Anne Vergison

Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium: case-control study

Objective To evaluate the effectiveness of rotavirus vaccination among young children in Belgium. Design Prospective case-control study. Setting Random sample of 39 Belgian hospitals, February 2008 to June 2010. Participants 215 children admitted to hospital with rotavirus gastroenteritis confirmed by polymerase chain reaction and 276 age and hospital matched controls. All children were of an eligible age to have received rotavirus vaccination (that is, born after 1 October 2006 and aged ≥14 weeks). Main outcome measure Vaccination status of children admitted to hospital with rotavirus gastroenteritis and matched controls. Results 99 children (48%) admitted with rotavirus gastroenteritis and 244 (91%) controls had received at least one dose of any rotavirus vaccine (P<0.001). The monovalent rotavirus vaccine accounted for 92% (n=594) of all rotavirus vaccine doses. With hospital admission as the outcome, the unadjusted effectiveness of two doses of the monovalent rotavirus vaccine was 90% (95% confidence interval 81% to 95%) overall, 91% (75% to 97%) in children aged 3-11 months, and 90% (76% to 96%) in those aged ≥12 months. The G2P[4] genotype accounted for 52% of cases confirmed by polymerase chain reaction with eligible matched controls. Vaccine effectiveness was 85% (64% to 94%) against G2P[4] and 95% (78% to 99%) against G1P[8]. In 25% of cases confirmed by polymerase chain reaction with eligible matched controls, there was reported co-infection with adenovirus, astrovirus and/or norovirus. Vaccine effectiveness against co-infected cases was 86% (52% to 96%). Effectiveness of at least one dose of any rotavirus vaccine (intention to vaccinate analysis) was 91% (82% to 95%). Conclusions Rotavirus vaccination is effective for the prevention of admission to hospital for rotavirus gastroenteritis among young children in Belgium, despite the high prevalence of G2P[4] and viral co-infection.

Impact of Pneumococcal Conjugate Vaccination on Otitis Media: A Systematic Review

Reduced rates of consultations for otitis media after introduction of pneumococcal conjugate vaccines (PCVs) have been overinterpreted. This systematic review suggests that PCV is only somewhat modestly effective against all-cause otitis media.

Reduction in pediatric rotavirus-related hospitalizations after universal rotavirus vaccination in Belgium.

Background: This study investigated the effect of pediatric vaccination against rotavirus on the number of rotavirus-related hospitalizations of children in Belgium. Methods: This retrospective database study was conducted at 12 pediatric hospitals in Belgium (546 pediatric beds, 30.6% of Belgian total). Children ≤5 years attending hospital for any reason were eligible if they had a rotavirus stool test at one of the study centers. The number of rotavirus-positive stool tests and hospitalizations for acute gastroenteritis (AGE) were compared for prevaccination (June 2004–May 2006) and postvaccination (June 2007–May 2009) study periods. Results: The number of rotavirus-positive stool tests in children who were ≤5 years of age decreased from an average of 881 in the prevaccination period to 368 in the first year postvaccination period and 199 in the second. In children 2 to 24 months of age, the percentage reductions were 65% (95% confidence interval [CI]: 62%, 69%) and 80% (95% CI: 77%, 83%) in the first and second years after vaccination, respectively, compared with prevaccination. In children <2 months, the reductions were 50% (95% CI: 36%, 64%) and 64% (95% CI: 49%, 76%), respectively, and in children >24 months the corresponding values were 20% (95% CI: 14%, 28%) and 64% (95% CI: 56%, 72%). The number of AGE-driven hospital admissions and hospitalization days for AGE declined by 33% and 36%, respectively, from prevaccination to the second year postvaccination in children ≤2 years of age. Conclusions: Pediatric rotavirus vaccination in Belgium significantly reduced rotavirus-related hospitalizations in the first and second years after introduction.

Microbiology of otitis media: a moving target.

Abstract The microbiology of acute otitis media (AOM) is linked to the nasopharyngeal commensal flora. This respiratory ecosystem undergoes various selective pressures, such as antibiotic consumption and vaccine use. Socio-economic conditions also influence the bacterial composition of the nasopharynx. Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae, Moraxella catarrhalis, and group A Streptococcus are the leading causes of bacterial AOM worldwide. This paper will discuss the causes and consequences of recent shifts in the underlying microbiology of AOM.

Rotavirus vaccines in Belgium: policy and impact.

Background: The current Belgian experience with rotavirus vaccination provides a unique perspective to look at the effect of vaccination. Shortly after introduction, a nation-wide recommendation was issued and despite the fact that both rotavirus vaccines are offered through partial reimbursement, vaccine uptake has already reached a high level (at least 90%). Methods: For the purpose of looking at the effectiveness of the Belgian rotavirus vaccination policy, 3 years after introduction, we retrospectively collated the publicly available data on the number of laboratory-confirmed rotavirus cases reported to a national network of sentinel laboratories during 1999 to 2010 and compared them with the available data on hospitalizations due to rotavirus gastroenteritis. Results: Both data sources (reported laboratory-diagnosed cases to a sentinel network as well as data on hospitalizations due to rotavirus gastroenteritis) show a decrease in the number of rotavirus infections and a 4- to 6-week delay in the onset of disease and the peak of incidence in the postvaccination period. Conclusions: Because this decline coincides with the increased vaccine uptake and is sustained during consecutive rotavirus seasons, the effect is mainly attributed to the rotavirus vaccination. The rapid increase in vaccine coverage, despite the partial reimbursement for the vaccines, is remarkable. Continued postlicensure surveillance is necessary to further investigate the effectiveness of the vaccines and to document the public health impact of the vaccination in reducing disease burden.

Antibiotic therapy for pediatric community-acquired pneumonia: do we know when, what and for how long to treat?

Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10–40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.

Impact of rotavirus vaccination on laboratory confirmed cases in Belgium

Rotavirus vaccines were introduced in Belgium in 2006 and recommended in the universal schedule in January 2007. We measured the impact of rotavirus vaccination through an active laboratory-based surveillance system. In 2008, the number of laboratory confirmed rotavirus cases declined by 61.4% (95% CI 60.2-62.6%) compared to the 2005-2006 pre-vaccination period, with the highest decline in children<1 year (80.1%; 95% CI 78.7-81.4%). The rotavirus season was delayed compared to pre-vaccination seasons. Laboratory data provide a crude estimation of vaccination impact, but analysis of in-patient data will be needed to assess the impact on severe disease.

Impact of conjugate 7-valent vaccination in Belgium: Addressing methodological challenges

In Belgium, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the national schedule in 2007. The early impact of PCV7 vaccination on paediatric invasive disease was estimated by comparing pre- and post-vaccination incidence from national surveillance. In children <2 year-olds, vaccine-serotype incidence declined by 96% but non-vaccine-types increased 2-3-fold. Overall invasive disease decreased by 23-46%, depending on adjustment for under-reporting and pre-vaccine trends. Non-vaccine-types 1 and 19A had increased before PCV7 use, suggesting the contribution of other factors. Estimation of PCV7 impact comparing pre- and post-vaccination data should adjust for pre-vaccine trends, and serotype dynamics need further exploration.

Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: Pharmacodynamic evaluation and comparison with isogenic normal-phenotype and revertant strains

ABSTRACT Small-colony variant (SCV) strains of Staphylococcus aureus show reduced antibiotic susceptibility and intracellular persistence, potentially explaining therapeutic failures. The activities of oxacillin, fusidic acid, clindamycin, gentamicin, rifampin, vancomycin, linezolid, quinupristin-dalfopristin, daptomycin, tigecycline, moxifloxacin, telavancin, and oritavancin have been examined in THP-1 macrophages infected by a stable thymidine-dependent SCV strain in comparison with normal-phenotype and revertant isogenic strains isolated from the same cystic fibrosis patient. The SCV strain grew slowly extracellularly and intracellularly (1- and 0.2-log CFU increase in 24 h, respectively). In confocal and electron microscopy, SCV and the normal-phenotype bacteria remain confined in acid vacuoles. All antibiotics tested, except tigecycline, caused a net reduction in bacterial counts that was both time and concentration dependent. At an extracellular concentration corresponding to the maximum concentration in human serum (total drug), oritavancin caused a 2-log CFU reduction at 24 h; rifampin, moxifloxacin, and quinupristin-dalfopristin caused a similar reduction at 72 h; and all other antibiotics had only a static effect at 24 h and a 1-log CFU reduction at 72 h. In concentration dependence experiments, response to oritavancin was bimodal (two successive plateaus of −0.4 and −3.1 log CFU); tigecycline, moxifloxacin, and rifampin showed maximal effects of −1.1 to −1.7 log CFU; and the other antibiotics produced results of −0.6 log CFU or less. Addition of thymidine restored intracellular growth of the SCV strain but did not modify the activity of antibiotics (except quinupristin-dalfopristin). All drugs (except tigecycline and oritavancin) showed higher intracellular activity against normal or revertant phenotypes than against SCV strains. The data may help rationalizing the design of further studies with intracellular SCV strains.

Epidemiologic Features of Invasive Pneumococcal Disease in Belgian Children: Passive Surveillance Is Not Enough

BACKGROUND. Reliable epidemiologic surveillance of infectious diseases is important for making rational choices for public health issues such as vaccination strategies. In Belgium, as in most European countries, surveillance relies on voluntary passive reporting from microbiology laboratories; therefore, reported incidence rates are probably inaccurate. METHODS. We conducted national, active, laboratory-based and clinically based surveillance of invasive pneumococcal disease in young children. RESULTS. During the study period, the incidences of invasive pneumococcal disease in children <2 years of age (104.4 cases per 105 person-years and 16.1 cases per 105 person-years for invasive pneumococcal disease and meningitis, respectively) and in children 0 to 59 months of age (59.5 cases per 105 person-years for invasive pneumococcal disease and 7.7 cases per 105 person-years for meningitis) were twice those reported previously through the passive surveillance system. Overall, 67% of the Streptococcus pneumoniae strains isolated from children <5 years of age belonged to 7-valent pneumococcal conjugate vaccine serotypes and 18% to vaccine-related serotypes (mainly serotype 19A). Erythromycin resistance was frequent, especially among children <2 years of age (59%). CONCLUSIONS. Under-reporting can explain the reported low incidence of invasive pneumococcal disease in countries (such as Belgium) that depend on a passive epidemiologic surveillance system, which could lead to erroneous choices in vaccination policies. There is a need for an active system of epidemiologic surveillance for vaccine-preventable diseases such as invasive pneumococcal disease, at the national or European level.