BACKGROUND

Candida infections range from oral candidiasis to candida endophthalmitis, peritonitis and candidemia. Invasive fungal disease or disseminated candidiasis is highly fatal among children. There are no studies done in the pediatric population to detect early candida infection to help identify those who will benefit from early and prompt medical treatment.

This study determined the value of Candida scoring (CS) as a predictive tool for invasive candidiasis among pediatric patients admitted in the intensive care units of a tertiary referral center.

This was a retrospective cross sectional study where 4184 charts of pediatric patients and admitted in the ICU between January 2018 to December 2020 were reviewed. Patients were scored upon admission, after 3 days, after 1 week and weekly thereafter until discharge or demise. The scoring tool used was developed by Leon et al., and uses four variables: presence of sepsis, use of total parenteral nutrition (TPN), presence of multifocal colonization and presence of surgery. Data collected for Candida scores were presented as frequencies and percentages.

There were 396 patients enrolled in this study and 25.7% were treated for candida infection. Majority were newborns where 78.7% had a CS >3, which is statistically significant, p =3 which is statistically significant. Among intubated patients, 84% had a CS of >3 and all patients on TPN had a CS of >3, both of which are significant. CS could correctly predict 64.6% of patients who will likely have candida infection.

Candida scoring is a tool that can be used in patients at high risk of developing Candida infection. In this study, a CS of >3 can be used to predict Candida infection in the ICU.

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*

Background and Objectives: Oral candidiasis (OC) is a well-known local side effect of inhaled corticosteroid (ICS) therapy in patients with asthma and chronic obstructive pulmonary disease (COPD). This study aimed to determine the prevalence of OC and its association with ICS-related factors in out-patient asthma and COPD patients of the Departments of Pulmonology and Pediatric Pulmonology of the Philippine General Hospital (PGH). Methods: This is a cross-sectional study conducted from October 2019 to January 2020. Data was collected through a two-part questionnaire accomplished by doctors and patients with asthma or COPD. Results. A total of 67 patients were included in the study. Oral candidiasis was observed in 4 (5.97%) ICS users, and the prevalence was 1.65% to 14.59% (95% CI, SE: 0.028946). Conclusion This study determined the prevalence of oral candidiasis in asthma and COPD patients and its association with ICS-related factors, including the dosage, medication, device, and duration of therapy. The prevalence of OC in ICS users in PGH cannot be interpreted as high or low due to the small number of respondents, but is consistent with OC prevalence found in related literature. Increased prevalence was observed in adult females with asthma under low dose ICS therapy with Fluticasone/Salmeterol DPI for more than a year. There was no statistically significant correlation among OC prevalence, age, sex, and components of ICS-therapy including dosage, medication, device, frequency, and duration of therapy. A large-scale study is recommended for more accurate assessment of OC prevalence in the population and to determine statistically significant associations among the factors. It is also recommended to quantifiably measure patient compliance, inhalation technique and instruction, and its association to OC prevalence. Findings may be used to strengthen patient education, preventive measures, and disease management to facilitate improved compliance and effective treatment outcomes.
Candidiasis, Oral ; Adrenal Cortex Hormones ; Asthma ; Pulmonary Disease, Chronic Obstructive

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.
Female ; Animals ; Humans ; Mice ; Candidiasis, Vulvovaginal/drug therapy* ; Inflammasomes/genetics* ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; 1-Butanol/pharmacology* ; Fluconazole/therapeutic use* ; Interleukin 1 Receptor Antagonist Protein/therapeutic use* ; Mice, Inbred C57BL ; Candida albicans ; Cytokines ; Drugs, Chinese Herbal/pharmacology* ; Ethanol ; RNA, Messenger ; Calcium-Binding Proteins/therapeutic use*

Candida vertebral osteomyelitis,a rare but challenging clinical disease without specific clinical manifestations,is prone to delay in diagnosis,with potential risks of serious complications.Therefore,early diagnosis is the key to improving the cure rate of this disease.A case of invasive candida lumbar osteomyelitis after gastrointestinal surgery is reported in this paper.We analyzed the clinical characteristics of the patient and reviewed the relevant literature,aiming to improve the early diagnosis and treatment of this disease.
Candida ; Candidiasis/drug therapy* ; Humans ; Lumbar Vertebrae ; Osteomyelitis/drug therapy*

This study aims to explore the effect of butyl alcohol extract of Baitouweng Decoction(BAEB) on vulvovaginal candidiasis(VVC) in mice and to clarify the mechanism from Toll-like receptors(TLRs)/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome. To be specific, female KM mice were randomized into control group(i.g., normal saline), model group, fluco-nazole group(i.g., 20 mg·kg~(-1)), and low-dose, medium-dose, and high-dose BAEB groups(i.g., 20, 40, and 80 mg·kg~(-1), respectively). VVC was induced in mice except the control group. After the modeling, administration began and lasted 7 days. The ge-neral conditions and body weight of mice were recorded every day. On the 1 st, 3 rd, 7 th, and 14 th after vaginal infection by Candida albicans, the fungal load in the vaginal lavage fluid of the mice was measured with the plate method, and the morphology of C. albicans in vaginal lavage fluid was observed based on Gram staining. After the mice were killed, vaginal tissues were subjected to hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining for vaginal histopathological analysis. The content of cytokines in vaginal lavage fluid, such as interleukin(IL)-1β, IL-18, tumor necrosis factor-α(TNF-α), IL-6, and S100 a8, was determined by enzyme-linked immunosorbent assay(ELISA), and content of reactive oxygen species(ROS) in vaginal tissues by tissue ROS detection kit. The protein expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and nuclear factor-κB(NF-κB) in vaginal tissues was detected by Western blot, and the levels and distribution of NLRP3, Dectin-1, Syk, MyD88, TLR2, and TLR4 in vaginal tissues were determined with the immunohistochemical method. The results show that BAEB can improve the general conditions of VVC mice, reduce the fungal load and C. albicans hyphae in vaginal secretion, decrease ROS content in vaginal tissues and content of cytokines in vaginal lavage fluid, and down-regulate the expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and NF-κB in vaginal tissues. The above results indicate that BAEB exerts therapeutic effect on VVC mice by down-regulating the key proteins in the TLRs/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome.
1-Butanol/therapeutic use* ; Animals ; Candida albicans ; Candidiasis, Vulvovaginal/drug therapy* ; Caspase 1/metabolism* ; Cytokines/metabolism* ; Female ; Humans ; Inflammasomes/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Plant Extracts/therapeutic use* ; Reactive Oxygen Species/metabolism* ; Signal Transduction ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Background: Vulvovaginal Candidiasis (VVC) is one of the frequent infections of the female genital tract and is the second most common cause of vaginal infections after bacterial vaginosis. According to the Centers for Disease Control and Prevention, azoles are the first‑line treatment for VVC. Among the azoles available in the Philippines, only miconazole and clotrimazole are recommended for both pregnant and non‑pregnant women. Objective: Compare the effect of miconazole versus clotrimazole in the treatment of vulvovaginal candidiasis among patients seen at the out‑patient department in a tertiary hospital Materials and Methods: This involved review of the records of patients diagnosed with VVC in a tertiary medical center from 2016 to 2020. All records of women, pregnant and non‑pregnant, wherein single‑dose 1200 mg miconazole or 6‑day 100 mg clotrimazole given vaginally were included Results: Eleven out of the 316 records (3.46%) remained symptomatic after treatment, about 18.1% (2/161) from those who used miconazole and 81.8% (9/155) from those treated with clotrimazole (p 0.027). In terms of failure rate, for miconazole it was 1.2% (2/161), whereas for clotrimazole it was 5.8% (9/155). None of the charts were found to have recorded adverse reaction to the given treatment Conclusion Single‑dose miconazole intravaginal regimen has a higher clinical cure rate than the 6‑day clotrimazole intravaginal treatment. Thereby, single‑dose intravaginal miconazole has the potential to improve patient compliance and treatment outcome at a lower cost
Clotrimazole ; Miconazole ; Vaginitis ; Candidiasis, Vulvovaginal

Aims: The present study determined Candida species occurrence in the mouth of HIV/AIDS, pregnant women and healthy individuals, and Candida susceptibility to antimycotics. Methodology and results: A cross-sectional study of the Candida species occurrence and their in vitro sensitivity to nystatin, clotrimazole, ketoconazole and fluconazole was studied. Oral swabs were taken from the dorsum of the tongue of 63 HIV/AIDS patients, 38 pregnant women and 53 apparently healthy humans served as control. All participants gave their consent. The samples were cultured for isolation of Candida species. The susceptibility of commonly used antimycotics against Candida species was determined using agar-well and disc-diffusion methods. The broth dilution method was adopted in the determination of the minimum inhibitory concentration of the drugs. The rate of Candida species colonization in HIV/AIDS patients was higher than that among pregnant women and apparently healthy humans. Candida albicans had the highest frequency. Candida species displayed higher sensitivity to nystatin and clotrimazole than ketoconazole and fluconazole. Candida albicans exhibiting low sensitivity to fluconazole were found in the mouth of AIDS patients, pregnant women and apparently healthy humans. Conclusion, significance and impact of study Candida species prevalence was highest among HIV patients. Candida albicans had the highest frequency among the study groups and had reduced susceptibility to fluconazole. The findings of the study underscore the need for regular surveillance and susceptibility testing of Candida isolates before prescription of antimycotics, especially in cases of chronic infection, as well as the development of safe and efficacious treatment alternatives since Candida isolates are becoming less susceptible to fluconazole.
Candidiasis ; Mouth Diseases ; HIV ; Pregnant Women

Candida is an intractable life-threatening pathogen. Candida infection is extremely difficult to eradicate, and thus is the major cause of morbidity and mortality in immunocompromised individuals. Morevover, the rapid spread of drug-resistant fungi has led to significant decreases in the therapeutic effects of clinical drugs. New anti-Candida agents are urgently needed to solve the complicated medical problem. Natural products with intricate structures have attracted great attention of researchers who make every endeavor to discover leading compounds for antifungal agents. Their novel mechanisms and diverse modes of action expand the variety of fungistatic agents and reduce the emergence of drug resistance. In recent decades, considerable effort has been devoted to finding unique antifungal agents from nature and revealing their unusual mechanisms, which results in important progress on the development of new antifungals, such as the novel cell wall inhibitors YW3548 and SCY-078 which are being tested in clinical trials. This review will present a brief summary on the landscape of anti-Candida natural products within the last decade. We will also discuss in-depth the research progress on diverse natural fungistatic agents along with their novel mechanisms.
Antifungal Agents/pharmacology* ; Biological Products/pharmacology* ; Candida/drug effects* ; Candidiasis/drug therapy* ; Humans ; Microbial Sensitivity Tests

OBJECTIVES: Human papillomavirus (HPV) is a kind of spherical DNA virus, which is related to many factors such as immune status and pregnancy. Due to the decrease of immunity, pregnant women are more likely to have HPV infection, which causes serious imbalance of vaginal microecology and is not beneficial to pregnancy outcome. Therefore, this study focuses on the impact of HPV infection on vaginal microecology and maternal and neonatal outcomes. METHODS: A total of 140 pregnant women with HPV infection during pregnancy, who received obstetric examination in the First Affiliated Hospital of Hainan Medical College from November 2017 to July 2019, were selected as a HPV infection group, and 150 normal pregnant women with HPV negative in the same period were selected as a control group. Vaginal secretions were collected from all the pregnant women at 28-34 weeks of gestation to evaluate vaginal pH, cleanliness and microecological status, and to record pregnancy outcomes for all pregnant women. RESULTS: The proportions of vaginal pH>4.5, constituent ratio of flora density and diversity of I-II, positive detection rate of vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV) in HPV infected pregnant women were significantly higher than those in the control group (all CONCLUSIONS Pregnant women with HPV infection during pregnancy are more likely to have vaginal microecological disorders, and can increase the risk of adverse pregnancy outcomes such as premature delivery and chorioamnionitis.
Candidiasis, Vulvovaginal ; Cesarean Section ; Female ; Humans ; Infant, Newborn ; Papillomavirus Infections/epidemiology* ; Pregnancy ; Vaginosis, Bacterial