Overview of meningococcal epidemiology and national immunization programs in children and adolescents in 8 Western European countries.

Background: In Europe, meningococcal (Men) vaccines are available against 5 of the 6 serogroups responsible of nearly all cases of invasive meningococcal disease (IMD). Meningococcal vaccination has been introduced in the national immunization programs (NIPs) for children and adolescents of numerous European countries, but with no consistent strategy across countries. Objectives: To describe IMD epidemiology, NIPs, and vaccination coverage rates (VCRs) in children and adolescents in 8 Western European countries. Methods: Epidemiological data (from 1999 to 2019), NIPs regarding meningococcal vaccination status, and VCRs were collected from the European Centre for Disease Prevention and Control (ECDC) and/or national websites. Results: MenB was the most common serogroup. In Belgium, Spain, France, the Netherlands, the United Kingdom (UK), and Portugal, incidence was greater for MenW than MenC. In 2019, MenB risk was covered in 2 countries (Italy, UK). MenC risk was covered in all countries, via MenC only (countries: N = 3), MenACWY only (N = 2), or MenC (infants/children) and MenACWY (adolescents) (N = 3) vaccination. VCRs were higher in children than adolescents. Conclusion: Our study confirmed the diversity of NIPs, including in neighboring European countries with similar factors like economic resources and epidemiological risk, thus indicating that other factors underlie NIPs. Convergence toward a more common immunization program including MenACWY and MenB vaccination would promote equity and safe travel regarding infectious diseases for young people, and possibly improve the understanding of vaccination by patients and healthcare professionals.

Different Clinical Presentations and Outcomes of Disseminated Varicella in Children With Primary and Acquired Immunodeficiencies.

Primary infection with varicella-zoster virus (VZV) causes chickenpox, a benign and self-limited disease in healthy children. In patients with primary or acquired immunodeficiencies, primary infection can be life-threatening, due to rapid dissemination of the virus to various organs [lung, gastrointestinal tract, liver, eye, central nervous system (CNS)]. We retrospectively described and compared the clinical presentations and outcomes of disseminated varicella infection (DV) in patients with acquired (AID) (n= 7) and primary (PID) (n= 12) immunodeficiencies. Patients with AID were on immunosuppression (mostly steroids) for nephrotic syndrome, solid organ transplantation or the treatment of hemopathies, whereas those with PID had combined immunodeficiency (CID) or severe CID (SCID). The course of the disease was severe and fulminant in patients with AID, with multiple organ failure, no rash or a delayed rash, whereas patients with CID and SICD presented typical signs of chickenpox, including a rash, with dissemination to other organs, including the lungs and CNS. In the PID group, antiviral treatment was prolonged until immune reconstitution after bone marrow transplantation, which was performed in 10/12 patients. Four patients died, and three experienced neurological sequelae. SCID patients had the worst outcome. Our findings highlight substantial differences in the clinical presentation and course of DV between children with AID and PID, suggesting differences in pathophysiology. Prevention, early diagnosis and treatment are required to improve outcome.

Recent changes of invasive meningococcal disease in France: arguments to revise the vaccination strategy in view of those of other countries.

In France, the incidence of invasive meningococcal disease (IMD) is around 1/100,000, with the following trends over the 2011-2018 period: a leading role of group B in subjects <15 years, a decrease of group C among <1 year since 2017, an increase of group W in all age groups including subjects <1 year since 2014 and a positive correlation between group Y and age group. In Europe, vaccination progressed with conjugate ACWY vaccines and proteins-based B vaccines. Their benefit-risk-cost balance is however not so obvious for area at low incidence (<2/100,000), explaining tremendous variations between countries, from no recommendation to recommend all available vaccines. In France, the calendar still includes only C with a good adhesion in infants but a fiasco of the catch-up campaign in adolescents and young adults. In Europe, it is time to consider not only national epidemiology but also trends in the neighborhood. The increase of group W cases encourages switching C to ACWY vaccine both in infants and adolescents. It is also time to protect infants with B vaccine. Large pedagogy on the disease is required to increase the adhesion to the vaccination and to recognize and treat earlier the residual cases.

Lifetime cost of meningococcal disease in France: Scenarios of severe meningitis and septicemia with purpura fulminans.

Invasive meningococcal disease (IMD) is life-threatening and can result in severe sequelae. In France, no data have been published on the costs of severe IMD cases. Two realistic scenarios were developed with national experts (clinicians and social workers): a 6-year-old child with purpura fulminans with amputation of both legs below the knee (case A) and a 3-year-old with meningitis and severe neurological sequelae (case B). Additional scenarios included other typical sequelae of IMD such as chronic kidney disease (CKD), profound deafness and epilepsy. Data on healthcare, disability, educational and other resource use were obtained from experts and families of patients with similar sequelae. Unit costs (2013) were mainly obtained from the literature and the National Health Insurance (NHI). Time horizon was based on life expectancies of patients (77 and 55 years, respectively). A 4% discount rate decreasing to 2% after 30 years was applied. Costs are presented from the perspective of the NHI, publicly funded organizations and patients' families or their private health insurances. purpura fulminans with amputations is associated with a lifelong discounted cost of €768,875. Adding CKD doubles the amount (€1,480,545). Meningitis with severe neuro-cognitive sequelae results in a lifelong discounted cost of €1,924,475. Adding profound deafness and epilepsy slightly increases the total cost (€2,267,251). The first year is the most expensive in both scenarios (€166,890 and €160,647 respectively). The main cost drivers for each scenario are prostheses and child/adult stays in healthcare facilities, respectively. Overall, patients' families or his private insurance had to pay around 13% of total cost (101,833€ and 258,817€, respectively). This study fills a gap in the body of knowledge on IMD sequelae care and lifetime costs in France. The potentially high economic burden of IMD, in addition to its physical, psychological and social burden, reinforces the need for prevention.

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.

[Aregenerative anemia and erythrocytes hemighosts: a case report]. / Anémie non régénérative et hématies fantômes : à propos d'un cas.

An 11 year old African boy without previous history was hospitalised for fever and a severe anaemia (haemoglobin = 55 g/L) with low reticulocyte count. Blood smear showed more than 35% of ghost red blood cells which allows the diagnosis of G6PD deficiency (< 1% of normal level). Anaemia was demonstrated as haemolytic and was associated with a drepanocytosis trait. Aspect of red blood cells on blood smear remains important for the diagnosis of congenital or acquired red blood cell diseases, even abnormalities are often of low specificity.

Interferon-gamma release assay performance for diagnosing tuberculosis disease in 0- to 5-year-old children.

QuantiFERON-TB Gold In-Tube performance was evaluated in 19 French immunocompetent children (0.29-5.36 years; median: 1.52) with active tuberculosis. The rate of indeterminates results was 0/19 and the rates of positivity were 6/10 and 9/9 in <2 and 2- to 5-year-old children, respectively. QuantiFERON-TB Gold In-Tube in association with tuberculin skin test could improve diagnosis of tuberculosis even in young children.

Post-mortem MRI reveals CPT2 deficiency after sudden infant death.

Inherited metabolic disorders are the cause of a small but significant number of sudden infant deaths in infants. We report on a boy who suddenly died at 10 months of age during an acute illness. Parents declined autopsy; nevertheless, they accepted a whole body MRI, which revealed hepatomegaly with steatosis. Acylcarnitine profile of a blood sample from neonatal Guthrie screening led to the diagnosis of type 2 carnitine palmitoyltransferase deficiency. To conclude, whole body MRI is useful in the investigation of some inherited metabolic causes of sudden infant death, which might prevent future deaths in the family. It is a good alternative when autopsy is refused.

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.

[Preventive vaccination strategy during the perinatal period]. / Vaccination autour de la naissance.

Preventive vaccination strategy around the birth is a global approach requiring the coordination of several actors. To be efficacious, general practitioners are in the front line to provide preventive care and health education. The perinatal period represents a privileged situation from listening to this approach of vaccine prevention. The raising awareness around the birth contains several additional steps to bring to the future mother and child the best protection against infectious diseases with vaccine prevention. By being vaccinated, parents and other family members indirectly provide protection to very young infants until they are old enough to be vaccinated and so directly protected themselves. Numerous opportunities exist to make sensitive the parents in this preventive way, for them and their child, whether it is from the adolescence in the adulthood above all parental project, on the occasion of a pregnancy, at birth, during the stay in maternity hospital, or along the first weeks of the postpartum. The general practitioner is the key actor to coordinate this global approach in perinatal health around the mother, his child and his family. The arrival of the newborn will be the opportunity to update vaccinations of the whole family particularly according chicken pox, measles, rubella, whooping cough and flu vaccines.

[Immunization against hepatitis B virus in France]. / Vaccination contre le virus de l'hépatite B en France.

Vaccine coverage against hepatitis B has really increased in French infants since march 2008, date of reimbursement of hexavalent vaccine. At the end of year 2009, 76% of infants have received at least one dosage of hepatitis B vaccine before the age of 6 months. On the contrary until the beginning of year 2008 only 30 to 40% have been vaccinated. Altogether with the reimbursement we have to take into account, knowledge of French epidemiological data, 280000 chronic carrier of hepatitis, whom half of them does not know her state and 1 300 deaths each year, and a change in the opinion by physicians and families. If this result can be considered as good, vaccine coverage of adolescents is not good, about 50% and need to be increased. All non vaccinated adolescent would have the opportunity to be vaccinated. Adolescent can be vaccinated between 11 and 15 years old with a 3 dosages schedule (0, 1, 6 months) or a 2 dosages schedule (0,6 months) with vaccines which contain 20 microgrammes Ag HBs.

[Immunization against pneumococci with conjugate vaccine]. / Vaccination contre le pneumocoque par le vaccin conjugué.

Three years after the generalization of the recommendation of Pneumococcal conjugate vaccine for all infants under two years of age, the rate of vaccine coverage is satisfactory for the primovaccination (above 85%) with a 2 + 1 schedule. Vaccine coverage is too low for the booster which is given too late (at 14,5 months of age) and not at of 12 months. This conjugate vaccine has a direct effect, due to the vaccine in the target population and indirect effect due to the action on the strains carriage which decreases the broadcasting of the vaccine serotype strains and protect non vaccinated populations. In 2007, invasive pneumococcal diseases (meningitis and bacteremia) have decreased about 3% in infants under two years of age but globally, the incidence of invasive pneumococcal disease has not been modified. There is a substitution for strains and a change in the serotypes distribution with a prominence of 19A and 7 F and 1 serotype. Added to the benefit on invasive pneumococcal diseases, there are others on pneumonia, otitis media and antibiotic resistance of pneumococcus. Six serotypes have been added to obtain the Prevenar 13 which replaces the seven valent vaccine. Prevenar 13 has the same recommendations as Prevenar and can be given by the same schedule 2 + 1 (2 months, 4 months, and 12 months) except in high risk children and premature newborns who have to be vaccinated by a 3 + 1 schedule. Epidemological surveillance of the strains has to be done, As for adults, the data are currently being analyzed.