Abstract: Healthcare workers (HCWs) are at increased risk of exposure to tuberculosis (TB). Traditionally, screening for latent TB infection (LTBI) is done using the tuberculin skin test (TST). Interferon-gamma release assays (IGRAs) are now increasingly being used for diagnosis of LTBI, but their role in HCW screening is unclear. A systematic review was conducted of all IGRA studies in HCWs to summarise their performance in cross-sectional and serial testing settings. By searching four electronic databases and other sources, all available studies using any one of the commercial IGRA assays in HCWs were retrieved and screened. 50 unique studies were identified which met the inclusion criteria including five from high TB incidence settings. Among 24 cross-sectional studies in low TB incidence settings, the pooled prevalence of positive IGRA using either test was significantly lower than for a positive TST. However, in high-incidence settings (n=2) there were no consistent differences in the prevalence of positive tests. IGRAs showed good correlation with occupational risk factors for TB exposure in low-incidence settings. Only 10 studies assessed use of IGRA for serial testing and all showed large variation in the rates of conversions and reversions, with no data suggesting that IGRAs are better at identifying the incidence of new TB infection than the TST. The use of IGRAs instead of TST for one-time screening may result in a lower prevalence of positive tests and fewer HCWs who require LTBI treatment, particularly in low TB incidence settings. However, the use of IGRAs for serial testing is complicated by lack of data on optimum cut-offs for serial testing and unclear interpretation and prognosis of conversions and reversions. Further longitudinal research will be required to inform guidelines on serial testing using IGRAs.
Abstract: Cooperation between different public and private health institutes involved in tuberculosis (TB) control has proven to enhance TB control in different settings. In China, such a mechanism has not been set up yet between Centers for Disease Control (CDCs) and university hospitals despite an increased TB incidence among students. This study aims to improve arrival of TB suspects identified by universities at the CDCs in order to manage them under standardized, directly observed treatment-short course (DOTS) conditions according to the National Tuberculosis Programme (NTP) guidelines.
Abstract: ABSTRACT: BACKGROUND: We carried out an investigation in five provinces in China to assess treatment adherence and identify factors associated with insufficient treatment adherence in tuberculosis (TB) patients in mountainous, rural areas of China. METHODS: In each of the five provinces, all counties with >80% mountainous area were stratified into three groups according to their gross domestic product. In each stratum, one county was randomly sampled. Study subjects were sampled from all smear positive TB cases registered in 2007 in the target counties. TB patients, village doctors, county doctors and directors of the TB prevention and control institutes were interviewed. Insufficient medication adherence was defined as taking less than 90% of anti-TB drug doses prescribed. Insufficient re-examination adherence was defined as having less than the recommended three sputum smear examinations during the treatment course. RESULTS: A minority of patients took drugs under direct observation: on average 29% during the intensive phase of treatment. In total, 524 TB patients were included, of whom 49 (9.4%) took less than 90% of all doses prescribed and 92 (17.6%) did not have all sputum smear examinations, with substantial variations between the provinces. In multivariable analysis, no direct observation of treatment during the intensive phase and the presence of adverse events were associated both with insufficient medication adherence and insufficient re-examination adherence. Overall, 79% of patients were adherent both to treatment and re-examinations. CONCLUSIONS: In these remote and poor areas of China, the TB control program is not fully functioning according to the guidelines. The majority of patients are not treated under direct observation, while direct observation by health care staff was associated with better adherence, both to drug therapy and re-examinations. Insufficient adherence increases the risk of unsuccessful treatment outcomes and development of drug resistance. Measures should be taken urgently in these areas to strengthen implementation of the international Stop TB strategy.
Abstract: Tuberculosis (TB) transmission is associated with patient-related risk factors. However, DNA fingerprint analysis has provided anecdotal evidence suggesting a role for bacteriological factors.
Abstract: This investigation of tuberculosis (TB) treatment regimens in 6 TB hospitals in China showed that only 18% of patients with new cases and 9% of patients with retreatment cases were prescribed standard TB treatment regimens. Adherence to treatment guidelines needs to be improved in TB hospitals to control multidrug-resistant TB in China.
Abstract: We conducted a case-control study to investigate risk factors for multidrug-resistant tuberculosis (MDR TB) in the People's Republic of China. Genotyping analysis was used to estimate the percentage of cases from recent transmission among 100 MDR TB case-patients hospitalized during April 2007-July 2009. Molecular subtyping of isolates showed that 41% of MDR TB strains clustered. Beijing genotype was found in 94% of the MDR TB isolates and 79% of the pan-susceptible isolates. In multivariate analysis, MDR TB was independently associated with Beijing genotype, retreatment for TB, symptoms lasting >3 months before first evaluation at the hospital, lack of health insurance, and being a farmer (vs. being a student). MDR TB was associated with Beijing genotype and lower socioeconomic status. A large percentage of MDR TB cases seemed to result from recent transmission. Early detection, effective treatment, and infection control measures for MDR TB are needed to reduce transmission.
Abstract: Within countries, poorer populations have greater health needs and less access to good medical care than better-off populations. This is particularly true for tuberculosis (TB), the archetypal disease of poverty. Innovations also tend to become available to better-off populations well before they become available to those who need them the most. In a new era of innovations for TB diagnosis and treatment, it is increasingly important not only to be sure that these innovations can work in terms of accuracy and efficacy, but also that they will work, especially for the poor. We argue that after an innovation or a group of innovations has been endorsed, based on demonstrated accuracy and/or efficacy, introduction into routine practice should proceed through implementation by research. Cluster-randomised pragmatic trials are suited to this approach, and permit the prospective collection of evidence needed for full impact assessment according to a previously published framework. The novel approach of linking transmission modelling with operational modelling provides a methodology for expanding and enhancing the range of evidence, and can be used alongside evidence from pragmatic implementation trials. This evidence from routine practice should then be used to ensure that innovations in TB control are used for positive action for all, and particularly the poor.
Abstract: Molecular epidemiologic studies may use genotypic clustering of isolates as an indicator of recent transmission. It has been shown that missing cases lead to underestimating clustering, and modelling studies suggested that they may also lead to underestimating odds ratios for clustering. Using a national, comprehensive database from the Netherlands covering 15 years between 1993 and 2007 and including over 12,000 patients and their isolates, the authors determined the effects of sampling at random, in time, and by geographic area. As expected, sampling reduced the observed clustering percentages. However, sampling did not reduce the observed odds ratios for clustering. The main explanations for this discrepancy with model outcomes were that a substantial proportion of clustered cases were found in large clusters and that risk factors for clustering tended to be-among clustered cases-also risk factors for large clusters. The authors conclude that, in settings where risk factors for clustering may be interpreted as risk factors for recent transmission, these risk factors are also associated with larger cluster sizes. As a result, odds ratios would show limited sampling bias.
Abstract: Yunnan province in China has a high tuberculosis (TB) burden. Cure rates in general are high, but they were below the target of 85% in 26 out of 129 counties in 2005. In these 26 counties we assessed which patient-related and treatment-related factors were associated with non-cure.
Abstract: This study aimed to determine to what extent tuberculosis trends in the Netherlands depend on secular trend, immigration and recent transmission. Data on patients in the Netherlands Tuberculosis Register in the period 1993-2007 were matched with restriction fragment length polymorphism (RFLP) patterns of Mycobacterium tuberculosis isolates. Index patients were defined as patients with pulmonary tuberculosis whose isolates had RFLP patterns not observed in another patient in the previous 2 yrs. Among 8,330 patients with pulmonary tuberculosis the isolates of 56% of native and 50% of foreign-born patients were clustered. Of these, 5,185 were included in detailed analysis: 1,376 native index patients, 2,822 foreign-born index patients and 987 secondary cases within 2 yrs of diagnosis of the index case. The incidence of native and foreign-born index patients declined by 6% and 2% per year, respectively. The number of secondary cases per index case was 0.24. The decline of native cases contributed most to the overall decline of tuberculosis rates and was largely explained by a declining prevalence of latent infection. Tuberculosis among immigrants was associated with immigration figures. Progress towards elimination of tuberculosis would benefit from intensifying diagnosis and treatment of latent infection among immigrants and global tuberculosis control.
Abstract: Health care delivery is particularly problematic in fragile states often connected with increased incidence of communicable diseases, among them tuberculosis. This article draws upon experiences in tuberculosis control in four fragile states from which four lessons learned were derived.
Abstract: Ghana has not conducted a national tuberculin survey or tuberculosis prevalence survey since the establishment of the National Tuberculosis Control Programme. The primary objective of this study was therefore to determine the prevalence of tuberculin skin sensitivity in Ghanaian school children aged 6-10 years in 8 out of 10 regions of Ghana between 2004 and 2006.
Abstract: The directly observed therapy-short course (DOTS) strategy was introduced in Shaanxi province, China to improve tuberculosis (TB) control by means of improved case detection (target: > = 70%) and treatment success rates (target: > = 85%) in new smear positive (SS+) TB patients. At a provincial level the targets were both reached in 2005. However in 30 (28%) out of 107 counties of Shaanxi province the cure rate was below 85%. This study aimed to investigate patient and treatment characteristics associated with non-cure after tuberculosis (TB) treatment in these counties.
Abstract: To assess the availability of second-line drugs (SLDs) and the use of drug susceptibility testing (DST) results for the treatment of tuberculosis (TB) in China.
Abstract: In 2004, an anti-tuberculosis (TB) drug resistance survey in Heilongjiang province, China, enrolled 1574 (79%) new and 421 (21%) retreatment patients. Multi-drug resistant (MDR) TB was detected in 7.2% of new and 30.4% of retreatment patients. All received treatment with standardized first-line drug (FLD) regimens.
Abstract: The Tuberculosis Surveillance and Research Unit (TSRU) held its last annual meeting in Helsinki, Finland, from 1 to 4 April 2008. Several topics of current interest for tuberculosis (TB) research and new research projects were presented and discussed in depth by 60 delegates from Europe, Africa and Asia. This paper summarises some of the highlights of the meeting which may be of interest to epidemiologists and managers active in the field of TB.
Abstract: Clostridium difficile-associated diarrhoea (CDAD) presents mainly as a nosocomial infection, usually after antimicrobial therapy. Many outbreaks have been attributed to C. difficile, some due to a new hyper-virulent strain that may cause more severe disease and a worse patient outcome. As a result of CDAD, large numbers of C. difficile spores may be excreted by affected patients. Spores then survive for months in the environment; they cannot be destroyed by standard alcohol-based hand disinfection, and persist despite usual environmental cleaning agents. All these factors increase the risk of C. difficile transmission. Once CDAD is diagnosed in a patient, immediate implementation of appropriate infection control measures is mandatory in order to prevent further spread within the hospital. The quality and quantity of antibiotic prescribing should be reviewed to minimise the selective pressure for CDAD. This article provides a review of the literature that can be used for evidence-based guidelines to limit the spread of C. difficile. These include early diagnosis of CDAD, surveillance of CDAD cases, education of staff, appropriate use of isolation precautions, hand hygiene, protective clothing, environmental cleaning and cleaning of medical equipment, good antibiotic stewardship, and specific measures during outbreaks. Existing local protocols and practices for the control of C. difficile should be carefully reviewed and modified if necessary.
Abstract: The first Dutch outbreak due to Clostridium difficile ribotype 027 was observed in mid-2005; by the end of that year, eight hospitals were affected. To study the relationship between hospital-wide antibiotic use and the incidence of 027-linked C. difficile-associated disease (CDAD) three study groups were made: group A, all eight hospitals with an 027-associated epidemic; group B, five of a total of six hospitals with occasional 027 cases, without an increase in CDAD; and group C, ten randomly selected hospitals with no reported 027 epidemics or isolated 027 cases. Quarterly data on CDAD incidences, hygiene measures and the use of fluoroquinolones, second- and third-generation cephalosporins, extended-spectrum penicillins, penicillins with beta-lactamase inhibitors, carbapenems, lincomycins and macrolides were collected for 2004 and 2005, and divided into pre-epidemic and epidemic periods. Using a multilevel Poisson regression analysis, CDAD incidence was linked to antibiotic use in the previous quarter and to certain hygiene measures. In the pre-epidemic period, the total use of the studied antibiotics was comparable between affected and unaffected hospitals. Higher use of second-generation cephalosporins, macrolides and all of the studied antibiotics were independently associated with a small increase in CDAD incidence [relative risk (95% confidence interval): 1.14 per increase of 100 defined daily doses per 10,000 bed days (1.06-1.23), 1.10 (1.01-1.19) and 1.02 (1.01-1.03), respectively]. However the effect was too small to predict which hospitals might be more prone to 027-associated outbreaks.
Abstract: The emergence of drug-resistant tuberculosis (TB) hampers TB control. Ten provinces in China performed drug resistance surveys among tuberculosis (TB) patients in 1996-2004 to assess levels of drug resistance.
Abstract: To describe how continuous validation of data on surgical site infection (SSI) is being performed in the Dutch National Nosocomial Infection Surveillance System (Preventie Ziekenhuisinfecties door Surveillance [PREZIES]), to assess the quality and accuracy of the PREZIES data, and to present the corresponding outcomes of the assessment.
Abstract: As there has been increasing interest in comparing surgical site infection (SSI) rates between countries, we compared the SSI surveillance data for The Netherlands ('PREZIES') and Germany ('KISS'). Both surveillance systems have comparable protocols with many similar risk factors, including SSI definitions developed by the Centers for Disease Control and Prevention and optional postdischarge surveillance. Nine surgical procedure categories from several specialities were included, the reporting of which were similar, with respect to content and with enough data for proper comparison. Differences for the SSI data were found between PREZIES and KISS for duration of surgery, wound contamination class, American Society of Anesthesiologists physical status classification and the postoperative duration of hospitalization. A significantly higher superficial SSI rate was found for seven surgical procedures according to PREZIES and a higher deep SSI rate for five procedures. When considering only deep SSI during hospitalization, the differences in SSI rates were much smaller. Differences in intensity of postdischarge surveillance led to 34% of SSI being detected after discharge for PREZIES and 21% for KISS. In conclusion, even though similar infection surveillance protocols are used in The Netherlands and Germany, differences occurred in the implementation. Comparisons between countries are most reliable if only deep SSIs during hospitalization are taken into account, since these SSI are not affected by postdischarge surveillance and the diagnostic sensitivity for deep SSI is probably more alike between countries than for superficial SSI.
Abstract: After reports of emerging outbreaks in Canada and the United States, Clostridium difficile-associated disease (CDAD) due to polymerase chain reaction ribotype 027 was detected in 2 medium-to-large hospitals in The Netherlands in 2005.
Abstract: We studied the epidemiology of varicella (chickenpox) and herpes zoster (shingles) in The Netherlands to assess the desirability to implement routine varicella zoster virus vaccination in The Netherlands. Data on seroprevalence of varicella zoster virus in the general population (1995-1996), consultations of general practitioners for varicella (2000-2002) and herpes zoster (1998-2001) and hospital admissions due to varicella (1994-2001) and herpes zoster (1994-2001) in The Netherlands were analysed. The seropositivity increased sharply with age from 18.4% for both 0- and 1-year-olds, to 48.9%, 59.0%, 75.7% and 93.0% for 2-, 3-, 4- and 5-year-olds, respectively, and varied between 97.5% and 100% for older age groups. The average annual incidence of GP-consultations amounted to 253.5 and 325.0 per 100,000 for varicella and herpes zoster, respectively. The incidence of hospital admission due to varicella and herpes zoster was 1.3 (2.3 including side diagnosis) and 2.7 (5.8) per 100,000, respectively. Whilst for varicella, the incidence of GP-consultations and hospital admissions were highest in childhood, for herpes zoster, these were highest in elderly. Insight into epidemiology of varicella zoster is needed for the assessment of the desirability of introduction of routine varicella zoster vaccination.
Abstract: In the Dutch surveillance for surgical site infections (SSIs), data from 70277 orthopaedic procedures with 1895 SSIs were collected between 1996 and 2003. The aims of this study were: (1) to analyse the trends in SSIs associated with Gram-positive and Gram-negative bacteria; (2) to estimate patient-related risk factors for deep and superficial SSIs after all orthopaedic procedures, with special attention to primary total hip arthroplasty (THA); and (3) to analyse inherent differences in infection risk between hospitals. A random effect model was used to estimate the odds ratios of patient-related risk factors for developing an SSI, and to describe the distribution of the most widespread bacterial species responsible for SSIs among hospitals. Gram-positive organisms, mainly staphylococci, were the main cause of both deep (84.0%) and superficial SSIs (69.1%) after orthopaedic procedures. The percentage of SSIs after THA caused by coagulase-negative staphylococci decreased over the surveillance period, while the contribution of Staphylococcus aureus increased. Temporary elevations in the incidence of the most widespread pathogen species were observed within hospitals. Patient-related factors such as the National Nosocomial Infections Surveillance System risk index or age had little effect on the predictive power of the random effect models. This study underlines the usefulness of a random effect model, which adjusts risk estimates for random variation between hospitals, in a multicentre study on risk factors for SSIs.
Abstract: Outbreaks due to Clostridium difficile polymerase chain reaction (PCR) ribotype 027, toxinotype III, were detected in 7 hospitals in the Netherlands from April 2005 to February 2006. One hospital experienced at the same time a second outbreak due to a toxin A-negative C. difficile PCR ribotype 017 toxinotype VIII strain. The outbreaks are difficult to control.
Abstract: To compare the number of surgical site infections (SSIs) registered after hospital discharge with respect to various surgical procedures and to identify the procedures for which postdischarge surveillance (PDS) is most important.
Abstract: 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.
Abstract: Recurrent otitis media may be related to defects in specific antibody production, as suggested previously. This might be reflected in lower antibody responses to vaccinations administered in the context of the national childhood vaccination program in children suffering from recurrent otitis media. In a cross-sectional study we determined the levels of antidiphtheria, antitetanus, anti- Haemophilus influenzae type b (anti-Hib) and antimeasles antibodies in sera of 163 children with two or more episodes of acute otitis media per year and in 143 children with repeated periods of persistent otitis media with effusion each lasting at least 3 months. The control group consisted of 521 age-matched healthy children, who were free of recurrent respiratory tract infections. Children with recurrent acute otitis media, including highly otitis-prone children, showed higher antidiphtheria and antitetanus antibody titers compared to controls. No differences were observed in anti-Hib and antimeasles antibody levels between children with recurrent acute otitis media and controls, nor did any of the antibody levels in children with persistent otitis media with effusion differ from those in controls. Therefore, the results of our study do not point toward a generalized immunological hyporesponsiveness in children with recurrent acute otitis media and persistent otitis media with effusion. Determination of antibody responses to regular vaccines is not indicative for otitis-proneness.
Abstract: We present a stochastic model for the spread of smallpox after a small number of index cases are introduced into a susceptible population. The model describes a branching process for the spread of the infection and the effects of intervention measures. We discuss scenarios in which ring vaccination of direct contacts of infected persons is sufficient to contain an epidemic. Ring vaccination can be successful if infectious cases are rapidly diagnosed. However, because of the inherent stochastic nature of epidemic outbreaks, both the size and duration of contained outbreaks are highly variable. Intervention requirements depend on the basic reproduction number (R0), for which different estimates exist. When faced with the decision of whether to rely on ring vaccination, the public health community should be aware that an epidemic might take time to subside even for an eventually successful intervention strategy.
Abstract: We investigated which vaccination schedule gives best protection to the vaccinating population, in case of a measles epidemic in pockets of unvaccinated individuals. We explored the effect of an additional measles vaccination (at 6 or 9 months), advancing the first measles-mumps-rubella (MMR) vaccination from 14 to 11 months, and advancing the second MMR from 9 to 4 years. Measures of protection among vaccinees (percentage of susceptibles, number of reported cases, percentage of lifetime spent susceptible) were estimated with a mathematical model of the impact of antibody level on seroconversion and immunity. Advancing the age of second MMR vaccination prevents considerably more cases among vaccinees than an extra early measles vaccination or advancing the age of first MMR vaccination.
Abstract: The immunity to vaccine-preventable diseases included in the Dutch immunisation programme in the general population and among orthodox reformed individuals who refuse vaccination was assessed. The programme induces good protection. However, a large proportion of adults lacks diphtheria and tetanus immunity. Measles, mumps and rubella seroprevalence was somewhat lower among vaccinated compared to unvaccinated cohorts. The prevalence of HibPS antibodies declined during 2.5 years after the fourth vaccination. However, protection occurs also by memory immunity. Herd immunity is sufficient among the general population, but not among orthodox reformed individuals. Immunosurveillance is an efficient way to evaluate the effects of immunisation programmes and identify risk groups for infection.
Abstract: To describe the initial effects of the large-scale vaccination campaign in June-July of 2002 (1-5- and 15-18-year-olds) and September-November of 2002 (6-14-year-olds) on the incidence of group-C meningococcal disease in the Netherlands.
Abstract: We evaluated different approaches for diagnosing measles virus (MV) infection in unvaccinated children and in healthy contact persons (n=194) during a measles epidemic in The Netherlands. MV RNA was detected by reverse-transcriptase polymerase chain reaction in throat-swab specimens from 93% of the patients with clinical symptoms. MV RNA was detected from 5 days before until 12 days after the onset of symptoms. Most patients (88%) also secreted MV RNA in their urine until 5 weeks after the onset of symptoms. Oral fluid proved to be the most practical specimen for the simultaneous detection of MV-specific IgM antibody and viral RNA, which, together, confirmed 93% of measles cases. Viral RNA was also detected in oropharyngeal specimens from 3 healthy contact persons with serological proof of MV infection. The results of this study emphasize the feasibility of combined detection of viral RNA and MV-specific IgM antibodies in oropharyngeal specimens for the diagnosis of clinical and subclinical MV infection.
Abstract: Six countries (Denmark, England and Wales, France, Germany, Italy and The Netherlands) conducted large serological surveys for mumps, in the mid-1990s, as part of the European Sero-Epidemiology Network (ESEN). The assay results were standardized and related to the schedules and coverage of the immunization programmes and the reported incidence of mumps. Low incidence of disease and few susceptibles amongst adolescents and young adults was observed in countries with high mumps vaccine coverage (e.g. The Netherlands). High disease incidence and large proportions of mumps virus antibody negative samples in adolescent and young adult age groups was noted in countries with poor vaccine coverage (e.g. Italy). The build-up of susceptibles in older children and adolescents in England and Wales, France, the former West Germany and Italy indicate the possibility of further mumps outbreaks in secondary school environments. To control mumps in western Europe, current MMR immunization programmes will need to be strengthened in a number of countries. Sero-surveillance of mumps is an important component of disease control and its usefulness will be enhanced by the development of an international mumps standard.
Abstract: To obtain insight into mumps immunity 9 years after introduction of vaccination in The Netherlands, antibodies were measured in a national sample (n = 8298) and in clustered religious groups with low vaccine acceptance (n = 254). All sera were tested by indirect ELISA, and agreement with neutralization assay was assessed in a subsample (n = 623). Overall seroprevalence in the adult age groups in the national sample was 96.2% (95% confidence interval 95.4-97.0%). Seroprevalence was somewhat lower in the vaccinated age groups, but still sufficient to maintain herd immunity. After the first dose of vaccine, an increase up to age three years to 93.2% (89.8-96.6%) and a subsequent decline in prevalence to 88.9% (81.7-96.0%) at age 7 years was seen. Seroprevalence in those eligible for two vaccinations was 94.4% (91.3-97.4%). In the religious groups, seroprevalence was generally lower in the age group 1-4 years (30% (18-95%)) than in the national sample, but similar in the older age groups. Seroprevalence as estimated by neutralization assay was only slightly lower for all age groups > or = 1 year. Therefore, the indirect ELISA is a reliable method for measuring mumps virus-specific antibodies in population-based studies. However, to allow for inter-laboratory comparison, international unitage should be developed.
Abstract: We assessed whether measles virus-specific antibody levels in the Dutch population as estimated by an enzyme-linked immunosorbent assay (ELISA) were comparable with estimates by virus neutralisation assay (NT), prompted by a relatively low ELISA seroprevalence in the 10-21-year-old group. We tested 791 sera from individuals aged 2-49 years both in ELISA and NT. Seroprevalence in the 10-21-year-old group was 93.4% (95% confidence interval (CI) 89.5-97.2%) in ELISA versus 97.2% (CI 94.7-99.6%) in NT. There was good agreement between NT and ELISA seroprevalences in the vaccinated 2-9-year-olds and the unvaccinated 22-49-year-olds.
Abstract: We investigated which vaccination schedule gives best protection to the vaccinating population, in case there is a measles epidemic in an area with low vaccine coverage. We considered combinations of an early measles vaccination (none, at 6 months or at 9 months), a measles-mumps-rubella (MMR) vaccination around the first birthday (at either 11 or 14 months), and MMR vaccination at an older age (at either 4 or 9 years). The different estimates on measures of protection (percentage of susceptibles, number of reported cases in an epidemic year, percentage of lifetime spent susceptible) relied on a mathematical model of decline of maternal antibody levels with age, and the impact of that antibody level on seroconversion and immunity. Model parameters were estimated from a Dutch population-based serological survey on measles antibodies. Different measures of protection favoured different vaccination schedules, but dropping the age of second MMR vaccination prevents considerably more cases than an extra early measles vaccination or dropping the age of first MMR vaccination.
Abstract: In 1999, an outbreak of Legionnaires' disease affected many visitors to a flower show in the Netherlands. To identify the source of the outbreak, we performed an environmental investigation, as well as a case-control study among visitors and a serologic cohort study among exhibitors to measure exposure to possible sources. Of 77,061 visitors, 188 became ill (133 confirmed and 55 probable cases), for an attack rate of 0.23% for visitors and 0.61% for exhibitors. Two whirlpool spas in halls 3 and 4 of the exhibition and a sprinkler in hall 8 were culture positive for Legionella pneumophila. One of three genotypes found in both whirlpool spas was identical to the isolates from 28 of 29 culture-positive patients. Persons who paused at the whirlpool spa in hall 3 were at increased risk for becoming ill. This study illustrates that whirlpool spas may be an important health hazard if disinfection fails.
Abstract: In 1999-2000, a measles epidemic occurred in The Netherlands, with 3292 reported cases; 94% of the affected patients had not been vaccinated. Only 1 patient had received 2 doses of vaccine. Three patients died, and 16% had complications. For the unvaccinated population, the incidence per 1000 inhabitants 15 months to 14 years old increased from 83 (95% confidence interval [CI], 53-113), in municipalities with vaccine coverage rates < or =90%, to 200 (95% CI, 153-247), in municipalities with coverage rates >95%; for the vaccinated population, the incidence increased from 0.2 (95% CI, 0.1-0.4) to 1.4 (95% CI, 0.9-1.9). Unvaccinated individuals were 224 times (95% CI, 148-460 times) more likely to acquire measles than were vaccinated individuals; the relative risk increased with decreasing vaccine coverage. Herd immunity outside unvaccinated clusters was high enough to prevent further transmission. More case patients came from the vaccine-accepting population living among unvaccinated clusters than from individuals who declined vaccination and who lived among the vaccine-accepting population.
Abstract: A measles epidemic occurred in the Netherlands in 1999 to 2000. We collected data on hospitalized and deceased cases to inform the public about the risks associated with measles infection.
Abstract: Even though the annual incidence rate of measles has dramatically decreased in industrialised countries since the implementation of universal immunisation programmes, cases continue to occur in countries where endemic measles transmission has been interrupted and in countries where adequate levels of immunisation coverage have not been maintained. The objective of this study is to develop a model to estimate the average cost per measles case and per adverse event following measles immunisation using the Netherlands (NL), the United Kingdom (UK) and Canada as examples.
Abstract: The European Regional Office of WHO has targeted measles for elimination from the region in 2007. Large national, age and sex stratified serological surveys of measles antibody were conducted in seven Western European countries from 1994-8 as part of the European Seroepidemiology Network. Three patterns were observed in the country-specific measles seroprofiles, ranging from (very) low susceptibility (four countries) to high susceptibility (one country). Susceptibility levels amongst 2-4-year-olds ranged from 2.9 to 29.8%, in 5-9-year-olds from 2.5 to 25% and 10-19-year-olds from 2.1% to 13.9%. A country's susceptibility profile was highly associated with vaccine coverage for the first dose. First dose coverage ranged from 91 to 97.5% for low susceptibility countries, 75 to 85% for intermediate susceptibility countries and 55% for the high susceptibility country. Only the high susceptibility country still reports epidemic measles. In low susceptibility countries, which have achieved or are very close to measles elimination, the priority will be to maintain high MMR vaccine coverage in all geopolitical units for both vaccine doses. In moderate susceptibility countries there is still some endemic transmission, but also risk of outbreaks as pools of susceptibles accumulate. In the high susceptibility country the priority will be to increase infant vaccine coverage and reduce regional variation in coverage levels.
Abstract: We assessed antibodies to the capsular polysaccharide of Haemophilus influenzae type b (HibPS) in the Dutch population a few years after a mass vaccination against H. influenzae (Hib) was begun. We observed sharp declines in the geometric mean titer (GMT) and the prevalence of HibPS antibodies at levels of < or =0.15 microg/mL in children who had received 4 doses of vaccine: from 8.65 microg/mL (prevalence, 99.4%) after 0-2 months to 0.8 microg/mL (prevalence, 83.3%) after 27-29 months. In adult groups, both the prevalence of HibPS antibodies and the GMT declined significantly with increasing age but remained high (prevalence, > or =83.7%; GMT, 0.73 > or = microg/mL). We conclude that the overall immunity in the Dutch population seems satisfactory. We draw our conclusions from the current serosurveillance study and from the sharp decline in invasive Hib disease noted after the introduction of vaccination. The key questions for the future are (1) whether Hib and cross-reacting organisms will circulate sufficiently to provide natural reexposure, and (2) how long memory immunity will persist after vaccination without reexposure.
Abstract: A 1999-2000 measles epidemic in the Netherlands started with an outbreak in an orthodox reformed elementary school with 7% vaccine coverage. The overall attack rate was 37%: 213 clinical cases among the 255 participating pupils (response 62%) and 327 household members. The attack rate ranged from 0% for the oldest groups of pupils to 88% for the youngest, who had not been exposed in previous measles epidemics. None of 25 vaccinated pupils had clinical symptoms. Among pupils with clinical symptoms, the self-reported complication rate was 25%. These data confirm that measles infection causes severe disease and that vaccination is the most effective means of preventing the disease and its complications. The data also show that clusters of persons refraining from vaccination interfere with measles elimination even in populations with very high overall vaccine coverage (96%).
Abstract: The prevalence of antibodies to hepatitis A virus was assessed in a Dutch nationwide sample (n = 7367). A questionnaire was used to study the association with various sociodemographic characteristics. Overall, 33.8% (95% CI 31.6-36%) of the population had hepatitis A antibodies. The seroprevalence was less than 10% in people under 35; it increased from 25% at 35 years to 85% at 79 years. For those 15-49 years of age, Turks (90.9%) and Moroccans (95.8%) had greater seroprevalence than autochthonous Dutch (20.2%) and other Western people (25%). Low or middle socio-economic status, as indicated by the highest educational level achieved, was associated with greater seroprevalence, independently of age and reported immunization (OR 2.11 and 1.45; 95% CI 1.67-2.67 and 1.11-1.89, respectively). These data suggest autochthonous Dutch and other Westerners born after World War II were exposed to hepatitis A during childhood less frequently than older birth cohorts. Thus, more susceptibility is likely in the coming decades. Since this means a greater risk of outbreaks in future years, and since morbidity and mortality are more frequent in older persons, studying the cost effectiveness of selective and general vaccination might be worthwhile.
Abstract: We assessed the tetanus immunity of the general Dutch population and of religious groups refusing vaccination by means of population-based study to evaluate the effect of tetanus vaccination. More than 95% of those born after the introduction of routine vaccination had tetanus antitoxin levels above the minimum protective level. After the sixth vaccination, a fall in tetanus antitoxin levels occurred. Nevertheless, immunisation in accordance with the routine programme most likely induces protection for much longer than two decades. Not only many members of religious groups who refuse vaccination, but also many adults born before the introduction of vaccination lack tetanus immunity. These cohorts might benefit most from (re)vaccination.
Abstract: A two-dose mass vaccination programme with a combined vaccine against measles, mumps and rubella (MMR) was adopted in the Netherlands in 1987, replacing the selective schoolgirl vaccination strategy introduced in 1974. To obtain insight into the effect of mass vaccination and the population's immunity, the antibody levels against rubella were studied in the general Dutch population and in religious groups refusing vaccination. In the national sample, we observed a high prevalence (96.5%) for rubella antibodies in vaccinated cohorts as well as in the older unvaccinated cohorts. No indications of rapidly waning immunity after vaccination were found. There are indications of low virus circulation in the last few years. The very high seroprevalence in women at childbearing age is consistent with the few reported cases of congenital rubella syndrome (CRS) at present. However, individuals in the age group of 1-9 years who are not vaccinated for religious or other reasons have a considerably lower seroprevalence and thus there is a potential risk of a CRS outbreak in the future.
Abstract: Serum antibodies against measles were measured in the Dutch general population and in municipalities with low vaccine coverage, where religious groups that refuse vaccination are clustered sociogeographically. The results suggest that wild measles virus may still circulate in municipalities with low vaccine coverage; the circulation in the general population seems to have decreased significantly right after the introduction of mass vaccination. The overall prevalence in the general population was high (95.7%, 95% confidence limits 95.3-96.2%); the seroprevalence in the age groups offered two vaccinations (91.7%, 95% confidence limits 89.4-94.0%) was lower than the level believed to be necessary for the elimination of measles. Protective levels of maternal antibodies in newborns have waned several months before the first vaccination is scheduled.
Abstract: Self-management plans are considered today an essential component of the management of asthma. The objective of the present study was (a) to explore patients' present practical knowledge of self-treatment of asthma, and (b) to provide an assessment of the effect of an educational program on this knowledge and self-treatment behaviour. Twenty four adults with asthma from the outpatient clinic of the Department of Pulmonary Medicine participated in a self-management program. They were provided with explanations on the symptoms and precipitating factors of their asthma, on its treatment with medication and their side-effects, and with personal written guidelines for self-adjustment of their medication. Prior to the program their practical knowledge of adequate self-treatment was investigated using a hypothetical scenario of a slow-onset asthma exacerbation. The effectiveness of the teaching and training program was evaluated by the change in knowledge prior to and 5 months after the program and self-reported behaviour of the participants at follow-up. (a) More than 60% of the patients lacked practical knowledge of self-treatment of a slow-onset exacerbation of asthma. (b) The educational program resulted in a significant increase (47%) of this knowledge. (c) Actual self-treatment behaviour, as recorded by the patients 5 months after completing the educational program, was adequate in only two of ten patients, who experienced an exacerbation during the study period. Many adults with asthma are deficient in practical knowledge of self-treatment of a slow-onset exacerbation. This knowledge was significantly augmented by an educational program. Nevertheless actual self-treatment behaviour at follow-up was inadequate in the majority of patients.