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Use of Fungal Diagnostics and Therapy in Pediatric Cancer Patients in Resource-Limited Settings

  • Mycology (J Perfect, Section Editor)
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Abstract

Fungal diseases are an important cause of mortality in immunocompromised hosts, and their incidence in pediatric cancer patients in low- to middle-income countries is underestimated. In this review, we present relevant, up-to-date information about the most common opportunistic and endemic fungal diseases among children with cancer, their geographic distribution, and recommended diagnostics and treatment. Efforts to improve the care of children with cancer and fungal disease must address the urgent need for sustainable and cost-effective solutions that improve training, fungal disease testing capability, and the use of available resources. We hope that the collective information presented here will be used to advise healthcare providers, regional and country health leaders, and policymakers of the current challenges in diagnosing and treating fungal infections in children with cancer in low- to middle-income countries.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. Hidden killers: human fungal infections. Sci Transl Med. 2012;4(165):165rv13.

    Article  PubMed  CAS  Google Scholar 

  2. Benedict K, Mody RK. Epidemiology of histoplasmosis outbreaks, United States, 1938–2013. Emerg Infect Dis. 2016;22(3).

  3. Hector RF, Rutherford GW, Tsang CA, Erhart LM, McCotter O, Anderson SM, et al. The public health impact of coccidioidomycosis in Arizona and California. Int J Environ Res Public Health. 2011;8(4):1150–73.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Giacomazzi J, Baethgen L, Carneiro LC, Millington MA, Denning DW, Colombo AL, et al. The burden of serious human fungal infections in Brazil. Mycoses. 2016;59(3):145–50.

    Article  PubMed  Google Scholar 

  5. Beardsley J, Denning DW, Chau NV, Yen NT, Crump JA, Day JN. Estimating the burden of fungal disease in Vietnam. Mycoses. 2015;58 Suppl 5:101–6.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Seitz AE, Adjemian J, Steiner CA, Prevots DR. Spatial epidemiology of blastomycosis hospitalizations: detecting clusters and identifying environmental risk factors. Med Mycol. 2015;53(5):447–54.

    Article  PubMed  Google Scholar 

  7. Ramirez Soto MC. Sporotrichosis: the story of an endemic region in Peru over 28 Years (1985 to 2012). PLoS One. 2015;10(6), e0127924.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Woods JP. Revisiting old friends: developments in understanding Histoplasma capsulatum pathogenesis. J Microbiol. 2016;54(3):265–76.

    Article  CAS  PubMed  Google Scholar 

  9. Magrath I, Steliarova-Foucher E, Epelman S, Ribeiro RC, Harif M, Li CK, et al. Paediatric cancer in low-income and middle-income countries. Lancet Oncol. 2013;14(3):e104–16.

    Article  PubMed  Google Scholar 

  10. Gupta S, Antillon FA, Bonilla M, Fu L, Howard SC, Ribeiro RC, et al. Treatment-related mortality in children with acute lymphoblastic leukemia in Central America. Cancer. 2011;117(20):4788–95.

    Article  PubMed  Google Scholar 

  11. Gupta S, Bonilla M, Valverde P, Fu L, Howard SC, Ribeiro RC, et al. Treatment-related mortality in children with acute myeloid leukaemia in Central America: incidence, timing and predictors. Eur J Cancer. 2012;48(9):1363–9.

    Article  PubMed  Google Scholar 

  12. Phillips RS, Sung L, Amman RA, Riley RD, Castagnola E, Haeusler GM, et al. Predicting microbiologically defined infection in febrile neutropenic episodes in children: global individual participant data multivariable meta-analysis. Br J Cancer. 2016;114(6):623–30.

    Article  PubMed  Google Scholar 

  13. Science M, Robinson PD, MacDonald T, Rassekh SR, Dupuis LL, Sung L. Guideline for primary antifungal prophylaxis for pediatric patients with cancer or hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2014;61(3):393–400.

    Article  PubMed  Google Scholar 

  14. 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 Oncol. 2014;15(8):e327–40. This manuscript is an excellent guideline for the diagnosis and management of invasive fungal infections in pediatric cancer patients and receipients of haemopoietic stem-cell transplantation.

    Article  PubMed  Google Scholar 

  15. Ribeiro RC. Improving survival of children with cancer worldwide: the st. Jude international outreach program approach. Stud Health Technol Inform. 2012;172:9–13.

    PubMed  Google Scholar 

  16. Ribeiro RC, Antillon F, Pedrosa F, Pui CH. Global pediatric oncology: lessons from partnerships between high-income countries and low- to mid-income countries. J Clin Oncol. 2016;34(1):53–61.

    Article  CAS  PubMed  Google Scholar 

  17. Teixeira GM, Bittencourt H, de Macedo AV, Martinho GH, Colosimo EA, Rezende SM. Assessing the influence of different comorbidities indexes on the outcomes of allogeneic hematopoietic stem cell transplantation in a developing country. PLoS One. 2015;10(9), e0137390.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Jaime-Perez JC, Heredia-Salazar AC, Cantu-Rodriguez OG, Gutierrez-Aguirre H, Villarreal-Villarreal CD, Mancias-Guerra C, et al. Cost structure and clinical outcome of a stem cell transplantation program in a developing country: the experience in northeast Mexico. Oncologist. 2015;20(4):386–92.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bazuaye N, Nwogoh B, Ikponmwen D, Irowa O, Okugbo S, Isa I, et al. First successful allogeneic hematopoietic stem cell transplantation for a sickle cell disease patient in a low resource country (Nigeria): a case report. Ann Transplant. 2014;19:210–3.

    Article  PubMed  Google Scholar 

  20. Romani L. Immunity to fungal infections. Nat Rev Immunol. 2011;11(4):275–88.

    Article  CAS  PubMed  Google Scholar 

  21. Colombo AL, Tobon A, Restrepo A, Queiroz-Telles F, Nucci M. Epidemiology of endemic systemic fungal infections in Latin America. Med Mycol. 2011;49(8):785–98.

    PubMed  Google Scholar 

  22. Pan B, Deng S, Liao W, Pan W. Endemic mycoses: overlooked diseases in China. Clin Infect Dis. 2013;56(10):1516–7.

    Article  PubMed  Google Scholar 

  23. Taicz M, Rosanova MT, Bes D, Lisdero ML, Iglesias V, Santos P, et al. Paracoccidioidomycosis in pediatric patients: a description of 4 cases. Rev Iberoam Micol. 2014;31(2):141–4.

    Article  PubMed  Google Scholar 

  24. Lortholary O, Charlier C, Lebeaux D, Lecuit M, Consigny PH. Fungal infections in immunocompromised travelers. Clin Infect Dis. 2013;56(6):861–9.

    Article  PubMed  CAS  Google Scholar 

  25. Bravo R, Pelayo-Katsanis LO, Shehab ZM, Katsanis E. Diagnostic and treatment challenges for the pediatric hematologist oncologist in endemic areas for coccidioidomycosis. J Pediatr Hematol Oncol. 2012;34(5):389–94.

    Article  PubMed  Google Scholar 

  26. Caniza MA, Melgar M, Cojulun AC. Infecciones en el paciente pediátrico con cáncer. Capítulo 59. In: L Madero, A Lassaleta y J Sevilla, editors. Hematología y Oncología Pediátricas. 3ra edición. Madrid, España: Ergon.

  27. Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev. 2011;24(2):247–80.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Vallabhaneni S, Mody RK, Walker T, Chiller T. The global burden of fungal diseases. Infect Dis Clin North Am. 2016;30(1):1–11. This manuscript describes fungal diseases, especially those with global impact, and identifies major knowledge gaps.

    Article  PubMed  Google Scholar 

  29. Wang X, van de Veerdonk FL, Netea MG. Basic genetics and immunology of Candida infections. Infect Dis Clin North Am. 2016;30(1):85–102.

    Article  PubMed  Google Scholar 

  30. Yapar N. Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag. 2014;10:95–105.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Palazzi DL, Arrieta A, Castagnola E, Halasa N, Hubbard S, Brozovich AA, et al. Candida speciation, antifungal treatment and adverse events in pediatric invasive candidiasis: results from 441 infections in a prospective, multi-national study. Pediatr Infect Dis J. 2014;33(12):1294–6.

    Article  PubMed  Google Scholar 

  32. Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, et al. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clin Infect Dis. 2015;60(6):892–9.

    Article  PubMed  Google Scholar 

  33. Benjamin Jr DK, Stoll BJ, Gantz MG, Walsh MC, Sanchez PJ, Das A, et al. Neonatal candidiasis: epidemiology, risk factors, and clinical judgment. Pediatrics. 2010;126(4):e865–73.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Santolaya ME, Alvarado T, Queiroz-Telles F, Colombo AL, Zurita J, Tiraboschi IN, et al. Active surveillance of candidemia in children from Latin America: a key requirement for improving disease outcome. Pediatr Infect Dis J. 2014;33(2):e40–4. This manuscript describes the epidemiology of candidemia in children in the Latin American region.

    Article  PubMed  Google Scholar 

  35. Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Ellis D, Tullio V, et al. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J Clin Microbiol. 2010;48(4):1366–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Doi AM, Pignatari AC, Edmond MB, Marra AR, Camargo LF, Siqueira RA, et al. Epidemiology and microbiologic characterization of nosocomial candidemia from a Brazilian national surveillance program. PLoS One. 2016;11(1), e0146909.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bothra M, Seth R, Kapil A, Dwivedi SN, Bhatnagar S, Xess I. Evaluation of predictors of adverse outcome in febrile neutropenic episodes in pediatric oncology patients. Indian J Pediatr. 2013;80(4):297–302.

    Article  PubMed  Google Scholar 

  38. Bhattacharyya A, Krishnan S, Saha V, Goel G, Bhattacharya S, Hmar L. Microbiology, infection control and infection related outcome in pediatric patients in an oncology center in Eastern India: experience from Tata Medical Center, Kolkata. Indian J Cancer. 2014;51(4):415–7.

    Article  PubMed  Google Scholar 

  39. Sahbudak BZ, Yilmaz KD, Karadas N, Sen S, Onder SZ, Akinci AB, et al. Proven and probable invasive fungal infections in children with acute lymphoblastic leukaemia: results from an university hospital, 2005-2013. Mycoses. 2015;58(4):225–32.

    Article  Google Scholar 

  40. Ye Q, Xu X, Zheng Y, Chen X. Etiology of septicemia in children with acute leukemia: 9-year experience from a children's hospital in China. J Pediatr Hematol Oncol. 2011;33(5):e186–91.

    Article  PubMed  Google Scholar 

  41. Riches ML, Trifilio S, Chen M, Ahn KW, Langston A, Lazarus HM, et al. Risk factors and impact of non-Aspergillus mold infections following allogeneic HCT: a CIBMTR infection and immune reconstitution analysis. Bone Marrow Transplant. 2016;51(2):277–82.

    Article  CAS  PubMed  Google Scholar 

  42. Wattier RL, Dvorak CC, Hoffman JA, Brozovich AA, Bin-Hussain I, Groll AH, et al. A prospective, international cohort study of invasive mold infections in children. J Pediatr Infect Dis Soc. 2015;4(4):313–22. This manuscript reports the current epidemiology and spectrum of invasive mold infections in children with immunosuppresion.

    Article  Google Scholar 

  43. Castagnola E, Cesaro S, Giacchino M, Livadiotti S, Tucci F, Zanazzo G, et al. Fungal infections in children with cancer: a prospective, multicenter surveillance study. Pediatr Infect Dis J. 2006;25(7):634–9.

    Article  PubMed  Google Scholar 

  44. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327–60.

    Article  CAS  PubMed  Google Scholar 

  45. Chakrabarti A, Chatterjee SS, Das A, Shivaprakash MR. Invasive aspergillosis in developing countries. Med Mycol. 2011;49 Suppl 1:S35–47.

    Article  PubMed  Google Scholar 

  46. Jain S, Kapoor G. Invasive aspergillosis in children with acute leukemia at a resource-limited oncology center. J Pediatr Hematol Oncol. 2015;37(1):e1–5.

    Article  PubMed  Google Scholar 

  47. Morris SK, Allen UD, Gupta S, Richardson SE. Breakthrough filamentous fungal infections in pediatric hematopoetic stem cell transplant and oncology patients receiving caspofungin. Can J Infect Dis Med Microbiol. 2012;23(4):179–82.

    PubMed  PubMed Central  Google Scholar 

  48. Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351(14):1391–402.

    Article  CAS  PubMed  Google Scholar 

  49. Cuervo G, Garcia-Vidal C, Nucci M, Puchades F, Fernandez-Ruiz M, Obed M, et al. Breakthrough candidaemia in the era of broad-spectrum antifungal therapies. Clin Microbiol Infect. 2016;22(2):181–8.

    Article  CAS  PubMed  Google Scholar 

  50. Krcmery V, Demitrovicova A, Kisac P. Breakthrough fungemia due to Candida glabrata during posaconazole prophylaxis in hematology patients treated with anidulafungin - report of 5 cases. J Chemother. 2011;23(5):310–1.

    Article  CAS  PubMed  Google Scholar 

  51. Myoken Y, Kyo T, Fujihara M, Sugata T, Mikami Y. Clinical significance of breakthrough fungemia caused by azole-resistant Candida tropicalis in patients with hematologic malignancies. Haematologica. 2004;89(3):378–80.

    PubMed  Google Scholar 

  52. Suzuki K, Sugawara Y, Sekine T, Nakase K, Katayama N. Breakthrough disseminated zygomycosis induced massive gastrointestinal bleeding in a patient with acute myeloid leukemia receiving micafungin. J Infect Chemother. 2009;15(1):42–5.

    Article  PubMed  Google Scholar 

  53. Vande Broek I, Schots R. Fatal cerebral zygomycosis breakthrough in a patient with acute lymphoblastic leukemia on voriconazole prophylaxis after cord blood SCT. Bone Marrow Transplant. 2009;44(11):765–6.

    Article  CAS  PubMed  Google Scholar 

  54. Mousset S, Bug G, Heinz WJ, Tintelnot K, Rickerts V. Breakthrough zygomycosis on posaconazole prophylaxis after allogeneic stem cell transplantation. Transpl Infect Dis. 2010;12(3):261–4.

    Article  CAS  PubMed  Google Scholar 

  55. Franco-Paredes C, Womack T, Bohlmeyer T, Sellers B, Hays A, Patel K, et al. Management of Cryptococcus gattii meningoencephalitis. Lancet Infect Dis. 2014.

  56. Maziarz EK, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2016;30(1):179–206.

    Article  PubMed  Google Scholar 

  57. Rajasingham R, Rolfes MA, Birkenkamp KE, Meya DB, Boulware DR. Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis. PLoS Med. 2012;9(9), e1001316.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Schelenz S, Barnes RA, Barton RC, Cleverley JR, Lucas SB, Kibbler CC, et al. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis. 2015;15(4):461–74.

    Article  PubMed  Google Scholar 

  59. Hage CA, Knox KS, Wheat LJ. Endemic mycoses: overlooked causes of community acquired pneumonia. Respir Med. 2012;106(6):769–76.

    Article  PubMed  Google Scholar 

  60. Marques SA. Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating. An Bras Dermatol. 2013;88(5):700–11.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Lopez-Martinez R, Hernandez-Hernandez F, Mendez-Tovar LJ, Manzano-Gayosso P, Bonifaz A, Arenas R, et al. Paracoccidioidomycosis in Mexico: clinical and epidemiological data from 93 new cases (1972-2012). Mycoses. 2014;57(9):525–30.

    Article  CAS  PubMed  Google Scholar 

  62. Ramos-E-Silva, Saraiva LE. Paracoccidioidomycosis. Dermatol Clin. 2008;26(2):257–69. vii.

    Article  CAS  PubMed  Google Scholar 

  63. Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23(2):367–81.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Bradsher Jr RW. The endemic mimic: blastomycosis an illness often misdiagnosed. Trans Am Clin Climatol Assoc. 2014;125:188–202.

    PubMed  PubMed Central  Google Scholar 

  65. Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(12):1801–12.

    Article  CAS  PubMed  Google Scholar 

  66. Mandegari E, Fu L, Arambu C, Montoya S, Pena A, Johnson KM, et al. Mucormycosis rhinosinusitis at diagnosis of acute lymphoblastic leukemia: diagnostics and management challenges in a low-middle-income country. J Pediatr Hematol Oncol. 2015;37(3):e173–7.

    Article  PubMed  Google Scholar 

  67. Horn DL, Freifeld AG, Schuster MG, Azie NE, Franks B, Kauffman CA. Treatment and outcomes of invasive fusariosis: review of 65 cases from the PATH Alliance((R)) registry. Mycoses. 2014;57(11):652–8.

    Article  PubMed  Google Scholar 

  68. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34(1):7–14.

    Article  CAS  PubMed  Google Scholar 

  69. de Pauw BE, 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. Clin Infect Dis. 2008;46(12):1813–21.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–e50. Excellent guidelines for the management of candidiasis, and essential reading for those caring for patients at risk for candidal infection.

    Article  PubMed  Google Scholar 

  71. Irmer H, Tarazona S, Sasse C, Olbermann P, Loeffler J, Krappmann S, et al. RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior. BMC Genomics. 2015;16:640.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Gorton RL, Ramnarain P, Barker K, Stone N, Rattenbury S, McHugh TD, et al. Comparative analysis of Gram's stain, PNA-FISH and Sepsityper with MALDI-TOF MS for the identification of yeast direct from positive blood cultures. Mycoses. 2014;57(10):592–601.

    Article  CAS  PubMed  Google Scholar 

  73. Patiroglu T, Unal E, Karakukcu M, Ozdemir MA, Tucer B, Yikilmaz A, et al. Multiple fungal brain abscesses in a child with acute lymphoblastic leukemia. Mycopathologia. 2012;174(5-6):505–9.

    Article  PubMed  Google Scholar 

  74. Silva GM, Silveira AR, Betania CA, Macedo DP, Neves RP. Disseminated fusariosis secondary to neuroblastoma with fatal outcome. Mycopathologia. 2013;176(3-4):233–6.

    Article  PubMed  Google Scholar 

  75. Bonifaz A, Tirado-Sanchez A, Calderon L, Romero-Cabello R, Kassack J, Ponce RM, et al. Mucormycosis in children: a study of 22 cases in a Mexican hospital. Mycoses. 2014;57 Suppl 3:79–84.

    Article  PubMed  Google Scholar 

  76. Powers-Fletcher MV, Hanson KE. Nonculture diagnostics in fungal disease. Infect Dis Clin North Am. 2016;30(1):37–49. This manuscript provides an excellent overview of fungal diagnostics using non-culture methods.

    Article  PubMed  Google Scholar 

  77. Saha DC, Goldman DL, Shao X, Casadevall A, Husain S, Limaye AP, et al. Serologic evidence for reactivation of cryptococcosis in solid-organ transplant recipients. Clin Vaccine Immunol. 2007;14(12):1550–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Miceli MH, Maertens J. Role of non-culture-based tests, with an emphasis on galactomannan testing for the diagnosis of invasive aspergillosis. Semin Respir Crit Care Med. 2015;36(5):650–61.

    Article  PubMed  Google Scholar 

  79. Duarte RF, Sanchez-Ortega I, Cuesta I, Arnan M, Patino B, de Fernandez SA, et al. Serum galactomannan-based early detection of invasive aspergillosis in hematology patients receiving effective antimold prophylaxis. Clin Infect Dis. 2014;59(12):1696–702.

    Article  PubMed  Google Scholar 

  80. Schwarzinger M, Sagaon-Teyssier L, Cabaret O, Bretagne S, Cordonnier C. Performance of serum biomarkers for the early detection of invasive aspergillosis in febrile, neutropenic patients: a multi-state model. PLoS One. 2013;8(6), e65776.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Ruhnke M, Bohme A, Buchheidt D, Cornely O, Donhuijsen K, Einsele H, et al. Diagnosis of invasive fungal infections in hematology and oncology—guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO). Ann Oncol. 2012;23(4):823–33.

    Article  CAS  PubMed  Google Scholar 

  82. Nguyen MH, Wissel MC, Shields RK, Salomoni MA, Hao B, Press EG, et al. Performance of Candida real-time polymerase chain reaction, beta-D-glucan assay, and blood cultures in the diagnosis of invasive candidiasis. Clin Infect Dis. 2012;54(9):1240–8.

    Article  CAS  PubMed  Google Scholar 

  83. Onishi A, Sugiyama D, Kogata Y, Saegusa J, Sugimoto T, Kawano S, et al. Diagnostic accuracy of serum 1,3-beta-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol. 2012;50(1):7–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Marty FM, Koo S. Role of (1-->3)-beta-D-glucan in the diagnosis of invasive aspergillosis. Med Mycol. 2009;47 Suppl 1:S233–40.

    Article  CAS  PubMed  Google Scholar 

  85. Dornbusch HJ, Groll A, Walsh TJ. Diagnosis of invasive fungal infections in immunocompromised children. Clin Microbiol Infect. 2010;16(9):1328–34.

    Article  CAS  PubMed  Google Scholar 

  86. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis. 2006;42(10):1417–27.

    Article  CAS  PubMed  Google Scholar 

  87. Guo YL, Chen YQ, Wang K, Qin SM, Wu C, Kong JL. Accuracy of BAL galactomannan in diagnosing invasive aspergillosis: a bivariate metaanalysis and systematic review. Chest. 2010;138(4):817–24.

    Article  PubMed  Google Scholar 

  88. Walsh TJ, Shoham S, Petraitiene R, Sein T, Schaufele R, Kelaher A, et al. Detection of galactomannan antigenemia in patients receiving piperacillin-tazobactam and correlations between in vitro, in vivo, and clinical properties of the drug-antigen interaction. J Clin Microbiol. 2004;42(10):4744–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Nucci M, Carlesse F, Cappellano P, Varon AG, Seber A, Garnica M, et al. Earlier diagnosis of invasive fusariosis with Aspergillus serum galactomannan testing. PLoS One. 2014;9(1), e87784.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Wheat LJ, Azar MM, Bahr NC, Spec A, Relich RF, Hage C. Histoplasmosis. Infect Dis Clin North Am. 2016;30(1):207–27.

    Article  PubMed  Google Scholar 

  91. Frost HM, Novicki TJ. Blastomyces antigen detection for diagnosis and management of blastomycosis. J Clin Microbiol. 2015;53(11):3660–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Durkin M, Estok L, Hospenthal D, Crum-Cianflone N, Swartzentruber S, Hackett E, et al. Detection of Coccidioides antigenemia following dissociation of immune complexes. Clin Vaccine Immunol. 2009;16(10):1453–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(3):291–322.

  94. Downey LC, Smith PB, Benjamin Jr DK, Cohen-Wolkowiez M. Recent advances in the detection of neonatal candidiasis. Curr Fungal Infect Rep. 2010;4(1):17–22.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Tissot F, Lamoth F, Hauser PM, Orasch C, Flückiger U, Siegemund M, et al. Beta-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Respir Crit Care Med. 2013;188(9):1100–9.

    Article  PubMed  Google Scholar 

  96. Huang HR, Fan LC, Rajbanshi B, Xu JF. Evaluation of a new cryptococcal antigen lateral flow immunoassay in serum, cerebrospinal fluid and urine for the diagnosis of cryptococcosis: a meta-analysis and systematic review. PLoS One. 2015;10(5), e0127117. doi:10.1371/journal.pone.0127117. eCollection 2015.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Pfaller MA. Application of culture-independent rapid diagnostic tests in the management of invasive candidiasis and cryptococcosis. J Fungi. 2015;1(2):217–51.

    Article  Google Scholar 

  98. 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. Clin Infect Dis. 2015;61(8):1293–303.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Ambasta A, Carson J, Church DL. The use of biomarkers and molecular methods for the earlier diagnosis of invasive aspergillosis in immunocompromised patients. Med Mycol. 2015;53(6):531–57.

    Article  PubMed  Google Scholar 

  100. Mandhaniya S, Iqbal S, Sharawat SK, Xess I, Bakhshi S. Diagnosis of invasive fungal infections using real-time PCR assay in paediatric acute leukaemia induction. Mycoses. 2012;55(4):372–9.

    Article  PubMed  Google Scholar 

  101. Nett JE, Andes DR. Antifungal agents: spectrum of activity, pharmacology, and clinical indications. Infect Dis Clin North Am. 2016;30(1):51–83. This manuscript provides an excellent overview of currently available antifungals.

    Article  PubMed  Google Scholar 

  102. Mehta PS, Wiernikowski JT, Petrilli JA, Barr RD. Essential medicines for pediatric oncology in developing countries. Pediatr Blood Cancer. 2013;60(5):889–91.

    Article  PubMed  Google Scholar 

  103. Kirby J, Ojha RP, Johnson KM, Bittner EC, Caniza MA. Challenges in managing infections among pediatric cancer patients: Suboptimal national essential medicines lists for low and middle income countries. Pediatr Blood Cancer. 2014.

  104. Xia Z, Yang R, Wang W, Cong L. Genotyping and antifungal drug susceptibility of Trichosporon asahii isolated from Chinese patients. Mycopathologia. 2012;173(2-3):127–33.

    Article  CAS  PubMed  Google Scholar 

  105. Sabatelli F, Patel R, Mann PA, Mendrick CA, Norris CC, Hare R, et al. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother. 2006;50(6):2009–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Felton T, Troke PF, Hope WW. Tissue penetration of antifungal agents. Clin Microbiol Rev. 2014;27(1):68–88. This manuscript is a good reference for tissue penetration of the various antifungals.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA, et al. Coccidioidomycosis. Clin Infect Dis. 2005;41(9):1217–23.

    Article  PubMed  Google Scholar 

  108. Skiada A, Lanternier F, Groll AH, Pagano L, Zimmerli S, Herbrecht R, et al. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica. 2013;98(4):492–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Girmenia C, Cimino G, Di CF, Micozzi A, Gentile G, Martino P. Effects of hydration with salt repletion on renal toxicity of conventional amphotericin B empirical therapy: a prospective study in patients with hematological malignancies. Support Care Cancer. 2005;13(12):987–92.

    Article  PubMed  Google Scholar 

  110. Turcu R, Patterson MJ, Omar S. Influence of sodium intake on Amphotericin B-induced nephrotoxicity among extremely premature infants. Pediatr Nephrol. 2009;24(3):497–505.

    Article  PubMed  Google Scholar 

  111. Fleming S, Yannakou CK, Haeusler GM, Clark J, Grigg A, Heath CH, et al. Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014. Intern Med J. 2014;44(12b):1283–97.

    Article  CAS  PubMed  Google Scholar 

  112. Cortez KJ, Roilides E, Quiroz-Telles F, Meletiadis J, Antachopoulos C, Knudsen T, et al. Infections caused by Scedosporium spp. Clin Microbiol Rev. 2008;21(1):157–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Wong EH, Revankar SG. Dematiaceous molds. Infect Dis Clin North Am. 2016;30(1):165–78.

    Article  PubMed  Google Scholar 

  114. Kudo K, Terui K, Sasaki S, Kamio T, Sato T, Ito E. Voriconazole for both successful treatment of disseminated Trichosporon asahii infection and subsequent cord blood transplantation in an infant with acute myelogenous leukemia. Bone Marrow Transplant. 2011;46(2):310–1.

    Article  CAS  PubMed  Google Scholar 

  115. Lackner M, de Hoog GS, Verweij PE, Najafzadeh MJ, Curfs-Breuker I, Klaassen CH, et al. Species-specific antifungal susceptibility patterns of Scedosporium and Pseudallescheria species. Antimicrob Agents Chemother. 2012;56(5):2635–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Schmitt-Hoffmann A, Roos B, Heep M, Schleimer M, Weidekamm E, Brown T, et al. Single-ascending-dose pharmacokinetics and safety of the novel broad-spectrum antifungal triazole BAL4815 after intravenous infusions (50, 100, and 200 milligrams) and oral administrations (100, 200, and 400 milligrams) of its prodrug, BAL8557, in healthy volunteers. Antimicrob Agents Chemother. 2006;50(1):279–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Walsh TJ, Driscoll T, Milligan PA, Wood ND, Schlamm H, Groll AH, et al. Pharmacokinetics, safety, and tolerability of voriconazole in immunocompromised children. Antimicrob Agents Chemother. 2010;54(10):4116–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Ashbee HR, Barnes RA, Johnson EM, Richardson MD, Gorton R, Hope WW. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother. 2014;69(5):1162–76.

    Article  CAS  PubMed  Google Scholar 

  119. Park WB, Kim NH, Kim KH, Lee SH, Nam WS, Yoon SH, et al. The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial. Clin Infect Dis. 2012;55(8):1080–7.

    Article  CAS  PubMed  Google Scholar 

  120. Laverdiere M, Bow EJ, Rotstein C, Autmizguine J, Broady R, Garber G, et al. Therapeutic drug monitoring for triazoles: a needs assessment review and recommendations from a Canadian perspective. Can J Infect Dis Med Microbiol. 2014;25(6):327–43.

    PubMed  PubMed Central  Google Scholar 

  121. Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother. 2009;53(1):24–34.

    Article  CAS  PubMed  Google Scholar 

  122. Reboli AC, Shorr AF, Rotstein C, Pappas PG, Kett DH, Schlamm HT, et al. Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome. BMC Infect Dis. 2011;11:261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, et al. Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005;33(5):676–82.

    Article  CAS  PubMed  Google Scholar 

  124. Morrissey CO, Slavin MA, O'Reilly MA, Daffy JR, Seymour JF, Schwarer AP, et al. Caspofungin as salvage monotherapy for invasive aspergillosis in patients with haematological malignancies or following allogeneic stem cell transplantation: efficacy and concomitant cyclosporin A. Mycoses. 2007;50 Suppl 1:24–37.

    Article  CAS  PubMed  Google Scholar 

  125. Groetzner J, Kaczmarek I, Wittwer T, Strauch J, Meiser B, Wahlers T, et al. Caspofungin as first-line therapy for the treatment of invasive aspergillosis after thoracic organ transplantation. J Heart Lung Transplant. 2008;27(1):1–6.

    Article  PubMed  Google Scholar 

  126. Morris MI, Villmann M. Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm. 2006;63(18):1693–703.

    Article  CAS  PubMed  Google Scholar 

  127. Israels T, Renner L, Hendricks M, Hesseling P, Howard S, Molyneux E. SIOP PODC: recommendations for supportive care of children with cancer in a low-income setting. Pediatr Blood Cancer. 2013;60(6):899–904.

    Article  PubMed  Google Scholar 

  128. Geist MJ, Egerer G, Burhenne J, Riedel KD, Mikus G. Induction of voriconazole metabolism by rifampin in a patient with acute myeloid leukemia: importance of interdisciplinary communication to prevent treatment errors with complex medications. Antimicrob Agents Chemother. 2007;51(9):3455–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the American Lebanese Syrian Associated Charities (ALSAC).We thank Cherise Guess, PhD, ELS, for excellent editing support.

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Authors and Affiliations

  1. Department of Infectious Diseases, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA

    Sheena Mukkada, Jeannette Kirby & Miguela A. Caniza

  2. Division of Infectious Diseases, Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, USA

    Sheena Mukkada

  3. Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Bangkok, Thailand, 10400

    Nopporn Apiwattanakul

  4. Department of Pathology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA

    Randall T. Hayden

  5. Department of Global Pediatric Medicine, St Jude Children’s Research Hospital, Memphis, TN, USA

    Miguela A. Caniza

  6. International Outreach Program, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Miguela A. Caniza

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  1. Sheena Mukkada
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  2. Jeannette Kirby
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  3. Nopporn Apiwattanakul
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  5. Miguela A. Caniza
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Correspondence to Miguela A. Caniza.

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Sheena Mukkada, Jeannette Kirby, Randall Hayden, and Miguela Caniza declare that they have no conflict of interest.

Nopporn Apiwattanakul reports personal fees from Astellas Pharma Co. Ltd. outside the submitted work.

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This article is part of the Topical Collection on Mycology

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Mukkada, S., Kirby, J., Apiwattanakul, N. et al. Use of Fungal Diagnostics and Therapy in Pediatric Cancer Patients in Resource-Limited Settings. Curr Clin Micro Rpt 3, 120–131 (2016). https://doi.org/10.1007/s40588-016-0038-2

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