Influenza: relation of mortality to morbidity parameters--Netherlands, 1970-1989.

The purpose of this study is to investigate the relationship between the number of influenza-like illness (ILI), weekly registered by the general practitioners (sentinel stations), and the monthly overall influenza mortality in people over 60 years of age, provided by the Dutch Statistical Bureau during the period July 1970 to June 1989. The quantitative impact of influenza-morbidity is expressed by three summary parameters, calculated from the 52 (53) weekly ILI-figures per season-year, (i) their sum (i.e. global extent of an epidemic), (ii) their standard deviation, and (iii) their maximum (i.e. peak number of ILI during an epidemic). In the analysis influenza A subtype is also included. These four parameters are mutually compared with respect to their predictability for yearly total influenza mortality in the 19 season-years available. In most cases, the standard deviation and the peak number of ILI are more powerful for prediction of mortality, than the global extent of the epidemic. The peak number of ILI is of special interest. It is particularly useful for estimating the effect on current influenza mortality during an ongoing epidemic. From the model it is possible to calculate a threshold (of weekly ILI) beyond which mortality increases proportionately more than the number of illness episodes. By using the peak value of morbidity it is possible to calculate the minimal impact of epidemic mortality. This study indicates that the weekly number of influenza-like illnesses has a certain prognostic value for the real impact of influenza. An electronic surveillance system could detect immediately the threshold above which influenza mortality increases more than proportionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of influenza on mortality in relation to age and underlying disease, 1967-1989.

Based on data from the Dutch Central Bureau of Statistics, the impact of influenza on mortality in The Netherlands was estimated for a 22.5-year period (1967-1989) in four age groups and three entities of disease, using Poisson regression techniques. Our analysis suggests that, on average, more than 2000 people died from influenza in The Netherlands each year, but in only a fraction of these deaths was influenza recognized as the cause of death. For each case of death registered as caused by influenza (registered influenza mortality), 2.6 additional cases of death registered as due to causes other than influenza, nevertheless, were influenza-related (non-registered influenza mortality). Therefore, the overall impact of influenza on mortality is estimated to be greater than registered influenza mortality by a factor of 3.6. Those under 60 years of age accounted for 5% of all non-registered influenza deaths, whereas people aged 60-69, 70-79 years and > 80 years accounted for 12%, 29% and 54% of such deaths, respectively. When extrapolating the figures for the Dutch population of 1989, we could attribute, on average per season-year, 82 deaths per 100,000 people > 60 years, 143 in people > 70 years, and 280 in people > 80 years. Of all non-registered influenza cases of death, 47% were estimated to occur in people with heart disease as a primarily reported cause of death, 23% in those with lung disease, and 30% in those with other diseases. This study stresses the serious effects of influenza, mainly in the elderly (95% of non-registered influenza mortality).(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of gastroenteritis among triathletes in relation to faecal pollution of fresh waters.

BACKGROUND: We conducted a prospective cohort study among endurance athletes to investigate the effects of microbiological water quality on the risk of gastroenteritis after bathing in fresh waters that meet current water quality standards. We aimed to establish quantitative relationships, in order to evaluate current bathing water standards. METHODS: The study was spread over two summers, during which 827 triathletes (swimmers) in seven Olympic distance triathlons and 773 participants in 15 run-bike-runs (non-swimming controls) participated. Intensive water quality monitoring was used to assess exposure to faecal indicator organisms and detailed questionnaires were used to collect data on the occurrence of health complaints and potential confounding factors. RESULTS: The microbiological water quality at the time of the triathlons met current Dutch and European bathing water standards. Dependent on the case definition studied, gastroenteritis developed in 0.4-5.2% of swimmers and 0.1-2.1% of non-swimmers in the week following exposure (odds ratio [OR] = 1.6-2.3). Attack rates and burden of disease varied with the case definition used. Among swimmers, the attack rate of gastroenteritis was significantly increased when the geometric mean concentration of thermotolerant coliforms in the water at the time of exposure was > or = 220/100 ml or the geometric mean concentration of Escherichia coli was > or = 355/100 ml (OR comparing high versus low exposure 2.9-4.7 dependent on the case definition studied). Thermotolerant coliform concentrations at these triathlons ranged from 100/100 ml (the EU guide level) to 960/100 ml (the EU imperative level is 2000/100 ml). Below the threshold levels attack rates were comparable with attack rates among non-swimmers. A relation with other indicators of faecal pollution was not observed. CONCLUSIONS: We observed that swimming in fresh waters that met the European imperative level for thermotolerant coliforms but failed the European guide level was associated with a significant risk of gastroenteritis among triathletes. This means that the current European imperative level for thermotolerant coliforms provides insufficient protection to gastrointestinal illness for those who are comparable with triathletes.

An age-period-cohort analysis of 50,875 AIDS cases among injecting drug users in Europe.

BACKGROUND: The long average incubation time from HIV infection to AIDS makes it difficult to estimate recent HIV transmission from AIDS incidence data. Age-period-cohort (APC) analysis can separate out the effects of age, calendar time and birth cohort to provide a clearer picture of transmission trends. METHODS: AIDS incidence data from 1981 to 1994 among intravenous drug users (IDU) for 12 Western European countries were used. Yearly incidences per 100,000 population or 100,000 person-years were calculated by age at diagnosis and 5-year birth cohort (1950-1954, 1955-1959, 1960-1964, 1965-1969 and 1970-1974), and corrected for reporting delay. Incidence patterns were compared between birth cohorts and countries. RESULTS: For most countries the impact was greatest on the cohort born 1960-1964. Comparing incidence patterns in the 1965-1969 to 1960-1964 cohorts suggest the epidemic has plateaued at low to intermediate levels in Austria, Greece and the North-Western European countries, and at high levels in France, Italy and Switzerland. For most countries transmission amongst the 1970-1974 as compared to the 1965-1969 cohorts could not be assessed due to small numbers and short follow-up time. In Spain the epidemic was uncontrolled with a high incidence among recent birth cohorts. In Portugal the epidemic was still at an early and expanding phase. CONCLUSIONS: The APC analysis revealed large country differences in the dynamics of the HIV/AIDS epidemic among IDU. Full interpretation of these differences is dependent on information from other sources about the local public health response and trends in drug injecting behaviours. Earlier introduction of the virus and higher prevalence of injecting drug use may explain some of the generally higher incidence in Southern European countries, but the larger part of it is most likely explained by local characteristics of drug users, such as younger age and more frequent sharing of needles and syringes, and a less effective public health response.

Different demographic and sexual correlates for chlamydial infection and gonorrhoea in Rotterdam.

BACKGROUND: The objective of the study was to estimate the prevalence of gonorrhoea and chlamydial infections and to determine sexual and demographic correlates for these sexually transmitted diseases (STD) among visitors of an STD clinic. METHODS: In 1994, a cross-sectional study was carried out among 2984 consecutive visitors of the STD clinic of the University Hospital Rotterdam. RESULTS: The prevalence of chlamydial infection was 12.1% for women and 12.3% for men. For gonorrhoea, prevalence was 3.2% and 6.0%, respectively. For men, gonorrhoea was independently associated with multiple partners in the last month, homosexual activities, a history of gonorrhoea, last sexual contact in the past 4-14 days and casual partners. In contrast, chlamydial infection was less likely to be found in homosexual men and male intravenous drug users. Additionally, chlamydial infection was independently associated with young age, multiple partners in the last 6 months and with last sexual contact in the past 2 months. For women, intravenous drug use (associated with commercial sex work) and a history of trichomoniasis were independent risk factors for gonorrhoea. Independent risk factors for chlamydial infection in women were: young age, two or three sexual partners during life and last sexual contact within 2 months. Chlamydial infection was uncommon in commercial sex workers. CONCLUSIONS: The differences in the epidemiological correlates suggest that chlamydial infection is more diffusely spread into the general population than gonorrhoea. Additionally, it is hypothesized that men acquire their chlamydial infection through less stable relationships and subsequently infect their regular female partner.

Type-specific identification of influenza viruses A, B and C by the polymerase chain reaction.

The aim of this study was to develop a polymerase chain reaction for specific detection of influenza A, B, and C RNA genomes. Three primer sets were selected from conserved regions of the genome coding for the non-structural proteins and were tested on 61 influenza A (22 H1N1, 9 H2N2, and 30 H3N2), 11 influenza B, and three influenza C isolates. Specific amplified products were obtained with all these strains after electrophoresis on a 2% agarose gel. The specificity of the reaction was increased by hybridization with oligonucleotide probes. When nucleic acids from a variety of micro-organisms from the respiratory tract were subjected to the PCR with these primers, no specific amplified products were generated. The sensitivity of the technique was found to be at the subpicogram level. The RNA-PCR was applied to 21 clinical specimens from patients with a culture/IF proven influenza infection. Six influenza A positive patients and 13 influenza B positive patients could be confirmed in the RNA-PCR. In two cases, influenza B positive IF specimens were found negative by the PCR. No virus could be isolated on eggs or tissue culture from these samples. RNA-PCR is a specific and sensitive technique for the detection of influenza virus genomes.

EU conference 'The Microbial Threat'.

A global or European strategy should be developed to deal with increasing antimicrobial resistance. This strategy includes surveillance of antimicrobial resistance and monitoring of the use of antimicrobial agents in animals and humans. In animals, surveillance should be focussed on potential transfer of resistant, zoonotic, food-born pathogens and resistance genes to humans. In humans the surveillance should be clinically relevant. Guidelines for rational therapy should be implemented and 'antibiotic teams' should be installed in each hospital to evaluate the prescription of antibiotics and its compliance with guidelines. Keeping animals for food production involves the responsibility for their well being. This includes treatment of infections. However, the use of feed additive, growth-promoting antimicrobials related to therapeutics in human medicine, should be banned immediately. Research aimed at intervention strategies for antimicrobial resistance should be given a high priority with adequate financing both nationally and in Europe. Well co-ordinated European research programmes should have priority; this includes the need to install a European multidisciplinary scientific advisory group.

Antibody response to tetravalent influenza subunit vaccine in patients infected with human immunodeficiency virus type 1.

The capacity of patients infected with human immunodeficiency virus (HIV) to develop an adequate antibody response to influenza vaccination in relation to the CD4 cell count has been studied in a prospective study. A total of 73 subjects (54 HIV-infected patients and 19 healthy control persons) were vaccinated with influenza subunit vaccine containing 15 mug hemagglutinin of each of the following strains: A/Beijing/353/89(H3N2), A/Singapore/6/86(H1N1), B/Panama/45/90, and B/Beijing/1/87. Hemagglutinin inhibition (HI) antibody titers were determined prior to vaccination, 3 weeks afterwards, and at the end of the influenza season. The percentage of subjects with HI antibody titers above the assumed protective level was significantly lower in the HIV-infected patients for all 4 vaccine strains compared with those in the control group (7-26% and 42-74%, respectively). There was an association between CD4 cell count and antibody response to the B/Panama strain only. The serologic response to tetravalent subunit influenza vaccine is severely impaired in the majority of HIV-infected patients compared with control subjects. The results of this study challenges the recommendation to vaccinate HIV-infected patients.

Economic evaluation of influenza vaccination. Assessment for The Netherlands.

OBJECTIVE: The objective of this study was to determine the costs associated with influenza and the cost effectiveness (net costs per life-year gained) of influenza vaccination in The Netherlands. DESIGN AND SETTING: The economic evaluation comprised a cost-of-illness assessment and a cost-effectiveness analysis, both of which were conducted from the healthcare perspective in The Netherlands. The modelling framework for the economic evaluation linked epidemiological aspects of influenza (e.g. incidence, mortality, years of life lost) to vaccination coverage and healthcare resource use. Healthcare resource use was specified for hospitalisations, general practitioner visits and drugs. INTERVENTION: The intervention assessed in the cost-effectiveness analysis was influenza vaccination. MAIN OUTCOME MEASURES AND RESULTS: The costs of influenza were estimated to be 31 million euros (EUR) for the influenza season 1995/96 in The Netherlands (EUR1 approximately $US1.1). For the extended programme in 1997/98, i.e. all elderly people, the cost-effectiveness ratio was estimated at EUR1820 per life-year gained. Sub-group analysis demonstrated that the programme had a more favourable cost effectiveness among the chronically ill elderly population (cost saving) than among the rest of the elderly population (EUR6900 per life-year gained). CONCLUSION: Influenza vaccination has a cost-effectiveness ratio that is better than or comparable to that of other implemented Dutch programmes in the prevention of infectious diseases.

Acute respiratory failure during pneumonia induced by Sendai virus.

In this study a model of acute respiratory failure due to viral pneumonia in rats, closely resembling ARDS, is presented. Severe respiratory failure with lethal outcome in four days was induced by infection concentrated Sendai virus aerosol. This model permits evaluation of different therapeutical approaches for improving gas exchange during ARDS. Furthermore, preliminary results of surfactant substitution therapy in this model are presented.

Surveillance of respiratory pathogens and influenza-like illnesses in general practices - The Netherlands, winter 1997-98.

The Netherlands Institute of Primary Health Care (NIVEL) has coordinated the activities of a sentinel surveillance network of 43 general practices since 1970. These practices care for 1% of the Dutch population, a sample representative of the national pop

European Antimicrobial Resistance Surveillance System (EARSS): objectives and organisation.

Effective European surveillance must have the agreement and active involvement of all participants, concluded a European Union (EU) conference on the need for surveillance of resistant microorganisms (the microbial threat), held in September 1998 in De

Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial.

OBJECTIVE: To assess the frequency and type of side effects after influenza vaccination in elderly people. DESIGN: Randomised double blind placebo controlled study. SETTING: 15 general practices in the southern Netherlands. SUBJECTS: 1806 patients aged 60 or older, of whom 904 received influenza vaccine and 902 placebo. MAIN OUTCOME MEASURES: Adverse reactions reported on postal questionnaire completed four weeks after vaccination. RESULTS: 210 (23%) patients given vaccine reported one or more adverse reactions compared with 127 (14%) given placebo. The frequency of local adverse reactions were 17.5% in the vaccine group and 7.3% in the placebo group (p < 0.001). There was no difference in systemic adverse reactions (11% v 9.4%; p = 0.34). In general, men reported fewer side effects than women. CONCLUSION: Only local side effects were more common in vaccinated patients and all side effects were mild.

[More information on infectious diseases provided by a national information system]. / Meer informatie over infectieziekten door landelijk systeem.

The Infectious Diseases Information System (ISIS) was established to improve the exchange of information about infectious diseases among those combating these diseases. Information about infectious diseases is obtained from municipal health services by means of a data processing system elaborated by the National Institute for Public Health and the Environment. After adjustment to the new Act on Combating and Tracing of Infectious Diseases it will be introduced nation-wide in 1998. Information about pathogens is obtained from medical microbiological laboratories (MMLs) through automatic storage of positive and negative results in a central data bank. After a pilot project had shown that the data from one MML, Arnhem, were complete and reliable, the MMLs of Roermond and Tilburg were also connected. For feedback of information to medical microbiologists and infectious diseases specialists, but also to, for instance, GPs, data from the whole country are presented daily on a public Internet site (http:/(/)www.isis.rivm.nl).

[Surveillance of communicable diseases in the European Union]. / Surveillance van infectieziekten in de Europese Unie.

Important developments are taking place in the Public Health framework in the European Union (EU). A number of international surveillance networks have been developed between the countries of the EU. The European Commission has initiated horizontal and disease specific programmes in the field of infectious disease surveillance. These have stimulated European co-operation for prevention and control of infectious diseases. Much topical information can be found on several Internet pages. The challenge is to set up networks for all public health relevant infectious diseases.

[Pharmaco-economic evaluations of new drugs: potential key to a more efficient allocation of the health care budget]. / Farmaco-economische evaluaties van nieuwe geneesmiddelen: mogelijk de sleutel tot een doelmatiger verdeling van het gezondheidszorgbudget.

In the light of rising expenditure on drugs and health care, a transparent, rational and careful decision-making process is required for the reimbursement of drugs. In the Netherlands, the Ministry of Health intends using pharmaco-economics in this process, i.e., new drugs will not only be judged on their clinical efficacy but also on their cost-effectiveness. Guidelines for pharmaco-economic research in the Netherlands have been published. According to these guidelines, a pharmaco-economic study must contain a cost-effectiveness analysis and/or a cost-utility analysis. In addition, a budgetary impact analysis is required. By 2005, all new drugs with therapeutic added value must supply a pharmaco-economic evaluation in order to apply for reimbursement. It will be the Minister of Health who decides whether a new drug will be reimbursed.

[Cost-effectiveness of influenza vaccination The Netherlands]. / Kosteneffectiviteit van influenzavaccinatie in Nederland.

OBJECTIVE: To determine the cost-effectiveness of influenza vaccination of all people aged 65 or over in the Netherlands. DESIGN: Model calculations. SETTING: National Institute of Public Health and Environment, Bilthoven, the Netherlands. METHOD: The cost-effectiveness of vaccination strategies was calculated using a mathematical model, with which the epidemiological effects in terms of morbidity and mortality as well as the direct costs of care of an influenza epidemic can be determined. The cost-effectiveness of non-intervention, of the current vaccination scenario for risk groups, and of an alternative scenario involving vaccination of all persons aged 65 or over and of all younger persons in risk groups, was calculated. RESULTS: Influenza-related care (the number of GP contacts and hospital days) and related costs decreased more with the alternative than with the current risk group scenario. Although the costs of care decreased when more people were vaccinated, the cost of vaccination increased more so that total net costs rose (55 million guilders versus 24 million). In the alternative scenario yearly 1115 life years more were won than with the current practice. CONCLUSION: Vaccinating all risk groups and all persons aged 65 or more has a favourable cost-effect ratio in comparison with other preventive intervention programmes.

[Indications for influenza vaccination in children with lung disorders. Dutch Association for Pediatric Medicine]. / Indicaties voor influenzavaccinatie bij kinderen met longaandoeningen. Nederlandse Vereniging voor Kindergeneeskunde.

The Dutch Association for Paediatric Medicine has formulated guidelines regarding influenza vaccination of children with pulmonary disease. Influenza virus is the most frequent cause of airway infections in humans over two years of age. It may lead to serious morbidity in children with pulmonary disease: exacerbations, (transient) disturbances in pulmonary function, and symptoms lasting weeks, but mortality is probably very low. The effects of influenza vaccination of children with pulmonary disease are similar to those in normal healthy children. A positive long-term effect on the asthma has never been demonstrated. It is advised that children with moderate to severe asthma who require treatment to be vaccinated against influenza every year. If the first vaccination ever occurs before the age of six years, it should be followed by a booster vaccination after four weeks. In both instances, a full vaccination dose should be administered.

[Infections and bacterial resistance in the community]. / Infecties en bacteriële resistentie in de open bevolking.

The frequency of resistance to antibiotics among community acquired pathogens and the number of drugs to which they are resistant are increasing world wide. Antimicrobial resistance in the Netherlands is still low. Resistance to antimicrobial drugs is clearly linked to consumption of antibiotics within and outside of the hospital. Use of antibiotics in veterinary medicine may also contribute to the occurrence of antimicrobial resistance in human pathogens. Strategies to limit the spread of resistant strains should include encouraging the judicious use of antimicrobial agents. Guidelines for antibiotic therapy should be based on results derived from well designed surveillance studies.

[Prevalence of HIV infection among drug users in Zuid-Limburg]. / Prevalentie van HIV-infectie onder druggebruikers in Zuid-Limburg.

OBJECTIVES: To assess the prevalence of HIV infection among intravenous (IDU) and non-intravenous drug users in Heerlen and Maastricht (Southern Netherlands), to detect subgroups of IDU with a higher risk of HIV infection, and to assess the risk of further spread of HIV. DESIGN: Cross-sectional study. SETTING: Heerlen, Kerkrade, Brunssum and Maastricht, the Netherlands. METHODS: Between August 15 and November 25, 1994, a saliva specimen and a short questionnaire were obtained from 449 drug users (340 IDU) in Heerlen (and environs) and Maastricht. Participants were recruited through methadone care (54%), syringe exchange (16%), a street prostitution project (3%), street recruitment (23%) and other drug users (4%). RESULTS: Of the 340 IDU 33 were infected (prevalence: 10% (95% confidence interval: 7-13)), among the 109 non-IDU no infections were found (0% (0-3)). IDU making use of the syringe exchange had a higher prevalence (odds ratio 3.13 (1.37-7.61)). In logistic regression analysis, this finding could not be explained by selection on more risky injecting. One in five currently injecting IDU reported having used someone else's used needle or syringe in the last 6 months. One in five IDU had a non-drug user as steady sexual partner. In sexual contacts between steady partners condom use was low. On the basis of self-reported serostatus it appeared that some infections have taken place in the last two years. CONCLUSIONS: The prevalence of HIV infections among IDU in Heerlen and Maastricht is about 10%. IDU using the syringe exchange have a higher prevalence. This means this prevention reaches the high-risk group, but probably can not avoid all infections. The risk of further spread among IDU is high. The risk of spread to non-IDU and non-drug users is present.