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Open Forum Infectious Diseases Oct 2019Rhinosinusitis, malignant otitis externa, and skull base osteomyelitis represent a spectrum of cranial invasive fungal disease (IFD). These syndromes have distinct...
BACKGROUND
Rhinosinusitis, malignant otitis externa, and skull base osteomyelitis represent a spectrum of cranial invasive fungal disease (IFD). These syndromes have distinct characteristics, yet they may progress to involve similar structures, resulting in inflammation and invasion of the adjacent internal carotid artery (ICA). Invasive fungal carotiditis can have devastating consequences, including cerebral infarction, subarachnoid hemorrhage, and death.
METHODS
We retrospectively studied all patients diagnosed with cranial IFD and carotid involvement at our institution from 2003 to 2018. We also searched Medline/PubMed for reports of or cranial infections with ICA involvement. All cases with mycologic evidence of cranial IFD and radiographic or pathologic evidence of ICA involvement were included.
RESULTS
We identified 78 cases of invasive fungal carotiditis between 1958 and 2018, including 4 cases at our own institution. Forty-one were caused by and 37 by species. Presenting symptoms included vision changes (73%), cranial nerve palsy (69%), and headache (42%). Carotid events included occlusion, aneurysm formation, and vessel rupture. Cerebral infarcts occurred in 50% of cases. Mortality at 6 weeks, 12 weeks, and 2 years was 27%, 41%, and 71% respectively. The median time from symptom onset to death was 150 days for cases due to and 51 days for cases due to species.
CONCLUSIONS
Invasive fungal carotiditis is a rare but morbid manifestation of cranial IFD. Early suspicion of IFD and administration of antifungal treatment, vascular imaging, and endovascular interventions should be considered to reduce the high mortality of this disease.
PubMed: 31660355
DOI: 10.1093/ofid/ofz392 -
Advances in Therapy Dec 2019Fungi are responsible for around 20% of microbiologically documented infections in intensive care units (ICU). In the last decade, the incidence of invasive fungal...
Fungi are responsible for around 20% of microbiologically documented infections in intensive care units (ICU). In the last decade, the incidence of invasive fungal infections (IFI), including candidemia, has increased steadily because of increased numbers of both immunocompromised and ICU patients. To improve the outcomes of patients with IFI, intensivists need to be aware of the inherent challenges. This narrative review summarizes the features of routinely used treatments directed against IFI in non-neutropenic ICU patients, which include three classes of antifungals: polyenes, azoles, and echinocandins. ICU patients' pathophysiological changes are responsible for deep changes in the pharmacokinetics of antifungals. Moreover, drug interactions affect the response to antifungal treatments. Consequently, appropriate antifungal dosage is a challenge under these special conditions. Dosages should be based on renal and liver function, and serum concentrations should be monitored. This review summarizes recent guidelines, focusing on bedside management.
Topics: Antifungal Agents; Azoles; Drug Interactions; Drug Monitoring; Echinocandins; Humans; Immunocompromised Host; Incidence; Intensive Care Units; Invasive Fungal Infections; Kidney Function Tests; Liver Function Tests; Polyenes; Practice Guidelines as Topic
PubMed: 31617055
DOI: 10.1007/s12325-019-01115-0 -
The Cochrane Database of Systematic... Sep 2019This is an update of the original review published in the Cochrane Database of Systematic Reviews Issue 10, 2015.Invasive aspergillosis (IA) is the most common... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an update of the original review published in the Cochrane Database of Systematic Reviews Issue 10, 2015.Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mould infection in immunocompromised people. Early diagnosis of IA and prompt administration of appropriate antifungal treatment are critical to the survival of people with IA. Antifungal drugs can be given as prophylaxis or empirical therapy, instigated on the basis of a diagnostic strategy (the pre-emptive approach) or for treating established disease. Consequently, there is an urgent need for research into both new diagnostic tools and drug treatment strategies. Increasingly, newer methods such as polymerase chain reaction (PCR) to detect fungal nucleic acids are being investigated.
OBJECTIVES
To provide an overall summary of the diagnostic accuracy of PCR-based tests on blood specimens for the diagnosis of IA in immunocompromised people.
SEARCH METHODS
We searched MEDLINE (1946 to June 2015) and Embase (1980 to June 2015). We also searched LILACS, DARE, Health Technology Assessment, Web of Science and Scopus to June 2015. We checked the reference lists of all the studies identified by the above methods and contacted relevant authors and researchers in the field. For this review update we updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3) in the Cochrane Library; MEDLINE via Ovid (June 2015 to March week 2 2018); and Embase via Ovid (June 2015 to 2018 week 12).
SELECTION CRITERIA
We included studies that: i) compared the results of blood PCR tests with the reference standard published by the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG); ii) reported data on false-positive, true-positive, false-negative and true-negative results of the diagnostic tests under investigation separately; and iii) evaluated the test(s) prospectively in cohorts of people from a relevant clinical population, defined as a group of individuals at high risk for invasive aspergillosis. Case-control and retrospective studies were excluded from the analysis.
DATA COLLECTION AND ANALYSIS
Authors independently assessed quality and extracted data. For PCR assays, we evaluated the requirement for either one or two consecutive samples to be positive for diagnostic accuracy. We investigated heterogeneity by subgroup analyses. We plotted estimates of sensitivity and specificity from each study in receiver operating characteristics (ROC) space and constructed forest plots for visual examination of variation in test accuracy. We performed meta-analyses using the bivariate model to produce summary estimates of sensitivity and specificity.
MAIN RESULTS
We included 29 primary studies (18 from the original review and 11 from this update), corresponding to 34 data sets, published between 2000 and 2018 in the meta-analyses, with a mean prevalence of proven or probable IA of 16.3 (median prevalence 11.1% , range 2.5% to 57.1%). Most patients had received chemotherapy for haematological malignancy or had undergone hematopoietic stem cell transplantation. Several PCR techniques were used among the included studies. The sensitivity and specificity of PCR for the diagnosis of IA varied according to the interpretative criteria used to define a test as positive. The summary estimates of sensitivity and specificity were 79.2% (95% confidence interval (CI) 71.0 to 85.5) and 79.6% (95% CI 69.9 to 86.6) for a single positive test result, and 59.6% (95% CI 40.7 to 76.0) and 95.1% (95% CI 87.0 to 98.2) for two consecutive positive test results.
AUTHORS' CONCLUSIONS
PCR shows moderate diagnostic accuracy when used as screening tests for IA in high-risk patient groups. Importantly the sensitivity of the test confers a high negative predictive value (NPV) such that a negative test allows the diagnosis to be excluded. Consecutive positives show good specificity in diagnosis of IA and could be used to trigger radiological and other investigations or for pre-emptive therapy in the absence of specific radiological signs when the clinical suspicion of infection is high. When a single PCR positive test is used as the diagnostic criterion for IA in a population of 100 people with a disease prevalence of 16.3% (overall mean prevalence), three people with IA would be missed (sensitivity 79.2%, 20.8% false negatives), and 17 people would be unnecessarily treated or referred for further tests (specificity of 79.6%, 21.4% false positives). If we use the two positive test requirement in a population with the same disease prevalence, it would mean that nine IA people would be missed (sensitivity 59.6%, 40.4% false negatives) and four people would be unnecessarily treated or referred for further tests (specificity of 95.1%, 4.9% false positives). Like galactomannan, PCR has good NPV for excluding disease, but the low prevalence of disease limits the ability to rule in a diagnosis. As these biomarkers detect different markers of disease, combining them is likely to prove more useful.
Topics: Aspergillosis; Case-Control Studies; Humans; Immunocompromised Host; Opportunistic Infections; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity
PubMed: 31478559
DOI: 10.1002/14651858.CD009551.pub4 -
Emerging Microbes & Infections 2019Histoplasmosis caused by the fungus is often lethal in patients with AIDS. Urine antigen testing is highly sensitive and much quicker for diagnosis than culture....
Histoplasmosis caused by the fungus is often lethal in patients with AIDS. Urine antigen testing is highly sensitive and much quicker for diagnosis than culture. Histoplasmosis has a patchy and incompletely appreciated distribution around the world especially in South East Asia. We conducted a systematic literature review of cases of all disease forms of histoplasmosis in SE Asia, not including the Indian sub-continent. We also reviewed all histoplasmin skin test mapping studies to determine localities of exposure. We found a total of 407 cases contracted or likely to have been contracted in SE Asia. Numbers of cases by country varied: Thailand (233), Malaysia (76), Indonesia (48) and Singapore (21), with few or no cases reported in other countries. Most cases (255 (63%)) were disseminated histoplasmosis and 177 (43%) cases were HIV associated. Areas of high histoplasmin skin test sensitivity prevalence were found in Myanmar, the Philippines, Indonesia, Thailand and Vietnam - 86.4%, 26.0%, 63.6%, 36.0% and 33.7%, respectively. We have drawn maps of these data. Further study is required to ascertain the extent of histoplasmosis within SE Asia. Diagnostic capability for patients with HIV infection is urgently required in SE Asia, to reduce mortality and mis-diagnosis as tuberculosis.
Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Aged, 80 and over; Asia, Southeastern; Child; Child, Preschool; Female; Histoplasma; Histoplasmosis; Humans; Male; Middle Aged; Prevalence; Topography, Medical; Young Adult
PubMed: 31364950
DOI: 10.1080/22221751.2019.1644539 -
PeerJ 2019Coral disease research encompasses five decades of undeniable progress. Since the first descriptions of anomalous signs, we have come to understand multiple processes...
Coral disease research encompasses five decades of undeniable progress. Since the first descriptions of anomalous signs, we have come to understand multiple processes and environmental drivers that interact with coral pathologies. In order to gain a better insight into the knowledge we already have, we explored how key topics in coral disease research have been related to each other using network analysis. We reviewed 719 papers and conference proceedings published from 1965 to 2017. From each study, four elements determined our network nodes: (1) studied disease(s); (2) host genus; (3) marine ecoregion(s) associated with the study site; and (4) research objectives. Basic properties of this network confirmed that there is a set of specific topics comprising the majority of research. The top five diseases, genera, and ecoregions studied accounted for over 48% of the research effort in all cases. The community structure analysis identified 15 clusters of topics with different degrees of overlap among them. These clusters represent the typical sets of elements that appear together for a given study. Our results show that while some coral diseases have been studied considering multiple aspects, the overall trend is for most diseases to be understood under a limited range of approaches, e.g., bacterial assemblages have been considerably studied in Yellow and Black band diseases while immune response has been better examined for the aspergillosis- system. Thus, our challenge in the near future is to identify and resolve potential gaps in order to achieve a more comprehensive progress on coral disease research.
PubMed: 31198644
DOI: 10.7717/peerj.7041 -
Infection and Drug Resistance 2019The aim of this study was to use a network meta-analysis to evaluate the relative efficacy of various agents at preventing invasive fungal infections (IFIs). In this...
The aim of this study was to use a network meta-analysis to evaluate the relative efficacy of various agents at preventing invasive fungal infections (IFIs). In this way, suitable prophylactic regimens may be selected for patients with hematopoietic stem cell transplantation (HSCT). We conducted a systematic review of randomized controlled trials comparing the prophylactic effects of two antifungal agents or an antifungal agent and a placebo administered to patients with HSCT. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry. Sixteen two-arm studies were identified. Compared with placebo, all six antifungal agents (amphotericin B, fluconazole, itraconazole, micafungin, posaconazole, and voriconazole) presented with greater efficacy at controlling proven IFIs. OR ranged from 0.08 to 0.29. Voriconazole (surface under the cumulative ranking curve [SUCRA]=71.6%), posaconazole (SUCRA=68.9%), and itraconazole (SUCRA=64.7%) were the three top-ranking drugs for preventing proven IFIs. Itraconazole ranked highest (SUCRA=83.1%) and had the greatest efficacy at preventing invasive candidiasis. Posaconazole and micafungin were the two top-ranking drugs (SUCRA=81.3% and 78.4%, respectively) at preventing invasive aspergillosis. Micafungin and voriconazole were the drugs of choice because they lowered mortality more than the other agents (SUCRA=74.6% and 61.1%, respectively). This study is the first network meta-analysis to explore the prophylactic effects of antifungal agents in patients with HSCT. Voriconazole was the best choice for the prevention of proven IFIs in HSCT patients.
PubMed: 31190920
DOI: 10.2147/IDR.S203579 -
The Cochrane Database of Systematic... May 2019Invasive aspergillosis (IA) is a life-threatening opportunistic mycosis that occurs in some people with a compromised immune system. The serum galactomannan...
BACKGROUND
Invasive aspergillosis (IA) is a life-threatening opportunistic mycosis that occurs in some people with a compromised immune system. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) rapidly gained widespread acceptance as part of the diagnostic work-up of a patient suspected of IA. Due to its non-invasive nature, it can be used as a routine screening test. The ELISA can also be performed on bronchoalveolar lavage (BAL), allowing sampling of the immediate vicinity of the infection. The invasive nature of acquiring BAL, however, changes the role of the galactomannan test significantly, for example by precluding its use as a routine screening test.
OBJECTIVES
To assess the diagnostic accuracy of galactomannan detection in BAL for the diagnosis of IA in people who are immunocompromised, at different cut-off values for test positivity, in accordance with the Cochrane Diagnostic Test Accuracy Handbook.
SEARCH METHODS
We searched three bibliographic databases including MEDLINE on 9 September 2016 for aspergillosis and galactomannan as text words and subject headings where appropriate. We checked reference lists of included studies for additional studies.
SELECTION CRITERIA
We included cohort studies that examined the accuracy of BAL galactomannan for the diagnosis of IA in immunocompromised patients if they used the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) classification as reference standard.
DATA COLLECTION AND ANALYSIS
Two review authors assessed study quality and extracted data. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used for quality assessment.
MAIN RESULTS
We included 17 studies in our review. All studies except one had a high risk of bias in two or more domains. The diagnostic performance of an optical density index (ODI) of 0.5 as cut-off value was reported in 12 studies (with 1123 patients). The estimated sensitivity was 0.88 (95% confidence interval (CI) 0.75 to 1.00) and specificity 0.81 (95% CI 0.71 to 0.91). The performance of an ODI of 1.0 as cut-off value could be determined in 11 studies (with 648 patients). The sensitivity was 0.78 (95% CI 0.61 to 0.95) and specificity 0.93 (95% CI 0.87 to 0.98). At a cut-off ODI of 1.5 or higher, the heterogeneity in specificity decreased significantly and was invariably >90%.
AUTHORS' CONCLUSIONS
The optimal cut-off value depends on the local incidence and clinical pathway. At a prevalence of 12% a hypothetical population of 1000 patients will consist of 120 patients with IA. At a cut-off value of 0.5 14 patients with IA will be missed and there will be 167 patients incorrectly diagnosed with IA. If we use the test at a cut-off value of 1.0, we will miss 26 patients with IA. And there will be 62 patients incorrectly diagnosed with invasive aspergillosis. The populations and results were very heterogeneous. Therefore, interpretation and extrapolation of these results has to be performed with caution. A test result of 1.5 ODI or higher appears a strong indicator of IA.
Topics: Aspergillosis; Biomarkers; Bronchoalveolar Lavage Fluid; Galactose; Humans; Immunocompromised Host; Invasive Fungal Infections; Mannans; Randomized Controlled Trials as Topic; Sensitivity and Specificity
PubMed: 31107543
DOI: 10.1002/14651858.CD012399.pub2 -
PloS One 2019Asthma is one of the neglected diseases in Africa with a high prevalence. Allergic fungal diseases have been reported to complicate asthma progression and treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asthma is one of the neglected diseases in Africa with a high prevalence. Allergic fungal diseases have been reported to complicate asthma progression and treatment outcomes. However, data about fungal asthma and its associated complications are limited in Africa. We aimed to estimate the burden of fungal asthma among adults and children in Africa using a systematic review.
METHODS
We first engaged the Institute for Health Metrics and Evaluation (IHME) to highlight the trend in morbidity and mortality attributed to asthma in Africa. We then searched PubMed, HINARI and Google Scholar for all studies of any design focusing on fungal asthma in any African country. Languages were restricted to English and French, but not year of publication. We estimated the weighted prevalence of allergic fungal infections among asthmatics with a 95% CI and pooled the results using a random effects model. This study is registered with PROSPERO, number CRD42019117319.
RESULTS
The IHME data showed that there has been a gradual increase in morbidity and mortality due to asthma in African adults with a prevalence of 4%. Our search retrieved 5233 citations. We retained 20 studies that met our selection criteria. These were from 13 African countries published between 1967 and 2018. There were eight cross-sectional studies and twelve review articles. The average asthma prevalence in Africa was 6% from these studies. The prevalence of fungal sensitisation was relatively high (3-52%) in the asthmatic population with an average of 28% and a pooled estimate of 23.3%, mostly due to Aspergillus species. Prevalence of Allergic bronchopulmonary apsergillosis was estimated at 1.6-21.2%. Diagnosis of fungal allergy was mostly made by skin prick tests. There was no data on the use of medication to manage fungal asthma. None of the studies evaluated the association between fungal allergy and asthma severity. Data were lacking in children.
CONCLUSION
There is a high prevalence of fungal sensitization among Africans with asthma. Fungal asthma is a significant problem in Africa but there remains a paucity of data on the epidemiology and associated complications. There is urgent need for national epidemiological studies to estimate the actual burden of fungal asthma in Africa.
Topics: Africa; Asthma; Fungi; Humans; Hypersensitivity; Mycoses; Prevalence; Prognosis
PubMed: 31095641
DOI: 10.1371/journal.pone.0216568 -
Revista Da Sociedade Brasileira de... 2018Invasive aspergillosis is a common fungal infection in immunocompromised individuals. Some studies have shown that toll-like receptor and dectin-1 genetic polymorphisms...
Invasive aspergillosis is a common fungal infection in immunocompromised individuals. Some studies have shown that toll-like receptor and dectin-1 genetic polymorphisms may alter signaling pathways, thus increasing an individual's susceptibility to invasive aspergillosis. We investigated the pertinent literature to determine whether polymorphisms in the genes encoding toll-like receptors and dectin-1 increase the susceptibility to invasive aspergillosis. This study systematically reviewed the literature using the databases PubMed/PMC, Scopus, and Web of Science using the keywords invasive aspergillosis, polymorphism, Toll-like, and Dectin-1. From the initial search, 415 studies were found and according to our inclusion and exclusion criteria, eight studies were selected. Several studies described single-nucleotide polymorphisms (SNPs) that are associated with a greater susceptibility to invasive aspergillosis. These SNPs were found in the genes that encode toll-like receptors 1, 3, 4, and 5 and the gene that encodes dectin-1; upon activation, both cellular receptors initiate a signaling cascade that can result in the production of cytokines and chemokines. Thus, our literature review uncovered a significant association between polymorphisms in the genes that encode toll-like receptors and dectin-1 and invasive aspergillosis. More studies should be performed to better understand the relationship between toll-like receptor and dectin-1 genetic polymorphisms and invasive aspergillosis susceptibility.
Topics: Aspergillosis; Genetic Predisposition to Disease; Humans; Lectins, C-Type; Polymorphism, Single Nucleotide; Toll-Like Receptors
PubMed: 30517524
DOI: 10.1590/0037-8682-0314-2018 -
Journal of Infection in Developing... Oct 2018The number of fungal infections occurring each year in Iran is not known. As the burden of fungal disease is a measure used to assess and compare the relative impact of...
INTRODUCTION
The number of fungal infections occurring each year in Iran is not known. As the burden of fungal disease is a measure used to assess and compare the relative impact of different type of fungal diseases on populations, we have estimated the burden of fungal diseases in Iran.
METHODOLOGY
We estimated the burden of human fungal diseases based on the specific populations at risk, existing epidemiological data in both local and international databases, and modelling previously described by the LIFE program (http://www.LIFE-worldwide.org).
RESULTS
Among the population of Iran (79,926,270 in 2016), 6,670,813 (8.3%) individuals are estimated to suffer from a fungal infection each year. A total of 2,791,568 women aged between 15 and 50 years are estimated to suffer from recurrent vulvovaginal candidiasis, annually. In addition, considering the 13.3% prevalence rate of tinea capitis in children, a total of 2,552,624 cases per year are estimated. The estimated burden of invasive aspergillosis in the 3 groups of patients with hematologic malignancy, lung cancer and chronic pulmonary obstructive disease was 6394 (8.0 per 100,000). The estimate for the burden of allergic disease related to fungi including allergic bronchopulmonary aspergillosis, severe asthma with fungal sensitization and allergic fungal rhinosinusitis was 272,095 (340 per 100,000). Based on the 28,663 cases of HIV infection reported, an estimated 900 and 113 cases with pneumocystosis and cryptococcal meningitis are annually anticipated, respectively.
CONCLUSION
Our estimates indicate that the importance of fungal infections is high but overlooked in Iran, which warrants further actions by health care authorities.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cost of Illness; Female; Humans; Incidence; Infant; Infant, Newborn; Iran; Male; Middle Aged; Mycoses; Prevalence; Young Adult
PubMed: 32004161
DOI: 10.3855/jidc.10476