Prevalence of de-O-acetylated serogroup C meningococci before the introduction of meningococcal serogroup C conjugate vaccines in the United Kingdom

Meningococcal serogroup C conjugate (MCC) vaccines have been introduced in the UK to combat the rise in serogroup C meningococcal disease. Serogroup C meningococci may occur naturally expressing either O-acetylated (Oac(+)) or de-O-acetylated (Oac(-)) polysaccharide capsules. In a small study in the USA in the 1970s 15% of serogroup C meningococcal case isolates were reported to be Oac(-) though the prevalence of these Oac(-) isolates has not been recorded in the UK. This is of interest as the first MCC vaccines to be introduced are Oac(+) and the potential impact of this on Oac(-) serogroup C isolates is unclear. Serogroup C isolates submitted to the Public Health Laboratory Service Meningococcal Reference Unit in January 1998 (n=113) and January 1999 (n=162) were investigated by dot blotting using monoclonals specific for Oac(+) and Oac(-) serogroup C polysaccharides. This revealed 12% Oac(-) isolates for both January 1998 and January 1999. The proportion of fatal cases was found to similar for both Oac(-) and Oac(+), 14 and 9% for 1998 and 5 and 3% for 1999, indicating that the pathogenic potential of these Oac(-) isolates is similar to Oac(+). The acetylation status of serogroup C isolates needs to be monitored throughout and after the introduction of MCC vaccines.     

Recent emergence of serogroup C meningococcal disease in Greece

The number of cases of meningococcal disease reported to the Meningitis Reference Laboratory in Athens rose dramatically in 1996-1997. The aims were (1) to determine if the increase was due to introduction of new strains, (2) to assess the geographic and age distribution of the cases, (3) to compare antibiotic sensitivity patterns of the current isolates with strains from the early 1990s. In 1993-1994, 15/19 (74%) of the cases for which information on age was available were in children < or = 5 years; in 1995-1997, 80/179 (45%) of cases were in children < or = 5 years and 99 (55%) in the older age range (P < 0.02). From 593 cases in 1993 1997, 214 (36%) isolates were available for characterisation. Serogroup B was predominant in the early 1990s, but by 1997, serogroup C accounted for 46/72 (64%) of isolates and serogroup B for 25/72 (35%). Serogroup B was predominant in children < or = 5 years (44/78, 56%) but only 19/99 (18%) of older children and adults (P=0.0000005). Sulfonamide resistance decreased from 10/22 (45%) in 1993-1994 to 27/192 (14%) in 1995-1997 (P<0.01). Multilocus enzyme electrophoresis of 70 strains obtained during this period identified the epidemic ET-15 clone in 24 (34.3)%. The profiles of the Greek ET-15 isolates were identical to C:2a:P1.2(P1.5) strains responsible for the epidemic in the Czech Republic which began in 1993. This genotype was not found in Greek strains isolated prior to 1993. We conclude that the increase in meningococcal disease is due to introduction of the epidemic serogroup C:2a:P1.2(P1.5) strain responsible for disease in the Czech Republic and Canada.     

Memory immune response generated in Cercopithecus aethiops against meningococcal polysaccharide serogroup C conjugate vaccine

The chemical conjugation of bacterial polysaccharide to carrier proteins has proved to be an efficient tool to improve the immunological response against these bacterial antigens. In this study, we characterized the antibody response generated in a non-human primate model against the meningococcal capsular polysaccharide serogroup C (CCPS) conjugated to the P64k protein. Similar to licensed vaccines the CCPS conjugate is able to generate a good memory immune response with antibody titers threefold higher than the free CCPS. Three different ELISA protocols were used to measure the antibody response and the importance of the coating antigen was demonstrated. The ELISA using the derivatized CCPS showed the best results and had a high correlation with the bactericidal activity. The antibodies elicited showed a high protective capacity when assayed in the infant rat protection model.     

Rapid laboratory detection of meningococcal disease outbreaks caused by serogroup C Neisseria meningitidis

Molecular subtyping is of significant importance to the recognition of outbreaks of meningococcal disease caused by serogroup C Neisseria meningitidis. We describe the application of multilocus variable number tandem repeat analysis (MLVA) for the molecular subtyping of N. meningitidis and compare its performance to that of pulsed-field gel electrophoresis (PFGE). For MLVA, a multiplex PCR assay targeting five variable number tandem repeat regions was developed and evaluated using a panel of sporadic and outbreak-associated serogroup C N. meningitidis isolates. MLVA was highly reproducible and provided results within 6 h. Overall, the discriminatory power of MLVA was equivalent to that of PFGE. The utilization of MLVA for subtyping N. meningitidis isolates provides a rapid and safer alternative to PFGE for identifying outbreaks of meningococcal disease. As such, it may provide public health officials with timely information that may minimize the spread of outbreak-related cases through prophylaxis.     

Second serogroup of Legionella quinlivanii isolated from two unrelated sources in the United Kingdom

R.J. BIRTLES, N. DOSHI, N.A. SAUNDERS AND T.G. HARRISON. 1991. A series of strains, presumptively identified as legionellas on the basis of their nutritional requirements and biochemical reactivity, were isolated from two unrelated environmental sources in the UK. Representatives of each of these series had a restriction endonuclease digest pattern indistinguishable from that of the Legionella quinlivanii type strain (1442-AUS-E) and the identity of these strains was confirmed by DNA homology studies. Serological examination of the two strains showed that they were distinct from the type strain 1442-AUS-E but indistinguishable from each other. A second serogroup, L. quinlivanii serogroup 2 (type strain LC870; NCTC 12434), is proposed to accommodate these strains.     

Second serogroup of Legionella quinlivanii isolated from two unrelated sources in the United Kingdom.

A series of strains, presumptively identified as legionellas on the basis of their nutritional requirements and biochemical reactivity, were isolated from two unrelated environmental sources in the UK. Representatives of each of these series had a restriction endonuclease digest pattern indistinguishable from that of the Legionella quinlivanii type strain (1442-AUS-E) and the identity of these strains was confirmed by DNA homology studies. Serological examination of the two strains showed that they were distinct from the type strain 1442-AUS-E but indistinguishable from each other. A second serogroup, L. quinlivanii serogroup 2 (type strain LC870; NCTC 12434), is proposed to accommodate these strains.     

Modelling cost effectiveness of meningococcal serogroup C conjugate vaccination campaign in England and Wales

ObjectivesTo assess the cost effectiveness of a meningococcal serogroup C conjugate vaccination campaign in 0-17 year olds.DesignCost effectiveness analysis from the perspective of the healthcare provider.SettingEngland and Wales.ResultsIn 1998-9, immediately before the introduction of meningococcal C vaccination, the burden of serogroup C disease was considerable, with an estimated 1137 cases in people aged 0-17 years and at least 72 deaths. The vaccination campaign is estimated to have cost between £126m ($180m, €207m) and £241m ($343m, €395m), depending on the price of the vaccine. Under base case assumptions the cost per life year saved from the vaccination campaign is estimated to be £6259. School based vaccination was more cost effective than general practice based vaccination because of lower delivery costs. Immunisation of infants aged under 1 year was the least cost effective component of the campaign because, although this maximises the life years gained, the three dose schedule required is more expensive than other methods of delivery. Estimates of the cost per life year saved were sensitive to assumptions on the future incidence of disease and the case fatality ratio.ConclusionsMeningococcal C vaccination is likely to be more cost effective in all age groups when the incidence of disease is high. It is also more cost effective when given to children aged 1-4 (by general practitioners) and to children and young people aged 5-17 years at school than when administered to infants under 12 months of age or young people aged 16-17 years who are not at school.

What is already known on this topic

The burden of group C meningococcal disease in England and Wales in the late 1990s was considerableIn November 1999 the United Kingdom was the first country to introduce mass vaccination against group C meningococcal diseaseThere are no published economic evaluations of the vaccination campaign

What this study adds

This economic evaluation supports the introduction of the meningococcal C vaccineSchool based vaccination is more cost effective than routine vaccination of infants because delivery costs are lower and fewer doses are required     

Presymptomatic testing for Huntington's disease in the United Kingdom. The United Kingdom Huntington's Disease Prediction Consortium.

OBJECTIVE--To evaluate the United Kingdom Huntington''s disease presymptomatic testing programme. DESIGN--Postal questionnaire survey to collect data on all tests performed by clinical genetics centres between 1987 and 1990. SETTING--Genetic centres providing presymptomatic testing in the United Kingdom. SUBJECTS--248 subjects at risk of Huntington''s disease who had presymptomatic testing at their request. MAIN OUTCOME MEASURES--Sex, age, prior risk, and risk after testing. RESULTS--The risk of carrying the Huntington disease gene was reduced for 151 (61%) of the applicants and raised for 97 (39%). 158 (64%) of the subjects were female and 90 (36%) male. The median age at which the results were given was 32.5 years. CONCLUSIONS--The demand for testing was lower than expected and may have reached its peak in 1990. The excess of low risk results was not fully explained by the age effect. All the genetics centres concerned have agreed a common service protocol which requires extensive pre-test counselling and post-test follow up. The worth of the procedure remains to be decided. The availability of a large body of pooled data from all the United Kingdom testing centres, which individually are likely to have only a few results, will form a valuable resource for monitoring the long term psychosocial impact of testing.     

Antigenic and genetic characterization of serogroup C meningococci isolated from invasive meningococcal disease cases in Canada from 1999 to 2003

Four hundred and forty-two serogroup C Neisseria meningitidis isolates from individual invasive meningococcal disease (IMD) patients in Canada during the period 1999 to 2003 were analyzed. The majority (84%) of the serogroup C meningococci were characterized by the serotype antigen 2a and belonged to the clonal complex of electrophoretic type ET-15. However, after more than a decade of endemic disease as well as a number of outbreaks and many vaccination campaigns, both genetic and antigenic variants of the serogroup C serotype 2a meningococci were noted. Such variants include strains characterized as C:2a:P1.5 and C:2a:P1.7,1 as well as a non-serotypeable phenotype due to a mutational hot spot on the serotype 2a PorB outer-membrane protein. Meningococci characterized by the antigen formula B:2a:P1.5,2 and B:2a:P1.7,1 have also been found, which suggests capsule switching. Besides the clonal group of ET-15/ET-37, small numbers of serogroup C isolates were found to belong to the clonal complexes of ST-8 (Cluster A4), ST-41/44 (Lineage 3), ST-35, and ST-269.     

Comparison of three ELISA protocols to measure antibody responses elicited against serogroup C meningococcal polysaccharide in mouse, monkey and human sera

In this study we compared the following ELISA protocols to measure antibody levels against serogroup C meningococcal polysaccharide: a traditional protocol using poly-L-Lysine mixed with the polysaccharide as coating antigen, a second protocol coating with a mixture of methylated human serum albumin with the C polysaccharide, a modified protocol coating with derivatized polysaccharide and a modification to the last one, specifically without adding ammonium thiocyanate to the sample buffer. Serum bactericidal activity of mouse, monkey and human sera were measured and correlation coefficients were calculated. For all serum types the modified ELISA protocol showed the highest correlation coefficients while the traditional protocol showed the lower ones. We demonstrated that the traditional protocol measures non-specific antibodies to the C polysaccharide, because no differences were detected between pre-immune and post-immune human sera (P>0.05), while the modified protocol detected the highest difference (P<0.01).     

Gall stones in sickle cell disease in the United Kingdom.

The prevalence of gall stones was studied prospectively by abdominal ultrasound examination in 131 patients with sickle cell disease aged 10-65 years. Of 95 patients with homozygous sickle cell disease, 55 (58%) had gall stones or had had a cholecystectomy. Gall stones were present in four out of 24 (17%) patients with haemoglobin S + C disease and two out of 12 (17%) with haemoglobin S beta thalassaemia. The presence of gall stones was not related to sex, geographical origin, or haematological variables and was not associated with abnormal results of liver function tests. Symptoms typical of biliary colic were reported by 32 out of 47 adult patients with gall stones, and cholecystitis or cholestasis was diagnosed in 18. Cholecystectomy was performed in 29 patients with good relief of symptoms in most cases. Postoperative complications were common, occurring in 10 of the 28 patients who could be evaluated, but not generally serious; they were considerably lessened by a preoperative exchange transfusion that reduced the haemoglobin S concentration to below 40%. It is suggested that all patients with sickle cell disease should be screened for gall stones and that elective cholecystectomy should be performed in those with symptoms or complications.     

Malaria in the United Kingdom

Over the past decade the United Kingdom had the second highest number of cases of imported malaria among European countries. There has been a substantial rise in recorded cases of malaria during the past three years though some of it may be due to improved notification. Fatal cases of malaria in visitors to Africa have averaged 6.5% of reported infections due to Plasmodium falciparum. Attacks of vivax malaria may occur several months after travellers return from a malarious country.     

Beta-glucuronidase activity of Vero cytotoxin-producing strains of Escherichia coli, including serogroup 0157, isolated in the United Kingdom

One hundred and twenty Vero cytotoxin-producing (VT⁺) strains of Escherichia coli 0157 (of H type 7 or non-motile) isolated in the UK, failed to ferment sorbitol after 24 h or to hydrolyse 4-methylumbelliferyl-beta- d -glucuronide (MUG). This combination of properties was not found in 167 of 169 other E. coli strains, including VT⁺strains of other serogroups and VT^-strains of serogroup 0157. As the two exceptions were rare VT^-strains of serotype 0157: H7, we conclude that, although biochemical tests can aid the isolation of VT⁺0157 strains, confirmation of VT production is necessary.     

Transmission pathways of foot-and-mouth disease virus in the United Kingdom in 2007

Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.