Prospective Study of a Real-Time PCR That Is Highly Sensitive, Specific, and Clinically Useful for Diagnosis of Meningococcal Disease in Children

Abstract

Due to the early administration of antibiotics, meningococcal disease is increasingly difficult to diagnose by culturing. Laboratory studies have shown PCR to be sensitive and specific, but there have been few clinical studies. The objectives of this study were to determine the diagnostic accuracy and clinical usefulness of meningococcal PCR through a prospective comparison of real-time PCR, nested PCR, and standard culturing of blood and cerebrospinal fluid (CSF). The setting was a tertiary-care pediatric hospital in Australia, and the participans were 118 children admitted with possible septicemia or meningitis. The main outcome measuressensitivity, specificity, and positive and negative predictive values-were compared to a "gold standard " fulfilling clinical and laboratory criteria. For 24 cases of meningococcal disease diagnosed by the gold standard, culturing of blood or CSF was positive for 15 (63%), nested PCR was positive for 21 (88%), and real-time PCR was positive for 23 (96%). The sensitivity, specificity, and positive and negative predictive values of real-time PCR (the most sensitive test) for all specimens were, respectively, 96% (95% confidence interval, 79 to 99%), 100% (95% confidence interval, 96 to100%), 100% (95% confidence interval, 85 to 100%), and 99% (95% confidence interval, 94 to 100%). Of 54 patients with suspected meningococcal disease at admission, 23 had positive PCR results. Only one PCR specimen was positive in a patient thought unlikely to have meningococcal disease at admission. Blood PCR remained positive for 33% of patients tested at up to 72 h. Real-time PCR has high positive and negative predictive values in this clinical setting, with better confirmation of cases than nested PCR. Targeting patients for PCR based on admission criteria appears to be practical, and the test may remain useful for several days after the start of antibiotic administration.Meningococcal septicemia and meningitis are life-threatening diseases. Rapid, accurate diagnosis is essential for optimal management of patients and the provision of prompt prophylaxis to contacts. Confirmation of the diagnosis allows physicians to use narrow-spectrum antibiotics, limit the duration of treatment, and provide prognostic information. It also provides vital disease burden information, including data to inform vaccine policy.It is becoming increasingly difficult to confirm the diagnosis of meningococcal infection by conventional microscopy and culturing techniques (6). Blood cultures are positive in about 50% of untreated patients with clinically suspected meningococcal septicemia. This rate is reduced to 5% when antibiotics have been administered prior to admission; primary care practitioners are encouraged in this practice early for suspected cases (8,9,19). Cerebrospinal fluid (CSF) microscopy or culturing is positive in 80 to 90% of untreated cases of meningococcal meningitis, but this rate is also reduced by prior antibiotic administration. In addition, many patients do not undergo a lumbar puncture early in t...

Meningococcemia in Adults: A Review of the Literature

“…In the UK, a fair amount of meningococcal disease has been diagnosed by PCR alone (55). A PCR has advantages over a culture analysis because it enables faster diagnosis; furthermore, its sensitivity (reportedly 96%) is not affected by the prior administration of antibiotics (56). The sensitivity of a PCR is higher than the sensitivities of CSF or blood culture analyses (56).…”

“…A PCR has advantages over a culture analysis because it enables faster diagnosis; furthermore, its sensitivity (reportedly 96%) is not affected by the prior administration of antibiotics (56). The sensitivity of a PCR is higher than the sensitivities of CSF or blood culture analyses (56). In addition, the PCR of skin biopsy cultures (100%) has been shown to be more sensitive than the PCR of blood cultures (58.8%) (44,57).…”

The efficiency of sodC gene / N. meningitidis detection in comparison with the classical methods for the diagnosis of meningococcal infection / Evaluarea eficienţei Real Time PCR TaqMan utilizând gena sodC / N. meningitidis în comparaţie cu metodele clasice utilizate în diagnosticul infecţiei meningococice

“…The real advantage of RT -PCR compared to culture is the fast availability of Brought to you by | MIT Libraries Authenticated Download Date | 5/9/18 3:44 PM results, about 2.5 hours after sampling of the samples to the laboratory, as demonstrated by our study. Other studies also show that RT-PCR results are available on the day of admission, compared with culture results requiring a minimum of 24-48 h for confirmation, thus allowing clinicians to initiate targeted therapy, to reduce the tests for other diagnoses, and to institute preventive measures specific for contacts (24,25).…”

Mutations in folP Associated with Elevated Sulfonamide MICs for Neisseria meningitidis Clinical Isolates from Five Continents

“…In the appropriate setting, detection of meningococcal DNA or RNA by PCR or other nucleic acid amplification methods may lead to a rapid diagnosis of invasive meningococcal disease, which is particularly important for infection control (9). Identification of molecular markers of antibiotic resistance in the absence of a culture isolate would be helpful not only for therapeutic and prophylaxis decisions but also in defining the evolving epidemiology of meningococcal disease and detection of emerging resistance.…”