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Stratifying Sepsis in Uganda Using Rapid Pathogen Diagnostics and Clinical Data: A Prospective Cohort Study

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  • 1 Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, New York;
  • | 2 Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York;
  • | 3 Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda;
  • | 4 Immunizable Diseases Unit, Uganda Virus Research Institute, Entebbe, Uganda;
  • | 5 Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda;
  • | 6 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
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ABSTRACT.

The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26–42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.

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Author Notes

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

Financial support: This work was supported by the National Institute of Allergy and Infectious Diseases (F32AI147528-01 to M. J. C.), the National Center for Advancing Translational Sciences (UL1TR001873 to Columbia University, sub-award to M. R. O.] the National Institutes of Health and the Stony Wold-Herbert Fund (M. J. C.), the Potts Memorial Foundation (M. J. C.), and the Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene (M. J. C.). Additional support was provided through the DELTAS Africa Initiative (grant no. 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences, Alliance for Accelerating Excellence in Science in Africa and is supported by the New Partnership for Africa’s Development Planning and Coordinating Agency with funding from the Wellcome Trust (grant no. 107743) and the UK government.

Disclaimer: The funders had no role in study design, data analysis and interpretation, manuscript preparation, or decision to publish.

Authors’ addresses: Matthew J. Cummings, Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, NY, and the Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, E-mail: mjc2244@columbia.edu. Barnabas Bakamutumaho, Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda, and the Immunizable Diseases Unit, Uganda Virus Research Institute, Entebbe, Uganda, E-mail: bbarnabas2001@yahoo.com. 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: nicowor@gmail.com, jkayiwa@yahoo.com, jonacla.j@gmail.com, tssekandi@gmail.com, and jjlutwama03@yahoo.com. Moses Muwanga and Christopher Nsereko, Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda, E-mails: docmuwanga@yahoo.com and chrisdoc23@yahoo.com. Matthew R. Baldwin, Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, NY, E-mail: mrb45@columbia.edu. Max R. O’Donnell, Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, NY, Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, E-mail: mo2130@columbia.edu.

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