Umbilical cortisol levels as an indicator of the fetal stress response to assisted vaginal delivery.

OBJECTIVES: While it is well established that delivery by elective caesarean section is less stressful for the fetus than normal vaginal delivery, little attention has been paid to the effect on the baby of an assisted delivery. STUDY DESIGN: We examined cortisol levels in venous cord blood from seven babies born by forceps, 10 by ventouse extraction, 28 by unassisted normal vaginal delivery, and 12 born by elective caesarean. Paired maternal bloods were taken immediately after delivery. RESULTS: Cord blood cortisol values were significantly different in the different groups (one-way ANOVA, P < 0.0001). The forceps group had the highest values and the caesarean group the lowest; both were different from the normal vaginal delivery group (P=0.019 and P=0.046, respectively). There was no effect of length of labour, or method of pain relief on cortisol levels. Maternal values were similar in the different groups, confirming that the differences observed derived from the fetus. CONCLUSIONS: There is increasing evidence that the stress experienced by the fetus or neonate can have long-term effects on the function of the hypothalamic-pituitary-adrenal axis in later life. We speculate that the stress caused by some assisted deliveries may contribute to this.

Characterizing the burden of invasive Pseudomonas infection on neonatal units in the UK between 2005 and 2011.

Concern about Pseudomonas infection in neonatal units has focused on outbreaks. This study analysed cases of invasive Pseudomonas infection in 18 UK neonatal units participating in the NeonIN Neonatal Infection Surveillance Network from January 2005 to December 2011. Forty-two cases were reported. The majority (35/42, 93%) of cases were late-onset (median 14 days, range 2-262 days), the highest incidence was seen in extremely-low-birthweight infants and all cases were sporadic. One-third of cases were known to be colonized prior to invasive disease. Attributable mortality was 18%. Opportunities for preventing invasive disease due to this important pathogen should be prioritized.

Management of suspected viral encephalitis in children - Association of British Neurologists and British Paediatric Allergy, Immunology and Infection Group national guidelines.

In the 1980s the outcome of patients with herpes simplex encephalitis was shown to be dramatically improved with aciclovir treatment. Delays in starting treatment, particularly beyond 48 h after hospital admission, are associated with a worse prognosis. Several comprehensive reviews of the investigation and management of encephalitis have been published. However, their impact on day-to-day clinical practice appears to be limited. The emergency management of meningitis in children and adults was revolutionised by the introduction of a simple algorithm as part of management guidelines. In February 2008 a group of clinicians met in Liverpool to begin the development process for clinical care guidelines based around a similar simple algorithm, supported by an evidence base, whose implementation is hoped would improve the management of patients with suspected encephalitis.

Missed opportunities for preventing group B streptococcus infection.

BACKGROUND: Group B streptococcus (GBS) is the most common cause of early onset (EO) neonatal infection in the UK. National guidelines for its prevention were introduced in 2003. We assessed the opportunities for prevention amongst cases of EO GBS using the electronic Neonatal Infection Surveillance Network (NeonIN). METHODS: Culture proven EO GBS cases occurring between 2004 and 2007 were identified prospectively in eight neonatal units participating in NeonIN. Data concerning risk factors, intrapartum antibiotic (IAP) use and infant outcome were collected retrospectively. RESULTS: There were 48 cases of GBS over the 4 years (0.52/1000 live-births); 22 male, median gestation 38 weeks. The most common clinical presentation was sepsis and the GBS-attributable mortality was 6%. Risk factors were present in 67% (32) and adequate IAP was given to six of these mothers (19%). If all women with risk factors received prophylaxis, 23 cases (48%) may have been prevented. CONCLUSIONS: Better GBS prevention strategies are required in the UK.

Lung-phase immunity to Schistosoma mansoni: definition of alveolar macrophage phenotypes after vaccination and challenge of mice.

Phenotypic changes in murine alveolar macrophages have been described in response to vaccination with irradiated cercariae and to a subsequent challenge with normal parasites. Flow cytometric analysis was used to quantify the proportions of cells strongly positive for a number of macrophage surface markers, detected by a panel of monoclonal primary antibodies and fluorescent secondary antibodies. The proportion of Ia+ macrophages sampled by bronchoalveolar lavage increased 5-fold over days 14 to 28 post-vaccination. This upregulation of Ia was accompanied by a sharp decrease in F4/80 expression between days 14 and 21. The low percentage of F4/80+ cells persisted for several weeks after vaccination, and no further change was stimulated by challenge parasites. These altered characteristics are consistent with the 'activation phenotype' induced by other infectious agents. After challenge of immune mice, further changes in macrophage phenotype were slight compared to the responses elicited by vaccination, or to those induced in the challenge control group; Ia expression increased to about three times normal levels. The phenotypic changes correspond both in magnitude and timing with the pattern of alveolar macrophage activation determined in a previous study. The limited changes in phenotype of alveolar macrophages from immunized mice after challenge could indicate that these cells become refractory to reactivation. Overall, the altered macrophage phenotype after vaccination and challenge provides circumstantial evidence for the action of cytokines, particularly interferon-gamma, in lung-phase immunity to schistosomes.

Lung-phase immunity to Schistosoma mansoni. Flow cytometric analysis of macrophage activation states in vaccinated mice.

A delayed-type hypersensitivity response has been postulated as the effector mechanism of lung-phase immunity to Schistosoma mansoni. We have sought evidence for this response by examining the state of alveolar macrophage activation in C57BL/6 mice vaccinated with radiation-attenuated cercariae, and challenged with normal parasites. As an index of activation, the capacity of macrophages to produce an oxidative burst upon stimulation with PMA, was measured at the single cell level by a flow cytometric method. Fourteen to 28 days after vaccination with 20-kr parasites, highly activated macrophages were recovered from the airways by bronchoalveolar lavage. Their probable role in resistance is to recruit T lymphocytes and macrophages to "arm" the lungs against subsequent challenge. The level of macrophage activation had declined to near background by the time challenge parasites arrived, although pulmonary leucocyte numbers remained elevated. Activated alveolar macrophages were not detected after vaccination with 80-kr parasites, which fail to reach the lungs or induce resistance. Challenge parasites, arriving in the lungs of 20-kr vaccinated mice, stimulated a rapid increase in the activation state of recruited macrophages, coincident with their retention in the pulmonary vasculature. These events occurred later in challenge control mice, with peak activation at day 21, when migration of parasites to the liver is complete. Mice vaccinated with 80-kr parasites lacked the accelerated response to challenge, behaving like the control group. The absence of activated peritoneal macrophages suggests a response restricted to organs such as the lungs, through which both vaccinating and challenge parasites migrate. We suggest that the role of activated alveolar macrophages in lung-phase immunity is to initiate and maintain the focal inflammatory responses which block onward migration of parasites and lead to their demise.

Schistosoma mansoni: circulating and pulmonary leucocyte responses related to the induction of protective immunity in mice by irradiated parasites.

The leucocyte responses in peripheral blood and pulmonary airways are described following vaccination of mice with radiation-attenuated parasites, and subsequent challenge with normal parasites. Percutaneous vaccination stimulated a large and sustained expansion of the circulating lymphocyte pool, more marked than after intradermal vaccination with lung schistosomula which induced comparable levels of resistance. Macrophages and lymphocytes infiltrated the pulmonary airways in response to vaccination by both routes, the lymphocytes being particularly abundant after intradermal vaccination. Exposure of mice to an equivalent number of normal cercariae induced an earlier lymphocytosis of short duration; far fewer macrophages and lymphocytes infiltrated the lungs than after vaccination. An intense but transient pulmonary eosinophilia peaked at 3 weeks after primary exposure to either normal or attenuated parasites. Percutaneous challenge of vaccinated mice elicited higher levels of circulating lymphocytes than challenge of unsensitized controls. However, whilst leucocyte numbers of all cell types were still elevated in the airways at challenge as a consequence of vaccination, no further cellular recruitment was observed coincident with parasite elimination. Our data are compatible with the hypothesis that the mechanism of immunity in once-vaccinated mice involves a T lymphocyte-macrophage interaction triggered by antigen release from lung schistosomula.