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.

We present a case of Nannizziopsis spp infection in an immunocompromised patient, describe clinical findings, investigation results and treatment. This rare fungal infection is reported in reptiles and humans, but not other mammals. There are only twenty case reports in medical literature to date, most in immunocompromised patients.

A 64-year-old kidney transplant recipient from urban Nigeria presented with a verrucous plaque on his dorsal left hand which has grown rapidly over the two months. He was concerned that it might represent cancer. On further examination he also had a subcutaneous fluctuant masses on his left flank and left upper arm, a fleshy mucosal plaque and a large tender fluctuant swelling over his right tibia. He was clinically well, but in the preceding months he reported haemoptysis and 7 kilograms weight loss.

Skin biopsies from multiple sites showed identical features: suppurative granulomatous inflammation and elongated elements consistent with fungal hyphae. Grocott special staining showed scattered fungal hyphae. Beta-D-glucan was raised at 441.4 pg/mL [3-6 pg/mL]. Subsequent molecular identification confirmed Nanniziopsis spp, likely to be N. guarroi. He was treated with intravenous amphotericin-B for 7 weeks and was then switched to oral posaconazole for one month with complete resolution.

Nannizziopsis is an emerging human pathogenic fungus that predominantly causes disease in immunocompromised individuals. This case highlights the importance of suspecting atypical fungal infection in immunocompromised individuals presenting with polymorphic skin lesions and the critical diagnostic role of skin biopsy and culture.

Objective To compare the clinical features and auxiliary examination results of sinus-originated intracranial aspergillosis（ICA）and rhino-orbito-cerebral mucormycosis（ROCM）. Methods A retrospective analysis was performed for the clinical data of seven patients with sinus-originated ICA and six patients with ROCM who were diagnosed and treated in our hospital from January 2018 to January 2023. Results The pathogenic factor of CNS fungal infection was observed in all patients with ROCM and 57.1% of the patients with sinus-originated ICA. Compared with the patients with sinus-originated ICA，the patients with ROCM were more likely to develop ocular symptoms and signs such as exophthalmos，periorbital swelling，and intraocular inflammation，as well as non-ocular symptoms and signs including fever，facial swelling，and facial nerve palsy. Compared with the patients with sinus-originated ICA，the patients with ROCM had significantly greater increases in blood glucose，erythrocyte sedimentation rate，C-reactive protein，and procalcitonin. Cranial magnetic resonance imaging showed that sinus-originated ICA often affected the paranasal sinuses，orbital apices，retro-orbital regions，and cavernous sinuses，while the patients with ROCM were more likely to have sinusitis，bone destruction，and mucormycosis invading cerebral vessels. As for treatment，50% of the patients with ROCM and 42.9% of the patients with sinus-originated ICA received antifungal therapy alone，while 50% of the patients with ROCM and 57.1% of the patients with sinus-originated ICA received a combination of medication and surgery. By follow-up to September 2023，50% of the patients with ROCM and 28.6% of the patients with sinus-originated ICA had no response to treatment and died. Conclusion Both sinus-originated ICA and ROCM have rapid progression，and ROCM survivors with diabetes are more likely to experience disabilities. Timely diagnosis and initiation of antifungal therapy，correction of underlying predisposing factors，and active surgical debridement are essential for the treatment of CNS fungal infections.
Aspergillus ; Mucormycosis

Mucormycosis is an important invasive fungal disease that is difficult to diagnose and treat, and has a high mortality rate. To improve the diagnosis and treatment of mucormycosis by clinicians, the Medical Mycology Society of Chinese Medicine and Education Association engaged multidisciplinary experts to compile this expert consensus. This consensus refers to the latest international guidelines for diagnosis and treatment of mucormycosis, combined with the characteristics and treatment needs of mucormycosis in China and covers the following eight aspects to provide reference for Chinese clinicians: pathogenic agents, high-risk factors, clinical types, imaging manifestations, etiological diagnosis, clinical diagnosis, treatment, and prevention.
Humans ; Mucormycosis/drug therapy* ; Consensus ; China

Introduction: Histoplasmosis is a disease of global distribution with diverse manifestations caused by the dimorphic fungus Histoplasma capsulatum. It is frequently described in severely immunocompromised and Human Immunodeficiency Virus (HIV)-positive individuals. Despite being widely reported in Southeast Asia, few cases have been reported in the Philippines. Case Report: A 53-year-old Filipino male who presented with umbilicated papules resembling molluscum contagiosum, and a previous history of a left lung mass with initial complaints of cough and hemoptysis. Gram stain of his sputum revealed the presence of fungal elements, otherwise not specified. In relation to this, a fine-needle aspiration biopsy of the suspected lung mass was done. However, findings were negative for malignant cells and fungi. Dermoscopy revealed central ulceration and necrosis with faint peripheral arborizing telangiectasia and surrounding superficial scaling. Histopathologic analysis revealed a diffuse granulomatous dermatitis, and Periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) stains showed numerous small yeast-like structures measuring approximately 3.74µm in diameter. Tissue culture of the skin lesion on the right thigh isolated fungal elements but was not specified. As histoplasmosis is an AIDS-defining infection and often found in immunocompromised states, screening for HIV was done which revealed negative results. Interestingly, disease distribution of histoplasmosis in the Philippines was frequently found in HIV-negative patients. Due to persistent serum creatinine elevation of over 300 µmol/L, renal biopsy was also done and revealed similar fungal elements. With these findings, a diagnosis of disseminated histoplasmosis was made. After a month of treatment with oral itraconazole, there was marked improvement of the patient’s skin lesions. Conclusion This case highlights the importance of recognizing cutaneous manifestations and maintaining a high index of suspicion for histoplasmosis in HIV-seronegative patients.
systemic fungal infections ; disseminated histoplasmosis ; itraconazole

Histoplasmosis is well-characterized as a fungal disease that more commonly occurs in North America, mostly endemic in Ohio and Mississippi river valleys. The clinical spectrum of histoplasmosis ranges from asymptomatic infection to a fatal disease. Progressive disseminated histoplasmosis is typically seen in immunocompromised individuals and presents with non-specific systemic symptoms associated with cutaneous manifestations of papules and nodules.? We report a case of a 28-year old Filipino female with a history of exposure to soil activities months before consult. The patient presented with a 3-week history of erythematous macules, vesicles, and pustules over the face, arms, and trunk, which evolve into papules and plaques with hemorrhagic crusting. Patient was initially diagnosed and treated as a case of varicella but had no improvement with initial management. Histopathologic findings were consistent with histoplasmosis. The patient was started with oral itraconazole, but unexpectedly expired before any improvement in cutaneous symptoms were noted.
Disseminated histoplasmosis ; Itraconazole

Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.
Humans ; Lectins ; Candida ; Candidemia ; Reproducibility of Results ; Polymerase Chain Reaction ; Nucleic Acids ; Magnetic Phenomena

Objective: To summarize the original CT features of Pneumocystis Jirovecii pneumonia in patients with hematological diseases. Methods: A retrospective analysis was carried out in 46 patients with proven pneumocystis pneumonia (PJP) in the Hospital of Hematology, Chinese Academy of Medical Sciences between January 2014 and December 2021. All patients had multiple chests CT and related laboratory examinations, imaging typing were conducted based on the initial CT presentation, and the distinct imaging types were analyzed against the clinical data. Results: In the analysis, there were 46 patients with proven pathogenesis, 33 males, and 13 females, with a median age of 37.5 (2-65) years. The diagnosis was validated by bronchoalveolar lavage fluid (BALF) hexamine silver staining in 11 patients and clinically diagnosed in 35 cases. Of the 35 clinically diagnosed patients, 16 were diagnosed by alveolar lavage fluid macrogenomic sequencing (BALF-mNGS) and 19 by peripheral blood macrogenomic sequencing (PB-mNGS) . The initial chest CT presentation was categorized into 4 types, including ground glass (GGO) type in 25 cases (56.5%) , nodular type in 10 cases (21.7%) , fibrosis type in 4 cases (8.7%) , and mixed type in 5 cases (13.0%) . There was no substantial discrepancy in CT types among confirmed patients, BALF-mNGS diagnosed patients and PB-mNGS diagnosed patients (χ(2)=11.039, P=0.087) . The CT manifestations of confirmed patients and PB-mNGS diagnosed patients were primarily GGO type (67.6%, 73.7%) , while that of BALF-mNGS diagnosed patients were nodular type (37.5%) . Of the 46 patients, 63.0% (29/46) had lymphocytopenia in the peripheral blood, 25.6% (10/39) with positive serum G test, and 77.1% (27/35) with elevated serum lactate dehydrogenase (LDH) . There were no great discrepancies in the rates of lymphopenia in peripheral blood, positive G-test, and increased LDH among different CT types (all P>0.05) . Conclusion: The initial chest CT findings of PJP in patients with hematological diseases were relatively prevalent with multiple GGO in both lungs. Nodular and fibrosis types were also the initial imaging findings for PJP.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Pneumonia, Pneumocystis/diagnostic imaging* ; Retrospective Studies ; Pneumocystis carinii ; Hematologic Diseases/complications* ; Tomography, X-Ray Computed ; Fibrosis

Humans ; Adult ; Mucormycosis ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Antifungal Agents

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*