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American Journal of  
Life Science and Innovation (AJLSI)

The Role of  CD64 and CRP in the Diagnosis of  Sepsis in Neonates 
Fatima Hakim Obaid1*, Kazem Mehdi Kazem1, Israa Khudhair Obayes2 

Volume 4 Issue 1, Year 2025
ISSN: 2833-1397 (Online)

DOI: https://doi.org/10.54536/ajlsi.v4i1.4176
https://journals.e-palli.com/home/index.php/ajlsi

Article Information ABSTRACT

Received: December 03, 2024

Accepted: January 08, 2025

Published: March 12, 2025

Sepsis is the body’s extensive reaction to an infection. It is a severe medical emergency. 
Without prompt treatment, sepsis can quickly lead to tissue damage, organ failure, and death. 
Neonatal sepsis is defined as a syndrome of  clinical features of  the spread of  infection 
and the presence of  bacteremia increase access to the bloodstream. Bacteria most often 
cause infantile septicemia. An infant may be exposed to infections in the hospital or at 
home. This work came to assess the role of  CRP and neutrophil CD64 in the diagnosis of  
sepsis in neonates and infants. This study is a case-control study, it involved two groups (60) 
patients and (20) controls of  one day to one year of  age during the period from May 2019 
to September 2020 of  neonates and infants admitted in Kerbala pediatric teaching hospital 
and Kerbala Primary health care centers. For a total of  80 children, two categories have been 
included and classified. the study showed the mean age for neonates of  sepsis was (7.40±13) 
days while the mean age for neonates of  control was (5.58±6.75)days, The mean age for 
infants of  sepsis was (4.1±7.971) months while the mean age for infants of  control was 
(4.01±5.66) months. in this research, CRP, PCT, and nCD64 are well-diagnostic biomarkers 
for early detection of  neonatal and infantile sepsis. The combination of  these biomarkers 
the diagnosis of  suspected early and late-onset neonatal sepsis based on ROC curve analysis.

Keywords

CD64,CRP, Neonates, PCT, 
Sepsis

1 Department of  Medical Microbiology, Hammurabi College of  Medicine, University of  Babylon. Babylon, Iraq
2  Department of  Diseases and forensic medicine, Hammurabi College of  Medicine, University of  Babylon, Hilla 51002, Iraq
* Corresponding author’s e-mail: fatimadaa92@gmail.com

INTRODUCTION
Sepsis is a life-threatening malfunction of  the organ due 
to a deregulated host reaction to infection (Singer et al., 
2016; Shankar-Hari et al., 2016; Seymour et al., 2016). 
It is one of  the very important Causes of  fatality for 
neonates and infants. If  left organic, Gram-negative 
sepsis is commonly correlated with rather greater death 
than gram-positive death (Moradi et al., 2015). One of  the 
major causes of  neonatal disease and death is bacterial 
sepsis with a prevalence of  1-5 Live births in 1000. free 
exposure to infection can occur during delivery, and its 
clinical presence can appear at birth or during the first 
days of  life (Sharma et al., 2020). Sepsis is the predominant 
cause of  neonatal and infantile death in developing 
countries, accounting for 30-50 percent of  total neonatal 
deaths annually (Gupta et al., 2014; Al-Karaw et al., 2024).
Neonatal sepsis (NS) is a systemic infection that occurs at 
≤28 days of  life in neonates and is a significant cause of  
neonate disease and death (Sankar et al., 2008). Neonatal 
sepsis is a clinical condition characterized by systemic 
signs of  bacterial invasion of  the bloodstream that causes 
circulatory reduction (Edmond & Zaidi, 2010; Kadhim 
et al., 2023).
Sepsis refers to the dispersed inflammatory response 
caused by microbial infections, in which the patient 
typically develops fever, tachycardia, and tachypnea. 
Severe sepsis is linked to at least one organ’s dysfunction. 
When extreme sepsis is supplemented by multiple organ 
system failures, the disease is called septic shock.
In clinical practice, a common problem is that the signs 
and symptoms of  bacterial infections typically overlap, 
particularly in the case of  respiratory tract infections, 
even after laboratory tests have been detected. In 

these circumstances, therefore, a laboratory test with 
more precision would expressively enhance the clinical 
differential diagnosis.

Neonatal sepsis (NS)
Neonatal sepsis is stated to be an infection involving 
the bloodstream in neonates less than 28 days old. 
Many systemic neonatal infections, such as meningitis, 
pneumonia, arthritis, and osteomyelitis, include neonatal 
sepsis. (Vergnano et al., 2005). Neonatal sepsis is one of  
the major causes of  disease and death among neonates 
in the developing world (Edmond & Zaidi, 2010). It has 
been well known that neonatal sepsis causes over 520,000 
deaths of  neonates yearly (Lawn et al., 2010).
 
Mode of  transmission of  early-onset sepsis and late-
onset sepsis
There are some routes of  infection for the neonates 
such as the ascending route that allows bacteria from the 
parental vaginal tract and cervix to enter the uterus before 
delivery, usually due to ruptured membranes or through 
the maternal-fetal vasculature. This is the most popular 
infection path in neonates, Descendent route the fetus 
acquires the pathogen as the neonates descends through 
the vagina at birth. Early-onset sepsis (EOS) is generally 
caused by vertically transferred by the mother to neonates 
before or after birth (Hornik et al., 2012; Abdullah et al., 
2021), these pathogens can rise the vagina, cervix, uterus, 
and amniotic fluid may be infected.
Treatment of  Neonatal sepsis: The World Health 
Organization (WHO) now recommends ampicillin or 
penicillin with gentamicin for both EOS and LOS as first-
line antimicrobials (Organization, 2013).



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Prevention of  Neonatal sepsis
The prevention of  neonatal sepsis requires the 
continuation of  what is understood and new prevention 
plans are being created. Parental treatment with the 
detection of  protective carriage of  GBS via universal 
screening for all prenatal women remains critical for the 
prevention of  early-onset sepsis group B Streptococcus 
(GBS). The guidelines for the prevention of  topical 
group B Streptococcus (GBS) emphasize the need 
for complete parental GBS screening at 37 weeks of  
gestation and include nucleic amplification tests (NAATs) 
as new diagnostic techniques that can be used to improve 
the identification of  group B Streptococcus (GBS) 
production.

Infantile septicemia (IS)
Bacteria most commonly cause infantile septicemia (IS). 
However, it can be triggered by other microorganisms 
too. Infants can be exposed in the hospital or at home 
to infections. The best ways to avoid sepsis are by early 
diagnosis and treatment. Antibiotic medicine begins as 
early as possible.

Treatment of  infantile sepsis
Early diagnosis and care is the only way to avoid sepsis. 
Importantly, the epidemiology of  aggressive infections 
is subject to change as a result of  injection drives 
(Henderson et al., 2010) and the increasing number of  
infants at risk of  getting healthcare-associated infections, 
including premature infants, the infant with a hateful 
disease, or after transplantation (Levy et al., 2012).

Prevention of  infantile septicemia
Prevention of  infantile septicemia, the start of  the 20th 
century, and the toll of  infectious diseases on the United 
States (US) population was high.

Risk factors of  sepsis
Risk Factors of  Neonatal Sepsis
Events that disrupt the amniotic cavity during pregnancy, 
such as cervical and amniocentesis, can increase the rate 
of  intra-amniotic infection and subsequent neonatal 
sepsis. Parental risk variables during effort include fever, 
infected placenta, Elongated rupture of  membranes (> 
18 h), premature birth, Preterm birth (< 37 weeks), and 
frequent vaginal checkups during pregnancy. While risk 
factors for late-onset neonatal sepsis (LOS) include an 
Infected hospital environment, Staying in the hospital for 
a long period, Low birth weight, Birth before 37 weeks, 
or birth more than 18 hours after the Amniotic sac for 
the mother (water) insolvent and long automatic drying.

Risk factors of  Infantile septicemia
The risk factors include the absence of  pregnancy care, 
unconfirmed or sick oversaw home deliveries, unclean 
and unsafe delivery observes and cord care, prematurity, 
low birth weight of  the infant, More than 18 hours before 
birth, the amniotic sac splits (ruptures), lack of  special 

breastfeeding, and delays in respect of  danger signs in 
both mother and infants (Lawn et al., 2005; Barnett et al., 
2006).

MATERIAL AND METHODS
Patients
This study involved two groups (60) patients and (20) 
controls of  one day to one year of  age during the period 
from May 2019 to September 2020 of  neonates and 
infants admitted to Kerbala Pediatric Teaching Hospital 
and Kerbala Primary Health Care Centers. A total of  
80 children in two categories have been included and 
classified. The first group was neonates and infants (a 
group of  sepsis), which consisted of  60 patients (40 
males and 20 females) who attend Kerbala teaching 
hospital during the period from May 2019 to September 
2020. The second group was a healthy control group, 
which consisted of  20 healthy control (12 males and 8 
females) who attend Kerbala primary health care centers. 
They are of  age and sex matching with patients who were 
diagnosed based on the clinical features and laboratory 
findings.

Inclusion criteria for neonates
• Fever (>38°C).
• Breathing problems. 
• Reduced movements. 
• Seizures.
• Bradycardia 
• Tachycardia

Signs of  pain, such as a very fast heart rate during work 
or delivery. 

• High fever (temperature above 38.1. 
• Breathing issues, such as very rapid breathing.
• Digestive concerns, such as low appetite.

Sample Collection
Approximately 3cc of  venous blood was obtained from 
each child (patient and control) preceded by sterilization 
of  the area with 60% ethanol. 2cc  of  blood was dispensed 
into an EDTA tube (for Complete Blood Count  (CBC) 
and neutrophil CD64), 1 cc of  blood (for CRP), 
Dispensed into a plain tube, the serum was separated by 
centrifugation and allowed to coagulate 4,000 round per 
minutes (RPM) for 10 minutes.

Serum inflammatory biomarker detection:
Venous blood sample for biomarkers was evaluated 
before exposure to antibiotics. The samples are placed 
in a plain tube and were separated by centrifugation at 
4,000 rounds per minute (RPM) for 10 minutes, CRP are 
detected by enzymatic immunoassay (EIA).

Statistical Analysis
Using the statistical SPSS v 22.0. Statistical analyses were 
performed to determine the optimal laboratory diagnostic 
parameters (CRP, CD64, and WBC) for predicting 
neonates and infants with sepsis, the receiver operating 



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characteristic (ROC) curve was developed to calculate the 
diagnostic importance of  blood biomarkers for predicting 
neonates and infants with sepsis. A ROC curve showed 
the false-positive rate on the x-axis (specificity) and the 
true-positive rate on the y-axis (sensitivity) for variable 
test cut-off  values. 

RESULTS AND DISCUSSIONS 
The clinical patterns of  the study groups
This study involved two groups (60) patients and (20) 
controls of  one day to one year of  age, The clinical 
patterns of  the study groups are summarized in Table 1.

Table 1: Clinical patterns (sepsis and control group) of  the study.
Clinical patterns Sepsis group  (n=60) Control group (n=20)

(neonates) (infants) (neonates) (infants)
Age days 7.40±13 124.70±239.13 5.58±6.75 120.4±170
Temperature 0.78±39.3 0.75±39.004 0.518±37.04 0.1±37
Gestational age (months) 0.91±9.4 0.65±8.94 0.40±9 0.66±8.75
Birth  weight (kg) 0.84±3.35 2.56±8.25 0.39±3.01 2.94±6.42
Total leukocyte count (mean±SD) 9.04±15.45 7.71±17.38 4.94±9.04 3.06±9.32
CRP, mg/L (mean±SD) 22.21±24.64 36.08±28.65 0.29±0.36 0.46±0.59
nCD64 (mean±SD) 53.90±18.49 66.33±15.63 14.79±19.65 11.85±16.51

Table 2: Comparison between the means and Std. the deviation between the Sepsis and controls of  the total sample 
(n=80).
Group Mean Std. Deviation Significance
CD64 Control 18.39500 14.14 <0.001*

Sepsis 64.5933 16.63
WBC Control 9.1530 4.41 <0.001*

Sepsis 17.0419 7.97
Age(days) Control 72.050 113.39 <0.001*

Sepsis 209.375 139.09
Temp Control 37.025 .41 <0.001*

Sepsis 39.066 .763
*=significant difference.                                                                                          

Types of  Delivery
The percentage of  the delivery of  neonatal and infantile 
of  the total samples patients and healthy control was 37 
out of  80 (37%) cesarean and 63 out of  80(63%) nature 
as in Figure 1.

Figure 1: Types of  delivery

Figure 2: The distribution of  Bleeding during pregnancy 
of  the mother among the total sample

Bleeding during pregnancy
The percentage of  bleeding during pregnancy in the 
total samples patients and healthy control were 19 out 

of  80(19%) mothers they get bleeding and 81 out of  80 
(81%) they have no bleeding. as in Figure 2.

Use of  Optimum inflammatory biomarker cut-off  
values for sepsis diagnosis
ROC analysis has been used to recognize the sensitivity, 
specificity, positive predictive value (PPV), negative 



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predictive value ( NPV), and AUC of  the tests for the 
optimal cut-off  values select, Comparison of  the nCD64, 
CRP, and WBC receiving operating characteristic (ROC) 

curves as markers for diagnosis of  neonatal and infantile 
sepsis as in Figure 3.

Figure 3: Comparison of  the nCD64, CRP, and WBC receiving operating characteristic (ROC) curves as markers for 
diagnosis of  neonatal and infantile sepsis.

Table 3: Area under the curve
Test Result 
Variable(s)

Area Std. Error Asymptotic Sig. Asymptotic 95% Confidence 
Interval
Lower Bound Upper Bound

CRP 1.000 .000 .000 1.000 1.000
WBC .836 .050 .000 .738 .934
CD64 .971 .015 .000 .942 1.000

The test outcome variable(s): WBC, CD64 has at least one 
relationship between the group of  positive real states and 
the group of  negative real states.
The optimum cut-off  value was (10) mg/L for CRP, (8.70) 
for WBC and (2.21) for CD64  in the diagnosis of  neonatal 
and infantile sepsis

Figure 4: The Receiver Operating Characteristic for CD64 as a diagnostic marker to detect neonatal and infantile 
sepsis in (case and control) among the total sample (n=80).

The Receiver Operating Characteristic  (ROC) for CD64 
as a diagnostic marker to detect neonatal and infantile 
sepsis in (sepsis and control ) and area under the curve 
(AUC) were (0.971) this indicates an excellent distinctive 
nature of  WBC count as a classifying index as in Figure 4.



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Discussion
Due to high morbidity and mortality, despite developments 
in medical therapeutics, sepsis remains a major global 
health issue (Angus et al., 2001; Todi et al., 2007).  Neonatal 
sepsis (NS) is a clinical condition that is potentially life-
threatening and requires early intervention.
In this study, the mean CRP for neonates of  the sepsis 
group was (22.21±24.64) mg/L, and the control group 
was (0.29±0.36) mg/L. While in Another study found 
that the mean CRP for the sepsis group was (9.31±13.60) 
mg/L, and the control group was (4.22 ± 2.66) mg/L 
(Adib et al., 2012).
as the cut-off  value by using ROC curves is the range 
of  reported statistical outcomes are as follows: sensitivity 
(100%), specificity (52.66%), positive predictive value 
(82.2%) negative predictive value (95 %), and AUC 
value are (0.951) (Sakha et al., 2008). Most studies have 
completed the importance of  CRP as an early marker of  
neonatal and infant sepsis. From other studies, we know 
CRP is a very early marker, but levels can become normal 
even if  the infection continues.
Serum CRP and PCT measures can help look at neonatal 
and infant sepsis. There must also be a rationally high 
sensitivity and specificity of  a capable diagnostic marker 
the test is negative if  the infection is absent) and a good 
PPV (infection is present when the test is positive),
Thus, both markers had a large diagnostic value more 
usefulness was shown by CRP levels. We used the 
following criteria based on the AUC level to verify 
diagnosis accuracy (Greiner et al., 2000).
Neutrophil CD64 (nCD64) is a receptor of  high affinity 
for monomeric IgG antibodies, which is so complex 
in the opsonized bacteria phagocytosis process. Since 
receptor expression on neutrophil surfaces increases 
approximately one hour after the invasion, infectious 
complications may be a relatively early marker. The 
neutrophil CD64 index is a potential hematologic marker 
of  sepsis. First, many studies have tested the utility of  this 
index in the NICU community, yet with good results in 
both the preterm and term populations, as well as in both 
EOS and LOS cases (Bhandari et al., 2008; Morsy et al., 
2008). In this study, The mean CD64 for neonates of  the 
sepsis group was (53.90±18.49), and the control group 
was (14.79±19.65). While in Another study found that 
the mean CD46 for the sepsis group was (4.08±28.65) 
and the control group was (3.01±13.42) (Ng et al., 2004). 

CONCLUSIONS
As compared to CRP, PCT, and nCD64 are well-
diagnostic biomarkers for early detection of  neonatal and 
infantile sepsis. The combination of  these biomarkers 
could increase sensitivity for the diagnosis of  suspected 
early and late-onset neonatal sepsis based on common 
serum biomarkers with the aid of  optimal cut-off  value 
based on ROC curve analysis. 

Recommendations
Further study is to find out or to highlight the association 

biomarkers CRP, PCT, CD64, and other clinical diagnoses 
or cases. Make other research to study other biomarkers 
in the diagnosis of  sepsis or septicemia.  

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