Background: Laboratory biomarkers are important adjuncts to clinical data in diagnosing neonatal sepsis. Available diagnostic tests often provide results 6 to 48 hours later. A bedside C-reactive protein (CRP) test may be able to exclude or diagnose sepsis within minutes. Objectives: The objectives were to validate the Alere AfinionTM point of care test (POCT) CRP in a tertiary neonatal unit against the gold standard CRP assay in use by the National Health Laboratory service and to determine the difference in time to obtaining a result between the two systems. Methods: A prospective observational study was conducted between February 2015 and June 2015. Neonates who were clinically indicated to undergo CRP testing were simultaneously tested using the POCT and laboratory assays. The sensitivities, specificities and predictive values for the POCT, with the laboratory test as the reference test were determined. The time to results between the two tests was compared. Results: There were 139 measured CRP sample pairs from patients with suspected or proven neonatal sepsis. Using 10 mg/L as the cutoff value for both CRP tests, the sensitivity, specificity, positive predictive value and negative predictive value were 97.4%, 99%, 97.4% and 99% respectively. The area under the receiver operating characteristic curve was 0.99 (p<0.001). The time to point of care result was 4 minutes. Laboratory results were registered at a mean of 4.7 hours but only checked after a mean of 6.8 hours. Conclusions: The POCT CRP and laboratory CRP test have excellent correlation in neonates and may be a useful, quick, reliable method to rationalise antibiotic usage, reduce costs and allow for earlier patient discharge.

Includes bibliographical references.

Background The surgical infant requires care in specialized neonatal units. Very low birth weight (VLBW) infants are a group particularly vulnerable to the risks and outcomes associated with preterm birth. There is an increased number of abdominal emergencies seen, attributed to improved survival in this birthweight category. Objectives To describe the short-term survival to discharge in VLBW infants following abdominal surgery at a South African public tertiary hospital and to examine the utility of common scoring systems for prognostication. Methods A retrospective study of VLBW infants with abdominal surgery was conducted in patients admitted to the neonatal unit at Groote Schuur Hospital between 2012 and 2016. CRIB and SNAPPE scores were calculated for patients where sufficient data was available. Results Fifty-two patients were included. The mean gestational age (GA) and birthweight (BW) were 29.5 weeks (SD 2.1) and 1102g (SD 197.8) respectively. Necrotizing enterocolitis was the most common (50%) surgical emergency. The leading postoperative complication was sepsis (37%). Fourty-two (81%) infants survived to discharge, the mean age at presentation 21 days (SD 21.1) with a mean hospital stay of 74 days in survivors vs 52 days in the non-survivors (p=0.06). There was no statistically significant difference in SNAPPE scores between survivors and non-survivors. Conclusion Abdominal emergencies have a high mortality and adds to the overall length of stay in VLBW infants. Neonatal scoring systems have proven to be useful adjuncts in predicting neonatal mortality, further study is warranted in infants who deteriorate due to surgical abdominal complications.

Background: Klebsiella pneumoniae (KP) is a significant paediatric bloodstream pathogen in children. There is little data about KP in South African children. The focus for the present study was to address this knowledge gap. Methods: This study addressed a retrospective case notes review on bloodstream Klebsiella pneumoniae infections at a children's hospital in Cape Town, South Africa 2006-2011 using conventional descriptive and comparative statistical methods. Results: Of 410 hospitalised children with laboratory confirmed KP bloodstream infection (KPBSI), 339 (83%) were presumed extended-spectrum β-lactamase (ESBL) producing isolates. The median age (interquartile range, IQR) was 5.0 (2-16) months, 212 (51.7%) were male, 82 (20%) were HIV-infected, and 241 (58.8%) were moderately or severely underweight. The infection was nosocomial or healthcare-associated in 389 (95%) children and community-acquired in 21 (5%) children. Significant risk factors for the acquisition of ESBL-KP bloodstream infection included cephalosporin exposure in the preceding 12 months prior to the KPBSI p=<0.0001: aRR 1.25 (95% CI: 1.15-1.36); and those who had intravenous infusions for more than 3 days prior to the KPBSI, p=0.004: aRR 1.18 (95% CI: 1.05-1.31).

<p><strong>Abstract</strong></p><p>The aim of this study was to investigate the reason why students contact adults if they are involved in any kind of bullying, what support they had received and wished for, as well as to investigate why student don’t contact adults. About of 150 students, 50 girls and 56 boys (70%) had experienced bullying of different kinds; some had more than one kind of experience. The students expressed that they had contacted adults when they “felt unwell” and to “stop bullying”. There were no statistical significant differences between bullied, bullies and bystanders or girls and boys regarding their contacts with adults and their satisfaction with received support. When the students had evaluated their contacts with adults 32 of 40 were content with the support. Regarding support from adults, students wish for “concrete solutions” and “that adults would listen more”. Reasons why student had not contacted adults were that they “dared not” and “did not know who to talk to”. To stop the bullying the students proposed “better knowledge and efficient actions against bullying” as well as “zero tolerance to bullying”.</p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p><strong> </strong></p><p><strong> </strong></p><p><strong> </strong></p><p><strong> </strong></p><p><strong> </strong></p><p><strong> </strong></p><p><strong>Keyworld: </strong>school students, bullying, adult support</p><p> </p><p> </p><p><strong> </strong></p>

Abstract The aim of this study was to investigate the reason why students contact adults if they are involved in any kind of bullying, what support they had received and wished for, as well as to investigate why student don’t contact adults. About of 150 students, 50 girls and 56 boys (70%) had experienced bullying of different kinds; some had more than one kind of experience. The students expressed that they had contacted adults when they “felt unwell” and to “stop bullying”. There were no statistical significant differences between bullied, bullies and bystanders or girls and boys regarding their contacts with adults and their satisfaction with received support. When the students had evaluated their contacts with adults 32 of 40 were content with the support. Regarding support from adults, students wish for “concrete solutions” and “that adults would listen more”. Reasons why student had not contacted adults were that they “dared not” and “did not know who to talk to”. To stop the bullying the students proposed “better knowledge and efficient actions against bullying” as well as “zero tolerance to bullying”.                                   Keyworld: school students, bullying, adult support

<p>The purposes of the thesis were to study associations between size at birth, short adult stature and risks of subnormal intellectual performance, high blood pressure, and overweight among males, and to study associations between size at birth, short adult stature and risk of overweight and giving birth to small for gestational age (SGA) infants among females.</p><p>The effect of short adult stature on intellectual performance among males was analyzed in two population-based cohort studies. Data were obtained from the Swedish Birth Register which was individually linked to the Swedish Conscript Register. Being born SGA was associated with increased risks of subnormal intellectual performance in all four dimensions included in the test, and lack of catch-up growth leading to short adult stature further increased this risk. If anything, logical performance was found to be most affected.</p><p>To estimate the risk of high blood pressure in males born SGA we used the Birth Register linked to the Conscript Register. Being born SGA was associated with a slightly increased risk of high systolic blood pressure, and being born light and ending up with short adult stature further increased this risk.</p><p>Association between short adult stature and overweight was analyzed in both males and females born SGA, in two different studies. In the male cohort data from the Birth Register was linked to the Conscript Register. In females the Birth Register was used twice, when the females were born and when they gave birth to their first child. In both the male and female cohort, there was an increased risk of becoming overweight among those born SGA who also ended up with short adult stature.</p><p>Finally, an intergeneration study was performed using the Birth Register to analyze associations between being born short for gestational age and giving birth to short infants. Catch-up growth to normal adult stature among women born short-for-gestational age was associated with reduced risk of giving birth to a short-for-gestational age infant.</p><p>Conclusions. Among males born SGA, short adult stature is associated with increased risk of subnormal intellectual performance, high blood pressure and overweight compared to those with normal adult stature. Similarly, among females born SGA, there is an increased risk of becoming overweight in those with short adult stature, compared with those not short as adult. Females born short for gestational age, with short adult stature are at increased risk of giving birth to a short infant.</p>

The purposes of the thesis were to study associations between size at birth, short adult stature and risks of subnormal intellectual performance, high blood pressure, and overweight among males, and to study associations between size at birth, short adult stature and risk of overweight and giving birth to small for gestational age (SGA) infants among females. The effect of short adult stature on intellectual performance among males was analyzed in two population-based cohort studies. Data were obtained from the Swedish Birth Register which was individually linked to the Swedish Conscript Register. Being born SGA was associated with increased risks of subnormal intellectual performance in all four dimensions included in the test, and lack of catch-up growth leading to short adult stature further increased this risk. If anything, logical performance was found to be most affected. To estimate the risk of high blood pressure in males born SGA we used the Birth Register linked to the Conscript Register. Being born SGA was associated with a slightly increased risk of high systolic blood pressure, and being born light and ending up with short adult stature further increased this risk. Association between short adult stature and overweight was analyzed in both males and females born SGA, in two different studies. In the male cohort data from the Birth Register was linked to the Conscript Register. In females the Birth Register was used twice, when the females were born and when they gave birth to their first child. In both the male and female cohort, there was an increased risk of becoming overweight among those born SGA who also ended up with short adult stature. Finally, an intergeneration study was performed using the Birth Register to analyze associations between being born short for gestational age and giving birth to short infants. Catch-up growth to normal adult stature among women born short-for-gestational age was associated with reduced risk of giving birth to a short-for-gestational age infant. Conclusions. Among males born SGA, short adult stature is associated with increased risk of subnormal intellectual performance, high blood pressure and overweight compared to those with normal adult stature. Similarly, among females born SGA, there is an increased risk of becoming overweight in those with short adult stature, compared with those not short as adult. Females born short for gestational age, with short adult stature are at increased risk of giving birth to a short infant.

Background: Immune responses are often divided into T helper 1 (Th1), Th2 and Treg like immunity. Allergy is associated with Th2 like responses to allergens and possibly to reduced regulatory functions. Activation via the CD2 receptor increases the production of the Th1 associated cytokine IFN-g and enhances the responses of activated T cells to IL-12. This may be due to an up-regulation of the signal-transducing β2-chain of the IL-12 receptor. CD2 function may be impaired in allergic children. As IL-12 is a strong promoter of Th1 like responses, this may be one contributing factor to the Th2-skewed immune responses found in allergic children. IL-27 and its receptor component WSX-1 may also play a role in Th1 like responses. The transcription factors T-bet, GATA-3 and Foxp3 are associated with Th1, Th2 and Treg type of immune responses, respectively. Aim: To investigate possible mechanisms behind the reduced Th1 and/or Treg associated immunity in relation to allergy by studying the CD2 induced regulation of IL-12Rβ2, WSX-1, T-bet, GATA-3 and Foxp3, as well as the production of different cytokines in children and adults. The aim was also to study the development of these factors during the first two years of life in relation to development of allergy in children from a country with high (Sweden) and low (Estonia) prevalence of allergy. Material and methods: Four different study groups were included; 32 12-year-old children, 38 7-year-old children, 61 children followed from birth to two years of age and 20 adults. Peripheral blood mononuclear cells were cultured with PHA (which partly signals via CD2), IL-2 and IL-12 alone and in combination or with anti-CD2 alone or combined with anti-CD28 antibodies. mRNA expression of cytokine receptors and transcription factors was analysed with real-time PCR and production of Th1, Th2 and Treg associated cytokines with ELISA. Results: We found lower PHA-induced IL-12Rβ2 and IFN-γ production in 12-year-old children with positive skin prick tests (SPT), compared with SPT negative children. We also found lower IL-2 induced IL-12Rβ2 in children with allergic airway symptoms and high IgE levels compared to children without a history of allergy and low IgE levels. This was accompanied with lower IL-2 and IL-12 induced IFN-γ. The spontaneous mRNA expression of IL-12Rβ2, WSX-1, T-bet, GATA-3 and Foxp3 was similar at birth and at 24 months. PHA induced up-regulation of all markers at all ages except for GATA-3, which was up-regulated in allergic children only at 6 and 12 months. PHA-induced T-bet and WSX-1 increased from birth to 24 months in non-allergic children. At a specific age, similar levels of all markers were found in allergic and non-allergic children, except for higher spontaneous IL-12Rβ2 at 24 months and higher PHA-induced WSX-1 at birth in allergic children. All cytokines increased with age. No clear differences were found between Swedish and Estonian children. CD2 stimulation induced Foxp3 and IL-10, while CD2 together with CD28 stimulation induced both Th1 and Th2 related transcription factors and cytokines. The combination also hampered the CD2 induced expression of Foxp3. Conclusions: The CD2 pathway and the response to IL-2 may be impaired in allergic children as lower IL-12Rβ2 and IFN-g were found in allergic, compared to non-allergic children. This difference was not found in adults. CD2 may be involved in induction of regulatory T cell responses as stimulation via CD2 in the absence of other co-stimulatory molecules induced Foxp3 and IL-10. Different developmental patterns of Th1 and Th2 associated factors may influence the development of allergic diseases in childhood.

This thesis presents four studies, all designed to improve the problematic diagnostic situation concerning infants with suspected sepsis. Study I included 401 neonates with suspected sepsis. Nine signs of sepsis and C-reactive protein were prospectively recorded and logistic regression was used to assess associations between these signs and a subsequently confirmed diagnosis of sepsis. C-reactive protein and five of the clinical signs were statistically significantly associated with a positive bloodculture. When the material was stratified by gestational age, differences between premature and full term infants were detected.Studies II and III were prospective studies that used samples collected from neonates with suspected sepsis to evaluate a novel real-timepolymerase chain reaction (PCR) method. The results where compared with simultaneously collected blood cultures. Study II used plasma samples and resulted in a sensitivity of 42% and specificity of 95%. In study III, the protocol was improved and adapted to whole blood samples which resulted in a sensitivity of 79% and specificity of 90%. Both protocols included species-specific probes and study III indicated that PCR has the potential to detect bacteria in culture-negative sepsis.Staphylococcus epidermidis is the most common pathogen in neonatal sepsis, but there is still a lack of typing methods suitable for large materials of S. epidermidis. In Study IV we therefore evaluated a new S. epidermidisgenotyping method based on PCR for the repeat regions of four genes thatencode for cell wall anchoring proteins. The method was applied to 49well-defined neonatal blood isolates of S. epidermidis. The combination ofsdrF and aap seemed to be optimal, resulting in a diversity index of 0.92.Conclusions • Bradycardia, apnoea, low blood pressure, feeding intolerance and distended abdomen are obvious early signs of neonatal sepsis. Premature and full-term infants differ in terms of the signs they display in neonatal sepsis. • Blood is superior to plasma for developing PCR methods for bacterial DNA detection. The PCR method described in study III can detect neonatal bacteraemia, but it can be further improved before it is used in routine care. • There has been a lack of useful typing methods for S. epidermidis.We can now present PCR of the genes for the cell wall anchoring proteins sdrF and aap as a novel and feasible approach when there is a need to type a large number of S. epidermidis isolates.