View clinical trials related to Septicaemia.
Filter by:Severe infections (sepsis) are a common cause of admission to the intensive care unit. They represent a significant health risk for patients in the short and medium term. They are particularly linked to a change in the function of immune cells. In some patients, a state of pseudo-dormancy of monocyte and macrophage-type immune cells, called immunosuppression of myeloid cells, is observed. This situation leads to a worsening of the infection, so it should be avoided because it represents a danger for the patient even when they ar receiving antibiotics. At present, these events are still very poorly understood. Research is essential to understand how this state of immunosuppression of myeloid cells is established in order to adapt existing treatments or find new ones. Laboratory studies on animal models of septicaemia have shown that this state of immunosuppression of myeloid cells is closely linked to a change in the production of energy by myeloid cells (monocytes and macrophages). The functioning of the mitochondria ("energy factory" of the cells) in these cells is impaired. Thus, restoring mitochondrial function in myeloid cells could be a therapeutic solution against the immunosuppression of myeloid cells during severe septicaemia. The objective of this study is to verify whether alterations in mitochondrial function in myeloid cells also occur in patients with bacterial infection compared to patients without bacterial infection.
Background: Nearly all the yearly 3.3 million neonatal deaths occur in low and middle income countries. Infections, including those affecting the umbilical cord (omphalitis) are a significant factor in approximately a third of these deaths. In fact, the odds of all-cause mortality are 46% higher among infants with umbilical cord infection than those without infection. Five large randomized controlled trials in Asia and Sub-Saharan Africa have examined the effect of multiple applications (for at least 7 days) of 4% chlorhexidine (CHX) on the umbilical cord on omphalitis and neonatal death. These studies show a consitent positive effect of multiple applications on omphalitis but not on neonatal mortality. Whereas there is mounting evidence for the effect of 7 day chlorhexidine application, there is no data from Africa and only one study from Asia that examines the effect of a single application of CHX as soon as possible after birth. In this single Asian study, CHX led to a reduction in the risk of mild-moderate omphalitis and neonatal death. It is important, in an African setting to explore the effect of a single application, which is programmatically much simpler to implement than daily application for 7 days. Therefore, the investigators' study will compare umbilical cord cleansing with a single application of 4% chlorhexidine at birth with dry cord care in both community and facility births on omphalitis and severe illness in the neonatal period. Methods: The chlorhexidine study is a community based, individually randomised controlled trial conducted on 4,760 mother-infant pairs in Uganda. The primary outcomes are severe illness and umbilical cord infection (omphalitis). Severe illness is defined as any illness associated with at least one of the following danger signs observed by study research assistants: inability to drink or breastfeed or (a history of) convulsions, lethargy or unconsciousness, vomiting of all feeds, and/or results in hospitalization and/or results in death. Discussion: This study will provide novel evidence, from a Sub-Saharan African setting of the effect of umbilical cord cleansing with a single application of 4% chlorhexidine at birth in both community and facility births.
BCG vaccination may have non-specific effects (NSE) i.e., additional benefits on childhood morbidity and mortality that are separate the vaccine's effect on the incidence of disseminated tuberculosis. Though the available literature is mostly from observational study designs, and is fraught with controversy, BCG vaccination at birth, in a high risk population of HIV exposed children, may protect infants against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy, when the immune system is more mature, may offer even greater protection. The appropriate timing of BCG vaccination could therefore be up for revision. This study will therefore compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV exposed (HE) babies. Methods: This is an individually randomized clinical trial in 4,500 HIV exposed infants. The intervention is an intra-dermal administration of 0.05 ml of BCG vaccine within 24 hours of birth while the comparator will be an intra-dermal administration of 0.05ml of BCG vaccine at 14 weeks of age. The main study outcomes include: 1. Severe illness in the first 14 weeks of life, 2. Innate and adaptive immune responses to mycobacterial, non-mycobacterial antigens and TLR-agonists 3. Severe illness in the first 14-52 weeks and 0-52 weeks of life. The study will be carried in two health centers and one district hospital in Uganda. Implications: A well-timed BCG vaccination could have important additional benefits in HE infants. This trial could inform the development of programmatically appropriate timing of BCG vaccination for HE infants.
2 recent national reports 'Why Children Die' and 'Are we there yet?'identified deficiencies in recognising and managing sick children. Key recommendations from both reviews included the development and adoption of 'track and trigger' or a paediatric early warning score (PEWS) to better identify the sick or deteriorating child. PEWS tools offer the potential to identify and respond sooner to clinical deterioration. Capillary refill time (CRT) is a measure of skin blood flow and is a vital part of many early warning and resuscitation scores. It is a sensitive marker of infection and dehydration in children. However, due to how it is performed and interpreted CRT is prone to marked variability between observers. We have Medical Research Council (MRC) funding to develop an automated capillary refill device and user interface to provide a paediatric continuous early warning (PaedCEW) monitoring system. The PaedCEW system would complement and support current clinical practice and aim to address the difficulties of recognising ill children. We aim to recruit 20 ill children on the Paediatric Intensive Care Unit (PICU) with 2 matched controls without significant illness from the Nottingham Children's Hospital. The 20 ill children will have their CRT (and PaedCEW score) monitored before, during and after admission to PICU. This will allow correlation with invasive (BP, central venous oxygen saturations, lactate) and noninvasive (CRT, heart rate, cardiac output) measures of cardiovascular status during periods of stability and compromise. Matched controls will be monitored for around 24 hours. This pilot study will allow development of our system. This is a proof of concept study. This study aims to demonstrate a novel device for measuring CRT. Its correlation with noninvasive measures of cardiovascular status will enable a pragmatic comparison with current clinical practice. In addition, correlation with invasive measures of cardiovascular status will enable us to calculate sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV).
Pneumococcus is a bacteria that causes disease of the respiratory tract (pneumonia and middle ear infections), blood poisoning, and meningitis. It is frequently carried by people in back of the throat without symptoms. Pneumococcal carriage in the Thames Valley region has been studied over the last 12 years with carriage rates having been shown to be reflective of disease potential and hence vaccine effect. During this time pneumococcal vaccines have been introduced into the routine immunisation schedules of this community. The PCV7 (A vaccine against 7 types of pneumococcus) vaccine has subsequently been noted to have had a significant impact in reducing vaccine serotype carriage and disease. Herd protection (indirect protection of unvaccinated individuals) has also been implicated with vaccine serotypes not being carried in parents of vaccinated children. The most common serotype carried since the introduction of PCV7 is 19A, which is included in the PCV13 vaccine (A vaccine against 13 types of pneumococcus). PCV13 has superseded PCV7 in the routine immunisation schedule, however its impact on carriage and disease in this community is yet to be evaluated.
The bacterium (germ) Neisseria meningitidis causes meningitis and blood poisoning. N meningitidis is classified into different serogroups (types), based on its outer polysaccharide (carbohydrate) capsule. Serogroups A,B,C,W & Y are responsible for the vast majority of meningococcal disease worldwide. Older vaccines against types A,C,W & Y contain part of the polysaccharide capsule of the germ. However, these polysaccharide vaccines do not provide long-term protection against disease and are less effective in young children, the group most at risk of meningococcal disease. Newer "conjugate" ACWY vaccines attach a polysaccharide to a protein carrier - these provoke a good response in young children and can provide long-term protection. White blood cells called B cells produce antibodies, which are the main components of protection against meningococcal disease. Although many studies have investigated the immune response to these vaccines in different age groups by measuring specific antibodies, there is limited information about the B cells underlying such an immune response. Several different subsets (populations) of B cells exist in the blood. Previous studies by the investigators group suggest that different numbers of B cells are produced in response to each vaccine type. However, little is understood about which subset of B cell is important for antibody production in response to these polysaccharide or conjugate vaccines. This study aims to provide detailed information on the immune response to meningococcal vaccines by investigating the appearance of B cells and their subsets in the blood after vaccination with the polysaccharide and conjugate vaccines. These observations will help us understand how polysaccharide and conjugate vaccines stimulate the immune system in different ways. This knowledge will help in the development of new vaccines that are effective across all age groups. The investigators aim to recruit 20 adults aged 30-70 from Oxfordshire. The study will be funded by the Oxford Vaccine Group.