Current Pediatrics Reports (2023) 11:21–28

https://doi.org/10.1007/s40124-023-00285-4

Recognizing Sepsis in Children in Low‑Resourced Settings: Guidelines

for Frontline Clinicians
Sagar Tungal1 · Nitin Dhochak1 · Rakesh Lodha1

Accepted: 20 March 2023 / Published online: 12 April 2023

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023

Abstract
Purpose of Review Sepsis is one of the leading causes of mortality among pediatric and neonatal age groups, with a major-
ity of the disease burden as well as morbidity and mortality being in low- and middle-income countries (LMICs). Early
recognition of sepsis is vital in preventing multiorgan dysfunction and thus improving outcomes. Heterogenous etiological
factors, multiple comorbidities affecting the disease course, subtle physical signs and symptoms early in the disease, lack
of trained personnel at the point of first contact, difficulty in implementing existing guidelines in resource-limited settings,
and multiple socioeconomic factors lead to delayed recognition as well as subsequent management of sepsis. Formulating
guidelines relevant to LMICs and training the frontline clinicians to recognize and manage the entity are essential to reduce
the overall disease burden.
Recent Findings The existing guidelines for the management of pediatric sepsis are difficult to translate into clinical practice,
especially in resource-limited settings. Reliance on multiple laboratory parameters for the recognition of sepsis, lack of con-
sideration for etiological factors other than bacterial sepsis, and lack of specificity of SIRS-based definitions in identifying
those at highest risk of death make implementation of the existing guidelines difficult and often impractical in resource-
limited settings. Early recognition bundles should be formulated after taking into account the common etiological agents
prevalent in LMICs, comorbidities like malnutrition, anaemia, TB, and HIV and also that rely more on symptoms and signs
and readily available resources than multiple laboratory tests for better recognition by frontline clinicians in these settings.
Scores like LqSOFA and FEAST-PET have shown promise in this direction but need validation in diverse conditions.
Summary Early recognition is vital in improving the clinical outcomes of children with sepsis. Recognition bundles in
low-resource settings should be tailored to the needs and resources available and should rely more on signs and symptoms.
Effective training of the frontline clinicians in recognition of this disease entity with simplified algorithms/bundles leads to
early recognition and management with improved overall outcomes.

Keywords Sepsis · Children · Low- and middle-income countries (LMICs) · Recognition bundle

Introduction highest in low- and middle-income countries (LMICs) [2].

Sepsis is an acute life-threatening condition due to dysregu-
lated immune response to a proven or suspected infectious
trigger leading to one or more organ dysfunction [1••].
Infectious trigger can be bacterial, viral, fungal, or protozoal
in nature. It is one of the leading causes of mortality and
morbidity in both pediatric and adult populations. Burden of
the disease as well as associated morbidity and mortality is
* Rakesh Lodha
rlodha1661@gmail.com
1
Department of Pediatrics, All India Institute of Medical
Sciences, Ansari Nagar, New Delhi 110029, India
Most of the children who die of sepsis have refractory shock
and/or multiple organ dysfunction syndrome (MODS) and
deaths usually occur within 48–72 h of initiation of treatment
[3, 4]. This underscores the importance of early recognition
and resuscitation of children with sepsis to reduce/prevent
the development of MODS and increased risk of mortality.
However, in LMICs, there are many barriers to the successful
implementation of recognition bundles both in community and
hospital settings, often leading to delayed recognition and initia-
tion of treatment as suggested in the existing guidelines [5, 6••].
To address the global burden of sepsis, the emphasis has to be
on addressing these barriers to the care of children with sepsis in
LMICs where the majority of the disease burden lies [7].

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Disease Burden
An estimated 1.2 million cases of childhood sepsis occur
every year all over the world [8]. Around 4% of all children
requiring hospitalization and 8% of all children requiring
ICU care in high-income countries have sepsis [9, 10••].
Sepsis accounts for around 20% of all global deaths, and
more than half of them occur in children [11]. More than
90% of these deaths occur in LMICs [12, 13]. Even these
numbers are likely to significantly under-estimate the actual
burden of the disease as many of infections are likely to be
labelled based on their primary organ of involvement (i.e.
diarrhoea, pneumonia, urinary tract infections) by the treat-
ing clinicians though sepsis and organ dysfunction may be
the common final pathway [14]. Mortality in children with
sepsis varies widely between the ICUs from 4% to as high as
50% depending upon the severity of illness, comorbidities,
and geographical location [10••, 15, 16].
Sepsis in LMICs
Compared to high-income countries, in LMICs, the infec-
tious causes for sepsis tend to be more heterogenous. Diar-
rheal diseases, tropical diseases like malaria, viral haem-
orrhagic fevers, and rickettsial infections are important
etiological agents for sepsis in these regions. Diagnosis of
these varied etiological agents, differing pathophysiology
and changes required for optimization of therapies in these
settings is often under-represented in the guidelines based
primarily on bacterial sepsis [17, 18••].
A significant fraction of children also tend to have various
comorbidities like malnutrition, HIV co-infection, tubercu-
losis, and anaemia that alter the clinical course, response
to standard therapy, and outcomes [17]. Uniform imple-
mentation of the sepsis guidelines in these settings may not
be appropriate [19••]. All these factors make sepsis in the
LMICs different from the spectrum commonly seen in high-
income countries and warrant optimization of the existing
guidelines to address these differences to provide best pos-
sible care with the existing resources.
Importance of Early Recognition of Sepsis
Sepsis-associated organ dysfunction carries with it a high
risk of morbidity and mortality. Early recognition of children
with sepsis before the onset of significant organ dysfunction
is, hence, crucial in improving the outcomes. Delayed recog-
nition of septic shock has been consistently associated with
worse clinical outcomes in both adult and pediatric popula-
tions [18••, 20]. In children with septic shock, each hour of
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Current Pediatrics Reports (2023) 11:21–28
delay in implementing appropriate resuscitation measures and
persistence of hemodynamic abnormalities is associated with
significantly increased odds of mortality (odds ratio [OR] of
1.5 and 2.3, respectively) [21].
Barriers for Early Recognition
There are multiple barriers for early recognition of sepsis in
LMICs, particularly outside the tertiary hospitals.
(a) Lack of consensus definitions/ criteria for sepsis in
children: It has been challenging to have a definition
of sepsis which is widely accepted and is relevant for
LMIC setting, both in terms of the wide spectrum of
etiology of sepsis and also the required resources for
diagnosis.
(b) Prehospital factors: Lack of knowledge, awareness, and
clinical training for the frontline workers is one of the
important hurdles. In many of the LMICs, significant
portion of the community-level healthcare delivery is
provided by nurses and multipurpose workers [22].
Even when a doctor is available, he/she is often not well
trained in taking care of sick children [23]. Lack of safe
transport and economic difficulties further delay the
initial evaluation and, hence, the recognition of sepsis
[24]. This overall delay has an important effect in the
outcomes of the children with sepsis in these countries.
(c) Hospital factors: Burden of sepsis including severe
forms with shock and multiorgan dysfunction is shared
across the health facilities from community centres to
the tertiary hospitals. Because of the lack of infrastruc-
ture, many of these children continue to receive care
outside intensive care units often by personnel with
no formal pediatric/critical care training [17]. Lack of
trained personnel leads to high patient to healthcare
provider ratios leading to inefficient care and less inten-
sive monitoring to detect the clinical worsening from
infection to sepsis to organ dysfunction [22]. Lack of
availability of laboratory facilities for the diagnosis of
infections, inflammatory response, various organ dys-
function, and measure lactate levels cause further delay
in recognition of the etiological agent and severity of
the organ dysfunction once sepsis is suspected.
Challenges in the Application
of the Pediatric Sepsis Definitions in LMICs
Despite being such an important public health problem, it
has so far been difficult to arrive at a gold standard defini-
tion for sepsis that has both good sensitivity and specificity
and can be applied in all settings.
Current Pediatrics Reports (2023) 11:21–28
Sepsis is a heterogenous condition with its clinical
course depending upon the etiological agent, host fac-
tors like genetics, nutritional status, and comorbidities,
and the early interventions. Delay in the presentation and
lack of adequate intensive care infrastructure to provide
organ support in the LMICs make early diagnosis of sepsis
before significant organ dysfunction all the more important
[14]. However, frontline workers in most of the LMICs
usually are not educated or trained to recognize early
stages of pediatric sepsis with subtle clinical signs.
So far, various definitions have been developed pri-
marily by consensus meetings for sepsis in children. 2005
International Pediatric Sepsis Consensus Conference
(IPSCC) definitions and criteria are still being used for
diagnosis pending further revisions [25]. These SIRS-
based definitions have good sensitivity but lack specificity
and have poor discriminative power to identify children at
higher risk of death [26]. This often leads to an increased
burden on healthcare systems because of a large number
of false positives. Need for laboratory tests like blood
count and renal and liver function tests for the diagnosis
of severe sepsis also hinders utility of these criteria in the
LMICs where many healthcare systems lack resources for
these investigations [26]. IPSCC definition is physician-
oriented and complex for frontline workers in LMICs,
hence limiting its utility to mainly in-hospital setting.
The difficulties in the translation of the guidelines
to clinical care have led to significant variability in the
reporting of sepsis. Weiss et al. in their large multicentre
point prevalence study showed that physician diagnosis
of severe sepsis among the children admitted to PICUs
achieved only moderate agreement (inter-rater agreement
(κ ± SE) = 0.57 ± 0.02) with the IPSCC criteria. Trained
physicians in the ICUs diagnosed severe sepsis more
broadly and only 69% of the children diagnosed as severe
sepsis met the consensus criteria [27••]. This study high-
lights the difficulties in translating the definitions in clini-
cal practice. Limitation of SIRS being seen as sole path-
way for organ dysfunction, limited utility in differentiating
infection-sepsis spectrum, and difficulties in translating
the criteria to clinical practice have underlined the need
for better definitions and criteria for pediatric sepsis [26].
In 2016, new definitions and criteria for sepsis in adults
were published (Sepsis-3) with “sepsis” defined as life-
threatening organ dysfunction caused by a dysregulated
host response to infection and “septic shock”- the subset
of sepsis with circulatory and cellular/metabolic dysfunc-
tion associated with a higher risk of mortality [1••]. The
definitions placed an emphasis on sepsis to be differenti-
ated from uncomplicated infection by organ dysfunction
as a result of a dysregulated host response to infection.
The guidelines used the Sequential Organ Failure Assess-
ment (SOFA) score to identify patients with new organ
23
dysfunction [26]. The definitions and criteria were only
for the adult population and the task force emphasized the
need to develop similar evidence-based, validated defini-
tions for pediatric populations [1••].
There have been attempts to apply Sepsis-3 criteria for
pediatric populations [28, 29]. A pediatric version of SOFA
score was developed and validated in pediatric populations
[28]. Another study by Agyeman et al. showed significant
reduction in the incidence of sepsis when organ dysfunction
criteria were applied for the diagnosis of sepsis in place of
SIRS. They also showed better discriminative power of organ
dysfunction-based criteria in predicting mortality. The study
highlighted the need to develop organ dysfunction-based cri-
teria for the diagnosis of pediatric sepsis as well [30].
Pediatric adaptations of Sepsis-3 criteria, however, must
take into account the differences in the pathophysiology and
clinical features of pediatric sepsis in contrast to the spec-
trum seen in adults [26]. The Sepsis-3 definitions typically
identify patients with higher disease severity. Retrospective
studies in pediatric shock have demonstrated that Sepsis-3
criteria were fulfilled by only 48% of children with sep-
tic shock as per IPSCC definition. Children who were not
identified by Sepsis-3 definition also had considerably high
mortality (37%) [31]. These suggest that direct adaptation of
Sepsis-3 definition is not appropriate for the pediatric popu-
lation and is likely to cause further underdiagnosis of sepsis
and septic shock. SOFA score relies on many laboratory-
based parameters. Hence, feasibility of utilizing these defini-
tions outside of intensive care settings and also in resource-
limited settings needs to be investigated [26].
Similar to the synthesis of evidence for the formulation of
adult Sepsis-3 criteria, the Society of Critical Care Medicine
(SCCM) formed the Pediatric Sepsis Definition Taskforce to
evaluate, develop, and validate criteria for the identification
of sepsis in children. The task force conducted a systematic
review with a goal of determining the ability of various demo-
graphic, clinical, laboratory, organ dysfunction, and illness
severity parameters to identify the children with more severe
illness due to infections. They evaluated over 50 variables
and their derived scores. They found higher odds of mortality
for patients with chronic conditions, malnutrition, oncologic
disorders, hypotension, need for inotropes and mechanical
ventilation, and decreased level of consciousness. The study
also showed significant differences in vaso-active inotrope
score, base deficit, pH, lactate, platelet counts, fibrinogen,
urea, creatinine, albumin, potassium, alanine aminotransferase
(ALT), and procalcitonin between non-survivors and survi-
vors. For continuous variables, the study could not come up
with thresholds for determining sepsis/mortality because of
lack of data but they provided the mean values among survi-
vors and non-survivors [32••]. These data will likely be used
to formulate new definitions and criteria for the diagnosis of
pediatric sepsis.
13
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Screening Tool to Identify Children at Risk
of Sepsis
Surviving sepsis campaign guidelines recommend develop-
ing effective screening tools consisting of combinations of
diagnosis and findings to rapidly identify children at risk of
sepsis. These tools however must be tailored to the needs of
each region.
One such screening tool was provided in the 2017 Amer-
ican College of Critical care Medicine (ACCM) guidelines
based on the thresholds of vital parameters as given by
Pediatric Advanced Life Support courses [33]. Sepsis-3
task force recommended the use of quick SOFA (qSOFA)
tool for the rapid recognition of adult patient patients with
suspected infection likely to be at risk of poor outcomes.
The tool comprises of only three variables: low systolic BP
(<100mmHg), high respiratory rate (>22/min), and altered
mental state (GCS<15) [1••, 34]. Both SOFA and qSOFA
have better prognostic performance than previous SIRS-
based criteria in adult patients in different settings [35–37].
Adaptations of qSOFA with age-specific cutoffs have
shown encouraging results in pediatric patients in emer-
gency departments [29, 38]. A systematic review and
meta-analysis on the topic included 11 studies and 172,569
patients. The study found age-adjusted qSOFA to have mod-
erate performance in predicting in-hospital mortality and
disease severity in children. Age-adjusted qSOFA achieved
AUC of 0.733 and a pooled diagnostic odds ratio (DOR) of
6.57. Significant areas of heterogeneity were noted in the use
of GCS to diagnose altered mental status in children and the
authors suggested the use of AVPU scale to improve the per-
formance [39]. Another potential limitation of age-adjusted
qSOFA is the use of low systolic BP as a parameter. It is well
known that hypotension develops late in the clinical course
in children compared to adults [40, 41]. Hence, it may not
be an ideal parameter in a screening tool.
To address these problems in age-adjusted qSOFA tool,
Romaine et al. developed the “Liverpool quick Sequential
Organ Failure Assessment (LqSOFA)” score (Table 1). The
tool comprises of respiratory rate, age-adjusted heart rate,
capillary refill time, and level of consciousness assessed
using AVPU scale. LqSOFA with ≥ 2 criteria demonstrated
similar sensitivity (0.6) and specificity (0.988) in predict-
ing mortality compared to age-adjusted qSOFA with ≥ 2
criteria. Compared with age-adjusted qSOFA ≥ 2 criteria,
LqSOFA ≥ 2 criteria showed better sensitivity (0.392 vs.
0.289) and similar specificity (0.992 vs. 0.991) in predicting
ICU admission within 48 h [42]. Simplicity of the score and
absence of any laboratory parameters make it an attractive
tool to be used in resource-limited settings. However, the
sensitivity of these tools is sub-optimal [42]. Further studies
are needed to validate the tool in LMICs.
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Current Pediatrics Reports (2023) 11:21–28
Table 1  Scoring thresholds for each component of LqSOFA [42]
Criterion Points allocated
1 point 0 point
CRT​ >3 s <3s
AVPU VPU Alert
HR >99th centile Bonafide et al. <99th centile
[43] age-specific thresholds Bonafide et al.
age-specific
thresholds
RR >99th centile Bonafide et al. <99th centile
age-specific thresholds Bonafide et al.
age-specific
thresholds
Recognition of Sepsis in LMICs
for the Frontline Workers
To improve the management of children under the age of
5 years with common illnesses in both the community and
healthcare settings in LMICs, WHO and UNICEF came up
with guidelines of Integrated Management of Childhood Ill-
ness for the healthcare workers coming in contact with children
who are ill in the community [44]. Guidelines took into con-
sideration the resources available, the comorbidities, and tropi-
cal diseases prevalent in the LMICs and came up with these
guidelines that predominantly relied on clinical symptoms and
signs to assess, classify, and treat the common illnesses. With
proper implementation and training, healthcare workers with
or without formal clinical training would be able to assess and
manage the children [44]. The guidelines’ emphasis of clinical
findings for the identification and classification of illnesses and
identification of the comorbidities is relevant to the LMIC set-
tings. However, the disease-specific classification fails to iden-
tify sepsis and related organ dysfunction as a final common
pathway of clinical deterioration for many of these diseases.
The guidelines for the recognition of sepsis in these settings
should rely on clinical findings, take into account the common
comorbidities and focus on identification of organ dysfunction
secondary to sepsis along with the source of infection.
Early recognition of shock in children with sepsis is
relatively easy where facilities for intensive monitoring are
available. However, recognizing this entity based on clinical
symptoms and signs requires proper training and frequent
and careful monitoring. The WHO in their Emergency Tri-
age and Treatment guidelines emphasized on the approach
of identifying the children with sepsis and shock rather than
individual disease entities [45]. WHO ETAT emphasizes on
recognizing danger signs and starting therapies rather than
giving etiology-specific labels. Signs suggestive of shock
as outlined in the guidelines include cold extremities, poor
pulses, and prolonged capillary refill time.
Current Pediatrics Reports (2023) 11:21–28 25

Utility of different sets of clinical parameters as clinical tools
for the recognition of sepsis has been tested in various stud-
ies. From the data of Fluid Expansion As Supportive Therapy
(FEAST) trial, the authors derived FEAST Pediatric Emer-
gency Triage (PET) score to identify children at highest risk
of mortality [46••]. The score consisted of 8 clinical variables:
temperature, heart rate, capillary refill time, conscious level,
severe pallor, respiratory distress, lung crepitations, and weak
pulse volume. Scores ranged from 0 to 10. The tool had an
AUROC of 0.82 (95% CI, 0.77–0.87) when applied to FEAST
trial dataset. Among the laboratory parameters, they found
lactate, pH and blood urea nitrogen to have the best discrimi-
nation value in predicting mortality [46]. Among the clinical
parameters, capillary refill time is consistently shown to predict
mortality in children with severe infections [46••, 47, 48] but
suffers from poor reproducibility and inter-observer variations
especially in dark-skinned individuals and when performed by
inexperienced clinicians [49, 50]. Among other parameters,
hypothermia, poor pulses, and depressed mental status have
been shown to be associated with poor outcomes and can be
incorporated in recognition bundles [46••, 51–53]. When-
ever available, pulse oximetry should be incorporated in the
screening tools considering the burden of pneumonia as a focus
for sepsis in LMICs [54]. Blood lactate is another laboratory
parameter that has consistently shown to be associated with
poor outcomes in children with infections [55–58].

Suggested Algorithm for Recognition of Sepsis in Children in LMICs

Child is brought with concern No

Sepsis unlikely
and/or temperature abnormality?

Yes

Any of the anger signs?

1. Gasping/absent breathing Yes
2. Central cyanosis l
3. Unconsciousness
4.

No

>1 symptoms Examine

present 1. Temperature(>38C or <36C)
2. Tachycardia
1. hing 3. Tachypnea
2. History of seizures 4. Poor pulse volume
3. Fast breathing with chest 5. Hypotension
6. Prolonged CFT
4. Loose stools 7. Mental status
5. Rash abnormality(Abnormal
6. Lethargy AVPU)
7. Decreased urine output 8. led skin
Wherever available
1. SpO2 (<92% on room air)
2. Serum Lactate (>2)
Once sepsis is recognized, look for:
1. Evidence of protein energy

2. History of HIV/TB in the family

3. Severe pallor >3 of the 8 parameters + one or
ters
Consider possibility of malaria, measles,
sial diseases
Sepsis

Conclusion These factors translate into worse clinical outcomes. There

Sepsis is one of the leading causes of morbidity and mortal-
ity among children in LMICs. The etiological factors are
more heterogenous and the clinical course is often altered
by comorbidities and delay in recognition and treatment.
are multiple barriers in translating the existing guidelines
on the management of sepsis in these regions. Hence, there
is a need for the development of guidelines keeping in mind
the epidemiology, existing infrastructure, and resources of
LMICs as the majority of the disease burden lies in these

13
26
regions. More emphasis on clinical signs and symptoms with
less emphasis on laboratory parameters in the definitions
is needed for better application and hence better recogni-
tion of the disease entity. Early recognition is essential for
improving the outcomes. Recognition bundles tailored to
the disease profile and resources available for each setting
should be developed and implemented.
Acknowledgements The authors wish to thank Dr. Shamiel Salie for
reviewing their manuscript.
Compliance with Ethical Standards
Conflict of Interest The authors declare no competing interests.
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