Role of procalcitonin in infants and children with infections

Introduction
Procalcitonin is an inactive protein or precursor of the hormone calcitonin. Calcitonin maintains calcium levels and is synthesized by the thyroid gland. Many tissues and organs synthesize Procalcitonin (PCT) in the body in response to invasion by pathogenic bacteria, fungi, and other parasites. Because of this, it acts as a marker in diagnosing bacterial and other infections, which is a remarkable fact! Parents should have an idea about the role of the PCT in infants (0-1 year of age) and all imperative aspects related to the same. PCT acts as a marker in detecting many infectious diseases in infants. A high concentration of plasma PCT was found in infants with severe infection, while PCT levels were very low in those with no infections. So, let’s become more erudite about Procalcitonin (PCT) and its role in infants and children with infections.

PCT is produced via parafollicular cells of the thyroid and the neuroendocrine cells of the lung and the intestine. It was first reported to be present in increased concentration in patients with systemic infections. Increased concentration has also been observed in other conditions such as trauma and surgery.

Let us probe into the Role of PCT in infants:
In healthy newborns, plasma PCT values increase gradually after birth. It reaches peak values after 24 hours (mean 1.5-2.5 ng/ml, range 0.1-20 ng/ml) and then decreases to normal values below 0.5 ng/ml by 48-72 hours of age. PCT has been proposed as an early marker of infections in neonates, the most common infection being sepsis. It is termed neonatal sepsis, categorized into early-onset neonatal sepsis and late-onset neonatal sepsis.
Transmission of pathogens from the mother to the fetus or newborn before or during delivery, resulting in early-onset sepsis. The bacteria named Streptococcus is the most common organism that attacks infants. Therefore, the early treatment of neonatal sepsis is very crucial. As a result, antibiotic therapy in newborn infants having risk factors for infection begins after birth, even when reliable infection markers are absent. In high-income countries, 4.0–7.4 percent of late-preterm and term neonates are given intravenous antibiotics within the first three days of life if early-onset sepsis is suspected.

Transmission of pathogens from the environment to the baby usually results in Late-onset sepsis (LOS) post-delivery, including after contact with healthcare providers. Moreover, infants requiring intravascular catheter insertion, or other invasive procedures that disrupt the mucosa, are at increased risk for developing LOS. According to the scientific data, the likelihood of infection increases from 25.6% to 84.4% when PCT is positive, while the possibility of infection declines from 25.6% to 5.3% when the PCT level is below 0.5 µg/L.10

Role of PCT in children:

Procalcitonin in Childhood Pneumonia:
Pneumonia is an infection in which the lungs fill with fluid or pus (purulent material). This leads to cough with phlegm or pus, fever, chills, and difficulty breathing.
A procalcitonin-based algorithm was used to guide antibiotic therapy in adults with CAP when antibiotics were discouraged for those with a procalcitonin level of <0.25 ng/mL. PCT levels >2 ng/mL could suggest bacterial pneumonia.

The role of procalcitonin in the early differential diagnosis of suspected children with COVID-19:
No clinical symptoms or mild symptoms, positive computed tomography findings, and family cluster infection are the main clinical features of COVID-19 in children. However, with good performance, procalcitonin can provide an important basis for differentiating COVID-19 alone and other viral infections or viral coinfection. PCT is also used in the detection of influenza, Tuberculosis in children.

The role of procalcitonin in other infections:
Procalcitonin (PCT) and CRP values with upper urinary tract infection were significantly higher than those with lower urinary tract infection. In addition, PCT has higher -sensitivity and specificity than CRP (C-reactive protein).

Is Procalcitonin Useful in critical pediatric patients?
Indeed, it is useful. The below points show how Procalcitonin is useful in pediatric patients:

1. Fever Without source (FWS) is a significant problem in young infants in an emergency department. Interestingly, PCT can be introduced in models to explain the different evolution of sepsis, such as the PIRO concept: predisposing, infection, response, and organism.
2. Another use of PCT in febrile patients is the differential diagnosis of lower urinary tract infection and pyelonephritis, with an upper cutoff point of 0.5 to 1 ng/mL.
3. PCT can also be used as a marker of infection and severity in Paraneoplastic syndromes, small cell lung cancer, hemato-oncology patients, localized bone infections, septic arthritis, and soft tissue infections.
4. Procalcitonin in critically ill patients is very important because of its contribution to the warning of a risk of nosocomial infection and its implications in life prognosis. High PCT should serve to warn about nosocomial infection in those patients without other causes of higher PCT, such as cardiopulmonary arrest and some kinds of surgeries, especially with PCT levels up to 2 ng/mL. It is also useful for diagnosing catheter-related infection in those patients in whom other infections are also under study.
5. Launes et al. demonstrated a 2-day antibiotic reduction in nosocomial infections without increasing complications in pediatric PICU patients. Also, in newborns with early-onset sepsis, there was the demonstration of reduction of almost a day (22.4 hours) in antibiotic therapy.
6. Procalcitonin in surgical procedures: There is frequent SIRS with fever after surgery. It is essential to find a specific biomarker to differentiate between bacterial infection and its absence to avoid unnecessary antibiotics. In children, the response of PCT also varies depending on the characteristics of the surgery. PCT levels may rise 2 ng/mL in major abdominal surgery, especially in infected surgery. This increase is short-lived, and PCT levels fall 24 to 36 hours after surgery.

Wrapping up:
Procalcitonin seems to be an excellent biomarker to diagnose and monitor critically ill pediatric patients with mild-to-moderate and severe bacterial infections. Procalcitonin also appears to decrease antibiotic exposure and shortens the PICU stay.

References:

1. Schrag SJ, Farley MM, Petit S, et al. Epidemiology of invasive early-onset neonatal sepsis, 2005 to 2014. Pediatrics. 2016;138: e20162013 http://pediatrics.aappublications.org/cgi/doi/10.1542/peds.2016-2013. [PubMed] [Google Scholar]
2. Davies MG, Hagen P-O. Systemic inflammatory response syndrome. Br J Surg. 1997;84:920–935. [PubMed] [Google Scholar]
3. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric Crit Care Med. 2005;6:2–8. [PubMed] [Google Scholar]
4. Bell K, Wattie M, Byth K, et al. Procalcitonin: a marker of bacteraemia in SIRS. Anaesth Intensive Care. 2003;31:629–636. [PubMed] [Google Scholar]
5. Journal of the Pediatric Infectious Diseases Society, Volume 7, Issue 1, March 2018, Pages 54–55, https://doi.org/10.1093/jpids/piw095
6. Is Procalcitonin Useful in Pediatric Critical Care Patients? Sara Bobillo-Perez, Javier Rodríguez-Fanjul, Iolanda Jordan GarciaFirst Published August 7, 2018 Review Article Find in PubMed https://doi.org/10.1177/1177271918792244