The Early Recognition and Management of Sepsis in Sub-Saharan African Adults: A Systematic Review and Meta-Analysis

Abstract

Sepsis is a common cause of morbidity and mortality in sub-Saharan African adults. Standardised management pathways have been documented to improve the survival of adults with sepsis from high-resource settings. Our aim was to assess the current evidence base for early sepsis interventions (recognition, empirical antibiotics, and resuscitation) in resource-poor settings of sub-Saharan Africa. We searched MEDLINE, EMBASE and CINHAL Plus databases to identify interventional studies for the early recognition and management of sepsis in sub-Saharan Africa (1 January 2000 to 1 August 2018) using a protocol-driven search strategy: adults, protocolised care pathway, and sub-Saharan Africa. We identified 725 publications of which three met criteria for final selection. Meta-analysis from two randomised controlled trials demonstrated that mortality was increased by ‘early goal-directed therapy’ interventions that increased fluid resuscitation (R.R. 1.26, 95% C.I. 1.00–1.58, p = 0.045; I2 53%). The third observational cohort study demonstrated improved survival after implementation of protocolised management for sepsis (mortality 33.0% vs. 45.7%, p = 0.005). No study incorporated standardised protocols for empirical antibiotic administration. High rates of pneumonia and mycobacteraemia were reported. There has been little research into the early recognition and management of sepsis in sub-Saharan Africa. Interventional trials of early goal-directed therapy have, to date, increased mortality. There is an urgent need to develop effective strategies to improve outcomes for adults with sepsis in sub-Saharan Africa.

Plasmodium Impairs Antibacterial Innate Immunity to Systemic Infections in Part Through Hemozoin-Bound Bioactive Molecules

“…Experimental studies to date have focused almost exclusively on NTS and it is unknown whether the mechanisms of Plasmodium -induced immune suppression to NTS will be important for Sp or other bacterial pathogens found in co-infections with malaria (e.g., Haemophilus influenzae, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pyogenes , etc. Berkley et al, 2005 ; Reddy et al, 2010 ; Colombatti et al, 2011 ; Scott et al, 2011 ; Were et al, 2011 ; Auma et al, 2013 ; Gomez-Perez et al, 2014 ; Mourembou et al, 2016 ; Morton et al, 2018 ). We report for the first time, to our knowledge, a murine Plasmodium and pneumococcal co-infection.…”

“…These infections resulted in 435,000 deaths in 2017 the majority of which occur in sub-Saharan Africa in children under the age of 5 years (Organization WH, 2018 ). In areas with endemic malaria, an association between Plasmodium infection and invasive bacterial infections has been reported, and malaria was identified as a major risk factor for developing bacteremia that correlated with a worse clinical outcome and higher morbidity (Berkley et al, 2005 ; Reddy et al, 2010 ; Colombatti et al, 2011 ; Scott et al, 2011 ; Were et al, 2011 ; Auma et al, 2013 ; Gomez-Perez et al, 2014 ; Morton et al, 2018 ). These reports implicate both gastrointestinal and pulmonary bacterial pathogens such as non-typhoid Salmonella (NTS) and Streptococcus pneumoniae (Sp), respectively, as the most common organisms isolated from blood of Plasmodium and bacteria co-infected individuals (Berkley et al, 2005 ; Reddy et al, 2010 ; Scott et al, 2011 ; Decuypere et al, 2016 ; Mourembou et al, 2016 ).…”

Examining Trends in Sepsis and Sepsis Management by Non-Physician Clinicians in a Rural Ugandan Emergency Department Over a Decade.

“…Sepsis is one of the most significant worldwide causes of morbidity and mortality, totaling 48.9 million annual cases and accounting for 11 million annual deaths, 19.7% of all global deaths, in the most recent analysis of the Global Burden of Disease Study from 2017 data. 1 Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, while septic shock is a subset of sepsis in which there are underlying circulatory, cellular, and metabolic abnormalities that are associated with an even greater risk of mortality.…”

“…17 However, these guidelines have been deemed not only impractical in sub-Saharan Africa (SSA) due to limited resources, but also potentially detrimental as "early goal-directed therapy" interventions that increased fluid resuscitation were found to increase mortality in SSA. 18,19 This difference in impact of fluid resuscitation on septic patients across settings may be related to a difference in patient populations that carry a high burden of malaria and other co-morbidities as well as a lack of intensive care facilities to provide supportive treatment in cases where fluids may exacerbate respiratory failure, heart failure, or renal failure. 7,8,19−22 In LMICs overall, recommendations for sepsis management have included early administration of antibiotics, fluid resuscitation, using epinephrine and dopamine administration to optimize tissue perfusion in those refractory to fluid resuscitation, frequent vital sign monitoring, corticosteroid administration when necessary, supplemental oxygenation, and identification of infectious sources.…”

“…8,27 Although these studies suggest some approaches to sepsis management, there is still overall limited research into effective sepsis-related interventions and their outcomes in SSA and in Uganda in particular. 19 In this study, we describe patients with sepsis and their management and outcomes in a rural Ugandan Emergency Department staffed by non-physician clinicians over a nine-year period.…”