Sara Sollai

Analysis of Different Recommendations From International Guidelines for the Management of Acute Pharyngitis in Adults and Children

BACKGROUND Streptococcal pharyngitis is a frequently observed condition, but its optimal management continues to be debated. OBJECTIVE The goal of this study was to evaluate the available guidelines, developed at the national level, for the management of streptococcal pharyngitis in Western countries, with a focus on their differences. METHODS A literature search was conducted of the Cochrane Library, EMBASE, TRIP, and MEDLINE databases from their inception (1993 for the Cochrane Library, 1980 for EMBASE, 1997 for TRIP, and 1966 for MEDLINE) through April 25, 2010. The following search terms were used: pharyngitis, sore throat, tonsillitis, pharyngotonsillitis, Streptococcus pyogenes, Group A β-haemolytic Streptococcus pyogenes, and streptococcal pharyngitis. Searches were limited to type of article or document (practice guideline or guideline) with no language restrictions or language limits. RESULTS Twelve national guidelines were identified: 6 from European countries (France, United Kingdom, Finland, Holland, Scotland, and Belgium), 5 from the United States, and 1 from Canada. Recommendations differ substantially with regard to the use of a rapid antigen diagnostic test or throat culture and the indications for antibiotic treatment. The North American, Finnish, and French guidelines recommend performing one timely microbiologic investigation in suspected cases, and prescribing antibiotics in confirmed cases to prevent suppurative complications and acute rheumatic fever. According to the remaining European guidelines, however, acute sore throat is considered a benign, self-limiting disease. Microbiologic tests are not routinely recommended by these latter guidelines, and antibiotic treatment is reserved for well-selected cases. The use of the Centor score, for evaluation of the risk of streptococcal infection, is recommended by several guidelines, but subsequent decisions on the basis of the results differ in terms of which subjects should undergo microbiologic investigation. All guidelines agree that narrow-spectrum penicillin is the first choice of antibiotic for the treatment of streptococcal pharyngitis and that treatment should last for 10 days to eradicate the microorganism. Once-daily amoxicillin was recommended by 2 US guidelines as equally effective. CONCLUSION The present review found substantial discrepancies in the recommendations for the management of pharyngitis among national guidelines in Europe and North America.

Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a 2013 update

BackgroundPrevious meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria.MethodsWe systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children.ResultsOverall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%).ConclusionsBoth IGRAs showed no better performance than TST in low income countries.

Utility of interferon-γ release assay results to monitor anti-tubercular treatment in adults and children.

BACKGROUND Interferon-γ release assays (IGRAs), including the commercially available T-SPOT.TB, QuantiFERON-TB Gold (QFT-G), and QuantiFERON-TB Gold In-Tube (QTF-G-IT), enable detection of circulating T lymphocytes responsive to specific Mycobacterium tuberculosis antigens. Studies of the potential role of serial IGRAs for assessment of response to anti-tubercular therapy are accumulating. OBJECTIVE The objective of this systematic review was to evaluate the potential clinical utility of serial IGRAs in anti-tubercular therapy. METHODS We conducted a literature search of the Cochrane Library and MEDLINE by PubMed, from database inception through October 1, 2011, for serial IGRA results in anti-tubercular therapy, in adults and children, using commercial stardardized assays. All types of articles in the English language were included. Meta-analysis was performed to estimate the pooled percentage of reversion from a positive to a negative IGRA value at 3- to 6-month follow-up. RESULTS According to inclusion and exclusion criteria, three T-SPOT.TB-based (n = 319 patients), three QFT-G-based (n = 75 patients), and seven QFT-G-IT-based (n = 558 patients) longitudinal studies were included. The percentage of patients with reversion from a positive to a negative IGRA value ranged from 5.71% to 13.93% for T-SPOT.TB, 5.26% to 71.05% for QFT-G, and 14.28% to 41.89% for QFT-G-IT assays. Meta-analysis estimation of reversion was feasible only for the QFT-G-IT assay, at 30.54% (95% CI, 22.89-38.75). In two pediatric studies, which were QFT-G-IT based (n = 122 children), the reported reversion rates were 14.28% and 20.33%, respectively. CONCLUSIONS Because IGRAs require time and cost resources, and reversion from positive to negative IGRA values occurs in a minority of treated patients, monitoring IGRA changes over time seems to have only speculative value in adults. Data in children are poor, but are in line with results reported in adults.

Potential Role of M. tuberculosis Specific IFN-γ and IL-2 ELISPOT Assays in Discriminating Children with Active or Latent Tuberculosis

Background Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI). Objective Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB. Methods Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens. Results Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs. Conclusion Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB.

Drug use and upper gastrointestinal complications in children: a case-control study

Objective To evaluate the risk of upper gastrointestinal complications (UGIC) associated with drug use in the paediatric population. Methods This study is part of a large Italian prospective multicentre study. The study population included children hospitalised for acute conditions through the emergency departments of eight clinical centres. Patients admitted for UGIC (defined as endoscopically confirmed gastroduodenal lesions or clinically defined haematemesis or melena) comprised the case series; children hospitalised for neurological disorders formed the control group. Information on drug and vaccine exposure was collected through parental interview during the childrens hospitalisation. Logistic regression was used to estimate ORs for the occurrence of UGIC associated with drug use adjusted for age, clinical centre and concomitant use of any drug. Results 486 children hospitalised for UGIC and 1930 for neurological disorders were enrolled between November 1999 and November 2010. Drug use was higher in cases than in controls (73% vs 54%; p<0.001). UGICs were associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) (adjusted OR 2.9, 95% CI 2.1 to 4.0), oral steroids (adjusted OR 2.9, 95% CI 1.7 to 4.8) and antibiotics (adjusted OR 2.3, 95% CI 1.8 to 3.1). The duration of use of these drug categories was short (range 1–8 days). Paracetamol showed a lower risk (adjusted OR 2.0, 95% CI 1.5 to 2.6) compared to ibuprofen (adjusted OR 3.7, 95% CI 2.3 to 5.9), although with partially overlapping CIs. Conclusions NSAIDs, oral steroids and antibiotics, even when administered for a short period, were associated with an increased risk of UGIC.

Performance of non-contact infrared thermometer for detecting febrile children in hospital and ambulatory settings

AIMS To assess the performance of the non-contact infrared thermometer compared with mercury-in-glass thermometer in children; to assess the diagnostic accuracy of non-contact infrared thermometer for detecting children with fever; to compare the discomfort caused by the two procedures in children aged > one month. BACKGROUND Non-contact infrared thermometer is a quick and non-invasive method to measure body temperature, not requiring sterilisation or disposables. It is a candidate for temperature recording in children. DESIGN Prospective multicenter study. METHODS Body temperature readings were taken from every child consecutively admitted to the Pediatric Emergency Departments or Pediatric Clinics participating in the study. Two bilateral axillary temperature measurements using the mercury-in-glass thermometers and three mid-forehead temperature measurements using the non-contact infrared thermometer were performed. RESULTS Two hundred and fifty-one children were enrolled in the study. Mean body temperature obtained by mercury-in-glass thermometer and non-contact infrared thermometer was 37.18 (SD 0.96) °C and 37.30 (SD 0.92) °C, respectively (p = 0.153). Non-contact infrared thermometer clinical repeatability was 0.108 (SD 0.095) °C, similar to that of the mercury-in-glass thermometer (0.11 SD 01 °C; p = 0.517). Bias was 0.0150 (SD 0.09) °C. The proportion of outliers >1 °C was 4/251 children (1.59%). A significant correlation between temperature values obtained with the two procedures was observed (r(2) = 0.84; p < 0.0001). The limits of agreement, by the Bland and Altman method, were -0.62 (95% CI: -0.47 to -0.67) and 0.76 (95% CI: 0.61-0.91). No significant correlation was evidenced between the difference of the body temperature values recorded by the two methods and age (p = 0.226), or room temperature (p = 0.756). Calculating the receiver operating characteristic curve to determine the best threshold for axillary temperature >38.0 °C, for a non-contact infrared thermometer temperature = 37.98 °C the sensitivity was 88.7% and the specificity 89.9%. Mean distress score (on a 5-point scale) was significantly lower using the non-contact infrared thermometer than using the mercury-in-glass thermometer (1.92 SD 0.56 and 2.40 SD0.93, respectively; p < 0.0001). CONCLUSION Non-contact infrared thermometer showed a good performance in our study population, has the advantage of measuring body temperature in two seconds and is comfortable for children. RELEVANCE TO CLINICAL PRACTICE Non-contact infrared thermometer may be taken into consideration when assessing body temperature in children aged > one month in hospital or ambulatory.

Effectiveness and safety of the A-H1N1 vaccine in children: A hospital-based case - Control study

Objective To verify whether vaccination against the A-H1N1 virus in the paediatric population was effective in preventing the occurrence of influenza-like illness (ILI) or was associated with adverse events of special interest. Design, setting and patients A case–control analysis was performed as part of surveillance of children hospitalised through the emergency departments of eight paediatric hospitals/wards for ILI, neurological disorders, non-infectious muco-cutaneous diseases and vasculitis, thrombocytopaenia and gastroduodenal lesions. Results Among 736 children enrolled from November 2009 to August 2010, only 25 had been vaccinated with the pandemic vaccine. Out of 268 children admitted for a diagnosis compatible with the adverse events of special interest, six had received the A-H1N1 vaccine, although none of the adverse events occurred within the predefined risk windows. Only 35 children out of 244 admitted with a diagnosis of ILI underwent laboratory testing: 11 were positive and 24 negative for the A-H1N1 virus. None of the A-H1N1 positive children had received the pandemic vaccine. The OR of ILI associated with any influenza vaccination was 0.9 (95% CI 0.1 to 5.5). Conclusions The study provides additional information on the benefit–risk profile of the pandemic vaccine. No sign of risk associated with the influenza A-H1N1 vaccine used in Italy was found, although several limitations were observed: in Italy, pandemic vaccination coverage was low, the epidemic was almost over by mid December 2009 and the A-H1N1 laboratory test was performed only during the epidemic phase (in <10% of children). This study supports the importance of the existing network of hospitals for the evaluation of signals relevant to new vaccines and drugs.

Interferon-gamma release assay sensitivity in children younger than 5 years is insufficient to replace the use of tuberculin skin test in western countries.

Tuberculin skin test, QuantiFERON-TB Gold In-Tube and T-SPOT.TB were performed in 338 children at risk for tuberculosis (TB), including 70 active TB cases. In children <5 years of age, QuantiFERON-TB Gold In-Tube sensitivity was 73.3% [95% confidence interval (CI): 57.5–89.1]; and T-SPOT.TB sensitivity was 59.3% (95% CI: 40.1–77.8); both were inferior to tuberculin skin test sensitivity (90.0%; 95% CI: 79.3–100). In children ≥5 years QuantiFERON-TB Gold In-Tube sensitivity was 92.5% (95% CI: 84.4–100); T-SPOT.TB sensitivity was 73.0% (95% CI: 58.6–87.3) ; and tuberculin skin test sensitivity was 97.5% (95% CI: 92.6–100).Test specificities were similar in all age groups.

Serial T-SPOT.TB and quantiFERON-TB-Gold In-Tube assays to monitor response to antitubercular treatment in Italian children with active or latent tuberculosis infection.

We performed a prospective study to investigate T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-G-IT) dynamics during antitubercular treatment in active tuberculosis (TB) or latent TB. Eighteen children with latent TB and 26 with TB were enrolled. At 6 months of follow-up reversion rate was 5.88% (95% CI:0−13.79) for QFT-G-IT; 9.09% (95% CI:0.59–17.58) for T-SPOT.TB (P=0.921) in TB cases. Significant decline in quantitative response was observed exclusively in TB cases. Our results suggest that serial IGRA have limited use in children receiving antitubercular treatment.

Vaccine effectiveness against severe laboratory-confirmed influenza in children: results of two consecutive seasons in Italy

OBJECTIVE To evaluate the effectiveness of seasonal influenza vaccine in preventing Emergency Department (ED) visits and hospitalisations for influenza like illness (ILI) in children. METHODS We conducted a test negative case-control study during the 2011-2012 and 2012-2013 influenza seasons. Eleven paediatric hospital/wards in seven Italian regions participated in the study. Consecutive children visiting the ED with an ILI, as diagnosed by the doctor according to the European Centre for Disease Control case definition, were eligible for the study. Data were collected from trained pharmacists/physicians by interviewing parents during the ED visit (or hospital admission) of their children. An influenza microbiological test (RT-PCR) was carried out in all children. RESULTS Seven-hundred and four children, from 6 months to 16 years of age, were enrolled: 262 children tested positive for one of the influenza viruses (cases) and 442 tested negative (controls). Cases were older than controls (median age 46 vs. 29 months), though with a similar prevalence of chronic conditions. Only 25 children (4%) were vaccinated in the study period. The overall age-adjusted vaccine effectiveness (VE) was 38% (95% confidence interval -52% to 75%). A higher VE was estimated for hospitalised children (53%; 95% confidence interval -45% to 85%). DISCUSSION This study supports the effectiveness of the seasonal influenza vaccine in preventing visits to the EDs and hospitalisations for ILI in children, although the estimates were not statistically significant and with wide confidence intervals. Future systematic reviews of available data will provide more robust evidence for recommending influenza vaccination in children.