Validation of the Emergency Department-Paediatric Early Warning Score (ED-PEWS) for use in low- and middle-income countries: A multicentre observational study.

Early recognition of children at risk of serious illness is essential in preventing morbidity and mortality, particularly in low- and middle-income countries (LMICs). This study aimed to validate the Emergency Department-Paediatric Early Warning Score (ED-PEWS) for use in acute care settings in LMICs. This observational study is based on previously collected clinical data from consecutive children attending four diverse settings in LMICs. Inclusion criteria and study periods (2010-2021) varied. We simulated the ED-PEWS, consisting of patient age, consciousness, work of breathing, respiratory rate, oxygen saturation, heart rate, and capillary refill time, based on the first available parameters. Discrimination was assessed by the area under the curve (AUC), sensitivity and specificity (previously defined cut-offs < 6 and ≥ 15). The outcome measure was for each setting a composite marker of high urgency. 41,917 visits from Gambia rural, 501 visits from Gambia urban, 2,608 visits from Suriname, and 1,682 visits from Tanzania were included. The proportion of high urgency was variable (range 4.6% to 24.9%). Performance ranged from AUC 0.80 (95%CI 0.70-0.89) in Gambia urban to 0.62 (95%CI 0.55-0.67) in Tanzania. The low-urgency cut-off showed a high sensitivity in all settings ranging from 0.83 (95%CI 0.81-0.84) to 1.00 (95%CI 0.97-1.00). The high-urgency cut-off showed a specificity ranging from 0.71 (95%CI 0.66-0.75) to 0.97 (95%CI 0.97-0.97). The ED-PEWS has a moderate to good performance for the recognition of high urgency children in these LMIC settings. The performance appears to have potential in improving the identification of high urgency children in LMICs.

Incidence of Early and Late Onset Neonatal Sepsis in Suriname: A National Tertiary Hospital Birth-cohort Study.

BACKGROUND: Early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) are important causes of neonatal mortality and morbidity. A pressing need for reliable and detailed data of low- and middle-income countries exists. This study aimed to describe the incidence and outcome of neonatal sepsis in the only tertiary hospital of Suriname, a middle-income country in South America. METHODS: Infants born at the Academic Hospital of Paramaribo from May 2017 through December 2018 were prospectively included at birth. Perinatal data, duration of antibiotic treatment, blood culture results and mortality data were gathered. Neonatal sepsis was defined as positive blood culture with a pathogenic microorganism within the first 28 days of life. RESULTS: Of the 2190 infants included, 483 (22%) were admitted to neonatal (intensive) care. The incidence of EONS was 2.1 (95% CI: 0.9-5) per 1000 live births, with no deaths. Antibiotics for suspected EONS were administrated to 189 (8.6%) infants, of whom 155 (82%) were born prematurely. The incidence of LONS cases was 145 (95% CI: 114-176) per 1000 admissions. Gramnegative bacteria accounted for 70% (48 out of 70) of causative organisms. Seventeen deaths were directly caused by sepsis (35 per 1000 admissions). CONCLUSIONS: Findings from this tertiary center birth cohort study in a middle-income setting indicate EONS incidence and outcomes comparable to high-income settings, whereas LONS is a more prevalent and significant challenge with a predominance of gram-negative bacteria, and high mortality.

Requirement of respiratory support in acute bronchiolitis in infants is linked to endothelial and neutrophil activation.

BACKGROUND: Evidence shows that activation of pulmonary vascular endothelium and neutrophils are involved in the pathophysiology of acute bronchiolitis. We hypothesized that levels of markers of endothelial activation and leukocyte counts are associated with requirement and duration of respiratory support. METHODS: Thirty-four infants with bronchiolitis and eight controls were included. Nasopharyngeal swabs and blood samples were taken at admission. Serum levels of Angiopoietin (Ang)-1, Ang-2, sP-selectin, sE-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), and leukocyte counts were measured. For univariate analysis, bronchiolitis cases were grouped into two groups, namely those not requiring and those requiring any form of respiratory support. To control for known risk factors for poor outcome (i.e., age, prematurity, and congenital heart disease), and for days post symptom onset, linear regression analysis was performed with duration of any type of respiratory support in days. RESULTS: Ang-2 levels, Ang-2/Ang-1 ratios, sE-selectin levels, immature neutrophil count, and neutrophil/lymphocyte ratio (NLR) were higher in acute bronchiolitis versus controls. Ang-2, and NLR levels were significantly higher, and lymphocyte counts significantly lower, in infants that required respiratory support versus those that did not. Ang-2 levels (ß: .32, 95% confidence interval [CI]: 0.19-1.19) and NLR (ß: .68, 95% CI: 0.17-1.19) were positive predictors for the duration of respiratory support. CONCLUSIONS: Markers of endothelial and neutrophil activation are associated with respiratory support for acute bronchiolitis. Admission Ang-2 levels and NLR may be promising markers to determine requirement of respiratory support and deserve further study.

Viral causes of severe acute respiratory infection in hospitalized children and association with outcomes: A two-year prospective surveillance study in Suriname.

BACKGROUND: Viruses are the most frequent cause of severe acute respiratory infection (SARI) in children. It is currently unknown whether presence of a virus, the number of viruses, or type of virus, are associated with clinical outcomes of pediatric SARI in developing countries. METHODS: Between 2012 and 2014 nasopharyngeal swabs and demographic and clinical variables were prospectively collected for surveillance of viral causes of SARI in Surinamese children within 48 hours after hospitalization. These swabs were tested for 18 respiratory viruses using a multiplex polymerase chain reaction (PCR) panel to identify the specific viral causes of SARI, unknown to the treating physicians. In post hoc analyses we evaluated if the PCR results, and demographic and clinical characteristics, were associated with course of disease, duration of respiratory support, and length of stay (LOS). RESULTS: Of a total of 316 analyzed children, 290 (92%) had one or more viruses. Rhinovirus/enterovirus (43%) and respiratory syncytial virus (34%) were most prevalent. Course of disease was mild in 234 (74%), moderate in 68 (22%), and severe in 14 (4%) children. Neither presence of a single virus, multiple viruses, or the type of virus, were different between groups. Prematurity and lower weight-for-age-z-score were independent predictors of a severe course of disease, longer duration of respiratory support, and longer LOS. CONCLUSIONS: Viruses are common causes of pediatric SARI in Suriname, yet not necessarily associated with clinical outcomes. In developing countries, demographic and clinical variables can help to identify children at-risk for worse outcome, while PCR testing may be reserved to identify specific viruses, such as influenza, in specific patient groups or during outbreaks.

Epidemiology and Mortality of Early-Onset Neonatal Sepsis in Suriname: A 2-Year Surveillance Study.

We conducted a nationwide surveillance study to produce reliable national estimates on incidence, etiology, and mortality of early-onset neonatal sepsis (EONS) in Suriname. The estimated national population incidence rate of EONS was 1.37 (95% CI: 0.90-1.99) per 1000 live births and in-hospital mortality was 25.9%.

Serum Levels of Markers of Endothelial Activation Are Not Associated with a Positive Blood Culture in Surinamese Children with Suspected Severe Infection.

BACKGROUND: Systemic serum levels of markers of endothelial activation are associated with infection. We hypothesize that levels of markers of endothelial activation are associated with the presence of a positive blood culture as a manifestation of a systemic infection in children with a suspected severe infection in Suriname. METHODS: In this prospective observational cohort study, children between 1 month and 18 years of age suspected of severe infection as assessed by the threating physician, and in whom laboratory testing and blood culturing was performed before start of intravenous antibiotic treatment, were recruited at the emergency department of the Academic Hospital Paramaribo, Suriname. Serum was collected at blood culturing and after 48-72 h of admission. Serum was stored for measurement of levels of Angiopoietin (Ang)-1, Ang-2, soluble (s)P-selectin, sE-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and platelet and endothelial cell adhesion molecule-1. RESULTS: Fifty-one children were included of whom 10 had a positive blood culture. Baseline characteristics were similar between children with and without a positive blood culture. No significant differences in serum levels of the Angiopoietins or soluble cellular adhesion molecules between groups were observed at start of antibiotic treatment nor after 48-72 h. CONCLUSIONS: The data from this study indicate that in children with severe infection, serum levels of markers of endothelial cell activation are not associated with a positive blood culture. Thus, having a positive bacterial blood culture may not be the only factor driving endothelial activation in this patient population.

Infectious pseudo-aneurysm of the left ventricle: a case report and a review of the literature.

BACKGROUND: In the workup of a pediatric patient with pericarditis we found evidence of a pseudo-aneurysm of the left ventricle, which is a rare complication of purulent pericarditis. CASE PRESENTATION: We present a case of a six-year-old girl who was diagnosed with pericarditis and a fistula between the pericardial and the intra-luminal space of the left ventricle of the heart. She was successfully treated with antibiotics and cardio-thoracic surgery. We found 23 published cases (21 with follow-up) of infectious pseudo-aneurysm of the heart, of which 19 underwent surgery, 5 had fatal outcome, and 2 who refused surgery survived. The majority of cases were associated with Staphylococcus aureus. The exact mechanisms of this rare complication remain unknown. CONCLUSIONS: A pseudo-aneurysm of the left ventricle is a rare and not well understood complication of a purulent pericarditis most commonly caused by Staphylococcus aureus infection. Because of risk of rupture, surgical intervention is advised.

Neutrophil-endothelial interactions in respiratory syncytial virus bronchiolitis: An understudied aspect with a potential for prediction of severity of disease.

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) causes significant morbidity and mortality among young infants worldwide. It is currently widely accepted that neutrophil influx into the airways is a hallmark of the pathophysiology. However, the exact mechanism of neutrophil migration from the vasculature into the alveolar space in RSV LRTI has received little attention. Data shows that endothelial cells become activated upon RSV infection, driving a 'pro-adhesive state' for circulating neutrophils with upregulation of endothelial intercellular adhesion molecule-1 (ICAM-1). During RSV LRTI different subsets of immature and mature neutrophils are present in the bloodstream, that upregulate integrins lymphocyte-function associated antigen (LFA)-1 and macrophage (Mac)-1, serving as ICAM-1 ligands. An alveolar gradient of interleukin-8 may serve as a potent chemoattractant for circulating neutrophils. Neutrophils from lung aspirates of RSV-infected infants show further signs of inflammatory and migratory activation, while soluble endothelial cell adhesion molecules (sCAMs), such as sICAM-1, have become measurable in the systemic circulation. Whether these mechanisms are solely responsible for neutrophil migration into the alveolar space remains under debate. However, data indicate that the currently postulated neutrophil influx into the lungs should rather be regarded as a neutrophil efflux from the vasculature, involving substantial neutrophil-endothelial interactions. Molecular patterns of these interactions may be clinically useful to predict outcomes of RSV LRTI and deserve further study.

Markers of endothelial cell activation in suspected late onset neonatal sepsis in Surinamese newborns: a pilot study.

BACKGROUND: Serum levels of markers of endothelial cell activation are associated with bacteremia and mortality in sepsis in adults, children, and newborns with early onset sepsis. We hypothesize that levels of these markers are associated with these outcomes in hospitalized newborns with suspected late onset neonatal sepsis (LONS). METHODS: In this prospective cohort study, newborns admitted to the tertiary neonatal care facility of Suriname were included upon clinical suspicion of LONS and before start of antibiotic treatment, between April 1, 2015 and May 31, 2016. Serum concentrations of angiopoietin-1, angiopoietin-2, and soluble isoforms of P-selectin, E-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), platelet and endothelial cell adhesion molecule-1 (sPECAM-1), matrix metalloproteinase-9 (MMP-9), neutrophil elastase, and tissue-inhibitor of metalloproteinases-1 (TIMP-1) were measured. RESULTS: Twenty-thee newborns were included. Baseline characteristics were similar between newborns with and without bacteremia and between non-survivors and survivors. Only soluble E-selectin (sE-selectin) was higher in newborns with bacteremia versus non-bacteremia (P=0.04) and lower in non-survivors (P=0.04). No conclusions could be made for sVCAM-1 due to high serum concentrations. CONCLUSIONS: In conclusion, the data from this pilot study indicate that serum levels of markers of endothelial cell activation are poorly associated with bacteremia and mortality.

Serum concentrations of endothelial cell adhesion molecules and their shedding enzymes and early onset sepsis in newborns in Suriname.

BACKGROUND: Early onset sepsis (EOS) is defined as onset of sepsis within 72 hours after birth. Leucocyte-endothelial interactions play a pivotal part in EOS pathophysiology. Endothelial cell adhesion molecules (CAMs) orchestrate these interactions and their soluble isoforms (sCAMs) are released into the vasculature by enzymes called sheddases. PURPOSE: This study was undertaken to explore further the pathophysiology of EOS and to investigate the potential of sCAM and their sheddases as potential biomarkers for EOS. METHODS: Stored serum aliquots were used from 71 Surinamese newborns suspected of EOS and 20 healthy newborns from an earlier study. Serum had been collected within 72 hours after birth and six (8.6%) newborns had a positive blood culture with gram-negative pathogens. Concentrations of sCAMs sP-selectin, sE-selectin, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and platelet and endothelial cell adhesion molecule-1, sheddases matrix metalloproteinase-9 (MMP-9) and neutrophil elastase (NE) and sheddase antagonist tissue-inhibitor of metalloproteinases-1 (TIMP-1) were measured simultaneously with Luminex and ELISA. RESULTS: MMP-9 and TIMP-1 levels were measured in serum of n=91 newborns and sCAMs and NE levels in serum of n=80 newborns, respectively. We found no differences in median concentrations of sCAMs, MMP-9 and TIMP-1 or NE between blood culture positive EOS, blood culture negative EOS and control groups at start of antibiotic treatment. CONCLUSIONS: Our data indicate that serum concentrations of sCAMs and their sheddases have no clinical utility as biomarkers for EOS. TRIAL REGISTRATION NUMBER: NCT02486783. Results.

Improved referral and survival of newborns after scaling up of intensive care in Suriname.

BACKGROUND: Scaling up neonatal care facilities in developing countries can improve survival of newborns. Recently, the only tertiary neonatal care facility in Suriname transitioned to a modern environment in which interventions to improve intensive care were performed. This study evaluates impact of this transition on referral pattern and outcomes of newborns. METHODS: A retrospective chart study amongst newborns admitted to the facility was performed and outcomes of newborns between two 9-month periods before and after the transition in March 2015 were compared. RESULTS: After the transition more intensive care was delivered (RR 1.23; 95% CI 1.07-1.42) and more outborn newborns were treated (RR 2.02; 95% CI 1.39-2.95) with similar birth weight in both periods (P=0.16). Mortality of inborn and outborn newborns was reduced (RR 0.62; 95% CI 0.41-0.94), along with mortality of sepsis (RR 0.37; 95% CI 0.17-0.81) and asphyxia (RR 0.21; 95% CI 0.51-0.87). Mortality of newborns with a birth weight <1000 grams (34.8%; RR 0.90; 95% CI 0.43-1.90) and incidence of sepsis (38.8%, 95% CI 33.3-44.6) and necrotizing enterocolitis (NEC) (12.5%, 95% CI 6.2-23.6) remained high after the transition. CONCLUSIONS: After scaling up intensive care at our neonatal care facility more outborn newborns were admitted and survival improved for both in- and outborn newborns. Challenges ahead are sustainability, further improvement of tertiary function, and prevention of NEC and sepsis.

Low Serum Angiopoietin-1, High Serum Angiopoietin-2, and High Ang-2/Ang-1 Protein Ratio are Associated with Early Onset Sepsis in Surinamese Newborns.

PURPOSE: Vascular inflammation and leakage in sepsis is mediated by Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) and their phosphorylation of the endothelial Tie-2 receptor. This study investigates levels of Ang-1 and Ang-2 in newborns to gain insight in the vascular pathophysiology of early onset sepsis (EOS) within 72 h after birth. METHODS: A prospective cohort study was performed among 71 Surinamese newborns treated with antibiotics for suspected EOS and 20 control newborns. Newborns with suspected EOS were divided in two groups: blood culture negative and positive EOS. Ang-1 and Ang-2 levels were measured in serum obtained at the start of antibiotic treatment and at re-evaluation after 48 to 72 h. RESULTS: In this cohort 8.5% of newborns had a positive blood culture. At the start of antibiotic treatment Ang-1 serum levels were lower (P < 0.01), and Ang-2 and Ang-2/Ang-1 serum protein ratios were higher (P < 0.01 and P < 0.01, respectively) in newborns with blood culture positive EOS than in controls. These levels were not dependent on timing of first blood draw after birth. After 48 to 72 h levels of Ang-1 further decreased in blood culture positive EOS, while in the other groups no change was observed. CONCLUSIONS: Our findings support the hypothesis that a disbalance in the Angiopoietins plays a role in the vascular pathophysiology of EOS.

Complete-genome sequencing elucidates outbreak dynamics of CA-MRSA USA300 (ST8-spa t008) in an academic hospital of Paramaribo, Republic of Suriname.

We report the investigation of an outbreak situation of methicillin-resistant Staphylococcus aureus (MRSA) that occurred at the Academic Hospital Paramaribo (AZP) in the Republic of Suriname from April to May 2013. We performed whole genome sequencing with complete gap closure for chromosomes and plasmids on all isolates. The outbreak involved 12 patients and 1 healthcare worker/nurse at the AZP. In total 24 isolates were investigated. spa typing, genome-wide single nucleotide polymorphism (SNP) analysis, ad hoc whole genome multilocus sequence typing (wgMLST), stable core genome MLST (cgMLST) and in silico PFGE were used to determine phylogenetic relatedness and to identify transmission. Whole-genome sequencing (WGS) showed that all isolates were members of genomic variants of the North American USA300 clone. However, WGS revealed a heterogeneous population structure of USA300 circulating at the AZP. We observed up to 8 SNPs or up to 5 alleles of difference by wgMLST when the isolates were recovered from different body sites of the same patient or if direct transmission between patients was most likely. This work describes the usefulness of complete genome sequencing of bacterial chromosomes and plasmids providing an unprecedented level of detail during outbreak investigations not being visible by using conventional typing methods.

[Dengue: a growing risk to travellers to tropical and sub-tropical regions]. / Dengue: een toenemend risico voor reizigers naar tropische en subtropische landen.

Dengue is currently the most common arboviral infection worldwide. Due to global climate change and other factors, the vector of the virus - the Aedes mosquito - has spread considerably over the past decades. Dengue is endemic in almost all tropical and sub-tropical regions of the world; meaning that approximately 40% of the world population is at risk of acquiring a dengue infection. The clinical features of dengue vary from a non-specific febrile illness (dengue fever) to at times fatal serious conditions such as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). Considering the limited possibilities of prevention it is anticipated that the incidence of dengue will increase in the future. It is expected that health-care providers in non-endemic regions will encounter dengue-infected patients with increasing frequency in their practices.

Severe persistent pulmonary hypertension of the newborn in a setting where limited resources exclude the use of inhaled nitric oxide: successful treatment with sildenafil.

UNLABELLED: We present the case of a full term neonate with severe persistent pulmonary hypertension of the newborn (PPHN) after birth asphyxia cared for at the St. Elizabeth Hospital in Curacao, Netherlands Antilles. Although the child was ventilated with high pressures and was given high doses of cardiovascular pressors, the arterial oxygen levels remained low with an alveolar-arterial O2 gradient of 651 mmHg. As a last resort, sildenafil (1.5 mg/kg) was given via a nasogastric tube. This resulted in an immediate and sustained elevation of arterial oxygenation and subsequent complete recovery. After administration of sildenafil there was a transient hypotension which was corrected by a single bolus of saline. CONCLUSION: We discuss the current treatment modalities of persistent pulmonary hypertension of the newborn and the potential use of phosphodiesterase 5 inhibitors such as sildenafil in a situation where the standard of practice with inhaled nitric oxide and extracorporeal membrane oxygenation is not available.