Distortion product otoacoustic emissions: towards reliable and valid early identification and monitoring of hearing in adults receiving ototoxic medication

Background: Multidrug-resistant tuberculosis (MDR-TB) patients receive aminoglycosides as part of their treatment. These drugs are ototoxic, and can cause permanent damage to the cochlea, resulting in a debilitating hearing loss, which has a negative impact on an individual's quality of life. Early detection and management of an ototoxic hearing loss can minimise the impact of the hearing loss on the person's social, emotional, and vocational wellbeing. While patients with MDR-TB are often very ill, it might be ideal to use an objective test that does not require active participation from the patient. In this way, the reliability and validity of the test will not be affected by the patient's state. Distortion product otoacoustic emissions (DPOAEs) at 2f1-f2 are a viable option, as it evaluates cochlear function, specifically the outer hair cells, which are affected first by ototoxic medication. Method: This thesis used a sequential study design aimed to determine the DPOAE stimulus parameters that yield (a) the highest level and the most reliable, sensitive and specific DPOAEs reported in the literature, (b) the highest level and the most reliable DPOAEs in healthy, normally hearing adults, and (c) the most sensitive and specific DPOAEs in participants with MDR-TB patients receiving ototoxic medication. High frequency pure tone audiometry (defined in this thesis as frequencies > 8 kHz) was used as the gold standard. Descriptive statistics, the intraclass correlation coefficient, Pearson's correlation coefficient and mixed model analyses were used to analyse the data. Results: Systematic review: The results of the systematic review indicated an L1/L2 setting of 75/75 dB SPL and f2/f1 value from 1.20 to 1.22 yielded the highest level DPOAEs. The systematic review results for stimulus parameters that yielded the highest test-retest reliability, sensitivity and specificity were inconclusive. Preliminary study with healthy normal hearing participants: The results of the preliminary study in healthy, normal-hearing participants indicated that the highest levels of DPOAEs were elicited with L1/L2 intensity levels of 65/65 and 65/55 dB SPL, and f2/f1 ratios of 1.18, 1.20 and 1.22, as determined by mixed model analyses (p < 0.05). These same stimulus parameters yielded the most reliable DPOAEs in both ears, as determined by intraclass correlation coefficient analysis. Main study with healthy, normal-hearing participants: Descriptive statistics and mixed model analysis showed stimulus intensity levels L1/L2 of 65/55 dB SPL, and f2/f1 ratios of 1.18 and 1.20, elicited the largest DPOAEs. The ratio of 1.20 yielded the largest DPOAEs < 5000 Hz and f2/f1 ratio of 1.18 the largest DPOAEs ≥ 5000 Hz. The second highest DPOAE levels were elicit by L1/L2 = 65/65 dB SPL and f2/f1 = 1.18. The test-retest reliability in this sample was not influenced by changing the stimulus parameters, and DPOAEs were only unreliable at an f2 frequency of 8 000 Hz. Study in participants with MDR-TB: Results in participants with MDR-TB receiving ototoxic medication indicated that the highest levels of DPOAEs were elicited with L1/L2 = 65/55 and an f2/f1 ratio of 1.18 at f2 ≥ 5000 Hz, followed by 65/65 and 1.18. For f2 < 5000 Hz, stimulus intensities of L1/L2 = 65/55 and an f2/f1 ratio of 1.20 yielded the largest DPOAE levels. Relating to sensitivity and specificity, the stimulus parameter combination of 65/55 dB and 1.18 detected the highest number of ears with outer hair cell damage in participants with MDR-TB receiving ototoxic medication. Conclusion: It should be considered to use an f2/f1 ratio of 1.18 for f2 ≥ 5000 Hz and 1.20 for f2 < 5000 Hz when monitoring for ototoxicity, to assist with early identification of outer hair cell damage, in conjunction with high frequency pure tone audiometry. This finding needs to be confirmed in a larger sample of participants with MDR-TB receiving ototoxic medication

Screening for childhood hearing impairment in resource-constrained settings: Opportunities and possibilities

Given the successful implementation of universal neonatal hearing screening and the value of such services in developed countries, we in developing countries should be asking ourselves ‘how’, and not ‘whether’, such services should be delivered in our contexts

Developing human rights competencies for South African health professional graduates.

Human rights are social or material entitlements which are recognised universally in national and international law and that address fundamental human needs. They inhere in all people by virtue of their humanity, and represent a standard to which governments can be held accountable

Aminoglycoside-induced hearing loss: South Africans at risk

South Africa is currently experiencing a TB epidemic with an estimated incidence of 940/100 000 population/year, and the country has been ranked 4th among the 22 high-burden TB countries worldwide by the World Health Organization (WHO). A potentially devastating threat to TB control is the emergence of multidrug-resistant TB (MDR-TB) and, more recently, extensively drug-resistant TB (XDR-TB), mainly as a result of poor drug adherence by TB patients and incorrect management or treatment regimens by health providers; however, direct transmission of drug-resistant strains also plays an important role. The MDR/XDR-TB strains necessitate prolonged chemotherapy for up to 2 years or more, and the use of more toxic second-line drugs including the aminoglycoside (streptomycin, kanamycin and amikacin) and polypeptide (capreomycin) antibiotics. In South Africa, in accordance with WHO guidelines, streptomycin is used for retreatment of TB while kanamycin, amikacin and capreomycin are used to treat MDR/XDR-TB

Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients

Background. Ototoxicity following aminoglycoside treatment for multidrug-resistant tuberculosis (MDR-TB) is a significant problem. This study documents the incidence of ototoxicity in HIV-positive and HIV-negative patients with MDR-TB and presents clinical guidelines relating to ototoxicity. Methods. A prospective cohort study of 153 MDR-TB patients with normal hearing and middle ear status at baseline controlling for 6 mitochondrial mutations associated with aminoglycoside-related ototoxicity, at Brooklyn Chest Hospital in Cape Town. Pure tone audiometry was performed monthly for 3 months to determine hearing loss. HIV status was recorded, as was the presence of 6 mutations in the MT-RNR1 gene. Results. Fifty-seven per cent developed high-frequency hearing loss. HIV-positive patients (70%) were more likely to develop hearing loss than HIV-negative patients (42%). Of 115 patients who were genetically screened, none had MT-RNR1 mutations. Conclusion. Ototoxic hearing loss is common in MDR-TB patients treated with aminoglycosides. HIV-positive patients are at increased risk of ototoxicity. Auditory monitoring and auditory rehabilitation should be an integral part of the package of care of MDR-TB patients

Clinical Considerations for Routine Auditory and Vestibular Monitoring in Patients with Cystic Fibrosis

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events

A comparison of pure tone thresholds and distortion product otoacoustic emission measures in patients with Tuberculosis receiving aminoglycosides

Includes bibliographical references (leaves 116-131)

Vuvuzelas at South African soccer matches: Risks for spectators′ hearing

South African Premier Soccer League (PSL) matches are known worldwide as some of the noisiest recreational events. Therefore, the objectives of this study were to i) measure noise levels during different PSL matches; ii) measure changes in auditory function after attending PSL matches; and iii) determine the factors that increase the risk of overexposure to noise during PSL matches. The study used a descriptive quantitative analytical pre- and post-exposure design. Participants (n = 19, and n = 10) attended two PSL matches. Each participant′s auditory function was assessed using distortion product oto-acoustic emissions (DPOAEs) before and after attending a PSL match. Peak and equivalent continuous noise levels as well as noise dose were measured during each match. Noise levels recorded during the poorly attended Match 1 were lesser than those of the well-attended Match 2. Participants attending Match 2 had statistically significant reduction in their DPOAE amplitudes after the match (P = 0.003) than those attending Match 1. Vuvuzela blowers and participants seated within 1 m from them were most at risk of harm to their hearing with significant reduction in DPOAE amplitudes post the match (P = 0.002 and P = 0.008, respectively). It was therefore concluded that noise levels at well-attended South African PSL matches pose a significant risk to spectators′ auditory function as shown by reduced DPOAE amplitude post match attendance. Three risk factors for overexposure to noise during the match were identified: blowing the vuvuzela, close proximity to the individual blowing the vuvuzela as well as spectator turnout at the match

Towards the preferred stimulus parameters for distortion product otoacoustic emissions in adults: a preliminary study

Background: Although distortion product otoacoustic emissions (DPOAEs) are useful in evaluating cochlear outer hair cell function, determining the optimal stimulus parameters could result in a more reliable, sensitive and specific diagnostic tool across the range of DPOAE applications.Objectives: To identify which stimulus parameters warrant further investigation for eliciting the largest and most reliable DPOAEs in adult humans.Method: A single group, repeated measures design involving a convenience sample of 20 normal-hearing participants between 19 and 24 years of age.Results: Descriptive statistics and mixed model analyses suggested L-1/L-2 intensity levels of 65/65 dB sound pressure level (SPL) and 65/55 dB SPL, and f(2)/f(1) ratios of 1.18, 1.20 and 1.22 elicited larger and more reliable DPOAEs in both ears.Conclusion: Further investigation of the 65/65 dB SPL and 65/55 dB SPL intensity levels and the 1.18, 1.20 and 1.22 f(2)/f(1) ratios is warranted to determine the stimulus parameters for eliciting the largest and most reliable DPOAEs in adult humans across the range of DPOAE applications