A Vulvovaginal Yeast Infection Caused by Cryptococcus victoriae in Vietnam: A Rare Case Report

Introduction

Vulvovaginitis caused by the Candida genus is a highly prevalent vaginal infection among women of childbearing age. ¹ While vulvovaginal infections are commonly associated with Candida species, there are rare cases involving other yeast species, such as Saccharomyces cerevisiae, Trichosporon asahii, and Kodamaea ohmeri, causing vulvovaginitis, albeit with lower occurrence rates. ² Notably, instances of vulvovaginal cryptococcosis are extremely rare in humans, with only a limited number of cases described for this specific causative species.^3,4 The most common cases of occurrences of infections due to the Cryptococcus genus occur in immunosuppressed patients.^3,5

Cryptococcus victoriae, also known as Vishniacozyma victoriae, is a recently identified yeast species categorized within the Tremellales order. This yeast species was first documented by Montes et al, ⁶ originating from soil samples collected from Botany Bay (Southern Victoria Land, Antarctica). Commonly found in cold areas of the world, its occurrence has also been observed in other geographical areas, albeit less frequently. ⁷ Furthermore, C victoriae is present in indoor environments with high predominance.^8-10 Previously, it was not established to have disease-causing capability due to its lack of a polysaccharide capsule and its inability to grow at human body temperature.^8,9,11

This report describes a rare case of vaginal infection in a human caused by C victoriae, which was identified through morphological and genetic analysis conducted in Vietnam. To the best of our knowledge, this is the first reported case of a vulvovaginal infection attributed to C victoriae in humans.

Case Report

The patient, a 58-year-old menopausal woman and farmer with a 10-year history of depression and uncontrolled type 2 diabetes mellitus until this examination, reported experiencing vulvar itching for 5 days. She was admitted to the 103 Military Medical Hospital (Hanoi, Vietnam) on November 28, 2019, with complaints of vulvar itching and vaginal discharge. Physical examination of the vagina revealed thin white exudate on the vulvar structures, an odor, and vulvar itching. Due to the suspected diagnosis of vulvovaginitis caused by the Candida, 2 vaginal swab specimens were collected using sterile cotton-tipped swab. These vaginal swabs were promptly transported to the Department of Medical Parasitology at Vietnam Military Medical University in Ha Noi, Vietnam, within 2 hours for yeast isolation. Examination results with 10% KOH revealed the presence of oval yeast. In addition, the vaginal swab sample was also cultured on CHROMagar Candida plates and incubated at 20°C to 25°C and 35°C for 4 days. After 2 days of culturing at 20°C to 25°C, mauve colonies emerged, displaying smooth, glossy, slim characteristics and a diameter of 0.5 to 1 mm, making them indistinguished from Candida glabrata colonies (Figure 1). Examination under the microscope of the culture after 48 hours indicated oval yeast, ranging in size from 3 to 5 µm in length to 2 to 3 µm in diameter, either single or in clusters without true hyphae or pseudohyphae (Figure 2). No growth was observed on CHROMagar Candida at 35°C. Subsequently, a subculture on Sabouraud dextrose agar (SDA) (Merck, Germany) was performed, and it was incubated at 20°C to 25°C for 48 hours. The cream-colored colonies produced were slightly mucoid and highly glossy (Figure 3A). After 3 days, the color changed to a pale yellow-pink shade (Figure 3B). Complete blood count and liver function tests were performed, and all results were within the normal range. Serological assessments for hepatitis B virus, hepatitis C virus, and HIV were negative. However, her fasting blood glucose concentration was 9.13 mmol/L. The isolated yeast was then amplified and sequenced using the ITS1-5.8S-ITS2 region as described previously. ¹² The fungus was identified as C victoriae using the BLAST tool and the sequence was deposited in the GenBank under accession number MW307706.1.

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Figure 1.

Mauve colonies of Cryptococcus victoriae on CHROMagar Candida medium.

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Figure 2.

Microscopic examination of Cryptococcus victoriae strain, showing oval yeast cells and budding cells. Scale bars 10 µm.

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Figure 3.

Cream-colored colonies produced, slightly mucoid (A), and pale yellow-pink colonies after 3 days on SDA medium (B).

Susceptibility testing of the isolation to amphotericin B (AMB), caspofungin (CAS), micafungin (MFG), fluconazole (FLC), itraconazole (ICZ), and voriconazole (VCZ) was carried out according to the recommendations proposed by the Clinical and Laboratory Standard Institute (CLSI) document M27-A3. ¹³ The minimum inhibitory concentration (MIC) values for AMB, CAS, MFG, FLC, ICZ, and VCZ were 1 μg/mL, 0.12 μg/mL, 0.015 μg/mL, 0.12 μg/mL, 0.06 μg/mL, and 0.015 μg/mL, respectively.

The patient was treated with topical clotrimazole and then received 200 mg of itraconazole daily for 7 days. Blood glucose levels were maintained within normal limits with 500 mg of Glucophage XR (Merck, Germany) 3 times a day. The 1-month treatment completely resolved the vulvar lesions, and no presence of yeast was observed in the samples of vaginal discharge after 1, 3, and 6 months of follow-up.

Discussion

Yeast infections, primarily caused by Candida, are the second most common cause of vulvovaginitis in women of reproductive age. ¹ Vulvovaginitis due to Cryptococcus is rarely reported and is often observed in immunocompromised patients, including those with diseases such as Hodgkin’s disease, lymphoma, leukemia, and multiple myeloma, as well as in individuals with HIV infection, immunodeficiency states, and cancer.^4,14,15 To the best of our knowledge, fewer than 10 human cases of cryptococcal vulvovaginitis have been reported worldwide,^3,4 with various Cryptococcus species identified, including Cryptococcus ungulaticus, Cryptococcus neoformans, Cryptococcus spp., and Cryptococcus magnus, but not C victoraie. ⁴ Nevertheless, there have been no findings of Cryptococcus spp. from Vietnam before. This is the first reported case of infections caused by Cryptococcus spp. in Vietnam.

The diagnosis of vulvovaginitis in this case was confirmed upon discovering symptoms and signs, including itching, vaginal discharge, and positive results of direct microscopic examination of vaginal discharge and culture method. ² The isolated fungus was identified as C victoriae, a rare yeast, using molecular tools to analyze the ITS1-5.8S-ITS2 region. Multiple previous studies have shown that this yeast grows optimally in nutrient-rich media. Therefore, the risk factors believed to be associated with vulvovaginitis caused by C victoriae were type 2 diabetes mellitus. In addition, this case also had a 10-year history of depression and menopause. However, an inconsistency was observed in the results, where the fungal culture grew at 20°C to 25°C but did not grow at 35°C on the culture medium, raising suspicion of a fungal etiology. Unfortunately, we did not initially suspect vulvovaginitis due to C victoriae, so both the cutaneous lesion imaging and pathology results are missing. Thus, the diagnosis of vulvovaginitis caused by C victoriae is not highly convincing. Whether C victoriae can cause a disease or it is an incidental finding in the patient’s vulvovaginal discharge are the important issues that need to be studied further.

Following MIC approval, the current case was treated with 2 antifungal drugs: topical clotrimazole and oral itraconazole, resulting in successful treatment. Vaginal fungal examinations were performed at months 1, 3, and 6 post-treatment, revealing no presence of yeast.

The case reported here underscores the role of Cryptococcus spp., especially C victoriae, as an opportunistic pathogen in the lower genital tract. Controlling fasting blood glucose concentration and other opportunistic factors is necessary to reduce the risk of opportunistic fungal infections.