The Indian Journal of Pediatrics

, Volume 85, Issue 12, pp 1090–1095 | Cite as

Prevalence and Predictors of Invasive Fungal Infections in Children with Persistent Febrile Neutropenia Treated for Acute Leukemia – A Prospective Study

  • Jogender Kumar
  • Amitabh Singh
  • Rachna SethEmail author
  • Immaculata Xess
  • Manisha Jana
  • Sushil Kumar Kabra
Original Article



To ascertain the prevalence of invasive fungal infections (IFI), predictors of IFI, identify etiological species and outcome (mortality/discharge) in persistent febrile neutropenia in children with acute leukemia.


It was a prospective, observational study conducted from January 2013 through June 2014 in a tertiary care centre in New Delhi. Children between 1 and 12 y of age, on chemotherapy for acute leukemia with persistent febrile neutropenia (> 96 h) were enrolled. These children were not on any antifungal prophylaxis. Diagnosis of IFI was based on European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. Prevalence and outcome was reported in mean ± 95% CI form and etiological species were presented in the form of the frequency distribution.


Three hundred nineteen episodes involving 187 children of febrile neutropenia were screened and 74 were enrolled. Prevalence of IFI was 22.97% (13.99–34.21). Positive cases were further classified into proven 3(17.6%), probable 11(64.8%) and possible 3(17.6%) according to EORTC/MSG criteria. On multivariate analysis, abnormal CXR and clinical sinusitis were important predictors of IFI. Most common fungi isolated was Aspergillus sp. followed by Candida sp. Mortality rate was 9.45% (3.89–18.52).


Thus, prevalence of IFI is very high in children with persistent febrile neutropenia who are not on antifungal prophylaxis. Abnormal chest x- ray and clinical sinusitis are important predictors of IFI.


Febrile neutropenia Leukemia Invasive fungal infection Prevalence Predictors 



JK: Conceived idea, collected data, prepared the manuscript; AS: Involved in data collection, analysis and preparing the manuscript; RS: Involved in idea, preparing the manuscript, evidence review and analysis; IX: Involved in microbiological support for fungal culture and serum galactomannan antigen test; MJ: Involved in reporting of X-rays, tomography and ultrasounds; SKK: Involved in idea, preparing the manuscript, evidence review and analysis. RS will act as guarantor for this paper.

Compliance with Ethical Standards

Conflict of Interest



  1. 1.
    Pizzo PA, Robichaud KJ, Wesley R, Commers JR. Fever in the pediatric and young adult patient with cancer. A prospective study of 1001 episodes. Medicine (Baltimore). 1982;61:153–65.CrossRefGoogle Scholar
  2. 2.
    Castagnola E, Fontana V, Caviglia I, et al. A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation. Clin Infect Dis. 2007;45:1296–304.CrossRefGoogle Scholar
  3. 3.
    Aytaç S, Yildirim I, Ceyhan M, et al. Risks and outcome of fungal infection in neutropenic children with hematologic diseases. Turk J Pediatr. 2010;52:121–5.PubMedGoogle Scholar
  4. 4.
    Bakhshi S, Padmanjali KS, Arya LS. Infections in childhood acute lymphoblastic leukemia: an analysis of 222 febrile neutropenic episodes. Pediatr Hematol Oncol. 2008;25:385–92.CrossRefGoogle Scholar
  5. 5.
    Gupta A, Singh M, Singh H, et al. Infections in acute myeloid leukemia: an analysis of 382 febrile episodes. Med Oncol. 2010;27:1037–45.CrossRefGoogle Scholar
  6. 6.
    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;80:297–302.CrossRefGoogle Scholar
  7. 7.
    Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34:7–14.CrossRefGoogle Scholar
  8. 8.
    Mor M, Gilad G, Kornreich L, Fisher S, Yaniv I, Levy I. Invasive fungal infections in pediatric oncology. Pediatr Blood Cancer. 2011;56:1092–7.CrossRefGoogle Scholar
  9. 9.
    De Pauw B, Walsh TJ, Donnelly JP, 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;46:1813–21.CrossRefGoogle Scholar
  10. 10.
    Wiley JM, Smith N, Leventhal BG, et al. Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors. J Clin Oncol. 1990;8:280–6.CrossRefGoogle Scholar
  11. 11.
    Das A, Oberoi S, Trehan A, et al. Invasive fungal disease in pediatric acute leukemia in the nontransplant setting: 8y' experience from a tertiary care center in North India. J Pediatr Hematol Oncol. 2017:1. Scholar
  12. 12.
    Seth R, Bhat AS. Management of common oncologic emergencies. Indian J Pediatr. 2011;78:709–17.CrossRefGoogle Scholar
  13. 13.
    Villarroel M, Avilés CL, Silva P, et al. Risk factors associated with invasive fungal disease in children with cancer and febrile neutropenia: a prospective multicenter evaluation. Pediatr Infect Dis J. 2010;29:816–21.CrossRefGoogle Scholar
  14. 14.
    Lai H-P, Chen Y-C, Chang L-Y, et al. Invasive fungal infection in children with persistent febrile neutropenia. J Formos Med Assoc Taiwan Yi Zhi. 2005;104:174–9.PubMedGoogle Scholar
  15. 15.
    Lehrnbecher T, Varwig D, Kaiser J, Reinhardt D, Klingebiel T, Creutzig U. Infectious complications in pediatric acute myeloid leukemia: analysis of the prospective multi-institutional clinical trial AML-BFM 93. Leukemia. 2004;18:72–7.CrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2018

Authors and Affiliations

  • Jogender Kumar
    • 1
  • Amitabh Singh
    • 1
  • Rachna Seth
    • 1
    Email author
  • Immaculata Xess
    • 2
  • Manisha Jana
    • 3
  • Sushil Kumar Kabra
    • 1
  1. 1.Department of PediatricsAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Department of MicrobiologyAll India Institute of Medical SciencesNew DelhiIndia
  3. 3.Department of RadiodiagnosisAll India Institute of Medical SciencesNew DelhiIndia

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