Tolerability of 2 doses of pandemic influenza vaccine (Focetria®) and of a prior dose of seasonal 2009-2010 influenza vaccination in the Netherlands.

In the Netherlands, people indicated for seasonal influenza vaccination are divided in 3 risk groups, i.e. those less than 60 y (y) with comorbidity and those 60 y and over with and without comorbidity. Those risk groups were also eligible for pandemic vaccination during the 2009 influenza A(H1N1) pandemic. We assessed tolerability of seasonal influenza vaccination and 2 doses of pandemic influenza A(H1N1) vaccine, adjuvanted with MF-59, administered 2 and 5 weeks after seasonal 2009-2010 vaccination among adults. Vaccinees were asked to return questionnaires on local and systemic adverse events (AEs) after each of 3 consecutive vaccinations given at the office of their General Practitioner. Sex- and risk group-specific AE-frequencies were calculated. Generalized Linear Mixed Model with seasonal vaccination as reference was used to calculate odds ratios (ORs) for AEs of the 2 pandemic doses. 5553 questionnaires (3251 vaccinees) were returned. Vaccinees reported any local AE after seasonal vaccination and both pandemic doses in 34%, 23%, and 18%, respectively. These percentages were 29%, 25%, and 16% for any systemic AE. Men reported fewer local and systemic AEs then women (p<0.0001). The risk of local (OR range 0.34-0.63) and systemic (OR range 0.39-0.99) AEs (overall, stratified by risk group and by sex) was lower after both pandemic doses compared to seasonal vaccination. This decreased risk was more pronounced after the second pandemic dose than after the first. Therefore, we conclude that MF59-adjuvanted pandemic vaccine given after seasonal vaccination was well tolerated.

[Possible exposure to rabies in anamnesis: rabies advice in the Netherlands]. / Mogelijke blootstelling aan rabiës in de anamnese: rabiesadvisering in Nederland.

Anamnestic incidences of four patients have highlighted the potential risk ofexposure to rabies. The first patient was a 30-year-old woman who rescued a bat from the mouth of her dog; it bit her on the right wrist. In the Netherlands, bats may be infected with the Lyssa virus. The Preparedness and Response Unit (PRU) of the Centre for Infectious Disease Control (CIDC) advised human rabies immunoglobulin (HRIG) and a full vaccination programme. The second patient was a 37-year-old woman, who caught a 'sick' squirrel and was subsequently bitten on her left hand. The advice was not to use post exposure prophylaxis since rabies is not prevalent amongst squirrels in the Netherlands. The third patient, a 55-year-old man, was bitten on his right calf by a dog in Sri Lanka. He was treated with HRIG and given the full vaccination course. The fourth patient was a 14-month-old boy who was scratched on the face by a cat in Turkey. He immediately received the first vaccination and upon return to the Netherlands was treated with HRIG and the other vaccinations. All patients remained without symptoms. A structured approach for risk assessment of each potential rabies incident is possible. It requires balancing a number of criteria: the species of animal, the endemicity of rabies in a country, the observed health or vaccination status of an animal, whether the animal can be tested for rabies, if the exposure was provoked or unprovoked, the type of injury and its location on the body of the injured, and the time interval between administration of HRIG and vaccine. In the Netherlands all health care providers are expected to perform a proper risk assessment. They may seek advice from regional health departments (Municipal Health Services), who, in turn, can be assisted by the PRU. HRIG and vaccine are only provided by the National Vaccine Institute in Bilthoven.

[Safety surveillance in the National Vaccination Programme; fewer adverse events with the DTP-IPV-Hib vaccine after the transition to an acellular pertussis component in 2005]. / Veiligheidsbewaking van Rijksvaccinatieprogramma; minder bijwerkingen van DKTP-Hib-combinatievaccin sinds overgang in 2005 naar vaccin met acellulaire kinkhoestcomponent.

OBJECTIVE: To determine the adverse reactions to the combined vaccine against diptheria, acellular pertussis, tetanus, poliomyelitis and Haemophilus Infuenzae type B (DTP-IPV-Hib) before and after the introduction of an acellular pertussis component. DESIGN: Descriptive. METHOD: Safety surveillance of the Dutch National Vaccination Programme is performed by the National Institute for Public Health and Environment (RIVM). It is based on an enhanced passive reporting system and complemented by targeted survey-based studies. The data obtained were analysed. RESULTS: The passive surveillance system showed a large increase in reports in 2004, probably linked to increased media attention on the efficacy and safety of the whole-cell DTP-IPV-Hib vaccine. The Health Council recommended transitioning to the use of a DTP-IPV-Hib vaccine with an acellular pertussis component, which was implemented in January 2005. The number of reports dropped sharply in 2005 to a level below that of 2002-2003. Results of a survey study on adverse events following DTP-IPV-Hib vaccination that began in late 2003 and continued in 2005 confirmed the wide coverage ofthe enhanced passive surveillance system and revealed low rates of underreporting of rare adverse events, such as collapse and convulsions. CONCLUSION: This study confirms the data from the passive surveillance system, which show that the newly introduced acellular DTP-IPV-Hib vaccine is associated with fewer adverse events than the whole-cell vaccine that was used previously.

[Increase in the number of invasive Haemophilus influenzae type b infections]. / Toename van het aantal invasieve infecties door Haemophilus influenzae type b.

OBJECTIVE: To describe the increase of invasive Haemophilus influenzae type b (Hib) infections in The Netherlands before and after the introduction of Hib vaccination in 1993, and to hypothesise about possible explanations. DESIGN: Descriptive. METHOD: Data on the prevalence of invasive Hib infections, such as meningitis and epiglottitis, during 1990-2004 were obtained from The Netherlands Reference Laboratory for Bacterial Meningitis, which collects Hib isolates from spinal fluid and blood from across the country. RESULTS: The incidence of invasive Hib infections decreased substantially for a few years after 1993. The total number of isolates was at a minimum in 1999 (n = 12) and increased to 49 in 2004. The annual number of patients with vaccine failure was 5 or less during 1995-2001, but was between 10 and 15 from 2002 onwards. A definite explanation for the increase in the incidence of invasive Hib infections cannot be given. Improbable causes are a surveillance artefact, an impaired response to the vaccine due to vaccination-scheme changes or interaction with other vaccines, or selection of Hib variants that are less sensitive to the vaccine-induced immunity. It most likely involves secondary vaccine failure: Hib carriership is decreased by mass vaccination, whereupon natural boosting occurs less frequently later in life. Subsequently, immunity decreases and susceptibility to invasive infection increases. Careful surveillance of invasive Hib infections in The Netherlands remains important.

[Protection of children born to hepatitis-B-infected mothers]. / Bescherming van kinderen geboren uit met hepatitis-B-virus geïnfecteerde moeders.

The vaccination schedule implemented on 1 March 2003 for the approximately 1000 Dutch children per year born to hepatitis-B-virus-infected mothers is under discussion. The Health Council of The Netherlands and TNO have both published reports which reveal that the current schedule does not fulfil its objectives, as too many children are completely missed and many of the vaccinated children do not receive their scheduled vaccinations on time. Furthermore, doubts have been expressed about the effectiveness of the present vaccination schedule. In line with one of the schedules proposed by the Health Council we suggest the introduction of a 4-dose vaccination, in which the first vaccination is given immediately after the birth of the child. The subsequent vaccinations can then take place after 2, 4 and 11 months. These are the ages at which other children are also vaccinated against hepatitis B in accordance with the Dutch national vaccination programme. Furthermore, we advise an improved surveillance to ensure compliance with the individual vaccination schedules for these children. If data from the hepatitis-B screening of pregnant women, the regional vaccination registers, and the vaccinations actually administered are linked, then it will be possible to take swift action if a child is late for a hepatitis-B vaccination. In our opinion, this can best be achieved if a single national organisation is made responsible for the entire process, starting from the collection of the hepatitis-B data of pregnant women up to concluding the scheme, whether or not the serologic response is checked.

[Increased risk of hepatitis B due to incomplete or untimely immunisation in one-quarter of infants of hepatitis-B-virus carriers]. / Verhoogd risico op hepatitis B door onvolledige of ontijdige immunisatie bij een kwart van de zuigelingen van hepatitis-B-virusdraagsters.

OBJECTIVE: To determine the frequency of an increased risk of infection in children of hepatitis-B-virus carriers due to incomplete or untimely hepatitis-B immunisation. DESIGN: Descriptive. METHOD: Dates of birth and hepatitis-B immunisations were collected for all documented children of hepatitis-B-virus carriers in the vaccination registers, born in 2000 in The Netherlands. To assess the possible increased risk of infection, criteria were drawn up for the completeness and timeliness of the immunisations and on the basis of these the number of children who possibly had an increased risk of infection was determined. RESULTS: In total, 731 of the 769 children (95%) had received hepatitis-B immunoglobulins and at least 3 vaccinations. For 200 children (26%) the deviation from the immunisation schedule was so great that the child was possibly (temporarily) inadequately protected. CONCLUSION: A quarter of the children of hepatitis-B-virus carriers were immunised incompletely or at the wrong time. This calls for an adjustment of the immunisation schedule and national guidelines in which the responsibilities and tasks are clearly defined.

Report of a US public health service workshop on hypotonic-hyporesponsive episode (HHE) after pertussis immunization.

Hypotonic-hyporesponsive episode (HHE) is a term used to describe a somewhat heterogenous group of clinical disorders that have been reported primarily in association with whole-cell pertussis vaccination. A 1991 review by the Institute of Medicine determined that the evidence available was indeed consistent with a causal relation between whole-cell pertussis-diphtheria-tetanus immunization and HHE, but that the evidence was insufficient to indicate a causal relationship between HHE and the subsequent development of permanent neurologic damage. More recent data from clinical trials conducted in Europe suggest that HHE also occurs after vaccination with acellular pertussis vaccines. The US Food and Drug Administration, in collaboration with the US Public Health Service, sponsored a workshop on HHE in Rockville, Maryland, on June 19, 1997. The primary goals of the workshop were to develop a case definition of HHE and to evaluate the general design and feasibility of possible studies of HHE using the federal Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system. The goals of such studies would be to understand better the acute HHE event and to evaluate the possibility of long-term sequelae. Case Definition. There has been no generally accepted definition of HHE, and a standard definition would be useful for vaccine safety work and would potentially facilitate interstudy comparisons of the growing number of licensed vaccines containing acellular pertussis components. The workshop defined HHE as an event of sudden onset occurring within 48 hours of immunization, with duration of the episode ranging from 1 minute to 48 hours, in children younger than 10 years of age. All of the following must be present: 1) limpness or hypotonia, 2) reduced responsiveness or hyporesponsiveness, and 3) pallor or cyanosis or failure to observe or to recall skin coloration. HHE is not considered to have occurred if there is a known cause for these signs (eg, postictal), if urticaria is present during the event, if normal skin coloration is observed throughout the episode, or if the child is simply sleeping. This inclusive (sensitive) case definition will allow investigators, through the technique of stratification according to certain characteristics (eg, time from vaccination to onset of HHE), to attempt to hone the definition and make it more specific. Refinement of the definition of HHE has been hindered by the lack of information on its pathophysiology and by the lack of pathognomonic signs, symptoms, and diagnostic tests. Another hindrance is that by the time the child presents for medical evaluation, the signs of HHE often have normalized. Moreover, different mechanisms may be involved in different individuals whose events meet this workshop's HHE definition. Further Study of HHE. Probably the most important question about HHE is whether it has any permanent sequelae. The workshop assessed the possible contribution VAERS-based studies could make to answering this question and found substantial methodologic problems; however, ongoing studies in Sweden and The Netherlands have the potential to provide useful information on this question. The most useful contribution of VAERS data would be in a descriptive study of HHE, with a possible case-control study of factors that may affect the risk of HHE after vaccination, rather than a study of possible permanent sequelae. The workshop participants felt that a detailed descriptive study of approximately 100 HHE events reported during a 1- to 2-year period could provide a more in-depth description of HHE cases in greater numbers than has been published previously, but the study would not address the issue of long-term sequelae of HHE. Better descriptive data may lead to new hypotheses concerning risk factors, etiology, and pathophysiology of HHE that might be evaluated further by studying subsequent cases and controls from VAERS or from other sources, depending on the hypoth