acute primary EBV infections (cranial neuritis and cerebellitis), one with chronic active infection (T/NK cell lymphoma with cranial neuritis), and seven with reactivated infections."

What incites new daily persistent headache in children? KJ Mack. Pediatr Neurol 2004 Aug;31(2):122-125. "This study asked what incites the development of a new daily persistent headache in children. A total of 175 children with chronic daily headache were prospectively identified and observed by the author. Of these patients, 40 (23%) with a new daily persistent headache were identified. These patients had no significant prior headache history. Seventeen patients (43%) had the onset of their symptoms during an infection. Of these patients, over half had positive Epstein-Barr virus serology at the onset of symptoms."

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Enterovirus 71

Attention-Deficit/Hyperactivity-Related Symptoms Among Children With Enterovirus 71 Infection of the Central Nervous System. SS Gau, LY Chang, LM Huang, TY Fan, YY Wu, TY Lin. Pediatrics 2008 Aug;122(2):e452-e458. "86 children 4 to 16 years old with virus-culture-confirmed enterovirus 71 infection and central nervous system involvement diagnosed 3 to 7 years before the study and 172 control subjects, matched for age, gender, and parents' education levels.... The children previously infected with enterovirus 71 had higher scores than matched control subjects on teacher- and mother-rated scales of inattention, hyperactivity-impulsivity, oppositional symptoms, and attention-deficit/hyperactivity disorder index. The rate of elevated attention-deficit/hyperactivity disorder-related symptoms among children with enterovirus 71 central nervous system infection was 20%, whereas that rate among matched control subjects was only 3%. They also had more internalizing problems. Their verbal and performance IQs, as well as verbal comprehension indices, were significantly inversely correlated with symptoms of inattention, hyperactivity-impulsivity, and attention-deficit/hyperactivity disorder index scores."

Confounding Issues

Effect of Maternal Smoking During Pregnancy on Offspring's Cognitive Ability: Empirical Evidence for Complete Confounding in the US National Longitudinal Survey of Youth. G. David Batty, PhD, Geoff Der, MS and Ian J. Deary, PhD. Pediatrics 2006 Sep;118(3):943-950.

BACKGROUND. Numerous studies have reported that maternal cigarette smoking during pregnancy is related to lower IQ scores in the offspring. Confounding is a crucial issue in interpreting this association.

METHODS. In the US National Longitudinal Survey of Youth 1979, IQ was ascertained serially during childhood using the Peabody Individual Achievement Test, the total score for which comprises results on 3 subtests: mathematics, reading comprehension, and reading recognition. Maternal IQ was assessed by using the Armed Forces Qualification Test. There were 5578 offspring (born to 3145 mothers) with complete information for maternal smoking habits, total Peabody Individual Achievement Test score, and covariates.

RESULTS. The offspring of mothers who smoked 1 pack of cigarettes per day during pregnancy had an IQ score (Peabody Individual Achievement Test total) that was, on average, 2.87 points lower than children born to nonsmoking mothers. Separate control for maternal education (0.27-IQ-point decrement) and, to a lesser degree, maternal IQ (1.51-IQ-point decrement) led to marked attenuation of the maternal-smoking–offspring-IQ relation. A similar pattern of results was seen when Peabody Individual Achievement Test subtest results were the outcomes of interest. The only exception was the Peabody Individual Achievement Test mathematics score, in which adjusting for maternal IQ essentially led to complete attenuation of the maternal-smoking–offspring-IQ gradient (0.66-IQ-point decrement). The impact of controlling for physical, behavioral, and other social indices was much less pronounced than for maternal education or IQ.

CONCLUSIONS. These findings suggest that previous studies that did not adjust for maternal education and/or IQ may have overestimated the association of maternal smoking with offspring cognitive ability.

Infections cause depression, delinquency

Depression in medical illness: the role of the immune system. R Yirmiya. West J Med 2000;173(5):333-336.

Raised levels of plasma interleukin-1beta in major and postviral depression. BM Owen, D Eccleston, LN Ferrier, H Young. Acta Psychiatrica Scandinavica 2001;103(3):226-228; and: Further evidence of cytokine involvement in major and post-viral depression. Veronica Rose, Doctor's Guide 2001 Apr 2.

Borna disease virus linked with severe mood disorders. Medscape - Reuters Health news re: Mol Psychiatry 2001;6:481-491. A more sensitive immune assay finds that immune complex levels are 10 times higher than with earlier methods.

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