Oliveira Bezerra Débora Cristina de, Oliveira de Barcelos Renata, Carvalho de Castro Ellen, Jardim Duarte Claudia Cristina, de Vasconcellos Carvalhaes Oliveira Raquel, Salgado de Sousa Torraca Tania, de Araújo-Melo Maria Helena, Pereira Bom Braga Frederico, Ramos Ferreira Terceiro Benivaldo, do Nascimento Brahim Paes Lúcia Regina, de Oliveira Schubach Armando, Valete-Rosalino Cláudia Maria
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (INI-FIOCRUZ), Rio de Janeiro, Brazil.
Department of Otorhinolaryngology and Ophthalmology, Faculty of Medicine, Federal University of Rio de Janeiro, (UFRJ), Rio de Janeiro, Brazil.
PLoS One. 2017 Jan 3;12(1):e0168492. doi: 10.1371/journal.pone.0168492. eCollection 2017.
Tegumentary Leishmaniasis (TL) is a neglected, non-contagious, infectious disease, caused by different protozoa species of the Leishmania genus that affects skin and mucous membranes. Meglumine Antimoniate (MA), the first drug of choice for TL treatment in Brazil, has already been associated with cochlear toxicity, which is defined as damages of the cochlea caused by exposure to chemical substances, resulting in reversible or irreversible hearing loss. Auditory monitoring for cochlear toxicity aims at the early detection of auditory disorders, enabling, when possible, hearing to be preserved or an early auditory rehabilitation. Although otoacoustic emissions (OAEs) are used in this monitoring, there is no consensus on the criteria that define cochlear toxicity by this examination. The objective of this study was to describe the characteristics of the OAEs in cochlear toxicity monitoring in TL patients using MA.
Prospective and longitudinal study of auditory monitoring of 35 patients with parasitological diagnosis of TL, with liminal tonal audiometry, high frequency audiometry, immitanciometry, distortion product evoked otoacoustic emissions (DPEOAEs) and transient evoked otoacoustic emissions (TEOAEs) before treatment, at the end of treatment, one month after the end of treatment and two months after the end of treatment.
80% male, with median age of 44 years (IIQ: 22-59). In the pre-treatment evaluation: 11.4% complained of hearing loss and 20% of tinnitus, 48.6% presented auditory alterations in liminal tonal audiometry (LTA, 65.2% in high frequency audiometry (HFA), 26.6% in DPEOAE and 51.4% in TEOAE. No association was verified between genre and alterations in the EOAE examinations. We observed that patients that presented disorders in DPEOAE examinations were 17 years older than those without alterations and that patients that showed disorders in TEOAEO examinations were 34 years older than those without disorders. The presence of alterations in DPEOAE and TEOAE before beginning treatment was associated with each other and with the presence of alterations in LTA and HFA, and only DPEOAE was associated with hearing loss. We observed a significantly higher number of alterations of DPEOAE at the end of treatment than during pre-treatment and values of the ratio signal/noise significantly smaller at the end of treatment than during pre-treatment in the frequencies of 2 kHz (difference of 1.7dB; p = 0.016) and 4 kHz (difference of 2.45dB; p = 0.016) in DPEOAE and in the range 1.75/2.5 kHz in TEOAE (difference of 2.9dB; p = 0.039).
The ototoxic signals observed in our study using EOAE indicated that both, DPEOAE and TEOAE are adequate and sensitive techniques for clinical monitoring of ototoxicity by MA. Their application is very simple, and their results help the physician to take the most adequate steps for each patient, thus avoiding permanent hearing damage.
皮肤利什曼病（TL）是一种被忽视的、非传染性的传染病，由利什曼原虫属的不同原生动物物种引起，会影响皮肤和黏膜。葡甲胺锑酸盐（MA）是巴西治疗TL的首选药物，它已被证实与耳蜗毒性有关，耳蜗毒性被定义为因接触化学物质而导致的耳蜗损伤，会造成可逆或不可逆的听力损失。对耳蜗毒性进行听觉监测旨在早期发现听觉障碍，尽可能地保护听力或进行早期听觉康复。尽管耳声发射（OAE）被用于此项监测，但对于通过该检查定义耳蜗毒性的标准尚无共识。本研究的目的是描述使用MA进行TL患者耳蜗毒性监测时OAE的特征。
对35例经寄生虫学诊断为TL的患者进行前瞻性纵向听觉监测研究，在治疗前、治疗结束时、治疗结束后1个月和治疗结束后2个月进行阈上纯音听力测定、高频听力测定、声导抗测量、畸变产物诱发耳声发射（DPEOAE）和瞬态诱发耳声发射（TEOAE）。
80%为男性，中位年龄44岁（四分位间距：22 - 59岁）。在治疗前评估中：11.4%主诉听力损失，20%主诉耳鸣，48.6%在阈上纯音听力测定（LTA）中出现听觉改变，65.2%在高频听力测定（HFA）中出现听觉改变，26.6%在DPEOAE中出现听觉改变，51.4%在TEOAE中出现听觉改变。在EOAE检查中，未发现性别与改变之间存在关联。我们观察到，在DPEOAE检查中出现异常的患者比未出现异常的患者大17岁，在TEOAE检查中出现异常的患者比未出现异常的患者大34岁。治疗开始前DPEOAE和TEOAE中出现的改变相互关联，且与LTA和HFA中的改变相关，只有DPEOAE与听力损失相关。我们观察到，治疗结束时DPEOAE的改变数量显著高于治疗前，且在2 kHz频率（差异为1.7dB；p = 0.016）和4 kHz频率（差异为2.45dB；p = 0.016）的DPEOAE以及1.75/2.5 kHz范围内的TEOAE中，治疗结束时的信噪比显著低于治疗前（差异为2.9dB；p = 0.039）。
我们使用EOAE在研究中观察到的耳毒性信号表明，DPEOAE和TEOAE都是用于MA耳毒性临床监测的合适且敏感的技术。它们的应用非常简单，其结果有助于医生为每位患者采取最适当的措施，从而避免永久性听力损伤。
