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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 -
PLoS Neglected Tropical Diseases Apr 2024Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL...
Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform.
BACKGROUND
Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform.
METHODS
A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology.
RESULTS
A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen.
CONCLUSIONS
Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.
Topics: Humans; Leishmaniasis, Visceral; Leishmaniasis, Cutaneous; Antiprotozoal Agents; Observational Studies as Topic; Clinical Trials as Topic; Feasibility Studies; Treatment Outcome; India; Bangladesh
PubMed: 38626228
DOI: 10.1371/journal.pntd.0011635 -
Medical Mycology Jun 2024In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and...
In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (∼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.
Topics: Humans; Drug Resistance, Fungal; Antifungal Agents; World Health Organization; Pichia; Incidence; Risk Factors; Candidiasis
PubMed: 38935911
DOI: 10.1093/mmy/myad132 -
Orofacial Cryptococcosis: A Challenging Clinical Report and a Systematic Analysis of the Literature.International Journal of Surgical... Feb 2024Cryptococcosis is a neglected fungal disease. The scarcity of studies on oral cryptococcosis is certainly due to rarity and/or underreporting of the disease, especially...
Cryptococcosis is a neglected fungal disease. The scarcity of studies on oral cryptococcosis is certainly due to rarity and/or underreporting of the disease, especially in Brazil. We describe an example of orofacial cryptococcosis affecting a 57-year-old man after heart transplantation, who presented with multiple erythematous ulcers and erosions distributed in the chin, nasal cavity, labial mucosa, hard palate, and buccal vestibule. Computed tomography revealed opacities and micronodules in the lungs. Histopathological features of the oral and pulmonary lesions were compatible with spp. Amphotericin B and fluconazole were used for treatment during hospitalization and itraconazole for prolonged therapy after hospital discharge. The patient has been under follow up for 6 months without signs of disease. According to a review conducted in PubMed, Web of Science, Scopus, Embase, and LILACS for data analysis of oral cryptococcosis, 26 reports were described in the literature. Predilection for men was observed (85%), with a male:female ratio of 5.5:1. The mean age of the individuals was 49 ± 15.3 years. Oral cryptococcosis mostly presented as an ulcer (= 17). The palate and tongue were the most affected sites (= 9 for each). Amphotericin B was the primary therapy utilized in most patients. Seventeen (65%) individuals survived. Knowledge of the clinicodemographic aspects of oral cryptococcosis is important for clinicians in decision making and surveillance.
Topics: Adult; Female; Humans; Male; Middle Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole
PubMed: 37143300
DOI: 10.1177/10668969231169048 -
Biofouling Feb 2024This study aimed to answer the question formulated according to the PICO strategy: 'Which essential oils show antimicrobial activity against biofilms formed on dental...
This study aimed to answer the question formulated according to the PICO strategy: 'Which essential oils show antimicrobial activity against biofilms formed on dental acrylic resin?' composed by population (dental acrylic resin), intervention (application of essential oils), comparison (denture cleansers, antifungal drugs, chlorhexidine, and oral mouthwashes), and outcome (antibiofilm activity). experimental studies evaluating the activity of EOs on biofilm formed on acrylic resin were included. PRISMA guidelines were followed, and the search was performed in the PubMed, Science Direct, Embase, and Lilacs databases and in the gray literature using Google Scholar and ProQuest in December 2023. A manual search of the reference lists of the included primary studies was performed. Of the 1467 articles identified, 37 were selected for full-text reading and 12 were included. Twelve EOs were evaluated, of which 11 showed activity against spp., 3 against , and 1 against . The EOs of and showed higher action than chlorhexidine, higher than Listerine, higher than nystatin, and higher than fluconazole and nystatin. However, chlorhexidine was more effective than and , sodium hypochlorite was more effective than , nystatin was more effective than , Amphotericin B more effective than and . In conclusion, the EOs of and showed antimicrobial activity to reduce biofilm on dental acrylic resin.
Topics: Acrylic Resins; Antifungal Agents; Biofilms; Candida albicans; Chlorhexidine; Nystatin; Oils, Volatile
PubMed: 38538551
DOI: 10.1080/08927014.2024.2332709 -
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 -
The Lancet Regional Health. Southeast... Mar 2024Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to...
BACKGROUND
Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to quantify the proportion of relapses observed at and beyond 6-months using the Infectious Diseases Data Observatory (IDDO) systematic review (SR) database.
METHODS
Studies in the IDDO SR database (1983-2021; 160 studies) were eligible for inclusion if follow-up was at least 6-months, relapse was clearly reported, and patients with HIV coinfections were excluded. Meta-analysis of single proportion was undertaken and the estimates were reported with 95% confidence intervals (CI).
FINDINGS
Overall, 131 studies enrolling 27,687 patients were included; 1193 patients relapsed. In the Indian sub-continent (ISC), relapse estimates at 6-months was 4.5% [95% CI: 2.6%-7.5%; = 66.2%] following single dose liposomal amphotericin B (L-AmB) and 1.5% [95% CI: 0.7%-3.3%; = 0%] for L-AmB in a combination therapy. In East Africa (EA), corresponding estimates were 3.8% [95% CI: 1.3%-10.9%; = 75.8%] following pentavalent antimony (PA), and 13.0% [95% CI: 4.3%-33.6%; = 0%] for PA + paromomycin. From 21 studies with follow-up longer than 6-months, 0.6% [95% CI: 0.2%-1.8%; = 0%] of patients relapsed after 6-months and estimated 27.6% [95% CI: 11.2%-53.4%; = 12%] of relapses would have been missed by a 6-month follow-up.
INTERPRETATION
The estimated relapse proportion ranged from 0.5% to 4.5% in ISC and 3.8%-13.0% in EA with the currently recommended drugs. Over one-quarter of relapses would be missed with 6-months follow-up suggesting a longer follow-up may be warranted.
FUNDING
Wellcome Trust (ref: 208378/Z/17/Z).
PubMed: 38482151
DOI: 10.1016/j.lansea.2023.100317