K. Cartwright

The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica

A total of 6234 nasopharyngeal swabs was collected during a survey of the population of Stonehouse, Gloucestershire in November 1986 as part of an investigation into an outbreak of meningococcal disease. The overall meningococcal carriage rate was 10.9%. The carriage rate rose with age from 2.1% in the 0- to 4-year-olds to a peak of 24.5% in the 15- to 19-year-olds, and thereafter declined steadily with age. Male carriers outnumbered female carriers of meningococci by 3:2. Group B (or non-groupable) type 15 sulphonamide-resistant strains which had caused the outbreak were isolated from 1.4% of subjects. The age distribution of carriers of these strains was similar to that of other meningococci apart from an additional peak in the 5-9-year age group and a more rapid decline in carriage with increasing age. Variations in the carriage rates of the outbreak strain were seen in children attending different schools and in the residents of different areas of the town. The low carriage rate of these strains in a community during a prolonged outbreak supports the hypothesis that these organisms are less transmissible but more virulent than other strains of pathogenic meningococci. Carriage of Neisseria lactamica, which is thought to be important in the development of meningococcal immunity, was most frequent in children under the age of 5 years and was six times commoner in this age group than carriage of Neisseria meningitidis. In older children and adults female carriers of N. lactamica increasingly outnumbered males in contrast to the male preponderance observed with meningococcal carriage.

Early treatment with parenteral penicillin in meningococcal disease.

OBJECTIVE--To measure the effect of parenteral antibiotics given before admission to hospital on mortality and on bacteriological investigations in meningococcal disease. DESIGN--Retrospective review of hospital notes and laboratory and public health medicine department records. SETTING--Three health districts in south west England. SUBJECTS--Patients with meningococcal disease in Gloucester district presenting between 1 January 1982 and 31 December 1991 (n = 190); patients with meningococcal disease in Plymouth (n = 118) and Bath (n = 73) districts presenting between 1 January 1988 and 31 December 1991 (total = 381). MAIN OUTCOME MEASURE--Number of deaths from meningococcal disease. RESULTS--Parenteral antibiotic given by general practitioners was associated with a substantial reduction in mortality (from 9% to 5%; relative risk 0.6, 95% confidence interval 0.2 to 1.5); patients with a rash were more likely to be given parenteral antibiotics, and mortality was further reduced (from 12% to 5%; 0.5, 0.2 to 1.4). In a district where such treatment was regularly encouraged its use increased from 5% to 40% of cases over 10 years (p = 0.00001). Treatment with parenteral antibiotics before admission made isolation of meningococci from blood and cerebrospinal fluid less likely but did not affect nasopharyngeal cultures. CONCLUSIONS--General practitioners should carry benzylpenicillin in their emergency bags at all times and should administer it promptly, preferably intravenously, whenever meningococcal disease is suspected, unless the patient has had an anaphylactic reaction to penicillin. Specimens for culture should include a nasopharyngeal swab.

Influenza A and meningococcal disease

Abstract There are several anecdotal accounts of the association between outbreaks of influenza and meningococcal disease. The exceptional increase in the number of cases of meningococcal infection 2 weeks after an influenza A outbreak in England and Wales during November and December, 1989, provided an opportunity to investigate the relation between the two events. Patients with meningococcal disease in December, 1989, were more likely than age-matched controls to show serological evidence of recent influenza A infection (odds ratio 3·9, 95% Cl 1·2-13·9). The most likely explanation for the association is immune suppression induced by influenza A, though a lowering of mucosal resistance to meningococcal invasion may also be a factor. Public health authorities should be aware of the association and should be prepared to alert medical practitioners and the public to the increased risk of meningococcal disease when influenza A outbreaks occur.

Smoking, the environment and meningococcal disease: a case control study

This case control study investigated environmental factors in 74 confirmed cases of meningococcal disease (MD). In children aged under 5, passive smoking in the home (30 or more cigarettes daily) was associated with an odds ratio (OR) of 7.5 (95% confidence interval (CI) 1.46-38.66). ORs increased both with the numbers of cigarettes smoked and with the number of smokers in the household, suggesting a dose-response relationship. MD in this age group was also significantly associated with household overcrowding (more than 1.5 persons per room) (OR 6.0, 95% CI 1.10-32.8), with kisses on the mouth with 4 or more contacts in the previous 2 weeks (OR 2.46, 95% CI 1.09-5.56), with exposure to dust from plaster, brick or stone in the previous 2 weeks (OR 2.24, 95% CI 1.07-4.65); and with changes in residence (OR 3.0, 95% CI 1.0-8.99), marital arguments (OR 3.0, 95% CI 1.26-7.17) and legal disputes in the previous 6 months (OR 3.10, 95% CI 1.24-7.78). These associations were independent of social class. Public health measures to lower the prevalence of cigarette smoking by parents of young children may reduce the incidence of MD. The influence of building dust and stressful life events merits further investigation.

Polymerase chain reaction for diagnosis of meningococcal meningitis

Meningococcal disease is normally suspected on clinical grounds but confirmed by isolation of Neisseria meningitidis from blood or cerebrospinal fluid (CSF), or by detection of gram-negative diplococci in CSF. After parenteral antibiotics are started the isolation rate of meningococci from blood cultures drops from 50% to less than 5% and the chances of CSF being positive by culture or microscopy are also reduced. We used the polymerase chain reaction (PCR) in a blinded study to detect meningococcal DNA in 54 CSF samples from patients with meningococcal disease or from controls. The PCR primers were specific for the meningococcal insertion sequence IS1106. The sensitivity and specificity of this PCR for diagnosis of meningococcal meningitis were both 91%. Sensitivity was not affected by prior antibiotic treatment. The IS1106 PCR is a rapid and sensitive test for confirmation of the diagnosis of meningococcal meningitis.

Effect of smoking on meningococcal carriage

A case-control study was done to examine whether certain environmental or medical factors were associated with meningococcal carriage. Questionnaires were posted to 138 meningococcal carriers and their controls, and to 52 carriers of Neisseria lactamica and their controls. Carriers were matched to controls by age, sex, and area of residence. The overall response rate was 89%. There were no differences in environmental or medical factors between N lactamica carriers and their controls, nor in household crowding, housing conditions, frequency of physical exercise, or upper respiratory disorders between meningococcal carriers and their controls. Active smoking and the presence of other smokers in the household were independently associated with meningococcal carriage; the risk of carriage increased significantly with heavier smoking.

AN OUTBREAK OF MENINGOCOCCAL DISEASE IN GLOUCESTERSHIRE

Between October, 1981, and March, 1986, there were 65 cases of meningococcal infection, about five times the expected number, in Gloucester Health District. The cases, mainly in teenagers and young adults, were clustered in the Stroud district and in the southern part of Gloucester City, and most were caused by a sulphonamide-resistant group B type 15 meningococcus. 2 patients died. Only 57% of meningitis cases were formally notified. 7 (11%) patients had septicaemia without meningitis, not a notifiable disease. All meningococcal disease should be made notifiable and meningococci should be serotyped routinely so that the epidemiology of the disease can be monitored before the introduction of suitable vaccines.

Invasive Haemophilus influenzae disease in adults.

We reviewed retrospectively all invasive Haemophilus influenzae (Hi) infections in adults ascertained from reference laboratory records and notifications from five NHS regions over the 5 years from 1 October 1990, a period encompassing the introduction of routine Hib childhood immunization (October 1992). A total of 446 cases were identified, a rate of 0.73 infections per 10(5) adults per annum. Though numbers of Hib infections in adults fell after the introduction of Hib vaccines for children (P = 0.035), and there was no increase in infections caused by other capsulated Hi serotypes, total numbers of invasive Hi infections increased due to a large rise in infections caused by non-capsulated Hi (ncHi) strains (P = 0.0067). There was an unexpectedly low rate of infections in those aged 75 years or more (P < 0.0001). The commonest clinical presentations were pneumonia with bacteraemia (227/350, 65%) and bacteraemia alone (62/350, 18%) and the highest rates of disease were in the 65-74 years age group (P < 0.0001). Clinical presentation was not influenced by the capsulation status of the invading Hi strain. 103/350 cases (29%) died within 1 month, and 207/350 (59%) within 6 months of their Hi infection. Case fatality rates were high in all age groups. Pre-existing diseases were noted in 220/350 cases and were associated with a higher case fatality rate (82% vs. 21%, P < 0.0001). After the introduction of Hib immunization in children, invasive Hib infections in unimmunized adults also declined, but the overall rate of invasive Hi disease in adults increased, with most infections now caused by non-capsulated strains. Physicians and microbiologists should be aware of the changing epidemiology, the high associated mortality and high risk of underlying disease. Invasive haemophilus infections in adults should be investigated and treated aggressively.

Induction of immunological memory in UK infants by a meningococcal A/C conjugate vaccine

The induction of immunological memory to serogroup A and C polysaccharides in UK infants immunized with three doses of a meningococcal A/C oligosaccharide CRM197 conjugate vaccine was investigated. Forty UK infants vaccinated previously with three doses of a meningococcal A/C oligosaccharide-CRM197 conjugate vaccine at 2, 3 and 4 months of age, were revaccinated at a mean age of 145.6 weeks with either a 10 or 50 microg dose of licensed meningococcal A/C polysaccharide vaccine. Serogroup-specific antibody and serum bactericidal antibody (SBA) responses were measured by enzyme-linked immunosorbent assay and serum bactericidal assays, respectively. Following challenge, anti-serogroup A and C polysaccharide antibody levels rose from pre-booster geometric mean concentrations (GMC) of 3.1 and 2.1 microg/ml respectively to 19.6 and 21.0 microg/ml 1 month post-booster. Serum bactericidal antibody geometric mean titres (GMTs) for serogroups A and C increased 156- and 113-fold from 2.1 and 7.1 pre-booster respectively to 327.4 and 800.7 post-booster. A serogroup A control group of 45 children received a 10 microg dose of licensed meningococcal A/C polysaccharide vaccine (with no prior history of serogroup A vaccination) had serogroup A SBA GMTs of 2.3 pre-vaccination rising to 8 post-vaccination with corresponding GMCs of 0.8 and 10.8 microg/ml. These rises in SBA following serogroup A/C conjugate vaccination are indicative of immunological priming.

Invasive pneumococcal infection in South and West England.

Variation in the incidence of invasive pneumococcal disease across South and West England, in 1995, was measured through a survey of microbiology laboratories. A 100% response rate was achieved. The incidence by laboratory varied between 5.2 and 20.4 per 100,000 catchment population (P < 0.001). Adjusting for pneumococcal vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture system used and for the age and sex structure of the population, did not account for this variation. When blood culture sampling rates were included in a logistic regression model, the variation between laboratories was much less and of lower statistical significance (P = 0.019). Higher rates of blood culture sampling were associated with a higher incidence of invasive pneumococcal disease. Consistently high sampling should be encouraged because a higher diagnostic rate should result in more selective prescribing of antibiotics, and secondly because improved ascertainment of severe pneumococcal infections is a prerequisite for the evaluation of new pneumococcal conjugate vaccines.