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Current Fungal Infection Reports

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01-12-2019 | Primary Immunodeficiency | Pediatric Fungal Infections (D Corzo-Leon, Section Editor)

From Culture to Fungal Biomarkers: the Diagnostic Route of Fungal Infections in Children with Primary Immunodeficiencies

Authors: Catherine Mark, Claire McGinn

Published in: Current Fungal Infection Reports | Issue 4/2019

Abstract

Purpose of Review

To provide an overview of the diagnostic tests available to identify invasive fungal disease (IFD) in children with a primary immunodeficiency and to evaluate the relative strengths and weaknesses of those tests.

Recent Findings

Novel tools to aid the diagnosis of IFD, such as fungal PCRs and lateral flow devices (for Aspergillus spp.), are emerging. However, the paucity of high-quality, multicentre clinical trials evaluating the performance of these diagnostic tools, particularly in the paediatric cohort of interest, remains a challenge. Children with primary immunodeficiencies are seldom referenced in existing studies.

Summary

It is difficult to provide recommendations for the majority of fungal diagnostic tests, with the exception of histopathology, microscopy, culture, and imaging modalities, due to their poorly studied and largely unvalidated nature. Moving forward, multicentre trials considering the role of these tools in the investigation of children with probable IFD and a primary immunodeficiency are strongly encouraged.

Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L, et al. Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey. Medicine (Baltimore). 2012;91:e1–19. https://doi.org/10.1097/MD.0b013e31825f95b9.CrossRefPubMedCentral

Garraffo A, Pilmis B, Toubiana J, Puel A, Mahlaoui N, Blanche O, et al. Invasive fungal infection in primary immunodeficiencies other than chronic granulomatous disease. Current Fungal Infection Reports. 2017;11:25–34. https://doi.org/10.1007/s12281-017-0273-x.CrossRef

Beauté J, Obenga G, Le Mignot L, Mahlaoui N, Bougnoux ME, Mouy R, et al. Epidemiology and outcome of invasive fungal diseases in patients with chronic granulomatous disease: a multicenter study in France. Pediatric Infectious Diseases Journal. 2011;30:57–62. https://doi.org/10.1097/INF.0b013e3181f13b23.CrossRef

Lanternier F, Cypowyj S, Picard C, Bustamante J, Lortholary O, Casanova JL, et al. Primary immunodeficiencies underlying fungal infections. Current Opinions in Pediatrics. 2013;25:736–47. https://doi.org/10.1097/MOP.0000000000000031.CrossRef

Antachopoulos C. Invasive fungal infections in congenital immunodeficiencies. Clinical Microbiology and Infection. 2010;16(9):1335–42. https://doi.org/10.1111/j.1469-0691.2010.03289.x.CrossRefPubMed

Odio CD, Milligan KL, McGowan K, Rudman Spergel AK, Bishop R, Boris L, et al. Endemic mycoses in patients with STAT3-mutated hyper-IgE (Job) syndrome. Journal of Allergy and Clinical Immunology. 2015;136:1411–3. https://doi.org/10.1016/j.jaci.2015.07.003.CrossRefPubMed

Pana ZD, Roilides E, Warris A, Groll AH, Zaoutis T. Epidemiology of Invasive Fungal Disease in Children. Journal of Pediatric Infectious Diseases Society. 2017;6(1):S3–S11. https://doi.org/10.1093/jpids/pix046.CrossRef

Jones N, Garcez T, Newman W, Denning D. Endogenous Candida endophthalmitis and osteomyelitis associated with CARD9 deficiency. BMJ Case Reports. 2016;3:2016. https://doi.org/10.1136/bcr-2015-214117.CrossRef

Drewniak A, Gazendam RP, Tool AT, Van Houdt M, Jansen MH, Van Hamme J. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood. 2013;121:2385–92. https://doi.org/10.1182/blood-2012-08-450551.CrossRefPubMed

10.

• De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from 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) consensus group. Clinical Infectious Diseases. 2008;46:1813–21. https://doi.org/10.1086/588660Provides the reader with clear definitions, and guidelines for the diagnosis of, possible, probable and proven IFD.CrossRefPubMedPubMedCentral

11.

Thomas KE, Owens CM, Veys PA, Novelli V, Costoli V. The radiological spectrum of invasive aspergillosis in children: a 10-year review. Pediatric Radiology. 2003;33:453–60. https://doi.org/10.1007/s00247-003-0919-4.CrossRefPubMed

12.

•• Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clinical Microbiology and Infection. 2018;24:e1–e38. https://doi.org/10.1016/j.cmi.2018.01.002Useful overview of the investigative work-up for patients with suspected IPA.CrossRefPubMed

13.

Rüchel R, Schaffrinski M. Versatile fluorescent staining of fungi in clinical specimens by using the optical brightener blankophor. Journal of Clinical Microbiology. 1999;37:2694–6.PubMedPubMedCentral

14.

Clancy CJ, Nguyen MH. Finding the "missing 50%" of invasive candidiasis: how non-culture diagnostics will improve understanding of disease spectrum and transform patient care. Clinical Infectious Diseases. 2013;56:1284–92. https://doi.org/10.1093/cid/cit006.CrossRefPubMed

15.

•Cuenca-Estrella M, Verweij PE, Arendrup MC, Arikan-Akdagli S, Bille J, Donnelly JP, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clinical Microbiology and Infection 2012:18(S7):9–18. Doi: https://doi.org/10.1111/1469-0691.12038. Useful inclusion of recommendations for paediatric patients. CrossRefPubMed

16.

Parta M, Hilligoss D, Kelly C, Kwatemaa N, Theobald N, Malech H, et al. Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in a Patient with Chronic Granulomatous Disease and Active Infection: A First Report. Journal of Clinical Immunology. 2015;35(7):675–80. https://doi.org/10.1007/s10875-015-0204-y.CrossRefPubMedPubMedCentral

17.

Liss B, Vehreschild JJ, Bangard C, Maintz D, Frank K, Gronke D, et al. Our 2015 approach to invasive pulmonary aspergillosis. Mycoses. 2016;58:375–82. https://doi.org/10.1111/myc.12319.CrossRef

18.

Sisli E, Ozdemir Sahan Y, Ayik MF, Nart D, Atay Y. A rare complication of chronic granulomatous disease in a child: constrictive aspergillus pericarditis. Archives of the Turkish Society of Cardiology. 2017;45(7):660–3. https://doi.org/10.5543/-tkda.2017.52284.CrossRefPubMed

19.

Maaloul I, Ameur SB, Chabchoub I, Kolsi R, Bahloul M, Kamoun T, et al. Fulminant mulch pneumonitis in a previously healthy child. Archives de Pediatrie. 2018;25(8):495–6. https://doi.org/10.1016/j.arcped.2018.09.003.CrossRefPubMed

20.

• Fujita Y, Ishiwada N, Takei H, Suwabe SI, Yarita K, Ohkusu M, et al. Usefulness of Gastric Aspirate Culture for Diagnosing Congenital Immunodeficiency in an Infant with Fungal Pneumonia Caused by Rasamsonia piperina. The Tohoku Journal of Experimental Medicine. 2019;247(4):265–9. https://doi.org/10.1620/tjem.247.265Authors present a novel means of obtaining tissue for fungal culture, of interest given the challenges this can provide in paediatric practice.CrossRefPubMed

21.

Sodhi KS, Khandelwal N, Saxena AK, Singh M, Agarwal R, Bhatia A, et al. Rapid lung MRI in children with pulmonary infections: time to change our diagnostic algorithms. Journal of Magnetic Resonance Imaging. 2016;43:1196–206. https://doi.org/10.1002/jmri.25082.CrossRefPubMed

22.

Maschmeyer G, Carratala J, Buchheidt D, Hamprecht A, Heussel CP, Kahl C, et al. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the infectious diseases working party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Annals of Oncology. 2015;26:21–33. https://doi.org/10.1093/annonc/mdu192.CrossRefPubMed

23.

• Davies BW, Gonzalez MO, Vaughn RC, Allen GC, Durairaj VD. Dacryocystitis as the initial presentation of invasive fungal sinusitis in immunocompromised children. Ophthalmic plastic and reconstructive surgery. 2016;32(4):e79–81. https://doi.org/10.1097/IOP.-0000000000000252Highlights the atypical presentation of IFD observed in vulnerable paediatric patients.CrossRefPubMed

24.

Bruno C, Minniti S, Vassanelli A, Pozzi-Mucelli R. Comparison of CT features of Aspergillus and bacterial pneumonia in severely neutropenic patients. Journal of Thoracic Imaging. 2007;22:160–5. https://doi.org/10.1097/RTI.0b013e31805f6a42.CrossRefPubMed

25.

Franquet T, Gimenez A, Hidalgo A. Imaging of opportunistic fungal infections in immunocompromised patient. European Journal of Radiologyl. 2004;51(2):130–8. https://doi.org/10.1016/j.ejrad.2004.03.007.CrossRef

26.

Althoff Souza C, Muller NL, Marchiori E, Escuissato DL, Franquet T. Pulmonary invasive aspergillosis and candidiasis in immunocompromised patients: a comparative study of the high-resolution CT findings. Journal of Thoracic Imaging. 2006;21:184–9. https://doi.org/10.1097/01.rti.0000213552.16011.ad.CrossRefPubMed

27.

Dotis J, Pana ZD, Roilides E. Non-Aspergillus fungal infections in chronic granulomatous disease. Mycoses. 2013;56:449–62. https://doi.org/10.1111/myc.12049.CrossRefPubMed

28.

Vinh DC, Shea YR, Jones PA, Freeman AF, Zelazny A, Holland SM. Chronic invasive aspergillosis caused by Aspergillus viridinutans. Emerging Infectious Diseases. 2009;15:1292–4. https://doi.org/10.3201/-eid1508.090251.CrossRefPubMedPubMedCentral

29.

Haidar G, Zerbe CS, Cheng M, Zelazny AM, Holland SM, Sheridan KR. Phellinus species: An emerging cause of refractory fungal infections in patients with X-linked chronic granulomatous disease. Mycoses. 2017;60(3):155–60. https://doi.org/10.1111/myc.12573.CrossRefPubMed

30.

• De Ravin SS, Parta M, Sutton DA, Wickes BL, Thompson EH, Wiederhold NP, et al. Paravertebral mushroom: identification of a novel species of Phellinus as a human pathogen in chronic granulomatous disease. Journal of Clinical Microbiology. 2014;52:2726–9. https://doi.org/10.1128/JCM.00667-14Important reminder that growth of indolent organisms can be encouraged by prophylactic prescription.CrossRefPubMedPubMedCentral

31.

Pappas PG, Kauffman CA, Andes D, Clancy CJ, Marr K, Ostrosky-Zeichner L, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2016;62(4):e1–e50. https://doi.org/10.1093/cid/civ933.CrossRefPubMed

32.

•• Hope WW, Castagnola E, Groll AH, Roilides E, Akova M, Arendrup MC, et al. ESCMID^* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clinical Microbiology and Infection. 2012;18:38–52. https://doi.org/10.1111/1469-0691.12040Guideline for the management of candidiasis, specifically in children.CrossRefPubMed

33.

• Groll AH, Castagnola E, Cesaro S, Dalle JH, Engelhard D, Hope W, et al. Fourth European Conference on Infections in Leukaemia(ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncology. 2014;15(8):e327–40. https://doi.org/10.1016/S1470-2045(14)70017-8Although largely pertaining to management of paediatric haemoncology patients, this paper provides an excellent overview of fungal diagnostic tools and was the first guideline devised for children with cancer and an IFD.CrossRefPubMed

34.

• Huppler AR, Fisher BT, Lehrnbecher T, Walsh TJ, Steinbach WJ. Role of Molecular Biomarkers in the Diagnosis of Invasive Fungal Diseases in Children. Journal of the Pediatric Infectious Disease Society. 2017;6(1):32–44. https://doi.org/10.1093/jpids/pix054Excellent overview of fungal biomarkers and their role in the diagnosis of IFD.CrossRef

35.

Theel E, Doern C. β-D-glucan testing is important for diagnosis of invasive fungal infections. Journal of Clinical Microbiology. 2013;51(11):3478–83. https://doi.org/10.1128/JCM.01737-13.CrossRefPubMedPubMedCentral

36.

Tran T, Beal S. Application of the 1,3-β-d-Glucan (Fungitell) Assay in the Diagnosis of Invasive Fungal Infections. Archives of Pathology and Laboratory Medicine. 2016;140(2):181–5. https://doi.org/10.5858/arpa.2014-0230-RS.CrossRefPubMed

37.

Fontana C, Gaziano R, Favaro M, Ia C, Pistoia E, Di Francesco P. (1-3)-β-D-Glucan vs Galactomannan Antigen in Diagnosing Invasive Fungal Infections (IFIs). Open Microbiology Journal. 2012;6:70–3. https://doi.org/10.2174/1874285801206010070.CrossRefPubMed

38.

Bernabé F, Chumpitazi F, Lebeau B, Faure-Cognet O, Hamidfar-Roy R, Timsit JF, et al. Characteristic and clinical relevance of Candida mannan test in the diagnosis of probable invasive candidiasis. Medical Mycology. 2014;52(5):462–71. https://doi.org/10.1093/mmy/myu018.CrossRef

39.

Del Bono V, Delfino E, Furfaro E, Mikulska M, Nicco E, Bruzzi P, et al. Clinical performance of the (1, 3)-Beta-D-glucan assay in early diagnosis of nosocomial Candida bloodstream infections. Clinical and Vaccine Immunology. 2011;18(12):2113–7. https://doi.org/10.1128/CVI.05408-11.CrossRefPubMed

40.

He S, Hang JP, Zhang L, Wang F, Zhang DC, Gong FH. A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-beta-D-glucan for invasive fungal infections: focus on cutoff levels. Journal of Microbiology, Immunology and Infection. 2015;48(4):351–61. https://doi.org/10.1016/j.jmii.-2014.06.009.CrossRef

41.

Smith PB, Benjamin DK Jr, Alexander BD, Johnson MD, Finkleman MA, Steinbavh WJ. Quantification of 1,3-beta-d-glucan levels in children: preliminary data for diagnostic use of the beta-glucan assay in a pediatric setting. Clinical and Vaccine Immunology. 2007;14(7):924–5. https://doi.org/10.1128/CVI.00025-07.CrossRefPubMed

42.

•• Calitri C, Caviglia I, Cangemi G, Furfaro E, Bandettini R, Fioredda F, et al. Performance of 1,3-β-D-glucan for diagnosing invasive fungal diseases in children. Mycoses. 2017;60(12):789–95. https://doi.org/10.1111/myc.12664Interesting study that questions the performance of 1,3-β-D-glucan in the paediatric cohort.CrossRefPubMed

43.

• Salvatore CM, Petraitiene R, Sitaras L, Hammad H, Leimena P, Toussi S, et al. Prospective study and analytical performance of serum (1->3)-β-d-glucan in pediatric patients. New Orleans, LA: Program and Abstracts of ID Week. Open Forum Infectious Diseases. 2016;3(1):1570. https://doi.org/10.1093/ofid/ofw172.1270Further explores the utility of 1,3-β-D-glucan in paediatric practice.CrossRef

44.

Naselli A, Faraci M, Lanino E, Morreale G, Cangemi G, Bandettini R, et al. Persistence of high-level (1,3)-β-d-glucan after candidemia following autologous peripheral SCT in a pediatric patient. Bone Marrow Transplant. 2015;50:137–8.CrossRef

45.

Roilides E, Pana ZD. Application of diagnostic markers to invasive aspergillosis in children. Annals of the New York Academy of Sciences. 2012;1272:1–8. https://doi.org/10.1111/j.1749-6632.2012.06828.x.CrossRefPubMed

46.

Fisher BT. The role of biomarkers for diagnosis of and therapeutic decisions related to invasive aspergillosis in children. Current Fungal Infection Reports. 2013;7(1):7–14. https://doi.org/10.1007/s12281-012-0127-5.CrossRefPubMedPubMedCentral

47.

• Henriet S, Verweij PE, Holland SM, Warris A. Invasive fungal infections in patients with chronic granulomatous disease. Advances in Experimental Medicine and Biology. 2013;764:27–55. https://doi.org/10.1007/978-1-4614-4726-9_3Particular focus on CGD: a disease process which has taught much about IFD and the relative merits of the available diagnostic tests.CrossRefPubMed

48.

Walsh TJ, Schaufele RL, Sein T. Gea-Banacloche J, Bishop M, Young N, et al. Reduced expression of galactomannan antigenemia in patients with invasive aspergillosis and chronic granulomatous disease or Job’s syndrome. Program and Abstracts of the 40th Annual Meeting of the Infectious Diseases Society of America; 24–27 October 2002; Chicago, IL.

49.

Lehrnbecher T, Robinson P, Fisher B, Alexander S, Ammann RA, Beauchemin M, et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem cell transplantation recipients: 2017 update. Journal of Clinical Oncology. 2017;35:2082–94. https://doi.org/10.1200/JCO.2016.71.7017.CrossRefPubMed

50.

•• Warris A, Lehrnbecher T, Roilides E, Castagnola E, Bruggemann RJM, Groll AH. Escmid-ecmm guideline: diagnosis and management of invasive aspergillosis in neonates and children. Clinical Microbiology and Infection. 2019. https://doi.org/10.1016/j.cmi.2019.05.019One of the key paediatric guidelines directing management of children with IA.CrossRef

51.

D'Haese J, Theunissen K, Vermeulen E, Schoemans H, De Vlieger G, Lammertijn L, et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. Journal of Clinical Microbiology. 2012;50(4):1258–63. https://doi.org/10.1128/JCM.06423-11.CrossRefPubMedPubMedCentral

52.

Duarte R, Sánchez-Ortega I, Cuesta I, Arnan M, Patiño B, Fernández de Sevilla A, et al. Serum galactomannan–based early detection of invasive Aspergillosis in hematology patients receiving effective anti-mold prophylaxis. Clinical Infectious Diseases. 2014;59(12):1696–702. https://doi.org/10.1093/cid/ciu673.CrossRefPubMed

53.

Thornton CR. Development of an immunochromatographic lateral flow device for rapid serodiagnosis of invasive aspergillosis. Clinical Vaccine Immunology. 2008;15(7):1095–105. https://doi.org/10.1128/CVI.00068-08.CrossRefPubMed

54.

Hoenigl M, Prattes J, Spiess B, Wagner J, Prueller F, Raggam RB, et al. Performance of galactomannan, beta-d-glucan, Aspergillus lateral-flow device, conventional culture, and PCR tests with bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis. Journal of Clinical Microbiology. 2014;52(6):2039–45. https://doi.org/10.1128/JCM.00467-14.CrossRefPubMedPubMedCentral

55.

White PL, Parr C, Thornton C, Barnes RA. Evaluation of real-time PCR, galactomannan enzyme-linked immunosorbent assay (ELISA) and a novel lateral flow device for diagnosis of invasive Aspergillosis. Journal of Clinical Microbiology. 2013;51(5):1510–6. https://doi.org/10.1128/JCM.03189-12.CrossRefPubMedPubMedCentral

56.

Marchetti O, Lamoth F, Mikulska M, Viscoli C, Verweij P, Bretagne S, et al. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplant. 2012;47(6):846–54. https://doi.org/10.1038/bmt.2011.178.CrossRefPubMed

57.

Oliveri S, Trovato L, Betta P, Romeo MG, Nicoletti G. Experience with the Platelia Candida ELISA for the diagnosis of invasive candidosis in neonatal patients. Clinical Microbiology and Infection. 2008;14(4):391–3. https://doi.org/10.1111/j.1469-0691.2007.01938.x.CrossRefPubMed

58.

• Mokaddas E, Burhamah MH, Khan ZU, Ahmad S. Levels of (1→3)-β-D-glucan, Candida mannan and Candida DNA in serum samples of pediatric cancer patients colonized with Candida species. BMC Infectious Diseases. 2010;10:292. https://doi.org/10.1186/1471-2334-10-292Highlights weaknesses of theCandidamannan assay when it is employed to as a diagnostic tool in paediatric patients.CrossRefPubMedPubMedCentral

59.

Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C. Third European Conference on Infections in Leukemia Group. 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. Critical Care. 2010;14(6):222. https://doi.org/10.1186/cc9365.CrossRef

60.

White PL, Wingard JR, Bretagne S, Loffler J, Patterson TF, Slavin MA, et al. Aspergillus polymerase chain reaction: systematic review of evidence for clinical use in comparison with antigen testing. Clinical Infectious Diseases. 2015;61:1293–303. https://doi.org/10.1093/cid/civ507.CrossRefPubMedPubMedCentral

61.

Hadir A, El-Mahallawy H, Shaker Hala A, Tarek M, Razak A. Evaluation of pan-fungal PCR assay and Aspergillus antigen detection in the diagnosis of invasive fungal infections in high risk paediatric cancer patients. Medical Mycology. 2006;44(8):733–9. https://doi.org/10.1080/13693780600939955.CrossRef

62.

Arendrup MC, Fisher BT, Zaoutis TE. Invasive fungal infections in the paediatric and neonatal population: diagnostics and management issues. Clinical Microbiology and Infection. 2009;15(7):613–24. https://doi.org/10.1111/j.1469-0691.2009.02909.x.CrossRefPubMed

63.

Frank-Michael C, Muller E, Trusen A, Weig M. Clinical Manifestations and diagnosis of invasive aspergillosis in immunocompromised children. European Journal of Paediatrics. 2002;161(11):563–74. https://doi.org/10.1007/s00431-002-1041-6.CrossRef

64.

• Boch T, Spiess B, Vehreschild JJ, Rath PM, Steinmann J, Heinz WJ, et al. Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-β-D-glucan, Aspergillus PCR, multifungal DNA-microarray, and Aspergillus azole resistance PCRs in blood and bronchoalveolar lavage samples: results of a prospective multicentre study. Clinical Microbiology and Infection. 2016;22(10):862–8. https://doi.org/10.1016/j.cmi.2016.06.021Interesting data: BAL vs serum testing.CrossRefPubMed

65.

Reinwald M, Konietzka CA, Kolve H, Uhlenbrock S, Ahike E, Hummel M, et al. Assessment of Aspergillus-specific PCR as a screening method for invasive aspergillosis in paediatric cancer patients and allogeneic haematopoietic stem cell recipients with suspected infections. Mycoses. 2014;57:537–43. https://doi.org/10.1111/myc.12192.CrossRefPubMed

66.

Hummel M, Spiess B, Roder J, van Komorowski G, Kürken M, Kentouche K, et al. Detection of Aspergillus DNA by a nested PCR assay is able to improve the diagnosis of invasive aspergillosis in paediatric patients. Journal of Medical Microbiology. 2009;58:1291–7. https://doi.org/10.1099/jmm.0.007393-0.CrossRefPubMed

67.

• Vrioni G, Theodoridou K, Tsiamis C, Mavrouli M, Kapsimali V, Rigopoulos D, et al. Use of Galactomannan antigen and Aspergillus DNA real time polymerase chain reaction as routine methods for invasive aspergillosis in immunosuppressed children in Greece. Clinical Therapeutics. 2018;40(6):918–24. https://doi.org/10.1016/j.clinthera.2018.05.002Supportive evidence for combining GM andAspergillusPCR, in the clinical setting.CrossRefPubMed

68.

Taira CL, Okay TS, Delgado AF, Ceccon ME, de Almeida MT, Del Negro GM. A multiplex nested PCR for the detection and identification of Candida species in blood samples of critically ill paediatric patients. BMC Infectious Diseases. 2014;14:406–2334. https://doi.org/10.1186/1471-2334-14-406.CrossRefPubMedPubMedCentral

69.

Lucignano B, Ranno S, Liesenfeld O, Pizzorno B, Putignani L, Bernaschi P, et al. Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. Journal of Clinical Microbiology. 2011;49:2252–8. https://doi.org/10.1128/JCM.02460-10.CrossRefPubMedPubMedCentral

70.

• Clancy C, Nguyen M. T2 magnetic resonance for the diagnosis of bloodstream infections:charting a path forward. Journal of Antimicrobial Chemotherapy. 2018;73(4):2–5. https://doi.org/10.1093/jac/dky050Exciting prospect, moving forward, to consider MR technology facilitating more rapid turnaround of PCR based methods.CrossRef

71.

Mylonakis E, Clancy CJ, Ostrosky-Zeichner L. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clinical Infectious Diseases. 2015;60:892–9.CrossRef

72.

Patch ME, Weisz E, Cubillos A. Impact of rapid, culture independent diagnosis of candidemia and invasive candidiasis in a community health system. Journal of Antimicrobial Chemotherapy. 2018;73(4):27–30.CrossRef

73.

Hamula C, Hughes K, Fisher B, Zaoutis T, Singh I, Velegraki A, et al. T2Candida provides rapid and accurate species identification in pediatric cases of candidemia. American Journal of Clinical Pathology. 2016;145(6):858–61. https://doi.org/10.1093/ajcp/aqw063.CrossRefPubMed

74.

Wellinghausen N, Siegel D, Winter J, Gebert S. Rapid diagnosis of candidemia by real-time PCR detection of Candida DNA in blood samples. Journal of Medical Microbiology. 2009;58:1106–11. https://doi.org/10.1099/jmm.0.007906-0.CrossRefPubMed

75.

Ao W, Klonoski J, Berlinghoff E, Jensen J, Afroz T, Munns D, et al. Rapid Detection and Differentiation of Clinically Relevant Candida Species Simultaneously from Blood Culture by Use of a Novel Signal Amplification Approach. Journal of clinical microbiology. 2017;56(1):e00982–17. https://doi.org/10.1128/JCM.00982-17.CrossRefPubMedPubMedCentral

76.

• Leroy-Freschini B, Treglia G, Argemi X, Bund C, Kessler R, Herbrecht R, et al. 18F-FDG PET/CT for invasive fungal infection in immunocompromised patients. QJM. 2018;111(9):613–22. https://doi.org/10.1093/qjmed/hcy128Study suggesting that an alternative approach to imaging could offer a means of treatment planning and more detailed definition of fungal disease.CrossRefPubMed

77.

Petrik M, Haas H, Laverman P, Schrettl M, Franssen GM, Blatzer M, et al. 68Ga-triacetylfusarinine C and 68Ga-ferrioxamine E for Aspergillus infection imaging: uptake specificity in various micro-organisms. Molecular Imaging and Biology. 2014;16(1):102–8. https://doi.org/10.1007/s11307-013-0654-7.CrossRefPubMed

Title: From Culture to Fungal Biomarkers: the Diagnostic Route of Fungal Infections in Children with Primary Immunodeficiencies
Authors: Catherine Mark
Claire McGinn
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Primary Immunodeficiency
Invasive Aspergillosis
Biomarkers
Published in: Current Fungal Infection Reports / Issue 4/2019
Print ISSN: 1936-3761
Electronic ISSN: 1936-377X
DOI: https://doi.org/10.1007/s12281-019-00356-4

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The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

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Other articles of this Issue 4/2019

Update of Vulvovaginal Candidiasis in Pregnant and Non-pregnant Patients

Congenital Cutaneous Candidiasis: Uncommon Entity or Underdiagnosed?

Pneumocystis jirovecii Pneumonia: Epidemiology, Clinical Manifestation and Diagnosis

Onychomycosis in Patients Living with HIV/AIDS

Diagnostic Aspects of Chronic Pulmonary Aspergillosis: Present and New Directions

Adult Tinea Capitis: a Clinical Entity in Increasing Frequency

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage