Lessons learned from the Amsterdam Cohort Studies among people who use drugs: a historical perspective.

The Netherlands is well known for its early adoption of harm reduction (HR) programs at the height of its heroin crisis in the 1970s/1980s, including the implementation of the first needle and syringe program worldwide. In this manuscript, we describe how the Amsterdam Cohort Studies (ACS) among people who use drugs (PWUD) was conceived within the context of the Dutch HR approach, including the challenges scientists faced while establishing this cohort. This required striking a balance between public health and individual benefit, solving research dilemmas in the face of uncertainty, developing controversial innovative and cutting-edge interventions, which changed the prevention landscape for PWUD, and using longitudinal cohort data to provide unique insights. Studies from the ACS covering follow-up between 1985 and 2016 revealed that participation in both opioid agonist therapy and needle and syringe programs led to a major decrease in the risk of HIV and hepatitis B and C infection acquisition. ACS data have shown that the observed decrease in incidence also likely included shifts in drug markets and drug culture over time, selective mortality among those with the highest levels of risk behaviour, demographic changes of the PWUD population, and progression of the HIV and HCV epidemics. Moreover, HR programs in the Netherlands provided services beyond care for drug use, such as social support and welfare services, likely contributing to its success in curbing the HIV and viral hepatitis epidemics, increasing access and retention to HIV and HCV care and ultimately decreases in overdose mortality over time. Given the low coverage of HR programs in certain regions, it is unsurprising that continued HIV and HCV outbreaks occur and that transmission is ongoing in many countries worldwide. If we aim to reach the World Health Organization viral hepatitis and HIV elimination targets in 2030, as well as to improve the life of PWUD beyond infection risk, comprehensive HR programs need to be integrated as a part of prevention services, as in the Netherlands. We should use the evidence generated by longstanding cohorts, including the ACS, as a basis for which implementation and improved coverage of integrated HR services can be achieved for PWUD worldwide.

Achieving a high cure rate with direct-acting antivirals for chronic Hepatitis C virus infection in Cameroon: a multi-clinic demonstration project.

OBJECTIVES: Highly effective direct-acting antivirals (DAAs) for Hepatitis C treatment are largely inaccessible in sub-Saharan Africa. Data on treatment feasibility and outcomes in clinical settings are limited. We assessed the feasibility of achieving a high (≥90%) cure rate with DAAs in six gastroenterology clinics in Cameroon. METHODS: Patients with chronic Hepatitis C virus (HCV) infection were treated for 12 or 24 weeks with ledipasvir/sofosbuvir, ledipasvir/sofosbuvir/ribavirin or sofosbuvir/ribavirin, depending on the stage of liver disease and HCV genotype. The cure rate was defined as the proportion of patients with a sustained virological response 12 weeks after treatment completion (SVR12) among all treatment completers. RESULTS: We identified 190 HCV RNA positive patients between September-2017 and August-2018, 161 (84.7%) of whom started treatment. 105 (65.2%) were female, median age was 61.3 years [IQR = 55.9-66.9] and 11 (6.8%) were HIV-positive. Median plasma HCV RNA was 6.0 log10 IU/mL [IQR = 5.6-6.4]. HCV genotypes identified were 1 (34.8%), 2 (13.7%), 4 (50.9%), 1 and 4 (0.6%); 46 (28.6%) strains of 160 single-genotype infections were non-subtypeable. Of 158 treatment completers, 152 (96.2%, 95%CI = 91.9-98.6%) achieved SVR12. Six patients did not achieve SVR12: five carried HCV with NS5A resistance mutations and one with NS5B resistance mutations. Three patients died before and two after treatment completion. The most common adverse events were asthenia (12.0%), headache (11.4%) and dizziness (18.9%). CONCLUSION: High cure rates of Hepatitis C with DAAs are achievable in clinical settings of Cameroon. However, the accessibility and provision of HCV screening, diagnosis, treatment, monitoring and care should be addressed for large-scale implementation.

OBJECTIFS: Les antiviraux à action directe (AAD) hautement efficaces pour le traitement de l'hépatite C sont largement inaccessibles en Afrique subsaharienne. Les données sur la faisabilité du traitement et les résultats en milieu clinique sont limités. Nous avons évalué la faisabilité d'atteindre un taux de guérison élevé (≥90%) avec les AAD dans six cliniques de gastro-entérologie au Cameroun. MÉTHODES: Les patients atteints d'une infection chronique par le virus de l'hépatite C (VHC) ont été traités pendant 12 ou 24 semaines avec le ledipasvir/sofosbuvir, le ledipasvir/sofosbuvir/ribavirine ou le sofosbuvir/ribavirine, selon le stade de la maladie du foie et le génotype du VHC. Le taux de guérison a été défini comme la proportion de patients présentant une réponse virologique soutenue 12 semaines après la fin du traitement (SVR12) parmi tous les patients ayant terminé le traitement. RÉSULTATS: Nous avons identifié 190 patients positifs pour l'ARN du VHC entre septembre 2017 et août 2018, dont 161 (84,7%) ont commencé le traitement. 105 (65,2%) étaient des femmes, l'âge médian était de 61,3 ans [IQR = 55,9-66,9] et 11 (6,8%) étaient positifs pour le VIH. L'ARN plasmatique médian était de 6,0 log10 UI/mL [IQR = 5,6-6,4]. Les génotypes du VHC identifiés étaient 1 (34,8%), 2 (13,7%), 4 (50,9%), 1 et 4 (0,6%); 46 (28,6%) souches provenant de 160 infections à génotype unique n'étaient pas sous-typables. Sur 158 patients ayant terminé le traitement, 152 (96,2%, IC95%: 91,9-98,6%) ont atteint la RVS12. Six patients n'ont pas atteint la RVS12: cinq portaient le VHC avec des mutations de résistance NS5A et un avec des mutations de résistance NS5B. Trois patients sont décédés avant et deux après la fin du traitement. Les événements indésirables les plus courants étaient l'asthénie (12,0%), les céphalées (11,4%) et les étourdissements (18,9%). CONCLUSION: Des taux élevés de guérison de l'hépatite C avec les AAD sont réalisables dans les milieux cliniques du Cameroun. Cependant, l'accessibilité et la fourniture du dépistage, le diagnostic, du traitement, de la surveillance et des soins du VHC devraient être adressés pour une mise en œuvre à grande échelle.

Mobility assessment of a rural population in the Netherlands using GPS measurements.

BACKGROUND: The home address is a common spatial proxy for exposure assessment in epidemiological studies but mobility may introduce exposure misclassification. Mobility can be assessed using self-reports or objectively measured using GPS logging but self-reports may not assess the same information as measured mobility. We aimed to assess mobility patterns of a rural population in the Netherlands using GPS measurements and self-reports and to compare GPS measured to self-reported data, and to evaluate correlates of differences in mobility patterns. METHOD: In total 870 participants filled in a questionnaire regarding their transport modes and carried a GPS-logger for 7 consecutive days. Transport modes were assigned to GPS-tracks based on speed patterns. Correlates of measured mobility data were evaluated using multiple linear regression. We calculated walking, biking and motorised transport durations based on GPS and self-reported data and compared outcomes. We used Cohen's kappa analyses to compare categorised self-reported and GPS measured data for time spent outdoors. RESULTS: Self-reported time spent walking and biking was strongly overestimated when compared to GPS measurements. Participants estimated their time spent in motorised transport accurately. Several variables were associated with differences in mobility patterns, we found for instance that obese people (BMI > 30 kg/m2) spent less time in non-motorised transport (GMR 0.69-0.74) and people with COPD tended to travel longer distances from home in motorised transport (GMR 1.42-1.51). CONCLUSIONS: If time spent walking outdoors and biking is relevant for the exposure to environmental factors, then relying on the home address as a proxy for exposure location may introduce misclassification. In addition, this misclassification is potentially differential, and specific groups of people will show stronger misclassification of exposure than others. Performing GPS measurements and identifying explanatory factors of mobility patterns may assist in regression calibration of self-reports in other studies.

Prospects of elimination of HIV with test-and-treat strategy.

Recently, there has been much debate about the prospects of eliminating HIV from high endemic countries by a test-and-treat strategy. This strategy entails regular HIV testing in the entire population and starting antiretroviral treatment immediately in all who are found to be HIV infected. We present the concept of the elimination threshold and investigate under what conditions of treatment uptake and dropout elimination of HIV is feasible. We used a deterministic model incorporating an accurate description of disease progression and variable infectivity. We derived explicit expressions for the basic reproduction number and the elimination threshold. Using estimates of exponential growth rates of HIV during the initial phase of epidemics, we investigated for which populations elimination is within reach. The concept of the elimination threshold allows an assessment of the prospects of elimination of HIV from information in the early phase of the epidemic. The relative elimination threshold quantifies prospects of elimination independently of the details of the transmission dynamics. Elimination of HIV by test-and-treat is only feasible for populations with very low reproduction numbers or if the reproduction number is lowered significantly as a result of additional interventions. Allowing low infectiousness during primary infection, the likelihood of elimination becomes somewhat higher. The elimination threshold is a powerful tool for assessing prospects of elimination from available data on epidemic growth rates of HIV. Empirical estimates of the epidemic growth rate from phylogenetic studies were used to assess the potential for elimination in specific populations.

Estimating the transfusion transmission risk of Q fever.

BACKGROUND: The Q fever outbreaks in the Netherlands in 2007 to 2009 initiated discussion on the necessity of measures to prevent transmission through blood products. Risk assessments help transfusion regulators decide when and where measures are required. This study assesses the transfusion transmission (TT) risk of Q fever using the European Up-Front Risk Assessment Tool (EUFRAT) model. STUDY DESIGN AND METHODS: We estimated the number of Q fever infections in recipients during the 2007 to 2009 outbreaks' peaks using selected notification data; estimates are calculated from the probability of a donor being infected. We compared this probability to the prevalence of infection estimated from an independent donation testing study and using the Biggerstaff model. We also quantified the risk reduction by implementing measures such as donation testing and donor deferral. RESULTS: At the peak of the 2007, 2008, and 2009 outbreaks, there were an estimated 0.21, 0.96, and 1.59 recipients infected with Q fever, respectively. Between June 1, 2009, and January 31, 2010, the probability of a donor being infected with Q fever in the high-incidence areas was estimated at 260 (95% confidence interval, 192-340) per 100,000 donors, consistent with results from the donation testing study. The EUFRAT estimates were also consistent with estimates from the Biggerstaff model. Scenario analyses showed that donation testing provided the largest risk reduction of various risk reduction strategies. CONCLUSION: The TT risk of Q fever during the 2007 to 2009 outbreaks was small, a result that is consistent with results of other studies. EUFRAT can be applied successfully to support decision making during outbreaks.

Twelve-month incidence and clearance of oral HPV infection in HIV-negative and HIV-infected men who have sex with men: the H2M cohort study.

BACKGROUND: Our aim was to compare the 12-month incidence and clearance of oral high-risk HPV infection between HIV-infected men who have sex with men (MSM) and HIV-negative MSM. METHODS: MSM aged 18 years or older were recruited in Amsterdam, the Netherlands. Questionnaire data and oral-rinse and gargle samples were collected at baseline, and after 6 and 12 months. HPV DNA was genotyped using the SPF10-PCR & DEIA-LiPA25 system (version 1). Determinants of oral HPV incidence and clearance were explored using Cox and logistic regression analyses respectively. RESULTS: 433 HIV-negative and 290 HIV-infected MSM were included in these analyses. The median follow-up time per participant was 12 months (range 3-15). During follow-up, 114 incident oral high-risk HPV infections were observed. The incidence rate of HPV-16 was 3.5/1000 person-months (PM) in HIV-infected and 0.9/1000 PM in HIV-negative MSM (IRR 4.1; 95% CI 1.3-13.2). The incidence rates of other high-risk HPV types ranged between 1.3-3.5/1000 PM in HIV-infected and 0.0-1.1/1000 PM in HIV-negative MSM. In multivariable analyses, HIV infection (adjusted hazard ratio [aHR] 3.8; 95% CI 2.3-6.2) and a higher number of recent oral sex partners (aHR 2.4 for ≥8 partners compared to ≤2; 95% CI 1.4-4.2) were associated with HPV incidence. Of the 111 baseline oral high-risk infections, 59 (53.2%) were cleared. In multivariable analyses, only a higher number of recent oral sex partners was associated with HPV clearance (adjusted odds ratio 3.4 for ≥8 compared to ≤2 partners; 95% CI 1.3-9.0). CONCLUSIONS: The incidence rate of oral high-risk HPV infection was higher in HIV-infected MSM and in those with a higher number of recent oral sex partners. Just over half of the oral high-risk HPV infections at baseline were cleared after 12 months, with a higher likelihood of clearance among MSM reporting higher numbers of recent oral sex partners, but no difference by HIV status.

Do sexual risk behaviour, risk perception and testing behaviour differ across generations of migrants?

BACKGROUND: Behaviour and related health outcomes of migrants have been suggested to shift towards the practices of the indigenous population of the host country. To investigate this, we studied generational differences in sexual behaviour between first- and second-generation migrants (FGMs and SGMs) in The Netherlands. METHODS: In 2003-05, persons aged 16-70 years with origins in Surinam, the Antilles and Aruba were interviewed on their sexual behaviour in The Netherlands and their country of origin. The relationship of generation, age at migration and sexual behaviour was studied by multinomial logistic regression analyses. RESULTS: Generational differences were observed regarding concurrent partnerships, anal sex and history of sexually transmitted infection. Compared with FGMs who migrated at an age >25 years, those who migrated between 10 and 25 years of age were more likely to report concurrency [odds ratio (OR): 1.52, 95% confidence interval (CI): 1.14-2.04], whereas SGMs were less likely to report concurrency (OR: 0.65, 95% CI: 0.43-0.98). FGMs who migrated before the age of 10 were more likely to have had anal sex (OR: 1.90, 95% CI: 1.34-2.71) or a sexually transmitted infection diagnosis (OR: 1.80, 95% CI: 1.20-2.71) than those who had migrated at >25 years of age. CONCLUSION: Our study shows that not only SGMs but also FGMs who migrated at an early age tend to differ from the sexual patterns of FGMs who migrated at an older age. Generational differences in sexual behaviour could be explained by acculturation and increased identity with the values of the host country.

No Evidence for an Association of HIV and Antiviral Treatment With Changes in Framingham Cardiovascular Risk Score in the Ndlovu Cohort Study.

BACKGROUND: HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease (CVD) risk in high-income countries. The authors studied the longitudinal association between HIV and ART and nonlaboratory Framingham Risk Score (FRS) in a middle-income country. METHODS AND RESULTS: This longitudinal analysis of the NCS (Ndlovu Cohort Study), South Africa used baseline to 36-month follow-up data. Demographics, HIV, ART status, and cardiometabolic measures were obtained. FRS was used as a CVD risk measure. Through linear mixed models, FRS trends over time and the association with HIV were studied. Analysis included 1136 participants, with 609 (54%) having HIV, and 495 (81%) taking ART. At baseline, 9.8% of participants had a high FRS. People living with HIV (PLHIV) had a 3.2% lower FRS than HIV-negative participants (P<0.001). FRS increased similarly for both groups over time. Other factors associated with FRS were secondary and higher education (ß value: -0.075, P<0.001; ß value: -0.084, P<0.001) and alcohol consumption (ß value: 0.011, P<0.001). CONCLUSIONS: CVD risk increased for all participants over 36 months, suggesting classic risk factors rather than HIV status or ART to be drivers of CVD risk. People living with HIV had a significantly lower FRS than their HIV-negative counterparts, possibly related to HIV itself or a more frequent interaction with healthcare services. No association of HIV and ART with changes in FRS over 36 months was observed, suggesting the need for research using clinical endpoints to elucidate the effects of HIV and ART on CVD risk. Population-based prevention of CVD risk factors in sub-Saharan Africa is warranted, regardless of HIV status.

Targeted vaccination programme successful in reducing acute hepatitis B in men having sex with men in Amsterdam, the Netherlands.

BACKGROUND & AIMS: In the Netherlands, transmission of hepatitis B virus occurs mainly within behavioural high-risk groups, such as in men who have sex with men. Therefore, a vaccination programme has targeted these high-risk groups. This study evaluates the impact of the vaccination programme targeting Amsterdam's large population of men who have sex with men from 1998 through 2011. METHODS: We used Amsterdam data from the national database of the vaccination programme for high-risk groups (January 1, 1998 to December 31, 2011). Programme and vaccination coverage were estimated with population statistics. Incidence of acute hepatitis B was analyzed with notification data from the Amsterdam Public Health Service (1992-2011). Mathematical modelling accounting for vaccination data and trends in sexual risk behaviour was used to explore the impact of the programme. RESULTS: At the end of 2011, programme coverage was estimated at 41% and vaccination coverage from 30% to 38%. Most participants (67%) were recruited from the outpatient department for sexually transmitted infections and outreach locations such as saunas and gay bars. Incidence of acute hepatitis B dropped sharply after 2005. The mathematical model in which those who engage most in high-risk sex are vaccinated, best explained the decline in incidence. CONCLUSIONS: Transmission of hepatitis B virus among Amsterdam's men who have sex with men has decreased, despite ongoing high-risk sexual behaviour. Vaccination programmes targeting men who have sex with men do not require full coverage; they may be effective when those who engage most in high-risk sex are reached.

Strategies for early detection of chronic Q-fever: a systematic review.

BACKGROUND: Chronic Q-fever, a condition with high morbidity and mortality, may develop after an acute infection with Coxiella burnetii (acute Q-fever). Several strategies have been suggested for early detection of chronic Q-fever, focusing on follow-up of known acute Q-fever patients and detection of asymptomatic or unknown chronic infections. As there is no international standard or consensus, the aims of this study were to summarise the available literature and assess the evidence for different follow-up and screening strategies. DESIGN: We conducted a systematic review by searching PubMed and Embase. Twenty articles were included, of which fourteen only provided information on follow-up of known acute Q-fever cases, four presented data on identification of previously unknown C. burnetii infections, and two had information on both topics. RESULTS: The conversion rate of acute to chronic Q-fever ranged from 0 to 5.0%. Most studies advised serological follow-up of acute Q-fever patients, but without consistent advice on optimum timing and duration. The recommendation to use echocardiography for all acute Q-fever patients to detect valvular damage remains controversial. Screening of high-risk patients in an outbreak setting is advised by studies investigating such strategy. CONCLUSIONS: There is sufficient evidence to support serological follow-up of all known acute Q-fever patients at least once during the first year following the acute infection, and more frequently in patients with known risk factors for chronic disease, such as heart valve- or vascular prosthesis. Screening of risk groups should be considered in outbreaks of Q-fever.

Hepatitis B vaccination of men who have sex with men in the Netherlands: should we vaccinate more men, younger men or high-risk men?

OBJECTIVES: The selective vaccination programme against hepatitis B virus (HBV) was introduced in the Netherlands in 2002 targeting high-risk groups, including men who have sex with men (MSM). Despite the high average age of vaccination in MSM, the number of notifications of acute HBV recently declined. We investigate whether this can be attributed to the selective vaccination programme. We examine how vaccination strategies could be improved and the impact of universal infant vaccination introduced in 2011. METHODS: We use a mathematical model for HBV transmission among MSM. The incidence of HBV was calculated from the model and from notification data of acute HBV. RESULTS: A decline was observed in the incidence of HBV since 2006, as calculated from the model; this decline was smaller than that observed in data if all MSM were equally likely to be vaccinated. Assuming that high-risk MSM were more likely to be vaccinated than low-risk MSM resulted in a steeper decline in modelled incidence and better agreement with observed incidence. Vaccinating MSM at a younger age or doubling the vaccination rate would increase the impact of selective vaccination, but is less effective than vaccinating high-risk MSM. CONCLUSIONS: Selective HBV vaccination of MSM in the Netherlands has had a substantial impact in reducing HBV incidence. The reduction suggests that vaccination rates among high-risk MSM were higher than those among low-risk MSM. Countries that have not yet reached 35-year cohorts with universal childhood vaccination should actively implement or continue selective high-risk MSM vaccination.

Distinct Neisseria gonorrhoeae transmission networks among men who have sex with men in Amsterdam, The Netherlands.

BACKGROUND: Molecular typing was used to elucidate Neisseria gonorrhoeae transmission networks among men who have sex with men (MSM) in Amsterdam, the Netherlands. We determined whether clusters of patients infected with specific N. gonorrhoeae genotypes were related to various epidemiological characteristics. METHODS: MSM (age ≥18 years) visiting the sexually transmitted infections (STI) clinic between July 2008 and August 2009 were eligible. After STI screening, participants completed a behavioral questionnaire concerning the previous 6 months. N. gonorrhoeae cultures were genotyped using multiple-locus variable-number tandem repeat analysis typing. RESULTS: We obtained 278 N. gonorrhoeae-positive isolates from 240 MSM. Five large clusters (≥10 isolates), a unique sixth cluster (n = 9), and 8 smaller clusters (5-9 isolates) were identified. Prevalence of human immunodeficiency virus differed between clusters I and VI (P = .003), ranging from 27.8% to 100%. Receptive unprotected anal intercourse was frequently reported by MSM (51.8%) but did not differ significantly among clusters. Significant differences were identified concerning the participant's history of syphilis (P = .030), having met partners at a popular sex venue in Amsterdam (P = .048), and meeting partners outside Amsterdam (P = .036). CONCLUSIONS: Distinct N. gonorrhoeae transmission networks were present in a mixed high-risk MSM population; concordance between clusters and epidemiological characteristics was present but not marked.

Recreational drug use during sex and sexually transmitted infections among clients of a city sexually transmitted infections clinic in Amsterdam, the Netherlands.

BACKGROUND: Recreational drug use is associated with high-risk sexual behavior and sexually transmitted infections (STIs). We assessed the prevalence of drug use during sex and the associations between such use and STI (chlamydia, gonorrhea, or syphilis). METHODS: During 3 periods in 2008 and 2009, attendees of an STI clinic in Amsterdam were interviewed about sexual behavior and drug use during sex and tested for STI. Associations between sex-related drug use and STI were assessed separately for heterosexual men, men who have sex with men (MSM), and women. We examined whether drug use was associated with STI after adjusting for high-risk sexual behavior. RESULTS: Nine hundred sixty-one heterosexual men, 673 MSM, and 1188 women participated in this study. Of these, 11.9% had chlamydia, 3.4% gonorrhea, and 1.2% syphilis. Sex-related drug use in the previous 6 months was reported by 22.6% of heterosexual men, 51.6% of MSM, and 16.0% of women. In multivariable analyses, adjusting for demographics (and high-risk sexual behavior in MSM), sex-related drug use was associated with STI in MSM (any drugs and poppers) and women (GHB and XTC) but not in heterosexual men. Stratified analysis in MSM showed that sex-related use of poppers was associated with STI in HIV-negative MSM but not in HIV-infected MSM. CONCLUSION: Clients reported frequent sex-related drug use, which was associated with STI in MSM and women. In MSM, sex-related drug use was associated with STI after adjusting for high-risk sexual behavior but only in HIV-negative MSM. Prevention measures targeted at decreasing sex-related drug use could reduce the incidence of STI.

Hepatitis C in the general population of various ethnic origins living in the Netherlands: should non-Western migrants be screened?

BACKGROUND & AIMS: Little is known about the HCV prevalence in non-Western migrant populations. To determine whether targeted HCV screening and prevention programs for migrants are needed, we examined HCV prevalence and determinants among non-Western, Western migrants, and the native Dutch population in the Netherlands. METHODS: Data were obtained from four surveys: (1) 3895 heterosexual visitors recruited during biannual surveys at the STI-clinic Amsterdam, 2007-2009; (2) random sample of 4563 pregnant women in Amsterdam, 2003; (3) population-based random sample of 1309 inhabitants of Amsterdam, 2004; (4) population-based random sample of 4428 people living in the Netherlands, 2006-2007. Characteristics associated with HCV-positivity were examined and phylogenetic analysis was used to obtain insight in the geographical origin of HCV strains. RESULTS: HCV seroprevalence in the four surveys was low (0.3-0.6%). In total 4860/14,195 (34%) were non-Western and 9329/14,195 (66%) Western participants (including Dutch). First-generation non-Western migrants were more likely to be HCV-positive (0.7-2.3%) than Western participants (0.1-0.4%). Except for survey 3, second-generation non-Western migrants had a lower HCV prevalence than first-generation migrants, comparable to Western migrants and the Dutch population. Phylogenetic analysis showed that the majority of the HCV-positive, first-generation non-Western non-European migrants were infected with endemic strains which are rarely observed in Europe. CONCLUSIONS: First-generation non-Western migrants are at increased risk for HCV. Phylogenetic analysis suggests that transmission likely took place in the country of origin, causing introduction but no further transmission of endemic HCV strains in the Netherlands. HCV screening and prevention programs should target first-generation, but not second-generation, non-Western migrants.

No impact of hepatitis C virus infection on mortality among drug users during the first decade after seroconversion.

BACKGROUND & AIMS: Most studies of progression of chronic hepatitis C virus (cHCV) infection were conducted in hospital settings and were therefore biased for patients with severe disease. We evaluated the long-term outcomes of hepatitis C virus (HCV) infection among injecting drug users, recruited from outside the hospital setting, and examined the effect of cHCV on mortality after seroconversion. METHODS: We studied data from 106 seroconverters with a documented or estimated date of HCV seroconversion. Cox proportional hazards analysis was used to determine the effect of HCV persistence, compared with HCV clearance, on survival after HCV seroconversion. The median follow-up time was 14.8 years (interquartile range, 7.8-19.6). RESULTS: cHCV infection developed in 71 of the subjects (67%; 95% confidence interval [CI], 57%-76%); 33 subjects died. One HCV-related death was observed 23 years after HCV seroconversion. Most causes of death were non-natural (n = 12) or acquired immune deficiency syndrome-related (n = 8). The effect of cHCV on mortality was nonproportional over time. When survival time was analyzed separately for 0-5 years, >5-10 years, and >10 years after HCV seroconversion, the age-adjusted hazard ratios for cHCV were 0.59 (95% CI, 0.16-2.20), 1.76 (95% CI, 0.36-8.53), and 8.28 (95% CI, 1.10-64.55), respectively, compared with resolved HCV infection. CONCLUSIONS: cHCV infection does not affect overall mortality in the first decade after seroconversion, compared with individuals who resolve HCV infection; however, during the second decade after infection, individuals with cHCV have an increased risk for all-cause mortality. Mortality from liver-related causes was low but might have been masked by competing mortality.

Evaluation of high-resolution typing methods for Chlamydia trachomatis in samples from heterosexual couples.

We aimed to compare conventional ompA typing of Chlamydia trachomatis with multilocus sequence typing (MLST) and multilocus variable-number tandem-repeat (VNTR) analysis (MLVA). Previously used MLST and MLVA systems were compared to modified versions that used shorter target regions and nested PCR. Heterosexual couples were selected from among persons with urogenital C. trachomatis infections visiting the sexually transmitted infection outpatient clinic in Amsterdam, The Netherlands. We identified 30 couples with a total of 65 C. trachomatis-positive samples on which MLST and MLVA for eight target regions were performed. All regions were successfully sequenced in 52 samples, resulting in a complete profile for 18 couples and 12 individuals. Nine ompA genovars from D to K, with two variants of genovar G, were found. The numbers of sequence type and MLVA type profiles were 20 for MLST and 21 for MLVA, and a combination of MLST and MLVA yielded 28 profiles, with discriminatory indexes (D) ranging from 0.95 to 0.99. Partners in 17 couples shared identical profiles, while partners in 1 couple had completely different profiles. Three persons had infections at multiple anatomical locations, and within each of these three individuals, all profiles were identical. The discriminatory capacity of all MLST and MLVA methods is much higher than that of ompA genotyping (D = 0.78). No genotype variation was found within the samples of the same person or from heterosexual couples with a putative single transmission. This shows that the chlamydial genome in clinical specimens has an appropriate polymorphism to enable epidemiological cluster analysis using MLST and MLVA.

How patterns of migration can influence the heterosexual transmission of HIV in The Netherlands.

OBJECTIVES: Migrants originating from countries with a high HIV prevalence account for a large number of heterosexually acquired HIV infections in western European countries. These migrants may be infected before migrating and they may engage in unsafe sexual practices both in the country of residence and in their country of origin. This report investigates how patterns of migration may affect the heterosexual HIV epidemic in The Netherlands. METHODS: A mathematical model was used that describes the transmission of HIV in heterosexual partnerships between African migrants, Caribbean migrants and the local Dutch population. Infection of migrants before migrating to The Netherlands and during trips to their country of origin was also accounted for. RESULTS: The incidence of HIV infection among adult heterosexuals in 2010 was 1.50 new infections per 100,000 individuals per year. If the number of migrants entering the country increases, then the incidence of HIV will increase, although this change among Dutch individuals will be negligible. Moreover, if HIV prevalence among those migrating to The Netherlands (at the time of entry to the country) is higher, then incidence in the respective ethnic group will increase; among other ethnic groups, the increase will be very small. CONCLUSIONS: Heterosexual transmission of HIV in The Netherlands occurs mostly within migrant communities. Limiting migration and introducing travel restrictions would probably have no effect on HIV incidence in countries with low HIV prevalence among heterosexuals. Policy making should focus on targeted interventions, to reduce the burden of disease in migrant communities in Europe.

Exploring the characteristics of a local demand for African wild meat: A focus group study of long-term Ghanaian residents in the Netherlands.

While there is a growing body of research documenting unregulated African wild meat imports into Europe from the Africa continent, the drivers of this demand are virtually unknown. This study employs focus group discussions and a survey questionnaire to examine the attitudes and practices related to African wild meat consumption in the city of Amsterdam, Netherlands. The Ghanaian community was selected as the object of this study, as it is the largest West African population in the Netherlands and represents an important part of Dutch society. We model our report on a recent US study of the Liberian community of Minneapolis, Minnesota, which allows for the comparison of results between two Western countries. The overall perceived health risk of consuming African wild meat in The Netherlands is low and unlikely to deter consumption. However, local prices for the meat may be prohibitive in some cases. Incentives include health benefits, cultural drivers and a strong preference for the taste of African wild meat over all local meat alternatives. The study calls for further research into the nature of the drivers of demand for African wild meat as well as its public health consequences, in the Netherlands and beyond.

Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men.

BACKGROUND & AIMS: Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM. METHODS: HIV-positive MSM diagnosed with recent HCV (n = 226) in England (107), The Netherlands (58), France (12), Germany (25), and Australia (24) between 2000 and 2006 were enrolled into a molecular phylogenetic study. Using real-time polymerase chain reaction (PCR), the NS5B region of the HCV genome (436 base pair) was amplified, sequenced, and compared with unrelated NS5B sequences. RESULTS: NS5B sequences were obtained from 200 (89%) cases. Circulating HCV genotypes were 1a (59%), 4d (23%), 3a (11%), 1b (5%), and 2b/c (3%). Phylogenetic analysis revealed 156 (78%) sequences that formed 11 clusters (bootstrap value > 70%) containing between 4 and 37 individual sequences. Country mixing was associated with larger cluster size (17 vs 4.5 sequences; P = .03). "Molecular clock" analysis indicated that the majority (85%) of transmissions occurred since 1996. CONCLUSIONS: Phylogenetic analysis revealed a large international network of HCV transmission among HIV-positive MSM. The rapid spread of HCV among neighboring countries is supported by the large proportion (74%) of European MSM infected with an HCV strain co-circulating in multiple European countries, the low evolutionary distances among HCV isolates from different countries, and the trend toward increased country mixing with increasing cluster size. Temporally, this epidemic coincides with the introduction of highly active antiretroviral therapy and associated increases in sexual risk behaviors. International collaborative public health efforts are needed to mitigate HCV transmission among this population.

Seroprevalence and determinants of eight high-risk human papillomavirus types in homosexual men, heterosexual men, and women: a population-based study in Amsterdam.

BACKGROUND: To determine differences in the seroprevalence of high-risk human papillomavirus (hrHPV) types between men having sex with men (MSM), heterosexual men and women, we analyzed seroprevalence and risk factors for 8 hrHPV in the general population of Amsterdam, the Netherlands. METHODS: We interviewed 1349 inhabitants aged ≥17 years and tested sera for antibodies against L1 capsid proteins of 8 hrHPV using Luminex-based multiplex serology. Risk factors for hrHPV were determined by multivariate Poisson analysis. RESULTS: Seroprevalences for 8 hrHPV ranged from 13.1% for HPV-45 to 31.4% for HPV-35. Seropositivity for HPV-16 and HPV-18 was more common in women and MSM than in heterosexual men. HPV-16 and -18 were more common in subjects also having antibodies against other hrHPV types (prevalence rate ratio [PRR], 2.12, 95% confidence interval [CI] 1.52-2.97; and PRR, 2.00; 95% CI, 1.43-2.81, respectively) and/or herpes simplex virus type 2 (PRR, 1.69; 95% CI, 1.32-2.16; and PRR, 1.47; 95% CI, 1.13-1.92, respectively). HPV-18 was more common in persons with a history of sexually transmitted infections (STI) (PRR, 1.64; 95% CI, 1.20-2.25). HPV-35, -45, and -58 were more common in non-European ethnic groups. CONCLUSIONS: Prevalence of 8 hrHPV antibodies was high in the Amsterdam population, especially in MSM.