Advances in the molecular and serological diagnosis of invasive fungal infection in haemato‐oncology patients

McLintock, Lorna; Jones, Brian

doi:10.1111/j.1365-2141.2004.05031.x

Cited by 32 publications

(36 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While there are several molecular and serological assays for the diagnosis of specific types of IFI, which can be detected by means of galactomannan, mannan, and DNA sequences (36), only the BG assay can be used for various fungal infections. For instance, the diagnostic accuracy of the galactomannan assay for invasive aspergillosis is similar to that of BG for IFI.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Serum 1,3-β- d -Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

et al. 2012

View full text Add to dashboard Cite

Serum 1,3-␤-D-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI).We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP. P neumocystis jiroveci pneumonia (PJP) continues to be a serious problem among immunocompromised patients despite the decreased number of cases among human immunodeficiency virus (HIV)-infected patients over the past decade with the widespread use of prophylaxis. The high mortality of patients requiring mechanical ventilation has remained unchanged, ranging from 50 to 60% (35). Although the gold standard for diagnosis is microscopic visualization of the organism, the methods are not sensitive, particularly in HIV-negative patients (31).The incidence of invasive fungal infection (IFI) has been increasing, especially among immunocompromised patients undergoing aggressive chemotherapy for cancer, bone marrow and organ transplantation, and advanced critical care. Despite advances in therapy, IFI is associated with considerable morbidity and a mortality rate of 30 to 70% for aspergillosis and 40 to 50% for candidiasis (15). Diagnosis of IFI is challenging because clinical and radiological signs and conventional microbiological and histological techniques are not sensitive enough (25). For these reasons, intensive research currently aims at the development of new diagnostic methods for PJP and IFI.One of these new diagnostic techniques is the assay for the serum 1,3-␤-D-glucan (BG) derived from major cell wall components of various medically important fungi. The Fungitell test (Associates of Cape Cod, Inc., East Falm...

show abstract

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Serum 1,3-β- d -Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

et al. 2012

View full text Add to dashboard Cite

show abstract

“…These new methods include PCR detection of fungal DNA and a variety of serologic tests such as detection of circulating fungal antigens or antifungal antibodies. For instance, the fungal cell wall component galactomannan has been shown to be a sensitive marker for invasive aspergillosis [20][21][22][23]. These new diagnostic tests may not only be of considerable benefit for high-risk patients who should be screened for fungal infections at regular intervals, but they have also proven to be useful in monitoring the response to antifungal therapy [19].…”

Section: Diagnosis Of Pulmonary Mycosismentioning

confidence: 99%

Modern management of respiratory failure due to pulmonary mycoses following allogeneic hematopoietic stem‐cell transplantation

Koldehoff

Zakrzewski

2005

American J Hematol

View full text Add to dashboard Cite

Pulmonary mycoses count among the most dangerous complications in allogeneic hematopoietic stem cell transplantation. Despite the establishment of antifungal chemoprophylaxis and empirical antifungal treatment, they frequently lead to respiratory failure and are still associated with an extraordinarily poor prognosis. However, the emergence of new antimycotics with alternative mechanisms of actions and decreased toxicity in combination with the development of new non culture-based diagnostic techniques may allow earlier, more aggressive and more effective antifungal treatment approaches. In addition, the optimized use of new technologies designed to augment spontaneous breathing efforts by patients, mechanical ventilation, as well as the advantages of early tracheostomy lead us to expect better outcomes in the treatment of respiratory failure due to pulmonary mycoses following allogeneic hematopoietic stem cell transplantation.

show abstract

“…Culture-based methods have poor diagnostic sensitivity for many fungal infections, which has led to the adoption of other diagnostic approaches, such as detection of fungal antigens. However, the galactomannan antigenbased assay and the glucan assay do not detect all fungal species (15,16,26). Accordingly, a negative antigen assay does not rule out fungal infection in a high-risk host, such as a stem cell transplant recipient with zygomycosis.…”

Section: Discussionmentioning

confidence: 99%

“…Culture-based and histological analyses often have poor diagnostic sensitivity, and histopathological findings frequently do not distinguish among fungal genera or species (15,18,26). Moreover, some molecular diagnostic tests, such as the galactomannan antigen assay, reliably detect only pathogens belonging to the genus Aspergillus, and the beta-glucan assay does not detect fungi in the zygomycete and basidiomycete taxa (11,15,16,26). Such shortcomings may lead to more empirical and unnecessary antifungal therapy because a fungal infection is not completely excluded by negative results in either of these assays.…”

mentioning

confidence: 99%

Sequencing and Analysis of Fungal rRNA Operons for Development of Broad-Range Fungal PCR Assays

Khot

Fredricks

2009

Appl Environ Microbiol

101

View full text Add to dashboard Cite

rRNA genes are attractive targets for developing PCR assays targeting human fungal pathogens. Most studies have focused on the 18S rRNA gene, internal transcribed spacers, and the 5 end of the 28S rRNA gene. An approximately 2,900-bp region of the 28S rRNA gene remains largely unexplored because sequences of many medically relevant fungi are either unavailable or undefined in genomic databases. The internal transcribed spacers and 28S rRNA gene of nine medically and phylogenetically important fungi were sequenced. In addition, 42 sequences from this region were acquired from public databases, resulting in an alignment of 51 fungal sequences spanning 30 fungal genera. For the nearly 3,950-bp region from the 3 end of 18S rRNA gene to the 3 end of the 28S rRNA gene, 27 broad-range PCR primers were designed such that their sequence homology with the human rRNA gene was minimal. All 62 possible amplicons in the size range from 75 to 400 bp from 27 primers were screened using fungal genomic DNA from 26 species spanning 14 genera. Eleven of the 62 amplicons did not cross-react with 1 g/PCR human DNA but simultaneously amplified 10 fg of fungal DNA. Phylogenetic distance matrices were calculated for regions covered by these 11 amplicons based on 51 fungi. Two of these 11 amplicons successfully amplified 30 fg of fungal DNA from 25 of 26 fungi and provided the most phylogenetic information for species identification based on the distance matrices. These PCR assays hold promise for detection and identification of fungal pathogens in human tissues.Rapid detection and accurate identification of fungal pathogens can be critical for initiating treatment in the earliest stages of infection and for guiding antifungal therapy. Culture-based and histological analyses often have poor diagnostic sensitivity, and histopathological findings frequently do not distinguish among fungal genera or species (15,18,26). Moreover, some molecular diagnostic tests, such as the galactomannan antigen assay, reliably detect only pathogens belonging to the genus Aspergillus, and the beta-glucan assay does not detect fungi in the zygomycete and basidiomycete taxa (11,15,16,26). Such shortcomings may lead to more empirical and unnecessary antifungal therapy because a fungal infection is not completely excluded by negative results in either of these assays.PCR assays for the detection of fungal pathogens are an appealing approach due to their potential for rapid, sensitive, and accurate diagnosis of fungal infections. rRNA genes are particularly attractive targets because multiple copies are present in each genome and the genes have conserved regions for designing broad-range primers and have more variable regions for identifying fungi. Most studies have focused on regions within the 18S rRNA gene (4, 23), internal transcribed spacers (ITS1 and ITS2), the 5.8S rRNA gene (2,3,8,9,14,22,25), and the 5Ј end of the 28S rRNA gene (D1-D2 hypervariable region) (1,5,8,13,17,20,24) for developing broad-range PCR primers targeting human fungal pathogens. The re...

show abstract

Advances in the molecular and serological diagnosis of invasive fungal infection in haemato‐oncology patients

Cited by 32 publications

References 81 publications

Diagnostic Accuracy of Serum 1,3-β- d -Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

Diagnostic Accuracy of Serum 1,3-β- d -Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

Modern management of respiratory failure due to pulmonary mycoses following allogeneic hematopoietic stem‐cell transplantation

Sequencing and Analysis of Fungal rRNA Operons for Development of Broad-Range Fungal PCR Assays

Contact Info

Product

Resources

About