Vulvovaginal Candidiasis: A Current Understanding and Burning Questions

Willems, Hubertine M. E.; Ahmed, Salman S.; Liu, Junyan; Xu, Zhenbo; Peters, Brian M.

doi:10.3390/jof6010027

Cited by 357Antifungal resistance and susceptibilityReproductive tract infections researchYeasts and Rust Fungi Studies

Vulvovaginal Candidiasis: A Current Understanding and Burning Questions

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Willems, Hubertine M. E., Ahmed, Salman S., Liu, Junyan, Xu, Zhenbo, Peters, Brian M.·2020·Journal of Fungi

DOI 10.3390/jof6010027PMC PMC7151053

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Abstract

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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The estimated annual economic impact of RVVC in the United States in 2010 from lost work hours was US$1 billion.
“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]
Symptoms of C. albicans and NAC infections are generally not clinically distinguishable, but diagnostic and treatment considerations differ.
“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]
Treatment failure on standard recommended regimens is common, as some NAC strains are inherently resistant to the azole drug class, have acquired resistance mechanisms, or have low susceptibility to commonly used antifungal agents.
“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]
Candida glabrata is the second-most prevalent Candida species in vulvovaginitis.
“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]
Conditions related to elevated estrogen levels, such as pregnancy, use of hormonal contraceptives, or hormonal replacement therapy, are VVC risk factors.
“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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Prospective Study of Vaginal Bacterial Flora and Other Risk Factors for Vulvovaginal Candidiasis
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Candida albicans-Secreted Aspartic Proteinases Modify the Epithelial Cytokine Response in an In Vitro Model of Vaginal Candidiasis
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Lipase 8 Affects the Pathogenesis ofCandida albicans
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NDV-3 protects mice from vulvovaginal candidiasis through T- and B-cell immune response
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Cellular and Molecular Biology of Candida albicans Estrogen Response
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Processing of predicted substrates of fungal Kex2 proteinases from Candida albicans, C. glabrata, Saccharomyces cerevisiae and Pichia pastoris
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Vulvovaginal candidiasis: histologic lesions are primarily polymicrobial and invasive and do not contain biofilms
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Distinct Protective Host Defenses against oral and vaginal Candidiasis
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Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis
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Lactobacillus rhamnosus inhibits Candida albicans virulence factors in vitro and modulates immune system in Galleria mellonella
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Microbiota of the upper and lower genital tract
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NLRP3 inflammasome is a key player in human vulvovaginal disease caused by Candida albicans
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Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC
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Acute Neutropenia Decreases Inflammation Associated with Murine Vaginal Candidiasis but Has No Effect on the Course of Infection
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Vulvovaginal Candidiasis as a Chronic Disease
Hong, E. S., Dixit, S., Fidel, P. L., Bradford, J. A., & Fischer, G. O. (2013) · Journal of Lower Genital Tract Disease · doi:10.1097/lgt.0b013e318287aced · Cited by 69 · see citing works
Vaginal Epithelial Cell-Derived S100 Alarmins Induced by Candida albicans via Pattern Recognition Receptor Interactions Are Sufficient but Not Necessary for the Acute Neutrophil Response during Experimental Vaginal Candidiasis
Yano, J., Palmer, G. E., EBERLE, K. E., Peters, B. M., Vogl, T. J., McKenzie, A. N. J., & Fidel, P. L. (2013) · Infection and Immunity · doi:10.1128/iai.00861-13 · Cited by 69 · see citing works
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Activation of MAPK/c-Fos induced responses in oral epithelial cells is specific to Candida albicans and Candida dubliniensis hyphae
Moyes, D. L., Murciano, C., Runglall, M., Kohli, A., Islam, A., & Naglik, J. R. (2011) · Medical Microbiology and Immunology · doi:10.1007/s00430-011-0209-y · Cited by 68 · see citing works
Vaginal microbiota of asymptomatic bacterial vaginosis and vulvovaginal candidiasis: Are they different from normal microbiota?
Pramanick, R., Mayadeo, N., Warke, H. S., Begum, S., Aich, P., & Aranha, C. C. (2019) · Microbial Pathogenesis · doi:10.1016/j.micpath.2019.103599 · Cited by 65 · see citing works
Experimental Models of Vaginal Candidiasis and Their Relevance to Human Candidiasis
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ALS1 and ALS3 gene expression and biofilm formation in Candida albicans isolated from vulvovaginal candidiasis
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Analysis of the Vaginal Microbiome by Next-Generation Sequencing and Evaluation of its Performance as a Clinical Diagnostic Tool in Vaginitis
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Biological properties and production of bacteriocins‐like‐inhibitory substances by Lactobacillus sp. strains from human vagina
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In vitro susceptibility profile of 200 recent clinical isolates of Candida spp. to topical antifungal treatments of vulvovaginal candidiasis, the imidazoles and nystatin agents
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Antifungal and Antivirulence Activity of Vaginal Lactobacillus Spp. Products against Candida Vaginal Isolates
dos Santos, C. I., França, Y. R., Campos, C. D. L., Bomfim, M. R. Q., de Melo, B. O., Holanda, R. A., dos Santos, V. L., Monteiro, S. G., Moffa, E. B., Monteiro, A. S., et al. (2019) · Pathogens · doi:10.3390/pathogens8030150 · Cited by 60 · see citing works
Microbial flora associated with Candida albicans vulvovaginitis
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Candida albicans Adhesion to and Invasion and Damage of Vaginal Epithelial Cells: Stage-Specific Inhibition by Clotrimazole and Bifonazole
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Can Lactobacillus fermentum LF10 and Lactobacillus acidophilus LA02 in a Slow-release Vaginal Product be Useful for Prevention of Recurrent Vulvovaginal Candidiasis?
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Human Anti-Als3p Antibodies Are Surrogate Markers of NDV-3A Vaccine Efficacy Against Recurrent Vulvovaginal Candidiasis
Uppuluri, P., Singh, S., Alqarihi, A., Schmidt, C. S., Hennessey, J. P., Yeaman, M. R., Filler, S. G., Edwards, J. E., & Ibrahim, A. S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01349 · Cited by 56 · see citing works
A simple clinical staging system that predicts progression to AIDS using CD4 count, oral thrush, and night sweats
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Differential Candida albicans lipase gene expression during alimentary tract colonization and infection.
Schofield, D., Westwater, C., Warner, T., & Balish, E. (2005) · FEMS Microbiology Letters · doi:10.1016/j.femsle.2005.02.015 · Cited by 54 · see citing works
A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis
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Comparative Analysis of the Capacity of the Candida Species To Elicit Vaginal Immunopathology
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Estradiol impairs the Th17 immune response against Candida albicans
Relloso, M., Aragoneses-Fenoll, L., Lasarte, S., Bourgeois, C., Romera, G., Kuchler, K., Corbí, A. L., Muñoz‐Fernández, M. Á., Nombela, C., Rodríguez‐Fernández, J. L., et al. (2011) · Journal of Leukocyte Biology · doi:10.1189/jlb.1110645 · Cited by 50 · see citing works
Factors involved in patient choice of oral or vaginal treatment for vulvovaginal candidiasis
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Cellular immunity of patients with recurrent or refractory vulvovaginal moniliasis
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Sex Hormones Coordinate Neutrophil Immunity in the Vagina by Controlling Chemokine Gradients
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The Interleukin (IL) 17R/IL-22R Signaling Axis Is Dispensable for Vulvovaginal Candidiasis Regardless of Estrogen Status
Peters, B. M., Coleman, B. M., Willems, H. M. E., Barker, K. S., Aggor, F. E. Y., Cipolla, E., Verma, A. H., Bishu, S., Huppler, A. R., Bruno, V. M., et al. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz649 · Cited by 44 · see citing works
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High rate of vaginal infections caused by non-C. albicans Candidaspecies among asymptomatic women
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Genetic Susceptibility of Mice to Candida albicans Vaginitis Correlates with Host Estrogen Sensitivity
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Anti-Candidaactivity of beneficial vaginal lactobacilli inin vitroassays and in a murine experimental model
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Spectrum of fungal infection in head and neck cancer patients on chemoradiotherapy
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Determinants of different Candida species infections of the genital tract in women
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Investigations by Cell-Mediated Immunologic Tests and Therapeutic Trials With Thymopentin in Vaginal Mycoses
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Prevalence and epidemiological characteristics of vaginal candidiasis in the UAE
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Fungal Profile of Vulvovaginal Candidiasis in a Tertiary Care Hospital
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A Rat Model of Neonatal Candidiasis Demonstrates the Importance of Lipases as Virulence Factors for Candida albicans and Candida parapsilosis
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Hydrolytic Gene Expression during Oroesophageal and Gastric Candidiasis in Immunocompetent and Immunodeficient Gnotobiotic Mice
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Second-Generation Antidiabetic Sulfonylureas Inhibit Candida albicans and Candidalysin-Mediated Activation of the NLRP3 Inflammasome
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Frequency and Significance of Drug Resistance in Vulvovaginal Candidiasis
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A Role for Yeast/Pseudohyphal Cells of Candida albicans in the Correlated Expression of NLRP3 Inflammasome Inducers in Women With Acute Vulvovaginal Candidiasis
Roselletti, E., Monari, C., Sabbatini, S., Perito, S., Vecchiarelli, A., Sobel, J. D., & Cassone, A. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02669 · Cited by 33 · see citing works
The role of human Dectin-1 Y238X gene polymorphism in recurrent vulvovaginal candidiasis infections
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A novel lipase/acyltransferase from the yeast Candida albicans: expression and characterisation of the recombinant enzyme
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Non-albicans Candida Vulvovaginitis
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Estrogen‐dependent induction of persistent vaginal candidosis in naïve mice
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Investigations by cell-mediated immunologic tests and therapeutic trials with thymopentin in vaginal mycoses
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Genomic and Phenotypic Variation in Morphogenetic Networks of Two Candida albicans Isolates Subtends Their Different Pathogenic Potential
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Overexpression of Candida albicans Secreted Aspartyl Proteinase 2 or 5 Is Not Sufficient for Exacerbation of Immunopathology in a Murine Model of Vaginitis
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Cellular immunity of patients with recurrent or refractory vulvovaginal moniliasis
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The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives
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 351 · see citing works
Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor
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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.
ORCID: Willems, Hubertine M. E.
Ahmed, Salman S.
Liu, Junyan
Xu, Zhenbo
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)
DOI: 10.3390/jof6010027
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 · 2019: 2
FWCI: 2.24
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
Keywords: vaginal candidiasis, Candida species, host immune response, vaginal microbiota, antifungal therapy, quality of life

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Vulvovaginal Candidiasis: A Current Understanding and Burning Questions

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