A pneumococcal conjugate vaccination programme reduced clinically suspected invasive disease in unvaccinated children.

AIM: The 10-valent pneumococcal conjugate vaccine was introduced to the Finnish national vaccination programme for children born since June 2010. We evaluated the changes in the rates of clinically suspected invasive pneumococcal disease (IPD) in unvaccinated children to estimate the indirect herd protection impact of the programme. METHODS: The target cohort for this ecological before and after comparison were unvaccinated children born from January 2008 to May 2010 and ineligible for the vaccination programme, who were followed up from 2011 to 2014. The reference cohort was age and season-matched children born in January 2003 to 2005 and followed up from 2006 to 2009. National data on hospital discharge codes compatible with IPD or unspecified sepsis were collected. RESULTS: We compared the follow-up periods of 2007-2009 in the reference cohort and 2012-2014 in the target cohort. The incidence of non-laboratory-confirmed IPD in unvaccinated children fell by 68%, from 47 to 15/100 000 person-years. When unspecified sepsis was added, the decrease was 39%, from 171 to 104/100 000 person-years. Laboratory confirmed IPD fell by 44%, from 15 to 8/100 000 person-years. CONCLUSION: The pneumococcal vaccination programme provided herd protection against clinically suspected IPD. The absolute reduction was almost 10-times higher than for just laboratory-confirmed disease.

Where are we in our understanding of the association between narcolepsy and one of the 2009 adjuvanted influenza A (H1N1) vaccines?

Evaluating new rare serious vaccine safety signals is difficult and complex work. To further assess the observed increase in narcolepsy cases seen in Europe with the 2009 pandemic H1N1 influenza vaccine, the International Alliance for Biological Standardization (IABS) invited a wide range of experts to a one day meeting in Geneva in October 2015 to present data and to discuss the implications. The presentations covered the following topics: clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaigns; epidemiological studies conducted to assess the risk of narcolepsy, other neurological and immune-related diseases following 2009 pandemic H1N1 influenza vaccine; potential biases influencing the different epidemiological study designs; potential genetic contribution to the development of narcolepsy; potential biological mechanisms for development of narcolepsy in this setting including the role of the virus itself, antigenic differences between the vaccines and differences in AS03-adjuvanted vaccines. The presentations were followed by fulsome roundtable discussions. Members from affected families also attended and made informal comments to round out the day's deliberations. This meeting emphasized the value added in bringing together in a neutral setting a wide range of experts and vaccine producers to discuss such a complex new serious adverse event following immunization.

Sunshine, rainfall, humidity and child pneumonia in the tropics: time-series analyses.

Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51-0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8-14 days earlier was 0·95 (95% CI 0·91-1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed.

Finland introduces rotavirus vaccine into the national vaccination programme in September 2009.

Supported by an economic evaluation, rotavirus vaccine is introduced into the national immunisation schedule in Finland. The vaccination programme has been estimated to be reasonably cost-effective. Given at the age of two, three and five months, the vaccine is expected to prevent annually in Finland among children under the age of five years approximately 2,000 rotavirus diarrhoea episodes needing hospitalisation, and over 10,000 outpatient visits. The impact of the programme will be evaluated in 2011 by repeating the economic analysis and carefully monitoring adverse events.

Invasive infections caused by Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae among children in St Petersburg, Russia.

This study investigated the causes of invasive bacterial infections in children aged <15 years in St Petersburg, Russia, during 2001-2003, using culture and antigen detection methods (rapid antigen latex agglutination (RAL)) for normally sterile body fluids. A pathogen was detected in 90 cases (culture 50, RAL 40). Neisseria meningitidis was the most common pathogen (66%), followed by Haemophilus influenzae (19%) and Streptococcus pneumoniae (16%). Meningitis was the main clinical diagnosis (68/90, 76%), with N. meningitidis serogroup B, H. influenzae type b (Hib), and S. pneumoniae serogroup 1 being the most common isolates. Hib was less prevalent in St Petersburg than it was in industrialised countries before the introduction of Hib vaccinations.

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002-2012.

BACKGROUND: In Finland a vaccination programme against human papillomavirus (HPV) was introduced in November 2013 for girls aged 11-12 years with a catchup for girls 13-15 years. Allegations that HPV vaccine is causing Guillain Barré syndrome (GBS) and non-specific diagnostic entities, such as chronic fatigue syndrome/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS), continue to surface. We examined population register-based incidence rates of CFS/SEID, GBS and POTS to provide baseline data for future HPV vaccine safety evaluations. METHODS: First diagnosis of CFS/SEID, GBS and POTS in girls aged 11-15 years were obtained from the National Hospital Discharge Register during 2002-2012. We considered the following ICD-10 codes: G93.3 for CFS; G61.0 for GBS and G90.9, G90.8, G93.3, I49.8 for POTS. We calculated incidence rates per 100,000 person-years with 95% confidence intervals (CI). RESULTS: In total, 9 CFS/SEID, 19 GBS and 72 POTS cases were identified. The overall incidence rate was 0.53/100,000 (95% CI; 0.27-1.01) for CFS/SEID, 1.11 (95% CI; 0.71-1.74) for GBS and 4.21 (95%CI; 3.34-5.30) for POTS. Significant relative increase in annual incidence rate with a peak in 2012 was observed in CFS/SEID (33% (95% CI; 3.0-70.3: p=0.029) and POTS (16.5% (95% CI; 7.8-25.9: p<0.05), but not in GBS (5.4% (95% CI; -8.4-21.3: p=0.460). CONCLUSIONS: Our findings provide baseline estimates of CFS/SEID, GBS and POTS incidences in Finland. However, rates based on register data should be interpreted with caution, especially for non-specific diagnostic entities for which internationally and even nationally agreed criteria are still being discussed. To assess the associations with HPV vaccine, methods using register linkage for cohort and self-controlled case series should be explored in addition to factors contributing to patients seeking care, treating physicians setting the diagnoses, and their preference of using of codes for these clinical entities.

Pneumococcal vaccination policy in Europe.

Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.

Pneumococcal vaccination policy in Europe.

Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.

Erythrocyte sedimentation rate, white blood cell count and serum C-reactive protein in assessing etiologic diagnosis of acute lower respiratory infections in children.

The clinical signs, symptoms and host responses (erythrocyte sedimentation rate, white blood cell count and C-reactive protein) were studied to distinguish bacterial from viral acute lower respiratory infection (ALRI) in 121 children hospitalized for ALRI. Etiologic diagnosis was based on blood culture, antibody assays and antigen detection. Children with bacterial involvement only were older than those with viral involvement alone (mean, 5.1 vs. 2.5 years), and their duration of respiratory symptoms had lasted longer (mean, 4.6 vs. 3.3 days). Children with unknown etiology had a shorter duration of fever before hospitalization than those with etiology identified with the methods used (mean, 1.6 vs. 2.9 days). The host response ranged widely within etiologic groups. The mean erythrocyte sedimentation rate did not differ significantly between the bacterial and viral ALRI (38 vs. 28 mm/hour); neither did white blood cell count (13.2 vs. 13.6 x 10(9)/liter) or C-reactive protein (68 vs. 49 mg/liter). No combination of clinical signs and host responses or any cutoff values could be shown to differentiate reliably bacterial from viral ALRI.

Bacterial antibody assays in the diagnosis of acute lower respiratory tract infection in children.

Bacterial antibodies were studied in acute, intermediate and convalescent phase sera (mean duration from first to last sample 36 days) of 121 children hospitalized for acute lower respiratory tract infection. Antibody responses were observed in 45% of all cases and in 29% of the 21 children < 1 year old. A total of 15 responses to Streptococcus pneumoniae (pneumolysin), 20 to Haemophilus influenzae, 9 to Moraxella catarrhalis, 3 to chlamydiae and 8 to Mycoplasma pneumoniae were found. In 79 patients with 4 consecutive samples available, 52% of the 31 responses were measurable within 5 days from admission. Overall the responses were not associated with upper respiratory tract bacterial findings or acute otitis media. Significantly more responses were found in the 121 children with acute lower respiratory tract infection than in healthy controls (P < 0.007). We conclude that bacterial antibody assays provide a useful tool in the study of the etiology of acute lower respiratory tract infection in young children, even if the interval between paired serum samples is short.

Effect of transplacentally acquired tetanus antibodies on the antibody responses to Haemophilus influenzae type b-tetanus toxoid conjugate and tetanus toxoid vaccines in Filipino infants.

BACKGROUND: Pregnant women in developing countries are vaccinated with tetanus toxoid (TT) to prevent neonatal tetanus. In populations in which the maternal TT-vaccination program is efficiently implemented, responses of the infant to TT and TT-conjugated vaccines such as Haemophilus influenzae type b (Hib) capsular polysaccaride (PS) TT-conjugate (Hib-TT) vaccine may be depressed. OBJECTIVES: To study the influence of transplacentally acquired anti-TT antibodies on responses to TT vaccination and to Hib-TT vaccine. METHODS: One hundred ninety-four healthy Filipino infants received three doses of a Hib conjugate (either Hib-TT, PRP-OMP or HbOC) with diphtheria-tetanus-pertussis vaccine (DTP) given simultaneously but in a separate syringe at the age of 6, 10 and 14 weeks (primary series). In addition 54 of the study children received a booster dose of Hib-TT at 9 months simultaneously with the measles vaccine. RESULTS: Transplacentally acquired anti-TT did not interfere with the anti-Hib PS antibody (anti-Hib PS) response to any of the conjugates. The transplacentally acquired anti-TT was not significantly associated with the concentration of anti-Hib PS either before or after the booster dose of Hib-TT. High concentrations (> or =1 IU/ml) of transplacentally acquired anti-TT inhibited the infants' anti-TT responses. CONCLUSIONS: High concentration of transplacentally acquired anti-TT did not depress anti-Hib PS responses to the Hib-TT vaccine. On the other hand the high anti-TT concentrations somewhat depressed the anti-TT responses of the infants. However, the anti-TT concentrations attained were in the protective range in all study children after either the primary series (DTP + Hib-TT) or the booster dose of Hib-TT.

The immunogenicity of three Haemophilus influenzae type B conjugate vaccines after a primary vaccination series in Philippine infants.

Serum antibody responses to three Haemophilus influenzae type b (Hib) capsular polysaccharide-protein conjugate vaccine (PRP-OMP, PRP-T, and HbOC) were evaluated in 174 Philippine infants after a primary vaccination series. Children were randomized to receive one of the Hib vaccines (Hib groups) or into a control group. Vaccination was carried out at six, 10 and 14 weeks of age based on the local Expanded Program of Immunization schedule. Sera were collected at six weeks of age for the Hib groups and one month after the third dose for all subjects. Anti-Hib concentrations were determined by the Farr-type radioimmunoassay. There were no significant differences (P = 0.3626) in the prevaccination anti-Hib geometric mean concentration (GMC) among the three Hib groups. Differences in the GMC after the primary series of three doses were significant (P < 0.0001); GMC was highest for PRP-T (6.62 micrograms/ml), followed by HbOC (1.9 micrograms/ml), then PRP-OMP (1.06 micrograms/ml), and lowest for the control group (0.11 microgram/ml). We conclude that all three Hib conjugate vaccines (PRP-T, HbOC, and PRP-OMP) were immunogenic after three primary doses among Philippine infants.

Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age.

BACKGROUND: Pneumonia, most commonly caused by Streptococcus pneumoniae (Pnc), is a major cause of morbidity and mortality among young children especially in developing countries. Recently, the prevalence of antibiotic-resistant Pnc has increased worldwide such that the effectiveness of preventive strategies, like the new pneumococcal conjugate vaccines (PCV) on rates of invasive pneumococcal disease (IPD) and pneumonia, needs to be evaluated. OBJECTIVES: To determine the efficacy of PCV in reducing the incidence of IPD due to vaccine serotypes (VT) and x-ray confirmed pneumonia with consolidation of unspecified etiology in children who received PCV before 12 months of age. SEARCH STRATEGY: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2004), MEDLINE (1990 to March 2004) and EMBASE (1990 to December 2003). Reference list of articles, and books of abstracts of relevant symposia, were hand searched. Researchers in the field were also contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, among children below two years with IPD and clinical/radiographic pneumonia as outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently identified eligible studies, assessed trial quality, and extracted data. Differences were resolved by discussion. The inverse variance method was used to pool effect sizes. MAIN RESULTS: We identified four trials assessing the efficacy of PCV in reducing the incidence of IPD, two on x-ray confirmed pneumonia as outcome, and one on clinical pneumonia, with or without x-ray confirmation. Results from pooling HIV-1 negative children from the South African study with the other studies were as follows: the pooled vaccine efficacy (VE) for vaccine-type IPD was 88% (95% confidence interval (CI) 73% to 94%; fixed effect and random effects models), the effect measure was statistically significant (p <0.00001) and there was no heterogeneity (p = 0.77I2 0%); the pooled VE for all-serotype IPD was 66% (95% CI 46% to 79%; fixed effect model), the effect measure was statistically significant (p <0.00001) and there was no statistical heterogeneity (p = 0.09, I2 51%); the pooled VE for x-ray confirmed pneumonia was 22% (95% CI 11% to 31%; both fixed effect and random effects models) and there was no statistical heterogeneity (p = 0.80, I2 0%). Analyses that included all the children in the South African study (HIV-1 negative and HIV-1 positive children) and pooled with data from the other studies gave very similar results. REVIEWERS' CONCLUSIONS: PCV is effective in reducing the incidence of IPD from all serotypes but exerts a greater effect in reducing VT IPD. Although PCV is also effective in reducing the incidence of x-ray confirmed pneumonia, there are still uncertainties about the definition of this outcome. Additional randomised controlled trials are currently in progress.

Development of a European electronic network on communicable diseases: the IDA-HSSCD programme.

The European Commission (EC) has stated that setting up disease surveillance and health monitoring systems that cover the EU is a priority, and has proposed the development of a Community wide network, relying on electronic, computer based communications

National Advisory Groups and their role in immunization policy-making processes in European countries.

During the twenty-first century, the development of national immunization programmes (NIP) has matured into robust processes where evidence-based methodologies and frameworks have increasingly been adopted. A key role in the decision-making and recommending processes is played by National Immunization Technical Advisory Groups (NITAGs). In a survey performed among European Union member states, Norway and Iceland, in February 2013, 85% of the 27 responding countries reported having established a NITAG, and of these, 45% have formal frameworks in place for the systematic development of vaccination recommendations. Independent of whether a formal framework is in place, common key factors are addressed by all NITAGs and also in countries without NITAGs. The four main factors addressed by all were: disease burden in the country, severity of the disease, vaccine effectiveness or efficacy, and vaccine safety at population level. Mathematical modelling and cost-effectiveness analyses are still not common tools. Differences in the relative weighting of these key factors, differences in data or assumptions on country-specific key factors, and differences in existing vaccination systems and financing, are likely to be reasons for differences in NITAG recommendations, and eventually NIPs, across Europe. Even if harmonization of NIPs is presently not a reasonable aim, systematic reviews and the development of mathematical/economic models could be performed at supranational level, thus sharing resources and easing the present work-load of NITAGs. Nevertheless, it has been argued that harmonization would ease central purchase of vaccines, thus reducing the price and increasing access to new vaccines.

EuSANH workshop "Reasons behind the differences in national vaccination schedules for under-five", European Public Health pre-conference workshop, Malta, 8 November 2012.

Vaccination schedules for under-five children in the EU member states differ markedly, mainly as a consequence of differences in programme organization, decision making and history, and to a limited extent by epidemiological differences. There is little willingness towards unification since little evidence exists to prefer one schedule over the others, but the differences might impact on public confidence. Monitoring key determinants influencing individual decision making on immunization ('soft impacts') is thus as important as other existing monitoring systems of the 'hard' impacts of immunization programmes, and both should focus on the impact of these schedule differences. Harmonization of vaccination schedules is not the main issue, but the reasons behind the differences should be explained in an understandable and coherent way to the public. Scientists and advisory bodies should look over the country borders and communicate any crucial information, in order to improve scientific consensus on immunization schedules and programmes. These were the main conclusions of a members' experts panel of the European network of independent science advisory bodies on health (EuSANH), at a workshop in November 2012.