Clinical Features, Laboratory Findings and Management of Meningococcal Meningitis in England and Wales: Report of a 1997 Survey

doi:10.1053/jinf.1999.0595

Journal of Infection

Volume 40, Issue 1, January 2000, Pages 74-79

https://doi.org/10.1053/jinf.1999.0595 Get rights and content

Abstract

Objectives: To describe the epidemiological, clinical and laboratory features of meningococcal meningitis and the effects of antibiotics on laboratory investigations under current clinical practices in England and Wales.

Methods: Using a telephone questionnaire, information was gathered on 103 cases with a clinical diagnosis of meningococcal meningitis. Included were cases with samples submitted to the Public Health Laboratory Service (PHLS), Meningococcal Reference Unit (MRU) over a 5-month period in 1997. Tests included microscopic examination, latex agglutination and culture for Neisseria meningitidis, and at MRU confirmation of identification and characterization of isolates and meningococal polymerase chain reaction (PCR) analysis on blood and cerebrospinal fluids (CSF).

Results: Clinically 45% of the cases had predominantly meningitis and 55% had septicaemia and meningitis. Only 29% of the cases received pre-admission benzylpenicillin, and 66% were given antibiotics within an hour of hospital attendance. Microbiological confirmation was achieved in 97 cases, 46 (44%) by traditional tests and 92 (89%) by PCR assay, including some with both. The blood culture positive rate was 23 (22%), but in predominant meningitis the rate was only 10% (5/46). PCR was the sole method of confirmation in 48 cases. Seventy percent of the plasma samples referred were reactive by PCR assay, but all samples taken more than 24 h after hospital antibiotics were non-reactive. PCR-based techniques increased the overall number of cases with a serogroup identified by 44%. Lumbar punctures were performed in 73 of the cases and microbiological confirmation was achieved in 67 (92%) of these cases, compared to 26/30 without lumbar puncture (LP). Eighty-nine percent of the CSF samples referred were reactive by PCR; 50% of the CSF samples taken more than 24 h after hospital antibiotics were reactive, whilst none were positive by culture or microscopy.

Conclusion: Due to variable clinical manifestations, early diagnosis and treatment was difficult. Laboratory confirmation has been improved by the introduction of PCR-based techniques. Meningococcal DNA was detected by molecular methods in CSF samples taken up to 72 h after commencement of antibiotics. During this period patients could be stabilized and the chances of complications attendant upon early LP reduced. In addition to providing accurate epidemiological information, confirming the diagnosis may alter the extent and length of follow-up.

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Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children: An observational cohort study
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Citation Excerpt :
One limitation of our study was that the proportion of positive cases (18%) was lower than in a previous study in our unit (33%),5 although this finding confirms that no bias towards more severe cases occurred in our present study. The blood culture positive rate of around 25% is similar to that in previous studies23,24 and the PCR-only rate of case ascertainment (77%) is slightly higher than reports from the national reference laboratory,24 indicating that we included a representative case mix of patients. This study was done during a period of historically low rates of meningococcal disease, with only 36 confirmed cases in Northern Ireland in 2011 compared with 94 cases in 2004, which has resulted in wider confidence intervals for our estimates of diagnostic accuracy.
Diagnosis of meningococcal disease relies on recognition of clinical signs and symptoms that are notoriously non-specific, variable, and often absent in the early stages of the disease. Loop-mediated isothermal amplification (LAMP) has previously been shown to be fast and effective for the molecular detection of meningococcal DNA in clinical specimens. We aimed to assess the diagnostic accuracy of meningococcal LAMP as a near-patient test in the emergency department.
For this observational cohort study of diagnostic accuracy, children aged 0–13 years presenting to the emergency department of the Royal Belfast Hospital for Sick Children (Belfast, UK) with suspected meningococcal disease were eligible for inclusion. Patients underwent a standard meningococcal pack of investigations testing for meningococcal disease. Respiratory (nasopharyngeal swab) and blood specimens were collected from patients and tested with near-patient meningococcal LAMP and the results were compared with those obtained by reference laboratory tests (culture and PCR of blood and cerebrospinal fluid).
Between Nov 1, 2009, and Jan 31, 2012, 161 eligible children presenting at the hospital underwent the meningococcal pack of investigations and were tested for meningococcal disease, of whom 148 consented and were enrolled in the study. Combined testing of respiratory and blood specimens with use of LAMP was accurate (sensitivity 89% [95% CI 72–96], specificity 100% [97–100], positive predictive value 100% [85–100]; negative predictive value 98% [93–99]) and diagnostically useful (positive likelihood ratio 213 [95% CI 13–infinity] and negative likelihood ratio 0·11 [0·04–0·32]). The median time required for near-patient testing from sample to result was 1 h 26 min (IQR 1 h 20 min–1 h 32 min).
Meningococcal LAMP is straightforward enough for use in any hospital with basic laboratory facilities, and near-patient testing with this method is both feasible and effective. By contrast with existing UK National Institute of Health and Care Excellence guidelines, we showed that molecular testing of non-invasive respiratory specimens from children is diagnostically accurate and clinically useful.
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Citation Excerpt :
The relatively compartmentalised inflammatory response triggered within the subarachnoid space is responsible for the symptoms and signs of meningitis [50]. Fever, vomiting, headache, photophobia, irritability, agitation, drowsiness and neck stiffness are typical manifestations of meningitis in children >5 years of age [51–54]. A rash may be present in up to 26% of cases [55], but is more likely to be absent, scanty or atypical than in septicaemia.
The clinical spectrum of invasive meningococcal disease is diverse with meningitis and/or septicaemia being the commonest modes of presentation. The severity of manifestations of meningococcal infection ranges from bacteraemia, associated with mild non-specific symptoms, to fulminant sepsis with multiorgan failure and death in approximately 10–15% of cases. Localised infections (such as conjunctivitis or septic arthritis) as well as chronic disease may be the sole clinical manifestations but can also lead to disseminated fulminant disease. Among survivors, disabling long-term sequelae can complicate meningococcal disease and result in potentially devastating effects on the quality of life of survivors, most of whom are infants, children and adolescents. The only rational approach to the prevention of meningococcal disease and the associated human suffering is through vaccination.

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^f1: Address all correspondence to: Dr L. Ragunathan, Dept. of Microbiology, Pathology Laboratory, Burnley General Hospital, Casterton Avenue, Burnley, BB10 2PQ, U.K.

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Regular ArticleClinical Features, Laboratory Findings and Management of Meningococcal Meningitis in England and Wales: Report of a 1997 Survey

Abstract

J Infect

J Infect

J Pediatr

The changing presentation of meningococcal disease

Eur J Pediatr

Prognostic factors in meningococcal disease

Scan J Infect

Changing pattern of case ascertainment and trends in meningococcal disease in England and Wales

Comm Dis Rep

Reducing case fatality by giving penicillin before admission to hospital

Br Med J

Early treatment with parenteral penicillin in meningococcal disease

Br Med J

Control of meningococcal disease: guidance for microbiologists

Comm Dis Rep

Regular Article
Clinical Features, Laboratory Findings and Management of Meningococcal Meningitis in England and Wales: Report of a 1997 Survey