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Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine in infants. A randomized controlled trial Snape M.D. et al JAMA. 2008;299(2):173-184 This paper describes a Phase II randomized controlled multi-centre trial of a novel tetravalent meningococcal vaccine (MenACWY). The authors indicate that the annual estimate of invasive meningococcal disease in the United States is between 1400 and 2800 cases, with the highest rate of disease in infants younger than one year and with a second peak in adolescence. Seventy five percent of these cases are caused by meningococcus serogroups C, W-135 or Y. The US Advisory Committee on Immunization Practices therefore advises immunization with a tetravalent glycoconjugate vaccine covering serogroups A, C, W-135 and Y for all 11-18y olds. However the currently licensed vaccine is poorly immunogenic in infancy, where the highest rate of disease is observed. The novel vaccine used in the trial differs from the currently licensed vaccine in that the capsular saccharides of serogroups A, C, W-135 and Y are individually conjugated to a natural mutant of the diphtheria toxin. The quantity and lengths of the saccharide chains are also different, as is the adjuvant. The paper reports results on the safety, reactogenicity and immunogenicity of this novel vaccine in infants. The study recruited healthy 2-month-old infants in Oxford, England and Halifax and Vancouver, Canada, and allowed for the assessment of three primary dosing schedules of MenACWY; 2,3 & 4 months in the UK, 2, 4 & 6 months in Canada and 2 & 4 months in both countries. A UK control group received a monoconjugate serogroup C vaccine at 2 & 4 months. At 12 months of age all UK groups received a booster dose of MenACWY along with 50% of those Canadian infants who had received MenACWY at 2 & 4 months. A plain polysaccharide tetravalent vaccine was administered to the remainder in this group, along with 50% of Canadian infants who received three doses of the novel vaccine, as a probe for the induction of immunological memory by MenACWY. The remainder of the three dose group received no further meningococcal vaccination. Safety and reactogenicity were evaluated immediately after administration, and then by self-reporting by the parents for one week following vaccination. Blood samples were collected before the first vaccination and one month after the final vaccination for the primary immunization schedules, as well as before and one month after the booster vaccination at 12 months. Human complement serum bactericidal activity assays (hSBA) for meningococcus serogroups A, C, W-135 and Y were performed by the manufacturers of the novel vaccine. The statistical analysis of the data, produced by the vaccine manufacturers, was independently repeated and reported in the paper. The primary objective was to assess the percentage of participants whose serum demonstrated standard serologic correlates of protection of hSBA titres greater than or equal to 1:4 for meningococcus serogroups A, C, W-135 and Y after three doses of the vaccine. The secondary objectives were to perform the same assessment following a two dose schedule and to determine if declining hSBA titres could be successfully increased by a booster dose of MenACWY at 12 months of age. Of the 421 participants enrolled in the study 381 were included in the per-protocol analysis for immunogenicity after the primary dosing schedules and 348 for the analysis after boosting. The authors report that according to the per-protocol analysis, the percentages (95% CIs) of those infants who received the primary immunization schedule of MenACWY at 2, 3 & 4 months of age with hSBA titres ≥ 1:4, were serogroup A, 93% (84%-98%); C, 96% (89%-99%); W-135, 97% (90%-100%); and Y, 94% (86%-98%). For the per-protocol analysis of recipients of MenACWY at 2, 4 & 6 months, the percentages (95% CIs) of responders were serogroup A, 81% (71%-89%); C, 98% (92%-100%); W-135, 99% (93%-100%); and Y, 98% (92%-100%). At least 84% of recipients of MenACWY at 2 & 4 months achieved hSBA titres ≥ 1:4 for serogroups C, W-135 and Y after primary immunization, as did at least 60% for serogroup A. At least 95% of primary and booster MenACWY recipients achieved hSBA titres ≥ 1:4 for serogroups C, W-135 and Y at 13 months of age, as did at least 84% for serogroup A. During the primary immunization course, post-vaccination pain on movement of the leg was observed in 7% of UK three dose recipients, 3% of Canadian two dose recipients and 4% of those control infants in the UK who received only the monoconjugate serogroup C vaccine at 2 & 4 months. The authors stated the limitations of the study, notably the inability to draw firm conclusions on either the safety of the vaccine due to the small study numbers or the effect on immunogenicity of/by concomitantly administered vaccines. They concluded that the novel MenACWY conjugate vaccine was well tolerated and immunogenic in the first year of life and that it extended the immune protection provided by the monovalent Men C vaccine in infancy to serogroups A, W-135 and Y. Mobile Laboratory to Improve Response to Meningitis Epidemics, Burkina Faso Epidemic Season 2004 Ouedraogo RT, Njanpop-Lafourcade BM, Jaillard P, Traore Y et al www.institut.veolia.org/ive/ressources/documents/1/254,aertciles-proof-on-mobile-lab.pdf This report describes the design, development and subsequent use of a mobile laboratory during the epidemic meningitis season in Burkina Faso. It also explains how initial problems were identified and overcome, and highlights plans for future use. The reasons for implementing the use of a mobile laboratory were:
During 2003, Mobile Laboratory 1 was designed and tested in the field. A small four-wheel drive vehicle was adapted and fitted with a refrigerator, hot plate, incubator, sink, microscope and centrifuge. Solar panels on the roof provided the electricity. Once in use in the field, several problems arose:
The design of Mobile Laboratory 2 addressed these problems by using an air conditioned vehicle with a detachable body that could remain on site as the laboratory whilst the vehicle was free to continue with the transportation of specimens. Electricity was provided by a diesel generator. Use of Mobile Laboratories 2. Emergency carriage study 3. Technician training Conclusions and Future Directions
However, the efficiency and benefits of these laboratories could be further improved by:
The role of healthcare delivery in the outcome of meningococcal disease in children: a case-control study of fatal and non-fatal cases National statistics and hospital records were used to identify all children under 17 years who died from meningococcal disease. These children were matched by age with three survivors from the same region of the country. Criteria were set to define optimal management and a panel of paediatricians assessed case records using a standardised form and scored patients for suboptimal management. The following three factors were found to be independently associated with an increased risk of death:
The study concluded that suboptimal healthcare delivery significantly reduced the likelihood of survival in children with meningococcal disease. The following actions may improve the outcome for these children:
This paper is very interesting and describes the study in detail. It highlights the need for better training and supervision of junior medical and nursing staff. It also highlights the importance of adhering to published protocols for the management of all life threatening disorders. Back to TopBacterial meningitis in Burkina Faso: Surveillance Using Field-Based Polymerase Chain Reaction Testing, Polymerase Chain Reaction (PCR) techniques are used widely for laboratory bacterial identification but their use in field conditions found in Africa is infrequently tested. The authors of this paper used PCR to conduct a surveillance study documenting the meningitis burden due to various etiological agents and to track the emerging role of meningococci serogroup W135 in epidemics of the disease. The results of the study reveal several interesting aspects of the picture of meningitis in Burkina Faso; the annual incidence of meningitis caused by the meningococcus and the pneumococcus were very similar, 19/100,000 and 17/100,000 respectively, among the meningococcal serogroups W135 predominated, and the case fatality proportion was highest for those persons suffering from pneumococcal meningitis (43%). Of the 1337 cases of suspected meningitis diagnosed on clinical criteria where a sample of cerebrospinal fluid was obtained, bacterial meningitis was confirmed in 409 (33%). The conclusions that might be drawn from this interesting paper are that the prevention and treatment of meningitis may need to focus as much on the pneumocoocus as on the meningococcus. Also, the questions are posed that either there may be another causative agent, which is remaining undetected in almost 70% of suspected cases of meningitis, or that the clinical criteria for meningitis are not well understood. Back to TopTo Tap or Not to Tap: High Likelihood of Meningitis Without Sepsis Among Very Low Birth Weight Infants VLBW infants (excluding those with intraventricular shunts) born at centres of the National Institute of Child Health and Human Development Neonatal Research Network in US from September 1, 1998, through December 31, 2001, were studied. Late-onset meningitis was defined by culture-based criteria and classified as meningitis with or without associated sepsis. Of 9641 VLBW infants who survived >3 days, 2877 (30%) had = 1 LPs, and 6056 (63%) had =1 BC performed after day 3. One hundred thirty-four infants had late-onset meningitis (1.4% of all patients; 5% of those with an LP). Pathogens associated with meningitis were similar to those associated with sepsis. One third (45 of 134) of the infants with meningitis had negative BCs. Lower gestational age and prior sepsis increased risk for meningitis. Compared with uninfected infants, those with meningitis had a longer time on mechanical ventilation (28 vs 18 days), had longer hospitalisations (91 vs 79 days), were more likely to have seizures (25% vs 2%), and were more likely to die (23% vs 2%). The authors concluded that meningitis is a serious complication among VLBW infants, associated with increased severity of illness and risk of death. Of note, one third of the infants with meningitis had meningitis in the absence of sepsis. Because CSF cultures were performed only half as often as BCs, this discordance in blood and CSF culture results suggests that meningitis may be underdiagnosed among VLBW infants. See full article on www.idinchildren.com Back to TopArchived ReviewsMeningococcal meningitis in Africa(PDF doc.) Long term outcome of neonatal meningitis (PDF doc.)
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