[VACCINATION AGAINST HEPATITIS B: WHAT'S UP?]. / Vaccination contre l'hépatite B: où en est-on?

The vaccination against hepatitis B has been shown to be effective and safe. 15 years after a scare suggesting a relationship between the HBV vaccine and the development of demyelinating diseases, studies have not confirmed this suspected link. The french HBV vaccination strategy in effect since the 1990's (vaccination of newborns, a catch-up campaign in children and adolescents and vaccination of high risk populations) is well adapted to the existing epidemiological situation. Vaccination coverage in newborns has increased significantly since 2008. Catch-up of children and adolescents is insufficient. The very limited data on vaccination coverage in populations at high risk of HBV suggests that coverage is largely insufficient. The mandatory vaccination of healthcare workers since 1991 has nearly completely eradicated worksite HBV. Nevertheless: persistent circulation of the virus and the risk of healthcare worker-patient transmission, and insufficient coverage justifies continued vaccination and mandatory proof of immunization. Specific vaccination protocols are needed because certain co-morbidities can reduce the probability and strength of the response to the vaccine. The physician should evaluate this risk case-by-case and adapt the vaccination protocol accordingly. Between 2007 and 2012, more than 200 patients have undergone liver transplantation associated with HBV (cirrhosis, hepatocellular carcinoma, fulminant hepatitis). Many of these transplantations could have been avoided thanks to vaccination, and these grafts could have been proposed to other patients.

[The immunization schedule]. / Le calendrier vaccinal.

Vaccination offers individual and collective protection against a number of infectious diseases. The immunisation schedule is updated every year and published by the French Ministry for Health. In 2013, the schedule was simplified in order to improve the vaccination coverage of the French population. Specific recommendations are made for health professionals.

Measles elimination efforts and 2008-2011 outbreak, France.

Although few measles cases were reported in France during 2006 and 2007, suggesting the country might have been close to eliminating the disease, a dramatic outbreak of >20,000 cases occurred during 2008-2011. Adolescents and young adults accounted for more than half of cases; median patient age increased from 12 to 16 years during the outbreak. The highest incidence rate was observed in children <1 year of age, reaching 135 cases/100,000 infants during the last epidemic wave. Almost 5,000 patients were hospitalized, including 1,023 for severe pneumonia and 27 for encephalitis/myelitis; 10 patients died. More than 80% of the cases during this period occurred in unvaccinated persons, reflecting heterogeneous vaccination coverage, where pockets of susceptible persons still remain. Although vaccine coverage among children improved, convincing susceptible young adults to get vaccinated remains a critical issue if the target to eliminate the disease by 2015 is to be met.

Adherence to antiretroviral therapy and acceptability of planned treatment interruptions in HIV-infected children.

There have been no paediatric randomised trials describing the effect of planned treatment interruptions (PTIs) of antiretroviral therapy (ART) on adherence, or evaluating acceptability of such a strategy. In PENTA 11, HIV-infected children were randomised to CD4-guided PTIs (n = 53) or continuous therapy (CT, n = 56). Carers, and children if appropriate, completed questionnaires on adherence to ART and acceptability of PTIs. There was no difference in reported adherence on ART between CT and PTI groups; non-adherence (reporting missed doses over the last 3 days or marking <100 % adherence since the last clinical visit on a visual analogue scale) was 18 % (20/111) and 14 % (12/83) on carer questionnaires in the CT and PTI groups respectively (odds ratios, OR (95 % CI) = 1.04 (0.20, 5.41), χ(2) (1) = 0.003, p = 0.96). Carers in Europe/USA reported non-adherence more often (31/121, 26 %) than in Thailand (1/73, 1 %; OR (95 % CI) = 54.65 (3.68, 810.55), χ(2) (1) = 8.45, p = 0.004). The majority of families indicated they were happy to have further PTIs (carer: 23/36, 64 %; children: 8/13, 62 %), however many reported more clinic visits during PTI were a problem (carer: 15/36, 42 %; children: 6/12, 50 %).

Long-term critical issues in pediatric renal transplant recipients: a single-center experience.

Data on long-term outcomes after pediatric renal transplantation (Tx) are still limited. We report on a 20-year single-center experience. Medical charts of all consecutive pediatric Tx performed between 1987 and 2007 were reviewed. Data of patients who had been transferred to adult units were extracted from the French databases of renal replacement therapies. Outcomes were assessed using Kaplan-Meier and Cox models. Two hundred forty Tx were performed in 219 children (24.1% pre-emptive and 17.5% living related donor Tx). Median age at Tx was 11.1 years and median follow-up was 10.4 years. Patient survival was 94%, 92%, and 91% at 5, 10, and 15 years post-Tx, respectively. Overall, transplant survival was 92%, 82%, 72%, and 59% at 1, 5, 10, and 15 years post-Tx, respectively. The expected death-censored graft half-life was 20 years. Sixteen patients developed malignancies during follow-up. Median height at 18 years of age was 166 cm in boys and 152 cm in girls with 68% of patients being in the normal range. The proportion of socially disadvantaged young people was higher than in general population. Excellent long-term outcomes can be achieved in pediatric renal Tx, but specific problems such as malignancies, growth, and social outcome remain challenging.

How French physicians manage with a future change in the primary vaccination of infants against diphtheria, tetanus, pertussis and poliomyelitis? A qualitative study with focus groups.

BACKGROUND: As in other European countries, the French vaccination schedule changes according to epidemiological and socio-economic situations. Further changes are planned for 2013, including the withdrawal of one dose for primary vaccination against diphtheria, tetanus, polio, pertussis and Haemophilus influenzae. A partnership between the French Technical Vaccination Committee and the French Institute for Health and Medical Research designed a study to assess primary care physicians' agreement about this modification. METHODS: Qualitative study with focus groups and semi-structured interviews in France. Four focus groups were conducted with physicians, supplemented by four individual interviews. RESULTS: The physicians of the survey had accepted the suggested vaccination schedule well. A few concerns had been underlined: fear of less follow-up care for infants resulting from the removal of one visit driven by the primary vaccination; fear of loss of vaccine efficacy; suspicion of the existence of financial arguments at the origin of this change; and adjustment to current vaccination schedule. Several suggestions were made: providing strong support from health authorities; developing stable and simple recommendations; providing effective tools for monitoring patient's vaccination status. CONCLUSIONS: Physicians' opinions suggested a good acceptance of a possible change about primary vaccination against diphtheria, tetanus, polio, pertussis and Haemophilus influenzae. Physicians' suggestions resulted from this qualitative study on a new vaccination schedule. It showed how that their involvement was feasible for preparing the implementation of a new vaccination schedule.

[Age for HPV vaccination: recommandations from the French high council of public health]. / Vaccins contre les papillomavirus humains (HPV) - Dernières recommandations du Haut conseil de la santé publique, et premiers résultats cliniques et virologiques.

The French high council of public health has recently amended age for HPV vaccination. The paper will describe reasons that have contributed to the development of these new guidelines. Parental and adolescent acceptance of HPV vaccination is reported as well as potential barriers among medical practices. First results of immunogenicity of vaccines using alternative dosing schedules are presented. Finally, preliminary data on clinical efficacy of the quadrivalent vaccine on genital warts and cervical precancerous lesions are presented. A decrease in the prevalence of infection with genotypes included in the vaccine has now been reported in several studies. This decrease may be partly attributable to herd immunity.

Macrolide-resistant Bordetella pertussis infection in newborn girl, France.

A macrolide antimicrobial drug was administered to a newborn with cough. On day 23 of hospitalization, macrolide-resistant Bordetella pertussis was isolated from nasopharyngeal aspirates. DNA sequencing and PCR-restriction fragment length polymorphism showed a 2047 A-to-G mutation in the 3 copies of the 23S rRNA gene. Monitoring for macrolide resistance is essential in infants <6 months of age.

Clinical, functional and genetic analysis of twenty-four patients with chronic granulomatous disease - identification of eight novel mutations in CYBB and NCF2 genes.

Chronic granulomatous disease is an inherited disorder in which phagocytes lack a functional NADPH oxidase and cannot produce superoxide anions. The most common form is caused by mutations in CYBB encoding gp91phox. We investigated 24 CGD patients and their families. Twenty-one mutations in CYBB were classified as X91(0), X91(+) or X91(-) variants according to cytochrome b (558) expression. Point mutations in encoding regions represented 50 % of the mutations found in CYBB, splice site mutations 27 %, deletions and insertions 23 %. Eight mutations in CYBB were novel leading to X91(0)CGD cases. Two of these were point mutations: c493G>T and a double mutation c625C>G in exon 6 and c1510C>T in exon 12 leading to a premature stop codon at Gly165 in gp91phox and missense mutations His209Arg/Thr503Ile respectively. Two novel splice mutations in 5'intronic regions of introns 1 and 6 were found. A novel deletion/insertion c1024_1026delCTG/insT results in a frameshift introducing a stop codon at position 346 in gp91phox. The last novel mutation was the insertion of a T at c1373 leading to a frameshift and a premature stop codon at position 484 in gp91phox. For the first time the precise size of two large mutations in CYBB was determined by array-comparative genomic hybridization and carriers' status were evaluated by multiplex ligation-dependent probe amplification assay. No clear correlation between clinical severity and CYBB mutations could be established. Of three mutations in CYBA, NCF1 and NCF2 leading to rare autosomal recessive CGD, one nonsense mutation c29G>A in exon 1 of NCF2 was new.

[Social representations of vaccination among patients and general practitioners: a study based on hierarchized evocation]. / Représentations sociales de la vaccination chez les patients et les médecins généralistes : une étude basée sur l'évocation hiérarchisée.

In France, there is a discrepancy between perceptions and practices related to vaccination, the causes of which are poorly understood. The purpose of this study was to examine and compare patients' and physicians' social representations of vaccination. A qualitative study based on hierarchized evocation was conducted on a sample of 30 patients and 30 general practitioners. The participants were asked to write down seven words or word groups (word associations) induced by the concept of "vaccination" and to rank them in order of importance. The associations were grouped by theme and sub-theme. Their frequency, connotations and importance were compared between the two groups. The results show that, overall, the physicians had a positive view of vaccination, while the patients had a more neutral view (polarity index: + 0.38 vs + 0.07, p < 0.01). Among both patients and general practitioners, vaccination tends to be perceived as a form of medical care mainly targeting children and aimed at prevention, and its effectiveness is considered to be implicit. However, the patients appeared to be more concerned about the potential side effects of certain vaccinations, while the GPs emphasized the harmlessness of vaccination. The participating GPs also tended to take a collective view of vaccination, while some patients criticized the lack of targeted vaccinations. Better communication on these key aspects of representations may help to increase confidence in vaccination and to close the gap between perception and practice.

Agreement between a regional pharmacovigilance centre and an adjudication committee regarding adverse drug reactions on a cohort of hospitalised children.

BACKGROUND AND PURPOSE: The EREMI project was set up to collect data on adverse drug reactions (ADRs) occurring due to off-label and/or unlicensed drugs prescribed to hospitalised children in France. These events were evaluated by a regional pharmacovigilance centre (RPC) and an adjudication committee (AC). The aim of this study was to assess the agreement between these two different entities on their evaluation of ADRs. EXPERIMENTAL APPROACH: The RPC first validated the ADRs and assessed their causality using the Naranjo scale. The AC assessed then ADRs using all available information, including the RPC evaluation. The agreement on severity and nature of ADRs, role of treatment (suspect or concomitant) and drug causality was calculated using Cohen's nonparametric kappa coefficient (k). KEY RESULTS: Three hundred and eighty-six events were reported in 219 children. The RPC excluded 65 events and validated 321 ADRs. Agreement was very good on nature of ADRs (k=0.85) and role of treatment (k=0.81), moderate on severity of ADRs (k=0.60) and very poor on drug causality (k=0.05). CONCLUSION AND IMPLICATIONS: Agreement between the RPC and the AC was not constant throughout this evaluation. They troubled to agree on severe ADRs and on drug causality.

Toxin profiling of Staphylococcus aureus strains involved in varicella superinfection.

The most common complications of varicella are bacterial skin and soft tissue infections, generally due to Staphylococcus aureus and group A beta-hemolytic streptococci. The aim of this study was to characterize the toxin and antibiotic resistance profiles of S. aureus isolates involved in varicella complications. Between 2002 and 2007, the French Reference Centre for Staphylococci collected 58 S. aureus isolates involved in varicella superinfection. All the isolates were characterized by screening for 12 toxin genes, agr typing, and mecA gene detection; some isolates were also studied by spa typing, multilocus sequence typing (MLST), and resistance profiling. A major toxin gene was detected in 53% (31/58) of the isolates (genes for exfoliative toxins A and B, 17.2%; Panton-Valentine leukocidin gene, 8.6%; toxic shock syndrome toxin 1 gene, 27.6%). Most clinical manifestations were directly compatible with the classical activity of these toxins. Nineteen isolates (33%) were resistant to methicillin, and 12 of these isolates belonged to an emerging agr-2, ST5 clone that harbors the toxic shock syndrome toxin 1 gene. These data should be considered in the management and treatment of patients with varicella complicated by S. aureus superinfection. Antibiotics that decrease toxin production, such as clindamycin, may provide benefit, and their efficacy against bacterial superinfections in children with varicella should be studied.

Prompt and successful toxin-targeting treatment of three patients with necrotizing pneumonia due to Staphylococcus aureus strains carrying the Panton-Valentine leukocidin genes.

Three patients with extensive necrotizing pneumonia due to Panton-Valentine leukocidin-positive Staphylococcus aureus strains and with aggravating factors (leukopenia count of less than 3x10(9)/liter in all three cases and hemoptysis in two cases) were successfully treated with toxin-suppressing agents introduced rapidly after hospital admission.

Hospitalization of newborns and young infants for chickenpox in France.

Chickenpox is often considered more severe during the first year of life, but its course is usually mild during the first 3 months of life, presumably owing to the persistence of maternal antibodies. Hospitalization and intravenous acyclovir therapy are generally restricted to severe cases but also systematically recommended in newborns in France, irrespective of the clinical severity of the infection. This recommendation was launched in 1998 when Varicella zoster virus (VZV)-specific immunoglobulins were not available in the country and has remained unchanged since. The aim of this prospective observational study was to describe complications of varicella infection in a population of 745 children hospitalized for varicella before 1 year of age, with a specific focus on newborns. Complications occurred in 65% of cases. They were very rare before the age of 1 month (10%) but their incidence then increased progressively with age and probably the disappearance of maternal antibodies: 42% (1-2 months), 66% (3-5 months), 70% (6-8 months), and 79% (9-12 months). Conclusion Chickenpox is usually mild in newborns because most of them are protected by VZV maternal antibodies. Unless the absence of maternal VZV immunity is demonstrated, newborns with mild chickenpox should not require antiviral therapy.

[Resistance to immunization]. / Les résistances à la vaccination.

Despite a well documented efficacy and a generally good adhesion of a large majority of the lay population and health care professionals as well, immunization is still the object of controversies. It affects several vaccines against hepatitis B, influenza, BCG, pertussis and measles. In most cases, polemics on vaccination result from a temporal association between a vaccination and the revelation of a serious disease, when the immunization is performed at the peak of incidence of the disease. Controversies can also be initiated by scientific publications, even though these are often biased, by a misinterpretation or the absence of official positions from the health care authorities, or by justice decisions, whose criteria differ from the scientists' ones and are therefore difficult to understand for the lay public. Furthermore, the scientific demonstration of the exclusion of a risk is difficult to obtain. In the past, it appeared to be very difficult to stop controversies. Improving the communication is the main issue, towards lay public as well as health care professionals. This implies to learn how to better use the media, to motivate and educate professionals who administer vaccine, and anticipate the eventuality of a temporal relationship between vaccination and occurrence of a serious disease by an improved management of the pharmacovigilance system.

[Measles vaccination]. / Vaccination contre la rougeole.

France is facing since 2008 a re-emerging measles outbreak affecting a high proportion of adults currently not or not correctly vaccinated. The non application since 30 years of the immunization program on measles mumps and rubella is the cause of this situation, despite the efficacy and the good tolerance of this vaccine has been demonstrated. The present epidemic is expected to go on, as long as the millions of measles susceptible people have not been either affected or vaccinated. A 95% protection rate is needed to interrupt the circulation of the virus. So, the objective of the French Plan for elimination of measles and congenital rubella is to reach at least a 95% vaccination coverage for the first dose and 80% for the second dose. The immunization recommendations should be strictly respected: first dose of MMR vaccine at 12 months and second dose within the second year of life. In this context, catch up immunization of children, adolescents and young adults (up to 30 year) not or not correctly vaccinated is particularly important, as well as the post exposure prophylactic measures, including vaccination.

Long-lasting extracorporeal albumin dialysis in a child with end-stage renal disease and severe cholestasis.

We report a case of long-lasting MARS therapy as a bridge to liver-kidney transplantation. A 26-month-old girl with congenital tubulointerstitial nephritis and severe liver fibrosis was placed on MARS for an acute-on-chronic liver failure due to sepsis. She underwent two sessions with good tolerance and recovered her previous neurological status. On the basis of pruritus, sleep, and vomiting improvement, repeated MARS sessions were performed to bridge her to combined liver-kidney transplantation. During eight months, 40 sessions were performed with the MARSmini kit and the MARS monitor (Gambro, Lyon, France). The treatment significantly decreased mean pruritus score from 2.2 +/- 0.9 to 0.8 +/- 0.6 night-time awakening and vomiting episodes. Body weight, height, and HC were -3.2, -3.5 and -2.2 SDS before and -1.7, -4.2, -2.0 SDS after eight months on MARS therapy, respectively. The arm circumference/HC ratio increased from 0.28 to 0.31. Mean total bilirubin serum levels were 303 +/- 72 micromol/L before and 214 +/- 42 micromol/L after MARS cycles. Long-lasting MARS dialysis is feasible in children, decreases adverse effects of severe chronic cholestasis, and may help to preserve nutritional status prior to combined liver-kidney transplantation.

Management of severely injured children in road accidents in France: impact of the acute care organization on the outcome.

OBJECTIVE: To examine the impact of acute care management on outcome in children severely injured in road accidents. DESIGN AND SETTING: Prospective follow-up study conducted in 12 French pediatric intensive care units over a 24-month period. PATIENTS: Excluding those in refractory shock or in brain death at admission, a total of 125 children aged <17 years admitted to the pediatric intensive care unit with severe trauma (Injury Severity Score > or =16) were included. RESULTS: Intracranial pressure (ICP) monitoring and admission into a trauma resuscitation room (TRR) were used as proxy markers for the center management aggressiveness. Centers which admitted to TRR and monitored ICP when indicated in >75% of cases were called aggressive centers. Children with an ICP monitoring indication admitted to a TRR and monitored, as well as those without an indication treated in a TRR, were judged appropriately managed. A poor outcome at pediatric intensive care unit discharge was defined as a difference between the baseline and discharge pediatric overall performance category above 3, or a hospital death. Children with traumatic brain injury appropriately managed in a less-aggressive center were more likely to have a poor outcome than those appropriately managed in an aggressive center (odds ratio 7.56, 95% confidence interval 1.5-38.4), after adjustment for severity, age, and type of road user. CONCLUSIONS: The management in a more aggressive center for children admitted to TRR and monitored for ICP, when indicated, is associated with a better outcome. This could be explained by a more extensive experience in trauma management.