Procalcitonin and C-Reactive Protein as Diagnostic Markers of Neonatal Sepsis

Abstract: Neonatal sepsis is a serious problem associated with significant neonatal morbidity and mortality. Diagnosis of neonatal sepsis may be difficult because the clinical presentations are often non-specific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. This study aimed to evaluate procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic markers of neonatal sepsis. Sixty neonates with suspected neonatal sepsis were recruited from the neonatal intensive care unit (NICU), Sohag university hospital, Egypt. They were allocated into two groups; early-onset neonatal sepsis (EONS; n=32) and late-onset neonatal sepsis (LONS; n=28). Blood samples were obtained from the participants for complete blood count (CBC), blood cultures, serum CRP and PCT analysis. Area under the receiver operating characteristic (ROC) curve (AUC), predictive values and diagnostic cut off values of CRP and PCT were evaluated. In total, 42 (70%) neonates were confirmed to have sepsis based on positive blood culture results. Serum levels of CRP and PCT were significantly higher in neonates with EONS than those with LONS (p=< 0.05). However, there was no significant statistical difference between the area under the curve (AUC) values of PCT and CRP in all studied cases, EONS or LONS cases (p=0.32, p= 0.29, p=0.28 respectively). In conclusion, PCT and CRP are reliable diagnostic markers of neonatal sepsis, which have the same diagnostic accuracy. CRP; being easily measurable and more affordable can be conveniently used as a good marker for the diagnosis of neonatal sepsis, especially in developing communities with poor resources

Diagnostic markers for early sepsis diagnosis in children with systemic inflammatory response syndrome

Sepsis caused by infection remains a major cause of mortality among children. One of the main reasons for high sepsis mortality rates is the inability to obtain early diagnosis. Sensitive and specific biomarkers are greatly needed in rapid diagnosis of sepsis. The main aim of study was to investigate the ability of high-mobility group box-1 protein (HMGB1), lipopolysaccharide-binding protein (LBP), Interleukin-6 (IL-6), procalcitonin (PCT) and C reactive protein (CRP) to differentiate sepsis patients. Eighty-four children with Systemic Inflammatory Response Syndrome (SIRS) were included in the prospective study. Sepsis was recognised in 23% (n = 19) of them. LBP, IL-6, CRP and PCT levels were significantly higher among the sepsis group (P < 0.05). HMGB1 levels in the sepsis patients did not significantly differ from SIRS patients. In ROC analysis in sepsis patients, identification markers LBP, IL6 and CRP performed quite similarly (P < 0.001), with the best result being for IL6. Our data suggest that in early sepsis diagnosis in children, LBP, IL-6, PCT and CRP are probably the superior diagnostic markers, with the best performance by IL6. LBP and IL-6 are superior markers for sepsis patients' disease process monitoring. HMGB1 does not have a diagnostic value for sepsis patient identification.publishersversionPeer reviewe

Die Evaluation von Humanem Guanylat-Bindungsprotein-1 als Marker im Blutserum für Entzündung und Sepsis

Background: Early detection of inflammation or beginning sepsis in patients plays an important role. Although there are some established markers, that indicate inflammation early, like white blood cells and CRP, the search for a more reliable and more specific marker is still relevant. Endothelial cells play an important role in inflammations. Analyses showed, that endothelial cells, which are activated by inflammatory cytokines, express particularly “human guanylate binding protein-1”. Here was investigated hGBP-1 as a potential marker of sepsis respectively of inflammation. Material and methods: Blood serums of patients of the Department of Surgery at the University hospital of Erlangen-Nürnberg were taken to explore the expression of hGBP-1. The collection of blood samples was accomplished in different states of inflammation. Thus the quality of hGBP-1 as marker of sepsis respectively of inflammation was tested. Furthermore hGBP-1 was compared to inflammation markers like white blood cells, CRP, IL-6 and Procalcitonin in blood serum. Results: Analysis shows, that hGBP-1 in serum is detectable. With a sensitivity of 7.5% and a specificity of 95.8% hGBP-1 serves as inflammation marker. The sensitivity for hGBP-1 as sepsis marker is 66.7% and the specificity is 97.3%. The fisher-yates exact test verifies a significant coherence. A correlation between hGBP-1 and white blood cell count is found in total patient population, in septic patient group and in patient group of inflammation. Conclusions: Because of the strong correlation between hGBP-1 and white blood cell count approves as established inflammation marker, hGBP-1 is certified to identify an inflammation. A significant coherence between hGBP-1 and septicaemia is confirmed. Another clinical trial would allow a better understanding of diagnostic value by means of predictive values of hGBP-1. Beyond that, blood products are detectable in different mediums and different ways. Therefore an exploration of hGBP-1 in another medium, such as bloodplasma, or by an advanced detection system is recommended.Einleitung: Die frühzeitige Erkennung einer Entzündung und beginnenden Sepsis bei Patienten ist immens wichtig. Trotz etablierter Entzündungsmarker im Blut, wie z.B. die Leukozytenzahl und CRP, ist die Suche nach einem sichereren und spezifischeren Marker immer noch aktuell. Endothelzellen spielen eine entscheidende Rolle bei entzündlichen Prozessen. Untersuchungen haben gezeigt, dass durch inflammatorische Zytokine aktivierte Endothelzellen insbesondere „Humanes Guanylat-Bindungsprotein-1“ (hGBP-1) exprimieren. Die Untersuchung von hGBP-1 als potentieller Sepsis- bzw. Entzündungsmarker liegt somit nahe. Material und Methode: Es wurden Blutserumproben von Patienten der Chirurgischen Universitätsklinik Erlangen-Nürnberg abgenommen und auf die Expression von hGBP-1 hin untersucht. Die Blutabnahmen wurden bei unterschiedlichen Entzündungszuständen durchgeführt und die Güte von hGBP-1 als Sepsis- bzw. Entzündungsmarker geprüft. Des Weiteren wurde hGBP-1 mit den Entzündungsmarkern Leukozyten, CRP, IL-6 und Procalcitonin im Serum verglichen. Ergebnisse: Der Nachweis von hGBP-1 im Blutserum ist möglich. Die Sensitivität von hGBP-1 als Entzündungsmarker liegt bei 7,5%, die Spezifität bei 95,8%. HGBP-1 als Sepsismarker hat eine Sensitivität von 66,7% und eine Spezifität von 97,3%. Im Exakten Fisher-Test wird hier ein signifikanter Zusammenhang bestätigt. HGBP-1 korreliert im Gesamt-Patientenkollektiv, bei septischen Patienten und in der Untergruppe der Patienten mit Entzündung signifikant mit der Leukozytenzahl. Diskussion: Durch die starke Korrelation mit der Leukozytenzahl als etablierter Entzündungsmarker wird bestätigt, dass hGBP-1 eine Entzündung anzeigt. Ein signifikanter Zusammenhang zur Sepsis ist belegt. Eine weitere Studie kann Aufschluss über die diagnostische Aussagekraft anhand der prädiktiven Werte von hGBP-1 geben. Zudem sind Blutprodukte in unterschiedlichen Medien unterschiedlich empfindlich nachweisbar. So ist eine Analyse von hGBP-1 in einem anderen Medium, wie z.B. Blutplasma, oder eine Verbesserung des Detektionssystems anzuraten

The assessment of selected novel feed ingredients to replace fishmeal on the nutrition and health status of ornamental fish

Chapter 3 has been published in the Journal of Fish and Shellfish immunology and Chapter 5 has been published in the Journal of AquacultureFour investigations were conducted to assess the effects of feeding selected novel feed ingredients on the nutrition and health status of ornamental fish. Each dietary ingredient was assessed by determining the effects on growth performance, feed utilisation, haematological status, serological status and immuno-competence of mirror carp, a model ornamental fish species. The first experiment was conducted to evaluate the effect of feeding a tropical earthworm meal (Perionyx escavatus) and soybean meal on the haemato-immunological response and growth performance of mirror carp (Cyprinus carpio). Fish were fed diets for a total of 88 days, fishmeal served as the main protein source in the control diet. Two remaining diets consisted of fishmeal fixed at 33 % provision of protein and the remaining 66 % protein was provided by soybean meal (SBM diet) or P. excavatus meal (EW diet). After 60 days of feeding fish fed EW diet showed a significant elevation in final body weight compared to fish fed a fishmeal diet and fish fed a SBM diet. Similar improvements were observed in feed utilisation efficiency. After intraperitoneal injection with heat inactivated Aeromonas hydrophila and 28 days of feeding EW diet to mirror carp showed decrease in some aspects of the innate immune response. Contrary to this, fish fed soybean meal showed signs of inflammation. The second experiment was conducted to evaluate the effect of feeding two plant protein concentrates and a combination of whey protein concentrate and casein protein on the growth performance, haematological and serological responses of mirror carp (C. carpio). Fish were fed diets for a total of 84 days, fishmeal served as the main protein source in the control diet. Three remaining diets consisted of fishmeal fixed at 33% provision of protein and the remaining 66% protein was provided by rice protein concentrate (RPC diet), corn protein concentrate (CPC) and a combination of whey protein concentrate (8%) and casein protein (58%) (WPC diet). After 84 days of feeding fish fed WPC diet showed a significant elevation in final body weight compared to fish fed a fishmeal diet and fish fed RPC and CPC diets. Similar improvements were observed in feed utilisation and protein efficiency. At the end of the trial feeding fish fed WPC diet showed a significant elevation in mean corpuscular haemoglobin levels compared to fish fed fishmeal and RPC diets. Serological analysis showed that feeding carp the WPC showed a significant increase in serum albumin and protein concentrations compared to fish fed fishmeal diet. The final experiment was conducted to evaluate the effect of feeding selected exotic ingredients on immune responses and expression of immune related genes in mirror carp (C. carpio). Fish were fed diets for a total of 63 days. Fishmeal served as the main protein source in the control diet and two experimental diets consisted of fishmeal fixed at 34% provision of protein and the remaining protein was provided either by earthworm meal (EW diet) or a combination of whey protein concentrate (8%) and casein (58 %) (WPC diet). At the start of the trial fish were injected intraperitoneally with A. hydrophila bacterin. Compared to fish fed fishmeal, a significant increase in mRNA expression of the pro-inflammatory cytokines IL-1β (24 h post injection) and TNFα (at 12 h and 48 h post injection) was observed in fish fed EW. Moreover a similar trend was observed for complement 3 (C3) gene, where fish fed EW showed significant elevations in mRNA expression values at both 12 and 48 h post injection compared to control fed fish. In contrast, fish fed WPC showed a significant decrease in C3 and TNF-α mRNA expression compared to fish fed fishmeal (48 h post injection). Fish fed EW and WPC diet showed a significant increase leukocyte levels compared to fish fed fishmeal 14 days post injection. Fish fed fishmeal presented significantly higher circulatory IgM levels at 7 d post injection compared to fish fed EW and WPC diets. In contrast, fish fed EW and WPC showed a significant increase in IgM levels at 28 d post injection. This study concludes that feeding fish non-plant based feed commodities had a positive effect on carp growth response, feed utilisation and immuno-competence. These findings are both novel and highly relevant for the ornamental industry where high value feed commodities are more acceptable.Biotechnology and Biological Sciences Research Council (BBSRC)and MARS Waltham Centre For Pet Car and Nutritio