Distinct activation of primary human BDCA1(+) dendritic cells upon interaction with stressed or infected ß cells.

Derailment of immune responses can lead to autoimmune type 1 diabetes, and this can be accelerated or even induced by local stress caused by inflammation or infection. Dendritic cells (DCs) shape both innate and adaptive immune responses. Here, we report on the responses of naturally occurring human myeloid BDCA1(+) DCs towards differentially stressed pancreatic ß cells. Our data show that BDCA1(+) DCs in human pancreas-draining lymph node (pdLN) suspensions and blood-derived BDCA1(+) DCs both effectively engulf ß cells, thus mimicking physiological conditions. Upon uptake of enterovirus-infected, but not mock-infected cells, BDCA1(+) DCs induced interferon (IFN)-α/ß responses, co-stimulatory molecules and proinflammatory cytokines and chemokines. Notably, induction of stress in ß cells by ultraviolet irradiation, culture in serum-free medium or cytokine-induced stress did not provoke strong DC activation, despite efficient phagocytosis. DC activation correlated with the amount of virus used to infect ß cells and required RNA within virally infected cells. DCs encountering enterovirus-infected ß cells, but not those incubated with mock-infected or stressed ß cells, suppressed T helper type 2 (Th2) cytokines and variably induced IFN-γ in allogeneic mixed lymphocyte reaction (MLR). Thus, stressed ß cells have little effect on human BDCA1(+) DC activation and function, while enterovirus-infected ß cells impact these cells significantly, which could help to explain their role in development of autoimmune diabetes in individuals at risk.

Human enterovirus surveillance in the Slovak Republic from 2001 to 2011.

We report the outcome of an 11-year programme monitoring sewage water and acute flaccid paralysis (AFP) cases as part of the World Health Organization (WHO) strategy for polio eradication in the Slovak Republic (SR). Polioviruses (PV) and non-polio enteroviruses (NPEV), prior to and after the change in polio vaccination strategy, were detected. Sewage treatment plant samples from 48 localities spread over the Western, Central and Eastern regions and clinical material from AFP cases were examined. The WHO standard procedures were followed with regard to virus isolation and identification. There were 538 commonly detected human enteroviruses (HEVs) including 213 (40%) coxsackie B viruses (CBV), 200 (37%) echoviruses and 113 (21%) Sabin-like PVs (PV1, 2, 3) including vaccine-derived poliovirus (VDPV) isolates. The percentage of PV isolates fell from 66% to 30% during 2001-2005 and thereafter fell to zero. CBV5, CBV2 and echovirus 3 were the NPEVs endemic during the study period.

[Influenza vaccination now from 60 years of age onwards]. / Griepvaccinatie, nu ook vanafde leeftijd van 60 jaar.

Currently, general practitioners and occupational health physicians in The Netherlands face the question whether their patients should be vaccinated against influenza. This follows the addition of two new groups to the list of persons to be vaccinated: those over sixty and people working in health care and health institutions with direct patient contact. These developments stir the hidden resistance to influenza vaccination. It should be clear to everyone that there is no doubt that the vaccination is efficacious and safe. However, the influenza activity in The Netherlands has been low over the last years, which limits the disease burden to be prevented byvaccination. Under these circumstances, the proportion of flu-like symptoms caused by other agents such as respiratory syncytial virus is increased, which may lead to the false impression that the influenza vaccine is not effective. A new pandemic may come at any time, and only then will the efforts to prevent influenza pay off.

Toxoplasmosis after renal transplantation: implications of a missed diagnosis.

We describe a renal transplant patient with a primary Toxoplasma gondii infection presenting as pneumonitis, with subsequent chorioretinitis and encephalitis. The diagnostic challenges of T. gondii infection in immunocompromised patients are discussed.

[Can emerging zoonoses be controlled?]. / Zijn opduikende zoönosen beheersbaar?

The report 'Emerging zoonoses' of the Health Council of the Netherlands was written on request from the Minister of Health, Welfare and Sport. It gives an expert view on how to anticipate zoonoses that could emerge in the near future by addressing questions regarding risk assessment, prevention, early detection, control and communication. Further emphasis in the report is given to developments within the European Union (EU). The report had to serve as the basis for a European policy conference on 16 and 17 September 2004 during the Dutch presidency of the EU. Some important developments announced by the Minister are: establishment of a National Centre for Infectious Diseases to advise the Minister and coordinate crisis control during outbreaks, measures to strengthen the regional structure of public health in the Netherlands, and a budget for the strengthening of public health research.

Influenza-associated encephalopathy: no evidence for neuroinvasion by influenza virus nor for reactivation of human herpesvirus 6 or 7.

During 2 consecutive influenza seasons we investigated the presence of influenza virus, human herpesvirus (HHV) type 6, and HHV-7 in cerebrospinal fluid samples from 9 white children suffering from influenza-associated encephalopathy. We conclude that it is unlikely that neuroinvasion by influenza virus or reactivation of either HHV-6 or HHV-7 is involved.

[Duration of follow-up after contact with HIV: 3 or 6 months]. / Duur van de follow-up na een HIV-risicocontact: 3 of 6 maanden.

The revised Netherlands guideline 'Sexually transmitted diseases and neonatal herpes' recommends shortening of the follow-up period from 6 to 3 months for HIV-testing after a risky contact and a period of 6 months in case of post-exposure prophylaxis. The newly adopted follow-up period has a precedent in Sweden, where, based on the same scientific arguments, the follow-up period has been reduced to 3 months. There is little scientific information on which to base the optimal duration of the follow-up period. Therefore, two different periods are used in the Netherlands: 3 months for medical practice in the field of sexually transmitted diseases and 6 months for occupational exposure of health care workers and for blood products.

[Avian influenza and oseltamivir; a retrospective view]. / Vogelpest en oseltamivir; een terugblik.

The outbreak of avian influenza A due to an H7N7 virus in Dutch poultry farms turned out to have public-health effects for those who were involved in the management of the epidemic and who were thus extensively exposed to contaminated excreta and dust. An outbreak-management team (OMT) of experts in virology, infectious diseases and public health advised the Dutch government with respect to the potential health effects on humans. Strict hygiene measures were advised. Moreover, vaccination against human influenza was advised to prevent emergence of a new pandemic virus in humans. Since the human influenza virus H3N2 circulated at the same time, a double infection and emergence of a new human virus was the main fear on which prevention was focused. Conjunctivitis was observed in about 10% of the people involved. The conjunctivitis was sometimes accompanied by mild flu-like symptoms and incidental transmission between humans occurred as well. Because of the unexpected high incidence of symptomatic infections, proven to be caused by the H7N7 strain, oseltamivir was advised as an additional control measure, both for the treatment of symptoms and prophylactically for those with prolonged occupational exposure. After the unfortunate death of a veterinarian due to pneumonia caused by the avian virus, the preventive policy was further extended to people with short and incidental exposure to infected flocks. It is concluded that the policy was adequate, in spite of the unforeseen victim.

[Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes']. / CBO-richtlijn 'seksueel overdraagbare aandoeningen en herpes neonatorum' (herziening).

The Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes' summarises the current scientific position on the diagnosis and treatment of a great number of sexually transmitted diseases (STD) and neonatal herpes. Symptomatic treatment of suspected Chlamydia trachomatis infection and gonorrhoea without previous diagnosis is not recommended. Treatment can be started immediately, once samples have been taken. Risk groups eligible for screening or proactive testing on C. trachomatis infection include: partners of C. trachomatis-positive persons, visitors of STD clinics, women who will undergo an abortion, mothers of newborns with conjunctivitis or pneumonitis, young persons of Surinam or Antillean descent, young women with new relationships and individuals whose history indicates risky sexual behaviour. A period of 3 months can be adopted between a risky contact and the HIV test (this used to be 6 months), unless post-exposure prophylaxis was used. For the treatment of early syphilis no distinction is drawn between HIV-infected and non-HIV-infected persons. It is no longer recommended that women in labour with a history of genital herpes are tested for the herpes simplex virus. Virological testing of the neonate is only advised if the mother shows signs of genital herpes during delivery.

Chronic active Epstein-Barr virus infection in an adult with no detectable immune deficiency.

INTRODUCTION: Epstein-Barr virus (EBV) establishes lifelong latent infection. In some patients the host-virus balance is disturbed, resulting in a chronic active EBV infection. The following case illustrates the difficulty in diagnosing and treating chronic EBV infection. CASE: A 30-year-old woman was referred because of recurrent swellings of lymphatic tissue of both eyelids, orbit and lymph nodes and general malaise since the age of 19. In the past, repeated biopsies showed MALT lymphoma and nonspecific lymphoid infiltrations. Now, a biopsy of an axillary lymph node showed paracortical hyperplasia with a polymorphous polyclonal lymphoid proliferation, and large numbers of EBV-encoded small RNA (EBER) positive cells, consistent with EBV infection. Laboratory investigation showed a high EBV viral load. No evidence of immunodeficiency was found. Chronic active EBV infection (CAEBV) was diagnosed. Treatment with high-dose acyclovir did not significantly reduce the viral load. Rituximab was given in an attempt to reduce the amount of EBV-infected B lymphocytes. However, soon after the second dose the patient died of a sub-arachnoidal haemorrhage. CONCLUSION: This case report illustrates CAEBV as a rare manifestation of EBV-induced disease, which will be detected more frequently with the use of EBV-EBER hybridisation of lymph nodes and polymerase chain reaction (PCR) for EBV DNA. The prognosis is poor with no established therapeutic strategies.

The pathogenesis of febrile seizures: is there a role for specific infections?

Although fever is regarded as the main trigger in the pathogenesis of febrile seizures (FS), it is not supposed to be the unique causative factor. In FS, there is a strong familial predisposition. This does not exclude infections as a causative factor because subtle genetic polymorphisms have been demonstrated to affect the course of infections. We review the literature on: (1) the role of fever, especially the height of temperature, its cause, and metabolic effects induced by temperature; (2) the role of heredity; (3) the role of cytokines which play a role in the induction of fever; and (4) the role of type of infection, with emphasis on newly identified agents and improved diagnostic techniques. With modern molecular techniques such as PCR, viruses have been detected in the CSF far more often than previously thought, even in the absence of pleocytosis of the CSF. This makes it difficult to distinguish FS from acute encephalitis. FS may be caused by neuroinvasion or intracerebral activation of viruses. Further studies should focus on these options because therapeutic intervention is possible and may prevent late sequelae such as recurrent FS and subsequent epilepsy.

Epidemiological survey of neonatal non-polio enterovirus infection in the Netherlands.

The epidemiological, virological, and clinical data of 119 infants less than 30 days of age with enteroviral infection collected from January 1993 to November 1995 by the diagnostic virology laboratories were analyzed retrospectively. Ninety-eight isolates (83%) were obtained in the period of May 1 to December 1 with a peak in the summer months. Sixty-five percent (n = 78) of neonates became ill within the first 2 weeks of life. Echoviruses and Coxsackie virus type B were isolated most frequently, in 77 (65%) and 29 (24%) infants, respectively. Diagnosis was made by viral isolation from stool, nasopharyngeal swab, cerebrospinal fluid, and blood. One hundred four (87%) infants developed fever and 25 (21%) infants had diarrhea. A clinical diagnosis of sepsis was made in 42 (35%) infants and meningitis was diagnosed in 28 (24%) cases. The great majority of sepsis cases (36/86%) occurred in infants less than 15 days of age. In conclusion, non-polio enteroviruses (especially echoviruses) are a common and underreported cause of neonatal infection in the Netherlands in the summer months and are associated with a clinical diagnosis of sepsis or meningitis cases in the first 2 weeks of life in a high proportion of cases.

Histopathologic findings in explanted heart tissue from patients with end-stage idiopathic dilated cardiomyopathy.

Explanted hearts were examined to determine whether specific histopathologic features are present in the myocardium of patients with end-stage idiopathic dilated cardiomyopathy (IDC). Extensive histopathologic examination by light microscopy, electron microscopy and immunohistochemistry revealed marked fibrosis in the hearts of 21 of 37 IDC patients and in 26 of 35 patients with heart diseases of known causes. Reactive (interstitial and perivascular) fibrosis predominated in the IDC hearts, whereas both reparative (replacement) fibrosis and reactive fibrosis were found in the comparison group. Endocardial fibroelastosis was found in nine patients with IDC and in 14 patients from the comparison group. Distinct patterns of fibrosis were the sole significant histopathologic difference between myocardial samples from patients with IDC and from those with heart diseases of known causes. The diffuse presence of reactive fibrosis in IDC patients suggests a more generalised dysfunction that affects the composition of the myocardial extracellular matrix.

[National hepatitis B vaccination closer to implementation, but not soon enough; recommendations from the Dutch Health Council]. / Algemene vaccinatie tegen hepatitis B naderbij, maar niet genoeg; advies van de Gezondheidsraad.

A Health Council Committee has advised the Minister of Health, Well-being and Sports not to implement universal hepatitis B vaccination in the Netherlands, as recommended by WHO and requested by members of the Dutch parliament. The Committee argued that the prevalence of hepatitis B carriers among the native Dutch population is so low (0.07%) that universal vaccination is not relevant. In contrast, vaccination was advised for children from parents who had immigrated from middle- and high-endemic countries to the Netherlands, because horizontal transmission is an important route of transmission among these people, as it is in their country of origin. This concerns an estimated 15% of the entire population. For the rest of the Dutch population the risk of horizontal transmission was considered negligible. Sexual transmission was considered more important. The optimal age of vaccination to prevent sexual transmission was considered to be shortly before puberty. The committee concludes that, as yet, no data is available to justify universal vaccination of this age group and highlights the need for additional studies, including those into the efficacy of existing preventive programs, before universal vaccination should be implemented. However, it can be argued that it is unlikely that sufficient information will be available for at least another five years, and it is certain that the risk of sexual transmission will increase during this time. Universal childhood vaccination is an investment in the youth which will pay out in the future, and which should therefore not be postponed.

[Emergent viral infections]. / Opkomende virusinfecties.

The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic infections such as dengue and hepatitis E, but also of hepatitis A, which is no longer endemic. Apart from import diseases new viruses have appeared (Nipah-virus and transfusion-transmitted virus). Existing viruses may suddenly cause more severe diseases, e.g. infection by enterovirus 71. The distribution area of a virus may change, e.g. in case of West Nile virus, an Egyptian encephalitis virus that appears to have established itself in the USA. Furthermore, there is no such thing as a completely new virus; it is always an existing virus that has adapted itself to another host or that was already present in humans but has only recently been discovered. A number of factors facilitate the emergence of new infectious diseases. These include intensive animal husbandry and the transport of animals. The unexpected appearance of West Nile virus in the western hemisphere was possibly due to animal transportation.

Psychological job demands as a risk factor for common cold in a Dutch working population.

OBJECTIVE: We investigated the effect of Psychological Job Demands (PJD) on the occurrence of the clinical symptoms of common cold. METHODS: Subjects, participating in a large prospective cohort study on psychological determinants of fatigue at work, were asked to fill in a questionnaire on the occurrence of common cold during the previous four months. High PJD were considered as a potential risk factor. Other factors such as age, gender, and having young children were considered as potential confounders. RESULTS: In logistic regression analysis, the adjusted odds ratio (OR) for having a recent cold in subjects reporting high PJD vs. those reporting low PJD was 1.20 (95% confidence interval (CI), 1.08-1.33). A higher risk emerged among those with young children (OR, 1.70; 95% CI, 1.47-1.96), those having a history of asthma (OR, 1.69; 95% CI, 1.28-2.22), or being under the age of 40 (OR, 1.28; 95% CI, 1.14-1.43) and among smokers (OR, 1.23; 95% CI, 1.09-1.38). CONCLUSION: The results support an association between PJD and common cold. In spite of the almost inevitable shortcoming of a large cohort study using questionnaires, this study gave us the opportunity to study the relationship between common cold and work-related factors in a nonexperimental setting with participants observed in a natural environment with all the normal everyday hassles.

Associations between infections and fatigue in a Dutch working population: results of the Maastricht Cohort Study on Fatigue at Work.

The relationship between fatigue and common infections was further explored, as part of a 3 year prospective cohort study on Fatigue at Work. The current study is based on seven successive questionnaires, covering the first 2 years of follow-up. The overall response at baseline was 45% (n = 12,140). On T1 10,592 (87.2% compared to baseline response) employees returned the questionnaire. For T2, T3, T4, T5 and T6, 10,270 (84.6%), 9655 (79.5%), 8956 (73.8%), 8692 (71.6%) and 8070 (66.5%) employees respectively returned the questionnaire. Self-administered questionnaires were used to determine the level of fatigue with the Checklist Individual Strength (CIS) and the occurrence of common cold, flu-like illness and gastroenteritis. Regression analysis using generalized estimated equations (GEE) were used for data analysis. We found a cross-sectional relationship between fatigue and the infections flu-like illness and gastroenteritis, and a longitudinal relationship between an infection as a predictor of fatigue. For fatigue as a predictor of an infection, we found odds ratios (ORs) of 1.35 (confidence interval (CI) 1.28-1.42) for flu-like illness and 1.33 (CI: 1.25-1.42) for gastroenteritis. The highest incidence of infections was found among employees who reported high fatigue levels on two successive occasions. The increased incidence of infections, is regarded as a substantial effect of fatigue because it is associated with significant absenteeism from work and leads to discomfort.

Enterovirus-induced production of pro-inflammatory and T-helper cytokines by human leukocytes.

Enteroviruses are associated with chronic inflammatory and autoimmune diseases in humans. In these conditions, the cytokine network is supposed to have an important role in inflammation and modulation of the (auto)immune response. In the present study, we demonstrate that coxsackie virus B4 and poliovirus type 1 induce production of pro-inflammatory cytokines IL-1 beta and TNF-alpha in freshly isolated human leucocytes. Furthermore, enteroviruses stimulate the production of cytokines belonging to Th(1)pathways (IFN-gamma, IL-2), and IL-10, which play a role in regulation of the cellular and humoral immune response.

[Incidence of herpes neonatorum in Netherlands]. / De incidentie van herpes neonatorum in Nederland.

OBJECTIVE: Investigation of the incidence of neonatal herpes in the Netherlands between 1992 and 1998. DESIGN: Inventory questionnaire survey. METHODS: All virological laboratories in the Netherlands were sent a questionnaire on the number of culture proven cases of neonatal herpes recorded between 1992 and 1998 and on the type of herpes simplex virus (HSV-1 or HSV-2). The gynaecological and paediatric departments of all university hospitals and of half of the general hospitals were sent questionnaires as well. Gynaecologists were asked how often caesarean section was performed in order to prevent neonatal herpes and how frequently pregnant women were seen with genital herpes. Paediatricians were asked how often they observed neonatal herpes, the type of HSV and the possible transmission route. Based on these data the figures for the whole of the Netherlands were estimated. RESULTS: The incidence of neonatal herpes in the Netherlands in the period 1992 to 1998 was 2.4 per 100,000 neonates. HSV-1 was the cause of neonatal herpes in 73%, HSV-2 in 9%, and in 18% of the cases the type of infection was not recorded. The number of pregnant women with genital herpes had increased, but, in agreement with a consensus statement, the gynaecologists hardly performed caesarean sections any more to prevent neonatal herpes (2 per year). CONCLUSIONS: The incidence of neonatal herpes in the Netherlands had not increased. There was no predominant role of HSV type 2 causing neonatal herpes.