Cost-effectiveness estimates for antenatal HIV testing in the Netherlands.

This paper provides an estimation of the lifetime health-care cost of HIV-infected children and an update of the cost-effectiveness of universal HIV-screening of pregnant women in Amsterdam (The Netherlands). During 2003-2005, we collected data concerning the prevalence of newly diagnosed HIV-infected pregnant women in Amsterdam. Also, data on resource utilization and HAART regimen for HIV-infected children was gathered from a national registry. Using Kaplan-Meier survival analysis, we estimated the life-expectancy of a vertically HIV-infected child at 19 years, with the corresponding lifetime health-care costs of 179,974 Euros. HIV-screening of pregnant women could prevent 2.4 HIV transmissions annually in Amsterdam, based on an estimated prevalence of nine yet undiagnosed HIV-positive pregnant women per 10,000 pregnancies. We show that universal HIV screening during pregnancy generates significant net cost savings and health benefits in most situations. Universal antenatal HIV screening is justified in Amsterdam from a health-economic point of view.

[The molecular epidemiology of hepatitis A in The Netherlands; the usefulness of typing isolated viral strains]. / Moleculaire epidemiologie van hepatitis A in Nederland; het nut van het typeren van geïsoleerde virusstammen.

OBJECTIVE: To investigate the epidemiological links between several outbreaks of hepatitis A in The Netherlands (2001-2004). DESIGN: Descriptive. METHOD: Blood samples taken in connection with reports of hepatitis A to municipal health centres from 2001-2004, were typed by determining the nucleotide sequence of the VP3-VP1 and the VP1-P2A regions of the genome of the hepatitis A virus (HAV). Genetic distances were represented graphically by means of a phylogenetic tree. RESULTS: The study into the spread of various subtypes of HAV showed a clear link between the HAV-(sub)genotype and risk of transmission: in men that have sex with men only genotype 1A occurred, in travellers to African countries genotype 1B was predominantly seen. CONCLUSION: A database containing various viral strains from people with hepatitis A in The Netherlands could, if kept up to date, be used as an aid in confirming the classical way of tracing sources as well as for the evaluation of preventative measures.

[Less refusal to participate in HIV screening among pregnant women in the Amsterdam region since the introduction of standard HIV screening using the opting-out method]. / Minder weigering van deelname aan HIV-screening door zwangeren in Amsterdam sedert de invoering van de standaard-HIV-screening--tenzij weigering ('opting-out'-methode).

In 2003 the Municipal Health Service in Amsterdam started to screen pregnant women for HIV according to the opting-out method. In this method the HIV test is routinely included in the prenatal screening along with hepatitis B virus (HBV) and syphilis. If the woman does not want to be tested for HIV then she must actively opt out of this test. This screening method was chosen because in the universal screening method used in 2002, women had to give their explicit consent to test for HIV and this led to a high refusal rate (13.6%), especially among women from AIDS-endemic countries. After the introduction of the opting-out method, the refusal rate fell from 3% in the first quarter of 2003 to 1.4% in the last quarter of 2003. None of the women refused to be tested for HBV or syphilis. In 2003, the HIV prevalence among pregnant women was 0.3% (35/13.621). The experiences with this screening method in Amsterdam were used to implement the national opting-out method for HIV screening in pregnant women, which was introduced on 1 January 2004.

HIV testing behaviour among heterosexual migrants in Amsterdam.

This cross-sectional study among heterosexual migrant groups in south-eastern Amsterdam, the city area where the largest migrant groups live, provides an insight into HIV testing behaviour in this particular group. Participants were recruited at street locations (May 1997-July 1998) and interviewed using structured questionnaires. They also donated saliva for HIV testing. In total, 705 males and 769 females were included in this study (Afro-Surinamese (45%), Dutch-Antilleans (15%) and West Africans (40%)). Prior HIV testing was reported by 38% of all migrants (556/1479), of which only a minority (28%) had actively requested HIV testing. Multivariate logistic regression showed that not actively requesting HIV testing was more likely among younger (< 23 years) migrants, especially women (ORwomen: 4.79, p < 0.01, ORmen: 1.81, p < 0.05). Furthermore, women without previous STI treatment (OR 2.19, p < 0.05) with Afro-Surinamese ethnicity (OR 2.12, p < 0.05), men without health insurance (OR 2.17, p < 0.05) and with low education (p < 0.01) were also more likely to not actively request HIV testing. Active requests for HIV testing in case of HIV risk should be facilitated by promoting HIV testing and by improving accurate self-assessment of risk for HIV infection, especially among the groups that do not actively request HIV testing. This would increase HIV awareness and provide the opportunity of better medical care earlier in HIV infection.

[HIV-screening among pregnant women in the region of Amsterdam in 2002]. / HIV-screening onder zwangere vrouwen in de regio Amsterdam in 2002.

In 2001, the Municipal Health Service started offering HIV tests to all pregnant women in and around Amsterdam. All midwives and all hospitals but one participated in this HIV screening. In 2002, of the 10,752 pregnant women offered HIV testing 13.6% refused. HIV antibodies were detected in 24 women (0.26%). The HIV prevalence was doubled compared to the prevalence in 1990-1991, but the number of newly HIV-infected pregnant women remained stable (0.1%). The high number of refusals, as a result of which many HIV-infected women might be missed, is alarming. For this reason, in January 2003, the Municipal Health Service started HIV testing by the opting-out approach. Under the opting-out approach, women are notified that an HIV test will be included in the standard test battery, together with tests for hepatitis B and syphilis, unless she explicitly refuses. It is expected that the opting-out approach for HIV screening of pregnant women will be implemented nationwide in 2003.

[Post-exposure treatment against HIV outside of the hospital in Amsterdam, January-December 2000]. / Postexpositiebehandeling tegen HIV buiten het ziekenhuis in Amsterdam, januari-december 2000.

The Infectious Diseases Department of the Amsterdam Public Health Service regularly sees people who have possibly been exposed to human body fluids infected with hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV), as a result of incidents in either a non-hospital-related occupation or during their leisure time. Until January 2000, people reporting possible exposure were referred to hospitals for HIV post-exposure prophylaxis (HIV-PEP), whereas for HBV and HCV, the tracing of the infection source and the follow-up took place at the Public Health Service clinic. Since the introduction of a new protocol in January 2000, the Public Health Service as well as a hospital can establish an indication for HIV-PEP and prescribe it. In 2000, 322 persons reported to the Public Health Service. The source was tested in 194 incidents and an HIV test was carried out on 104 occasions. In 19 cases HIV antibodies were found or the source was known to be HIV positive. A total of 50 people were prescribed HIV-PEP; 16 times after a needle-stick accident, 22 times after a sexual accident, 6 times after a bite-wound and 6 times after direct exposure to human blood. The sources of 30 PEP recipients could be tested and after this 16 recipients could stop with the treatment due to a negative HIV test. In 4 cases PEP treatment was stopped following a review of the indication. Therefore, 30 people had an indication to complete the PEP treatment. Of these, more than 80% reported side effects and 3 people had to withdraw from the treatment at an early stage because of this. The implementation of the protocol has resulted in less confusion because the follow-up now takes place at one location. Compared to other studies, the average time between exposure and treatment is shorter and compliance is good. In the period up to 15 May 2001, no seroconversions had been observed.

Cost-effectiveness of partner pharmacotherapy in screening women for asymptomatic infection with Chlamydia Trachomatis.

OBJECTIVE: To assess the cost-effectiveness of pharmacotherapy for male partners in screening women for asymptomatic infection with Chlamydia trachomatis (CT). METHODS AND DATA: A pharmacoeconomic decision analysis model was constructed for the health outcomes of a CT screening program, such as averted cases of pelvic inflammatory disease and infertility (major outcomes). Reinfection in the absence of partner pharmacotherapy was included in the model. Cost-effectiveness from a societal perspective was estimated for prevalence data from a selective opportunistic screening program in Amsterdam. For diagnosis of asymptomatic CT infection a Ligase Chain Reaction (LCR) test on urine was used; for pharmacotherapy of women and partners azithromycin was used. By linking health outcomes with health care costs and productivity losses, averted costs were estimated. Cost-effectiveness was expressed as net costs per major outcome averted. RESULTS: Partner pharmacotherapy reduces net costs per major outcome averted of the screening program by approximately 50%. Sensitivity analysis indicates significant improvements in cost-effectiveness of the screening program, even when relevant assumptions are varied. Within the broader framework of the screening program, partner pharmacotherapy is a cost-saving activity. CONCLUSIONS: Inclusion of partner pharmacotherpy provides significant improvements in overall cost-effectiveness of the CT screening program among women aged 15 to 29. Partner pharmacotherapy lowers net costs per major outcome averted to the realm where implementation of the screening program should be considered. Considering the cost-saving potential, male partner pharmacotherapy should be pursued within the broader framework of a CT screening program for women. Reinfection should be included in any future pharmacoeconomic model of CT screening. Further work on this type of model should also be directed to linking cost-effectiveness to epidemiological models for the long-term spread of infectious diseases in populations.

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.

Prevalence and risk factors of HSV-1 and HSV-2 antibodies in European HIV infected women.

OBJECTIVES: To investigate the prevalence and risk factors of HSV-1 and HSV-2 antibodies in HIV infected women and the association between recurrent genital ulcerations and HIV disease progression in HSV-2 positive women. METHODS: The presence of HSV antibodies was tested in 276 of the 487 women participating in a European cohort study of HIV infected women. Prevalence rate ratios described the association between HSV infection and its risk factors, using log binomial regression. Generalised estimating equations (GEE) analysis was performed to determine the impact of markers of HIV disease progression on recurrent genital ulcerations. RESULTS: The prevalence of HSV-1 and HSV-2 antibodies was 76% (95% confidence interval (95% CI): 71-81) and 42% (95% CI: 36-50); 30% (95% CI: 24-35) of the women had antibodies against both HSV-1 and HSV-2. The prevalence of HSV-1 was 86% (95% CI: 80-92) in southern Europe compared with 69% (95% CI: 57-79) and 67% (95% CI: 55-77) in central and northern Europe (p=0.002). This geographical variation remained after adjustment for other risk factors. An increasing number of years of sexual activity (p=0.0002) and a history of prostitution (p=0.0001) were independently associated with HSV-2 prevalence. In HSV-2 positive women, symptomatic cases of HSV infection were minimal, but increased with decreasing CD4 count. CONCLUSION: In HIV infected women, the prevalence of HSV antibodies is high and symptomatic cases of HSV infection are minimal, but increase with decreasing CD4 count. HSV-2 but not HSV-1 was related to sexual behaviour (that is, a history of prostitution and the number of sexually active years) in this group of HIV infected women.

[Screening for asymptomatic Chlamydia trachomatis infection in pregnancy; cost-effectiveness favorable at a minimum prevalence rate of 3% or more]. / Screening op asymptomatische infectie met Chlamydia trachomatis in de zwangerschap; gunstige kosteneffectiviteit bij een prevalentie van tenminste 3%.

OBJECTIVE: To estimate the cost-effectiveness of antenatal screening for Chlamydia trachomatis. DESIGN: Pharmaco-economic model analysis. METHOD: The risks of C. trachomatis infection during pregnancy and of complications of the infection as well as the cost of screening for complications (pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, infertility and neonatal pneumonia) and of treatment were estimated. Assumed were a ligase chain reaction on urine and treatment of identified infected cases with erythromycin or amoxicillin (second choice). Cost-effectiveness was calculated and presented in net direct and indirect costs per major complication averted. RESULTS: For C. trachomatis prevalences in pregnancy above 4% benefits exceed the costs. For prevalences between 2.82% and 4.00% net costs are positive, but a major complication averted costs less than f 1000.-. Considering sensitivity analysis as well, screening for C. trachomatis at prevalences above 3% costs less than f 1000.-per major complication averted and might even save costs. No recent Dutch data on C. trachomatis prevalence in pregnancy are published however. CONCLUSION: Given the current information, antenatal C. trachomatis screening can be recommended from a pharmaco-economic perspective if C. trachomatis prevalence in pregnancy is 3% or more.

[Pharmaco-economic evaluation of mandatory HIV-screening in pregnancy; a cost-efficacy analysis in Amsterdam]. / Farmaco-economische evaluatie van universele HIV-screening in de zwangerschap; een kosteneffectiviteitsanalyse voor Amsterdam.

OBJECTIVE: To estimate the cost effectiveness of universal screening for HIV of pregnant women in Amsterdam. DESIGN: Pharmaco-economic model calculation. METHOD: An estimate was made of the minimal and maximal prevalences of undiagnosed HIV infection during pregnancy for the whole of Amsterdam, based on epidemiological data from observation among pregnant women in two Amsterdam hospitals and one obstetrical practice. The calculation was based on universal screening with an ELISA test. The interventions after screening comprised pharmacotherapy during pregnancy, delivery by caesarean section and breast-milk substitution. The issues of pharmaco-economic analysis were whether or not costs were reduced and net costs per year of life gained; the question was also studied at what lifetime costs of care for HIV infected children the net costs would be nil (costs equal benefits). RESULTS: Universal HIV screening in Amsterdam required a total investment of about Dfl 300,000.-per annum. In many of the analysed options for HIV screening the financial profits exceeded the investment. Variation of assumptions showed that the net costs of HIV screening under all conditions investigated would remain below Dfl 1,200.-per life year gained. CONCLUSION: Universal HIV screening of pregnant women in Amsterdam showed a favourable cost effectiveness. The calculations indicated a possibility of reducing costs.

[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]. / Opportunistische screening op genitale infecties met Chlamydia trachomatis onder de seksueel actieve bevolking in Amsterdam. III. Kosteneffectiviteitsanalyse van screening bij vrouwen uitgebreid met de rol van herinfectie en partnermeebehandeling.

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.

[Opportunistic screening for genital infections with Chlamydia trachomatis among the sexually active population of Amsterdam. Il Over 90% participation and almost 5% prevalence]. / Opportunistische screening op genitale infecties met Chlamydia trachomatis onder de seksueel actieve bevolking in Amsterdam. I. Meer dan 90% deelname en bijna 5% prevalentie.

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.

[Opportunistic screening for genital infections with Chlamydia trachomatis in sexually active population of Amsterdam. II. Cost-effectiveness analysis of screening women]. / Opportunistische screening op genitale infecties met Chlamydia trachomatis onder de seksueel actieve bevolking in Amsterdam. II. Kosteneffectiviteitsanalyse van screening bij vrouwen.

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.

Adhesion molecule expression on skin endothelia in atopic dermatitis: effects of TNF-alpha and IL-4.

BACKGROUND: Atopic dermatitis (AD) is characterized by skin infiltrates of leukocytes, such as lymphocytes and eosinophils. OBJECTIVE: To describe the mechanisms determining this inflammatory process, we have analyzed expression of adhesion molecules and their regulation on skin endothelial cells (ECs). METHODS: Expression of adhesion molecules on ECs was analyzed by immunohistochemistry by using Ulex europaeus agglutin 1 as a pan-endothelial marker. RESULTS: Vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin were not found in skin of nonatopic individuals, whereas expression of these surface molecules was observed in nonlesional skin of patients with AD and was even more pronounced in lesional skin or after epicutaneous application of aeroallergen. Induction of adhesion molecule expression was examined on both macrovascular ECs from human umbilical cord vein (HUVECs) and human microvascular ECs (HMEC-1) from skin. TNF-alpha very potently upregulated adhesion molecule expression in vitro on both EC cell types. To verify the in vivo relevance of TNF-alpha, we performed TNF-alpha staining in the skin. TNF-alpha was observed in the dermis of nonatopic skin, both in chymase-containing mast cells and CD68+ macrophages. The increase in the number of TNF-alpha-containing cells was concomitant with the increase in adhesion molecule expression in the skin of patients with AD. IL-4 is supposed to be important in atopic diseases because of its IgE- and VCAM-1-inducing properties. However, IL-4 addition failed to induce VCAM-1 expression on HMEC-1, although in the same set of experiments, a clear induction of VCAM-1 expression by IL-4 on HUVECs was demonstrated. Flow cytometry revealed the absence of 11-4 receptor alpha-chains on HMEC-1 and their presence on HUVECs. Immunohistochemistry examination on skin sections showed no binding of the IL-4R alpha-chain antibodies to ECs. CONCLUSION: We conclude that adhesion molecule expression is increased in the skin of patients with AD. Most probably, this increased expression is not a (direct) effect of IL-4 on skin endothelium, but other cytokines, such as TNF-alpha, might be responsible for this increased adhesion molecule expression. Continuous adhesion molecule expression may facilitate T-cell extravasation in a nonantigen-specific manner, thus explaining the presence of increased T-cell numbers in nonlesional skin of patients with AD.

Incidence and risk factors for pneumonia in HIV infected and non-infected drug users.

OBJECTIVE: To study the incidence and risk factors for pneumonia in a cohort of HIV infected and non-infected drug users (DU). DESIGN: A prospective epidemiological study. SETTING AND PATIENTS: Injecting and non-injecting DU who attended the Municipal Health Service in Amsterdam for follow-up visits in the study. MAIN RESULTS: 203 HIV infected and 437 non-infected DU were followed for a total of 1749 person-years. HIV infected DU reported 111 episodes of pneumonia, which required hospitalization in 29 cases, and HIV negative DU reported 55 episodes, which required hospitalization in nine cases. The incidences among HIV positive and HIV negative DU were 0.19 and 0.05 per person-year respectively. With multivariate Poisson regression current injecting (RR 2.13), recent seroconversion (RR 3.92), asthmatic constitution (RR 2.72), CD4+ cell count between 200-500 (RR 1.67 compared to > 500), CD4+ cell count less than 200 (RR 2.23 compared to > 500) and a previous history of pneumonia (RR 2.43) were independently associated with self-reported pneumonia among HIV infected DU. Among HIV negative DU heroin smoking (RR 1.87), asthmatic constitution (RR 3.62) and a previous history of pneumonia (RR 2.84) were independently associated with self-reported pneumonia. Also a higher Quetelet Index (QI) appeared to be protective (QI > or = 21 RR 0.42, QI 19-21 RR 0.82 compared to QI < 19) among HIV negative DU. Risk factors for reported and hospitalized cases of pneumonia were comparable among HIV positive DU. CONCLUSIONS: HIV infected DU are at increased risk for pneumonia and the rate increases with lower CD4 cell counts. Also behavioural characteristics, such as injecting drug use and smoking heroin, and clinical history variables, such as a history of pneumonia or an asthmatic constitution, are risk factors for pneumonia among DU. Pneumococcal vaccination should not only be focused on HIV positive DU but also on the identified risk groups among HIV negative DU.

Development and evaluation of screening strategies for Chlamydia trachomatis infections in an STD clinic.

OBJECTIVES: To identify predictors for Chlamydia trachomatis infection among visitors of an STD clinic in Amsterdam in 1986-1988. To design predictor-based screening programmes for C trachomatis. To evaluate the chosen screening strategy in 1993. METHODS: In 1986-1988, 947 heterosexual men and 648 women participated in the study. A medical history was recorded, a physical examination took place and samples were taken for laboratory diagnostics. Information for 1993 was available from routine databases. RESULTS: C trachomatis infections in heterosexual men in 1986-1988 (prevalence 15.8%) were independently associated with: age under 26 years, being an STD contact, coitarche below 13, last sexual contact with a non-prostitute, (muco)-purulent urethral discharge and ten or more leukocytes per microscopic field of urethral smear or urine. For women (prevalence 21.5%) independent predictors were age under 26, no history of STD, being an STD contact, cervical friability, (muco)purulent cervical discharge, presence of clue cells and ten or more leukocytes per field of urethral smear. Screening men with one anamnestic predictor for C trachomatis and ten or more leukocytes in smear or urine (59% of men) would detect 93% of the cases in 1986-1988. For females only universal screening proved to be suitable. After the introduction of a screening strategy in 1989 (universal for women, indicated by urethritis for men), a strong decline was found in the C trachomatis prevalence for all subgroups in 1993, excluding prostitute's clients and Turkish men. CONCLUSIONS: In 1993 the overall C trachomatis prevalence had declined among the attendants of the STD clinic. It seems likely that this fall was caused both by the screening programme and the reduction of risk behaviour.