Opinion
EDITORIAL
qSOFA Score for Patients With Sepsis
in Low- and Middle-Income Countries
Neill K. J. Adhikari, MDCM, MSc; Gordon D. Rubenfeld, MD, MS
In the past 2 years, sepsis has received considerable atten-
tion from the global community. In 2017, the World Health As-
sembly passed a resolution urging all 194 UN Member States
to implement actions to reduce the burden of sepsis, and for
the World Health Organization to
report on the public health im-
Related article plications of sepsis and its global
consequences.1 It has become
clear that early resuscitation targeted to hemodynamic goals
is more expensive and no more effective than routine care in
high-income countries.2 In Zambia, a protocolized resuscita-
tion strategy actually increased mortality.3 These data and other
studies4 continue to suggest that some evidence on sepsis
therapy does not generalize on a global scale.
In addition, in 2016, the Sepsis-3 expert panel5 developed
a new consensus definition of sepsis as “life-threatening or-
gan dysfunction caused by a dysregulated host response to in-
fection,” with organ dysfunction operationalized by a 2-point
increase in the Sequential (Sepsis-Related) Organ Failure
Assessment score (SOFA). 6 The SOFA score (range, 0-24)
has 6 variables that require 2 clinical and 4 laboratory
assessments.
In the revamped definition, the decades-old concept of sys-
temic inflammatory response syndrome (SIRS)7 was aban-
doned for several reasons. First, SIRS criteria of deranged tem-
perature, white blood cell count, heart rate, and respiratory rate
do not uniformly reflect organ dysfunction and are not con-
cordant with the current conceptual model of sepsis. Second,
SIRS criteria lack specificity, with approximately 50% of pa-
tients in hospital but not in the intensive care unit having at
least 2 criteria at some time, of whom far fewer have infec-
tion and organ dysfunction.8 Third, determination of SIRS man-
dates measurement of the white blood cell count, which im-
pedes feasibility.
Simply based on the distribution of the global population
and epidemiologic data from high-income countries, it is esti-
mated that almost 90% of the annual 19 million sepsis cases
occur in low- and middle-income countries (LMICs), where the
barriers to improving outcomes are numerous.9 These chal-
lenges start well before any acute medical care is provided, with
major disparities in income, living conditions, sanitation of the
built environment, and access to basic public health interven-
tions and ambulatory care. For patients with sepsis who sur-
vive to access an often distant hospital, treatment might in-
clude counterfeit antimicrobials, limited surgical and obstetrical
interventions, and intensive care that might or might not have
life support interventions. Amid these daunting circum-
jama.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: on 05/20/2018
stances, the prompt identification of patients with sepsis among
those that access acute care, to administer timely antibiotics
and resuscitation, is at least as great a challenge in resource-
limited settings in LMICs as it is for wealthier regions.
The 2016 Sepsis-3 Consensus Conference recognized
that using SOFA as part of the sepsis definition outside the
intensive care unit would be impractical. Therefore, the
group used data from US and German hospitals to derive the
quick SOFA (qSOFA) score, which includes 2 vital signs and
a brief neurological assessment in a single measure.10 The
score consists of 1 point for each of hypotension (systolic
blood pressure ≤100 mm Hg), tachypnea (respiratory rate
≥22/min), and altered mental status; a positive score is
defined as 2 or 3 points. Considering the domains of reliabil-
ity, validity, and feasibility when evaluating diagnostic
criteria,11 qSOFA is superior to the SIRS criteria regarding
content validity (agreement with the concept of organ dys-
function as part of sepsis) and feasibility (no laboratory tests
required).
In the initial description, qSOFA had moderate ability to
discriminate between survivors and decedents in noninten-
sive care unit patients with suspected infection (area under the
receiver operating characteristic curve [AUC], 0.81) com-
pared with SIRS (AUC, 0.76). A recent systematic review12 of
studies conducted primarily in high-income countries found
lower discrimination for both qSOFA and SIRS compared with
the original description10 (AUC, 0.72 for qSOFA and 0.64 for
SIRS for patients outside the intensive care unit, calculated
from the reported diagnostic odds ratios13), with qSOFA hav-
ing lower sensitivity and higher specificity for mortality com-
pared with SIRS.
In this issue of JAMA, Rudd and colleagues14 analyzed 8
cohort studies and 1 randomized clinical trial, including
6569 adult patients with suspected infection from 10 LMICs
in Africa, Asia, and the Caribbean. There was substantial
clinical heterogeneity in types of infection (any infection,
suspected Lassa fever, malaria, dengue), location within the
hospital (emergency department, ward, intensive care unit),
and hospital mortality (range, 1.3%-22%). In the 9 studies,
83% of the patients (7 studies) were from hospitals with
intensive care units that included mechanical ventilation
and vasopressors, which is a higher level of resource than
available in many low-income countries. The extent of miss-
ing variables was problematic: 61% for white blood cell
counts, 20% for altered mental status, and 5.3% for mortal-
ity, for example, with wide range of missing variables
among studies. The authors developed a predictive model
(Reprinted) JAMA Published online May 20, 2018 E1
 Opinion Editorial

for hospital mortality using baseline risk factors of age, sex,
HIV status, and transfer status from another center, and
then evaluated the discrimination using this model and
with addition of qSOFA or SIRS. As a predictor of mortality,
qSOFA was overall better than SIRS (AUC, 0.69 and 0.59,
respectively); when added to the baseline model (AUC,
0.56; close to a coin toss), the model with qSOFA (AUC,
0.70) was better than with SIRS (AUC, 0.59).
For researchers studying sepsis in low-resource settings
in LMICs, the feasibility of qSOFA is an important and useful
feature. Although the Sepsis-3 publications make it clear
that sepsis is not defined by qSOFA, its performance in the
study by Rudd and colleagues14 suggests it might be used
that way in resource-limited settings. This approach would
be similar to ultrasonography and oxygen saturation as sub-
stitutions for chest radiography and arterial blood gas analy-
sis in the Kigali modification of the acute respiratory dis-
tress syndrome definition.15 It is particularly reassuring to
see the performance of qSOFA validated across the diverse
pathogens of HIV, tuberculosis, malaria, and dengue rou-
tinely encountered in many LMICs, all of which would have
been uncommon or absent in the derivation data sets and
whose protean manifestations might have affected qSOFA
performance. For local epidemiologic and quality improve-
ment studies, identifying sepsis cases without laboratory
testing—if shown to be sufficiently comparable to SOFA-
defined sepsis—would facilitate comparative studies of
hospital-based incidence and temporal trends, and initia-
tives to improve outcomes. For clinical trials, enrollment of
patients with sepsis defined by a positive qSOFA would be a
form of prognostic enrichment, selecting patients at higher
risk of a sepsis-related poor outcome.
Even if the available data show that qSOFA risk stratifies
patients with suspected infection somewhat better than SIRS,
there remains confusion over what, if any, clinical direction it
provides. Does a positive qSOFA mandate further investiga-
tion, as suggested by Sepsis-3,5 or increased monitoring? Can
an infected patient with a negative qSOFA be safely dis-
charged home? For clinicians in LMICs, where clinician time,
investigations, and intensive care are all markedly con-
strained, these questions are more pressing and the answers
even less clear.
qSOFA might be used to define sepsis in LMICs where SOFA
scoring is unfeasible, but that is definitely not how Sepsis-3 in-
tends it to be used.5 qSOFA might be used, incorrectly, to iden-
tify infected patients; however, it is unlikely to outperform
SIRS, which includes fever and elevated white blood cell count,
or clinical evaluations targeted at specific sources of infection.16
qSOFA might be used as a triage aid like the Pneumonia Se-
verity Index,17 which also risk stratifies infected patients and
has been validated as a decision tool; however, Sepsis-3 spe-
cifically indicates that qSOFA is not to be used in that fashion.5
qSOFA might simply be a valuable warning score indicating
which patients deserve additional testing and monitoring.
However, its superiority to other early warning scores has not
been demonstrated,18 and there are reasons to favor a more
generalizable early warning strategy to improve outcomes of
all patients, not just those with sepsis. Particularly in LMICs,
such a strategy is likely to include more than a warning and
may involve protocols to improve vital signs measurement and
documentation, with algorithms for clinicians to initiate emer-
gency treatment.19
Ultimately, the most relevant questions about qSOFA are
whether it can be used to improve patient outcomes in re-
source-limited settings by providing a fast and feasible defi-
nition of sepsis, or in wealthier hospitals by ensuring that the
next step of clinical and laboratory assessment of organ fail-
ure is rapidly done. On these questions, the jury is still out;
answers will require further data from rigorously conducted
studies.

ARTICLE INFORMATION
Author Affiliations: Department of Critical Care
Medicine, Sunnybrook Health Sciences Centre,
Interdepartmental Division of Critical Care Medicine,
University of Toronto, Toronto, Ontario, Canada.
Corresponding Author: Neill K. J. Adhikari, MDCM,
MSc, Department of Critical Care Medicine,
Sunnybrook Health Sciences Centre and University
of Toronto, 2075 Bayview Ave, Room D1.08,
Toronto, ON M4N 3M5, Canada (neill.adhikari
@utoronto.ca).
Published Online: May 20, 2018.
doi:10.1001/jama.2018.6413
Conflict of Interest Disclosures: Both authors
have completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
REFERENCES
1. Reinhart K, Daniels R, Kissoon N, Machado FR,
Schachter RD, Finfer S. Recognizing sepsis as a
global health priority: a WHO resolution. N Engl J Med.
2017;377(5):414-417.
2. Rowan KM, Angus DC, Bailey M, et al; PRISM
Investigators. Early, goal-directed therapy for septic
shock: a patient-level meta-analysis. N Engl J Med.
2017;376(23):2223-2234.
3. Andrews B, Semler MW, Muchemwa L, et al.
Effect of an early resuscitation protocol on
in-hospital mortality among adults with sepsis and
hypotension: a randomized clinical trial. JAMA.
2017;318(13):1233-1240.
4. Maitland K, Kiguli S, Opoka RO, et al; FEAST Trial
Group. Mortality after fluid bolus in African children
with severe infection. N Engl J Med. 2011;364(26):
2483-2495.
5. Singer M, Deutschman CS, Seymour CW, et al.
The Third International Consensus Definitions for
Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315
(8):801-810.
6. Vincent JL, Moreno R, Takala J, et al. The SOFA
(Sepsis-related Organ Failure Assessment) score to
describe organ dysfunction/failure: on behalf of the
Working Group on Sepsis-Related Problems of the
European Society of Intensive Care Medicine.
Intensive Care Med. 1996;22(7):707-710.
7. Bone RC, Balk RA, Cerra FB, et al; The
ACCP/SCCM Consensus Conference Committee.
American College of Chest Physicians/Society of
Critical Care Medicine. Definitions for sepsis and
organ failure and guidelines for the use of
innovative therapies in sepsis. Chest. 1992;101(6):
1644-1655.
8. Churpek MM, Zadravecz FJ, Winslow C, Howell
MD, Edelson DP. Incidence and prognostic value of
the systemic inflammatory response syndrome and
organ dysfunctions in ward patients. Am J Respir
Crit Care Med. 2015;192(8):958-964.
9. Fleischmann C, Scherag A, Adhikari NK, et al;
International Forum of Acute Care Trialists.
Assessment of global incidence and mortality of
hospital-treated sepsis. current estimates and
limitations. Am J Respir Crit Care Med. 2016;193(3):
259-272.
10. Seymour CW, Liu VX, Iwashyna TJ, et al.
Assessment of clinical criteria for sepsis: for the
Third International Consensus Definitions for Sepsis
and Septic Shock (Sepsis-3). JAMA. 2016;315(8):
762-774.
11. Seymour CW, Coopersmith CM, Deutschman CS,
et al. Application of a framework to assess the
usefulness of alternative sepsis criteria. Crit Care Med.
2016;44(3):e122-e130.
12. Fernando SM, Tran A, Taljaard M, et al.
Prognostic accuracy of the Quick Sequential Organ

E2 JAMA Published online May 20, 2018 (Reprinted) jama.com

© 2018 American Medical Association. All rights reserved.

Downloaded From: on 05/20/2018


Failure Assessment for mortality in patients with
suspected infection: a systematic review and
meta-analysis. Ann Intern Med. 2018;168(4):266-275.
13. Walter SD. Properties of the summary receiver
operating characteristic (SROC) curve for diagnostic
test data. Stat Med. 2002;21(9):1237-1256.
14. Rudd KE, Seymour CW, Aluisio AR, et al; Sepsis
Assessment and Identification in Low Resource
Settings (SAILORS) Collaboration. Association of
the Quick Sequential (Sepsis-Related) Organ Failure
Assessment (qSOFA) score with excess hospital
mortality in adults with suspected infection in low-
jama.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: on 05/20/2018
and middle-income countries [published online
May 20, 2018]. JAMA. doi:10.1001/jama.2018.6229
15. Riviello ED, Kiviri W, Twagirumugabe T, et al.
Hospital incidence and outcomes of the acute
respiratory distress syndrome using the Kigali
modification of the Berlin definition. Am J Respir
Crit Care Med. 2016;193(1):52-59.
16. Attia J, Hatala R, Cook DJ, Wong JG. The
rational clinical examination: does this adult patient
have acute meningitis? JAMA. 1999;282(2):175-181.
17. Fine MJ, Auble TE, Yealy DM, et al. A prediction
rule to identify low-risk patients with
(Reprinted) JAMA Published online May 20, 2018
Editorial Opinion
community-acquired pneumonia. N Engl J Med.
1997;336(4):243-250.
18. Churpek MM, Snyder A, Han X, et al. Quick
Sepsis-related Organ Failure Assessment, systemic
inflammatory response syndrome, and early
warning scores for detecting clinical deterioration in
infected patients outside the intensive care unit.
Am J Respir Crit Care Med. 2017;195(7):906-911.
19. Baker T, Schell CO, Lugazia E, et al. Vital signs
directed therapy: improving care in an intensive
care unit in a low-income country. PLoS One. 2015;
10(12):e0144801.
E3