The Association of Gene Polymorphisms With Invasive Bacterial Infections in Neonates and Young Infants

Summary

Invasive bacterial infections (IBIs) are globally significant, with high mortality rates, particularly within the critical 0-3 month age bracket. The first three months of life mark a peak in IBI prevalence, with an estimated 10-20% of febrile presentations in this age group resulting in an IBI diagnosis. Although multiple factors are implicated in this heightened vulnerability, the precise mechanisms driving the differential development of IBIs among similarly situated infants remain unclear. Genetic diversity and susceptibility are increasingly recognized as influential factors. Extensive literature demonstrates a correlation between genetic polymorphisms and susceptibility to invasive bacterial infections.

This study aims to explore the association of gene polymorphisms TLR4 rs2149356 (c.261-468T\>G), LTA rs2229094 (c.37T\>C), and RFP175 rs1585110 (c.246+8853G\>A) with the occurrence of invasive bacterial infections in the population of children aged under 3 months.

We conducted a prospective observational study at a leading tertiary care hospital. The cohort included 100 infants aged 0-3 months diagnosed with IBIs alongside 100 control infants presenting for non-infectious conditions such as trauma, infantile colic, and hyperbilirubinemia. Cases with any symptoms suggesting an infection were excluded from the control group. Invasive bacterial infections categorized in this study included meningitis, pneumonia, sepsis, bacteremia, urinary tract infections, and invasive bacterial gastroenteritis. Diagnostic criteria were stringent: meningitis was confirmed via signs of bacterial infection in cerebrospinal fluid; pneumonia through auscultatory findings and radiographic evidence of pulmonary infiltrates; bacteremia by positive blood cultures; urinary tract infections by significant bacterial cultures from sterile catheterization; and gastroenteritis by the identification of pathogenic organisms in stool cultures. No additional blood was taken from the patients for the study. Instead, blood samples that were collected for tests determined by the physicians due to the patients' condition in the emergency department were retrieved from the laboratory after the requested tests were completed and reused for the study.

Conditions

• Polymorphism, Genetic
• Bacterial Infections
• Infant

Interventions

OTHER

Specific single nucleotide polymorphisms

Next-generation sequencing was performed to analyze the TLR4, LTA, and RFP175 genes, with a focus on specific single nucleotide polymorphisms

Sponsors & Collaborators

• Ege University

  lead OTHER

Principal Investigators

• Ali Yurtseven, MD · Ege University, School of Medicine Department of Pediatrics, Izmir, Turkey.

Study Design

Allocation

NA

Purpose

SCREENING

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Day

Max Age

3 Months

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-04-25

Primary Completion

2023-12-20

Completion

2024-03-15

Countries

• Turkey (Türkiye)

Study Locations