A longitudinal observational study of aetiology and long-term outcomes of sepsis in Malawi revealing the key role of disseminated tuberculosis.

Background Sepsis protocols in sub-Saharan Africa (sSA) are typically extrapolated from high-income settings, yet sepsis in sSA 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 outcome in Blantyre, Malawi to inform design of treatment strategies tailored to sSA. Methods We recruited 225 adults meeting a sepsis case-definition defined by fever and organ dysfunction, in an observational cohort study at a single tertiary centre. Aetiology was defined using culture, antigen detection, serology and PCR. Effect of treatments on 28-day outcomes were assessed by Bayesian logistic regression. Results 143/213 (67%) of participants were HIV-infected. We identified a diagnosis in 145/225 (64%) participants: most commonly tuberculosis (34%) followed by invasive bacterial (17%) and arboviral infections (13%) and malaria (9%) Tuberculosis was associated with HIV infection whereas malaria and arboviruses with the absence of HIV infection. Antituberculous chemotherapy was associated with survival (aOR 28-day death 0.17 [95% CrI 0.05-0.49] for receipt of antituberculous therapy). Of those with confirmed aetiology, 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 aetiology. Novel antimicrobial strategies for sepsis tailored to sSA – including consideration of empiric antitubercular therapy in the HIV-infected - should be developed and trialed.