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Associations between Organ Dysfunction Scoring Systems and Dysregulated Host Responses in Adults with Severe Infection in Uganda: A Prospective Cohort Study

Jonathan Tiao Department of Medicine, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York;

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Barnabas Bakamutumaho Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda;
Immunizable Diseases Unit, Uganda Virus Research Institute, Entebbe, Uganda;

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Nicholas Owor Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda;

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John Kayiwa Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda;

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Joyce Namulondo Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda;

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Timothy Byaruhanga Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda;

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Moses Muwanga Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda;

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Christopher Nsereko Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda;

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Irene Nayiga Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda;

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Xiaoyu Che Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York;
Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York;

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W. Ian Lipkin Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York;
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York;
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York;

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Julius J. Lutwama Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda;

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Max R. O’Donnell Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York;
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York;
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York

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Matthew J. Cummings Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York;
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York

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DOI:
https://doi.org/10.4269/ajtmh.24-0618
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Ahead of Print
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Scoring systems for organ dysfunction (e.g., the quick Sepsis-related Organ Failure Assessment [qSOFA], Modified Early Warning Score [MEWS], and Universal Vital Assessment [UVA]) are proposed as clinical criteria for sepsis. The content validity of these scoring systems is poorly understood in sub-Saharan Africa, where the global sepsis burden is concentrated. In a prospective cohort of 288 adults hospitalized with suspected sepsis in Uganda, we show that qSOFA, MEWS, and UVA scores were significantly associated with soluble mediators of innate and adaptive immune activation, endothelial dysfunction, and fibrinolysis. Results were consistent after adjustment for demographics, illness duration, and HIV or malaria coinfection. In resource-limited settings in sub-Saharan Africa, organ dysfunction scores may stratify patients at highest risk of poor outcomes and those with more dysregulated host responses. Further studies are needed to better define these relationships, including the temporal dynamics of dysregulated host responses and organ dysfunction in sepsis.

Author Notes

Financial support: This work was supported by the National Center for Advancing Translational Sciences (Grant no. UL1TR001873 to Columbia University, subaward to M. R. O’Donnell), the National Institute of Allergy and Infectious Diseases (Grant no. K23AI163364 to M. J. Cummings), and the MakCHS–Berkeley–Yale Pulmonary Complications of AIDS Research Training Program (Grant no. D43TW009607, subaward to B. Bakamutumaho) from the Fogarty International Center, NIH. Additional support was provided by the Burroughs Wellcome Fund/the American Society of Tropical Medicine and Hygiene (to M. J. Cummings).

Disclosures: Each enrolled participant 18 years old or older or their surrogate provided written informed consent. The study was approved by ethics committees at Columbia University (AAAR1450), the Uganda Virus Research Institute (GC/127/17/02-06/582), and the Uganda National Council for Science and Technology (HS2308).

Authors’ contributions: J. Tiao and M. J. Cummings conceived the study and its design. B. Bakamutumaho, N. Owor, J. Kayiwa, J. Namulondo, T. Byaruhanga, M. Muwanga, C. Nsereko, I. Nayiga, and J. J. Lutwama collected, organized, and entered clinical data and blood samples and contributed to pathogen diagnostics. J. Tiao performed statistical analyses. J. Tiao, B. Bakamutumaho, X. Che, W. I. Lipkin, M. R. O’Donnell, and M. J. Cummings contributed to data analysis and interpretation. J. Tiao and M. J. Cummings drafted the manuscript. All authors critically revised the drafted manuscript and approved of the submitted manuscript.

Data availability: Analytic R code is available in GitHub at https://github.com/JT17/organ_dysfunction_scoring_systems/blob/main/qsofa_mews_uva_ordinal_regression.R. Deidentified data will be made available to researchers affiliated with an appropriate institution after mutual signing of a data access agreement and obtainment of necessary ethics approvals.

Current contact information: Jonathan Tiao, Department of Medicine, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, NY, E-mail: jt3105@cumc.columbia.edu. Barnabas Bakamutumaho, Nicholas Owor, John Kayiwa, Joyce Namulondo, Timothy Byaruhanga, and Julius J. Lutwama, Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda, E-mails: bbarnabas2001@yahoo.com, nicowor@gmail.com, jkayiwa@yahoo.com, jonacla.j@gmail.com, tssekandi@gmail.com, and jjlutwama03@yahoo.com. Moses Muwanga, Christopher Nsereko, and Irene Nayiga, Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda, E-mails: fahimmuwanga@gmail.com, chrisdoc23@yahoo.com, and inayiga2@gmail.com. Xiaoyu Che and W. Ian Lipkin, Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, E-mails: xc2273@cumc.columbia.edu and wil2001@cumc.columbia.edu. Max R. O’Donnell and Matthew J. Cummings, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, E-mails: mo2130@cumc.columbia.edu and mjc2244@columbia.edu.

Address correspondence to Matthew J. Cummings, Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, 622 West 168th St., PH 8E-101, New York, NY 10032. E-mail: mjc2244@columbia.edu
Copyright:
© American Society of Tropical Medicine and Hygiene 2025
Received:
15 Sep 2024
|
Accepted:
02 Feb 2025
|
Published Online:
22 Apr 2025
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
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