2006; 3:17-32 Issue No. 4 EDITORIAL: OTOTOXICITY Ian J Mackenzie MD MSc ical experimentation and a careful and accurate Liverpool School of Tropical Medicine recording system of any Pembroke Place side effects a drug gener- Liverpool L3 5QA ates. Subtle side effects, UK like tinnitus and deafness, are not identified until Email: [email protected] many people are affected and it is reported in the he majority of illnesses world- medical literature. It is wide are treated with medication. difficult, particularly in TMedicines have been used in the animal experiments, to treatment of illness for hundreds of years. record tinnitus or deafness The medicines of today are sophisticated as a side effect of a drug, and their development is at the forefront even though the hearing of science. Medicines have eradicated and balance systems are some diseases and controlled others. The anatomically very delicate Teaching and learning at a School for the Deaf in Afghanistan successful conquering of some cancers, and sensitive to toxins. previously thought untreatable, show Photo: SHIP/CBM the ingenuity and science that has been Ototoxicity the problem may be whether or not to part of their development. However, the The term ototoxicity covers any damage prescribe certain essential drugs know- development of new drugs takes a long to hearing and balance caused by a toxin, ing that there is a high chance of leav- time and is a very expensive process. as it affects the end organs of the eighth ing the patient with a long term hearing deficit. There is little information on the Side Effects of Medicines cranial nerve. The toxin can enter the body by ingestion, inhalation or with side effects of herbal and homeopathic Drugs of all sorts have known side effects skin contact. When a patient needs life- medication. which can only be discovered by clin- saving medication for severe illness, The long term cost to the community CONTENTS of ototoxicity is not known but hearing impairment, deafness, tinnitus or dizzi- Community Ear and Hearing Health 2006; 3:17-32 Issue No.4 ness can cause difficulties with language EDITORIAL Ian J Mackenzie 17 development and learning in children, LEAD ARTICLES: OTOTOXICITY and with work communication and Deafness Caused by Ototoxicity in Developing Rajan N Patel 18 performance. Countries Solvent Exposure at the Workplace: Adrian Fuente 22 In many instances, these side effects are Workers’ Hearing in Jeopardy not present if drugs are prescribed prop- erly. Some drugs may interact with each Ototoxicity: A Canadian View Peter W Alberti 24 other and lead to increased toxicity, but Molecular Diagnosis of Mitochondrial Genes: Min-Xin Guan 25 these interactions are not well under- Early Detection and Prevention of Aminoglycoside stood. When the cause of deafness is not Ototoxicity identified, it is important to review occu- REPORTS pation and medication to see if there is The Need of a Programme for the Prevention of Diego J Santana-Hernández 28 any toxin responsible for the deafness. Hearing Impairment in Beni State, Bolivia Ototoxicity is more common than often Atfaluna News Update Geraldine Shawa 30 suggested and in most cases is a prevent- ABSTRACTS 31 able cause of deafness. COMMUNITY EAR AND HEARING HEALTH: 2006; 3: 17-32 Issue No. 4 www.icthesworldcare.com 17 Ototoxicity in Developing Countries DEAFNESS CAUSED BY OTOTOXICITY IN DEVELOPING COUNTRIES Rajan N Patel Table 1: Grades of Hearing Impairment Medical Student Grade of impairment Corresponding audiometric ISO* value Department of Child and Reproductive 0 - None 25 dB or better Health 1 – Slight 26-40 dB Liverpool School of Tropical Medicine Pembroke Place 2 – Moderate 41-60 dB Liverpool L3 5QA 3 - Severe 61-80 dB UK 4 – Profound 81 dB or greater *International Organization for Standardization Email: [email protected] his report attempts to review million people in the world had a disa- Grades of Hearing Impairment systematically the current liter- bling hearing impairment and that two- Deafness can be expressed as a complete ature on deafness caused by thirds of these people lived in develop- loss in the ability to hear from one or T ing countries.2 Furthermore, Torrigiani ototoxicity in developing countries and both ears. It can also be described as a make an appraisal of its current status in Geneva outlined that avoidable hearing threshold of 81dB or greater, in different regions of the developing hearing impairment and deafness are averaged at frequencies 0.5, 1, 2, 4 kHz.2 world. This involves critically assessing an important public health problem, Table 1 provides the different grades of research and accessing routine electronic particularly in low-income countries. hearing impairment.2 literature databases. Although infectious conditions, such as otitis media, account for the largest Ototoxicity and its Causes Deafness Worldwide proportion of conductive hearing loss, Ototoxicity refers to the harmful effect Deafness is a worldwide problem. It is damage to sensori-neural hearing caused of a drug, chemical substance or heavy estimated that 1:1000 children are born by ototoxic medication has been increas- metal on the organ of hearing or balance, deaf, while 2:1000 children are born ingly reported from countries in recent which may lead to a hearing impair- 3 hard of hearing.1 In 2002, the World years. ment, and/or balance problems. Table 2 Health Organization estimated that 250 displays some of these substances.3 Table 2: Causes of Hearing Impairment and/or Balance Problems Aminoglycosides Gentamicin, streptomycin, kanamycin, amikacin, tobramycin, neomycin, netilmicin, polymyxin-B Macrolides Erythromycin, azithromycin, clarithromycin Loop diuretics Furosemide, bumetanide, ethacrinic acid Salicylates Antimalarials Quinine, chloroquine (high dosage) Non-steroid anti-inflammatory drugs Naproxen, indomethacin (no definite findings) Anti-neoplastic drugs Cisplatin, bleomycin, carboplatinum Chelating agents Desferoxamine Topical otological preparations Antibiotic solutions: Neomycin Aminoglycosides Polymyxin-B Chloramphenicol Fosfomycin Anti-inflammatory: Propylene-glycol, hydrocortisone Antiseptic: Chlorohexidine, povidone-iodine (?) Acidifying: 2% acetic acid solution (?) Chemical agents Heavy metals: Mercury, lead (Industrial pollution, cosmetics). Solvents: Toluene, styrene Others: Arsenic, cobalt, cyanides, benzene, propylene-glycol, potassium bromide 18 www.icthesworldcare.com COMMUNITY EAR AND HEARING HEALTH: 2006; 3: 17-32 Issue No. 4 Ototoxicity in Developing Countries Ototoxicity tends to be thought of in caused by the prescription of ototoxic which the main criterion for classify- the context of drug administration lead- drugs, one should assume that preven- ing economies is gross national income ing to damage of the cochlea or vestib- tive measures could be taken effectively. (GNI) per capita. Based on its GNI per ular portion of the inner ear, causing Minja makes reference to the prevent- capita, every economy is classified as transitional or permanent sensorineural ability of deafness due to ototoxicity, low income, middle income (subdivided hearing loss (SNHL) and/or vertigo. despite its variety of causes.1 Suggestions into lower middle and upper middle), Antibiotics, diuretics and anti-malarial will be made regarding methods and or high income. Table 3 identifies some pharmaceuticals have been implicated strategies for the prevention of ototoxic- of the developing countries that will be as potentially toxic to both the auditory ity in developing countries. discussed in this report, and others that and vestibular systems. Kanamycin and are noteworthy.7 neomycin are perhaps the most alarm- Another report refers to the extensive use ing ototoxic drugs at this time.4 This and abuse of aminoglycosides and how To summarise this introduction to report will later discuss and evaluate the they are a major concern.3 It suggests ototoxicity-induced deafness, it is impor- current status of ototoxicity due to these that the most common cause of hearing tant to note that the global magnitude of substances. This will be accomplished by impairment from ototoxic damage by the problem is not accurately known assessing and reviewing different litera- drugs is due to injectable aminoglyco- and that there is a great need for more ture written about the use of these chem- sides. It is also implied that gentamicin detailed research on ototoxicity. icals in various regions of the world, and is cheaper than newly available alterna- in particular, the developing world. tives and, hence, is more widely avail- Discussion and Results able. Additionally, WHO recognises that This report will now analyse and review While aminoglycosides have been largely the global resurgence of tuberculosis is the literature found. It will discuss the replaced over the last decades by modern leading to greater use of streptomycin.3 current status of ototoxicity in develop- antibiotics with fewer side effects, they For example, in South Africa, strepto- ing countries by comparing results from remain a mainstay in medicine. In fact, mycin and kanamycin form part of the clinical studies carried out. It will then they may be the most commonly used drug regimen administered to multi- assess the disagreements, strengths and antibiotics worldwide, chiefly due to drug resistant tuberculosis (MDR-TB) weaknesses of various papers. The prob- their use in developing countries. Their sufferers.6 One of the aims of this report lems facing people in developing coun- high efficacy, coupled with