Clinical trials: consent in children.
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Adolescent↗
Biomedical subjects
Andrew J Pollard
Publications and source records attributed to Andrew J Pollard.
Eligibility of overseas visitors and people of uncertain residential status for NHS treatment.
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Communicable Disease Control↗
The last of the meningococcus?
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Bacterial Vaccines↗
Cerebral infarct and meningitis secondary to Lemierre's syndrome.
The case is reported of a young man with Fusobacterium necrophorum septicemia who developed cavernous sinus thrombosis, meningitis, carotid artery stenosis and stroke. This article presents the only reported case of arterial stroke in Lemierre's syndrome. Clinical presentation, diagnostic difficulty and treatment are discussed.
Adolescent↗
Depressive pseudodementia in a child with autism.
Depression is rare in early childhood and unusual in autism in this age group. We describe a female child aged 6 years with autism who presented with regression of developmental skills previously gained. Her sleep and appetite were poor, her affect was sad, and she had morbid speech content. She responded to treatment with antidepressant medication. When this clinical picture occurs in adults it is called depressive pseudodementia; paediatric neurologists and neuropsychiatrists need to be aware of it in children.
Amitriptyline↗
Reactivation of the bacille Calmette-Guérin scar following immune reconstitution during treatment of infant acute lymphoblastic leukemia.
The authors describe an infant presenting at 2 weeks of age with congenital acute lymphoblastic leukemia who had previously received routine bacille Calmette-Guérin (BCG) vaccination at birth. The risk of BCG dissemination in immunocompromised infants is discussed and the use of antimycobacterial prophylaxis in such cases considered.
Antineoplastic Combined Chemotherapy Protocols↗
Resolution of orbitocerebral aspergillosis during combination treatment with voriconazole and amphotericin plus adjunctive cytokine therapy.
Orbitocerebral aspergillosis has a very high fatality rate and cure is unusual. We describe the successful management of a child with cereberal aspergillosis who had a dramatic response to therapy with a combination of liposomal amphotericin and voriconazole with adjunctive cytokine therapy during immunosuppresive chemotherapy for acute lymphoblastic leukaemia.
Amphotericin B↗
Haemophilus influenzae type b conjugate vaccines.
Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children worldwide. During childhood, acquisition of antibody directed against the polysaccharide capsule of the organism, presumably as a result of asymptomatic carriage, confers protection and disease is much less common after the age of 4 years. Like other polysaccharides, the polyribosyl ribitol phosphate (PRP) of the Hib capsule is a T-independent antigen and not immunogenic when administered as a vaccine in infancy. Because the highest rates of disease occur in the first 2 years of life, efficacious Hib vaccines have been designed by covalently linking the PRP capsule to a carrier protein that recruits T-cell help for the polysaccharide immune response and induces anti-PRP antibody production even in the first 6 months of life. Introduction of Hib protein-polysaccharide conjugate vaccines into many industrialized countries over the past 15 years has resulted in the virtual elimination of invasive Hib disease. However, despite the success of the vaccine programme several factors may interfere with the effectiveness of the vaccine in the routine programme, as observed in the UK recently. Such factors may include interference with other concomitant vaccines, waning immunity in the absence of booster doses of vaccine, and reduced natural boosting as a result of decreased transmission of the organism. However, the burden of disease remains highest in resource-poor countries and urgent efforts are needed to provide the benefits of this vaccine for children living in regions where it cannot be used for economic and logistical reasons.
Bacterial Capsules↗
Differential post-transcriptional activation of human phagocytes by different Pseudomonas aeruginosa isolates.
Pseudomonas aeruginosa is a pulmonary pathogen in individuals with impaired mucociliary clearance such as cystic fibrosis or mechanical ventilation. Non-opsonic phagocytosis of P. aeruginosa can be mediated by either CR3 or CD14 and different strains appear to have a bias towards one or the other receptor. Strain Fc808 is ingested through CD14 whereas P1 (Fc194) uses CR3. In an in vitro culture system, the inflammatory response of macrophages to these two different strains of P. aeruginosa was divergent at the protein level, with higher IL-6 and tumour necrosis factor (TNF)-alpha production generated in response to strain P1 and higher IL-1 beta production in response to strain Fc808. Interaction of macrophages with these two bacterial strains induced distinct gene expression patterns as detected by gene array analysis, with prominence of genes encoding pro-inflammatory cytokines, surface receptors, transcription factors and proteins involved in phagocytosis. However, comparison of gene expression data and cytokine response data with the two bacterial strains indicated that production of IL-1 beta, IL-6 and TNF-alpha was under differential post-transcriptional control. Interestingly, this effect did not correlate with receptor bias but instead was related to the different LPSs of the two strains. The use of specific mitogen-activated protein kinase (MAPK) inhibitors suggested a role for extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in the differential cytokine production by strains P1 and Fc808. These results indicate that strains of the same species of bacteria may induce differential macrophage phagocytic and inflammatory responses with likely consequence for bacterial clearance and host injury.
Cell Line↗
Meningococcal vaccines.
Meningococcal disease is one of the most feared and serious infections in the young and its prevention by vaccination is an important goal. The high degree of antigenic variability of the organism makes the meningococcus a challenging target for vaccine prevention. Meningococcal polysaccharide vaccines against serogroup A and C are efficacious and have been widely used, often in combination with serogroup Y and W135 components. Their relative lack of immunogenicity in young children and infants can be overcome by conjugation to a protein carrier. The effectiveness of serogroup C glycoconjugate vaccines in children of all ages has been demonstrated and they have now been introduced into routine vaccination schedules. Conjugate vaccines against other serogroups, including A, Y, and W135 will soon be available and it is hoped they may emulate this success. Prevention of serogroup B disease has proven more elusive. Several serogroup B vaccines based on outer membrane vesicles have been shown to be immunogenic and reasonably effective in adults and older children, but the protection offered by them is chiefly strain-specific. Multivalent recombinant PorA vaccines have been developed to broaden the protective effect, but no efficacy data are available as yet. Intensive efforts have been directed at other outer membrane protein vaccine candidates and lipopolysaccharide, and some of these have been shown to offer protection in experimental animal models. Nonpathogenic Neisseriae spp. such as Neisseria lactamica are also possible vaccine candidates. Previously unknown proteins have been identified from in silico analysis of the meningococcal genome and their vaccine potential explored. However, none of these has yet been presented as the 'universal' protective antigen and work in this field continues to be held back by our limited knowledge concerning the mechanisms of natural protection against serogroup B meningococci.
Adolescent↗
Disease susceptibility to ST11 complex meningococci bearing serogroup C or W135 polysaccharide capsules, North America.
Clusters of meningococcal disease caused by a hyperinvasive lineage of Neisseria meningitidis, the ST11 complex, bearing a serogroup C polysaccharide capsule, have been prominent in Europe and North America since the early 1990s. This situation has led to expensive public health measures for outbreak control and, finally, to the introduction of a serogroup C glyconjugate vaccine into the primary immunization schedule in the United Kingdom and elsewhere. ST11 complex meningococci may also express serogroup W135 polysaccharide capsules. We investigated the level of population immunity to this hyperinvasive clone in association with the appearance of outbreaks of meningococcal disease in southern British Columbia. We found that most adults and almost all children were apparently susceptible to infection with ST11 complex meningococci bearing both C and W135 polysaccharide capsules, which suggests that a vaccine program directed against only serogroup C meningococci may be insufficient to prevent hyperinvasive ST11 disease.
Adolescent↗
Global epidemiology of meningococcal disease and vaccine efficacy.
BACKGROUND: Control of meningococcal infection has a high priority in many industrialized nations, because of the high mortality rates associated with invasive infection, the public health effects of disease outbreaks, and the position of Neisseria meningitidis as a leading infectious cause of death in childhood. Throughout the past 200 years, epidemics of meningococcal infection have been noted in Europe, Africa, Asia, the United States, and New Zealand. The proportions of cases caused by the 5 predominant capsular types (A, B, C, Y, and W135) associated with the disease vary among different regions and within specific geographic areas with time. Comprehensive disease control can be achieved only with the use of vaccines that target all of these disease-causing serogroups. METHODS: Routine immunization with a new generation of conjugate vaccines against serogroup C meningococci in the United Kingdom since 1999 has had a major effect on serogroup C disease in the region. The success of the vaccine involves 2 mechanisms, ie, (1) direct protective effects for vaccinated individuals through induction of bactericidal antibodies and (2) reductions in nasopharyngeal carriage of the organism and consequent generation of herd immunity through reductions in transmission to unimmunized individuals. CONCLUSIONS: Ongoing development of tetravalent A, C, Y, and W135 conjugate vaccines raises the hope that disease caused by these serogroups can be controlled in the near future. However, development of effective strategies to control serogroup B meningococcal disease is still needed for comprehensive control of meningococcal disease.
Global Health↗
Epidemic meningococcal disease in sub-Saharan Africa--towards a sustainable solution?
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Africa South of the Sahara↗
Age dependence of in vitro survival of meningococci in whole blood during childhood.
OBJECTIVES: To determine the association between the ability of a different strains of meningococci to survive in whole blood and the age of the donor. METHODS: A panel of serogroup B and a serogroup C strain of Neisseria meningitidis was tested in an ex vivo whole blood model. Blood from 81 healthy children and 20 adults and from children during convalescence from serogroup B (55 patients) or serogroup C (43 patients) meningococcal infection was assessed. RESULTS: Age-dependent acquisition of whole blood killing of serogroup B and C bacterial isolates was demonstrated in healthy children with an inverse relationship to the reported incidence of disease. After infection with serogroup B or C meningococci, evidence of whole blood killing of the bacteria was found even in blood from children <2 years of age, the survival of a serogroup B strain, MC58, being reduced compared with that in healthy children (median, 64% compared with 194.5% survival at 90 min). In both affected children and controls, there was a significant correlation between whole blood killing of strain MC58 and of other serogroup B and C meningococci. CONCLUSIONS: The whole blood model measures both humoral and cellular mechanisms responsible for the bactericidal activity of blood. The model was first described 80 years ago, but this is the first description of its age dependency. Acquisition of bactericidal activity was more rapid in children infected and is directed at various strains of meningococci, indicating the presence of a cross-reactive antigen(s).
Adolescent↗
Tropical disease vaccines.
Infectious diseases remain a key cause of morbidity and mortality in the Tropics. Many of these diseases are already preventable by effective vaccines. The Extended Program of Immunization provides protection against six serious infections. However, this program is still not optimally implemented in all developing countries. The Extended Program of Immunization could benefit from the addition of several vaccines, but unfortunately the cost is prohibitive in many areas of the Tropics. For some of the most important infections, such as malaria and HIV, vaccines are not yet available. Novel strategies for vaccine development and policy implementation offer the best hope to combat the infections targeted by the World Health Organization as causing the highest annual death toll worldwide.
AIDS Vaccines↗
Immunologic memory with no detectable bactericidal antibody response to a first dose of meningococcal serogroup C conjugate vaccine at four years.
Fourteen children with no detectable bactericidal antibody response to a first dose of meningococcal C conjugate vaccine at 4 years of age were given a booster dose of the same vaccine 2 years later. A rapid 1000-fold rise in postimmunization bactericidal antibody titers, a measured either 7 or 14 days later, suggested previous immunologic priming.
Antibodies, Bacterial↗
Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene and arterial oxygen saturation at high altitude.
There is a significant genetic influence on arterial oxygen saturation (Sa(O(2))) in high-altitude (HA) residents. It is not known whether this is true of lowlanders ascending to HA. The I allele of the angiotensin-converting enzyme (ACE) gene is associated with low ACE activity and elite endurance performance. An excess of the I allele has also been reported in South American natives living over 3,000 m and among elite HA mountaineers who demonstrate extreme endurance in a hypoxic environment, where maintenance of Sa(O(2)) is crucial to performance. We postulated that the I allele may confer an advantage at HA through genotype-dependent alterations in Sa(O(2)). Rapid ascent (n = 32) and slow ascent groups (n = 40), ascending to approximately 5,000 m over 12.0 and 18.5 days, respectively, had their Sa(O(2)) assessed throughout and compared with their ACE genotype. Resting Sa(O(2)) was independent of the ACE genotype and remained so for the slow ascent group, in whom the fall in Sa(O(2)) with ascent was genotype independent. However, Sa(O(2)) with ascent was significantly associated with the ACE genotype in the rapid ascent group (p = 0.01) with a relatively sustained Sa(O(2)) in the II subjects. These data are the first to report an association of the I allele with the maintenance of Sa(O(2)) at HA.
Adult↗
Meningococcal vaccines.
The successful introduction of a protein-polysaccharide conjugate vaccine against serogroup C meningococci into the UK infant immunization schedule, in combination with a catch-up campaign for individuals less than 18 years of age, has seen virtually all group C disease eliminated in childhood. From being a devastating disease with a very high mortality, the possibility of eradicating invasive meningococcal disease now seems eminently feasible. Since similar technology is likely to facilitate prevention of disease caused be serogroup A, Y and W135 meningococci, the major hurdle in achieving the goal of eradication is development of a safe and immunogenic vaccine against serogroup B infections. Outer membrane vesicle vaccines remain in development and further trials are anticipated. Through the recent availability of the meningococcal genome sequence, many new vaccine candidates are being identified and there is increasing optimism that a solution to the problem can be found.
Animals↗