Improved case confirmation in meningococcal disease with whole blood Taqman PCR. (Original Article)

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From: Archives of Disease in Childhood(Vol. 86, Issue 6)
Publisher: BMJ Publishing Group Ltd.
Document Type: Article
Length: 3,049 words

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Background: The clinical diagnosis of meningococcal disease (MCD) can be difficult. Nan-culture methods like the previous ELISA meningacoccal PCR improved case confirmation rates, but were not ideal. A Taqman meningococcal PCR, using DNA extracted from serum (S-Taqman), which has an improved sensitivity compared to the ELISA method in vitro, was introduced into clinical practice in July 1997. A new whole blood DNA extraction method for Taqman (WB-Taqman) was introduced in September 1999.

Aims: To determine the degree of improvement in the confirmation rate in clinically diagnosed MCD, following the introduction of WB-Taqman.

Methods: A total of 192 patients (WB-Taqman) with possible or probable MCD, including those admitted to our paediatric intensive care unit, were studied. Admission EDTA samples obtained were sent for bacterial DNA detection at the Meningococcal Reference Unit (MRU), Manchester. These patients were compared to 319 patients with possible and probable MCD, seen at the same hospital prior to the introduction of WB-Taqman.

Results: Following the introduction of WB-Taqman, 82 of the 95 probable cases (88%) had a positive meningococcal PCR result. This gives a diagnostic sensitivity and specificity for WB-Taqman of 87% and 100% respectively. Following WB-Taqman all blood culture positive patients were also PCR positive. Confirmation of cases by PCR rose from 47% (S-Taqman, n = 166) to 88% (WB-Taqman). When all confirmatory tests were included, case confirmation increased from 72% (S-Taqman) to 94% (WB-Taqman).

Conclusion: The sensitivity of PCR in confirming clinical MCD has improved significantly with this new method. The gold standard for confirming cases of MCD is now the WB-Taqman PCR.

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In the western world, meningococcal disease (MCD) remains the leading infective cause of death in children outside the neonatal period. The spectrum of clinical presentation is highly variable, ranging from meningitis or septicaemia alone to a combination of the two. A clinical diagnosis is often difficult as the classic triad of an unwell patient with a temperature and a petechial rash is not specific to MCD. Over 20% of patients with MCD have either no rash or only a maculopapular rash, again making clinical diagnosis difficult. (2) This difficulty in diagnosis means that up to two thirds of patients treated do not have MCD, while some with true disease are missed. Adding to this dilemma there is no real gold standard for diagnosis of MCD. Clinical diagnosis, if the patient is assessed from admission until discharge, combined with a raised C reactive protein (CRP), will confirm or exclude the vast majority of confirmed and unconfirmed cases respectively. (3) Previously the sensitivities of blood culture and polymerase chain reaction (PCR) for confirmation of MCD were 31% and 47% respectively, and when all diagnostic tests were combined, 72% of cases were confirmed. (4) The addition of specific convalescent antibody detection can increase case confirmation rates up to 90% or more, but results from serology are not available until at least six weeks post illness.

What was needed was a method that could reliably and rapidly confirm the presence of Neisseria meningitidis. The decrease in...

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Gale Document Number: GALE|A87145610