Severe Outcomes and Risk Factors of Non-Neutropenic Fever Episodes in Hospitalized Children with Cancer in Kenya

Samuel Kipchumba¹Kenneth Busby²Dennis Njenga³Julia Dettinger⁴Lenah Nyamusi³Sandra Langat^3,5Gilbert Olbara⁶Cheryl A Moyer⁷Terry A Vik^3,8C. Nathan Nessle^10,9*Festus Njuguna^11*

• ¹Child Health and Pediatrics, Moi University, Eldoret, Kenya
• ²Pediatric Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
• ³Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya
• ⁴Department of Global Health, School of Medicine, University of Washington, Seattle, Washington, United States
• ⁵Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, Netherlands
• ⁶Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya
• ⁷Department of Learning Health Sciences, School of Medicine, University of Michigan, Ann Arbor, Michigan, United States
• ⁸Pediatric Hematology-Oncology, School of Medicine, Indiana University Bloomington, Indianapolis, Indiana, United States
• ⁹Division of Pediatric Hematology-Oncology, Department of Pediatrics, School of Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, United States
• ¹⁰Fogarty International Center (NIH), Bethesda, Maryland, United States
• ¹¹Department of Child Health and Pediatrics, Moi University, Eldoret, Kenya

Compared to febrile neutropenia (FN), non-neutropenic fever (NNF) episodes in children with cancer have not been associated with severe outcomes. Risk factors for severe outcomes in FN and NNF episodes in children with cancer from low-middle-income countries (LMIC) are incompletely described. A prospective, observational cohort study was conducted at a tertiary public referral hospital in western Kenya. Inclusion criteria were age ≤14 years, cancer diagnosis, hospitalized, fever >38.5°C or persistently >38°C. Neutropenia was an absolute count (ANC) <500 K/µL. Severe outcomes were BSI or death. Statistical analysis detected significance between groups and a univariate analysis was conducted. Of the 99 fevers, 54.5% were NNF episodes. Over 66% of NNF episodes were in patients with solid tumors. More severe outcomes were observed in NNF episodes compared to FN [BSI: 7.4% (4/54) vs. 4.4% (2/45); death: 7.4% (4/54) vs. 4.4% (2/45)], yet no deaths occurred in episodes with BSI. Acute leukemia not in remission (OR= 8.67, 95% CI [CI: 2.3- 32.62]; p= 0.002) and concern for disease relapse (OR= 14.17,]; p= 0.012) were significantly associated severe outcomes. Time to antibiotic administration (9 hours) did not differ by ANC. Under half (45.5%) of fever episodes had a blood culture ordered, with 93.9% obtained after administration of antibiotics. Non-neutropenic fever episodes had more severe outcomes. Prompt fever management is recommended in all children with cancer treated in an LMIC setting. Pediatric oncology treatment centers in LMICs should rigorously evaluate their fever management clinical practice. Clinical risk factors were identified, but a risk-stratified approach in an LMIC setting is not recommended. Urgent attention is needed to identify areas of clinical improvement.