Comparison of the tolerability of newly introduced childhood vaccines in the Netherlands.

In 2011, the 7-valent conjugated pneumococcal vaccine (PCV7) was replaced by the 10-valent vaccine (PCV10) and universal hepatitis B vaccination has been introduced in the Netherlands. A questionnaire study was conducted to assess the tolerability of DTaP-IPV-Hib + PCV7 (PCV7-cohort), DTaP-IPV-Hib + PCV10 (PCV10-cohort), and DTaP-IPV-Hib-HepB + PCV10 (HepB-cohort). Parents were asked to report in questionnaires local reactions and systemic adverse events (AEs) before and after vaccination of their infant at 2, 3, 4, and 11 months of age. For 29.0 and 29.4% infants of the PCV7-cohort, at least one local reaction was reported in the week after the first dose of DTaP-IPV (left leg) and PCV-7 vaccination (right leg). Significantly more infants from the PCV10-cohort (45.1%, p < 0.001 and 44.6%, p < 0.001) and HepB-cohort (42.6%, p < 0.001 and 41.9%, p < 0.001) reported at least one local reaction. This effect was less pronounced after the successive doses. Most of the infants experienced at least one systemic AE, and after dose 4, this was higher for infants in the PCV10-cohort (65.9%, p = 0.047) and HepB-cohort (70.6%, p = 0.000) compared to the PCV7-cohort (62.3%). CONCLUSION: Addition of antigens to a vaccine resulted in a higher reactogenicity, but the AEs were in general mild and transient. What is Known: • Assessment of adverse events is crucial for achieving the highest safety in immunization programs, in order to inform public health actions and maintain public confidence in immunization programs. What is New: • Newly introduced vaccines DTaP-IPV-Hib-HepB and PCV10 are generally safe and well tolerated in infants. • These results are useful for information purposes and for monitoring variations in rates of AEs in the general population or in the target group over time.

Baseline incidence of intussusception in early childhood before rotavirus vaccine introduction, the Netherlands, January 2008 to December 2012.

Intussusception is a rare, potentially life-threatening condition in early childhood. It gained attention due to an unexpected association with the first rotavirus vaccine, RotaShield, which was subsequently withdrawn from the market. Across Europe, broad variations in intussusception incidence rates have been reported. This study provides a first estimate of intussusception incidence in young children in the Netherlands from 1 January 2008 to 31 December 2012, which could be used for future rotavirus safety monitoring. Our estimates are based on two different sources: electronic medical records from the primary healthcare database (IPCI), as well as administrative data from the Dutch hospital register (LBZ). The results from our study indicate a low rate of intussusception. Overall incidence rate in children < 36 months of age was 21.2 per 100,000 person-years (95% confidence interval (CI): 12.5-34.3) based on primary healthcare data and 22.6 per 100,000 person-years (95% CI: 20.9-24.4) based on hospital administrative data. The estimates suggest the upper and lower bound of the expected number of cases.

Reactogenicity and safety of second trimester maternal tetanus, diphtheria and acellular pertussis vaccination in the Netherlands.

BACKGROUND: Maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination is offered to all pregnant women during their second trimester in the Netherlands since December 2019. We assessed second trimester Tdap vaccination reactogenicity and compared with third trimester data from a similar study. For safety assessment, adverse pregnancy outcomes were compared with national data from 2018, before Tdap vaccine-introduction. METHODS: Pregnant women were included between August 2019-December 2021 and received Tdap vaccination between 20 and 24w gestational age (GA). Participants completed a questionnaire on solicited local reactions and systemic adverse events (AEs) within one week after vaccination. Results were compared with historical data on reactogenicity from women vaccinated between 30 and 33w GA (n = 58). Regarding safety-related outcomes, each participant was matched to four unvaccinated pregnant women from the Dutch Perinatal Registry, based on living area, parity and age. RESULTS: Among 723 participants who completed the questionnaire, 488 (67.5 %) experienced ≥ 1 local reaction with pain at the injection site as most reported reaction (62.3 %), and 460 (63.6 %) experienced ≥ 1 systemic AE with stiffness in muscles/joints (38.9 %), fatigue (28.9 %), headache (14.5 %) and common cold-like symptoms (11.0 %) most frequently reported. 4 women (0.6 %) reported fever (≥38.0˚C). Symptoms were considered mild and transient within days. No difference in AEs were found between vaccination at 20-24w versus 30-33w GA. 723 participants were matched to 2,424 unvaccinated pregnant women with no increased rates of premature labor, small-for-gestational-age, or other adverse pregnancy outcomes. CONCLUSIONS: Second trimester maternal Tdap vaccination appears safe and well-tolerated. Comparison between second versus third trimester vaccination yielded no reactogenicity concerns.

Guillain-Barré syndrome: background incidence rates in The Netherlands.

Guillain-Barré syndrome (GBS) is a (sub)acute polyradiculoneuropathy, which may occur following immunization. To interpret the occurrence of GBS after introduction of large-scale immunization programmes, it is important to define recent background incidence rates (IRs) of GBS. We used a general practitioner electronic medical record database to assess age-specific GBS IRs between 1996 and 2008 in The Netherlands. All possible GBS cases were manually reviewed. Validated incident cases were reviewed by a neurologist (B. J.) for diagnostic certainty using the GBS case definition of the Brighton Collaboration (BC). In a population of 638,891 persons, we identified 23 validated incident GBS cases (mean age 46 years). IR was 1.14 per 100,000 person years (95% confidence interval [CI] 0.67-1.61) and was lower for people under 50 years (0.76; 95%CI 0.41-1.32) compared with elderly of 50 years or older (1.80; 95%CI 0.98-3.05). Only six cases fulfilled level 1 or 2 of diagnostic certainty of the BC case definition. IR of GBS increases with age. As vaccinations are often targeted at specific age groups, age-specific rates should be used to monitor GBS observed versus expected rates after introduction of large-scale vaccination programmes.

Parental reports of adverse events following simultaneously given dT-IPV and MMR vaccines in healthy 9-year-old children.

In the Netherlands, children at 9 years of age receive a booster dT-IPV together with their second measles, mumps, and rubella (MMR) vaccination within the national immunization program. Safety is monitored continuously by enhanced passive surveillance. This population-based study was conducted to obtain more information on adverse events after vaccination at 9 years of age. Questionnaires on local and systemic reactions were distributed 1 and 3 weeks after vaccination, respectively, to parents of 1,250 healthy children who received their MMR and diphtheria, tetanus, and inactivated poliovirus injection (dT-IPV) vaccination as scheduled. Response to the questionnaires was 57.0% and 46.5%, respectively. Local reactions occurred in 86.5% of the children within 7 days after vaccination, more often at the dT-IPV (83.4%) than at the MMR site (32.7%). Pain was the most reported symptom (80.8% at the dT-IPV site; 29.1% at the MMR site). Systemic events occurred in 33.4% children within 7 days after vaccination, with headache as the most frequently reported (20.8%). Systemic events occurred in 20.8% children 8-21 days after vaccination. Children with local reactions at only the dT-IPV site had significantly more systemic events (19.3%) than those without local reactions (3.4%, p < 0.01). Such difference was not found for the MMR site. No serious adverse events were reported. Medical intervention was applied to 133 children (130 used analgesics and for three children the GP was consulted by phone). In conclusion, the frequency of reported local reactions is high, especially at the dT-IPV site, but all symptoms were transient. However, the use of reduced antigen content vaccines in association with the occurrence of adverse events is meaningful to explore. Furthermore, the overall rates are useful for monitoring variations in adverse events rates in the general population.

Two doses of pandemic influenza A(H1N1) vaccine: tolerability in healthy young children in the Netherlands.

During the 2009 influenza pandemic, children aged 6 months up to and including 4 years, without chronic illness, were vaccinated with two doses of Pandemrix(®) through mass vaccination in the Netherlands. During the vaccination campaign a warning was issued about fever after the second dose of Pandemrix(®). Therefore, we investigated the tolerability of both doses Pandemrix(®) in these children. Among parents of children eligible for vaccination, 1500 questionnaires were distributed during both, the first and second mass vaccination session. We asked for the occurrence, time interval, and duration of local reactions and systemic adverse events (AEs). The responses were 36.7% and 29.5% after each dose, respectively. Local reactions were reported in 40.4% and 39.3%, most frequently, pain at the injection site. After the first and second dose, 29.6% and 30.7% of all children experienced fever (mean temperature 38.8{degree sign}C). Other systemic AEs were reported in 41.6% and 42.9% of the children. No differences were seen between the first and second dose for all reported AEs except for pallor. One child was hospitalized after the first dose, but a causal relation to the vaccination was considered improbable. In conclusion, fever was frequently reported in children 6 months up to and including 4 years of age after the first and second dose of Pandemrix(®). However, for almost all AEs, including fever, no dose effect was observed. Reported AEs were mostly mild and all were transient.

Background incidence rates of adverse pregnancy outcomes in the Netherlands: Data of 2006-2018.

OBJECTIVE: Maternal vaccination is an effective and safe intervention to protect newborns against infectious diseases shortly after birth. We assessed background rates of adverse pregnancy outcomes before the implementation of a maternal pertussis immunisation programme in the Netherlands, to put into perspective the safety concerns about such outcomes following immunisation. STUDY DESIGN: In this retrospective cross-sectional study, annual numbers of pregnancy outcomes derived from the Dutch Perinatal Registry were used to calculate incidence rates per 10,000 in the 2006-2018 period. Births of ≥500 g birth weight and ≥24 + 0 w gestational age were included. Trends with moving-average-lines over the past 3 years were plotted, with 95 % confidence interval. RESULTS: From 2006 through 2018, yearly numbers of pregnancies ranged between 158,868-175,710. Numbers of newborns ranged between 161,307-178,874, of whom 160,838-178,177 were live-born. Most outcomes were stable over time. Between 2006-2011, occurrence of labour induction increased by 68 %, and postpartum hemorrhage increased by 25 %. Both stabilised from 2011 onwards. Perinatal mortality up to day 7 or 28 postpartum decreased by 38 % and 37 %, respectively. Occurrence of low Apgar score among preterm infants born before 37 + 0 w gestational age and among term infants increased by 19 % and 27 %, respectively. CONCLUSION: Our study on background incidences showed notable increases over time in occurrence of labour induction, postpartum hemorrhage and low Apgar score, while showing a considerable decrease in overall perinatal mortality. These findings should be considered when interpreting data on adverse events occurring since the maternal pertussis immunisation programme was implemented.

Discolored leg syndrome after vaccination--descriptive epidemiology.

Discoloration of the leg following vaccination is a relatively unknown entity. We carried out a study of discolored leg syndrome (DLS) during a 10-year consecutive period with the objective of characterizing DLS in infants following vaccination received in the Dutch National Vaccination Program as well as its occurrence and association with different vaccines. Discolored leg syndrome was defined as an even or patchy red, blue or purple discoloration of the leg(s) and/or leg petechiae with or without swelling. All reports of adverse events following immunization that were made to the passive surveillance system between 1994 and 2003 were included-a total of 1162 identified cases. Red, blue, purple discoloration and isolated petechiae were reported in 39, 19, 27 and 14% of these cases, respectively. Of these 1162 cases, 1105 were considered to be related to the vaccination, based on a predefined risk window with symptom onset after vaccination (48 h for discolorations and 2 weeks for petechiae). Of the 1105 cases, about 50% occurred after DTP-IPV+Hib1 vaccinations, and 30% occurred after DTP-IPV+Hib2 vaccinations. Discolored leg syndrome was frequently accompanied by fierce crying (78%). The median time interval between vaccination and the occurrence of DLS was 3.8 +/- 46.7 h, and the median duration was short (2 +/- 61.7 h). Advancing the vaccination schedule from 3 to 2 months of age caused a small increase in DLS. Discolored leg syndrome manifested mainly after the first and/or second vaccination. In addition to dose, the occurrence of DLS may be slightly age-dependent and self-limiting. The pathophysiology is unknown but may be the result of a vasomotor reaction. Future studies should elucidate the recurrence rate, identify risk factors and assess late outcomes.

Differences by sex in IgG levels following infant and childhood vaccinations: An individual participant data meta-analysis of vaccination studies.

BACKGROUND: If immune responses to vaccination differ between males and females, sex-specific vaccination schedules may be indicated. We systematically reanalysed childhood vaccination studies conducted in The Netherlands for sex-differences in IgG-responses. To assess the impact of potential sex-differences in IgG-responses, we explored sex-differences in vaccine failure/effectiveness and reactogenicity. METHODS: Six studies with IgG-measurements for 1577 children following infant pneumococcal (PCV7/PCV10/PCV13) and/or DTaP-IPV-Hib(-HepB) vaccinations, or the pre-school DTaP-IPV booster were included. We performed one-stage individual participant data meta-analyses per time-point of the effect of sex on IgG levels against pneumococcal serotypes, diphtheria toxoid, tetanus toxoid, pertussis Ptx/FHA/Prn and Hib-PRP using linear mixed models. Using existing study data, we compared reactogenicity after PCV7/PCV10 and DTaP-IPV-Hib(-HepB) vaccination in girls and boys. Vaccine failure/effectiveness was compared between girls and boys for invasive pneumococcal disease (IPD), invasive Hib disease and pertussis using notification data. RESULTS: For pneumococcal vaccination, the geometric mean concentration ratio of IgG levels in girls versus boys pooled across serotypes was 1.15 (95%CI 0.91-1.45) 1 month following the primary series, 1.16 (1.02-1.32) at age 8 months, 1.12 (1.02-1.23) pre-booster (age 11 months) and 0.99 (0.89-1.10) post-booster (age 12 months). Diphtheria toxoid, tetanus toxoid, pertussis Ptx/FHA/Prn and Hib-PRP IgG levels did not differ between girls and boys, except for Hib post-booster (1.24; 95%CI 1.01-1.52) and tetanus before pre-school booster (0.71; 0.53-0.95). We found no difference between boys and girls in reactogenicity at age 4 or 11 months or in vaccine failure/effectiveness for IPD, invasive Hib disease or pertussis. CONCLUSION: For most vaccine antigens investigated, there were no consistent differences in vaccine-induced IgG levels. Vaccine-induced pneumococcal IgG levels were slightly higher in girls, but only between the primary series and the 11-month booster. These results, along with similar reactogenicity and vaccine failure/effectiveness, support the uniform infant vaccination schedule in the Dutch national immunisation programme.

Elevated Immune Response Among Children 4 Years of Age With Pronounced Local Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis Vaccination.

BACKGROUND: In the Netherlands, acellular pertussis vaccines replaced the more reactogenic whole-cell pertussis vaccines. This replacement in the primary immunization schedule of infants coincided with a significant increase in pronounced local adverse events (AEs) in 4 years old children shortly after the administration of a fifth diphtheria, tetanus, acellular pertussis and inactivated polio (DTaP-IPV) vaccine. The objective of this study was to investigate possible differences in vaccine antigen-specific immune responses between children with and without a pronounced local AE after the fifth DTaP-IPV vaccination. METHODS: Blood was sampled in 2 groups of 4-year-olds: a case group reporting pronounced local swelling and/or erythema up to extensive limb swelling at the injection site (n = 30) and a control group (n = 30). Peripheral blood mononuclear cells were stimulated with individual vaccine antigens. Plasma antigen-specific IgG, IgG subclass and total IgE concentrations and T-cell cytokine [interferon-gamma, interleukin (IL)-13, IL-17 and IL-10] production by stimulated peripheral blood mononuclear cells were determined by multiplex bead-based fluorescent multiplex immunoassays. RESULTS: In children with AEs, significantly higher total IgE and vaccine antigen-specific IgG and IgG4 responses as well as levels of the T-helper 2 (Th2) cytokine IL-13 were found after pertussis, tetanus and diphtheria stimulation compared with controls. CONCLUSIONS: Children with pronounced local reactions show higher humoral and cellular immune responses. Acellular vaccines are known to skew toward more Th2 responses. The pronounced local AEs may be associated with more Th2 skewing after the fifth DTaP-IPV vaccination, but other biologic factors may also impact the occurrence of these pronounced local reactions.

Effect of vaccinations on seizure risk and disease course in Dravet syndrome.

OBJECTIVE: To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). METHODS: We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared. RESULTS: Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at first nonvaccination-associated seizure, age at first report of developmental delay, or cognitive outcome. The risk of subsequent vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination. CONCLUSIONS: Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific.

Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study: oral contraceptives and the risk of ischemic stroke.

BACKGROUND AND PURPOSE: Epidemiological studies have shown an increased risk of venous thrombosis in women taking third-generation oral contraceptives, ie, those containing the progestogens desogestrel or gestodene. This study assesses the risk of ischemic stroke with several types of oral contraceptives. METHODS: A multicenter, population-based, case-control study was performed in 9 Dutch centers in women aged 18 to 49 years. Women with a first ischemic stroke were compared with control women without vascular diseases. The control subjects were recruited by random-digit dialing and were stratified by age, area of residence, and year of stroke. All patients and control subjects filled in a questionnaire about the use of oral contraceptives and risk factors for ischemic stroke. Odds ratios were adjusted for the stratification factors. RESULTS: Two hundred three women with an ischemic stroke and 925 control women were included. The risk of stroke in women using any type of oral contraceptives versus none was 2.3 (95% CI 1.6 to 3.3). Current users of first-generation oral contraceptives had an odds ratio of 1.7 (95% CI 0.7 to 4.4). Low-dose second-generation oral contraceptives increased the risk of stroke 2.4 times (95% CI 1.6 to 3.7), and third-generation oral contraceptives increased the risk of stroke 2.0 times (95% CI 1.2 to 3.5). The risk of stroke in women using third-generation oral contraceptives was not different from that in women using second-generation oral contraceptives (odds ratio 1.0, 95% CI 0.6 to 1.8). CONCLUSIONS: Third-generation oral contraceptives (containing desogestrel or gestodene) confer the same risk of first ischemic stroke as second-generation oral contraceptives (containing levonorgestrel).

Increased pregnancy loss in young women with aortoiliac disease.

BACKGROUND: During clinical evaluation of young women with peripheral arterial occlusive disease, we were surprised by the high prevalence of pregnancy loss in women with segmental stenosis confined to the aortoiliac segment. We wondered if increased occurrence of miscarriage is the result of high expression of vascular and obstetrical risk factors in these patients, or if it is related to localization of disease. In a case-control study designed to investigate risk factors for peripheral arterial occlusive disease in young women, we assessed the risk of miscarriage in these patients according to level of obstruction. METHODS: A total of 202 female patients, aged 18-49 years and 466 healthy control women from a population based case-control study, donated venous blood samples and filled out a structured questionnaire concerning classical cardiovascular risk factors and obstetrical history. In all patients, diagnosis of peripheral arterial occlusive disease was confirmed by intra-arterial angiography. Patients were classified into two groups: those with and those without stenosis of the aortoiliac segment (aortoiliac disease). RESULTS: In 77 of the 202 patients (38%) with peripheral arterial occlusive disease, the obstruction was confined to the aortoiliac segment. The occurrence of miscarriage was high (42%) in young women with aortoiliac disease. Compared to healthy controls, the risk of miscarriage increased 3-fold (OR 3.1; 95% CI 1.8-5.6) in these patients. Adjustment for obstetrical and vascular risk factors did not affect the risk estimate. CONCLUSION: This is the first study that identifies aortoiliac disease as a risk factor for pregnancy loss in young women. The risk of miscarriage is increased 3-fold in women with aortoiliac disease. The presence of vascular and obstetrical risk factors did not affect the strength of the association. Pregnancy loss could be the first sign of insufficient aortic circulation in these patients.

Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus infections and the risk of peripheral arterial disease in young women.

Sero-epidemiological case control studies have observed positive relations between infections with Chlamydia pneumoniae, Helicobacter pylori or cytomegalovirus (CMV) and the occurrence of coronary artery disease (CAD) and stroke. Moreover, positive relations between 'infection burden' and CAD and the role of inflammation have recently been described. However, the relations between infection, inflammation and the occurrence of peripheral arterial disease (PAD) have not been reported so far. We performed a multi-centre population-based case-control study, using serum samples of 228 young female PAD patients and 643 control women to determine IgG antibody titres and C-reactive protein. The odds ratios for PAD in women with serological evidence for infection with C. pneumoniae, H. pylori or CMV were 2.0 (95% CI; 1.3-3.1), 1.6 (95% CI; 1.1-2.2) and 1.6 (95% CI; 1.1-2.3), respectively. The cumulative number of infections was positively related to the risk of PAD; the odds ratio was 1.5 (95% CI; 1.0-2.4), 2.7 (95% CI; 1.6-4.4) and 3.5 (95% CI; 1.5-8.1) for women with one, two or three infections, respectively. This increased risk, related to the 'infection burden', was found again in the subgroup of women with a high CRP level, but not in the subgroup with a low CRP level. Infections might be a causal component in the development of PAD. The risk of PAD is not only related to a single pathogen in particular, but also to the cumulative number of infections. The positive relation between 'infection burden' and PAD was only found in women with a high CRP level, which indicates that inflammation might be involved in the process that leads to PAD.

Novel risk factors for peripheral arterial disease in young women.

PURPOSE: To investigate traditional and novel risk factors (homocysteine and C-reactive protein levels, and exposure to infections) for peripheral arterial disease in young women. SUBJECTS AND METHODS: In a multicenter, population-based, case-control study, 212 young women (mean [+/- SD] age, 48.2 +/- 7.0 years) with peripheral arterial disease and 475 healthy control women (mean age, 45.5 +/- 8.1 years) completed a standardized questionnaire and provided blood samples. Peripheral arterial disease was angiographically confirmed if a stenotic lesion (more than 50% reduction of the lumen) was present in at least one major peripheral artery. Hyperhomocysteinemia was defined as a nonfasting plasma homocysteine level exceeding the 90th percentile of the control group. History of infectious diseases was determined by questionnaire. RESULTS: Elevated C-reactive protein levels were associated with an increased likelihood of peripheral arterial disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.8 to 8.5 for women in the third quartile; OR = 3.1; 95% CI: 1.4 to 6.8 for women in the fourth quartile; both comparisons with women in the first quartile). Hyperhomocysteinemia was not associated with a significantly increased risk of peripheral arterial disease (OR = 1.6; 95% CI: 0.9 to 3.0). A history of chickenpox, shingles, mumps, pneumonia, chronic bronchitis, peptic ulcer, or periodontitis was independently related to peripheral arterial disease, with adjusted odds ratios varying from 1.7 (95% CI: 1.0 to 3.1) for mumps to 3.4 (95% CI: 1.5 to 7.7) for peptic ulcer. The risk of peripheral arterial disease increased with the number of these infections; exposure to five or more infections increased the odds 3.7-fold (95% CI: 1.7 to 8.2). This association was not affected by the level of C-reactive protein. CONCLUSION: Our results do not support a strong relation between homocysteine and peripheral arterial disease in young women. However, an elevated C-reactive protein level and several types of symptomatic infection were associated with peripheral arterial disease.

Disease burden of foodborne pathogens in the Netherlands, 2009.

To inform risk management decisions on control, prevention and surveillance of foodborne disease, the disease burden of foodborne pathogens is estimated using Disability Adjusted Life Years as a summary metric of public health. Fourteen pathogens that can be transmitted by food are included in the study (four infectious bacteria, three toxin-producing bacteria, four viruses and three protozoa). Data represent the burden in the Netherlands in 2009. The incidence of community-acquired non-consulting cases, patients consulting their general practitioner, those admitted to hospital, as well as the incidence of sequelae and fatal cases is estimated using surveillance data, cohort studies and published data. Disease burden includes estimates of duration and disability weights for non-fatal cases and loss of statistical life expectancy for fatal cases. Results at pathogen level are combined with data from an expert survey to assess the fraction of cases attributable to food, and the main food groups contributing to transmission. Among 1.8 million cases of disease (approx. 10,600 per 100,000) and 233 deaths (1.4 per 100,000) by these fourteen pathogens, approximately one-third (680,000 cases; 4100 per 100,000) and 78 deaths (0.5 per 100,000) are attributable to foodborne transmission. The total burden is 13,500 DALY (82 DALY per 100,000). On a population level, Toxoplasma gondii, thermophilic Campylobacter spp., rotaviruses, noroviruses and Salmonella spp. cause the highest disease burden. The burden per case is highest for perinatal listeriosis and congenital toxoplasmosis. Approximately 45% of the total burden is attributed to food. T. gondii and Campylobacter spp. appear to be key targets for additional intervention efforts, with a focus on food and environmental pathways. The ranking of foodborne pathogens based on burden is very different compared to when only incidence is considered. The burden of acute disease is a relatively small part of the total burden. In the Netherlands, the burden of foodborne pathogens is similar to the burden of upper respiratory and urinary tract infections.

Comparison of the tolerability of an acellular pertussis-containing vaccine given as the fifth booster dose in differently primed children.

BACKGROUND: In 2005, an acellular pertussis-containing DTP-IPV-Hib vaccine for infants replaced the whole-cell combination vaccine in the National Immunisation Programme of the Netherlands. From 2008 onwards, an increase in local reactions to boosters was seen in an enhanced passive reporting system of adverse events following immunisation. METHOD: A cross-sectional study was conducted to assess the difference in tolerability of a DTaP-IPV booster in four-year-old children primed in infancy with either three doses DTaP-IPV-Hib (aP-primed) or three doses of DTwP-IPV-Hib (wP-primed). Parents were asked to report in a questionnaire the local reactions and systemic adverse events that developed within one week after booster administration. RESULTS: Children in the aP-primed group experienced significantly more local reactions (36.1% versus 58.5%; OR 2.7; 95% CI 2.2-3.3) and also more systemic events (11.0% versus 20.6%; OR 2.2; 95% CI 1.6-3.0) after the DTaP-IPV booster than wP-primed children. Besides, aP-primed children more often used acetaminophen (13.1% versus 6.7%); were more frequently absent from school, preschool, crèche or other activities (4.2% versus 1.5%), and more often had contact with the healthcare system (4.5% versus 1.6%) within one week after the booster than wP-primed children. CONCLUSION: The frequency of adverse events after DTaP-IPV booster immunisation in four year old children is higher in children primed with DTaP-IPV-Hib than in children primed with DTwP-IPV-Hib. However, for primary and booster vaccinations together, immunisation with acellular pertussis combination vaccines results in fewer adverse events than vaccination of whole cell combination vaccines. So, both the effectiveness and adverse events needs consideration in the discussion with regard to optimal timing of booster dose of DTaP-IPV.

[Safety of the bivalent human papillomavirus vaccine--results following administration of more than 192,000 doses]. / Veiligheid van bivalent Humaan papillomavirus-vaccin: resultaten na toediening van ruim 192.000 doses.

AIM: To study the safety profile of the bivalent human papillomavirus (HPV) vaccine following administration of a first dose to 192,119 13-16-year-old girls in the context of a catch-up campaign. DESIGN: Descriptive. METHODS: The safety of the HPV campaign underwent surveillance in three ways: via a spontaneous reporting system, whereby anyone could report a possible undesirable effect; following completion and validation a diagnosis was made and the causal relationship with the vaccination assessed. Secondly, general healthcare service (GGD) physicians reported effects that occurred during the vaccination sessions. Thirdly, we conducted a questionnaire survey of frequent possible side effects, in which we asked about effects that occurred up to 1 week after the vaccine. RESULTS: 446 reports were received via the spontaneous reporting system (degree of reporting: 23.2:10,000). 16% of reports were mainly local effects; 84% were systemic effects, including 8 severe effects. 157 girls consulted their general practitioner or went to a hospital (degree of reporting: 8:10,000). 59% of the reports were of a side effect; in 41% a concurrent event was coincidental. There were 638 reports during the vaccination sessions (degree of reporting 45:10,000). The largest number were vasovegetative effects, including fainting or near-fainting (n = 569; degree of reporting: 40:10,000). The degree of reporting of tightness of the chest or skin effects was 2:10,000. The assistance of a general practitioner or ambulance was summoned for 10 girls (degree of reporting: 0.7:10,000). The questionnaire study (response 68.7%; n = 3646) showed that 92.1% of the girls had local effects. In 1.6% these symptoms were severe. Systemic effects occurred in 91.7%; 0.7% had fever (>or= 39.5 degrees C). 1.5% of girls called for medical assistance. CONCLUSION: During intensive surveillance of safety of the HPV campaign, no unexpected or serious side effects with a causal relationship with the vaccination occurred following administration of 192,119 doses. In accordance with data from foreign studies, side effects may be common, but are in general mild and short-lived.

Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial.

A plausible mechanism to explain thrombotic risk differences associated with the use of second- and third-generation oral contraceptives (OCs), particularly in carriers of factor V(Leiden), is still lacking. In a double-blind trial, 51 women without and 35 women with factor V(Leiden) were randomized to either a second- (30 microg ethinylestradiol/150 microg levonorgestrel) or third- (30 microg ethinylestradiol/150 microg desogestrel) generation OC. After 2 cycles of use and a wash-out of 2 cycles, the participants continued with the corresponding progestagen-only preparation. Hemostatic variables that probe the activity of the anticoagulant protein C system were determined. Compared with levonorgestrel, desogestrel-containing OCs significantly decreased protein S and increased activated protein C (APC) resistance in both groups. OCs with desogestrel had the most pronounced effects in carriers of factor V(Leiden). Progestagen-only preparations caused changes of anticoagulant parameters opposite to those of combined OCs, which in a number of cases were more pronounced with levonorgestrel. Our data show that progestagens in combined OCs counteract the thrombotic effect of the estrogen component. The higher thrombotic risk associated with third-generation OCs compared with second-generation OCs may be explained by the fact that desogestrel appeared less antithrombotic than levonorgestrel, especially in women with factor V(Leiden).

Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction.

We investigated the effect of prothrombotic coagulation defects in combination with smoking and other conventional risk factors on the risk of myocardial infarction in young women. In 217 women with a first myocardial infarction before the age of 50 years and 763 healthy control women from a population-based case-control study, factor V Leiden and prothrombin 20210A status were determined. Data on major cardiovascular risk factors and oral contraceptive use were combined with the presence or absence of these prothrombotic mutations, and compared between patients and controls. The overall odds ratio for myocardial infarction in the presence of a coagulation defect was 1.1 [95% confidence interval (CI) 0.6-1.9]. The combination of a prothrombotic mutation and current smoking increased the risk of myocardial infarction 12-fold (95% CI 5.7-27) compared with non-smokers without a coagulation defect. Among women who smoked cigarettes, factor V Leiden presence versus absence increased the risk of myocardial infarction by 2.0 (95% CI 0.9-4.6), and prothrombin 20210A presence versus absence had an odds ratio of 1.0 (95% CI 0.3-3.5). We conclude that factor V Leiden and prothrombin 20210A do not add substantially to the overall risk of myocardial infarction in young women. However, in women who smoke, the presence of factor V Leiden increased the risk of myocardial infarction twofold.