Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx

Abstract Background Plasmodium falciparum-infected erythrocytes sequester in the microcirculation due to interaction between surface-expressed parasite proteins and endothelial receptors. Endothelial cells are covered in a carbohydrate-rich glycocalyx that shields against undesired leukocyte adhesion. It was investigated if the cellular glycocalyx affects the binding of P. falciparum-infected erythrocytes to CD36 in vitro. Methods Glycocalyx growth was followed in vitro by using azido sugars and cationized ferritin detecting O-glycoproteins and negatively charged proteoglycans, respectively. P. falciparum (clone FCR3/IT) was selected on Chinese hamster ovary (CHO) cells transfected with human CD36. Cytoadhesion to CHO CD36 at 1–4 days after seeding was quantified by using a static binding assay. Results The glycocalyx thickness of CHO cells increased during 4 days in culture as assessed by metabolic labelling of glycans with azido sugars and with electron microscopy studying the binding of cationized ferritin to cell surfaces. The functional importance of this process was addressed in binding assays by using CHO cells transfected with CD36. In parallel with the maturation of the glycocalyx, antibody-binding to CD36 was inhibited, despite stable expression of CD36. P. falciparum selected for CD36-binding recognized CD36 on CHO cells on the first day in culture, but the binding was lost after 2–4 days. Conclusion The endothelial glycocalyx affects parasite cytoadhesion in vitro, an effect that has previously been ignored. The previously reported loss of glycocalyx during experimental malaria may play an important role in the pathogenesis of malaria complications by allowing the close interaction between infected erythrocytes and endothelial receptors

Diagnostic utility of procalcitonin versus C-reactive protein as markers for early-onset neonatal sepsis at Korle-Bu Teaching Hospital

Introduction: Symptoms of sepsis are non-specific among neonates and diagnosis requires a high index of suspicion. The study sought to evaluate the utility of procalcitonin (PCT) versus C-reactive protein (CRP) in diagnosing early-onset neonatal sepsis.Methods: This was a crosssectional study in which neonates admitted to the neonatal intensive care unit, with signs suggesting sepsis were categorized according to an adapted criteria from Tollner's sepsis score and case definition of bloodstream infection as: ''highly probable'', ''probable'' and ''less probable''. Laboratory investigations including blood culture, complete blood count, PCT and CRP levels were done before first antimicrobial drug administration.Results: A total of 62 neonates less than 12 hours postnatal age (0.16-9.82 hours) were recruited. Proportion of neonates with PCT>2 ng/mL was 91% (20/22) in the ''highly probable'' group compared to 31.6% (6/19) in the ''probable group'' (p<0.001). Neonates with CRP>5 mg/L was 54.4% (12/22) in the ''highly probable'' group compared to 26.3% (5/19) in the ''probable group'' (p = 0.07). The receiver operator characteristics for PCT and CRP were; sensitivity (87.5% vrs 50%), specificity (63.0% vrs 72.2%), positive predictive value (44.1% vrs 37.5%) and negative predictive value (93.8% vrs 81.3%), respectively.Conclusion: PCT was a better predictive marker for neonatal sepsis within the first 12 hours of life than CRP in this setting, however, its low specificity relative to CRP suggests that neonates without patent infection are more likely to be incorrectly diagnosed with sepsis using this test.Keywords: Diagnostic marker, neonatal sepsis, predictive value, sensitivity, specificit

Diagnostic utility of procalcitonin versus C-reactive protein as markers for early-onset neonatal sepsis at Korle-Bu Teaching Hospital

Introduction: Symptoms of sepsis are non-specific among neonates and diagnosis requires a high index of suspicion. The study sought to evaluate the utility of procalcitonin (PCT) versus C-reactive protein (CRP) in diagnosing early-onset neonatal sepsis.Methods: This was a crosssectional study in which neonates admitted to the neonatal intensive care unit, with signs suggesting sepsis were categorized according to an adapted criteria from Tollner's sepsis score and case definition of bloodstream infection as: ''highly probable'', ''probable'' and ''less probable''. Laboratory investigations including blood culture, complete blood count, PCT and CRP levels were done before first antimicrobial drug administration.Results: A total of 62 neonates less than 12 hours postnatal age (0.16-9.82 hours) were recruited. Proportion of neonates with PCT>2 ng/mL was 91% (20/22) in the ''highly probable'' group compared to 31.6% (6/19) in the ''probable group'' (p<0.001). Neonates with CRP>5 mg/L was 54.4% (12/22) in the ''highly probable'' group compared to 26.3% (5/19) in the ''probable group'' (p = 0.07). The receiver operator characteristics for PCT and CRP were; sensitivity (87.5% vrs 50%), specificity (63.0% vrs 72.2%), positive predictive value (44.1% vrs 37.5%) and negative predictive value (93.8% vrs 81.3%), respectively.Conclusion: PCT was a better predictive marker for neonatal sepsis within the first 12 hours of life than CRP in this setting, however, its low specificity relative to CRP suggests that neonates without patent infection are more likely to be incorrectly diagnosed with sepsis using this test.Keywords: Diagnostic marker, neonatal sepsis, predictive value, sensitivity, specificit

Antibiotic prescribing in paediatric inpatients in Ghana: a multi-centre point prevalence survey

Abstract Background Excessive and inappropriate use of antibiotics in hospitalised patients contributes to the development and spread of antibiotic resistance. Implementing a stewardship programme to curb the problem requires information on antibiotic use. This study describes a multicentre point prevalence of antibiotic use among paediatric inpatients in Ghana. Methods Data were extracted from a multicentre point prevalence survey of hospital acquired infections in Ghana. Data were collected between September 2016 and December 2016 from ten hospitals through inpatient folder and chart reviews using European Centre for Disease Control (ECDC) adapted data collection instrument. From each site, data were collected within a 12-h period (8 am to 8 pm) by a primary team of research investigators and a select group of health professionals from each participating hospital. Results Among 716 paediatric inpatients, 506 (70.6%; 95% confidence interval (CI): 67.2 to 74.0%) were on antibiotics. A significant proportion of antibiotics (82.9%) was prescribed for infants compared to neonates (63.9%) and adolescents (60.0%). The majority of patients (n = 251, 49.6%) were prescribed two antibiotics at the time of the survey. The top five classes of antibiotics prescribed were third generation cephalosporins (n = 154, 18.5%) aminoglycosides (n = 149, 17.9%), second generation cephalosporins (n = 103,12.4%), beta lactam resistant penicillins (n = 83, 10.0%) and nitroimidazoles (n = 82, 9.9%). The majority of antibiotics (n = 508, 61.0%) were prescribed for community acquired infections. The top three agents for managing community acquired infections were ceftriaxone (n = 97, 19.1%), gentamicin (n = 85, 16.7%) and cefuroxime (n = 73, 14.4%). Conclusion This study points to high use of antibiotics among paediatric inpatients in Ghana. Cephalosporin use may offer an important target for reduction through antibiotic stewardship programmes