[Pertussis worldwide. Vaccinating children and adults]. / La coqueluche dans le monde. Vacciner l'enfant et l'adulte.

Pertussis (whooping cough) is an important cause of morbidity and mortality in infants world-wide, and continues to be a public health concern despite high vaccination coverage. The disease, caused by bacterium Bordetella pertussis, is present in all countries. Before vaccines became widely available in the 1950s, pertussis was one of the most common childhood diseases worldwide. According to WHO, estimation of deaths was 4 millions/year in 1950 and 100 000/year in 2015. But morbidity remains important with a high circulation of the bacterium determining atypical clinical forms after whole cell or acellular vaccines use. This is due mainly to the absence of booster doses in adolescents and adults. Major progress are generalisation of PCR and vaccination of mother during pregnancy. A resurgence of pertussis is observed after generalisation of acellular vaccines use. In China the progression of allele ptxPl was found in all areas following the use of acellular vaccine. This allele, rare before acellullar vaccine, is linked to a macrolide resistance, and reaches more than 30% of strains isolated in hospitalised children.These evolutions must be evaluated in clinical forms and genotyping of all strains, in all areas.

Recovery from childhood community-acquired pneumonia in a developing country: Prognostic value of serum procalcitonin.

BACKGROUND: Childhood community-acquired pneumonia is a common and potentially life-threatening illness in developing countries. We assessed the prognostic value of serum procalcitonin level upon admission on clinical response to antibiotic treatment. METHODS: Out of 89 patients, the median (IQR) age was 19(12-29) months and 60% were boys. Viral (49.5%), typical bacterial (38%) and atypical bacterial (12.5%) infections as well as probable pneumococcal infections (26%) were diagnosed. RESULTS: Seventy-five (84%) children became afebrile ≤48h after treatment. In 14 children who remained febrile after 48h of treatment, median[IQR] serum procalcitonin (ng/ml) level on admission was higher than in those with rapid recovery (2.1[0.8-3.7] vs 0.6[0.1-2.2]; P=0.025). In the slow-responding children, pneumococcal infections were more common (71% vs 17%; P<0.001). Procalcitonin concentrations on admission were higher in children with pneumococcal pneumonia compared to children with non-pneumococcal pneumonia (2[0.7-4.2] vs 0.5[0.08-2.1]; P=0.002). The ROC curve found that <0.25ng/ml of serum procalcitonin had a high negative predictive value (93%[95%CI:80%-99%]) for pneumococcal infection. All children that remained febrile after 48h of treatment had procalcitonin >0.25ng/ml on admission. The majority of children with pneumonia in a developing country become afebrile within 48h after onset of antibiotic treatment. CONCLUSIONS: Serum procalcitonin <0.25ng/ml predicted rapid clinical response and non-pneumococcal etiology.

Invasive pneumococcal disease in children can reveal a primary immunodeficiency.

BACKGROUND: About 10% of pediatric patients with invasive pneumococcal disease (IPD) die from the disease. Some primary immunodeficiencies (PIDs) are known to confer predisposition to IPD. However, a systematic search for these PIDs has never been carried out in children presenting with IPD. METHODS: We prospectively identified pediatric cases of IPD requiring hospitalization between 2005 and 2011 in 28 pediatric wards throughout France. IPD was defined as a positive pneumococcal culture, polymerase chain reaction result, and/or soluble antigen detection at a normally sterile site. The immunological assessment included abdominal ultrasound, whole-blood counts and smears, determinations of plasma immunoglobulin and complement levels, and the evaluation of proinflammatory cytokines. RESULTS: We included 163 children with IPD (male-to-female ratio, 1.3; median age, 13 months). Seventeen children had recurrent IPD. Meningitis was the most frequent type of infection (87%); other infections included pleuropneumonitis, isolated bloodstream infection, osteomyelitis, endocarditis, and mastoiditis. One patient with recurrent meningitis had a congenital cerebrospinal fluid fistula. The results of immunological explorations were abnormal in 26 children (16%), and a PID was identified in 17 patients (10%), including 1 case of MyD88 deficiency, 3 of complement fraction C2 or C3 deficiencies, 1 of isolated congenital asplenia, and 2 of Bruton disease (X-linked agammaglobulinemia). The proportion of PIDs was much higher in children aged >2 years than in younger children (26% vs 3%; P < .001). CONCLUSIONS: Children with IPD should undergo immunological investigations, particularly those aged >2 years, as PIDs may be discovered in up to 26% of cases.

European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014.

OBJECTIVES: These guidelines update and extend evidence-based indications for the management of children with acute gastroenteritis in Europe. METHODS: The guideline development group formulated questions, identified data, and formulated recommendations. The latter were graded with the Muir Gray system and, in parallel, with the Grading of Recommendations, Assessment, Development and Evaluations system. RESULTS: Gastroenteritis severity is linked to etiology, and rotavirus is the most severe infectious agent and is frequently associated with dehydration. Dehydration reflects severity and should be monitored by established score systems. Investigations are generally not needed. Oral rehydration with hypoosmolar solution is the major treatment and should start as soon as possible. Breast-feeding should not be interrupted. Regular feeding should continue with no dietary changes including milk. Data suggest that in the hospital setting, in non-breast-fed infants and young children, lactose-free feeds can be considered in the management of gastroenteritis. Active therapy may reduce the duration and severity of diarrhea. Effective interventions include administration of specific probiotics such as Lactobacillus GG or Saccharomyces boulardii, diosmectite or racecadotril. Anti-infectious drugs should be given in exceptional cases. Ondansetron is effective against vomiting, but its routine use requires safety clearance given the warning about severe cardiac effects. Hospitalization should generally be reserved for children requiring enteral/parenteral rehydration; most cases may be managed in an outpatients setting. Enteral rehydration is superior to intravenous rehydration. Ultrarapid schemes of intravenous rehydration are not superior to standard schemes and may be associated with higher readmission rates. CONCLUSIONS: Acute gastroenteritis is best managed using a few simple, well-defined medical interventions.

Association of procalcitonin with acute pyelonephritis and renal scars in pediatric UTI.

BACKGROUND AND OBJECTIVE: Urinary tract infections (UTIs) are common childhood bacterial infections that may involve renal parenchymal infection (acute pyelonephritis [APN]) followed by late scarring. Prompt, high-quality diagnosis of APN and later identification of children with scarring are important for preventing future complications. Examination via dimercaptosuccinic acid scanning is the current clinical gold standard but is not routinely performed. A more accessible assay could therefore prove useful. Our goal was to study procalcitonin as a predictor for both APN and scarring in children with UTI. METHODS: A systematic review and meta-analysis of individual patient data were performed; all data were gathered from children with UTIs who had undergone both procalcitonin measurement and dimercaptosuccinic acid scanning. RESULTS: A total of 1011 patients (APN in 60.6%, late scarring in 25.7%) were included from 18 studies. Procalcitonin as a continuous, class, and binary variable was associated with APN and scarring (P < .001) and demonstrated a significantly higher (P < .05) area under the receiver operating characteristic curve than either C-reactive protein or white blood cell count for both pathologies. Procalcitonin ≥0.5 ng/mL yielded an adjusted odds ratio of 7.9 (95% confidence interval [CI]: 5.8-10.9) with 71% sensitivity (95% CI: 67-74) and 72% specificity (95% CI: 67-76) for APN. Procalcitonin ≥0.5 ng/mL was significantly associated with late scarring (adjusted odds ratio: 3.4 [95% CI: 2.1-5.7]) with 79% sensitivity (95% CI: 71-85) and 50% specificity (95% CI: 45-54). CONCLUSIONS: Procalcitonin was a more robust predictor compared with C-reactive protein or white blood cell count for selectively identifying children who had APN during the early stages of UTI, as well as those with late scarring.

Risk factors associated with extended-spectrum ß-lactamase-producing Enterobacteriaceae carriage at admission in an infant cohort at a tertiary teaching hospital in France.

We describe risk factors associated with extended-spectrum ß-lactamase-producing Enterobacteriaceae fecal carriage at admission in an infant population. 12.6% were carrying extended-spectrum ß-lactamase-producing Enterobacteriaceae. Klebsiella pneumoniae, and Escherichia coli were the most frequently identified species. Prior antibiotic therapy (P = .016; odds ratio, 4.07; 95% confidence interval: 1.29-12.81) and the presence tracheostomy or gastrostomy (P = .018; odds ratio, 3.62; 95% confidence interval: 1.24-10.53) were independently associated with carriage at admission.

Risk associated with a systematic search of extended-spectrum ß-lactamase-producing Enterobacteriaceae.

We evaluated 74 children with previous fecal extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae colonization who were hospitalized and receiving a course of antibiotic therapy for suspected infection. Sixty-four patients (86.5%) received a carbapenem agent. Only 3 patients were infected with an ESBL-producing Enterobacteriaceae. Sixty-one (95%) initial antibiotic courses were considered excessive and required deescalation; however, deescalation was accomplished in only 38 patients (62%). This suggests the need for an ESBL control program to decrease carbapenem use and thereby limit carbapenem resistance in gram-negative bacilli.

Procalcitonin predicts response to beta-lactam treatment in hospitalized children with community-acquired pneumonia.

BACKGROUND: Antibiotic treatment of community-acquired pneumonia (CAP) in children remains mostly empirical because clinical and paraclinical findings poorly discriminate the principal causes of CAP. Fast response to beta-lactam treatment can be considered a proxy of pneumococcal aetiology. We aimed to identify the best biological predictor of response to beta-lactam therapy in children hospitalized for CAP. METHODS: A retrospective, single-centre cohort study included all consecutive patients 1 month to 16 years old hospitalized in a teaching hospital in Paris, France, because of CAP empirically treated with a beta-lactam alone from 2003 to 2010. Uni- and multivariate analyses were used to study the ability of routine biological parameters available in the Emergency Department to predict a favourable response to beta-lactam (defined as apyrexia within 48 hours of treatment onset). RESULTS: Among the 125 included patients, 85% (106) showed a favourable response to beta-lactam. In multivariate logistic regression, we found procalcitonin (PCT) the only independent predictor of apyrexia (p = 0.008). The adjusted odds ratio for the decadic logarithm of PCT was 4.3 (95% CI 1.5-12.7). At ≥ 3 ng/mL, PCT had 55.7% sensitivity (45.7-65.3), 78.9% specificity (54.4-93.9), 93.7% positive predictive value (84.5-98.2), 24.2% negative predictive value (14.2-36.7), 2.64 positive likelihood ratio (1.09-6.42) and 0.56 negative likelihood ratio (0.41-0.77). In the 4 children with a PCT level ≥ 3 ng/mL and who showed no response to beta-lactam treatment, secondary pleural effusion had developed in 3, and viral co-infection was documented in 1. CONCLUSIONS: PCT is the best independent biologic predictor of favourable response to beta-lactam therapy in children hospitalized for CAP. Thus, a high PCT level is highly suggestive of pneumococcal aetiology. However, a 3-ng/mL cut-off does not seem compatible with daily medical practice, and additional research is needed to further define the role of PCT in managing CAP in children.

Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule.

PURPOSE: Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS: We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS: A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS: A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.

Molecular and clinical characterization of rotavirus from diarrheal infants admitted to pediatric emergency units in france.

BACKGROUND: rotaviruses are the major cause of acute gastroenteritis in young children worldwide, and require careful surveillance, especially in the context of vaccination programs. Prospective surveillance is required to monitor and characterize rotavirus infections, including viral and clinical data, and to detect the emergence of potentially epidemic strains. METHODS: between 2006 and 2009, stool samples and clinical records were collected from 2044 children with acute diarrhea admitted to the pediatric emergency units of 13 French university hospitals. Rotaviruses were detected in stools, then genotyped by reverse transcription-polymerase chain reaction with regard to their outer capsid proteins VP4 and VP7. RESULTS: the genotyping of 1947 rotaviruses showed that G1 (61.7%) and G9 (27.4%) strains were predominant and stable, followed by G2 (6.5%), G3 (4.0%), and G4 (2.5%) strains. Most strains were associated with P[8] (92.9%). Overall, 31 uncommon strains and possible zoonotic reassortants were detected including G12 and G8 strains, some being closely related to bovine strains. No difference in clinical presentation and severity was found among genotypes. CONCLUSIONS: the relative stability of rotavirus genotypes currently cocirculating in France may ensure vaccine effectiveness in the short and medium term. However, the likely emergence of G12 and G8 strains should be monitored during ongoing and future vaccination programs, especially as all genotypes can cause severe infections. Special attention should be paid to the emergence of new rotavirus reassortants not included in current rotavirus vaccines.

Prediction of high-grade vesicoureteral reflux after pediatric urinary tract infection: external validation study of procalcitonin-based decision rule.

BACKGROUND: Predicting vesico-ureteral reflux (VUR) ≥3 at the time of the first urinary tract infection (UTI) would make it possible to restrict cystography to high-risk children. We previously derived the following clinical decision rule for that purpose: cystography should be performed in cases with ureteral dilation and a serum procalcitonin level ≥0.17 ng/mL, or without ureteral dilatation when the serum procalcitonin level ≥0.63 ng/mL. The rule yielded a 86% sensitivity with a 46% specificity. We aimed to test its reproducibility. STUDY DESIGN: A secondary analysis of prospective series of children with a first UTI. The rule was applied, and predictive ability was calculated. RESULTS: The study included 413 patients (157 boys, VUR ≥3 in 11%) from eight centers in five countries. The rule offered a 46% specificity (95% CI, 41-52), not different from the one in the derivation study. However, the sensitivity significantly decreased to 64% (95%CI, 50-76), leading to a difference of 20% (95%CI, 17-36). In all, 16 (34%) patients among the 47 with VUR ≥3 were misdiagnosed by the rule. This lack of reproducibility might result primarily from a difference between derivation and validation populations regarding inflammatory parameters (CRP, PCT); the validation set samples may have been collected earlier than for the derivation one. CONCLUSIONS: The rule built to predict VUR ≥3 had a stable specificity (ie. 46%), but a decreased sensitivity (ie. 64%) because of the time variability of PCT measurement. Some refinement may be warranted.

[Epidemiology of parasitic diseases, hypereosinophilia, IgE from tropical and European parasitological origins]. / Epidémiologie des parasitoses, hyperéosinophilies sanguines et IgE d'origines parasitaires en milieux tempérés et tropicaux.

Etiologic investigations of hypereosinophilia, often accompanied by IgE elevation, depends on the patient's geographic origin and travel history. In France, helminth diseases are the only parasitoses associated with hypereosinophilia. Some, such as oxyurosis in children, are frequent but generally mild. More severe but less frequent infections include distomatoses, trichinellosis, taeniasis, echinococcosis and visceral larva migrans. Among subjects originating from or having travelled to tropical areas with poor hygiene, eosinophilia may be due to early intense polyparasitism and has little etiologic value. In Gabon, a warm, humid country in equatorial Africa, schoolchildren harbor an average of three different parasites capable of inducing hypereosinophilia or serum IgE elevation. These children's eosinophil counts start to rise at very young age, after weaning and contact with soil, and continue to increase rapidly until adulthood. Average values across all age groups are 1580 eosinophils/mm3 and 3300 kU IgE/L. Direct diagnosis of chronic parasitic infections is often possible in this setting, and specific treatments can be prescribed. In contrast, hypereosinophilia has less etiologic significance in patients originating from or having travelled to the tropics and who present to European parasitology units. Direct examination is rarely positive, and the etiologic diagnosis will thus be guided by epidemiologic, clinical and serologic findings. These findings are sometimes sufficient to initiate probabilistic treatment with albendazole, ivermectin and praziquentel.

Distinguishing between bacterial and aseptic meningitis in children: European comparison of two clinical decision rules.

BACKGROUND: Clinical decision rules (CDRs) could be helpful to safely distinguish between bacterial and aseptic meningitis (AM). OBJECTIVE: To compare the performance of two of these CDRs for children: the Bacterial Meningitis Score (BMS) and the Meningitest. DESIGN: Secondary analysis of retrospective multicentre hospital-based cohort study. SETTING: Six paediatric emergency or intensive care units of tertiary care centres in five European countries. PATIENTS: Consecutive children aged 29 days to 18 years presenting with acute meningitis and procalcitonin (PCT) measurement. Intervention None. MAIN OUTCOME MEASURES: The sensitivity and specificity of the BMS (start antibiotics in case of seizure, positive cerebrospinal fluid (CSF) Gram staining, blood neutrophil count ≥10 ×10(9)/l, CSF protein level ≥80 mg/dl or CSF neutrophil count ≥1000 ×10(6)/l) and the Meningitest (start antibiotics in case of seizure, purpura, toxic appearance, PCT level ≥0.5 ng/ml, positive CSF Gram staining or CSF protein level ≥50 mg/dl) were compared using a McNemar test. RESULTS: 198 patients (mean age 4.8 years) from six centres in five European countries were included; 96 had bacterial meningitis. The BMS and Meningitest both showed 100% sensitivity (95% CI 96% to 100%). The BMS had a significantly higher specificity (52%, 95% CI 42% to 62% vs 36%, 95% CI 27% to 46%; p<10(-)8). CONCLUSION: The Meningitest and the BMS were both 100% sensitive. This result provides level II evidence for the sensitivity of both rules, which can be used cautiously. However, use of the BMS could safely avoid significantly more unnecessary antibiotic treatments for children with AM than can the Meningitest in this population.

Underestimation of influenza viral infection in childhood asthma exacerbations.

Bocavirus was found in 11.6% of hospitalized children and 13% of ambulatory patients with exacerbations of asthma, and respiratory syncytial virus was found in 13.5% and 17.7%, respectively. In addition, influenza A virus was detected in 2.6% of hospitalized children and 14.1% (P<.001) of ambulatory-treated patients. Thus, the influenza burden in asthma may be underestimated.

Procalcitonin is useful in identifying bacteraemia among children with pneumonia.

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was > or =2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT > or =2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.

Hospitalization for severe bacterial infections in children after exposure to NSAIDs: a prospective adverse drug reaction reporting study.

BACKGROUND: NSAIDs are widely used to treat fever and pain in children, but their possible role in the progression of some bacterial infections is controversial. OBJECTIVE: This study was performed to analyse reported cases of severe bacterial infection associated with NSAID exposure in children admitted for this reason to a general paediatric department. METHODS: This study was based on the reporting system of hospital admissions for severe bacterial infections in children after NSAID exposure, and followed the recommendations of the European Guidelines of Pharmacovigilance for medicines used in a paediatric population. Data were prospectively collected and reported by active daily surveillance in the department from November 2002 to November 2005. RESULTS: Thirty-two cases of severe bacterial infections (cellulitis, soft tissue abscesses, parapneumonic empyema, necrotizing pneumonia, adenophlegmon [fever and a tender, warm and easily compressible neck mass] and lateral or retropharyngeal abscesses) were identified in children who had received NSAIDs, principally ibuprofen, in an exposure window of 15 days before the beginning of the signs of infection. Staphylococcus aureus, group A streptococci and Streptococcus pneumoniae were identified. Seven (22%) children required surgical treatment, and four (13%) were hospitalized in an intensive care unit. CONCLUSIONS: The frequency of hospitalization for severe bacterial infection as a possible adverse effect of NSAID use was 0.6% (95% CI 0.4, 0.9) of all admissions during the study period. The frequency of severe bacterial infections after exposure to NSAIDs was elevated (one case per month) in the department studied. Further work is necessary to confirm these findings, given the potential for recruitment and protopathic biases in our study.

Impressive renal damage after acute pyelonephritis in a child.

Urinary tract infection (UTI) is one of the most common bacterial infections in children, and its role in the pathogenesis of scarred kidney is debated. We report on a 7-year-old child who presented with severe UTI. The early (day 4) renal computed tomography (CT) scan showed normal-sized kidneys (110 mm on the left, 105 mm on the right), whereas the control CT scan and dimercaptosuccinic acid (DMSA) scan, performed 1 and 2 months later, respectively, showed a small scarred right kidney (60 mm) with a 12% residual function. An intermittent right vesicoureteral reflux (VUR) was diagnosed by direct isotopic cystography and then treated by Cohen vesicoureteral reimplantation. The patient remained free of infectious recurrence, hypertension, or renal function decrease. This report demonstrates that one episode of acute pyelonephritis can lead to severe renal scarring. Whereas antenatal lesions are thought to have a stronger role in the causal pathway for reflux nephropathy than is UTI in addition to VUR, this observation reminds us that UTI can truly play an important role in damaging kidneys.