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PLoS Neglected Tropical Diseases Apr 2020Mycetoma is one of the badly neglected tropical diseases, characterised by subcutaneous painless swelling, multiple sinuses, and discharge containing aggregates of the...
Mycetoma is one of the badly neglected tropical diseases, characterised by subcutaneous painless swelling, multiple sinuses, and discharge containing aggregates of the infecting organism known as grains. Risk factors conferring susceptibility to mycetoma include environmental factors and pathogen factors such as virulence and the infecting dose, in addition to host factors such as immunological and genetic predisposition. Epidemiological evidence suggests that host genetic factors may regulate susceptibility to mycetoma and other fungal infections, but they are likely to be complex genetic traits in which multiple genes interact with each other and environmental factors, as well as the pathogen, to cause disease. This paper reviews what is known about genetic predisposition to fungal infections that might be relevant to mycetoma, as well as all studies carried out to explore host genetic susceptibility to mycetoma. Most studies were investigating polymorphisms in candidate genes related to the host immune response. A total of 13 genes had allelic variants found to be associated with mycetoma, and these genes lie in different pathways and systems such as innate and adaptive immune systems, sex hormone biosynthesis, and some genes coding for host enzymes. None of these studies have been replicated. Advances in genomic science and the supporting technology have paved the way for large-scale genome-wide association and next generation sequencing (NGS) studies, underpinning a new strategy to systematically interrogate the genome for variants associated with mycetoma. Dissecting the contribution of host genetic variation to susceptibility to mycetoma will enable the identification of pathways that are potential targets for new treatments for mycetoma and will also enhance the ability to stratify 'at-risk' individuals, allowing the possibility of developing preventive and personalised clinical care strategies in the future.
Topics: Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Immunologic Factors; Male; Mycetoma; Polymorphism, Genetic; Risk Factors
PubMed: 32352976
DOI: 10.1371/journal.pntd.0008053 -
Mycoses Apr 2021Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause...
Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause invasive infections. In this study, we aimed to perform a systematic review of all reported invasive dermatophytosis cases over the past 20 years. We performed systematic searches in PubMed/Medline, EMBASE and Web of Science and identified 123 papers reporting 160 individual cases of invasive dermatophytosis between 2000 and 2020. Our study included 103 (64.4%) males, and the mean age at diagnosis was 43.0 years (range: 3-87 years). The most common predisposing factor was superficial dermatophytosis (56.9%), followed by solid organ transplantation (26.9%), the use of topical immunosuppressants (15.6%), gene mutations (14.4%), diabetes (14.4%) and trauma (6.9%). Trichophyton (T.) rubrum was the most prevalent pathogen (53.1%) responsible for invasive dermatophytosis, followed by T. mentagrophytes (7.5%), Microsporum canis (6.9%), T. tonsurans (5.6%), T. interdigitale (5.0%) and T. violaceum (3.8%). Patients with CARD9 or STAT3 mutations were prone to have mixed infection of two or more dermatophytes, present with eosinophilia and high IgE, and develop disseminated infections. Overall mortality was 7.9%, and the mortality in patients with and without gene mutations was 17.4% and 5.5%, respectively. Most of the normal host patients responded well to oral antifungal agents, while gene-deficient patients usually required lifelong treatment to stabilise their infection status. Our review indicated the importance of preventive treatment of superficial tinea in patients with immunosuppression and gene deficiencies to avoid the development of invasive dermatophytosis.
Topics: Antifungal Agents; Dermatomycoses; Humans; Invasive Fungal Infections; Organ Transplantation; Risk Factors; Skin
PubMed: 33217082
DOI: 10.1111/myc.13212 -
Transfusion Sep 2015Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound... (Review)
Review
BACKGROUND
Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound neutropenia and/or systemic corticosteroid use. Treatment guidelines for IF are not well established, including the role of granulocyte transfusions (GTs) to counter neutropenia.
STUDY DESIGN AND METHODS
We conducted a systematic review, identifying IF cases where GTs were used as adjunctive therapy to antifungal agents and also report a single-center case series detailing our experience (1996-2012) of all IF cases treated with antifungal agents and GTs. In the systematic review cases, GTs were predominantly collected from nonstimulated donors whereas, in the case series, they were universally derived from dexamethasone- and granulocyte-colony-stimulating factor-stimulated donors.
RESULTS
Twenty-three patients met inclusion criteria for the systematic review and 11 for the case series. Response rates after GTs were 30 and 91% in the review and case series, respectively. Survival to hospital discharge remained low at 30 and 45%, respectively. Ten patients in the systematic review and three in the case series failed to achieve hematopoietic recovery and none of these survived. In the case series, donor-stimulated GTs generated mean "same-day" neutrophil increments of 3.35 × 10(9) ± 1.24 × 10(9) /L and mean overall posttransfusion neutrophil increments of 2.46 × 10(9) ± 0.85 × 10(9) /L. Progressive decrements in neutrophil response to GTs in two cases were attributed to GT-related HLA alloimmunization.
CONCLUSION
In patients with IF, donor-stimulated GTs may contribute to high response rates by effectively bridging periods of neutropenia or marrow suppression. However, their utility in the absence of neutrophil recovery remains questionable.
Topics: Female; Fusariosis; Granulocytes; Humans; Leukocyte Transfusion; Male
PubMed: 25857209
DOI: 10.1111/trf.13099 -
Pediatric Dermatology Nov 2022Onychomycosis is one of the most common nail diseases in adults but is described as infrequent in children. Data are, however, scattered and diverse. Studies have... (Review)
Review
Onychomycosis is one of the most common nail diseases in adults but is described as infrequent in children. Data are, however, scattered and diverse. Studies have nevertheless suggested that the prevalence of onychomycosis is increasing in children lately and the aim of this review was therefore to examine this problem. Two authors individually searched PubMed, Embase, and Cochrane Library for articles on epidemiology and prevalence of onychomycosis in children. The literature search was conducted in accordance per PRISMA guidelines. In total 1042 articles were identified of which 23 were eligible for inclusion. One of the articles presented two studies and a total of 24 studies were therefore included. Seventeen studies presented data of the prevalence of onychomycosis in children in the general population and seven studies among children visiting a dermatological and pediatric department or clinic. The prevalence ranged from 0% to 7.66% with an overall discrete increase of 0.66% during the period 1972 to 2014 in population studies (not statistically significant). This review supports a trend towards an increased prevalence of onychomycosis in children, albeit based on a paucity of studies. The data suggests an increasing prevalence of onychomycosis with age, and co-infection with tinea pedis (reported in 25% of the studies). The most common pathogen reported was Trichophyton rubrum and onychomycosis was more prevalent in toenails compared to fingernails. The general characteristics of onychomycosis in children are thus similar to those described in adults.
Topics: Adult; Child; Humans; Nails; Onychomycosis; Prevalence; Tinea Pedis; Trichophyton
PubMed: 36130720
DOI: 10.1111/pde.15100 -
Mycoses Jun 2023A systematic review was conducted to investigate the prevalence of onychomycosis in patients with diabetes. The association of onychomycosis with risk factors in... (Review)
Review
BACKGROUND
A systematic review was conducted to investigate the prevalence of onychomycosis in patients with diabetes. The association of onychomycosis with risk factors in patients with diabetic foot syndrome was also examined.
METHODS
The recommendations in the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist were applied, and the included studies were assessed using the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) method. Searches were conducted in October 2022 using PubMed (Medline) and Scopus for clinical studies, clinical trials, comparative studies, observational studies, and randomised clinical trials or controlled clinical trials addressing the prevalence and consequences of onychomycosis in patients with diabetes, diagnoses or treatments. Two authors performed the study selection and data extraction, and any discrepancies between the two reviewers were resolved through discussion with a third reviewer.
RESULTS
The systematic review included ten studies that met the inclusion criteria, and these studies enrolled 5664 patients with diabetes. Among these patients, 29.18% had onychomycosis that was mainly caused by Trichophyton rubrum. A significant association was found between the occurrence of onychomycosis and the presence of diabetic neuropathy (p = .012) and elevated glycosylated haemoglobin values (p = .039). There was no significant association between onychomycosis and ulceration (p = .185). Eight studies had a grade 4 level of evidence and a grade C recommendation, and one study had a grade 1b level of evidence and a grade A recommendation.
CONCLUSION
The information described in the literature is insufficient and heterogeneous regarding the association of risk factors and ulceration in patients with diabetic foot compared with developing onychomycosis. There is also a need to implement onychomycosis diagnostic testing instead of relying only on a clinical diagnosis. Additional prospective, randomised, comparative studies are needed to increase the quality of studies in the literature.
Topics: Humans; Diabetic Foot; Onychomycosis; Prospective Studies; Risk Factors; Diabetes Mellitus
PubMed: 36790078
DOI: 10.1111/myc.13577 -
International Journal of Dermatology Oct 2017There is a worrying lack of epidemiological data on the geographical distribution and burden of subcutaneous mycoses in Peru, hindering the implementation of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is a worrying lack of epidemiological data on the geographical distribution and burden of subcutaneous mycoses in Peru, hindering the implementation of surveillance and control programs.
OBJECTIVES
This study aimed to estimate the disease burden of subcutaneous mycoses in Peru and identify which fungal species were commonly associated with these mycoses.
METHODS
We performed a meta-analysis after a systematic review of the published literature in PubMed, LILACS, and SciELO to estimate the burden of subcutaneous mycoses in 25 regions in Peru. The disease burden was determined in terms of prevalence (number of cases per 100,000 inhabitants) and the number of reported cases per year per region.
RESULTS
A total of 26 studies were eligible for inclusion. Results showed that sporotrichosis was the most common subcutaneous mycosis (99.7%), whereas lobomycosis, chromoblastomycosis, and subcutaneous phaeohyphomycosis were rare. Cases of eumycetoma and subcutaneous zygomycosis were not found. Of the 25 regions, the burden of sporotrichosis was estimated for four regions classified as endemic; in nine regions, only isolated cases were reported. The highest burden of sporotrichosis was in Apurimac (15 cases/100,000 inhabitants; 57 cases/year), followed by Cajamarca (3/100,000 inhabitants; 30/year), Cusco (0.5/100,000 inhabitants; 4/year), and La Libertad (0.2/100,000 inhabitants; 2/year). In two regions, the mycoses predominantly affected children.
CONCLUSIONS
Sporotrichosis is the most common subcutaneous mycosis in Peru, with a high disease burden in Apurimac. Chromoblastomycosis, lobomycosis, and subcutaneous phaeohyphomycosis are rare mycoses in Peru.
Topics: Chromoblastomycosis; Endemic Diseases; Humans; Lobomycosis; Peru; Phaeohyphomycosis; Sporotrichosis; Subcutaneous Tissue
PubMed: 28670680
DOI: 10.1111/ijd.13665 -
Infection Jun 2015Sporotrichosis is a fungal infection of man and animals caused by Sporothrix complex. It usually presents as a lymphocutaneous form, but disseminated disease may occur.... (Review)
Review
Sporotrichosis is a fungal infection of man and animals caused by Sporothrix complex. It usually presents as a lymphocutaneous form, but disseminated disease may occur. Given the paucity of data about HIV/AIDS and sporotrichosis co-infection, a systematic review of reported cases of HIV-associated sporotrichosis found via Pubmed (1984-2013) was done. A total of 39 papers were included, and 58 patients' data analyzed. Thirty-three (56.9 %) cases were from Brazil and 18 (31 %) from the USA. Patients' mean age was 37.8 ± 10.4 years; males predominated (84.5 %). The median CD4(+) cell count was 97 cells/mm(3). The most common clinical forms were disseminated and disseminated cutaneous with 33 (56.9 %) and 10 (17.5 %) patients, respectively. There was a correlation between CD4(+) count and clinical categories (p = 0.002). Mortality was 30 % and there was a correlation between central nervous system involvement and death (p < 0.001).
Topics: Age Distribution; Animals; Brazil; CD4 Lymphocyte Count; HIV Infections; Humans; Sex Distribution; Sporothrix; Sporotrichosis; United States
PubMed: 25701221
DOI: 10.1007/s15010-015-0746-1 -
Photodiagnosis and Photodynamic Therapy Sep 2016Other than a cosmetic concern, Onychomycosis is also a prevalent nail disease, which is extremely difficult to treat, and sometimes is refractory to conventional... (Review)
Review
Other than a cosmetic concern, Onychomycosis is also a prevalent nail disease, which is extremely difficult to treat, and sometimes is refractory to conventional therapy. Moreover, many patients are not eligible to take oral antifungals owing to polypharmacy and comorbidities. Systemic side effects seen with oral antifungals have lead to patient nonadherence and adverse events. Therefore, newer therapies are being investigated for onychomycosis that would be free of systemic complications posed by oral therapy. Photodynamic therapy (PDT) is one of those being currently studied, which involves the use of photosensitizer and a light source to excite the photosensitizer to generate reactive oxygen species. The present review will put some light on PDT as an upcoming treatment modality for onychomycosis. We performed a systematic review of the literature to find the articles relevant to the use of PDT for onychomycosis. From the primary search of 43 articles, 17 papers are included in this review.
Topics: Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Onychomycosis; Photochemotherapy; Photosensitizing Agents; Treatment Outcome
PubMed: 27477248
DOI: 10.1016/j.pdpdt.2016.07.010 -
The British Journal of Dermatology Aug 2017Nonpurulent cellulitis is an acute bacterial infection of the dermal and subdermal tissues that is not associated with purulent drainage, discharge or abscess. The... (Meta-Analysis)
Meta-Analysis Review
Nonpurulent cellulitis is an acute bacterial infection of the dermal and subdermal tissues that is not associated with purulent drainage, discharge or abscess. The objectives of this systematic review and meta-analysis were to identify and appraise all controlled observational studies that have examined risk factors for the development of nonpurulent cellulitis of the leg (NPLC). A systematic literature search of electronic databases and grey literature sources was performed in July 2015. The Newcastle-Ottawa Scale (NOS) was used to assess methodological quality of included studies. Of 3059 potentially eligible studies retrieved and screened, six case-control studies were included. An increased risk of developing NPLC was associated with previous cellulitis [odds ratio (OR) 40·3, 95% confidence interval (CI) 22·6-72·0], wound (OR 19·1, 95% CI 9·1-40·0), current leg ulcers (OR 13·7, 95% CI 7·9-23·6), lymphoedema/chronic leg oedema (OR 6·8, 95% CI 3·5-13·3), excoriating skin diseases (OR 4·4, 95% CI 2·7-7·1), tinea pedis (OR 3·2, 95% CI 1·9-5·3) and body mass index > 30 kg m (OR 2·4, 95% CI 1·4-4·0). Diabetes, smoking and alcohol consumption were not associated with NPLC. Although diabetics may have been underrepresented in the included studies, local risk factors appear to play a more significant role in the development of NPLC than do systemic risk factors. Clinicians should consider the treatment of modifiable risk factors including leg oedema, wounds, ulcers, areas of skin breakdown and toe-web intertrigo while administering antibiotic treatment for NPLC.
Topics: Alcohol Drinking; Cellulitis; Humans; Leg Injuries; Leg Ulcer; Lymphedema; Obesity; Observational Studies as Topic; Recurrence; Risk Factors; Skin Diseases, Bacterial; Smoking; Tinea Pedis
PubMed: 27864837
DOI: 10.1111/bjd.15186 -
PLoS Neglected Tropical Diseases Apr 2020Mycetoma is considered a neglected tropical disease globally. However, data on its burden and the associated complications in Uganda are limited. Hence we aimed to...
Mycetoma is considered a neglected tropical disease globally. However, data on its burden and the associated complications in Uganda are limited. Hence we aimed to estimate its burden in Uganda. Firstly, a systematic PubMed search for all studies of any design on mycetoma in Uganda without restriction to the year of publication was conducted. A retrospective review of all the biopsy reports at the Pathology Reference Laboratory, Department of Pathology, Makerere University, Kampala, Uganda from January 1950 to September 2019 was conducted to identify any reports on mycetoma histological diagnosis. During the 70-years study period, 30 cases were identified by the literature review, with 249 additional cases identified by review of biopsy reports (total of 279 cases). The average incidence was estimated at 0.32/100,000 persons and prevalence of 8.32/100,000 persons per decade. However, there was a general decline in the number of cases detected recently. Males and the age group of 21-30 years were the most affected by mycetoma in Uganda, and only 7% of the cases were children. The highest number of cases was recorded from Kampala (n = 30) and Jinja (n = 19) districts. The majority of the cases (68%) were referred from surgical units. The foot was the most affected part of the body (72%). Ten per cent of the cases had bone involvement of which 58% required amputation. Fungi were the most common causative agents (89%) followed by Nocardia species (5%) and Actinomycetes (4%). The index of clinical suspicion of mycetoma was low (45%) with a very large differential diagnosis. Mycetoma is a relatively rare disease in Uganda, mostly caused by fungi, and there is a big gap in data and epidemiological studies. More systematic studies are warranted to define the true burden of mycetoma in Uganda.
Topics: Actinomycetaceae; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Child, Preschool; Cost of Illness; Female; Fungi; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Mycetoma; Neglected Diseases; Nocardia; Prevalence; Sex Factors; Tropical Climate; Uganda; Young Adult
PubMed: 32348300
DOI: 10.1371/journal.pntd.0008240