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Biomedical subjects

J Groen

Publications and source records attributed to J Groen.

At least 19 recordsLinked to original sources

Epstein-Barr virus and disease activity in multiple sclerosis.

OBJECTIVES: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA. METHODS: This was a prospective study with 73 RR MS patients followed for an average of 1.7 years with frequent neurological examination and blood sampling. Antibodies to various EBV proteins were measured by ELISA and plasma EBV DNA was measured by PCR. RESULTS: All MS patients had IgG antibodies to EBV (viral capsid antigen (VCA) and/or EBV nuclear antigen (EBNA)), irrespective whether samples were taken at stable disease or exacerbation. A significantly elevated percentage of the patients (48%) had antibodies against EBV antigens (early antigen, EA) that indicate active viral replication, compared with the age matched healthy controls (25%). Antibodies against a control herpesvirus, cytomegalovirus, were similar between the two groups. The percentage of EA positive individuals and EA titres did not differ between stable disease or exacerbation. Anti-VCA IgM was positive in three cases, unrelated to disease activity. Using a highly sensitive PCR on 51 samples taken at exacerbation visits, only three patients were found to have one timepoint with viraemia, and this viraemia was unrelated to disease activity. Of special note was the fact that anti-EA seropositive patients remained seropositive during follow up, with stable titres over time. We hypothesised that these patients may constitute a subgroup with higher disease activity, due to the triggering effect of a chronic attempt of the virus to reactivate. The EA positive group did not differ from the EA negative with respect to clinical disease activity or other characteristics. However, in the EA positive group, analysis with gadolinium enhanced MRI indicated more MRI disease activity. CONCLUSIONS: There was no evidence for increased clinical disease activity in the subgroup of MS patients with serological signs of EBV reactivation. However, the observation that chronic EBV reactivation may be associated with increased inflammatory activity as assessed by gadolinium enhanced MRI lesions should be reproduced in a larger and independent dataset.

Adult↗

Seroprevalence of hepatitis A virus antibodies in Turkish and Moroccan children in Rotterdam.

Seasonal fluctuations in hepatitis A have been observed in the Netherlands related to Turkish and Moroccan children after visiting their home countries. This study determined the prevalence and associated factors of hepatitis A virus (HAV) antibodies in Turkish and Moroccan children in Rotterdam. A random sample was taken of children in Rotterdam, aged 5-16 years, of Turkish and Moroccan origin, together with a random sample of native Dutch children aged 5-7 and 14-16 years. Blood was collected by finger prick on filter paper. IgG and IgM anti-HAV was detected by an enzyme-linked immunoassay (EIA). The 319 Turkish, 329 Moroccan, and 248 native Dutch children participated in the study. In Turkish children, IgG anti-HAV increased from 2.2% to 22.2% over the age groups. In Moroccan children, IgG anti-HAV increased from 10.2% to 57.7%. In native Dutch children, 0.8% had IgG anti-HAV in the youngest and 3.1% in the oldest age group. The percentage IgG-positive also having IgM anti-HAV was 21% in Turkish, and 41% in Moroccan children. No IgG-positive native Dutch children had IgM anti-HAV. The prevalence of IgG anti-HAV was associated with increased age, being Moroccan, longer stay in the country of origin before migrating to the Netherlands, and known contact to HAV. The majority of Turkish and Moroccan children aged 4-16 years in Rotterdam are not protected against HAV, but do have a high risk of becoming infected while visiting their native country. Active vaccination against HAV of these children is indicated, with as primary aim their own protection. Prevention of HAV-transmission in the general community should be seen as a secondary benefit. In addition, possible Dutch contacts of nonvaccinated Turkish and Moroccan children, such as day care workers and teachers, should also be vaccinated against HAV.

Adolescent↗

Evaluation of a multiplex reverse transcriptase PCR ELISA for the detection of nine respiratory tract pathogens.

BACKGROUND: A multiplex reverse transcription (RT) polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) was previously developed to detect nine different microorganisms: enterovirus (EV), influenza virus type A (IVA) and type B (IVB), respiratory syncytial virus (RSV), parainfluenzavirus type 1 (PIV1) and type 3 (PIV3), adenovirus (AV), Mycoplasma pneumoniae (Mpn), Chlamydia pneumoniae (Cpn) in a single test. These organisms do not usually colonize the respiratory tract of humans, but, if present, it may be assumed they are involved in respiratory disease. OBJECTIVES AND STUDY DESIGN: The m-RT-PCR-ELISA was tested on (i) culture supernatants of unknown contents, (ii) by determining the analytical sensitivity of 10-fold serial dilutions of culture supernatants and (iii) by determining clinical sensitivity in a retrospective study on 411 clinical specimens. The specimens were re-tested in parallel by m-RT-PCR-ELISA versus the gold standard culture and immunfluorescence, and versus individual RT-PCR. RESULTS: (i) The 9-valent m-RT-PCR-ELISA shows 83% to 100% concordant results on 103 culture supernatants containing different organisms. (ii) The analytical sensitivity was as follows: higher sensitivity of the 9-valent m-RT-PCR-ELISA in comparison to culture in the cases of PIV3, IVA and IVB (factor 10) and AV and EV (factor 100), and lower sensitivity in case of RSV and PIV1 (factor 10). (iii) The agreement with the gold standard in the kappa statistic was excellent for RSV (kappa = 0.937), IVA (kappa = 0.940), very good for PIV1 (kappa = 0.914), IVB (kappa = 0.907) and satisfactory for PIV3 (kappa = 0.410). For AV, EV and Mpn the m-RT-PCR-ELISA preliminary could be qualified as very good, based on the data derived on culture supernatants. Information about the validity for Cpn is limited. CONCLUSION: The m-RT-PCR-ELISA is a feasible, sensitive and specific method for detection of a broad spectrum of organisms. It is suitable for individual as well as epidemiological diagnosis.

Adenoviridae↗

[Arthralgia and rash from Australia caused by Ross river virus].

A 58-year-old entomologist presented with disabling arthralgia after a recent visit to the Northern Territory of Australia. A faint maculopapular rash was noticed on the trunk and limbs. The presumptive diagnosis of RRV disease was confirmed by the finding of IgM and IgG antibodies against RRV in serum. RRV, a mosquito-transmitted alpha virus, is the most common cause of arboviral disease in Australia. This disease, initially referred to as epidemic polyarthritis, is characterised by joint pain, rash and constitutional manifestations. The reservoir of RRV are marsupials, other mammals and birds, but mosquitoes may also transmit the disease between humans. The diagnosis is mainly based on RRV-specific serology. In case of arthritis viral RNA sometimes can be detected in synovium biopsies by PCR. No specific therapy is available; the prognosis is favourable. Prevention is based on protection against mosquito bites by wearing clothes to protect the skin, and by using insect repellents.

Alphavirus Infections↗

Infections and course of disease in mild forms of Guillain-Barré syndrome.

OBJECTIVE: Twenty-eight percent of patients with the Guillain-Barré syndrome remain able to walk unaided. Studying patients with the mild form of Guillain-Barré syndrome can further contribute to knowledge of the spectrum of the syndrome and explore whether this subgroup may need treatment with IV immunoglobulin. METHODS: Patients fulfilling the National Institute of Neurologic and Communicative Disorders and Stroke criteria for Guillain--Barré syndrome were included in a nationwide survey over a 2-year period. Clinical characteristics and serum samples were collected prospectively. In addition, a questionnaire was completed concerning the course and outcome of the disease. RESULTS: A total of 139 patients were included. Nineteen of the patients (14%) included were mildly affected, and 120 (86%) were severely affected. Infections with Epstein-Barr virus were found more frequently in mildly affected patients (p = 0.02). Antiganglioside antibodies were less frequently found in the mildly affected patients (p = 0.03). The degree of severity of the disease between mildly and severely affected patients was different on the day of admission (p < 0.01). Thereafter, the groups showed a remarkably similar rate of progression. Thirty-eight percent of mildly affected patients report problems in hand function and an inability to run at 3 and 6 months (all women, p = 0.02). CONCLUSION: The difference in severity of Guillain--Barré syndrome seems to be determined in an early phase of the disease. Preceding infections and antiganglioside antibodies may influence the initial immune attack, determining the severity of the disease. The presence of residual signs in patients with mild disease may advocate the use of early treatment in mildly affected patients.

Bacterial Infections↗

Serologic evidence of ehrlichiosis among humans and wild animals in The Netherlands.

The seroprevalence of antibodies directed against granulocytic and monocytic Ehrlichia was determined by use of human granulocytic ehrlichiosis agent and Ehrlichia chaffeensis as surrogate antigens. Seven hundred twenty-one serum samples were collected between 1992 and 1999 from febrile patients with unresolved aetiology (n=108), patients suspected of having Lyme disease (n=174), forestry workers (n=154) and healthy controls (n=54) as well as from wild deer (n=96), hares (n=60), wild boar (n=15) and red foxes (n=60). Reactive antibodies against granulocytic Ehrlichia were detected in 4% of febrile patients with unresolved aetiology and in 4% of patients suspected of having Lyme disease. Among the forestry workers, 1% tested positive for antibodies against granulocytic Ehrlichia, whereas all the healthy controls were negative. Antibody reaction against monocytic Ehrlichia was detected in only 2% of the febrile patients. Granulocytic Ehrlichia and monocytic Ehrlichia-reactive serum antibodies were detected in 22% and 3% of the deer samples, respectively, and in 2% of the hares. In wild boars and in red foxes, only serum antibodies reactive against monocytic Ehrlichia were detected in 13% and 7%, respectively. The demonstration of the presence of both granulocytic and monocytic Ehrlichia-reactive serum antibodies among humans and wild animals in The Netherlands indicates that patients suspected of having Lyme disease and febrile patients with unresolved aetiology should be tested for the presence of granulocytic and monocytic Ehrlichia antibodies or by polymerase chain reaction. Furthermore, granulocytic Ehrlichia are most prevalent in humans and animals in The Netherlands.

Adult↗

Cross-reactive anti-galactocerebroside antibodies and Mycoplasma pneumoniae infections in Guillain-Barré syndrome.

Anti-galactocerebroside (GalC) antibodies are reported to be present in GBS patients with preceding Mycoplasma pneumoniae (MP) infection. We investigated the presence of anti-GalC reactivity in serum of a large group of GBS patients using ELISA and compared this with healthy controls and individuals with an uncomplicated MP infection. Anti-GalC antibody reactivity was present in 12% of the GBS patients. Furthermore, anti-GalC antibodies were associated with MP infections, a relatively mild form of the disease and demyelinating features. Anti-GalC antibodies cross-reacted with MP antigen. In conclusion, anti-GalC antibodies in GBS patients may be induced by molecular mimicry with MP.

Autoantibodies↗

Measles in suburban Khartoum: an epidemiological and clinical study.

Clinical and epidemiological data were collected from 187 clinically diagnosed measles patients in Haj Yousif area, suburban Khartoum. Laboratory tests confirmed the diagnosis in 141 (75%) of the cases, but demonstrated that in 46 (25%) patients the clinical symptoms were not caused by an acute measles virus (MV) infection. According to their vaccination card, 59% of the laboratory-confirmed measles cases had been vaccinated for measles. Compared with non-measles rash disease cases, confirmed measles cases more often had severe illness (P < 0.0001), were dehydrated (P=0.01) at presentation and less likely to recover without complications [OR 0.19 (95% CI 0.09, 0.39)]. There was no difference in death rate (P=0.20). Underweight [weight-for-age Z score (WAZ) <or= -2 SD] was an independent predictor of recovery with complications [OR 0.4 (95% CI 0.2, 0.99)]. Severe measles cases (those who developed diarrhoea, pneumonia, otitis media, encephalitis or haemorrhagic rash) had similar vaccination rates and time intervals since vaccination as uncomplicated measles cases. Although severe measles had lower WAZ-scores (P=0.004), none of the nutritional parameters studied were predictive of outcome. Mortality was higher in the severe measles group [OR 8.8 (95% CI 1.7, 85.2)]. In 11 of 141 confirmed measles cases serological evidence of a recent infection with another virus was found, most commonly varicella zoster virus and dengue virus; spotted fever and rubella were among the most frequent diagnoses in 17 of 47 cases of the non-measles cases.

Adolescent↗

Safety and immunogenicity of a novel recombinant subunit respiratory syncytial virus vaccine (BBG2Na) in healthy young adults.

A novel recombinant respiratory syncytial virus (RSV) subunit vaccine, designated BBG2Na, was administered to 108 healthy adults randomly assigned to receive 10, 100, or 300 microg of BBG2Na in aluminum phosphate or saline placebo. Each subject received 1, 2, or 3 intramuscular injections of the assigned dose at monthly intervals. Local and systemic reactions were mild, and no evidence of harmful properties of BBG2Na was reported. The highest ELISA and virus-neutralizing (VN) antibody responses were evident in the 100- and 300-microg groups; second or third injections provided no significant boosts against RSV-derived antigens. BBG2Na induced > or 2-fold and > or =4-fold increases in G2Na-specific ELISA units in up to 100% and 57% of subjects, respectively; corresponding RSV-A-specific responses were 89% and 67%. Furthermore, up to 71% of subjects had > or =2-fold VN titer increases. Antibody responses to 2 murine lung protective epitopes were also highly boosted after vaccination. Therefore, BBG2Na is safe, well tolerated, and highly immunogenic in RSV-seropositive adults.

Adolescent↗

[Patient with West Nile fever in the Netherlands].

A 45-year-old patient was admitted with high fever and inadequate behaviour. She had recently stayed in Israel. Extensive investigation suggested a viral infection, but the cause was not established. Her partner suggested the possibility of West Nile virus infection, based upon information he had found on the Internet. Serology was performed and specific IgM and IgG antibodies were demonstrated, but a paired serum sample was not available. The patient recovered spontaneously. The West Nile virus is endemic in Israel, Africa, Asia and the Balkans. It is transmitted by mosquitoes. The incubation time is 1-3 weeks. The disease is characterised by fever, malaise, maculopapular exanthema and lymphadenopathy. Complications are encephalitis, pancreatitis, hepatitis and myocarditis. However, these symptoms are present in less than 5% of all infections. A full-blown encephalitis has a mortality rate of 50%. There is no specific therapy, but prevention by means of controlling the mosquito population is feasible. The diagnosis is made by the detection of West Nile virus-specific IgM antibodies in serum or cerebrospinal fluid. However, in the acute stage viral RNA detection by a polymerase chain reaction in the serum is also possible.

Acute Disease↗

Prevention of measles in Sudan: a prospective study on vaccination, diagnosis and epidemiology.

Despite the availability of safe and effective live attenuated vaccines, measles continues to be endemic in many developing countries. Control and elimination of measles will be especially difficult in East Africa, because of its limited infrastructure and political instability. We have studied diagnostic and epidemiological aspects of measles in suburban Khartoum, Sudan. Prospective studies were carried out in a cohort of clinically diagnosed measles cases and in a cohort of newborns, which were both followed up for 2 years. The studies intended to provide a rational basis for improvement of measles vaccination strategies, and strengthen measles research infrastructure in Khartoum.

Antibodies, Viral↗

A newly discovered human pneumovirus isolated from young children with respiratory tract disease.

From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.

Adolescent↗

Diagnosing visceral leishmaniasis with the recombinant K39 strip test: experience from the Sudan.

We compared a strip test employing recombinant K39 (rK39) antigen and protein A/colloidal gold as read-out agents with the rK39 ELISA for IgM and IgG antibodies and the direct agglutination test (DAT) using 55 sera from patients with parasitologically confirmed visceral leishmaniasis (VL). The rK39 strip test was positive in 37/55 (67%), the DAT in 50/55 (91%) at > or = 1 : 1600 cut-off value and in 47/55 (85%) at > or = 1 : 6400 cut-off value. The rK39-ELISA gave positive IgG results for all sera; those who had a positive strip test had significantly higher IgG levels than those with a negative strip test (31.1 (SD=3.6) and 17.7 U/ml (SD=9.8), respectively, P < 0.0001). A total of 31/55 (56%) sera showed a positive IgM result; of these 27 (49%) had a positive strip test. We tested 115 apparently cured VL patients with the strip test during follow-up; 68 were also tested with DAT. In the strip test, 25-43% of patients had a positive result at time points 3, 6, 9 and 12 months after treatment; for DAT (cut-off > or = 1 : 1600) these results were 67-83%. In neither test did a significant decrease in positivity rates occur over time (P=0.37 for the strip test, P=0.17 for the DAT). No correlation (P=0.33) was found between a positive strip test and a positive DAT result (cut-off > or = 1: 1600), indicating that the strip test and DAT are complementary rather than interchangeable. Of 61 endemic controls two (3%) had a positive strip test result; both had a positive leishmanin skin test. The rK39 strip test has the ideal format for use in the field, but its sensitivity is limited; like DAT, but to a lesser extent, it remains positive after treatment.

Adolescent↗

Prevalence and association between herpes simplex virus types 1 and 2-specific antibodies in attendees at a sexually transmitted disease clinic.

BACKGROUND: Seroprevalence of herpes simplex virus type 1 (HSV-1) and HSV-2 was determined in 1993 and 1998 in a randomly selected study group of 1024 and 654 attendees, respectively, at the sexually transmitted disease (STD) clinic of the University Hospital Rotterdam-Dijkzigt, The Netherlands. Correlations of HSV-1 and HSV-2 seropositivity were investigated. The relationship between HSV-1 and HSV-2 antibodies was also studied. METHODS: Data were collected in a cross-sectional study from February 1993 until February 1994 and from January 1998 until December 1998. Glycoprotein G (gG) HSV type specific serum IgG was determined. RESULTS: Seroprevalence of HSV-1 was 68% versus 59% (1993 versus 1998, chi(2)-test P < 0.001), of HSV-2 it was 30% versus 22% (1993 versus 1998, chi(2)-test P < 0.001). Using logistic regression analyses, HSV-1 and HSV-2 seropositivity were significantly associated with age and ethnicity in both groups. In 1993, HSV-1 seropositivity also correlated with lower level of education and female gender, whereas in 1998 it correlated with 'number of sexual partners in the past 6 months' and 'present diagnosis of STD'. In both groups, HSV-2 seropositivity was also more prevalent in females and related to sexual lifestyle variables. In an exposure-disease model, HSV-1 seropositivity was not correlated with HSV-2 seropositivity (odds ratio 1993 = 1.1, 95% CI : 0.8--1.7; odds ratio in 1998 = 1.0, 95% CI : 0.5--1.8). CONCLUSIONS: Seroprevalence of HSV-1 and HSV-2 is falling among STD clinic attendees in Rotterdam. A changing pattern of risk factors for HSV-1 seropositivity indicates increasing sexual transmission of HSV-1. Seropositivity for HSV-2 correlated with known risk factors. A previous HSV-1 infection does not reduce susceptibility to subsequent genital HSV-2 infections.

Adolescent↗