Vulvovaginal Candidiasis: Epidemiology and Risk Factors, Pathogenesis, Resistance, and New Therapeutic Options


Purpose of Review

Vulvovaginal candidiasis (VVC) is an infection of the vaginal mucosa caused by fungi of the genus Candida and can become pathogenic under special conditions. It affects about 75% of women at least once in life and is characterized by leukorrhea, intense pruritus, vulvar hyperemia, dysuria, and dyspareunia. The imbalance between the microbiota and these yeasts causes candidiasis. In addition, recurrent vulvovaginal candidiasis (RVVC) can affect a very significant number, approximately 138 million women worldwide. Pregnancy, diabetes mellitus, use of hormonal contraceptives, hormone replacement therapy, antibiotics and steroids, immunosuppressive diseases, and hygienic habits are contributing factors. The evaluation of VVC and RVVC requires clinical criteria associated with laboratory findings, the latter being essential for an accurate diagnosis and a satisfactory therapeutic result.

Recent Findings

New drug formulations already known or carriers promise to increase the effectiveness of the antifungal activity of drugs against VVC and RVVC.


This review aims to describe the epidemiology, pathogenesis, clinical and laboratory diagnosis, resistance, and new therapeutic options in primary and recurrent VVC and RVVC infections.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.

    Farage MA, Miller KW, Sobel JD. Infectious diseases : research and treatment dynamics of the vaginal ecosystem-hormonal influences. Infect Dis Res Treat. 2010;3:1–15.

    Google Scholar 

  2. 2.

    •• Rudramurthy SM, Singh S. Candida infections in immunocompetent hosts: pathogenesis and diagnosis. Curr Fungal Infect Rep. 2020;14:233–45. This paper presents the understanding of the pathogenesis of infections in critically ill non-neutropenic individuals can help in identifying potential diagnostic and therapeutic targets.

    Article  Google Scholar 

  3. 3.

    Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol Elsevier Inc. 2016;214:15–21.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Dovnik A, Golle A, Novak D, Arko D, Takač I. Treatment of vulvovaginal candidiasis: a review of the literature. Acta Dermatovenerologica Alpina, Pannonica Adriat. 2015;24:5–7.

    Article  Google Scholar 

  5. 5.

    Sobel JD. Candida vaginitis. Infect Dis Clin Pract. 1994;3:334–9.

    Article  Google Scholar 

  6. 6.

    Mitchell H. Vaginal discharge—causes, diagnosis, and treatment. Bmj. 2004;328:1306–8.

    PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Sobel JD. Vaginitis. N Engl J Med. 1997;337:1896–903.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Sobel JD, Faro S, Force RW, Foxman B, Ledger WJ, Nyirjesy PR, et al. Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol. 1998;178:203–11.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Gonçalves B, Ferreira C, Alves CT, Henriques M, Azeredo J, Silva S. Vulvovaginal candidiasis: epidemiology, microbiology and risk factors. Crit Rev Microbiol. 2016;42:905–27.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  10. 10.

    Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010;23:253–73.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Blostein F, Levin-Sparenberg E, Wagner J, Foxman B. Recurrent vulvovaginal candidiasis. Ann Epidemiol Elsevier Inc; 2017; 27 : 575-582.e3. Available from:

  12. 12.

    Anderson MR, Klink K, Cohrssen A. Evaluation of vaginal complaints. Jama. 2004;291:1368–79 Available from:

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Ono F, Yasumoto S. Genital candidiasis. Nippon rinsho Japanese J Clin Med. 2009;67:157–61.

    Google Scholar 

  14. 14.

    Hardy L, Cerca N, Jespers V, Vaneechoutte M, Crucitti T. Bacterial biofilms in the vagina. Res Microbiol Elsevier Masson SAS; 2017; 168 : 865–74. Available from:

  15. 15.

    Jung HS, Ehlers MM, Lombaard H, Redelinghuys MJ, Kock MM. Etiology of bacterial vaginosis and polymicrobial biofilm formation. Crit Rev Microbiol Taylor 8 Francis; 2017; 43 : 651–67. Available from:

  16. 16.

    •• Harriott MM, Lilly EA, Rodriguez TE, Fidel PL, Noverr MC. Candida albicans forms biofilms on the vaginal mucosa. Microbiology. 2010;156:3635–44 The data this paper show for the first time that C. albicans forms biofilms in vivo on vaginal epithelium, and that in vivo biotic biofilm formation requires regulators of biofilm formation (BCR1) and morphogenesis (EFG1).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Muzny CA, Schwebke JR. Biofilms: an underappreciated mechanism of treatment failure and recurrence in vaginal infections. Clin Infect Dis. 2015;61:601–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Sobel JD. Editorial commentary: vaginal biofilm: much ado about nothing, or a new therapeutic challenge? Clin Infect Dis. 2015;61:607–8.

    PubMed  Article  Google Scholar 

  19. 19.

    Sobel JD, Wiesenfeld HC, Martens M, Danna P, Hooton TM, Rompalo A, et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med 2004; 351 : 876-883+946.

  20. 20.

    Paladine HL, Desai UA. Vaginitis: Diagnosis and Treatment. 2018 : 321–9.

  21. 21.

    Chen S, Slavin M, Nguyen Q, Marriott D, Playford EG, Ellis D, et al. Active surveillance for candidemia, Australia. Emerg Infect Dis. 2006;12:1508–16.

    PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Nyirjesy P, Sobel JD. Genital mycotic infections in patients with diabetes. Postgrad Med. 2013;125:33–46.

    PubMed  Article  Google Scholar 

  23. 23.

    Wang FJ, Zhang D, Liu ZH, Wu WX, Bai HH, Dong HY. Species distribution and in vitro antifungal susceptibility of vulvovaginal Candida isolates in China. Chin Med J (Engl). 2016;129:1161–5.

    CAS  Article  Google Scholar 

  24. 24.

    Dias LB, de Melhem MSC, Szeszs MW, Filho JM, Hahn RC. Vulvovaginal candidiasis in Mato Grosso, Brazil: pregnancy status, causative species and drugs tests. Brazilian J Microbiol. 2011;42:1300–7.

    Article  Google Scholar 

  25. 25.

    Gamarra S, Morano S, Dudiuk C, Mancilla E, Nardin ME, de los Angeles Méndez E, et al. Epidemiology and antifungal susceptibilities of yeasts causing vulvovaginitis in a teaching hospital. Mycopathologia. 2014;178:251–8.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    •• Khan M, Ahmed J, Gul A, Ikram A, Lalani FK. Antifungal susceptibility testing of vulvovaginal Candida species among women attending antenatal clinic in tertiary care hospitals of Peshawar. Infect Drug Resist. 2018;11:447–56 In this study, frequency of VVC was noted to be high in the second trimester of pregnancy, with the highest frequency of C. albicans isolated, followed by C. tropicalis and C. krusei. Antifungal susceptibility testing revealed that fluconazole was exceedingly resistant against Candida species (62%), followed by clotrimazole (59.3%) and nystatin (58.3%).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Rathod SD, Klausner JD, Krupp K, Reingold AL, Madhivanan P. Epidemiologic features of vulvovaginal candidiasis among reproductive-age women in India. Infect Dis Obstet Gynecol. 2012;2012:1–8.

    Article  Google Scholar 

  28. 28.

    Nurat AA, Ola BG, Olushola SM, Mikhail TA, Ayodeji AS. Detection and epidemiology of vulvovaginal candidiasis among asymptomatic pregnant women attending a tertiary hospital in Ogbomoso, Nigeria. International Journal of Biomedical Research. 2015;6:518–23.

    Article  Google Scholar 

  29. 29.

    Tietz HJ, Hopp M, Schmalreck A, Sterry W, Czaika V. Candida africana sp. nov., a new human pathogen or a variant of Candida albicans? Mycoses. 2001;44:437–45.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Odds FC, Bougnoux ME, Shaw DJ, Bain JM, Davidson AD, Diogo D, et al. Molecular phylogenetics of Candida albicans. Eukaryot Cell. 2007;6:1041–52.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Alonso-Vargas R, Elorduy L, Eraso E, Cano JF, Guarro J, Pontón J, et al. Isolation of Candida africana, probable atypical strains of Candida albicans, from a patient with vaginitis. Med Mycol. 2008;46:167–70.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Nnadi NE, Ayanbimpe GM, Scordino F, Okolo MO, Enweani IB, Criseo G, et al. Isolation and molecular characterization of Candida africana from Jos, Nigeria. Med Mycol. 2012;50:765–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Sullivan DJ, Westerneng TJ, Haynes KA, Bennett DE, Coleman DC. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals. Microbiology 1995; 141 : 1507–1521.

  34. 34.

    Romeo O, Criseo G. Molecular epidemiology of Candida albicans and its closely related yeasts Candida dubliniensis and Candida africana. J Clin Microbiol. 2009;47:212–4.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Coleman DC, Sullivan DJ, Bennett DE, Moran CP, Barry HJ, Shanley DB. Candidiasis: The emergence of a novel species, Candida dubliniensis. Aids. 1997;11:557–67.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  36. 36.

    Criseo G, Scordino F, Romeo O. Current methods for identifying clinically important cryptic Candida species. J Microbiol Methods Elsevier B.V. 2015;111:50–6.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Jewtuchowicz VM, Mujica MT, Brusca MI, Sordelli N, Malzone MC, Pola SJ, et al. Phenotypic and genotypic identification of Candida dubliniensis from subgingival sites in immunocompetent subjects in Argentina. Oral Microbiol Immunol. 2008;23:505–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  38. 38.

    Mtibaa L, Fakhfakh N, Kallel A, Belhadj S, Belhaj Salah N, Bada N, et al. Les candidoses vulvovaginales : étiologies, symptômes et facteurs de risque. J Mycol Med Elsevier Masson SAS. 2017;27:153–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Sardi JCO, Duque C, Camargo GACG, Hofling JF, Gonalves RB. Periodontal conditions and prevalence of putative periodontopathogens and Candida spp. in insulin-dependent type 2 diabetic and non-diabetic patients with chronic periodontitis - a pilot study. Arch Oral Biol. 2011;56:1098–105.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Bassyouni RH, Wegdan AA, Abdelmoneim A, Said W, Aboelnaga F. Phospholipase and aspartyl proteinase activities of candida species causing vulvovaginal candidiasis in patients with type 2 diabetes mellitus. J Microbiol Biotechnol. 2015;25:1734–41.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Beltrame A, Matteelli A, Carvalho ACC, Saleri N, Casalini C, Capone S, et al. Vaginal colonization with Candida spp. in human immunodeficiency virus - Infected women: a cohort study. Int J STD AIDS. 2006;17:260–6.

    PubMed  Article  Google Scholar 

  42. 42.

    Ohmit SE, Sobel JD, Schuman P, Duerr A, Mayer K, Rompalo A, et al. Longitudinal study of mucosal candida species colonization and candidiasis among human immunodeficiency virus (HIV)–seropositive and at-risk HIV-seronegative women. J Infect Dis. 2003;188:118–27.

    PubMed  Article  Google Scholar 

  43. 43.

    De Rossi T, Lozovoy MAB, da Silva V, Fernandes EV, Geraldino TH, Costa IC, et al. Interações entre Candida albicans e hospedeiro. Semin Ciências Biológicas e da Saúde. 2011;32:15–28.

    Article  Google Scholar 

  44. 44.

    Wira CR, Fahey JV, Sentman CL, Pioli PA, Shen L. Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol Rev. 2005;206:306–35.

    PubMed  Article  Google Scholar 

  45. 45.

    Tamura NK, Negri MFN, Bonassoli LA, Svidzinski TIE. Fatores de virulência de Candida spp isoladas de cateteres venosos e mãos de servidores hospitalares. Rev Soc Bras Med Trop. 2007;40:91–3.

    PubMed  Article  Google Scholar 

  46. 46.

    Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. FEMS Microbiol Rev. 2012;36:288–305.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Kumamoto CA, Vinces MD. Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence. Cell Microbiol. 2005;7:1546–54.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Jayatilake JAMS, Samaranayake YH, Cheung LK, Samaranayake LP. Quantitative evaluation of tissue invasion by wild type, hyphal and SAP mutants of Candida albicans, and non-albicans Candida species in reconstituted human oral epithelium. J Oral Pathol Med. 2006;35:484–91.

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Hostetter MK. Adhesins and ligands involved in the interaction of Candida spp. with epithelial and endothelial surfaces. Clin Microbiol Rev. 1994;7:29–42.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Hube B, Sanglard D, Odds FC, Hess D, Brown AJP, Gow NAR, et al. Disruption of each of the secreted aspartyl proteinase genes attenuates virulence. Infect Immun. 1997;65:3529–38.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. 51.

    Naglik JR, Richardson JP, Moyes DL. Candida albicans pathogenicity and epithelial immunity. PLoS Pathog. 2014;10:1–5.

    Article  CAS  Google Scholar 

  52. 52.

    Sardi JCO, Duque C, Mariano FS, Marques MR, Höfling JF, Gonçalves RB. Adhesion and invasion of Candida albicans from periodontal pockets of patients with chronic periodontitis and diabetes to gingival human fibroblasts. Med Mycol. 2012;50:43–9.

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Sardi, J.C, Scorzoni, L., Bernardi, T., Fusco-Almeida, A.M., Mendes Giannini, M.J. Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J. Med. Microbiol. 2013 62: 10-24.

  54. 54.

    Jeanmonodo R JD. Candidiasis, vaginal (vulvovaginal candidiasis). Treasure Island (FL): StatPearls Publishing; 2018. Available from:

  55. 55.

    Ebrahimy F, Dolatian M, Moatar F, Alavi MH. Comparison of the therapeutic effects of Garcin® and fluconazole on Candida vaginitis. Singapore Med J. 2015;56:567–72.

    PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Mohandas V, Ballal M. Distribution of Candida species in different clinical samples and their virulence: biofilm formation, proteinase and phospholipase production: a study on hospitalized patients in Southern India. J Glob Infect Dis. 2011;3:4–8.

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Ozcan SK, Budak F, Yucesoy G, Susever S, Willke A. Prevalence, susceptibility profile and proteinase production of yeasts causing vulvovaginitis in Turkish women. Apmis. 2006;114:139–45.

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Lian CH, Da Liu W. Differential expression of Candida albicans secreted aspartyl proteinase in human vulvovaginal candidiasis. Mycoses. 2007;50:383–90.

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Sardi JDCO, Pitangui NDS, Rodríguez-Arellanes G, Taylor ML, Fusco-Almeida AM, Mendes-Giannini MJS. Highlights in pathogenic fungal biofilms. Rev Iberoam Micol. 2014;31:22–9.

    Article  Google Scholar 

  60. 60.

    Williams DW, Jordan RPC, Wei X-Q, Alves CT, Wise MP, Wilson MJ, et al. Interactions of Candida albicans with host epithelial surfaces. J Oral Microbiol. 2013;5:22434.

    Article  CAS  Google Scholar 

  61. 61.

    Dantas ADS, Day A, Ikeh M, Kos I, Achan B, Quinn J. Oxidative stress responses in the human fungal pathogen, Candida albicans. Biomolecules. 2015;5:142–65.

    CAS  Article  Google Scholar 

  62. 62.

    Moudgal V, Sobel J. Antifungals to treat Candida albicans. Expert Opin Pharmacother. 2010;11:2037–48.

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Felix TC, de Brito Röder DVD, dos Santos Pedroso R. Alternative and complementary therapies for vulvovaginal candidiasis. Folia Microbiol (Praha) Folia Microbiologica. 2019;64:133–41.

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    CDC. CDC. 2018. Fungal diseases - vaginal candidiasis [online], Available from:

  65. 65.

    Feuerschuette OHM, Silveira SK, Feuerschuette I, Corrêa T, Grando L, Trepani A. Candidíase vaginal recorrente: manejo clínico. Femina. 2010;38:31–6 Available from:

    Google Scholar 

  66. 66.

    Colombo AL, Guimarães T, Camargo LFA, Richtmann R, de Queiroz-Telles F, Salles MJC, et al. Brazilian guidelines for the management of candidiasis - a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical. Brazilian J Infect Dis Elsevier Editora Ltda. 2013;17:283–312.

    Article  Google Scholar 

  67. 67.

    Romero-Cerecero O, Islas-Garduño AL, Zamilpa A, Tortoriello J. Effectiveness of Ageratina pichinchensis extract in patients with vulvovaginal candidiasis. A randomized, double-blind, and controlled pilot study. Phyther Res. 2017;31:885–90.

    CAS  Article  Google Scholar 

  68. 68.

    •• Saffari E, Mohammad-Alizadeh-Charandabi S, Adibpour M, Mirghafourvand M, Javadzadeh Y. Comparing the effects of Calendula officinalis and clotrimazole on vaginal Candidiasis: a randomized controlled trial. Women Heal. 2017;57:1145–60 This study examined the effects of Calendula officinalis vaginal cream on the treatment of vaginal Candidiasis.

    Article  Google Scholar 

  69. 69.

    Imhof M, Lipovac M, Kurz C, Barta J, Verhoeven HC, Huber JC. Propolis solution for the treatment of chronic vaginitis. Int J Gynecol Obstet. 2005;89:127–32.

    CAS  Article  Google Scholar 

  70. 70.

    Kesarwani K, Gupta R. Bioavailability enhancers of herbal origin: an overview. Asian Pac J Trop Biomed. 2013;3:253–66.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Zida A, Bamba S, Yacouba A, Ouedraogo-Traore R, Guiguemdé RT. Substances naturelles actives sur Candida albicans, sources de nouveaux médicaments antifongiques : revue de la littérature. J Mycol Med Elsevier Masson SAS. 2017;27:1–19.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Ghosh V, Saranya S, Mukherjee A, Chandrasekaran N. Antibacterial microemulsion prevents sepsis and triggers healing of wound in Wistar rats. Colloids Surfaces B Biointerfaces. 2013;105:152–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Souza RO, Henrique de Lima T, Oréfice RL, de Freitas Araújo MG, de Lima Moura SA, Magalhães JT, et al. Amphotericin B-loaded poly(lactic-co-glycolic acid) nanofibers: an alternative therapy scheme for local treatment of vulvovaginal candidiasis. J Pharm Sci. 2018;107:2674–85.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    •• Takalkar D, Desai N. Nanolipid gel of an antimycotic drug for treating vulvovaginal candidiasis—development and evaluation. AAPS PharmSciTech. 2018;19:1297–307 This paper focuses on the development and evaluation of mucoadhesive vaginal gel of fluconazole using nanolipid carriers to enhance tissue deposition in treating vulvovaginal candidiasis.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  75. 75.

    de Santi MESO, Prates RA, França CM, Lopes RG, Sousa AS, Ferreira LR, et al. Antimicrobial photodynamic therapy as a new approach for the treatment of vulvovaginal candidiasis: preliminary results. Lasers Med Sci. 2018;33:1925–31.

    PubMed  Article  PubMed Central  Google Scholar 

  76. 76.

    Wan Tso GH, Reales-Calderon JA, Pavelka N. The elusive anti-candida vaccine: lessons from the past and opportunities for the future. Front Immunol. 2018;9.

  77. 77.

    Edwards JE, Schwartz MM, Schmidt CS, Sobel JD, Nyirjesy P, Schodel F, et al. A fungal immunotherapeutic vaccine (NDV-3A) for treatment of recurrent vulvovaginal candidiasis-a phase 2 randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2018;66:1928–36.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Download references


This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information



Corresponding author

Correspondence to Janaina de Cássia Orlandi Sardi.

Ethics declarations

Conflict of Interest


Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Epidemiology of Fungal Infections

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

de Cássia Orlandi Sardi, J., Silva, D.R., Anibal, P.C. et al. Vulvovaginal Candidiasis: Epidemiology and Risk Factors, Pathogenesis, Resistance, and New Therapeutic Options. Curr Fungal Infect Rep (2021).

Download citation


  • Diagnosis
  • Pathogenesis
  • Resistance
  • Therapeutic
  • Vulvovaginal candidiasis