Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease-A Meta-Analysis.

BACKGROUND: Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source. METHODS AND FINDINGS: Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive) were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92) for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9). Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US $ -13,371.94) per correctly treated patient. CONCLUSIONS: Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost-effective; it was also a superior biomarker in infants. Further research is recommended for point-of-care procalcitonin testing and Markov modelling to incorporate cost per QALY with a life-time model.

Molecular testing of respiratory swabs aids early recognition of meningococcal disease in children.

Early meningococcal disease (MD) diagnosis is difficult. We assessed rapid molecular testing of respiratory specimens. We performed genotyping of respiratory swabs, blood, and cerebrospinal fluid from children with suspected disease and nasal swabs (NSs) from matched controls. Thirty-nine of 104 suspected cases had confirmed disease. Four controls were carriers. Throat swab ctrA and porA testing for detection of disease gave a sensitivity of 81% (17/21), specificity of 100% (44/44), positive predictive value (PPV) of 100% (17/17), negative predictive value (NPV) of 92% (44/48), and relative risk of 12. NS ctrA and porA testing gave a sensitivity of 51% (20/39), specificity of 95% (62/65), PPV of 87% (20/23), NPV of 77% (62/81), and relative risk of 4. Including only the 86 NSs taken within 48 h of presentation, the results were sensitivity of 60% (18/30), specificity of 96% (54/56), PPV of 90% (18/20), NPV of 82% (54/66), and relative risk of 5. Swab type agreement was excellent (kappa 0.80, P < 0.001). There was exact phylogenetic agreement from different specimen sites for individuals. Carried genosubtypes were P1.7 and P1.21-7. Prehospital rapid molecular testing of easily obtained respiratory specimens could accelerate diagnosis of MD.

Respiratory viruses do not trigger meningococcal disease in children.

OBJECTIVES: To determine whether the nasopharyngitis prodrome of meningococcal disease is caused by the disease itself or respiratory viral coinfection. METHODS: Case control study of children with suspected meningococcal disease. Nasal swabs and a respiratory history were obtained from suspected cases and matched controls. Molecular testing for 12 respiratory viruses was used. RESULTS: 104 suspected cases and controls were recruited. Detection rates for respiratory viruses were 27% (28/104) for suspected cases and 29% (30/104) for controls. Rhinoviruses (43/58, 74%) and adenoviruses (14/58, 24%) occurred most frequently with 3 coinfections. 39 (38%) suspected cases were confirmed as meningococcal disease with a detection rate for respiratory viruses of 26% (10/39). No significant difference was found in the respiratory viral detection rate between this group and their controls, Odds ratio=1.0 (95% CI 0.3 to 3.3). Prodromal respiratory symptoms were significantly more likely for suspected cases (77/104, 74%) than controls (55/104, 53%), Odds ratio 2.8 (95% CI 1.4 to 6.0), but were equally common in confirmed (28/39, 72%) and unconfirmed cases (49/65, 75%), Odds ratio 0.8 (95% CI 0.3 to 2.3). CONCLUSIONS: This study found no evidence that respiratory viral infections contribute to the prodrome of meningococcal disease. Rhinovirus and adenovirus detection by nasal swab is common in well and unwell children.

A ten year review of atrioventricular septal defects.

OBJECTIVES: To review all cases of atrioventricular septal defects in Northern Ireland from January 1990 to February 1999, examining clinical and morphological features, management, and outcome. METHODS: A retrospective case note analysis of 106 subjects with comparisons between subgroups. RESULTS: An atrioventricular septal defect was part of a more complex abnormality in 50 of the patients (47%). Down's syndrome was present in 57 (54%). Cardiac surgery was performed in 81%. The defects were unrestrictive in 69 patients (65%), 45 of whom had Down's syndrome. Complex associated abnormalities existed in 36 patients, and 10 of these died without cardiac surgery. Operative mortality was 9.5% for those with co-existing Down's syndrome group, and 14.3% for the chromosomally normal patients. The ventricular components of the septal defect were restrictive in 23 patients (22%), with 9 having Down's syndrome. Spontaneous closure occurred in more than half of these patients. Mortality was zero. The septal defect was exclusively at atrial level in 14 patients ("primum" defects--13%), and 3 of these had Down's syndrome. Operative mortality was again zero. Median duration of postoperative follow-up was 3 and a half years. Overall, moderate to severe left atrioventricular valvar regurgitation was observed postoperatively in 23% at follow-up. CONCLUSIONS: Mortality was highest in the atrioventricular septal defects with an unrestrictive ventricular component. Uncomplicated cases had good outcomes. Patients without Down's syndrome tended to have more associated cardiac abnormalities, and to have more postoperative arrhythmias. Approximately half of the defects with restrictive ventricular components closed spontaneously. Moderate postoperative left atrioventricular valvar regurgitation was commonest in patients with the defect exclusively at atrial level.