Sepsis is a major contributor to the global burden of disease. The majority of sepsis cases and deaths are estimated to occur in low and middle-income countries. Barriers to reducing the global burden of sepsis include difficulty quantifying attributable morbidity and mortality, low awareness, poverty and health inequity, and under-resourced and low-resilience public health and acute health care delivery systems. Important differences in the populations at risk, infecting pathogens, and clinical capacity to manage sepsis in high and low-resource settings necessitate context-specific approaches to this significant problem. We review these challenges and propose strategies to overcome them. These strategies include strengthening health systems, accurately identifying and quantifying sepsis cases, conducting inclusive research, establishing data-driven and context-specific management guidelines, promoting creative clinical interventions, and advocacy.

Annually, there are about 20 million cases of sepsis, defined as life-threatening acute organ dysfunction caused by a dysregulated host response to infection,¹ leading to more than 5 million deaths, with most of the burden in low- and middle-income countries (LMICs).² There is no reference standard that allows easy, accurate diagnosis of sepsis.^1,3 Although the 1991 International Consensus Definition Task Force proposed the systemic inflammatory response syndrome (SIRS) criteria to identify patients with a septic host response,⁴ these criteria do not measure whether the response is injurious, and their utility is limited.^1,3 In 2016, the Sepsis-3 Task Force proposed that, for patients with suspected infection, an increase of 2 points in the Sequential (Sepsis-Related) Organ Failure Assessment (SOFA) score could serve as clinical criteria for sepsis.¹ This approach was justified based on content validity (SOFA reflects the facets of organ dysfunction) and predictive validity (the proposed criteria predict downstream events associated with the condition of interest).⁵ However, the utility of SOFA is limited outside the intensive care unit (ICU) because many SOFA variables are not measured routinely.

There is a critical shortage of blood available for transfusion in many low- and middle-income countries. The consequences of this scarcity are dire, resulting in uncounted morbidity and mortality from trauma, obstetric hemorrhage, and pediatric anemias, among numerous other conditions. The process of collecting blood from a donor to administering it to a patient involves many facets from donor availability to blood processing to blood delivery. Each step faces particular challenges in low- and middle-income countries. Optimizing existing strategies and introducing new approaches will be imperative to ensure a safe and sufficient blood supply worldwide.

Objective: The objective of the study was to evaluate the association between neonatal abstinence syndrome (NAS) and long-term childhood morbidity and infant mortality. Study Design: We conducted a cohort study of infants born in Washington State during 1990 to 2008 who were diagnosed with NAS (n=1900) or were unexposed (n=12,283, frequency matched by birth year). 5-year hospital readmissions and infant mortality were ascertained. Results: Children with history of NAS had increased risk of readmission during the first 5 years of life relative to unexposed children; this remained statistically significant after adjustment for maternal age, maternal education, gestational age and intrapartum smoking status (readmission rates: NAS=21.3%, unexposed=12.7%, adjusted relative risk (aRR) 1.54, 95% confidence interval (CI) 1.37 to 1.73). NAS was associated with increased unadjusted infant mortality risk, but this did not persist after adjustment (aRR 1.94, 95% CI 0.99 to 3.80). Conclusion: The observed increased risk for childhood hospital readmission following NAS diagnosis argues for development of early childhood interventions to prevent morbidity.

Objectives: Delayed initiation of appropriate antimicrobials is linked to higher sepsis mortality. We investigated interphysician variation in septic patients’ door-to-antimicrobial time. Design: Retrospective cohort study. Setting: Emergency department of an academic medical center. Subjects: Adult patients treated with antimicrobials in the emergency department between 2009 and 2015 for fluid-refractory severe sepsis or septic shock. Patients who were transferred, received antimicrobials prior to emergency department arrival, or were treated by an attending physician who cared for less than five study patients were excluded. Interventions: None. Measurements and Main Results: We employed multivariable linear regression to evaluate the association between treating attending physician and door-to-antimicrobial time after adjustment for illness severity (Acute Physiology and Chronic Health Evaluation II score), patient age, prehospital or arrival hypotension, admission from a long-term care facility, mode of arrival, weekend or nighttime admission, source of infection, and trainee involvement in care. Among 421 eligible patients, 74% received antimicrobials within 3 hours of emergency department arrival. After covariate adjustment, attending physicians’ (n = 40) median door-to-antimicrobial times varied significantly, ranging from 71 to 359 minutes (p = 0.002). The percentage of each physician’s patients whose antimicrobials began within 3 hours of emergency department arrival ranged from 0% to 100%. Overall, 12% of variability in antimicrobial timing was explained by the attending physician compared with 4% attributable to illness severity as measured by the Acute Physiology and Chronic Health Evaluation II score (p < 0.001). Some but not all physicians started antimicrobials later for patients who were normotensive on presentation (p = 0.017) or who had a source of infection other than pneumonia (p = 0.006). The adjusted odds of in-hospital mortality increased by 20% for each 1 hour increase in door-to-antimicrobial time (p = 0.046). Conclusions: Among patients with severe sepsis or septic shock receiving antimicrobials in the emergency department, door-to-antimicrobial times varied five-fold among treating physicians. Given the association between antimicrobial delay and mortality, interventions to reduce physician variation in antimicrobial initiation are likely indicated.

Infection and sepsis are leading causes of death worldwide but the epidemiology and outcomes are not well understood in resource-limited settings. We conducted a four-year prospective observational study from March 2013 to February 2017 to examine the clinical epidemiology and outcomes of adults admitted with community-acquired infection in a resource-limited tertiary-care hospital in Ubon Ratchathani province, Northeast Thailand. Hospitalized patients with infection and accompanying systemic manifestations of infection within 24 hours of admission were enrolled. Subjects were classified as having sepsis if they had a modified sequential organ failure assessment (SOFA) score ≥2 at enrollment. This study was registered with ClinicalTrials.gov, number NCT02217592. A total of 4,989 patients were analyzed. Of the cohort, 2,659 (53%) were male and the median age was 57 years (range 18–101). Of these, 1,173 (24%) patients presented primarily to the study hospital, 3,524 (71%) were transferred from 25 district hospitals or 8 smaller hospitals in the province, and 292 (6%) were transferred from one of 30 hospitals in other provinces. Three thousand seven hundred and sixteen (74%) patients were classified as having sepsis. Patients with sepsis had an older age distribution and a greater prevalence of comorbidities compared to patients without sepsis. Twenty eight-day mortality was 21% (765/3,716) in sepsis and 4% (54/1,273) in non-sepsis patients (p<0.001). After adjusting for gender, age, and comorbidities, sepsis on admission (adjusted hazard ratio [HR] 3.30; 95% confidence interval [CI] 2.48–4.41, p<0.001), blood culture positive for pathogenic organisms (adjusted HR 2.21; 95% CI 1.89–2.58, p<0.001) and transfer from other hospitals (adjusted HR 2.18; 95% CI 1.69–2.81, p<0.001) were independently associated with mortality. In conclusion, mortality of community-acquired sepsis in Northeast Thailand is considerable and transferred patients with infection are at increased risk of death. To reduce mortality of sepsis in this and other resource-limited setting, facilitating rapid detection of sepsis in all levels of healthcare facilities, establishing guidelines for transfer of sepsis patients, and initiating sepsis care prior to and during transfer may be beneficial.