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Biomedical subjects

G J van Doornum

Publications and source records attributed to G J van Doornum.

At least 19 recordsLinked to original sources
PubMed2005

Virus specific immune responses after human neoadjuvant adenovirus-mediated suicide gene therapy for prostate cancer.

PURPOSE: Neoadjuvant gene therapy potentially improves the outcome of primary treatment of prostate cancer by radical prostatectomy in patients with high risk of recurrence. We conducted a Phase I escalating dose study with a replication-defective adenovirus expressing the herpes simplex virus-thymidine kinase gene (Adv-HSV-tk vector). The primary end point was toxicity, while the evaluation of the patients' cellular and humoral immune responses served as a secondary endpoint. MATERIAL AND METHODS: The Adv-HSV-tk vector was injected into the prostate in two doses (2x10(10) to 2x10(11) viral particles), followed by ganciclovir twice daily for 14 days and retropubic radical prostatectomy on day 21. Adenovirus-specific neutralizing, IgG and IgA antibodies were evaluated. Peripheral blood mononuclear cells (PBMC) were stimulated by Adv-HSV-tk and analysed for IFN-gamma production and 3H-thymidine incorporation. Prostate specimens were immunostained for B (CD20+) and for T (CD3+) lymphocytes. RESULTS: Toxicity was minor in all 8 patients treated. In the prostate, no virus related cytopathic effect could be observed. Dose-dependent infiltration of T and B lymphocytes in the whole prostate and in tumor areas was observed. Boosting of adenovirus-specific antibody responses was observed in 7 patients, and an increased adenovirus-specific PBMC proliferation and IFN-gamma production was seen after Adv-HSV-tk stimulation. CONCLUSION: Neo-adjuvant adenovirus-mediated cytotoxic gene therapy prior to prostatectomy for prostate cancer is feasible and safe in an outpatient setting for intraprostatic vector doses up to 2x10(11) viral particles. Activation of the immune system was observed. Application of higher vector doses may be considered.

Adenocarcinoma↗
PubMed2001

The impact of immigration on env HIV-1 subtype distribution among heterosexuals in the Netherlands: influx of subtype B and non-B strains.

OBJECTIVE: To examine the epidemiological factors influencing the distribution and spread of HIV-1 subtypes among heterosexuals in the Netherlands. METHOD: A nationwide serosurveillance in 21 HIV/AIDS centres from 1997 to 1999 involved 200 individuals for whom the mode of HIV transmission was heterosexual contact or unknown. HIV-1 subtypes were determined by phylogenetic analysis of env V3 sequences and correlated with sociodemographic characteristics of the subjects and their sexual partners. RESULTS: HIV-1 subtype B infection occurred in 121 subjects (60%). Non-B subtypes were identified in 31 (A), 24 (C), 10 (D), six (E), four (F) and three (G) individuals; one had an unclassified subtype. The proportion of subtype B was about 60% in four of the six regions of the Netherlands, but in the Northwest and Southwest regions these proportions were 76% and 46%, respectively. The Surinamese and Antilleans, large immigrant groups, were all infected with subtype B, as were almost all individuals with an unknown source. The proportions of non-B viruses did not change significantly over time in Amsterdam, where subtyping was available from 1988 onward, but a shift in the various subtype B strains was observed, suggesting introductions of new subtype B strains in Amsterdam. CONCLUSION: To date, HIV-1 non-B subtypes in the Netherlands are still found predominantly among heterosexuals with an epidemiological link with sub-Saharan Africa. Despite continuing introductions of non-B subtypes, the B/non-B distribution has been stable over time, most likely as a result of introductions of subtype B strains from Caribbean and South American countries.

Female↗
PubMed2001

Evaluation of the hepatitis B antenatal screening and neonatal immunization program in Amsterdam, 1993-1998.

In the enhanced antenatal hepatitis B screening and neonatal immunization program in Amsterdam, 691 hepatitis B surface antigen (HBsAg) positive expectant mothers were reported in the period 1993-1998. The coverage of the screening was calculated at 97%. HBsAg-prevalence was high in women from Ghana and South-East Asia, and lowest in Dutch women. Hepatitis B immune globulin (HBIg) was administered within 24h to 95.9% of the neonates; 99.7% completed the vaccination series. About 6 weeks after the third vaccination the titer antiHBs was > or =100 IU/l in 85% of children; in 12% the titers were 10-100 IU/l; 3% had titers <10 IU/l, of whom 3/521 initially had HBsAg. Low birth weight (OR 3.77), being a boy (OR 1.64) and country of origin were predictors of low postvaccination titers. Coordinated by 0.5 full time equivalent (fte) additional staff, the program was relatively cheap and successful.

Adult↗
PubMed2001

Evaluation of hepatitis C antibody testing in saliva specimens collected by two different systems in comparison with HCV antibody and HCV RNA in serum.

Two different ELISA assays, the Ortho HCV 3.0 ELISA (Ortho Diagnostics Systems) and the Mono-Lisa anti-HCV Plus (Sanofi Diagnostics Pasteur) were evaluated for the detection of hepatitis C virus (HCV) antibody in saliva samples. Specimens were collected from 152 individuals who participated in a longitudinal cohort study on HIV infection, and who used illicit drugs. Saliva specimens were collected using two different systems: Salivette (Sarstedt) and Omni-Sal (Saliva Diagnostic Systems). Saliva specimens were tested following modified protocols by both ELISAs, and the results were compared with serum specimens that were tested according to the instructions of the manufacturer. Serum samples of 102 (67%) participants were positive by both assays, and 50 persons were negative for HCV antibody. A total of 99 of the 102 serum specimens were confirmed as positive using Ortho Riba HCV 3.0 (Ortho Diagnostics System) and Deciscan HCV (Sanofi Diagnostics Pasteur), and 3 yielded discrepant results. As no cut-off level is known for testing saliva samples by ELISA, 3 different levels were chosen: mean (M) + 1 standard deviation (SD), M + 2 SD, and M + 3 SD of the optical densities of saliva tests of the 50 HCV serum antibody negative persons. At a level of M + 1 SD and M + 2 SD the Salivette/Mono-Lisa combination gave the greatest proportion of HCV antibody positive saliva specimens obtained from the 102 HCV serum antibody positive participants, 88% and 79%, respectively. Differences between the various collection systems and assay combinations were not significant statistically. In 76 of the 102 persons with HCV antibodies in serum, HCV RNA was detected in serum. Salivary presence of HCV RNA, however, could not be demonstrated. The results show that the assays compared are unsuitable for diagnostic use, but the sensitivities of the assays are acceptable for use in epidemiological studies.

Adult↗
PubMed2001

Diagnosing genital ulcer disease in a clinic for sexually transmitted diseases in Amsterdam, The Netherlands.

The most common etiologic agents of genital ulcer disease (GUD) are herpes simplex virus type 1 (HSV-1), HSV-2, Treponema pallidum, and Haemophilus ducreyi. In an outpatient clinic for sexually transmitted diseases in Amsterdam, The Netherlands, specimens from 372 patients with GUD were collected from February to November 1996. Sera were collected at the time of the symptoms and, for most patients, also during follow-up visits. Swabs in viral transport medium were used for HSV culture and for detection of DNA. The most prevalent pathogen found was HSV-2, which was detected by culture in 35% of the patients and by PCR in 48% of the patients. Also, HSV-1 infection was more often detected by PCR (7.8%) than by culture (5.6%). Evidence for an active infection with T. pallidum was found in 1.9% of the patients, using serological tests. A multiplex PCR for simultaneous T. pallidum and H. ducreyi DNA detection was positive for T. pallidum in 3.3% of the samples and for H. ducreyi in only 0.9% (3 out of 368) of the samples. The sensitivity of the PCR was superior to that of culture for HSV detection and to that of serology for T. pallidum detection. Specific H. ducreyi immunoglobulin G antibodies were detected in sera of 5.2% of the patients, with no concordance between serology and PCR. In 37% of the cases, none of the tested microorganisms was detected. Performance of PCR in addition to conventional techniques significantly improved the diagnosis of GUD.

Chancroid↗
PubMed2001

Comparison between the LCx Probe system and the COBAS AMPLICOR system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients attending a clinic for treatment of sexually transmitted diseases in Amsterdam, The Netherlands.

Two assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae were compared: the LCx Probe system (the LCx system; Abbott Diagnostic Laboratories, North Chicago, Ill.) and the COBAS AMPLICOR C. trachomatis/N. gonorrhoeae system (the COBAS AMPLICOR system; Roche Diagnostic Systems, Branchburg, N.J.). Endocervical swab specimens, male urethral swab specimens, and female and male urine specimens were collected from 503 female and 498 male visitors attending a sexually transmitted diseases clinic in Amsterdam, The Netherlands. Prevalences for C. trachomatis were 12.5% (63 of 503) and 10.0% (50 of 498) in females and males, respectively. The prevalences for N. gonorrhoeae were 1.2% (6 of 503) and 4.2% (21 of 498) in females and males, respectively. Both assays showed high values for sensitivity and specificity with regard to the detection of C. trachomatis in endocervical swab specimens, male urethral swab specimens, and female and male urine specimens. The sensitivities for the LCx system were 92.1, 90.0, 88.9, and 94.0% for each type of specimen, respectively; and the sensitivies for the COBAS AMPLICOR system were 96.8, 98.0, 82.5, and 92.0% for each type of specimen, respectively. Specificities ranged between 98.4 and 100%. The sensitivity of the LCx system for the detection of N. gonorrhoeae was 100% for female cervical swab and urine specimens and male urethral swab specimens, while for male urine specimens the sensitivity was 95.2%; the specificity was 100% for all types of specimens. For the detection of N. gonorrhoeae by the COBAS AMPLICOR assay, the sensitivity for female cervical swab and male urethral swab specimens was 100%, that for female urine specimens was 66.7%, and that for male urine specimens was 95.2%. However, the predictive values of a positive test for female cervical swab specimens and urine specimens were 31.6 and 36.4%, respectively. Sequence analysis of the amplimers obtained by an in-house 16S rRNA PCR of the solely COBAS AMPLICOR system-positive swab specimens revealed neither N. gonorrhoeae nor other Neisseria spp. The COBAS AMPLICOR assay was considered not suitable for screening for infections with N. gonorrhoeae. If this assay is used for detection of N. gonorrhoeae, confirmation of positive results by a reliable test is mandatory.

Ambulatory Care↗
PubMed2001

Molecular epidemiology of hepatitis A virus in Amsterdam, the Netherlands.

The transmission of sporadic community-acquired hepatitis A virus (HAV) among different risk groups in Amsterdam was verified by applying molecular techniques on fecal samples. These were collected in 1997/1998 from 33 persons with HAV infection that was confirmed serologically. From 8 of these persons serial stool samples were collected. Nested RT-PCR targeting the VP3-VP1 and VP1-P2a regions followed by sequence analysis established the duration of fecal HAV RNA excretion in stool and the epidemiological molecular relationships between patients. The samples of 31 patients were RT-PCR positive, of which 24 were positive for both regions. Fecal HAV shedding was found to occur for at least 33 days after onset of disease, which was the longest time span tested. Sequencing showed that the hepatitis A virus subgenotype circulating among persons from Moroccan descent (type IB) was different from the subgenotype circulating among Dutch homosexual men (type IA). If the latter is endemic in the Netherlands, its presence is of importance to the national vaccination strategy.

Adolescent↗
PubMed2000

Strong decline in herpes simplex virus antibodies over time among young homosexual men is associated with changing sexual behavior.

The objective of this study was to evaluate whether the change in sexual behavior among homosexual men observed after the start of the acquired immunodeficiency syndrome epidemic resulted in a change in herpes simplex virus (HSV) seroprevalence in this group over time. In a cross-sectional study, the prevalence of herpesvirus types 1 (HSV1) and 2 (HSV2) was determined at study entry in 1984-1985 and 1995-1997 among 532 young (aged < or = 30 years) homosexual men participating in the Amsterdam Cohort Studies on HIV/AIDS. Risk factors for the presence of HSV antibodies, including human immunodeficiency virus infection, were evaluated, and their influence on HSV prevalence over time was assessed. A strong decrease in HSV1 and HSV2 seroprevalence, from 80.6% to 59.0% and from 51.3% to 19.0%, respectively, was observed between the two time periods. This decrease was not markedly influenced by various demographic and socioeconomic factors. After data were controlled for several markers of sexual activity (such as number of sex partners, human immunodeficiency virus infection, and past episode(s) of gonorrhea), it appeared that the decline in HSV seroprevalence was explained by a concurrent decrease in the presence of these markers. The authors conclude that among young homosexual men in this study, the strong decrease in HSV seroprevalence was associated with a concurrent shift in sexual behavior. Furthermore, these data suggest an increasing sexual component in HSV1 transmission over time.

Adult↗
PubMed2000

Emerging group-A rotavirus and a nosocomial outbreak of diarrhoea.

A P[6]G9 group-A rotavirus caused a protracted hospital outbreak of neonatal diarrhoea in The Netherlands. The outbreak lasted 5 months with 52 cases and an average attack rate of 40%, 46 cases were in an incubator section for neonates under 1 month of age. Rotavirus P161G9 was detected by RT-PCR in stool samples from the 31 cases tested. Emergence of this genotype in Europe may have implications for neonates lacking protective maternal antibodies and for the development of rotavirus vaccines.

Cross Infection↗
PubMed2000

Seroepidemiology of human papillomavirus type 73: a sexually transmitted low-risk virus.

Human papillomavirus type 73 (HPV 73) has been detected in some invasive cervical cancers and has been cloned from a squamous-cell carcinoma of the esophagus, but the epidemiology of this infection and its associated risk of cancer is unknown. We investigated the seroepidemiology of this virus using virus-like particles. The IgG response to HPV 73 appeared to be HPV type-specific, since a comparison of HPV 73 antibody levels before and after infection with HPV 6, 11, 16, 18 or 33 found no evidence of cross-induction of HPV 73 antibodies and since there was little correlation between the antibody levels to HPV 73 and the other 5 investigated HPV types. In both a cross-sectional serosurvey that included 274 women and a 7-year follow-up study that enrolled 98 women, HPV 73 seropositivity was found to be strongly dependent on the number of lifetime sexual partners [OR for > 4 vs. 0 to 1 partners: 6.0 (95%CI: 1.4-53.6) and 7.9 (95% CI: 2.8-28.3), respectively]. Finally, the risk for HPV 73 seropositive women to develop CIN was investigated in a prospective study nested in a cohort of 15,234 Swedish women. The population-based HPV 73 seroprevalence in Sweden was 14%. No excess risk for CIN was found (OR: 0.77). We conclude that HPV 73 is a mainly sexually transmitted, probably mostly transient, infection that does not confer any measurably increased risk for CIN development.

Adult↗
PubMed2000

Urogenital Chlamydia trachomatis serovars in men and women with a symptomatic or asymptomatic infection: an association with clinical manifestations?

To determine whether certain Chlamydia trachomatis serovars are preferentially associated with a symptomatic or an asymptomatic course of infection, C. trachomatis serovar distributions were analyzed in symptomatically and asymptomatically infected persons. Furthermore, a possible association between C. trachomatis serovars and specific clinical symptoms was investigated. C. trachomatis-positive urine specimens from 219 asymptomatically infected men and women were obtained from population-based screening programs in Amsterdam. Two hundred twenty-one C. trachomatis-positive cervical and urethral swabs from symptomatically and asymptomatically infected men and women were obtained from several hospital-based departments. Serovars were determined using PCR-based genotyping, i.e., restriction fragment length polymorphism analysis of the nested-PCR-amplified omp1 gene. The most prevalent C. trachomatis serovars, D, E, and F, showed no association with either a symptomatic or asymptomatic course of infection. The most prominent differences found were (i) the association of serovar Ga with symptoms in men (P = 0.0027), specifically, dysuria (P < 0.0001), and (ii) detection of serovar Ia more often in asymptomatically infected people (men and women) (P = 0.035). Furthermore, in women, serovar K was associated with vaginal discharge (P = 0.002) and serovar variants were found only in women (P = 0.045).

Adolescent↗
PubMed1999

[Opportunistic screening for genital infections with Chlamydia trachomatis among the sexually active population in Amsterdam. III. Cost-effectiveness analysis of screening women and the role of reinfection and partner treatment].

The role of reinfection and the importance of partner treatment were added to a pharmacoeconomic model for the analysis of a GP-based opportunistic screening programme for Chlamydia trachomatis (CT) in sexually active women in Amsterdam. A favourable cost-effectiveness was found for partner treatment. Partner treatment was cost saving and overall net costs per major outcome averted by the screening programme were reduced by 40% or more due to partner treatment. From a pharmacoeconomic point of view partner treatment should be routinely provided in the framework of a CT screening programme for Amsterdam women.

Adolescent↗
PubMed1999

[Positive results from serologic screening for syphilis in pregnancy in the Amsterdam region, 1991-1995].

OBJECTIVE: To evaluate the results of screening of pregnant women for syphilis in the region of Amsterdam, the Netherlands. DESIGN: Descriptive study and cost-benefit analysis. METHODS: In the period 1991-1995, physicians and midwives from the Amsterdam region sent serum samples of pregnant women to the Regional Public Health Laboratory of the Municipal Health Service (GG & GD) to be screened for syphilis. All physicians who had sent in specimens with a positive result of the Treponema pallidum haemagglutination assay (TPHA) and a confirming test result were asked, in the year of the screening, by telephone or in writing, what diagnosis they had made in the woman in question. Collection of these data was handled by the social nursing staffs of the outpatient clinics for sexually transmitted diseases in Amsterdam. The costs of laboratory tests and follow-up of the children were compared with the positive effects of special treatment and education avoided by antibiotic treatment. RESULTS: 54,344 serum samples were sent in. In the city of Amsterdam the coverage was 87.4%. In 81 women (0.15%) all the serological tests for syphilis were positive. From this group, 37 women had already been treated and 24 women were treated as a result of this screening programme (most of them had a foreign nationality), 10 for early syphilis and 14 for syphilis of unknown duration, preventing the birth of an estimated five to six children with congenital syphilis. The cost-benefit ratio was 1:15. CONCLUSION: Continuation of screening for syphilis during pregnancy in the Amsterdam region remains useful.

Cost of Illness↗
PubMed1999

[Opportunistic screening for genital infections with Chlamydia trachomatis among the sexually active population of Amsterdam. Il Over 90% participation and almost 5% prevalence].

OBJECTIVE: To determine in an opportunistic screening programme for Chlamydia trachomatis (CT) the participation and the CT prevalence among the heterosexual population. METHODS: Heterosexually active men and women, 15-40 years old, who consulted a general practitioner in Amsterdam, the Netherlands, in the period May 1996-April 1997, without symptoms of a sexually transmitted disease, were asked after informed consent had been given to provide a first-voided urine sample and a few sociodemographic data. The urine was investigated for CT by means of a ligase chain reaction. In case of a CT infection, the general practitioner was asked for information on treatment and partner notification. RESULTS: A total of 3689 persons were eligible for the study of whom 214 (5.8%) refused participation. Men refused more often than women (9.0% and 4.3% respectively). No relation was found with ethnic background or health care insurance (national health cost insurance/private medical insurance). Refusers were somewhat younger than participants (not statistically significant). CT was diagnosed in 4.9% (95% confidence interval (95% CI): 4.1-5.9) of the women and in 4.7% (95% CI: 3.6-6.1) of the men. In women a decreasing trend was seen in the prevalence of CT with an increase in age: from 13.4% in the group 15-19 years old to 2.3% in the group 35-40 years old. Independent of age a higher prevalence was found in Surinam Creole women. In 83% of the CT patients the general practitioner spoke with the patient about partner notification; usually there was one partner. CONCLUSION: There was a high participation rate (94%) in this opportunistic screening programme in which urine was tested for presence of CT. The CT prevalence in this asymptomatic population was almost 5%, but it was significantly higher in young women and women from Surinam. It is proposed to start such a screening programme in all general practices in Amsterdam.

Adolescent↗
PubMed1999

[Opportunistic screening for genital infections with Chlamydia trachomatis in sexually active population of Amsterdam. II. Cost-effectiveness analysis of screening women].

OBJECTIVE: To estimate the cost effectiveness of Chlamydia trachomatis (CT) screening of young women visiting general practitioners. DESIGN: Economic model analysis. METHODS: Data on the health care needs for CT complications were derived from various sources; costing was done using estimated cost prices, charges and the friction cost method; epidemiological data were derived from a pilot study among 22 general practices in Amsterdam, the Netherlands. The analyses were carried out assuming screening with ligase chain reaction test of a urine sample and treatment of identified cases of infection with single-dose azitromycin. The model intervention consisted of screening all heterosexually active women aged 15-19, 15-24, 15-29, or 15-34 years (strategies 1, 2, 3 and 4, respectively). Cost effectiveness was presented in net direct and indirect costs per woman cured and per major outcome averted (pelvic inflammatory disease (PID), chronic pelvic pain, ectopic pregnancy, infertility and pneumonia of newborns). RESULTS: The first two strategies were cost saving. For the third strategy net costs per woman cured and per major outcome averted were almost 110.- Dutch guilders (DFL) and over DFL 300, respectively. The last strategy costs over DFL 320 per woman cured and over DFL 910 per major outcome averted. The cost effectiveness was sensitive to the assumed probability of progression of CT infection to PID. CONCLUSION: Universal implementation of the screening programme investigated in Amsterdam for women aged 15-24 years would result in approximately equal savings and costs. Screening of all 15-29-year-old women would require a net investment of DFL 350,000.

Adolescent↗
PubMed1998

HIV surveillance among sexually transmitted disease clinic attenders in Amsterdam, 1991-1996.

OBJECTIVE: To determine trends in HIV prevalence among attenders of a clinic for sexually transmitted diseases (STD), with emphasis on heterosexuals who did not have a history of injecting drug use. METHODS: Anonymous unlinked HIV surveys with individual consent, conducted each half year from 1991 to 1996 (except 1993) among STD clinic attenders who came for evaluation of a possible new STD episode. RESULTS: Of 10,940 eligible attenders 10,046 (92%) accepted HIV testing. Of all tested attenders, 312 (3.1%) were HIV-infected. Overall HIV prevalence decreased significantly from 4.6% in 1991 to 2.8% in 1996. HIV prevalence among heterosexual men and women who were not injecting drug users was less than 1% in all but one survey period. Except for one woman, none of the 48 HIV-infected heterosexuals was aware of their current serostatus. Among HIV-infected heterosexuals, 21 out of 28 males (75%) and 18 out of 20 females (90%) were of non-Dutch origin. HIV prevalence was 16% among all homosexual men, and 12% among young homosexual men aged < 30 years. HIV prevalence among young homosexual men decreased significantly over time. Among HIV-infected homosexual men, 58% of older men and 59% of younger men were not aware of their current HIV infection. Rates of current STD were generally significantly higher among HIV-infected participants compared with non-HIV-infected participants. CONCLUSIONS: Although HIV prevalence among heterosexual clinic attenders is low, there is a clear potential for ongoing sexual HIV transmission. Most heterosexually acquired HIV infections are found in non-Dutch persons. This observation suggests migration of HIV-infected heterosexuals or the separation of Dutch and non-Dutch heterosexual networks. Awareness of serostatus is almost non-existent among HIV-infected heterosexuals, and is low among male homosexual clinic attenders. To increase awareness of current HIV serostatus and possibly decrease risk behaviour, HIV counselling and testing should be offered actively to all clinic attenders.

AIDS Serodiagnosis↗
PubMed1998

Prevalence and correlates of herpes simplex virus type 2 infection: evaluation of behavioural risk factors.

OBJECTIVE: To examine the prevalence and correlates of infection with herpes simplex virus type 2 (HSV-2) among sexually transmitted disease (STD) clinic attenders, we studied the prevalence of antibodies to HSV-2 and their association with risk behaviour. METHODS: Data were collected in a cross-sectional study among STD clinic attenders in Amsterdam. Seropositivity for HSV-2 was determined in 1798 serum samples by means of a monoclonal antibody-blocking enzyme-linked immunoassay. RESULTS: The prevalence of HSV-2 antibodies was higher than expected: 32.3% in a population in which 3% had current genital herpes and 8% gave a history of genital herpes. Of those with HSV-2 antibodies, only 18% had a history of genital herpes. A strong independent association with the presence of HSV-2 antibodies was found for sexual behaviour, more specifically: homosexual orientation, increasing number of years of sexual activity, increasing number of lifetime partners, number of past gonococcal infections, having receptive anal and (or) vaginal contact. CONCLUSION: The presence of HSV-2 antibodies had a strong association with past sexual behaviour and, for both sexes, with receptive anal intercourse. HSV-2 antibodies may be used as a surrogate marker of sexual risk behaviour in comparing different populations over time.

Adult↗