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

NCT06985160 | Completed

• 1 other identifier: 21975
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief 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

Keywords

genetic polymorphisms, infant, invasive bacterial infections

Outcome Measures

Primary Outcomes (1)

• Correlation between specific gene polymorphisms and the occurrence of invasive bacterial infections in infants under 3 months

  This outcome measures the correlation between the presence of the following gene polymorphisms: TLR4 rs2149356 (c.261-468T\>G), LTA rs2229094 (c.37T\>C), and RFP175 rs1585110 (c.246+8853G\>A), and the occurrence of laboratory-confirmed invasive bacterial infections (IBI) in infants aged \<3 months. Genotyping will be performed using PCR-based methods. IBIs will be categorized into one or more of the following based on predefined diagnostic criteria: Meningitis: confirmed by cerebrospinal fluid (CSF) pleocytosis and laboratory indicators of bacterial infection in CSF. Pneumonia: diagnosed based on auscultatory findings and radiographic evidence of pulmonary infiltrates. Sepsis and bacteremia: identified by positive blood cultures. Urinary tract infection: defined by a significant number of bacterial colonies in urine obtained by sterile catheterization. Invasive bacterial gastroenteritis: diagnosed by isolation of pathogenic bacteria in stool cultures.

  2 weeks

Study Arms (1)

gene polymorphisms

OTHER

The cohort included 100 infants aged 0-3 months diagnosed with IBIs alongside 100 control infants presenting for non-infectious conditions.

Other: Specific single nucleotide polymorphisms

Interventions

Specific single nucleotide polymorphisms OTHER

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

gene polymorphisms

Eligibility Criteria

• Age: 1 Day - 3 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Infants aged between 1 day and 90 days (under 3 months)
• Hospitalized for evaluation of suspected invasive bacterial infections
• Informed consent obtained from parent(s) or legal guardian(s)
• Blood, urine, cerebrospinal fluid (CSF), or stool samples collected within 72 hours of admission
• Genetic material (blood sample) available for DNA extraction

You may not qualify if:

• Known or suspected congenital immunodeficiency
• Previous diagnosis of genetic syndromes affecting immune function
• Major congenital anomalies or chromosomal abnormalities
• Antibiotic therapy initiated more than 24 hours before sample collection
• Parental refusal to participate or withdraw consent

Sponsors & Collaborators

• Ege University: lead

Study Sites (2)

Ege University School of Medicine

Izmir, İzmir, 35100, Turkey (Türkiye)

Location

Ege University School of Medicine

Izmir, Turkey (Türkiye)

Location

Related Publications (8)

• Gomez B, Mintegi S, Bressan S, Da Dalt L, Gervaix A, Lacroix L; European Group for Validation of the Step-by-Step Approach. Validation of the "Step-by-Step" Approach in the Management of Young Febrile Infants. Pediatrics. 2016 Aug;138(2):e20154381. doi: 10.1542/peds.2015-4381. Epub 2016 Jul 5.

  PMID: 27382134 BACKGROUND

• Carrasco-Colom J, Jordan I, Alsina L, Garcia-Garcia JJ, Cambra-Lasaosa FJ, Martin-Mateos MA, Juan M, Munoz-Almagro C. Association of Polymorphisms in IRAK1, IRAK4 and MyD88, and Severe Invasive Pneumococcal Disease. Pediatr Infect Dis J. 2015 Sep;34(9):1008-13. doi: 10.1097/INF.0000000000000779.

  PMID: 26075815 BACKGROUND

• Ladhani SN, Davila S, Hibberd ML, Heath PT, Ramsay ME, Slack MP, Pollard AJ, Booy R. Association between single-nucleotide polymorphisms in Mal/TIRAP and interleukin-10 genes and susceptibility to invasive haemophilus influenzae serotype b infection in immunized children. Clin Infect Dis. 2010 Oct 1;51(7):761-7. doi: 10.1086/656236.

  PMID: 20804371 BACKGROUND

• Zhao J, Gu Q, Wang L, Xu W, Chu L, Wang Y, Li Z, Wu S, Xu J, Hu Z, Shu Q, Fang X. Low-Copy Number Polymorphism in DEFA1/DEFA3 Is Associated with Susceptibility to Hospital-Acquired Infections in Critically Ill Patients. Mediators Inflamm. 2018 May 22;2018:2152650. doi: 10.1155/2018/2152650. eCollection 2018.

  PMID: 29950924 BACKGROUND

• Chen Q, Yang Y, Hou J, Shu Q, Yin Y, Fu W, Han F, Hou T, Zeng C, Nemeth E, Linzmeier R, Ganz T, Fang X. Increased gene copy number of DEFA1/DEFA3 worsens sepsis by inducing endothelial pyroptosis. Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):3161-3170. doi: 10.1073/pnas.1812947116. Epub 2019 Feb 4.

  PMID: 30718392 BACKGROUND

• Delongui F, Carvalho Grion CM, Ehara Watanabe MA, Morimoto HK, Bonametti AM, Maeda Oda JM, Kallaur AP, Matsuo T, Reiche EM. Association of tumor necrosis factor beta genetic polymorphism and sepsis susceptibility. Exp Ther Med. 2011 Mar;2(2):349-356. doi: 10.3892/etm.2011.213. Epub 2011 Jan 20.

  PMID: 22977509 BACKGROUND

• Esposito S, Bosis S, Orenti A, Spena S, Montinaro V, Bianchini S, Zampiero A, Principi N. Genetic polymorphisms and the development of invasive bacterial infections in children. Int J Immunopathol Pharmacol. 2016 Mar;29(1):99-104. doi: 10.1177/0394632015622961. Epub 2015 Dec 18.

  PMID: 26684632 BACKGROUND

• Yurtseven A, Durmusalioglu EA, Turan B, Saz EU. Correlation between single nucleotide polymorphisms in TLR4, LTA and RFP175 genes and susceptibility to invasive bacterial infections in infants under three months of age: A case control study. Pak J Med Sci. 2025 Dec;41(12):3498-3502. doi: 10.12669/pjms.41.12.12651.

  PMID: 41450988 DERIVED

MeSH Terms

Conditions

Bacterial Infections

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Officials

• Ali Yurtseven, MD

  Ege University, School of Medicine Department of Pediatrics, Izmir, Turkey.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 3, 2024
• First Posted: May 22, 2025
• Study Start: April 25, 2020
• Primary Completion: December 20, 2023
• Study Completion: March 15, 2024
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2)