title: Alterations in Evoked Otoacoustic Emissions by the Use of Meglumine Antimoniate in American Tegumentary Leishmaniasis Patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (INI-FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Débora Cristina de
authors.initials: DC
authors.lastname: Oliveira Bezerra
authors.affiliation: Department of Otorhinolaryngology and Ophthalmology, Faculty of Medicine, Federal University of Rio de Janeiro, (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Oliveira de Barcelos
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (INI-FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Ellen
authors.initials: E
authors.lastname: Carvalho de Castro
authors.affiliation: Department of Otorhinolaryngology and Ophthalmology, Faculty of Medicine, Federal University of Rio de Janeiro, (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Claudia Cristina
authors.initials: CC
authors.lastname: Jardim Duarte
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (INI-FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: de Vasconcellos Carvalhaes Oliveira
authors.affiliation: Department of Otorhinolaryngology and Ophthalmology, Faculty of Medicine, Federal University of Rio de Janeiro, (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Tania
authors.initials: T
authors.lastname: Salgado de Sousa Torraca
authors.affiliation: Department of Otorhinolaryngology, Faculty of Medicine, Federal University of the State of the Rio de Janeiro, (UNIRIO), Rio de Janeiro, Brazil.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: de Araújo-Melo
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (INI-FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Frederico
authors.initials: F
authors.lastname: Pereira Bom Braga
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (INI-FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Benivaldo
authors.initials: B
authors.lastname: Ramos Ferreira Terceiro
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (INI-FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Lúcia Regina
authors.initials: LR
authors.lastname: do Nascimento Brahim Paes
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (INI-FIOCRUZ), Rio de Janeiro, Brazil.|Brazilian National Council for Scientific and Technological Development (CNPq), Brasilia, Brazil.|Carlos Chagas Filho Foundation for Research Support of the state of Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil.
authors.forename: Armando
authors.initials: A
authors.lastname: de Oliveira Schubach
authors.affiliation: 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.|Carlos Chagas Filho Foundation for Research Support of the state of Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil.|Hygiene and Tropical Medicine Institute (IHMT), New University of Lisbon (UNL), Lisbon, Portugal.
authors.forename: Cláudia Maria
authors.identifier: http://orcid.org/0000-0003-3110-9271
authors.initials: CM
authors.lastname: Valete-Rosalino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold / Q000502:physiology; D001938:Brazil; D003051:Cochlea / Q000187:drug effects; D005260:Female; D006309:Hearing; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008137:Longitudinal Studies; D008297:Male; D008536:Meglumine / Q000009:adverse effects*; D000077485:Meglumine Antimoniate; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects*; D017084:Otoacoustic Emissions, Spontaneous; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate