Infection, Sepsis and Meningitis in Surinamese Neonates

NCT02486783 | Completed DMC

• 1 other identifier: VG 021-14A
• Study Type: observational
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

Suriname is a small developing country in South America with a population of half a million people. Early neonatal death in Suriname is high with 16 per 1000 live births. Unpublished data from the Suriname Perinatal and Infant Mortality Survey estimate contribution of infection to early neonatal mortality at 25% (4 per 1000 live births) of all deaths. In comparison, incidence rates of neonatal sepsis alone are 3.5 per 1000 live births. These numbers indicate an increased burden of neonatal infection in Suriname versus the U.S. In any case about 40 newborns that die each year of infection are a huge loss, also considering the small Surinamese community. Despite this overall idea on the impact of infectious disease in Surinamese neonates exact information regarding incidence, type of infection (e.g., localized, viral, early-onset or late-onset sepsis), risk factors (e.g., insufficient antenatal care, maternal Group B-Streptococcus status), etiology, microbial causes, morbidity, antibiotic treatment (type and duration), and epidemiological determinants (e.g., gestational age, sex, ethnicity) are lacking. From a clinical perspective, there is still a challenge to identify neonates with infection. Neonates are often admitted with ambivalent clinical symptoms and receive preventive antibiotics that are costly, promote pathogen-resistance, and have negative long-term effects (i.e., on the development of the intestinal bacterial flora). Currently, assessment of blood leukocyte or trombocyte counts and levels of CRP are insufficiently sensitive to be used as biomarkers, while confirmation of actual sepsis or meningitis by positive culture results is relatively rare (0.5-3% in the United States). This complicates decisions on duration of antibiotic treatment and hospitalization significantly, while no other biomarkers exist. The circulating isoforms of adhesion molecules (cAMs), which mediate interactions of leukocytes with the vascular endothelium, have been proposed as biomarkers for infection and sepsis. During infection they accumulate in the bloodstream as a result of shedding, which represents their removal from cell surfaces of endothelial cells and leukocytes by enzymes called sheddases. Recently, we have reviewed mechanisms behind shedding of cAMs in neonatal, pediatric and adult sepsis. The shedding process reflects a critical and active process in orchestrating interaction between leukocytes and the endothelium for an effective host response, while minimizing collateral tissue damage. As a result, both plasma levels of cAMs and their sheddases are subject to change during infection and sepsis. Additionally, compelling, albeit limited, data suggest changes of levels of cAMs in CSF in adult and pediatric meningitis. To date, some evidence exists of changes in levels of cAMs during malaria (in children from Malawi) and sepsis, although not sensitive enough to predict outcomes in the clinic. Those levels have never been assessed simultaneously with levels of their sheddases in blood or CSF as a diagnostic tool. We propose that this combined approach may provide more detailed information about the extent of inflammatory activation in neonates.While a balance in levels is maintained under resting conditions or mild (local) infection, it may be perturbed during sepsis or meningitis . Thus, simultaneous measurement of these levels could promote early identification of infection, and may even distinguish between mild infection, systemic infection or meningitis. Currently, manufacturers are rapidly developing Luminex® technology as an advanced, fast, high-throughput and clinically feasible bedside tool for such an approach. We hypothesize that incidence rates of neonates with infection in Suriname are high. We further hypothesize that, upon signs of infection, the simultaneous measurement of cAMs and their SEs in serum and CSF discriminates between infected and non-infected neonates. We aim to: 1) identify and follow neonates at the Academic Hospital Paramaribo with signs of infection to establish incidence rates of infection, and 2) investigate diagnostic potential of our proposed biomarker combination in these neonates for infection, type of infection (e.g., local (mild), sepsis or meningitis) and outcomes.

Conditions

Neonatal Sepsis; Neonatal Infection; Neonatal Meningitis

Outcome Measures

Primary Outcomes (1)

• Presence of infection upon signs of infection

  Descision on duration of antibiotics (48 hours or 7 days) and blood and liquor culture results

  Within 7 days

Secondary Outcomes (2)

• Infection related mortality

  7 day and 30 day

• Overall mortality due to infection

  1 year

Study Arms (5)

Baseline controls (no signs of infection)

Neonates admitted for serial blood draws for uncomplicated hyperbilirubinemia

Signs of infection A

No infection: antibiotics stopped after 48 hours; negative cultures

Signs of infection B

Clinical infection: 7 day antibiotics; negative cultures

Signs of infection C

Sepsis: positive bacterial blood culture

Signs of infection D

Meningitis: positive bacterial CSF culture

Eligibility Criteria

• Age: Up to 1 Month
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Newborns at the Academic Hospital Paramaribo without signs of infection (baseline controls) and with signs of infection admitted for infection work up and antibiotic treatment.

You may qualify if:

• This study aims to include all neonates presenting here and at the high and medium care facilities with clinical signs of infection, sepsis or meningitis (age: 0-1 month) that require infection work up (i.e., laboratory testing and culturing):
• Baseline controls: uncomplicated jaunice, no other signs of infection
• Clinical signs of infection: tachypnea, dyspnea, apnea, grunting, tachycardia, bradycardia, hypotension, poor perfusion, vomitus, abdominal distension, constipation, poor feeding, lethargy, irritability, convulsions, temperature instability, pale, yellow, bleak, petechiae, bruising, bleeding.

You may not qualify if:

• Extreme prematurity: gestational below 32 weeks of gestational age
• Extreme dysmaturity: birthweight below 1500 grams
• Maternal HIV or malignancy

Sponsors & Collaborators

• Academic Hospital Paramaribo: lead
• University Medical Center Groningen: collaborator

Study Sites (1)

Academic Hospital Paramaribo

Paramaribo, Suriname

Location

Related Publications (2)

• Zonneveld R, Martinelli R, Shapiro NI, Kuijpers TW, Plotz FB, Carman CV. Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults. Crit Care. 2014 Feb 18;18(2):204. doi: 10.1186/cc13733.

  PMID: 24602331 BACKGROUND

• Zonneveld R, Jongman RM, Juliana A, Molema G, van Meurs M, Plotz FB. Serum concentrations of endothelial cell adhesion molecules and their shedding enzymes and early onset sepsis in newborns in Suriname. BMJ Paediatr Open. 2018 Oct 9;2(1):e000312. doi: 10.1136/bmjpo-2018-000312. eCollection 2018.

  PMID: 30397669 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples

MeSH Terms

Conditions

Neonatal Sepsis

Condition Hierarchy (Ancestors)

Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Grietje Molema, PhD

  University Medical Center Groningen, The Netherlands

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 27, 2015
• First Posted: July 1, 2015
• Study Start: May 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 21, 2016

Record last verified: 2016-10

Locations

SU (1)