Status: Funded - Open
Infection, sepsis and meningitis in Surinamese neonates: Novel diagnostic strategies
Rens Zonneveld, MD
Abstract (approximately 250 words)
Neonatal infectious disease has high impact and mortality in Suriname, yet exact incidence is unknown. From a clinical point of view, confirmation or exclusion of neonatal infection remains challenging. Neonates are often admitted with signs of infection and receive preventive antibiotic treatments, while awaiting culture results. Clinical signs of infection can be subtle, while normal blood leukocyte counts and CRP levels lack sensitivity to exclude infection. Thus, the development of diagnostic tools for accurate and early identification or exclusion of neonatal infection remains necessary. Candidate biomarkers are circulating adhesion molecules (cAMs) and their shedding enzymes (SEs), present in blood and spinal fluid (CSF). Blood and cerebral spinal fluid levels of circulating adhesion molecules (e.g., selectins, ICAM-1, VCAM-1) and their shedding enzymes (ADAMs, MMPs, TIMPs) are dependent on each other and have potential relevance for infectious disease in the clinic. However, their levels were never assessed simultaneously in blood nor measured in neonatal CSF as a diagnostic tool. The objective of this study is to determine incidence and impact of neonatal infection in Suriname, along with the simultaneous measurement of cAMs and SEs in neonatal serum as an early indicator of disease status (i.e., no infection vs. infection) in neonates with signs of infection and type of infection (i.e., mild (local) vs. systemic infection (sepsis)), and in CSF for neonatal meningitis. The combination of our epidemiological and novel diagnostic approach may represent an essential step in reducing mortality of neonatal infection in Suriname.
BACKGROUND: High infection related early neonatal mortality indicates a huge burden of neonatal infectious disease in Suriname, but exact incidence and epidemiological determinants are unknown. Upon signs of neonatal infection, confirmation or exclusion of infection remains challenging for which assessing changes in levels of circulating adhesion molecules and their related shedding enzymes in serum and CSF could be helpful.
GAP: Incidence and epidemiological determinants of neonatal infection in Suriname and proper diagnostic tools for its early confirmation or exclusion.
HYPOTHESIS: 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.
METHODS: During a one-year period we will prospectively include neonates with clinical signs of infection (see below) admitted at the Academic Hospital Paramaribo for infection work up, laboratory testing, culturing and antibiotic treatment according to local protocol. We will obtain serum (at t=0 and 48 hours) and CSF (at t=0 hours) for measurement of circulating adhesion molecules and their associated shedding enzymes.
IMPACT: The results of this project lead to a more complete registration (e.g., incidence, risk factors, etiology, microbial cause) of infectious disease amongst newborns in Suriname, which will have immediate impact on prevention and management regimens. Additionally, our proposed diagnostic approach could promote early identification of infected newborns for rapid start of treatments. At the same time, we may be able to prevent unnecessary treatments and related side effects in uninfected ones.
University Medical Center Groningen