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      Performance of a new Candida anti-mannan IgM and IgG assays in the diagnosis of candidemia

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          ABSTRACT

          Candida is one of the most frequent pathogens of bloodstream infections, which is associated with high morbidity and mortality rates. Rapid immunological detection methods are essential in the early diagnosis of candidemia. Anti-mannan is one of host-derived biomarkers against cell wall components of Candida. We conducted this study to evaluate the diagnostic performance of two anti-mannan assays (IgM, IgG) for candidemia through the analysis of 40 candidemia patients, 48 participants with Candida colonization and 213 participants with neither Candida colonization nor Candida infections (13 patients with other bloodstream infections, 145 hospitalized patients and 55 healthy controls). The performance of the two assays were evaluated by calculating their sensitivity and specificity. The sensitivity ranged from 0.78 to 0.80 for the IgM assay and 0.68 to 0.75 for the IgG assay. The specificity ranged from 0.97 to 0.98 for the IgM assay and 0.91 to 0.94 for the IgG assay. The diagnostic performance of the anti-mannan IgM assay was better than that of IgG, with higher sensitivity and specificity. Combining the two assays (positive results of single or both assays are both considered as positive) could improve the sensitivity up to 0.93 (0.79-0.98) and only slightly reduce the specificity (0.93(0.89-0.95)). The anti-mannan IgM, IgG assays are rapid and cost-effective assays that may be probably useful in the diagnosis of candidemia.

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          Finding the "missing 50%" of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care.

          Blood cultures are limited for diagnosing invasive candidiasis by poor sensitivity and slow turn-around time. New diagnostics are needed to complement cultures, in particular to identify the "missing 50%" of patients who are blood culture-negative. Mannan/anti-mannan immunoglobulin G, β-D-glucan (BDG) and polymerase chain reaction (PCR) assays can diagnose candidemia before blood cultures and show promising sensitivity/specificity, but they are not widely investigated in blood culture-negative, deep-seated candidiasis. In a recent study, BDG and PCR were superior to blood cultures in deep-seated candidiasis, suggesting they may identify currently undiagnosed patients and expand our understanding of disease spectrum. Positive predictive values of nonculture tests are limited by the low prevalence of invasive candidiasis, which mandates that results be interpreted judiciously. When used as biomarkers that assess a patient's risk of having invasive candidiasis, tests will facilitate preemptive antifungal strategies. Because negative predictive values are excellent, tests will also be useful for ruling out invasive candidiasis and discontinuing unnecessary antifungal therapy.
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            ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures.

            As the mortality associated with invasive Candida infections remains high, it is important to make optimal use of available diagnostic tools to initiate antifungal therapy as early as possible and to select the most appropriate antifungal drug. A panel of experts of the European Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) undertook a data review and compiled guidelines for the clinical utility and accuracy of different diagnostic tests and procedures for detection of Candida infections. Recommendations about the microbiological investigation and detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis, and oropharyngeal, oesophageal, and vaginal candidiasis were included. In addition, remarks about antifungal susceptibility testing and therapeutic drug monitoring were made. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.
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              The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia

              Introduction Timely diagnosis of invasive candidiasis (IC) remains difficult as the clinical presentation is not specific and blood cultures lack sensitivity and need a long incubation time. Thus, non-culture-based methods for diagnosing IC have been developed. Mannan antigen (Mn) and anti-mannan antibodies (A-Mn) are present in patients with IC. On behalf of the Third European Conference on Infections in Leukemia, the performance of these tests was analysed and reviewed. Methods The literature was searched for studies using the commercially available sandwich enzyme-linked immunosorbent assays (Platelia™, Bio-Rad Laboratories, Marnes-la-Coquette, France) for detecting Mn and A-Mn in serum. The target condition of this review was IC defined according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity, specificity and diagnostic odds ratios (DOR) were calculated for Mn, A-Mn and combined Mn/A-Mn testing. Results Overall, 14 studies that comprised 453 patients and 767 controls were reviewed. The patient populations included in the studies were mainly haematological and cancer cases in seven studies and mainly intensive care unit and surgery cases in the other seven studies. All studies but one were retrospective in design. Mn sensitivity was 58% (95% confidence interval [CI], 53-62); specificity, 93% (95% CI, 91-94) and DOR, 18 (95% CI 12-28). A-Mn sensitivity was 59% (95% CI, 54-65); specificity, 83% (95% CI, 79-97) and DOR, 12 (95% CI 7-21). Combined Mn/A-Mn sensitivity was 83% (95% CI, 79-87); specificity, 86% (95% CI, 82-90) and DOR, 58 (95% CI 27-122). Significant heterogeneity of the studies was detected. The sensitivity of both Mn and A-Mn varied for different Candida species, and it was the highest for C. albicans, followed by C. glabrata and C. tropicalis. In 73% of 45 patients with candidemia, at least one of the serological tests was positive before the culture results, with mean time advantage being 6 days for Mn and 7 days for A-Mn. In 21 patients with hepatosplenic IC, 18 (86%) had Mn or A-Mn positive test results at a median of 16 days before radiological detection of liver or spleen lesions. Conclusions Mn and A-Mn are useful for diagnosis of IC. The performance of combined Mn/A-Mn testing is superior to either Mn or A-Mn testing.
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                Author and article information

                Journal
                Rev Inst Med Trop Sao Paulo
                Rev. Inst. Med. Trop. Sao Paulo
                rimtsp
                Revista do Instituto de Medicina Tropical de São Paulo
                Instituto de Medicina Tropical
                0036-4665
                1678-9946
                11 May 2020
                2020
                : 62
                : e25
                Affiliations
                [1 ]Sichuan University, West China Hospital, Department of Laboratory Medicine, Chengdu, China
                Author notes
                Correspondence to: Ying Ma Sichuan University, West China Hospital, Department of Laboratory Medicine, Chengdu, 610000, China Tel: +86 28 85422618 E-mail: majiying72@ 123456hotmail.com

                AUTHORS’ CONTRIBUTIONS

                Concept, design: Ying Ma; literature search, clinical studies, experimental studies: Mei Kang; data acquisition, data analysis, statistical analysis: Ziwei Kuang, Dongdong Li; manuscript preparation, manuscript editing, and manuscript review: Yanming Meng, Tingting Wang.

                CONFLICT OF INTERESTS

                No potential conflict of interests relevant to this article were reported.

                Author information
                http://orcid.org/0000-0003-1490-2622
                Article
                00214
                10.1590/S1678-9946202062025
                7232961
                32428065
                954ba654-5b02-4f8c-b681-0151249df8e0

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 November 2019
                : 1 March 2020
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 24
                Categories
                Original Article

                candidemia,anti-mannan,diagnosis
                candidemia, anti-mannan, diagnosis

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