Importance of TORCH Profile in Hearing Impaired Paediatric Population Planned for Cochlear Implant: A Study From an Eastern India Tertiary Care Centre

Abstract

TORCH group of infections are one of the most common causes of bilateral profound hearing loss in a developing country like ours. Seroprevalance is quite high in eastern part of our country. Screening for TORCH infections in children’s with profound hearing loss has significant prognostic, planning and policy forming implications. To evaluate the seroprevalance of TORCH infections in prospective cochlear implant children and its significance. Ours is a retrospective study conducted from 2017 to 2018 on 50 children with bilateral profound hearing loss attending the Department of ENT at AIIMS, Patna. Thorough clinical and audiological assessment of the patients was done using objective tests like OAE (otoacoustic emission), ABR (auditory brainstem response) and subjective tests like BOA(behavioural audiometry) and PTA (puretone audiometry) wherever feasible. Blood samples were collected and serotesting was done using ELISA for Toxoplasma, Rubella, Cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) (TORCH). We found that IgM was negative for all patients. Seroprevalance for IgG was 16.3% for toxoplasma, 74.4% for rubella, 69.8% for CMV and 20.9% for HSV. All the children had bilateral severe to profound loss on ABR and bilateral REFER on OAE. As prevalence of TORCH infection is quite common in India and is an established risk factor for sensorineural hearing loss with multisystem involvement screening for the same will help in early identification and in decision making for cochlear implantation thus improving the prognosis and also aid in policy making.

Introduction

Hearing loss in children constitutes a considerable handicap because it is an invisible disability and compromises optimal development and personal achievement of a child. Hearing loss in a child may develop from causes before birth (prenatal), during birth (perinatal) or thereafter (postnatal).In the Indian subcontinent, the national statistics report nearly 63 million people suffer from severe-to-profound hearing disability, which puts the estimate of childhood deafness at about 22 million. A nation-wide survey by the National Program for Prevention and Control of Deafness has concluded that deafness is the commonest congenital anomaly to affect the huge 1.30 billion strong Indian population, with the incidence being 31000 live births [1]. The acronym TORCH (Toxoplasma, Rubella, Cytomegalovirus/CMV, Herpes Simplex Virus/HSV) was introduced in 1971 by Nahmis et al. [2]. Sensorineural hearing loss is a common sequelae of TORCH group of infections, especially in developing country like ours were multiple factors come into play which are essentially preventable. Advent of Cochlear implantation has greatly improved the prognosis and quality of life of such group of patients, although various factors have to be taken into account considering multisystem involvement of TORCH agents and psychosocial factors. Our study aims to answer questions regarding the relevance of screening of prospective cochlear implantee for TORCH group of infections and also highlights implication for policy making at both state and national level with intersectoral coordination. Preventing TORCH infections in the prenatal stage in the mother can have tremendous impact in lowering down the incidence of congenital hearing loss in our country.

Aim and Objective

• Our study aims to evaluate the seroprevalence of TORCH infections in established cases of children with bilateral profound hearing loss.

• Significance of TORCH screening in a prospective cochlear implantee.

Material and Method

Ours is a retrospective study which was carried out on patients who were examined and screened for prospective cochlear implant .Our study was conducted over a period of one year from 2017 to 2018.

Study area: All India Institute Of Medical Sciences, Patna, Bihar

Study period: One year, 2017 to 2018

Study population and source of data: Patients who were deemed prospective cochlear implantee and had undergone cochlear implantation at AIIMS, Patna.

Study Design: Retrospective Study

Sample size: 50

Method of collection of data: Convenient sampling.

Study tool: Following history taking and clinical examination, patients were subjected to a battery of objective and subjective audiological tests to confirm the diagnosis. Objective tests like OAE (Otoacoustic emissions), BERA (Brainstem Evoked Response Audiometry) and subjective tests like BOA ( Behaviour Observation Audiometry) and PTA ( Pure Tone Audiometry) wherever feasible were performed and the patients were classified into different categories based on severity of hearing loss.These tests were performed by audiological experts and were repeated at least twice to confirm measurements.

After initial screening and diagnosis of severe to profound hearing loss the patients attended our dedicated cochlear implant clinic for further evaluation. Repeat detailed history taking, clinical and endoscopic otological examination along with comprehensive counselling of parents was done. Patients were sent for Pediatric medicine opinion for a detailed physical examination and to rule out congenital anomalies and child psychologist for Intelligence and developmental quotient assessment. Once the patient was labelled as a prospective cochlear implantee second line of investigations were advised which included taking blood samples for TORCH serology and serotesting was done using ELISA. The normal values for TORCH IgG titers used as control were 0 to 13.05 IU/ml for Toxoplasma, 0 to 15 IU/ml for Rubella, 0 to 1 A.I for Cytomegalovirus (CMV) and 0 to 0.9 A.I for Herpes (HSV).

Results

The present study includes 50 cases of severe to profound hearing loss that were evaluated and underwent cochlear implant in our department over a period of one year. Out of 50 cases that underwent cochlear implant 43 were found to be TORCH positive. IgM titres were negative for all patients. The result and observations of the study were recorded, analyzed and shown in tables (Table 1, Fig. 1).

1. Age distribution:

   Majority of the patients presented within 1st to 3rd years of life accounting for approximately 42% closely followed by 4th to 6th years accounting for approximately 40% of total cases.

2. Sex distribution:

   Of 43 patients males accounted for 58.1% and females accounted for41.9%. The Male to female ratio was 1.4:1 (Table 2, Fig. 2).

3. Age with sex distribution:

   Majority of the patients in both sexes presented within 1st to 6th year of life (Table 3, Fig. 3).

4. Seroprevalence of IgG titres:

In our study we found that IgM was negative for all patients. Seroprevalence for IgG was 16.3% for Toxoplasma, 74.4 % for Rubella, 69.8% for CMV and 20.9% for HSV. Most common infection being Rubella followed by CMV, HSV and Toxoplasma .All the children had bilateral severe to profound hearing loss on BERA and on OAE (Table 4, Fig. 4).

Table 1.

Distribution of TORCH positive patients in different age groups

Age in years	No. of cases	Percentage (%)
< 1	1	2.3
1–3	18	41.9
4–6	17	39.5
7–9	4	9.3
> 9	3	7
Total	43	100

Majority of the patients presented within 1st to 3rd years of life accounting for approximately 42 % closely followed by 4th to 6th years accounting for approximately 40% of total cases

Fig. 1.

Bar diagram distribution of TORCH positive patients in different age groups

Table 2.

Sex distribution

	No. of cases	Percentage
Female	18	41.9%
Male	25	58.1%
Total	43	100%

This table showing distribution of TORCH positive patients among males and females

Of 43 patients males accounted for 58.1% and females accounted for41.9%. The Male to female ratio was 1.4:1

Fig. 2.

The pie chart sowing gender distribution

Table 3.

Age with sex distribution

Age (Years)	Female	%	Male	%
< 1	0	0	1	4
1–3	8	44.4	9	36
4–6	8	44.4	10	40
7–9	1	5.6	3	12
> 9	1	5.6	2	8
Total	18	100	25	100

This table showing distribution of TORCH positive patients among various age and sex

Majority of the patients in both sexes presented within 1st to 6th year of life

Fig. 3.

Bar diagram showing distribution of TORCH positive patients among various age and sex

Table 4.

aSeroprevalence of IgG titres, b Reference interval for IgG titres

a
TORCH IgG TITRE
TORCH	Total	Positive	(%)
Toxoplasma	43	7	16.3
Rubella	43	32	74.4
CMV	43	30	69.8
HSV	43	9	20.9

b
TORCH PROFILE IgG	Biological reference interval
Toxoplasma	0–13.05
Rubella	0–15
CMV	0–1
HSV	0–0.9

Table showing distribution of IgG titres

In our study we found that IgM was negative for all patients. Seroprevalence for IgG was 16.3% for Toxoplasma, 74.4 % for Rubella, 69.8% for CMV and 20.9% for HSV. Most common infection being Rubella followed by CMV, HSV and Toxoplasma .All the children had bilateral severe to profound hearing loss on BERA and on OAE

Fig. 4.

Bar diagram showing percentage of IgG titres among torch positive patients

Discussion

The aetiology of sensorineural hearing (SSNHL) loss is unknown in as many as 40% of children, even though some evidence suggests that it can be viral in origin [3]. Majority of the patients presented within 1st to 3rd years of life accounting for approximately 42 % closely followed by 4th to 6th years accounting for approximately 40% of total cases (Table1) (Fig. 1). Majority of the patients in both sexes presented within 1st to 6th year of life (Table 3) (Fig. 3). Of 43 patients males accounted for 58.1% and females accounted for41.9%. The Male to female ratio was 1:4 (Table 2) (Fig. 2). Congenital Cytomegalovirus (CMV) is one of the most common cause of nonhereditary SNHL in children, second only to genetic mutations, and therefore potentially preventable [3]. Although the causes may vary and disparity exists from region to region. Especially in developing countries like ours, causes vary from state to state. In our study which caters to state of Bihar where Rubella is quite common we found that seroprevalence of Rubella was highest among patient with severe to profound hearing loss and was closely followed by CMV. The types of antibody used for screening for TORCH infection include IgG and IgM. In general, antibodies of the IgM class are indicative of a recent infection, while IgG antibodies denote past infection. The presence of IgG antibodies to an aetiological agent is indicative of immunity to that specific agent, while IgM specific to an agent provides a 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; Patients showing sera conversion or a four-fold rise in IgG antibody titre should have an IgM specific antibody determination [7].

Many authors have reported congenital cytomegalovirus (CMV) as the most common cause of nonhereditary SNHL in children [3].CMV is typically acquired early in life and may be acquired in utero , its transmission to fetuses can occur during primary maternal infection (accounting for 40–50% of cases of congenital CMV) or reactivation during pregnancy. Only 5–10% of infected neonates will show signs of CMV infection at birth [4].Hearing loss can be seen in both symptomatic and asymptomatically infected children with the average age of diagnosis being 27–33 months. Delayed SNHL, can manifest months or years after birth which gets missed easily on initial hearing screening. Thus CMV may be underlying cause of many cases of idiopathic SNHL in children.

Global prevalence of CMV infection is reported to be approximately between 40 and 80%, but may vary in developed (45 %) and in developing countries (100 %) [5]. Serological surveys in different parts of India have shown 80–90 % prevalence of CMV IgG antibodies in women of childbearing age [6]. In our study we found that the seroprevalence rate for IgG CMV infection was 69.8 % in children with bilateral severe to profound hearing loss (Table 4) (Fig. 4).

Rubella, also known as the German measles, is a potent teratogen if acquired during pregnancy [7]. Congenital RubellaSyndrome (CRS)manifests as, microcephaly, mentalretardation, thrombocytopenia, cardiac anomalies, and a characteristic rash [8].SNHL is the most common sequelae of Congenital Rubella infection (58%) and is most often seen when maternal Rubella infection occurs in first trimester . Hearing loss typically manifests in the first 6–12 months of life, although it can present at birth [9]. The virus causes direct cochlear damage and cell death in the Organ of Corti and StriaVascularis [10]. Alterations in the composition of endolymph due to strial damage have also been described [11]. The 2008 estimates suggest that the highest CRS burden is in the developing world, i.e., Southeast Asian region (approximately 48%) and African region (approximately 38%) [12, 13]. In studies evaluating seroprevalence of Rubella among the Indian population, 10–30% of adolescent girls and 12–30% of women in the reproductive age group were found to be susceptible to Rubella infection [14]. Systematic review based on published studies in India indicated that 1–15% of all infants suspected to have intrauterine infection had laboratory evidence of CRS [14]. In India, Rubella vaccination was not included in Universal Immunization Programme (UIP) for quite some time. It was only included in Indian Academy of Paediatrician (IAP) immunization schedule as a part of MMR vaccination at 9th and 15th month. So high prevalence of Rubella IgG titre may actually be due to infection. In our study also we found similar seroprevalence of Rubella IgG to be as high as 74.4% (Table 4).

HSV types 1 and 2 have been implicated as causes of hearing loss. Congenital herpes infection typically arises due to exposure during delivery. Neonatal herpes is commonly acquired from women who develop infection late during pregnancy, who have active herpetic lesions in the birth canal or they may be serologically positive and have asymptomatic viral shedding. Neonatal HSV1 infection occurs in 1/2000 to 1/8000 and HSV2 in 5.9/100,000 live births [15, 16]. Hearing lossis a commonsequelae of neonatal infection and is more commonly associated with HSV1 as compared to HSV2 [17]. It can be bilateral or unilateral severe to profound SNHL [17]. HSV1 causing hearing loss following infection or reactivation of latent infection is bilateral and severe [17–19]. The incidence of SNHL in congenital HSV is approximately 10 %, although data is limited. It supports findings in our study where we found the seroprevalence of HSV IgG to be 16 % (Table 4).

Toxoplasma gondii is a ubiquitous protozoan with a worldwide distribution. Infection with T. gondii is acquired through meat and meat products, from the environment through poor hygiene, and via contaminated surface water. Most infants with congenital toxoplasmosis are asymptomatic initially, although 80–90% may develop eye and neurological diseases later in life. In infants, the presence of T. gondii-specific IgM or the persistence of IgG beyond 12 months of age is suggestive of congenital infection. The prevalence of toxoplasmosis associated hearing loss in infected newborns is 0–26 %. In our study seroprevalence for IgG was found to be 10 % Table 4).

TORCH infection are significant cause of congenital hearing loss in developing countries like ours because of high risk of exposure of females of reproductive age group and pregnant females to these agents. Lower socio economic status, lack of health awareness, lesser institutional deliveries, lack of access to timely healthcare, inadequate neonatal care, poor literacy level and high rate of consanguinity are other contributing factors. Congenital hearing loss secondary to TORCH group of agents is essentially preventable. Apart from strengthening the basic socio economic framework and perinatal healthcare a simple tool like vaccination against Rubella can go a longway in reducing the disease burden. National Family Health Survey-III (2005–2006), UIP coverage countrywide was just 44% compared to 36% (1992-93) and 42% (1998-99) in previous surveys. Even in Kerala, coverage had actually declined to 75% from 80% (1998–1999) [20]. In our state of Bihar as per the National family health survey—4 (15–16) data it is 61.7 % , District level household & facility survey/Annual health survey—3 (12–13) data it is 59.7%. Our national average of UIP coverage is still less than 50%. Rubella vaccination was not part of the UIP in India till very late. Recommendation to do the same was made in 2014 by the Ministry of health and family welfare. Although it was not until 2017 when rubella containing vaccine (RCV) in the form of MR (mumps rubella) vaccine was given by both public and private healthcare practitioners. Before that it was only the private sector which was providing the RCV vaccine as it itself is very costly. This discrepancy in accessibility to RCV among population has also led to a short term increase in congenital rubella syndrome (CRS). If childhood RCV coverage falls below a critical threshold, CRS incidence can actually increase beyond Rubella endemic CRS levels by increasing the average age of infection without sufficiently reducing rubella incidence [21–23]. A short-term (annual) increase in congenital rubella syndrome post-rubella vaccination introduction, i.e. an increase in congenital rubella syndrome in any given year, was observed in Greece after a Rubella outbreak in 1993 [22] and in Costa Rica after a 1998–1999 rubella outbreak [23, 24]. 80% Rubella vaccine coverage is sufficient to avoid long-term increases in congenital rubella syndrome incidence post-rubella vaccine introduction across a range of demographic and epidemiological contexts [21, 25, 26]. As such, population-based rubellaserological surveys or non-age biased incidence data are needed to inform unknown transmission drivers [27, 28]. Additionally, these types of data sources will be invaluable in the future to evaluate the success of the rubella vaccine introduction, and to determine the need for future supplemental immunisation activities.

Conclusion

Screening for TORCH infections does not affect the treatment plan for patients undergoing cochlear implant. Our study however emphasises the importance of TORCH screening in a prospective cochlear implant candidate and its importance as a tool to establish the aetiology. It is important in counselling of parents regarding results as these patients have other comorbidities which may affect the auditory and speech milestones post cochlear implant. It also differentiates between past and recent/active infection which would direct proper treatment agents.

In case of Rubella there is no antiviral therapy, our study also impresses upon the fact that with relatively high seroprevalence in Indian subcontinent, administration of Rubella vaccination as a part of UIP requires more fervent efforts to reduce the disease burden.

Seroprevalence studies like ours also lays foundation for assessment of success and failure of vaccination and targeted policies addressing TORCH infections. Timely active intervention also helps to reduce the damage and prospective cochlear implant candidates will do better following surgery.

Our study has implications in planning of both preventive and therapeutic strategies at local and national level to reduce avoidable and curable cause of hearing loss in children. It can be achieved by implementing targeted immunization programmes, following recommended treatment protocols and above all, creating awareness among stakeholders.

Authors contribution

All authors have made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; drafted the work or revised it critically for important intellectual content; approved the version to be published; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declarations

Conflict of interest

There is no conflict of interest among authors.

Ethical Approval

Ethical approval was taken by All India Institutes of medical sciences, Patna ethical committee.