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Volume 24, Number 8—August 2018
Online Report

Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings

David W. DenningComments to Author , Iain D. Page, Jeremiah Chakaya, Kauser Jabeen, Cecilia M. Jude, Muriel Cornet, Ana Alastruey-Izquierdo, Felix Bongomin, Paul Bowyer, Arunaloke Chakrabarti, Sara Gago, John Guto, Bruno Hochhegger, Martin Hoenigl, Muhammad Irfan, Nicholas Irurhe, Koichi Izumikawa, Bruce Kirenga, Veronica Manduku, Samihah Moazam, Rita O. Oladele, Malcolm D. Richardson, Juan Luis Rodriguez Tudela, Anna Rozaliyani, Helmut J.F. Salzer, Richard Sawyer, Nasilele F. Simukulwa, Alena Skrahina, Charlotte Sriruttan, Findra Setianingrum, Bayu A.P. Wilopo, Donald C. Cole, and Haileyesus Getahun
Author affiliations: University of Manchester, Manchester, UK (D.W. Denning, I.D. Page, F. Bongomin, P. Bowyer, S. Gago, R.O. Oladele, C. Sriruttan, F. Setianingrum, B.A.P. Wilopo); Wythenshawe Hospital Manchester University NHS Foundation Trust, Manchester (D.W. Denning, I.D. Page, S. Moazam, M.D. Richardson, R. Sawyer); The Global Action Fund for Fungal Infections, Geneva, Switzerland (D.W. Denning, J. Guto, J.L. Rodriguez Tudela); Kenya Medical Research Institute, Nairobi, Kenya (J. Chakaya, V. Manduku); Aga Khan University, Karachi, Pakistan (K. Jabeen, M. Irfan); Olive View–UCLA Medical Center, Sylmar, California, USA (C.M. Jude); Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France (M. Cornet); Instituto de Salud Carlos III, Madrid, Spain (A. Alastruey-Izquierdo); Postgraduate Institute of Medical Education and Research, Chandigarh, India (A. Chakrabarti); Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil (B. Hochhegger); University of California San Diego, San Diego, California, USA (M. Hoenigl); Medical University of Graz, Graz, Austria (M. Hoenigl); Center for Biomarker Research in Medicine, Graz (M. Hoenigl); Lagos University Teaching Hospital, Lagos, Nigeria (N. Irurhe); Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan (K. Izumikawa); Mulago Hospital and Makerere University, Kampala, Uganda (B. Kirenga); University of Lagos, Lagos (R.O. Oladele); Universitas Indonesia, Jakarta, Indonesia (A. Rozaliyani, F. Setianingrum); Research Center Borstel, Borstel, Germany (H.J.F. Salzer); Royal Liverpool University Hospital, Liverpool, UK (N.F. Simukulwa); The Republican Scientific and Practical Centre for Pulmonology and TB, Minsk, Belarus (A. Skrahina, C. Sriruttan); National Institute for Communicable Diseases, Johannesburg, South Africa (C. Sriruttan); University of the Witwatersrand, Johannesburg (C. Sriruttan); Universitas Padjadjaran, Bandung, Indonesia (B.A.P. Wilopo); University of Toronto, Toronto, Ontario, Canada (D.C. Cole); World Health Organization, Geneva (H. Getahun)

Main Article

Table 2

Performance of commercially available Aspergillus diagnostic serology tests for CPA*

Reference
Study population
Assay†
Cutoff
Sensitivity, %
Specificity, %
ROC/AUC (95% CI)
(56) 28 CPA patients DD, Microgen 89.3 ND ND


Bio-Rad galactomannan
GM index >0.5
50
ND
ND
(57) 51 CPA patients and 341 controls‡ Bio-Rad Platelia Aspergillus IgG 10 AU/ml 90.2 89.6 ND


Serion/Virion ELISA classic Aspergillus IgG
70 AU/mL
88.8
84.4
ND
(25) 49 simple aspergilloma patients IBL culture filtrate ELISA ND 99 ND ND


Bio-Rad galactomannan
GM index >0.5
23
ND
ND
(58) 116 CPA patients Bio-Rad Platelia Aspergillus IgG 10 AU/mL 86 ND ND
ThermoFisher Scientific ImmunoCAP 40 mg/L 85 ND ND


DD

56
ND
ND
(59) 168 CPA patients Bio-Rad galactomannan GM index >0.5 23 ND 0.538 (0.496–0.580)


DD
ND
98
ND
ND
(60)
89 CPA patients, 10 aspergilloma patients, 212 blood healthy donors
Aspergillus LDBio Western blot IgG kit
ND
CPA, 91.0; aspergilloma, 90.0
ND
ND
(49) 241 CPA patients, 100 blood donors from Uganda Dynamiker 65 AU/mL 77 97 0.918 (0.89–0.946)
Omega (Genesis) Aspergillus IgG ELISA kit 20 AU/mL 75 99 0.902 (0.871–0.933)
Immulite Siemens 10 mg/L 96 98 0.991 (0.982–1)
ThermoFisher Scientific Immunocap 20 mg/L 96 98 0.996 (0.992–1)
Serion/Virion ELISA classic Aspergillus IgG 35 AU/mL 90 98 0.973 (0.96–0.987)


Precipitins (Microgen)
ND
59
100
ND
(50) 17 simple aspergilloma patients, 62 CPA patients, 25 CNPA patients, 205 controls§ Bordier OD>1 Simple aspergilloma, 95.6; CPA, 97.4; CNPA: 100 90.3 0.997 (0.962–0.991)
Bio-Rad Platelia Aspergillus IgG 10 AU/mL Simple aspergilloma, 95.6; CPA, 97.4; CNPA, 100 91.3 0.951 (0.928–0.974)


Serion/Virion ELISA classic Aspergillus IgG
70 AU/mL
Simple aspergilloma, 78.3; CPA, 82.0; CNPA, 82.9
81.5
0.897 (0.863–0.931)
(51)
51 possible CPA patients, 96 proven CPA patients, 122 controls¶
ThermoFisher Scientific ImmunoCAP
50 mg/L
Possible CPA, 39.2; Proven CPA, 97.9
ND
0.94 (0.912–0.972)
(61) 241 CPA patients, 152 healthy controls from the Netherlands Siemens Immulite 25 mg/L 92.9 99.3 0.948 (0.921–0.975)
241 CPA patients, 141 healthy controls from Belgium ThermoFisher Scientific ImmunoCAP 50 mg/L 83.8 95.6 0.956 (0.937–0.974)
241 CPA patients, 222 healthy controls from France Serion 50 U/mL 84.2 91 0.944 (0.925–0.964)

118 CPA patients, 222 healthy controls from France
Bio-Rad
1.5 AU/mL
93.2
98.2
0.955 (0.922–0.988)
(62) 241 CPA patients, 299 healthy controls from Uganda Siemens Immulite 15 mg/L 94.6 98 0.984 (0.972–0.997)
241 CPA patients, 398 patients with treated TB from Uganda Siemens Immulite 15 mg/L 94.6 94.5 0.972 (0.959–0.985)
241 CPA patients, 234 patients with treated TB, radiologically screened for CPA from Uganda Siemens Immulite 25 mg/L 92.9 98.7 0.979 (0.967–0.992)

*AU, absorbance units; CPA, chronic pulmonary aspergillosis; CNPA, chronic necrotizing pulmonary aspergillosis; DD, double diffusion (precipitins); GM, galactomannan; ROC/AUC, receiver operating characteristic/area under the curve; OD, optical density;TB, tuberculosis; ND, not determined (did not test enough control serum to assess).
†Bio-Rad, Marnes-la-Coquette, France; Bordier, Crissier, Switzerland; DD, in-house test (58); Dynamiker, Tianjin, China; IBL, Hamburg, Germany; LDBio Diagnostics, Lyon, France; Microgen, Camberley, UK; Omega, Alva, Scotland, UK; Serion/Virion, Würzburg, Germany; Siemens, Camberley, UK; ThermoFisher, Uppsala, Switzerland.
‡Population included 26 patients with Aspergillus bronchial colonization, 44 patients with 1 positive Aspergillus culture considered as colonization, 49 patients with negative microbiological results, and 222 pregnant women.
§Control groups comprised 14 patients colonized with Aspergillus and 191 patients with respiratory symptoms.
¶Possible CPA, Aspergillus precipitin negative and a persistently elevated inflammation marker; proven CPA, Aspergillus precipitin positive and a persistently elevated inflammation marker; control, other chronic respiratory disease (any Aspergillus precipitin and temporary elevated inflammation marker).

Main Article

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