Hearing Loss and Herpes Simplex

Transcription

1 H. AL MUHAIMEED AND S. M. ZAKZOUK Hearing Loss and Herpes Simplex by Hamad Al Muhaimeed, MD and Siraj M. Zakzouk, MD Department oforl, King Abbdul Aziz University Hospital, P.O. Box 245, Riyadh 11411, KSA Summary A survey to identify the aetiology of impairment among Saudi children was carried out. Children were divided into two groups according to presence or absence of laboratory evidence of herpes simplex virus infection 'at risk' and 'not at risk'. Serological tests for herpes simplex virus infection were performed on 1054 children. We found positive IgM antibody against herpes simplex virus, type 1 (HSV,) in the blood of 82 of the 1054 children (8 per cent), and positive IgM antibody against herpes simplex virus type 2 (HSV 2 ) in eight of the 1054 children (0.8 per cent) ages ranged between 12 months and 14 years). Forty-six of the eighty-two infected children (56 per cent) with HSV, were found to have bilateral sensorineural loss (16 of 26 children of the at risk group and 30 of 56 from the 'not at risk' group). Only one case of the eight infected children with HSV 2 was found to have bilateral sensorineural loss of moderate degree. This case was in the 'not at risk' group. Hearing impairment was bilateral in all 46 cases, profound in seven, moderate to severe in 23 and mild in 16. Known causes of bearing impairment were excluded together with impairment due to multiple TORCH agents. The high prevalence of bearing impairment among children due to herpes simplex virus infection is described. Introduction Hearing impairment of various types are known to be a prominent finding in diseased infants and children who experience disseminated intra-uterine infections by intracellular organisms. Cooper in stated that impairment, either alone or in combination with other defects, is the single most common abnormality resulting from congenitaliy acquired rubella and it is the one most easily overlooked in infancy. Other than rubella, the specific role in impairment of the other TORCH agents (Toxoplasma gondii, cytomegalovirus and herpes simplex) know to produce similar abnormalities like rubella in the infected fetus and the newborn remains to be fully documented. 2 Herpes simplex viruses are large, enveloped viruses containing DNA. The two types have major genomic and antigenic differences. Type I (HSV,) usually involves the face and skin above the waist. Type 2 (HSVJ usually involves the genitalia and skin below the waist in adults. However, either type of virus can be found in either site, depending on the source of the infection. 3 Acknowledgements We would like to thank the King Abdul Aziz City for Science and Technology for support; to all the doctors, nurses, laboratory technicians, social workers, and support staff at King Abdul Aziz University Hospital. Special thanks are given to Professor A. Hussain for the laboratory work. The incidence of neonatal HSV infection is low; estimates range from 1 per 3000 to 1 per live births. Herpes simplex virus is most frequently transmitted to an infant during passage through an infected maternal lower genital tract during birth or by an ascending infection. In children, infection with HSV, results primarily from direct contact with infected oral secretions or lesions. Infections with HSV 2 usually results from direct contact with infected genital secretions or lesions through sexual activity. 3 The present study is a comprehensive clinical and laboratory hospital-based investigation aiming to assess the prevalence of impairment due to herpes simplex infection in children. To our knowledge, this is the first major study of its type to be conducted in Saudi Arabia. Patients and Methods This study was conducted in a 3-year period from 1988 to 1991, and included 1054 infants and children, aged 12 months to 14 years attending the ENT clinics at King Abdul Aziz University Hospital, Riyadh, and presenting with suspicion of impairment. They were divided in two groups: 'at risk' and those 'not at risk' for impairment to see if there is any predilection to HSV,_ 2 in the 'at risk' group. Those 'at risk' for impairment were identified according to the presence of one or more of the following: 1. family history of childhood impairment; 20 Journal of Tropical Pediatrics Vol. 43 February 1997 Oxford University Press 1997

2 H. AL MUHAIMEED AND S. M. ZAK2OUK 2. identification of congenital or prenatal infections known to contribute to impairment, e.g. TORCH agents (Joxoplasma gondii, syphilis, rubella, cytomegalovirus (CMV), herpes simplex); 3. anatomic malformations of the head or neck, e.g. abnormalities associated with craniofacial syndrome, cleft palate and lip, abnormalities of the pinna or external auditory canal; 4. birth weight less than 1500 g; 5. hyperbilirubinaemia at levels which are potentially toxic; 6. bacterial meningitis. All these infants and children were exposed to full ORL clinical examination after taking a detailed history from their parents including social and family history. The of children 6 years and younger was evaluated by Brain Stem Evoked Response (Type Amplaid MK15), and of older children by Pure Tone Audiometry (Type GSI 10). Tympanometry was done in all children. Tympanometry does not evaluate levels, but may give information on the topical site of a lesion. Blood samples were collected and sent to the laboratory for the detection of IgG, to TORCH agents using an enzyme immunoassay (Virgo, ELISA reagents, and automated Virgo equipment Model 400 At). The tests were carried out according to the instructions of the manufacturers. Appropriate positive and negative controls were used. Fisher exact test was used to test for statistical significance. The results of children positive to herpes simplex virus 1-2 only will be presented in this paper. Results Out of total of 1054 infants and children, (29 per cent) were identified as 'at risk' for impairment and (71 per cent) were identified as 'not at risk' group. Table 1 shows the distribution by age and sex of the 'at risk' children. About two-thirds (63 per cent) were males and approximately a third (37 per cent) females, while two-thirds (66 per cent) were 6 years and below, and the remaining were older than 6 years; 3 per cent were more than 12 years of age. Age and sex Age group = /<6 years >6 years >12 years TABLE distribution Number 202 (66.2) 103 (33.8) 10 (3.3) 1 of 'at risk' Male 125(61.9) 67 (65) 5(50) 192 (63.0) children Female 77 (38.1) 36(35) 5(50) 113(37.0) In the 'not at risk' children, 56 per cent were males and 44 per cent were females (Table 2). Age distribution in this group is similar to that of the 'at risk' group; 65 per cent were 6 years and below, and 35 per cent, were older than 6 years; about 1 per cent were older than 12 years of age. Laboratory analysis of serum samples (Table 3) indicates comparable prevalence of IgG to HSVj, (61 per cent) in the at risk group as compared to the 'not at risk' group (59 per cent). The prevalence of IgM antibody to HSV! is also comparable in the two groups: 9 per cent in the at risk group and 8 per cent in the not at risk group. Of the positive 82 cases, 55 per cent were males and 45 per cent were females. Table 4 shows similar prevalence of IgG to HSV 2 (28 per cent) in the at risk group as compared to that in the 'not at risk' group (27 per cent). The prevalence of IgM TABLE 2 Age and sex distribution of those Age group "/<6 years >6 years > 12 years Number 487 (65.0) 262 (35.0) 'not at risk' children Male 275 (56.5) 144 (55) 3 (50) 419 (55.9) Female 212 (43.5) 118 (45) 3(50) 330 (44.1) TABLE 3 IgG and positive to herpes simplex virus I (HSV t ) in the sera of all children no. of sera tested 1054 for IgG tohsv, 186(61) 444 (59.3) 630 (59.8) for IgM to HSV, 26 (8.5) 56(7.5) 82 (7.8) TABLE 4 IgG and positive to herpes simplex virus 2 (HSV 2 ) in the sera of all children no. of sera tested 1054 for IgG to HSV 2 86 (28.2) 203 (27.1) 289 (27.4) for IgM tohsv 2 8 (0.8) Journal of Tropical Pediatrics Vol.43 February

3 H. AL MUHAIMEED AND S. M. ZAKZOUK antibody to the same virus is comparable in the two groups: 0.7 per cent in the 'at risk' group and 0.8 per cent in the 'not at risk group'. Sex distribution in the positive eight cases is 58 per cent males and 42 per cent females. Forty-six (4 per cent) of those IgM positive to HSV, suffered impairment of varying degrees (Table 5) and all of the 46 cases were under the age of 8 years. One case of the positive eight cases to HSV 2 suffered from moderate loss (Table 6). Sixteen out of 26 (62 per cent) from the 'at risk' group and 30 out of 56 (54 per cent) children from the other group were found to have impairment. The difference between the two groups is not statistically significant (i>>0.05). If we look to the positive cases for HSV 2 there is only one case in the 'not at risk' group with moderate impairment and no impairment in the 'at risk' group. The difference between the two groups is not significant Evoked response audiometry and pure tone audiometry studies showed that seven (15 per cent) children had bilateral profound sensorineural loss, 23 (50 per cent) had moderate sensorineural loss and 16 (35 per cent) had mild loss (Fig. 1). Children with known causes of loss were excluded. Discussion As far as we are aware, this is the first hospital-based study conducted in Saudi Arabia to find out the frequency of childhood deafness/ impairment due to herpes simplex viruses. The classification of patients into two groups 'at risk' and 'not at risk' was adopted to enable the effective identification clinically, and the confirmation of herpes simplex virus infection was by a reliable ELISA technique, as well as audiological tests. The new ELISA test used in this study was shown to be sensitive, specific, and reliable, 4 " 6 in the detection of the presence of IgG and to HSV]_2, presumed to be aetiologically associated with deafness. The prevalence of Herpes simplex type I infection in our study is 8 per cent (82/1054), while that of herpes simplex type 2 infection is 0.8 per cent (8/1054). Out of 82 infected children with HSV,, 46 (4 per cent) had varying degrees if impaired. Only one case (0.1 per cent) out of eight infected children with HSV 2 had moderate sensory neural loss. In general, of the IgM class are indicative of a recent infection, while IgG denote past infection or exposure to a certain agent of viral, bacterial, fungal, or parasitic origin. The presence of IgG to an aetiological agent is indicative of immunity to that specific agent, while IgM specific to an agent provides a valuable confirmatory test of a current or recent infection. Besides, serum conversion or a four-fold rise in specific IgG antibody titre suggests recently acquired infection; however, the results maybe misleading specially if the serum samples are not run simultaneously with controls to avoid the day to day TABLE 5 IgM positive sera to HSV t of normal and impaired children w/im paired 16 (5.2) 30(4) 46 (4.4) w/normal 10 (3.3) 26 (3.5) 36 (3.4) (%) of sera 26 (8.5) 56(7.5) 82 (7.8) TABLE 6 IgM positive sera to HSV2 of normal and impaired children w/impaired w/normal (%) of sera At nsk 0 1 (0.1) 1 (0.1) 5(0.7) 7(0.7) 8 (0.8) 22 Journal of Tropical Pediatrics Vol. 43 February 1997

4 H. AL MUHAIMEED AND S. M. ZAKZOUK Mild loss 16 cases Profound loss 7 cases FIG. 1. Distribution of level among impaired positive children to HSV,. laboratory variations. Patients showing sera conversion or a four-fold rise in IgG antibody titre should have an IgM specific antibody determination.7 Pregnant women with a history of genital herpes carry the risk of neonatal HSV2 infection. However, as reported earlier, a low prevalence rate of 6 per cent of IgG to HSV2 in comparison to other TORCH agents was determined in pregnant Saudi women.8 Only one case of impairment with variable and abnormal speech has been encountered during the course of this study and this has been found to be due to HSV2. This undermines the role of HSV 2 as a significant aetiological agent of impairment and concurs with the fact that incidence of infections due to HSV2 is extremely low in pregnant Saudi women as is obvious by the low incidence of HSV 2 IgG 2 and in children (Table 4). The number of 16 (5 per cent) cases (at risk) and 30 (4 per cent) cases (not at risk) of impaired children with a laboratory diagnosis of HSVj IgM positivity is unique and significant finding since this was unexpected in view of the fact that HSV! has, to date, not been shown to be a potential TORCH agent, but the fact that HSV) has been associated with impairment in 'at risk' children in a substantial number of clinically and laboratory confirmed cases has undoubtedly classfied it as a significant agent. Another important feature is the detected association of tonsillitis and/or adenoids with impairment in the majority of cases with HSVi IgM positivity. This indicates that the impairment in these cases most likely was not of a congenital nature, but as a result of upper respiratory tract infection, predominantly associated with tonsillitis. This hypothesis is based on the results of a study of tonsillitis9 in 13 cases out of 52 clinically diagnosed cases of tonsillitis. No viral cytopathic effects were noted in monkey kidney or human Journal of Tropical Pediatrics Vol.43 February 1997 embryonic cell cultures, and direct tests for commonly encountered respiratory pathogens like adenoviruses, RSV, influenza (A,B) and para influenza viruses were negative. Due to non-availability at that time of an effective, sensitive, specific, and reliable laboratory test for HSV, it was only possible to conceive HSVi, as a likely candidate clinically. Another aspect of relevant importance in consideration is the recent report of the high prevalence (60 per cent) of HSV( IgG in children.10 Interestingly enough a similar prevalence rate of HSV! IgG (61 per cent in 'at risk'; 56 per cent in 'not at risk', 60 per cent in overall) in children investigated in this study was found. Thus, HSVI, could be considered as a significant aetiological agent other than the TORCH agent contributing to impairment particularly in association with tonsillitis. In this study, children were identified as 'at risk' of deafness/ impairment and in 16 (5 per cent) of them it was possible to identify the HSVi as an only possible aetiological agent. Ten (3 per cent) children who were positive to HSVi were found to have normal. On the other hand, in the 'not at risk' group 30 of (4 per cent) children with HSVi had impairment. Twenty-six (4 per cent) positive children to HSV, were normal. Only one case in the 'not at risk' group positive to HSV2 had moderate impairment. Five (0.7 per cent) positive cases to HSV2 were normal. In the 'at risk' group two (0.7 per cent) positive children to HSV2 were normal and no one case with impairment. These findings indicate clearly that HSV are potential aetiological factors in sensorineural loss. The difference in impairment due to HSV 1 " 2 infections between the two groups is statistically insignificant (P>0.05) and this indicates no specific predilection of herpes simplex in the 'at risk' group. Moderate loss 23 cases

5 H AL MUHAIMEED AND S. M. ZAKZOUK Approximately, 15 per cent of children with impairment have bilateral profound sensorineural loss, 50 per cent moderate loss and 35 per cent mild loss. Although the incidence of herpes simplex infection is not common, it remains a preventable cause of severe handicap in childhood; in this study it is an important cause of bilateral moderate sensorineural loss. Such affected children need special rehabilitative measures, therefore, special precaution measure should be anticipated. Many preventive measures should be adapted to reduce herpes simplex vims morbidity, e.g. pregnant women with infected genitalia should be screened and those infected should receive treatment. Newborns whose mothers have active genital lesions should be nursed carefully and followed closely for possible HSV morbidity. Besides, educational programmes on both the epidemiology of herpes simplex, mode of transmission, and careful attention to all infected lesions, are some additional steps which will no doubt help to minimi7^ acquired infection. Such efforts should be directed to all reproductive women as well as day care women and workers in centres for handicapped children. Conclusions Our study indicates a high prevalence of audiologic problems in children with herpes simplex infection. Many of these children have profound sensorineural loss which necessitates special rehabilitative measures and education. Early diagnosis of herpes simplex infection is necessary to identify a population at risk for audiological problems. Health educational programmes should be provided for all women in the reproductive age to minimize the incidence of herpes simplex infection. References 1. Cooper LZ. Congenital rubella in the United States, in Kingman S, Gershan AA (eds). Infection of the fetus and newborn infant. New York: Alan R Liss Inc., 1975; 3: Hossain A, Bakir TMF, Ramia S. Immune status of Saudi women to TORCH agents. J Trop Paediat 1986; 32: George P, Scott G, Caroline B, et al Redboot report of the Committee on Infectious Diseases, 23rd edn. Am Acad Paediat 1994; Hanshaw JB, Scheimer AP, Moxley LM, et al. School failure and deafness after silent congenital CMV infection. N Engl J Med 1976; 295: Hossain A, Kurstak E. Diagnostic and clinical virology. In: Kurstak E (ed.), Applied virology research, Vol. 2. New York: Plenum Press, pp Hossain A, Ramia S, Bakir TMF. Comparison of haemagglutination test, enzyme-linked immunosorbent assay and indirect immunofluorescence antibody test for determination of rubella immune status. J Trop Med Hyg 1988; 91: George P, Caroline BH, Martha LL, et al. Report of the Committee on Infectious Diseases. Am Acad Pediat 1988; 21: Hossain A, Bakir TF, Siddique MA, et at. Genital herpes simplex virus infections: laboratory Confirmation Disease Patient s. Int J Gynecol Obstet 1989; 29: Hossain A, Bakir TF, Zakzouk SM, Sengupta DK. Tonsillitis and respiratory tract infections of viral etiology in a developing country. Annl Trop Pediat 1988; 8(2): Hossain A. HSV, and VZV Infections in a developing country. J Trop Pediat 1989; 35: Journal of Tropical Pediatrics Vol. 43 February 1997