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

Author:

Lewis Joseph M123ORCID,Mphasa Madlitso1,Keyala Lucy1,Banda Rachel1,Smith Emma L12,Duggan Jackie4,Brooks Tim4,Catton Matthew4,Mallewa Jane5,Katha Grace5,Gordon Stephen B12,Faragher Brian2,Gordon Melita A13,Rylance Jamie12,Feasey Nicholas A12

Affiliation:

1. Malawi Liverpool Wellcome Programme, Blantyre, Malawi

2. Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom

3. Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom

4. Rare and Imported Pathogens Laboratory, Public Health  England, United Kingdom

5. College of Medicine, University of Malawi, Malawi

Abstract

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.

Funder

Wellcome Trust

Malawi-Liverpool-Wellcome Programme

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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