Optical Identification of Middle Ear Infection

molecules Review Optical Identification of Middle Ear Infection Alisha Prasad y , Syed Mohammad Abid Hasan y and Manas Ranjan Gartia * Department of Mechanical and Industrial Engineering, Louisiana State University, Baton Rouge, LA 70803, USA; [email protected] (A.P.); [email protected] (S.M.A.H.) * Correspondence: [email protected] These authors contributed equally to this work. y Academic Editor: Kamilla Malek Received: 31 March 2020; Accepted: 29 April 2020; Published: 9 May 2020 Abstract: Ear infection is one of the most commonly occurring inflammation diseases in the world, especially for children. Almost every child encounters at least one episode of ear infection before he/she reaches the age of seven. The typical treatment currently followed by physicians is visual inspection and antibiotic prescription. In most cases, a lack of improper treatment results in severe bacterial infection. Therefore, it is necessary to design and explore advanced practices for effective diagnosis. In this review paper, we present the various types of ear infection and the related pathogens responsible for middle ear infection. We outline the conventional techniques along with clinical trials using those techniques to detect ear infections. Further, we highlight the need for emerging techniques to reduce ear infection complications. Finally, we emphasize the utility of Raman spectroscopy as a prospective non-invasive technique for the identification of middle ear infection. Keywords: middle ear infection; bacterial infection; otitis media; otoscope; drug-resistant microbial; label-free method; Raman spectroscopy 1. Introduction Ear infection or otitis media (OM) is a commonly found illness in children under the age of three [1–5]. The healthcare cost due to ear infections in the U.S. is estimated to be $3–5 billion annually [6–8]. There are three types of OM, acute otitis media (AOM), otitis media with effusion (OME), and chronic otitis media with effusion [9–13]. AOM occurs in the middle ear due to bacterial infection resulting in the buildup of fluid. OME also results in the buildup of fluid in the middle ear area due to inflammation and is much more severe than AOM. The symptom of both AOM and OME is the swelling of the tympanic membrane (TM). This makes it difficult to diagnose AOM from OME clinically. The typical diagnostic is based on pneumatic otoscopy, which is the gold standard to differentiate AOM from OME [14]. The pneumatic otoscope measures the deflection of TM under pressure by creating an air-tight seal. The response will change when there is fluid buildup behind the TM. In addition to the complicated process of creating an air-tight seal, the pneumatic otoscope can neither identify the bacteria involved in the infection nor distinguish viral infections from bacterial infections. Failure to differentiate viral and bacterial infections and/or AOM from OME may lead to the prescription of antibiotics, leading to drug-resistant microorganisms. Therefore, accurate detection and identification of bacteria responsible for OM is a clinically unmet need. The three most common bacteria that are responsible for AOM and OME are Streptococcus pneumoniae (Gram-positive) [15,16], Haemophilus influenza (Gram-negative), and Moraxella catarrhalis (Gram-negative) [17–21]. Humans asymptomatically harbor these bacteria, and they primarily colonize in the upper respiratory tract and scantily populate the lower respiratory tract. These bacteria normally act as symbiotic partners, which ultimately protect the host from getting colonized by possibly more pathogenic or antibiotic-resistant organisms. Fluid buildup in the middle ear with a moist and warm Molecules 2020, 25, 2239; doi:10.3390/molecules25092239 www.mdpi.com/journal/molecules Molecules 2020, 25, 2239 2 of 16 Molecules 2020, 25, x FOR PEER REVIEW 2 of 16 environment provides ready access and a well-suited place for bacterial growth and is the main acause moist of and AOM warm [20 ].environment Acute mastoiditis provides is another ready acce typess of and bacterial a well-suited infection place resulting for bacterial from untreated growth andacute is otitisthe main media, cause prompting of AOM serious[20]. Acute exertion mastoiditis and intrusion is another of the type mastoid of bacterial cells in infection the mastoid resulting bone fromlocated untreated behind theacute ear otitis [22]. media, In current prompting clinical settings,serious exertion Gram staining and intrusion is a routine of the procedure mastoid followed, cells in thewherein mastoid ear bone swabs located are collected behind for the analysis ear [22]. of theIn current bacteria. clinical The major settings, drawback Gram associatedstaining is with a routine Gram procedurestaining is followed, that although wherein it helps ear swabs in bacterial are collected classification, for analysis it gives of nothe information bacteria. The about major the drawback bacterial associatedstrain. This with misinformation Gram staining may is cause that thealthough bacterial it infectionhelps in tobacterial recur as classification, the prescribed it antibioticsgives no informationmight be resistant about the to thebacterial infection. strain. In This a recent misinformation study, it was may found cause that the onlybacterial in 25% infection of the to cases, recur a asspecific the prescribed bacteria stain antibiotics was found might in be the resistant culture; however,to the infection. in nearly In 80%a recent of the study, same it cases was offound OME, that the onlyspecific in 25% DNA-RNA of the cases, of the a specific pathogens bacteria were stain accurately was found detected in the by culture; polymerase however, chain in reactionnearly 80% (PCR) of themethod same [ 19cases]. This of suggestOME, thatthe specific the combination DNA-RNA of molecular of the pathogens biology techniques were accurately (like analysis detected of DNA, by polymeraseRNA, protein) chain is neededreaction in (PCR) addition method to the [19]. microbiology This suggest techniques that the combination (bacterial staining)of molecular for accuratebiology techniquesexamination (like of theanalysis pathogen. of DNA, Although RNA, protein) these techniques is needed arein addition useful, the to the main microbiology drawbacks techniques include the (bacterialrequirement staining) of specialized for accurate expensive examination equipment, of the highlypathogen. skilled Although lab personnel, these techniques and time-consuming are useful, thesample main preparation. drawbacks include the requirement of specialized expensive equipment, highly skilled lab personnel,Although and time-consuming most infections are sample a result preparation. of bacterial invasion, there are a few ear infections such as vestibularAlthough neuronitis, most infections infectious are myringitis, a result of and bacterial herpes invasion, zoster of there the ear, are whicha few ear are infections caused by such viruses. as vestibularVestibular neuronitis, neuritis is causedinfectious by themyringitis, inflammation and herpes of the zoster vestibular of the nerve, ear, which which are is situated caused by at theviruses. inner Vestibularear (Figure neuritis1a). Acute is caused mastoiditis by the is ainflammation type of bacterial of the infection vestibular resulting nerve, from which untreated is situated acute at otitis the innermedia, ear prompting (Figure 1a). serious Acute exertionmastoiditis and is intrusiona type of bacterial of the mastoid infection cells resulting in the mastoidfrom untreated bone located acute otitisbehind media, the ear prompting [22]. As seen serious from exertion Figure1b, and the intrusion eardrum ofof a the healthy mastoid ear lookscells pinkishin the mastoid gray, whereas bone locatedthe otitis behind media the infected ear [22]. middle As seen ear from in Figure Figure1c has1b, the a red, eardrum bulging of eardrum. a healthy ear looks pinkish gray, whereas the otitis media infected middle ear in Figure 1c has a red, bulging eardrum. Figure 1. (a) Anatomy of a human ear. Adopted and modified from [9]. (b) Healthy human ear. (c) Figure 1. (a) Anatomy of a human ear. Adopted and modified from . (b) Healthy human ear. (c) Infected human ear. Adopted and modified from [23], Copyright Microbiology[9] Society, 2015. Infected human ear. Adopted and modified from [23], Copyright Microbiology Society, 2015. In this manuscript, we reviewed the current and emerging optical techniques useful for the detectionIn this of manuscript, ear infection, we and reviewed in Table1 ,the we current list them an ind detail.emerging However, optical in techniques some cases, useful the sensitivity for the detectionand specificity of ear informationinfection, and for in earTable infection 1, we list were them not in found. detail. However,However, wein some included cases, the the performance sensitivity andparameters specificity for information those cases for based ear infection on the same were technologynot found. However, that has beenwe included applied the in similarperformance fields. parametersAccurate identification for those cases of bacteriabased on will the provide same tech physiciansnology that additional has been information applied in to similar prescribe fields. the Accurateproper treatment identification plan whileof bacteria avoiding will antimicrobial provide physicians drug resistance. additional We information also highlighted to prescribe the Raman the proper treatment plan while avoiding antimicrobial drug resistance. We also highlighted the Raman spectroscopy-based

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