A Longitudinal, Observational Study of Etiology and Long-Term Outcomes of Sepsis in Malawi Revealing the Key Role of Disseminated Tuberculosis

Joseph M. Lewis*, Madlitso Mphasa, Lucy Keyala, Rachel Banda, Emma L. Smith, Jackie Duggan, Tim Brooks, Matthew Catton, Jane Mallewa, Grace Katha, Stephen B. Gordon, Brian Faragher, Melita A. Gordon, Jamie Rylance, Nicholas A. Feasey

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sepsis protocols in sub-Saharan Africa are typically extrapolated from high-income settings, yet sepsis in sub-Saharan Africa is likely caused by distinct pathogens and may require novel treatment strategies. Data to guide such strategies are lacking. We aimed to define causes and modifiable factors associated with sepsis outcomes in Blantyre, Malawi, in order to inform the design of treatment strategies tailored to sub-Saharan Africa. Methods: We recruited 225 adults who met a sepsis case definition defined by fever and organ dysfunction in an observational cohort study at a single tertiary center. Etiology was defined using culture, antigen detection, serology, and polymerase chain reaction. The effect of treatment on 28-day outcomes was assessed using Bayesian logistic regression. Results: There were 143 of 213 (67%) participants living with human immunodeficiency virus (HIV). We identified a diagnosis in 145 of 225 (64%) participants, most commonly tuberculosis (TB; 34%) followed by invasive bacterial infections (17%), arboviral infections (13%), and malaria (9%). TB was associated with HIV infection, whereas malaria and arboviruses with the absence of HIV infection. Antituberculous chemotherapy was associated with survival (adjusted odds ratio for 28-day death, 0.17; 95% credible interval, 0.05-0.49 for receipt of antituberculous therapy). Of those with confirmed etiology, 83% received the broad-spectrum antibacterial ceftriaxone, but it would be expected to be active in only 24%. Conclusions: Sepsis in Blantyre, Malawi, is caused by a range of pathogens; the majority are not susceptible to the broad-spectrum antibacterials that most patients receive. HIV status is a key determinant of etiology. Novel antimicrobial strategies for sepsis tailored to sub-Saharan Africa, including consideration of empiric antituberculous therapy in individuals living with HIV, should be developed and trialed.

Original languageEnglish
Pages (from-to)1840-1849
Number of pages10
JournalClinical Infectious Diseases
Volume74
Issue number10
DOIs
Publication statusPublished - 15 May 2022

Bibliographical note

Funding Information:
This work was supported by the Wellcome Trust (109105z/15/a to J. M. L. and 206545/Z/17/Z, the core grant to the Malawi- Liverpool-Wellcome Programme).

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Keywords

  • Africa south of the Sahara
  • HIV
  • antimicrobial resistance
  • critical illness
  • tuberculosis

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