{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T16:30:30Z","timestamp":1793809830415,"version":"4.6.1"},"reference-count":40,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,11,4]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>In low- and middle-income settings, microbiologic evaluation of chemotherapy-associated febrile illness is limited by cost. Cost-effective diagnostic algorithms could streamline evaluation for chemotherapy-associated febrile illness where comprehensive testing is not possible, particularly in HIV- and tuberculosis (TB)-endemic settings. In this study, we created a decision analytic model to evaluate costs, diagnostic yield, and cost-effectiveness of diagnostic algorithms for adult inpatients with solid tumors who developed chemotherapy-associated febrile illness in Uganda. Given the high prevalence of HIV, TB, and malaria, diagnostics included serum cryptococcal antigen (CrAg) lateral flow assay, Alere TB urinary lipoarabinomannan (LAM), malaria rapid testing, and aerobic blood cultures. We considered the following testing algorithms: 1) a comprehensive approach where all tests were performed on all participants and 2) stepwise algorithms where tests were performed in series and stopped with the first positive result. Prevalence data and test performance were taken from the published literature. A comprehensive testing strategy yielded 32.2% correct diagnoses at a cost of $97.85 per correct diagnosis. Of the stepwise strategies, testing CrAg first yielded the cheapest strategy at a cost of $85.49 per correct diagnosis and the highest number of appropriate diagnoses (29.9%). The incremental cost-effectiveness ratio was $234 per additional correct diagnosis for the comprehensive strategy when compared with the sequential strategy. Although comprehensive diagnostic testing is optimal for patients who experience chemotherapy-associated febrile illness, if this strategy is unavailable, stepwise testing with CrAg first and then, TB LAM is optimal to maximize correct diagnosis and minimize costs.<\/jats:p>","DOI":"10.4269\/ajtmh.26-0069","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:37:29Z","timestamp":1788878249000},"page":"955-962","source":"Crossref","is-referenced-by-count":0,"title":["Cost-Effective Diagnostic Algorithms for Ugandan Patients with Solid Tumors Who Develop Chemotherapy-Associated Febrile Illness"],"prefix":"10.4269","volume":"115","author":[{"given":"Elizabeth A.","family":"Gulleen","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota, USA;"},{"name":"Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immaculate","family":"Mbarusha","sequence":"additional","affiliation":[{"name":"Uganda Cancer Institute, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Mubiru","sequence":"additional","affiliation":[{"name":"Uganda Cancer Institute, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Pedun","sequence":"additional","affiliation":[{"name":"Uganda Cancer Institute, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Lubwama","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Makerere University, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nixon","family":"Niyonzima","sequence":"additional","affiliation":[{"name":"Uganda Cancer Institute, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Sekyanzi","sequence":"additional","affiliation":[{"name":"Uganda Cancer Institute, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrahams","family":"Omoding","sequence":"additional","affiliation":[{"name":"Uganda Cancer Institute, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Phipps","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA;"},{"name":"Allergy and Infectious Diseases Division, Department of Medicine, University of 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Cancer","first-page":"2893","article-title":"Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008","volume":"127","author":"Ferlay","year":"2010"},{"issue":"4","key":"b4","series-title":"Clin Infect Dis","first-page":"e56","article-title":"Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America","volume":"52","author":"Freifeld","year":"2011"},{"issue":"4","key":"b5","series-title":"J Oncol Pharm Pract","first-page":"278","article-title":"Association of time to antibiotics and clinical outcomes in adult hematologic malignancy patients with febrile neutropenia","volume":"23","author":"Butts","year":"2017"},{"issue":"6","key":"b6","series-title":"Oncol Nurs Forum","first-page":"661","article-title":"Implementation of an evidence-based order set to impact initial antibiotic time intervals in adult febrile neutropenia","volume":"38","author":"Best","year":"2011"},{"issue":"1","key":"b7","series-title":"Antimicrob Agents Chemother","first-page":"e01974-19","article-title":"A systematic review and meta-analysis of the prevalence of community-onset bloodstream infections among hospitalized patients in Africa and Asia","volume":"64","author":"Marchello","year":"2019"},{"issue":"8","key":"b8","series-title":"Clin Microbiol Infect","first-page":"808","article-title":"The epidemiology of febrile illness in sub-Saharan Africa: Implications for diagnosis and management","volume":"24","author":"Maze","year":"2018"},{"issue":"6","key":"b9","series-title":"Lancet Infect Dis","first-page":"417","article-title":"Community-acquired bloodstream infections in Africa: A systematic review and meta-analysis","volume":"10","author":"Reddy","year":"2010"},{"key":"b10","series-title":"J Glob Oncol","first-page":"1","article-title":"HIV status and associated clinical characteristics among adult patients with cancer at the Uganda Cancer Institute","volume":"4","author":"Bender Ignacio","year":"2018"},{"issue":"11","key":"b11","series-title":"Open Forum Infect Dis","first-page":"ofad508","article-title":"Etiology of fever and associated outcomes among adults receiving chemotherapy for the treatment of solid tumors in Uganda","volume":"10","author":"Gulleen","year":"2023"},{"issue":"8","key":"b12","series-title":"Open Forum Infect Dis","first-page":"ofab389","article-title":"Risks of opportunistic infections in people with human immunodeficiency virus with cancers treated with chemotherapy","volume":"8","author":"Makinson","year":"2021"},{"key":"b13","series-title":"Clin Infect Dis","first-page":"S156","article-title":"Impact of the introduction of a package of diagnostic tools, diagnostic algorithm, and training and communication on outpatient acute fever case management at 3 diverse sites in Uganda: Results of a randomized controlled trial","volume":"77","author":"Kapisi","year":"2023"},{"key":"b14","series-title":"Front Med (Lausanne)","first-page":"131","article-title":"Best practices of blood cultures in low- and middle-income countries","volume":"6","author":"Ombelet","year":"2019"},{"issue":"12","key":"b15","series-title":"Open Forum Infect Dis","first-page":"ofae682","article-title":"Etiology, risk factors, and outcomes of bacteremia in patients with hematologic malignancies and febrile neutropenia in Uganda","volume":"11","author":"Lubwama","year":"2024"},{"key":"b16","series-title":"Clin Infect Dis","first-page":"S125","article-title":"Advancing access to diagnostic tools essential for universal health coverage and antimicrobial resistance prevention: An overview of trials in sub-Saharan Africa","volume":"77","author":"Olliaro","year":"2023"},{"issue":"1","key":"b17","series-title":"Nat Microbiol","first-page":"46","article-title":"REASSURED diagnostics to inform disease control strategies, strengthen 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