The DOI matches its Crossref record; 149 of the 149 references it cites were found in a registry or an index.
Vulvovaginal Candidiasis: A Current Understanding and Burning Questions
Open accessAbstract
Candida albicans, along with other closely related Candida species, are the primary causative agents of vulvovaginal candidiasis (VVC)—a multifactorial infectious disease of the lower female reproductive tract resulting in pathologic inflammation. Unlike other forms of candidiasis, VVC is a disease of immunocompetent and otherwise healthy women, most predominant during their child-bearing years. While VVC is non-lethal, its high global incidence and profound negative impact on quality-of-life necessitates further understanding of the host and fungal factors that drive disease pathogenesis. In this review, we cover the current state of our understanding of the epidemiology, host response, fungal pathogenicity mechanisms, impact of the microbiome, and novel approaches to treatment of this most prevalent human candidal infection. We also offer insight into the latest advancements in the VVC field and identify important questions that still remain.
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![Figure 1 An updated working model of the immunopathogenesis of C. albicans vaginitis. (a) Yeast forms of C. albicans asymptomatically colonize the vaginal epithelium despite the presence of numerous pattern recognition receptors (PRR) on the epithelial surface. (b) C. albicans begins to undergo the yeast-to-hypha switch under morphogenesis-inducing conditions (e.g., increases in estrogen, elevated vaginal pH, and microbiome disruption). Augmented recognition by PRRs, increased hyphal biomass, expression of hypha-associated virulence factors (candidalysin, secreted aspartyl proteinases (SAPs)) activates NLRP3 inflammasome signaling, eliciting inflammatory cytokines and chemokines (e.g., IL-1β, S100A8/9 alarmins) in the vaginal epithelium, resulting in initial migration of polymorphonuclear leukocytes (PMNs) from the lamina propria (L.P.) to the vaginal lumen. (c) Failure to adequately reduce immunopathological triggers results in the continued expression of innate immune effectors by the vaginal epithelium. These initial signals, coupled with the secondary amplification of immune effectors by recruited PMNs, contribute to symptomatic infection and characteristic immunopathology. Figure adapted from: PLoS Pathog. 2014 Apr; 10(4): e1003965 [47].](/paper-figures/74991d556bbc4c5f9e5888bdb7777cfd/vulvovaginal-candidiasis-a-current-understanding-and-burning-questions-figure-1.jpg)
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In the citing paper
“the estimated annual economic impact of RVVC in the United States in 2010 from lost work hours was US$1 billion.2,4,8”
From Clinical challenges in diagnosis and treatment of recurrent vulvovaginal candidiasis (2022) · cites this paper as [8]
In the citing paper
“Symptoms of C. albicans and NAC infections are generally not clinically distinguishable, 1 but diagnostic and treatment considerations differ. 8”
From Clinical challenges in diagnosis and treatment of recurrent vulvovaginal candidiasis (2022) · cites this paper as [8]
In the citing paper
“Treatment failure on standard recommended regimens is common, as some NAC strains are inherently resistant to the azole drug class, have acquired resistance mechanisms, 8 or have low susceptibility to commonly used antifungal agents, 27”
From Clinical challenges in diagnosis and treatment of recurrent vulvovaginal candidiasis (2022) · cites this paper as [8]
In the citing paper
“Candida glabrata is the second-most prevalent Candida species in vulvovaginitis 8”
From Clinical challenges in diagnosis and treatment of recurrent vulvovaginal candidiasis (2022) · cites this paper as [8]
In the citing paper
“All conditions related to elevated estrogen levels, such as pregnancy and the use of hormonal contraceptives or hormonal replacement therapy, are VVC risk factors [10,68].”
From Treatment of Vulvovaginal Candidiasis—An Overview of Guidelines and the Latest Treatment Methods (2023) · cites this paper as [68]
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Citations
Cites
Vaginal microbiome of reproductive-age women
Ravel, J., Gajer, P., Abdo, Z., Schneider, G. M., Koenig, S. S. K., McCulle, S. L., Karlebach, S., Gorle, R., Russell, J., Tacket, C. O., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002611107 · Cited by 4,254
The Danger Model: A Renewed Sense of Self
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Pappas, P. G., Kauffman, C. A., Andes, D. R., Clancy, C. J., Marr, K. A., Ostrosky-Zeichner, L., Reboli, A. C., Schuster, M. G., Vazquez, J. A., Walsh, T. J., et al. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/civ933 · Cited by 4,200
Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision
Bongomin, F., Gago, S., Oladele, R., & Denning, D. (2017) · Journal of Fungi · doi:10.3390/jof3040057 · Cited by 2,953 · cited 1×
“009% 7,800,000,000 702,000 [8] Oropharyngeal 15,337,200 HIV/AIDS 2 72.”
Nonfilamentous C. albicans Mutants Are Avirulent
Lo, H.-J., Köhler, J. R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A., & Fink, G. R. (1997) · Cell · doi:10.1016/s0092-8674(00)80358-x · Cited by 1,809
Pappas, P. G., Kauffman, C. A., Andes, D. R., Clancy, C. J., Marr, K. A., Ostrosky-Zeichner, L., Reboli, A. C., Schuster, M. G., Vazquez, J. A., Walsh, T. J., et al. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/civ1194 · Cited by 1,298
Mouse Estrous Cycle Identification Tool and Images
Byers, S. L., Wiles, M. V., Dunn, S. L., & Taft, R. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035538 · Cited by 1,220
Growth of Candida albicans hyphae
Sudbery, P. E. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2636 · Cited by 1,110
Dectin-1 Is A Major β-Glucan Receptor On Macrophages
Brown, G. D., Taylor, P. R., Reid, D. M., Willment, J. A., Williams, D. L., Martínez‐Pomares, L., Wong, S. Y. C., & Gordon, S. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020470 · Cited by 1,015
Chen, C., Song, X., Wei, W., Zhong, H., Dai, J., Lan, Z., Li, F., Yu, X., Feng, Q., Wang, Z., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00901-0 · Cited by 1,010
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d’Enfert, C., Kaune, A.-K., Alaban, L. R., Chakraborty, S., Cole, N. L., Delavy, M., Kosmala, D., Marsaux, B., Fróis-Martins, R., Morelli, M., et al. (2020) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaa060 · Cited by 377
Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor
Ho, J., Yang, X., Nikou, S.-A., Kichik, N., Donkin, A. J., Ponde, N. O., Richardson, J. P., Gratacap, R. L., Archambault, L. S., Zwirner, C. P., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09915-2 · Cited by 194
Guideline: Vulvovaginal Candidosis (AWMF 015/072, Level S2k)
Farr, A., Effendy, I., Frey Tirri, B., Hof, H., Mayser, P., Petricevic, L., Ruhnke, M., Schaller, M., Schaefer, A. P. A., Sustr, V., et al. (2021) · Mycoses · doi:10.1111/myc.13248 · Cited by 184
Liu, P., Lu, Y., Li, R., & Chen, X. F. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1153894 · Cited by 122
Czechowicz, P., Nowicka, J., & Gościniak, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23115895 · Cited by 122
Metadata
- Authors
- Willems, H. M. E., Ahmed, S. S., Liu, J., Xu, Z., & Peters, B. M.
- Affiliations
- University of Tennessee Health Science Center (US)
- South China University of Technology (CN)
- Corresponding author
- Peters, Brian M.
- Venue
- Journal of Fungi
- Publisher
- MDPI AG
- Published
- 2020-02-25
- Volume
- 6
- Issue
- 1
- Pages
- 27
- ISSN
- 2309-608X (ISSN-L)
- PMC
- PMC7151053
- OpenAlex
- W3007795453
- Cited by
- 357
- References
- 148
- Citations by year
- 2026: 48 · 2025: 61 · 2024: 56 · 2023: 64 · 2022: 65 · 2021: 41 · 2020: 20
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Journal of Fungi (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Allergy and Infectious Diseases (AI134796, AI141829)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Life Sciences › Immunology and Microbiology › Microbiology › Yeasts and Rust Fungi Studies
- Keywords
- vaginal candidiasis, Candida species, host immune response, vaginal microbiota, antifungal therapy, quality of life
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