Introduction
Materials and methods
Studies and patients
Search methods for identification of studies
Statistical analysis
Results
Literature research and description of studies
First author, year of publication, country, type of study | Cutoff value of Mn and A-Mn, number of samples to declare positive | Underlying condition/risk factor for IC | Diagnostic criteria for Candidainfection (number of patients with different sites of IC) | No. of patients and no. of samples | No. (%) of patients with C. albicans | No. of control patients and samples | Type of control group | |
---|---|---|---|---|---|---|---|---|
1 | Verduyn Lunel et al., 2009, Netherlands, retrospective [31] | Mn ≥ 0.25 ng/ml A-Mn ≥ 5 AU/ml Single sample | Chemotherapy | Culture from a sterile site | 21 and 242 divided into: neutropenic for less or more than 15 days: 10 and 11, respectively | 12 (57%) | 30 and 390 | Patients with haematological malignancies |
2 | Ellis et al., 2009, UAE, prospective [26] | Mn ≥ 0.25 ng/ml; A-Mn ≥ 2.5 AU/ml Two consecutive samples positive for both Mn and A-Mn | Haematological malignancies | IC EORTC (5 candidemia and 7 hepatosplenic IC) | 12 and 216 | 1 | 74 | High-risk patients without IC (50 febrile neutropenia, 24 mould infection) |
3 | Sendid et al., 2008, France, retrospective [37] | Mn ≥ 0.5 ng/ml A-Mn ≥ 10 AU/ml Single sample | Mostly ICU and surgery, 14; haematological malignancy 2. | Candidemia | 18 and 69 | 18 (100%) | None | - |
4 | Oliveri et al., 2008, Italy, ND [24] | Mn ≥ 0.5 ng/ml Two samples | Neonatal ICU | Candidemia and probable IC defined as presence of sign and symptoms despite broad spectrum antibiotics + Candida colonisation | 18 (12 candidemia and 6 probable IC) and 18 | ND | 52 and 52 | Neonates from the same ward without IC |
5 | Alam et al., 2007, Kuwait, retrospective [28] | Mn ≥ 0.5 ng/ml A-Mn ≥ 10 AU/ml Single sample | Mostly ICU; 2 haematological malignancies | Candidemia | 27 and 32 | 18 (67%) | 26 and 26 | 10 patients with vaginal candidiasis, 16 healthy controls (39 patients with clinically suspected IC were not considered as a control group) |
6 | Fujita et al., 2006, Japan, retrospective [29] | Mn ≥ 0.5 ng/ml Single sample | Solid tumour, 69; haematological malignancy, 8; other, 28 | Candidemia | 105 and 251 | 49 (33%) | 175 and 178 | Febrile patients with or without bacteraemia |
7 | Prella et al., 2005, Switzerland, retrospective [25] | Mn ≥ 0.25 ng/ml A-Mn ≥ 5 AU/ml Two samples | Haematological malignancies | IC proven and probable according to EORTC (12 candidemia, 14 hepatosplenic IC) | 26 and ND | 5 (19%) | 25 and 163 | Patients with haematological malignancy and noncandidal infection |
8 | White et al., 2005, UK, retrospective [32] | Mn ≥ 0.5 ng/ml Single sample | Haematological malignancies, 14; other, 6 | IC EORTC for haematological patients and culture or underlying condition + signs and symptoms + colonisation for nonhaematological (2 proven, 13 probable hepatosplenic and 5 probable in non haematological) | 20 and ND | ND | 67 and ND | High-risk patients (not included 18 haematology patients with possible IC) |
9 | Sendid et al., 2004, France, retrospective [33] | Mn ≥ 0.5 ng/ml Single sample | Mostly ICU and surgery, 21; haematological malignancy, 3; other, 2. | Signs and symptoms + culture (19 candidemia, other culture sites included BAL in 5, bronchial biopsy and pleural liquid in 1) | 26 and 90 | 18 (69%) | 118 and 148 | 70 healthy donors, 10 patients with IFD, 24 high risk patients, mostly ICU, 14 subjects with high rheumatoid factor titres |
10 | Sendid et al., 2003, France, retrospective [27] | Mn ≥ 0.5 ng/ml A-Mn ≥ 10 AU/ml Single sample | Haematological malignancies | Candidemia due to C. tropicalis | 7 and 82 | 0 | 12 and 48 | Febrile neutropenic patients without candidemia |
11 | Sendid et al., 2002, retrospective [17] | Mn ≥ 0.5 ng/ml A-Mn ≥ 10 AU/ml Single sample | Mostly ICU and surgery, 41; haematological malignancies, 10; other, 12 | Signs and symptoms + culture (58 candidemia, 2 peritoneum cultures, 2 spleen cultures) | 63 and 204 | 21 (33%) and C. glabrata, 12; C. tropicalis, 10; C. parapsilosis, 10; C. krusei, 8 | None | - |
12 | Persat et al., 2002, France, retrospective [34] | Mn ≥ 0.5 ng/ml A-Mn ≥ 10 AU/ml Single sample | Cancer, 7; haematological malignancy, 6; surgery, 2; other, 7 | IC EORTC | 22 and 22 | 14 (64%) | 38 and 38 | 10 healthy individuals, 10 patients at risk but without IC, 18 with Candida colonisation |
13 | Yera et al., 2001, France, retrospective [18] | Mn ≥ 0.5 ng/ml A-Mn ≥ 10 AU/ml Single sample | ICU and surgery, 32; haematological malignancies, 11; other, 2 | Candidemia | 45 and 137 | 23 (51%) | None | - |
14 | Sendid et al., 1999, France, retrospective [16] | Mn ≥ 0.5 ng/ml A-Mn ≥ 10 AU/ml Single sample | ICU and surgery, 32; haematological malignancy, 1, other, 10 | Signs and symptoms + culture from a sterile site (23 candidemia, 14 surgery drain cultures) | 43 and 162 | 43 (100%) | 150 and 230 | 98 healthy blood donors and 52 hospitalised patients without IC (of them 29 with IFD: 12 IA, 13 cryptococcosis and 4 PCP) |
Sensitivity, specificity and diagnostic odds ratio
Study | Sensitivity (95% CI), absolute numbers: true positives/total | Specificity (95% CI), absolute numbers: true negatives/total | DOR (95% CI) | ||||||
---|---|---|---|---|---|---|---|---|---|
Mn | A-Mn | Mn/A-Mn | Mn | A-Mn | Mn/A-Mn | Mn | A-Mn | Mn/A-Mn | |
1. Verduyn Lunel et al., 2009 [31] | 0.38 (0.18-0.62), 8/21 | 0.52 (0.30-0.74), 11/21 | 0.71 (0.48-0.89), 15/21 | 0.83 (0.65-0.94), 25/30 | 0.90 (0.73-0.98), 27/30 | - | 3.1 (0.8-11.3) | 9.9 (2.3-43) | - |
2. Ellis et al., 2009 [26]b | 0.75 (0.43-0.95), 9/12 | 1.00 (0.74-1.00), 12/12 | 1.00 (0.74-100), 12/12 | 0.65 (0.53-0.76), 48/74 | 0.38 (0.27-0.50), 28/74 | 0.80 (0.69-0.88), 59/74 | 5.5 (1.4-22.3) | 15.3 (0.9-268.9) | 96 (5.4-1712) |
3. Sendid et al., 2008 [37] | 0.67 (0.41-0.87), 12/18 | 0.78 (0.52-0.94), 14/18 | 0.94 (0.73-0.99), 17/18 | - | - | - | - | - | - |
4. Oliveri et al., 2008 [24] | 0.94 (0.73-0.99), 17/18 | - | - | 0.94 (0.84-0.99), 49/52 | - | - | 277.7 (27-2852.3) | - | - |
5. Alam et al., 2007 [28] | 0.48 (0.29-0.68), 13/27 | 0.52 (0.32-0.71), 14/27 | 0.81 (0.62-0.94), 22/27 | 1.00 (0.87-1.00), 26/26 | 0.92 (0.75-0.99), 24/26 | 0. 92 (0.75-0.99), 24/26 | 49.3 (2.7-891.8) | 12.9 (2.5-65.8) | 52.8 (9.3-300.5) |
6. Fujita et al., 2006 [29] | 0.53 (0.43-0.63), 56/105 | - | - | 0.92 (0.87-0.96), 161/175 | 13.1 (6.7-25.6) | - | - | ||
7. Prella et al., 2005 [25] | 0.31 (0.14-0.52), 8/26 | 0.81 (0.61-0.93), 21/26 | 0.88 (0.70-0.98), 23/26 | 0.96 (0.80-0.99), 24/25 | 0.88 (0.69-0.97), 22/25 | 0.84 (0.64-0.95), 21/25 (all 4 colonised) | 10.7 (1.2-93.1) | 30.8 (6.5-145.3) | 40.3 (8.1-201.3) |
8. White et al., 2005 [32] | 0.75 (0.51-0.91), 15/20 | - | - | 0.97 (0.90-0.99), 65/67 | - | - | 97.5 (17.2-551.8) | - | - |
9. Sendid et al., 2004 [33] | 0.69 (0.48-0.86), 18/26 | - | - | 0.97 (0.93-0.99), 115/118 | - | - | 86.3 (20.9-355.7) | - | - |
10. Sendid et al., 2003 [27] | 1.00 (0.59-1.00), 7/7 | 0.71 (0.29-0.96), 5/7 | 1.00 (0.59-1.00), 7/7 | 0.92 (0.62-0.99), 11/12 | 1.00 (0.74-1.00), 12/12 | 0.92 (0.62-0.99), 11/12 | 115 (4.1-3213.5) | 55 (2.2-1346,2) | 115 (4.1-3213.5) |
11. Sendid et al., 2002 [17] | 0.52 (0.39-0.65), 33/63 | 0.44 (0.32-0.58), 28/63 | 0.76 (0.64-0.86), 48/63 | - | - | - | - | - | - |
12. Persat et al., 2002 [34] | 0.86 (0.65-0.97), 19/22 | 0.59 (0.36-0.79), 13/22 | 0.95 (0.77-0.99), 21/22 | 0.79 (0.63-0.90), 30/38 | 0.63 (0.46-0.78), 24/38 | 0.53 (0.36-0.69), 20/38 | 23.8 (5.6-100.8) | 2.48 (0.9-7.3) | 23.3 (2.8-191.5) |
13. Yera et al., 2001 [18] | 0.58 (0.42-0.72), 26/45 | 0.53 (0.38-0.68), 24/45 | 0.78 (0.63-0.89), 35/45 | - | - | - | - | - | - |
14. Sendid et al., 1999 [16] | 0.42 (0.27-0.58), 18/43 | 0.56 (0.40-0.71), 24/43 | 0.84 (0.69-0.93), 36/43 | 0.98 (0.94-0.99), 147/150 | 0.97 (0.92-0.99), 145/150 | 0.95 (0.90-0.98), 142/150 | 35.3 (9.7-128.6) | 36.6 (12.5-107.4) | 91.3 (31.1-268.4) |
Median of all the studies (range) | 0.62 (0.31-1.0) | 0.57 (0.44-1.0) | 0.86 (0.71-1.0) | 0.94 (0.65-1.0) | 0.9 (0.38-1.0) | 0. 88 (0.53-0.92) | |||
Pooled overall | 0.58 (0.53-0.62), 259/453 | 0.59 (0.54-0.65), 166/284 2 | 0.83 (0.79-0.87), 236/284c | 0.93 (0.91-0.94), 701/767d | 0.83 (0.79-0.87), 282/355e | 0.86 (0.82-0.90), 277/325f | 18.6 (12.5-27.7)d | 12.1 (7-20.8)e | 57.5 (27.1-122)f |
Study | Mn | A-Mn | Mn/A-Mn | Mn | A-Mn | Mn/A-Mn |
---|---|---|---|---|---|---|
Verduyn Lunel, 2009 [31] | 0.17 (0.13-0.22), 41/240 | 0.39 (0.33-0.45), 93/238 | - | 0.95 (0.92-0.97), 379/390 | 0.87 (0.83-0.90), 347/384 | - |
Sendid, 2008 [37] | 0.67 (0.55-0.77), 46/69 | 0.35 (0.25-0.47), 24/69 | - | - | - | - |
Fujita, 2006 [29] | 0.45 (0.39-0.51), 112/251 | - | - | 0.92 (0.87-0.95), 164/178 | ||
Sendid et al., 2003 [27] | 0.54 (0.43-0.64), 44/82 | 0.23 (0.15-0.33), 19/82 | 0.68 (0.58-0.77), 56/82 | 0.98 (0.89-0.99), 47/48 | 1 (0.93-1.0), 48/48 | 0.98 (0.89-0.99), 47/48 |
Sendid et al., 2002 [17] | 0.35 (0.29-0.42), 72/204 | 0.27 (0.22-0.34), 56/204 | 0.55 (0.49-0.62), 113/204 | - | - | - |
Sendid et al., 1999 [16] | 0.27 (0.20-0.34), 43/162 | 0.39 (0.32-0.47), 63/162 | 0.62 (0.55-0.69), 101/162 | 0.99 (0.96-0.99), 227/230 | 0.96 (0.93-0.98), 221/230 | 0.94 (0.91-0.97), 218/230 |
Median of all the studies (range) | 0.40 (0.17-0.67) | 0.35 (0.23-0.39) | 0.62 (0.55-0.68) | 0.97 (0.92-0.99) | 0.96 (0.87-1.0) | 0.96 (0.94-0.98) |
Different Candidaspecies
Species | Study | Number of isolates | Sensitivity | ||
---|---|---|---|---|---|
Mn | A-Mn | Mn/A-Mn | |||
C. albicans
| Fujita et al., 2006 [29] | 49 | 78% | ||
Sendid et al., 2002 [17] | 21 | 62% | 67% | 100% | |
C. tropicalis
| Sendid et al., 2002 [17] | 10 | 70% | 60% | 80% |
Fujita et al., 2006 [29] | 9 | 67% | |||
Sendid et al., 2003 [27] | 7 | 100% | 71% | 100% | |
C. glabrata
| Sendid et al., 2002 [17] | 12 | 58% | 83% | 83% |
Fujita et al., 2006 [29] | 11 | 36% | |||
C. guilliermondi
| Fujita et al., 2006 [29] | 11 | 27% | ||
C. parapsilosis
| Fujita et al., 2006 [29] | 20 | 15% | ||
Sendid et al., 2002 [17] | 10 | 30% | 10% | 40% | |
C. krusei
| Sendid et al., 2002 [17] | 8 | 25% | 38% | 50% |
Fujita et al., 2006 [29] | 2 | 0 |
Timing of diagnosis
Possible invasive candidiasis and colonisation
Discussion
Conclusions
Key messages
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Diagnosis of IC is difficult in high-risk patients, thus noninvasive tests that detect Candida components in the serum of patients with IC have been developed.
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Performance of Mn and A-Mn antibody tests was analysed and reviewed on behalf of ECIL-3.
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Overall, 14 studies that included haematological malignancy and ICU patients were reviewed.
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Moderate sensitivity and good specificity of Mn and A-Mn were found (Mn, 58% and 93%; A-Mn, 59% and 83%, respectively).
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Combined Mn/A-Mn testing was better than each test alone (sensitivity 83% and specificity 86%).
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Combined Ma/A-Mn testing improves the diagnosis of IC in ICU or surgery and haematology patients.