EFFECTIVE METHODS OF TREATMENT AND PREVENTION OF ACUTE OTIT MEDIA DISEASE

301

Otitis media is among the most common types of ear diseases. It affects the middle ear, causing fluid buildup behind the eardrum. This can lead to swelling and an earache. Otitis media is a group of inflammatory diseases of the middle ear. One of the three main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, increased crying, and poor sleep. Decreased eating and a fever may also be present. The other main type is otitis media with effusion (OME), typically not associated with symptoms, although occasionally a feeling of fullness is described; it is defined as the presence of non-infectious fluid in the middle ear for more than three months

Name of journalRE-HEALTH
Number of edition3.2-2020
View count301

Web Address https://cyberleninka.ru/article/n/effektivnye-metody-lecheniya-i-profilaktiki-ostrogo-srednego-otita

DOI10.24411/2181-0443/2020-10128

Date of creation in the UzSCI system31-01-2021

Read count238

Date of publication30-01-2021

Main LanguageIngliz

PagesЭФФЕКТИВНЫЕ МЕТОДЫ ЛЕЧЕНИЯ И ПРОФИЛАКТИКИ ОСТРОГО СРЕДНЕГО ОТИТА

Tags

OME

Otitis media

middle ear

AOM

Русский

Средний отит - один из самых распространенных видов заболеваний уха. Это влияет на среднее ухо, что приводит к скоплению жидкости за барабанной перепонкой. Это может привести к отеку и боли в ушах. Средний отит - воспалительное заболевание среднего уха. Существует три основных типа, один из которых - острый средний отит (ОСО), быстро развивающаяся инфекция, которая обычно вызывает боль в ушах. У маленьких детей это может привести к боли в ухе, усилению плача и нарушениям сна. Кроме того, это может вызвать потерю аппетита и жар. Второй основной тип - это, как правило, бессимптомный экссудативный средний отит (ЭСО), при котором неинфекционная жидкость обнаруживается в среднем ухе более трех месяцев. Хронический гнойный средний отит (ХГСО) - это воспаление среднего уха, в результате которого ухо опорожняется (лечится) более трех месяцев.

Tags

Средний отит

среднее ухо

ОСО

ЭСО

Ўзбек

Otit media quloq kasalliklarining eng keng tarqalgan turlaridan biridir. Bu o'rta quloqqa ta'sir qiladi, bu esa quloq pardasi orqasida suyuqlik to'planishiga olib keladi. Bu shish va quloq og'rig'iga olib kelishi mumkin. Otit media o'rta quloqning yallig'lanish kasalligidir. Uchta asosiy turi bor, biri bu o'tkir otit media (O’OM), tez boshlanadigan infektsiya bo'lib, odatda quloq og'rig'iga sabab bo’ladi. Yosh bolalarda bu quloqni tortishga, yig'lashni kuchayishiga va uyquning buzilishiga mumkin. Qo’shimcha ravishda ishtaha yo’qolishi va isitmaga ham sabab bo'lishi mumkin. Ikkinchi asosiy turi - bu odatda simptomlar bilan bog'liq bo'lmagan ekssudativ (OME) otitis media hisoblanib, bu turida uch oydan ko'proq vaqt davomida o'rta quloqda yuqumli bo'lmagan suyuqlik mavjudligi aniqlanadi. Surunkali yiringli otit media (SYOM) - bu o'rta quloqning yallig'lanishi, natijada quloq uch oydan ko'p vaqt davomida bo'shatiladi (muolaja qilinadi).

Tags

Otit media

o’rta quloq

O’OM

OME

English

Otitis media is among the most common types of ear diseases. It affects the middle ear, causing fluid buildup behind the eardrum. This can lead to swelling and an earache. Otitis media is a group of inflammatory diseases of the middle ear. One of the three main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, increased crying, and poor sleep. Decreased eating and a fever may also be present. The other main type is otitis media with effusion (OME), typically not associated with symptoms, although occasionally a feeling of fullness is described; it is defined as the presence of non-infectious fluid in the middle ear for more than three months

Tags

OME

Otitis media

middle ear

AOM

№ Author name position Name of organisation

1 Nugmanov O.J. . ASMI

2 Raximov S.K. . ASMI

3 Abdumutalipov Ulugbek Shuxrat ogli U.S. . ASMI

4 Xaydarov I.I. . ASMI

№ Name of reference

1 1. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013;131:e964–999.

2 2. Palmu AA, Herva E, Savolainen H, et al. Association of clinical signs and symptoms with bacterial findings in acute otitis media. Clin Infect Dis. 2004;38:234–242.

3 3. Pichichero ME, Reed MD. Variations in amoxicillin pharmacokinetic/ pharmacodynamic parameters may explain treatment failures in acute otitis media. Paediatr Drugs. 2009;11:243–249.

4 4. Tähtinen PA, Laine MK, Huovinen P, et al. A placebo-controlled trial of antimicrobial treatment for acute otitis media. N Engl J Med. 2011;364:116–126.

5 5. Johnson CE, Belman S. The role of antibacterial therapy of acute otitis media in promoting drug resistance. Paediatr Drugs. 2001;3:639–647.

6 6. Thompson PL, Gilbert RE, Long PF, et al. Has UK guidance affected general practitioner antibiotic prescribing for otitis media in children? J Public Health (Oxf). 2008;30:479–486.

7 7. Marchisio P, Tagliabue M, Klersy C, et al. Patterns in acute otitis media drug prescriptions: a survey of Italian pediatricians and otolaryngologists. Expert Rev Anti Infect Ther. 2014;12:1159–1163.

8 8. Haggard M. Poor adherence to antibiotic prescribing guidelines in acute otitis media–obstacles, implications, and possible solutions. Eur J Pediatr. 2011;170:323–332.

9 9. Venekamp RP, Prasad V, Hay AD. Are topical antibiotics an alternative to oral antibiotics for children with acute otitis media and ear discharge? BMJ. 2016;352:i308.

10 10. Al-Mahallawi AM, Khowessah OM, Shoukri RA. Enhanced non invasive trans -tympanic delivery of ciprofloxacin through encapsulation into nano-spanlastic vesicles: fabrication, in-vitro characterization, and comparative ex-vivo permeation studies. Int J Pharm. 2017;522:157–164.

11 11. Abdelbary AA, Abd-Elsalam WH, Al-Mahallawi AM. Fabrication of levofloxacin polyethylene glycol decorated nanoliposomes for enhanced management of acute otitis media: statistical optimization, trans-

12 12. Mittal R, Parrish JM, Soni M, et al. Microbial otitis media: recent advancements in treatment, current challenges and opportunities. J Med Microbiol. 2018;67:1417–1425.

13 13. Kurabi A, Pak KK, Bernhardt M, et al. Discovery of a biological mechanism of active transport through the tympanic membrane to the middle ear. Sci Rep. 2016;6:22663.

14 14. Chang RYK, Wallin M, Lin Y, et al. Phage therapy for respiratory infections. Adv Drug Deliv Rev. 2018;133:76–86.

15 15. El-Shibiny A, El-Sahhar S. Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria. Can J Microbiol. 2017;63:865–879.

16 16. Kurabi A, Schaerer D, Chang L, et al. Optimisation of peptides that actively cross the tympanic membrane by random amino acid extension: a phage display study. J Drug Target. 2018;26:127–134.

17 17. Bakaletz LO. Bacterial biofilms in the upper airway—evidence for role in pathology and implications for treatment of otitis media. Paediatr Respir Rev. 2012;13:154–159.

18 18. Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010;8:623–633.

19 19. Cope EK, Goldstein-Daruech N, Kofonow JM, et al. Regulation of virulence gene expression resulting

20 20. Haggard M. Otitis media: prospects for prevention. Vaccine. 2008;26((Suppl. 7)):G20–G24.

21 21. Jurcisek JA, Bookwalter JE, Baker BD, et al. The PilA protein of nontypeable Haemophilus influenzae plays a role in biofilm formation, adherence to epithelial cells and colonization of the mammalian upper respiratory tract. Mol Microbiol. 2007;65:1288–1299.

22 22. Mokrzan EM, Ward MO, Bakaletz LO. Type IV pilus expression is upregulated in nontypeable Haemophilus influenzae biofilms formed at the temperature of the human nasopharynx. J Bacteriol. 2016;198:2619–2630.

23 23. Novotny LA, Jurcisek JA, Jr WMO, et al. Antibodies against the majority subunit of type IV pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media. Mol Microbiol. 2015;96:276–292.

24 24. Novotny LA, Clements JD, Goodman SD, et al. Transcutaneous immunization with a band-aid prevents experimental otitis media in a polymicrobial model. Clin Vaccine Immunol. 2017;24:e00563– 16.

25 25. Mokrzan EM, Novotny LA, Brockman KL, et al. Antibodies against the majority subunit (PilA) of the type IV pilus of nontypeable Haemophilus influenzae disperse Moraxella catarrhalis from a dual-species biofilm. MBio. 2018;9:e02423–18.

26 26. Lappan R, Imbrogno K, Sikazwe C, et al. A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera. BMC Microbiol. 2018;18:13.

27 27. Coleman, A., & Cervin, A. (2018). Probiotics in the treatment of otitis media. The past, the present and the future. International Journal of Pediatric Otorhinolaryngology. doi:10.1016/j.ijporl.2018.10.023.

28 28. FAO/WHO, Guidelines for the Evaluation of Probiotics in Food. City: FAO/WHO, 2002.

29 29. Eiseman B, Silen W, Bascom GS, Kauvar AJ. 1958. Surgery 1958; 44: 854-859.

30 30. van Nood E, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JFWM, Tijssen JGP, Speelman P, Dijkgraaf MGW, Keller JJ. 2013. New Engl. J. Med. 2013; 368: 407-415.

31 31. Moayyedi P, Yuan Y, Baharith H, Ford A. 2017. Med. J. Aust. 2017; 207: 166-172.

32 32. AlFaleh K, Anabrees J. 2014. Cochrane Database of Systematic Reviews 2014.

33 33. Dominguez-Bello MG, Costello EK, Contrera M, Mgris M, Hidalgo G, Fierer N, Knight R. 2010. Proc. Natl. Acad. Sci. U S A 2010; 107: 11971-11975.

34 34. Bosch AATM, Levin E, van Houten MA, Hasrat R, Kalkman G, Biesroek G, de Steenhuijsen Piters WAA, de Groot PKCM, Pernet P, Keijer BJF, Sanders EAM, Bogaert D. 2016. EBioMedicine 2016; 9: 336-345.

35 35. Biesbroek G, Tsivtsivadze E, Sanders E, Montijn R, Veenhoven R, Keijer BJF, Bogaert D. 2014. Am. J. Respir. Crit. Care Medicine 2014; 190: 1283-1292.

36 36. Biesbroek G, Bosch AATM, Wang X, Keijer BJF, Veenhoven R, Sanders E, Bogaert D. 2014. Am. J. Respir. Crit. Care Medicine 2014; 190: 298-308.

37 37. Sakwinska O, Bastic Schmid V, Berger B, Bruttin A, Keitel K, Legpage M, Moine D, Ngom Bru C, Brüssow H, Gervaix A. 2014. J. Clin. Microbiol. 2014; 52: 1590-1594.

38 38. Pettigrew M, Laufer A, Gent J, Kong Y, Fennie K, Metlay J. 2012. Appl. Environ. Microbiol. 2012; 78: 6262-6270.

39 39. Sato S, Kiyono H. 2012. Curr. Opin. Virol. 2012; 2: 225-232.

40 40. Brugman S, Perdijk O, van Neerven RJJ, Savelkoul HFJ. 2015. Arch. Immunol. Ther. Exp. 2015; 63: 251-268.

41 41. Lappan R, Imbrogno K, Sikazwe C, et al. A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera. BMC Microbiol. 2018;18:13.

42 42. Cárdenas N, Martín V, Arroyo R, et al. Prevention of recurrent acute otitis media in children through the use of lactobacillus salivarius PS7, a target-specific probiotic strain. Nutrients. 2019;11:E376.

43 43. Marchisio P, Santagati M, Scillato M, et al. Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children. Eur J Clin Microbiol Infect Dis. 2015;34:2377–2383.

44 44. Krammer F, Palese P. Advances in the development of influenza virus vaccines. Nat Rev Drug Discov. 2015;14:167–182.

45 45. Houser K, Subbarao K. Influenza vaccines: challenges and solutions. Cell Host Microbe. 2015;17:295–300.

46 46. Norhayati MN, Ho JJ, Azman MY. Influenza vaccines for preventing acute otitis media in infants and children. Cochrane Database Syst Rev. 2017 Oct 17;10: CD010089.

47 47. Vemula SV, Sayedahmed EE, Sambhara S, et al. Vaccine approaches conferring cross-protection against influenza viruses. Expert Rev Vaccines. 2017;16:1141–1154.

48 48. Villafana T, Falloon J, Griffin MP, et al. Passive and active immunization against respiratory syncytial virus for the young and old. Expert Rev Vaccines. 2017;16:1–13.

49 49. Glanville N, Johnston SL. Challenges in developing a cross-serotype rhinovirus vaccine. Curr Opin Virol. 2015;11:83–88.

50 50. Fougeroux C, Holst PJ. Future prospects for the development of cost-effective adenovirus vaccines. Int J Mol Sci. 2017;18:E686.

51 51. Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet. 2011;378:1962–1973.

52 52. Scott P, Rutjes AWS, Bermetz L, et al. Pneumococcal conjugate vaccines: a systematic review of data from randomized controlled trials and observational studies of childhood schedules using 7-, 9-, 10- and 13-valent vaccines; [cited 2019 Apr 25].

53 53. Esposito S, Principi N. Safety and tolerability of pneumococcal vaccines in children. Expert Opin Drug Saf. 2016;15:777–785.

54 54. Vojtek I, Nordgren M, Hoet B. Impact of pneumococcal conjugate vaccines on otitis media: A review of measurement and interpretation challenges. Int J Pediatr Otorhinolaryngol. 2017;100:174–182.

55 55. Ben-Shimol S, Givon-Lavi N, Leibovitz E, et al. Near- elimination of otitis media caused by 13-valent pneumococcal conjugate vaccine (PCV) serotypes in southern Israel shortly after sequential introduction of 7-valent/13-valent PCV. Clin Infect Dis. 2014;59::1724–1732.

56 56. Pichichero M, Kaur R, Scott DA, et al. Effectiveness of 13-valent pneumococcal conjugate vaccination for protection against acute otitis media caused by Streptococcus pneumoniae in healthy young children: a prospective observational study. Lancet Child Adolesc Health. 2018;2:561–568.

57 57. Quirk SJ, Haraldsson G, Erlendsdóttir H, et al. Effect of vaccination on pneumococci isolated from the nasopharynx of healthy children and the middle ear of children with otitis media in Iceland. J Clin Microbiol. 2018;56:e01046–18.

58 58. Morales M, Ludwig G, Ercibengoa M, et al. Changes in the serotype distribution of Streptococcus pneumoniae causing otitis media after PCV13 introduction in Spain. PLoS One. 2018;13:e0209048.

59 59. Allemann A, Frey PM, Brugger SD, et al. Pneumococcal carriage and serotype variation before and after introduction of pneumococcal conjugate vaccines in patients with acute otitis media in Switzerland. Vaccine. 2017;35:1946–1953.

60 60. Halgrimson WR, Chan KH, Abzug MJ, et al. Incidence of acute mastoiditis in Colorado children in the pneumococcal conjugate vaccine era. Pediatr Infect Dis J. 2014;33:453–457.

61 61. Kaplan SL, Center KJ, Barson WJ, et al. Multicenter surveillance of Streptococcus pneumoniae isolates from middle ear and mastoid cultures in the 13-valent pneumococcal conjugate vaccine era. Clin Infect Dis. 2015;60:1339–1345.

62 62. Marchisio P, Esposito S, Picca M, et al. Serotypes not Included in 13-valent pneumococcal vaccine as causes of acute otitis media with spontaneous tympanic membrane perforation in a geographic area with high vaccination coverage. Pediatr Infect Dis J. 2017;36:521–523.

63 63. Rappuoli R, Bottomley MJ, D’Oro U, et al. Reverse vaccinology 2.0: human immunology instructs vaccine antigen design. J Exp Med. 2016;213::469–481.

64 64. Skinner JM, Indrawati L, Cannon J, et al. Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model. Vaccine. 2011;29:8870–8876.

65 65. Pichichero ME Pneumococcal whole-cell and protein-based vaccines: changing the paradigm. Expert Rev Vaccines. 2017;16::1181–1190.

66 66. Greenberg D, Hoover PA, Vesikari T, et al. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants. Vaccine. 2018;36:6883–6891.

67 67. Feavers I, Knezevic I, Powell M, et al. Challenges in the evaluation and licensing of new pneumococcal vaccines, 7–8 July 2008, Ottawa, Canada. Vaccine. 2009;27:3681–3688.

Waiting

№	Author name	position	Name of organisation
1	Nugmanov O.J.	.	ASMI
2	Raximov S.K.	.	ASMI
3	Abdumutalipov Ulugbek Shuxrat ogli U.S.	.	ASMI
4	Xaydarov I.I.	.	ASMI

№	Name of reference
1	1. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013;131:e964–999.
2	2. Palmu AA, Herva E, Savolainen H, et al. Association of clinical signs and symptoms with bacterial findings in acute otitis media. Clin Infect Dis. 2004;38:234–242.
3	3. Pichichero ME, Reed MD. Variations in amoxicillin pharmacokinetic/ pharmacodynamic parameters may explain treatment failures in acute otitis media. Paediatr Drugs. 2009;11:243–249.
4	4. Tähtinen PA, Laine MK, Huovinen P, et al. A placebo-controlled trial of antimicrobial treatment for acute otitis media. N Engl J Med. 2011;364:116–126.
5	5. Johnson CE, Belman S. The role of antibacterial therapy of acute otitis media in promoting drug resistance. Paediatr Drugs. 2001;3:639–647.
6	6. Thompson PL, Gilbert RE, Long PF, et al. Has UK guidance affected general practitioner antibiotic prescribing for otitis media in children? J Public Health (Oxf). 2008;30:479–486.
7	7. Marchisio P, Tagliabue M, Klersy C, et al. Patterns in acute otitis media drug prescriptions: a survey of Italian pediatricians and otolaryngologists. Expert Rev Anti Infect Ther. 2014;12:1159–1163.
8	8. Haggard M. Poor adherence to antibiotic prescribing guidelines in acute otitis media–obstacles, implications, and possible solutions. Eur J Pediatr. 2011;170:323–332.
9	9. Venekamp RP, Prasad V, Hay AD. Are topical antibiotics an alternative to oral antibiotics for children with acute otitis media and ear discharge? BMJ. 2016;352:i308.
10	10. Al-Mahallawi AM, Khowessah OM, Shoukri RA. Enhanced non invasive trans -tympanic delivery of ciprofloxacin through encapsulation into nano-spanlastic vesicles: fabrication, in-vitro characterization, and comparative ex-vivo permeation studies. Int J Pharm. 2017;522:157–164.
11	11. Abdelbary AA, Abd-Elsalam WH, Al-Mahallawi AM. Fabrication of levofloxacin polyethylene glycol decorated nanoliposomes for enhanced management of acute otitis media: statistical optimization, trans-
12	12. Mittal R, Parrish JM, Soni M, et al. Microbial otitis media: recent advancements in treatment, current challenges and opportunities. J Med Microbiol. 2018;67:1417–1425.
13	13. Kurabi A, Pak KK, Bernhardt M, et al. Discovery of a biological mechanism of active transport through the tympanic membrane to the middle ear. Sci Rep. 2016;6:22663.
14	14. Chang RYK, Wallin M, Lin Y, et al. Phage therapy for respiratory infections. Adv Drug Deliv Rev. 2018;133:76–86.
15	15. El-Shibiny A, El-Sahhar S. Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria. Can J Microbiol. 2017;63:865–879.
16	16. Kurabi A, Schaerer D, Chang L, et al. Optimisation of peptides that actively cross the tympanic membrane by random amino acid extension: a phage display study. J Drug Target. 2018;26:127–134.
17	17. Bakaletz LO. Bacterial biofilms in the upper airway—evidence for role in pathology and implications for treatment of otitis media. Paediatr Respir Rev. 2012;13:154–159.
18	18. Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010;8:623–633.
19	19. Cope EK, Goldstein-Daruech N, Kofonow JM, et al. Regulation of virulence gene expression resulting
20	20. Haggard M. Otitis media: prospects for prevention. Vaccine. 2008;26((Suppl. 7)):G20–G24.
21	21. Jurcisek JA, Bookwalter JE, Baker BD, et al. The PilA protein of nontypeable Haemophilus influenzae plays a role in biofilm formation, adherence to epithelial cells and colonization of the mammalian upper respiratory tract. Mol Microbiol. 2007;65:1288–1299.
22	22. Mokrzan EM, Ward MO, Bakaletz LO. Type IV pilus expression is upregulated in nontypeable Haemophilus influenzae biofilms formed at the temperature of the human nasopharynx. J Bacteriol. 2016;198:2619–2630.
23	23. Novotny LA, Jurcisek JA, Jr WMO, et al. Antibodies against the majority subunit of type IV pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media. Mol Microbiol. 2015;96:276–292.
24	24. Novotny LA, Clements JD, Goodman SD, et al. Transcutaneous immunization with a band-aid prevents experimental otitis media in a polymicrobial model. Clin Vaccine Immunol. 2017;24:e00563– 16.
25	25. Mokrzan EM, Novotny LA, Brockman KL, et al. Antibodies against the majority subunit (PilA) of the type IV pilus of nontypeable Haemophilus influenzae disperse Moraxella catarrhalis from a dual-species biofilm. MBio. 2018;9:e02423–18.
26	26. Lappan R, Imbrogno K, Sikazwe C, et al. A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera. BMC Microbiol. 2018;18:13.
27	27. Coleman, A., & Cervin, A. (2018). Probiotics in the treatment of otitis media. The past, the present and the future. International Journal of Pediatric Otorhinolaryngology. doi:10.1016/j.ijporl.2018.10.023.
28	28. FAO/WHO, Guidelines for the Evaluation of Probiotics in Food. City: FAO/WHO, 2002.
29	29. Eiseman B, Silen W, Bascom GS, Kauvar AJ. 1958. Surgery 1958; 44: 854-859.
30	30. van Nood E, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JFWM, Tijssen JGP, Speelman P, Dijkgraaf MGW, Keller JJ. 2013. New Engl. J. Med. 2013; 368: 407-415.
31	31. Moayyedi P, Yuan Y, Baharith H, Ford A. 2017. Med. J. Aust. 2017; 207: 166-172.
32	32. AlFaleh K, Anabrees J. 2014. Cochrane Database of Systematic Reviews 2014.
33	33. Dominguez-Bello MG, Costello EK, Contrera M, Mgris M, Hidalgo G, Fierer N, Knight R. 2010. Proc. Natl. Acad. Sci. U S A 2010; 107: 11971-11975.
34	34. Bosch AATM, Levin E, van Houten MA, Hasrat R, Kalkman G, Biesroek G, de Steenhuijsen Piters WAA, de Groot PKCM, Pernet P, Keijer BJF, Sanders EAM, Bogaert D. 2016. EBioMedicine 2016; 9: 336-345.
35	35. Biesbroek G, Tsivtsivadze E, Sanders E, Montijn R, Veenhoven R, Keijer BJF, Bogaert D. 2014. Am. J. Respir. Crit. Care Medicine 2014; 190: 1283-1292.
36	36. Biesbroek G, Bosch AATM, Wang X, Keijer BJF, Veenhoven R, Sanders E, Bogaert D. 2014. Am. J. Respir. Crit. Care Medicine 2014; 190: 298-308.
37	37. Sakwinska O, Bastic Schmid V, Berger B, Bruttin A, Keitel K, Legpage M, Moine D, Ngom Bru C, Brüssow H, Gervaix A. 2014. J. Clin. Microbiol. 2014; 52: 1590-1594.
38	38. Pettigrew M, Laufer A, Gent J, Kong Y, Fennie K, Metlay J. 2012. Appl. Environ. Microbiol. 2012; 78: 6262-6270.
39	39. Sato S, Kiyono H. 2012. Curr. Opin. Virol. 2012; 2: 225-232.
40	40. Brugman S, Perdijk O, van Neerven RJJ, Savelkoul HFJ. 2015. Arch. Immunol. Ther. Exp. 2015; 63: 251-268.
41	41. Lappan R, Imbrogno K, Sikazwe C, et al. A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera. BMC Microbiol. 2018;18:13.
42	42. Cárdenas N, Martín V, Arroyo R, et al. Prevention of recurrent acute otitis media in children through the use of lactobacillus salivarius PS7, a target-specific probiotic strain. Nutrients. 2019;11:E376.
43	43. Marchisio P, Santagati M, Scillato M, et al. Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children. Eur J Clin Microbiol Infect Dis. 2015;34:2377–2383.
44	44. Krammer F, Palese P. Advances in the development of influenza virus vaccines. Nat Rev Drug Discov. 2015;14:167–182.
45	45. Houser K, Subbarao K. Influenza vaccines: challenges and solutions. Cell Host Microbe. 2015;17:295–300.
46	46. Norhayati MN, Ho JJ, Azman MY. Influenza vaccines for preventing acute otitis media in infants and children. Cochrane Database Syst Rev. 2017 Oct 17;10: CD010089.
47	47. Vemula SV, Sayedahmed EE, Sambhara S, et al. Vaccine approaches conferring cross-protection against influenza viruses. Expert Rev Vaccines. 2017;16:1141–1154.
48	48. Villafana T, Falloon J, Griffin MP, et al. Passive and active immunization against respiratory syncytial virus for the young and old. Expert Rev Vaccines. 2017;16:1–13.
49	49. Glanville N, Johnston SL. Challenges in developing a cross-serotype rhinovirus vaccine. Curr Opin Virol. 2015;11:83–88.
50	50. Fougeroux C, Holst PJ. Future prospects for the development of cost-effective adenovirus vaccines. Int J Mol Sci. 2017;18:E686.
51	51. Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet. 2011;378:1962–1973.
52	52. Scott P, Rutjes AWS, Bermetz L, et al. Pneumococcal conjugate vaccines: a systematic review of data from randomized controlled trials and observational studies of childhood schedules using 7-, 9-, 10- and 13-valent vaccines; [cited 2019 Apr 25].
53	53. Esposito S, Principi N. Safety and tolerability of pneumococcal vaccines in children. Expert Opin Drug Saf. 2016;15:777–785.
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