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Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic review aimed to evaluate the epidemiology and impact of eumycetoma. PubMed and Web of Science were searched to identify studies published between 1 January 2011 and 19 February 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 14 studies were eligible for inclusion. Morbidity was frequent with moderate to severe impairment of quality of life in 60.3%, amputation in up to 38.5%, and recurrent or long-term disease in 31.8%-73.5% of patients. Potential risk factors included male gender (56.6%-79.6%), younger age (11-30 years; 64%), and farming occupation (62.1%-69.7%). Mycetoma was predominantly reported in Sudan, particularly in central Sudan (37%-76.6% of cases). An annual incidence of 0.1/100 000 persons and 0.32/100 000 persons/decade was reported in the Philippines and Uganda, respectively. In Uganda, a decline in incidence from 3.37 to 0.32/100 000 persons between two consecutive 10-year periods (2000-2009 and 2010-2019) was detected. A community-based, multi-pronged prevention programme was associated with a reduction in amputation rates from 62.8% to 11.9%. With the pre-specified criteria, no studies of antifungal drug susceptibility, mortality, and hospital lengths of stay were identified. Future research should include larger cohort studies, greater drug susceptibility testing, and global surveillance to develop evidence-based treatment guidelines and to determine more accurately the incidence and trends over time.
Topics: Humans; Mycetoma; Incidence; Antifungal Agents; World Health Organization; Risk Factors; Male; Female; Quality of Life
PubMed: 38935904
DOI: 10.1093/mmy/myae044 -
Medical Mycology Jun 2024Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges,...
Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%-44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4-32 mg/l), while resistance to amphotericin B (MIC: 0.125-0.16 mg/l), itraconazole (MICs: 0.004-0.125 mg/l), and voriconazole (MICs: 0.004-0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat.
Topics: Humans; Histoplasmosis; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Histoplasma; Prevalence; Immunocompromised Host
PubMed: 38935903
DOI: 10.1093/mmy/myae039 -
Medical Mycology Jun 2024Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform...
Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform the World Health Organization's first Fungal Priority Pathogen List. PubMed and Web of Science were used to identify studies reporting on annual incidence, mortality, morbidity, antifungal resistance, preventability, and distribution/emergence in the past 10 years. Mortality rates due to C. neoformans were 41%-61%. Complications included acute renal impairment, raised intracranial pressure needing shunts, and blindness. There was moderate evidence of reduced susceptibility (MIC range 16-32 mg/l) of C. neoformans to fluconazole, itraconazole, ketoconazole, voriconazole, and amphotericin B. Cryptococcus gattii infections comprised 11%-33% of all cases of invasive cryptococcosis globally. The mortality rates were 10%-23% for central nervous system (CNS) and pulmonary infections, and ∼43% for bloodstream infections. Complications described included neurological sequelae (17%-27% in C. gattii infections) and immune reconstitution inflammatory syndrome. MICs were generally low for amphotericin B (MICs: 0.25-0.5 mg/l), 5-flucytosine (MIC range: 0.5-2 mg/l), itraconazole, posaconazole, and voriconazole (MIC range: 0.06-0.5 mg/l). There is a need for increased surveillance of disease phenotype and outcome, long-term disability, and drug susceptibility to inform robust estimates of disease burden.
Topics: Humans; Cryptococcosis; Antifungal Agents; Cryptococcus gattii; Cryptococcus neoformans; Drug Resistance, Fungal; World Health Organization; Microbial Sensitivity Tests
PubMed: 38935902
DOI: 10.1093/mmy/myae043 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.
Topics: Humans; Mucorales; Antifungal Agents; Mucormycosis; World Health Organization; Risk Factors; Invasive Fungal Infections; Microbial Sensitivity Tests; Prevalence; Drug Resistance, Fungal; Incidence; Global Health
PubMed: 38935901
DOI: 10.1093/mmy/myad130 -
Medical Mycology Jun 2024The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and...
The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46-68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%-100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06-1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%-8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.
Topics: Humans; Antifungal Agents; Drug Resistance, Fungal; World Health Organization; Candidiasis; Candida auris; Microbial Sensitivity Tests; Candidemia; Disease Outbreaks; Candida; Incidence
PubMed: 38935900
DOI: 10.1093/mmy/myae042 -
The British Journal of General Practice... Jun 2024Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC... (Comparative Study)
Comparative Study Review
BACKGROUND
Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC presents commonly across primary care and, despite its mild symptoms, carries psychological burden and has a significant impact on women's quality of life. UK guidelines support treatment via oral or topical azole antifungal agents. Recent evidence attests to the superiority of novel non-azole antifungals. Thus, rigorous financial assessment of both antifungals is necessary for optimal VVC treatment allocation in UK primary care.
AIM
To evaluate the cost-effectiveness of ibrexafungerp against the gold standard fluconazole as first-line treatment of VVC within the NHS.
METHOD
A systematic review on the efficacy of ibrexafungerp and fluconazole in acute VVC was conducted. Cost-effectiveness analysis was initiated using health outcome data from the DOVE trial, a Phase 2 RCT. Costs in pound sterling were ascertained in monetary units, and effectiveness determined as reduced need for follow-up medication.
RESULTS
An incremental cost-effectiveness ratio of £2185.74 was determined. This suggests oral ibrexafungerp being largely more costly yet slightly more effective than fluconazole, and thus has unfavourable net benefit. Two sensitivity analyses were conducted considering follow-up medication combination and market price, which provided confidence in the calculated cost-effectiveness ratio.
CONCLUSION
This analysis highlights fluconazole's cost-effectiveness in current UK guidelines and favourability.
Topics: Humans; Fluconazole; Female; Cost-Benefit Analysis; Candidiasis, Vulvovaginal; Antifungal Agents; Administration, Oral; United Kingdom; Amphotericin B; State Medicine; Primary Health Care; Acute Disease; Treatment Outcome; Cost-Effectiveness Analysis; Glycosides; Triterpenes
PubMed: 38902100
DOI: 10.3399/bjgp24X738189 -
Clinical Infectious Diseases : An... Jun 2024This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different...
BACKGROUND
This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations.
METHODS
A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined.
RESULTS
Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients.
CONCLUSIONS
On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.
PubMed: 38860786
DOI: 10.1093/cid/ciae239 -
Italian Journal of Pediatrics Jun 2024The purpose of this study was to review the literature on the clinical use of voriconazole (VRC) in pediatric patients. MEDLINE, Embase, PubMed, Web of Science, and... (Review)
Review
The purpose of this study was to review the literature on the clinical use of voriconazole (VRC) in pediatric patients. MEDLINE, Embase, PubMed, Web of Science, and Cochrane Library were searched from January 1, 2000, to August 15, 2023 for relevant clinical studies on VRC use in pediatric patients. Data were collected based on inclusion and exclusion criteria, and a systematic review was performed on recent research related to the use of VRC in pediatric patients. This systematic review included a total of 35 observational studies among which there were 16 studies investigating factors influencing VRC plasma trough concentrations (C) in pediatric patients, 14 studies exploring VRC maintenance doses required to achieve target range of C, and 11 studies focusing on population pharmacokinetic (PPK) research of VRC in pediatric patients. Our study found that the C of VRC were influenced by both genetic and non-genetic factors. The optimal dosing of VRC was correlated with age in pediatric patients, and younger children usually required higher VRC doses to achieve target C compared to older children. Establishing a PPK model for VRC can assist in achieving more precise individualized dosing in children.
Topics: Voriconazole; Humans; Antifungal Agents; Child; Dose-Response Relationship, Drug; Mycoses
PubMed: 38853280
DOI: 10.1186/s13052-024-01684-z -
Frontiers in Cellular and Infection... 2024Sporotrichosis is a subcutaneous mycosis caused by fungi of the genus sp. Phenotypic and genotypic differences have been associated with their geographic distribution,... (Review)
Review
INTRODUCTION
Sporotrichosis is a subcutaneous mycosis caused by fungi of the genus sp. Phenotypic and genotypic differences have been associated with their geographic distribution, virulence, or clinical manifestation of sporotrichosis. In the past decade, the interest in identifying species of the sp. has been increasing, due to its epidemiological importance and, in consequence, is important to know how to preserve them for future studies, in culture collection.
AIMS
The purposes of this study were to analyze the global distribution of environmental isolates and/or causal agents of sporotrichosis identified by polyphasic taxonomy, with mandatory use of molecular identification, and to evaluate the percentages and distribution of isolates stored in culture collections.
METHODS
A systematic review of articles on animal and human sporotrichosis and/or environmental isolation of the fungus, from 2007 to 2023, was done. Results: Our results demonstrated that, , , and were the most identified species. With respect to the deposit and maintenance of species, we observed that only 17% of the strains of sp. isolated in the world are preserved in a culture collection.
CONCLUSIONS
This systematic review confirmed a difficulty in obtaining the frequency of species stored in culture collection and insufficient data on the molecular identification mainly of animal sporotrichosis and isolation of sp. in environmental samples.
Topics: Sporothrix; Sporotrichosis; Animals; Humans; Environmental Microbiology; Preservation, Biological
PubMed: 38828263
DOI: 10.3389/fcimb.2024.1382508 -
BMC Infectious Diseases May 2024Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients.
METHODS
Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model.
RESULTS
Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I > 50.00%, P < 0.01), except for caspofungin (I = 0.00%, P = 0.65).
CONCLUSIONS
Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin.
REGISTRATION
The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).
Topics: Humans; Candidiasis, Oral; Antifungal Agents; HIV Infections; Drug Resistance, Fungal; Candida; Prevalence; Microbial Sensitivity Tests; AIDS-Related Opportunistic Infections; Fluconazole
PubMed: 38822256
DOI: 10.1186/s12879-024-09442-6