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Op e n  Ac c e ss  
F u l l  L e n g t h  A r t i c l e  

C - Reactive Protein as A Predictor of Sepsis in Children Up 
to 5 Years of Age 

Itrat Fatima1, Gulbin Shahid2, Syeda Sana Ali3, Nasera Bhatti4 

1Assistant Professor, Bone Marrow Transplant, Children’s Hospital, Pakistan Institute of Medical Sciences, Islamabad 
2Assistant Professor, Dept. of Pediatrics, Children’s Hospital, Pakistan Institute of Medical Sciences, Islamabad 

3Postgraduate Trainee, Children`s Hospital, Pakistan Institute of Medical Sciences, Islamabad  
4 Professor of Pediatrics, Children`s Hospital, Pakistan Institute of Medical Sciences, Islamabad 

A B S T R A C T  

Objective: To determine frequency of raised CRP levels in children clinically diagnosed to have sepsis. 

Patients and Methods: In this cross-sectional study, a total of 91 children up to 5-year age, clinically diagnosed as 

having sepsis, were enrolled and were screened for a raised CRP level. The outcome of the study was recorded as the 

frequency of raised CRP level in children clinically suspected of having sepsis. 

Results: The results of the study showed that 95.6% (87/91) of our patients had a raised CRP level.  

Conclusion: CRP can be used as an early sensitive tool for diagnosis of bacterial sepsis. 

Key words:  Biomarkers, C- reactive protein, Sepsis. 

Author`s Contribution 
1Conception, Synthesis and Planning of the 
research, Interpretation and analysis 
2,3Active participation in active 
methodology & Discussion,4 Review the 
study. 

Address of Correspondence 
Dr. Itrat Fatima 
itratfatima012@gmail.com 

Article info. 
Received: Feb 14, 2017 
Accepted: Mar 15, 2017 
 

Cite this article: Fatima I, Shahid G, Ali SS, Bhatti N C - Reactive Protein as A Predictor of Sepsis 
in Children Up to 5 Years of Age. JIMDC. 2017; 6(1):22-26. 
 

Funding Source: Nil 
Conflict of Interest: Nil 

I n t r o d u c t i o n  
 

C-reactive protein (CRP) is an acute-phase reactant 

whose level in the serum rises with inflammation. It is of 

hepatic origin and is a protein that increases following IL-6 

secretion by macrophages,1 in response to a wide range 

of acute and chronic inflammatory conditions such as 

bacterial, viral or fungal infections, rheumatic disorders, 

autoimmune disorders, malignancies and conditions 

causing tissue injury and necrosis.2 CRP rises within 6 

hours of the onset of inflammation and may rise up to 10, 

000 folds peaking at 48 hours. It has a half-life of about 

19 hours which is constant and hence its level is 

determined by its rate of production and therefore by the 

severity of the precipitating cause.3 It may be concluded 

that CRP is a good indicator of inflammation and may be 

used to screen for inflammation. Evaluations have been 

done to determine its diagnostic strength in this context.2  

CRP is an abnormal protein as it is not found in the serum 

of a healthy person, but increases in a matter of hours 

after onset of tissue damage or destruction, regardless of 

the cause, and disappears equally rapidly after the 

destructive process has ceased. CRP is not subject to 

normal variation, as is the erythrocyte sedimentation rate 

(ESR) and is independent of the hematocrit. In this 

respect, it is generally found to be more useful and 

sensitive marker of acute inflammatory disease than 

ESR.4  

Combined usage of total leucocyte count (TLC) and CRP 

gives a better positive predictive value in the diagnosis of 

inflammatory conditions.5 CRP is not only useful in 

determining the presence of an inflammatory disease but 

is also helpful in following its progress and effectiveness 

of treatment. In particular serial measurements of CRP is 

O R I G I N A L  A R T I C L E  

mailto:itratfatima012@gmail.com


 

                           23 J I M D C   2 0 1 7  23 

very useful, for instance when one has to decide about 

the duration of antibiotic therapy in infections.6-10 The 

present study was conducted to determine the frequency 

of raised levels of qualitative CRP in children clinically 

suspected of having sepsis in our setup.   

    P a t i e n t s  a n d  M e t h o d s  

This cross-sectional study was conducted at the 

Children’s Hospital, Pakistan Institute of Medical Sciences 

(PIMS), Islamabad. The sample size was calculated as 91 

by WHO sample calculator with an anticipated population 

of 17% at 95% confidence level and absolute precision of 

0.07. A total of 91 children up to 5 years of age clinically 

suspected of having septicemia were enrolled by non-

probability consecutive sampling. Children with liver 

disease, trauma, chronic kidney disease, suspected 

rheumatic disease or other focal infections like 

pneumonia, urinary tract infections were excluded from 

the study. Clinical impression of sepsis was made if the 

patient had several of the considered signs and 

symptoms of sepsis namely fever, reluctance to feed, 

lethargy, purpura/bleeding or altered level of 

consciousness. Approval from the hospital ethical 

committee was taken. An informed written consent was 

taken from parent/caregiver after explaining the 

importance of the study. Patient profile including name, 

age sex, address, hospital number, serial number, date of 

inclusion in the study were noted. If the patient was sick, 

he /she was first stabilized before blood samples were 

taken for TLC and CRP levels.  All information was 

collected and entered into a proforma especially designed 

for this study. The data was analyzed on a computer 

using SPSS version 10.  Mean was calculated for 

numerical variables like age and total leukocyte count. 

Frequency and percentages were presented for 

categorical variables i.e. gender, positive CRP. CRP 

>5mg/dl was taken as positive. 

R e s u l t s  

In our study a total of 91 cases clinically suspected of 

having sepsis were enrolled. The mean age of the 

patients was 2.6 years ranging from 0.1 to 5 years. 

Among these, 41 (45%) of the patients were between 3 

and 5 years, 24(26.4%) were less than 1 year and 26(28. 

5%) were between 1 to 3 years. There were 54 (59%) 

males and 37 (41%) females with a male to female ratio 

of 1.4:1. As regards clinical signs and symptoms of 

sepsis, almost all patients 88(96.7%) had a fever. Other 

significant clinical findings were purpura/bleeding from 

different sites in 57 (62.2%), reluctance to feed in 

51(56%), lethargy also in 51 (56%), poor tolerance to 

feeding in 33(36.2%) and altered level of consciousness 

in 24(26.3%)–Figure 1.  

88

51 51

24

33

57

0

10

20

30

40

50

60

70

80

90

N
o

 o
f 

p
a

ti
e

n
ts

Fever Reluctant to feed Lethargic Altered level of

consciousness

Poor tolerance to

feed

Bruising or

bleeding from any

site

Clinical findings

 Figure 1: Clinical findings in study patients (N = 91) 

Total leucocyte count was measured in all the study 

patients. The mean TLC was 18713/cmm ranging from 

13400 to 30000/cmm. Majority of the patients- 56(61.5%) 

had TLC between 15001 and 20000cmm, 19(20.8%) had 

TLC between 13000 and 15000/cmm whereas 10(10.9%) 

had TLC between 20001 and 25000/cmm and 6 (6.5%) 

were found to have TLC between 25001 and 30000/cmm- 

Table 1. 

 As per our study objective the frequency of raised CRP 

was measured in all the patients. Vast majority of the 

patients- 87(95.6%) were found to have an increased 

CRP level while in only 4(4.4%) patients, CRP was not 

raised- Table 2. 

Table 1. Total Leukocyte Count in the study patients 
(N = 91) 

TLC (cmm) Number (%) 

13000 to 15000 19 (20.9) 

15001 to 20000 56 (61.5) 

20001 to 25000 10 (11) 

25001 to 30000 6 (6.6) 

Table 2: CRP findings in study patients (n = 91) 

C-reactive protein Number (%) 

    Increased 

   Not increased 

87 (95.6) 

04 (4.4) 



 

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D i s c u s s i o n  

CRP has been fairly extensively studied as a useful 

marker of bacterial sepsis in neonates and children. 11-15 

Other studies which have also reviewed the same.16, 17 

Ammo K et al prospectively studied the utility of CRP and 

ESR as a diagnostic marker for sepsis in neonates, 

evaluating 293 episodes of sepsis in 163 infants.18 

Complete blood counts with differentials, blood cultures, 

CRP and ESR were measured. As expected hematologic 

profile of sepsis episodes were characterized by higher 

white blood cell counts among other indices. In their study 

the CRP and ESR in combination with absolute neutrophil 

count had the highest negative predictive value (93%) for 

ruling out sepsis and 95% sensitivity for diagnosing 

sepsis. They concluded that CRP and ESR are highly 

sensitive markers for neonatal sepsis and recommended 

prospective studies incorporating CRP and ESR into a 

sepsis scoring system. In comparison, our study though 

not confined to neonates, had a number of neonates as 

part of the study population. Though we did not evaluate 

the data of neonates separately but in general we also 

concluded that raised TLC and CRP levels were present 

in the vast majority of patients clinically diagnosed to have 

sepsis. Sidra Younis et al also studied the diagnostic 

accuracy of CRP in neonatal sepsis.12 They enrolled 59 

consecutive patients with risk factors and clinical features 

suggestive of sepsis. CRP and blood cultures were taken 

from all patients. In their study, the sensitivity, specificity, 

positive predictive value and negative predictive value of 

raised CRP were found to be 97.3%, 95.2%, 97.3% and 

95.2% respectively. Blood cultures were positive in 64.4% 

and raised CRP was found in 64.5% cases. They 

concluded that CRP has high sensitivity and specificity for 

establishing the diagnosis of neonatal sepsis which is 

comparable to that of blood culture results. In comparison, 

our study only included patients who were clinically 

diagnosed to have sepsis and CRP was not compared to 

blood cultures and this was a limitation of our study. 

Michal Kyr et al studied the role of the time course of CRP 

levels in association with clinical outcomes in children with 

different septic conditions in an intensive care 

environment.19 They performed a retrospective analysis of 

99 patients with inflammatory response syndrome, sepsis 

or septic shock syndrome. They monitored the CRP level 

for 10 days following the onset of the septic condition and 

determined that there is a significant effect of septic 

condition and diagnosis on the course of CRP levels. In 

patients who did not progress to septic shock, CRP blood 

levels decreased rapidly after reaching peak values in 

contrast to the values in patients with septic shock in 

whom CRP levels decreased slowly. They concluded that 

the more severe the systemic reaction to the insult, the 

higher and the more prolonged the CRP levels. Their 

study population had an average age of 7.6 years with a 

range of 0.1-18.5 years an age range which was much 

higher than in our study (mean age, 2.6 years with a 

range of 0.1-5 years). Moreover, we did not do 

quantitative or serial CRP levels in our study. Both studies 

emphasize the role of CRP in sepsis, however, the study 

by Michal Kyr et al goes a step further in evaluating the 

role of serial measurements of CRP and understanding 

the pattern of change in levels of CRP and relating it to 

sepsis severity. 

Lanziotti et al published an excellent review on the use of 

biomarkers in the screening, diagnosis, prognosis (risk 

stratification), monitoring of therapeutic response and 

rationale use of antibiotics (e.g. determining the adequate 

treatment length) in children with sepsis.20 Their emphasis 

was on evaluating the role of CRP, procalcitonin, 

interleukin 6, 8 and 18 and a few other markers in this 

context. They evaluated five main publications on the use 

of CRP in pediatric infection/sepsis and concluded that 

the use of biomarkers, including CRP, in pediatric sepsis 

cases is promising, although their use should always be 

correlated with clinical evaluation.21-25 They emphasized 

that combined use of multiple biomarkers has a much 

better sensitivity and specificity in the diagnosis and 

prognosis of sepsis compared to the use of a single 

biomarker. In their view biomarkers, such as CRP and 

procalcitonin have shown a key role in clinical practice 

and CRP is especially useful for the evaluation of the 

response to antibiotic treatment when evaluated serially. 

Other advantages of CRP that they enumerated were that 

it is easily available, has low cost, peaks 36-50 hours after 

an inflammatory trigger and is not affected by 

immunosuppression, renal dysfunction or corticosteroid 

use. They also sited limitations of CRP testing in that it 

has variable sensitivity for detecting bacterial infections 

(lower when a single level is measured) and also that it 



 

                           25 J I M D C   2 0 1 7  25 

has low accuracy. Thus, they concluded that the dynamic 

and judicious use of CRP combined with clinical criteria 

and/or other biomarkers has great value and should be 

considered in sepsis diagnosis and especially in sepsis 

treatment evaluation where it probably has a better role 

than in the diagnosis. 

Our study certainly had a number of limitations. Firstly, it 

was a descriptive series only looking at the frequency of 

raised CRP levels in children clinically suspected of 

having sepsis. A control group or a validating test like 

blood culture would have helped to measure actual 

accuracy. Selection bias always remains a possibility in 

observational studies with convenient sampling 

procedures. Moreover, we did not do quantitative or serial 

CRP measurements as were done in most of the above-

cited studies. However, our study did carry the 

advantages of being the first study of its kind in our local 

setting, including a number of neonatal and preschool 

children in the study population and using an easily 

available low cost test like CRP and determining whether 

it could be used as an early surrogate marker of infection 

in children clinically suspected of having sepsis. 

C o n c l u s i o n  

In children, up to 5 years of age clinically suspected of 

having sepsis a raised total white cell count along with a 

raised CRP are present in the vast majority and therefore 

these two indicators together may be used as early 

surrogate markers of sepsis in this paediatric age group. 

Better powered studies are needed in our setup to 

validate this conclusion. 

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