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.

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.

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.

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.

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.

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.

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.

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.

Prediction of human active mobility in rural areas: development and validity tests of three different approaches.

BACKGROUND/AIM: Active mobility may play a relevant role in the assessment of environmental exposures (e.g. traffic-related air pollution, livestock emissions), but data about actual mobility patterns are work intensive to collect, especially in large study populations, therefore estimation methods for active mobility may be relevant for exposure assessment in different types of studies. We previously collected mobility patterns in a group of 941 participants in a rural setting in the Netherlands, using week-long GPS tracking. We had information regarding personal characteristics, self-reported data regarding weekly mobility patterns and spatial characteristics. The goal of this study was to develop versatile estimates of active mobility, test their accuracy using GPS measurements and explore the implications for exposure assessment studies. METHODS: We estimated hours/week spent on active mobility based on personal characteristics (e.g. age, sex, pre-existing conditions), self-reported data (e.g. hours spent commuting per bike) or spatial predictors such as home and work address. Estimated hours/week spent on active mobility were compared with GPS measured hours/week, using linear regression and kappa statistics. RESULTS: Estimated and measured hours/week spent on active mobility had low correspondence, even the best predicting estimation method based on self-reported data, resulted in a R2 of 0.09 and Cohen's kappa of 0.07. A visual check indicated that, although predicted routes to work appeared to match GPS measured tracks, only a small proportion of active mobility was captured in this way, thus resulting in a low validity of overall predicted active mobility. CONCLUSIONS: We were unable to develop a method that could accurately estimate active mobility, the best performing method was based on detailed self-reported information but still resulted in low correspondence. For future studies aiming to evaluate the contribution of home-work traffic to exposure, applying spatial predictors may be appropriate. Measurements still represent the best possible tool to evaluate mobility patterns.

Relationship between Coxiella burnetii (Q fever) antibody serology and time spent outdoors.

BACKGROUND/AIM: From 2007 through 2010, the Netherlands experienced the largest recorded Q fever outbreak to date. People living closer to Coxiella burnetii infected goat farms were at increased risk for acute Q fever. Time spent outdoors near infected farms may have contributed to exposure to C. burnetii. The aim of this study was to retrospectively evaluate whether hours/week spent outdoors, in the vicinity of previously C. burnetii infected goat farms, was associated with presence of antibodies against C. burnetii in residents of a rural area in the Netherlands. METHODS: Between 2014-2015, we collected C. burnetii antibody serology and self-reported data about habitual hours/week spent outdoors near the home from 2494 adults. From a subgroup we collected 941 GPS tracks, enabling analyses of active mobility in the outbreak region. Participants were categorised as exposed if they spent time within specified distances (500m, 1000m, 2000m, or 4000m) of C. burnetii infected goat farms. We evaluated whether time spent near these farms was associated with positive C. burnetii serology using spline analyses and logistic regression. RESULTS: People that spent more hours/week outdoors near infected farms had a significantly increased risk for positive C. burnetii serology (time spent within 2000m of a C. burnetii abortion-wave positive farm, OR 3.6 (1.2-10.6)), compared to people spending less hours/week outdoors. CONCLUSIONS: Outdoor exposure contributed to the risk of becoming C. burnetii serology positive. These associations were stronger if people spent more time near C. burnetii infected farms. Outdoor exposure should, if feasible, be included in outbreak investigations.

Cardiovascular Disease Burden in Rural Africa: Does HIV and Antiretroviral Treatment Play a Role?: Baseline Analysis of the Ndlovu Cohort Study.

Background HIV is associated with an increased risk of cardiovascular disease (CVD) in high-income countries. Little is known about the CVD burden in sub-Saharan Africa, where 70% of the world's HIV-positive population lives. This study aims to provide insight into the burden of CVD risk in a rural setting in sub-Saharan Africa considering HIV infection and antiretroviral therapy (ART). Methods and Results A cross-sectional analysis was conducted of the baseline of the Ndlovu Cohort study including HIV-negative and HIV-positive participants in rural South Africa between 2014 and 2017. Information was collected on demographics, socioeconomic status, and CVD risk factors. Carotid intima-media thickness measurement was performed. The influence of HIV and ART on the burden of CVD was determined by comparing HIV-positive participants who were ART naive on first-line or second-line ART with HIV-negative participants. In total, 1927 participants were included, of whom 887 (46%) were HIV positive and 54% women. The median age was 38 years. Overall, 690 participants (79%) were on ART, with 613 (89%) on first-line and 77 (11%) on second-line therapy. Participants with HIV had lower values for most of the CVD risk factors but higher C-reactive protein levels than HIV-negative participants. ART-naive, HIV-positive participants had similar carotid intima-media thickness compared with HIV-negative participants but carotid intima-media thickness was increased for participants on ART aged 30 years and older compared with HIV-negative participants. Conclusions HIV-positive participants presented with a favorable CVD risk profile compared with HIV-negative participants. However, carotid intima-media thickness was increased in HIV-positive participants on ART, indicating a higher burden of subclinical CVD for the HIV-positive population.

Heart Rate Variability, HIV and the Risk of Cardiovascular Diseases in Rural South Africa.

Background: Antiretroviral therapy (ART) transformed human immunodeficiency virus (HIV) infection into a chronic disease. Possible HIV-associated complications have emerged including cardiovascular diseases (CVD). Objectives: This study aims to determine the heart rate variability (HRV) distribution and association between HRV and HIV treated with ART in a rural African population. Methods: This cross-sectional study included 325 participants of the Ndlovu Cohort Study, South Africa. HRV was measured using a standardized five-minute resting ECG and assessed by the standard deviation of normal RR intervals (SDNN), root of mean squares of successive RR differences (RMSSD), percentage of RR intervals greater than 50 milliseconds different from its predecessor (pNN50), total-, low- and high-frequency power. CVD risk factors were assessed using measurements (blood pressure, anthropometry, cholesterol) and questionnaires (e.g. socio-demographics, alcohol, smoking, physical activity, age, diabetes). We used a Wilcoxon rank test to assess differences in medians between HIV-infected and HIV-uninfected participants and multivariable linear regression to investigate associations between HRV and HIV treated with ART. Conclusions: Of the participants, 196 (61.4%) were HIV-infected treated with ART and 123 (38.6%) were HIV-uninfected. HIV-infected consumed less alcohol, 52% versus 35%, smoked less, were less physically active, more often attained lower education, 26% versus 14%, and had lower systolic blood pressure, 134 mmHg versus 140 mmHg, compared to HIV-uninfected. Medians of all HRV parameters were lower for HIV-infected participants. The model fully adjusted for CVD risk factors showed a significant inverse association between HIV treated with ART and log RMSSD (-0.16) and log pnn50 (-0.61). Although HIV-infected participants treated with ART presented with less CVD risk factors they had a lower HRV indicating an increased risk of CVD. Highlights: - African HIV-infected participants on ART had less conventional CVD risk factors than HIV-uninfected.- However, HIV-infected participants had lower HRV than HIV-uninfected participants.- Lower HRV of the HIV-infected participants indicates that they are at a higher risk for CVD.

Response to imported case of Marburg hemorrhagic fever, the Netherland.

On July 10, 2008, Marburg hemorrhagic fever was confirmed in a Dutch patient who had vacationed recently in Uganda. Exposure most likely occurred in the Python Cave (Maramagambo Forest), which harbors bat species that elsewhere in Africa have been found positive for Marburg virus. A multidisciplinary response team was convened to perform a structured risk assessment, perform risk classification of contacts, issue guidelines for follow-up, provide information, and monitor the crisis response. In total, 130 contacts were identified (66 classified as high risk and 64 as low risk) and monitored for 21 days after their last possible exposure. The case raised questions specific to international travel, postexposure prophylaxis for Marburg virus, and laboratory testing of contacts with fever. We present lessons learned and results of the follow-up serosurvey of contacts and focus on factors that prevented overreaction during an event with a high public health impact.

Molecular sequence data of hepatitis B virus and genetic diversity after vaccination.

The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.

Frequent HCV reinfection and superinfection in a cohort of injecting drug users in Amsterdam.

BACKGROUND/AIMS: This study investigates the occurrence of HCV reinfection and superinfection among HCV seroconverters participating in the Amsterdam Cohort Studies among drug users from 1985 through 2005. METHODS: HCV seroconverters (n=59) were tested for HCV RNA at five different time points: the last visit before seroconversion (t=-1), the first visit after seroconversion (t=1), six months after (t=2) and one year after (t=3) seroconversion, and the last visit prior to November 2005 (t=4). If HCV RNA was present, part of the NS5B region was amplified and sequenced. Additional phylogenetic analysis and cloning was performed to establish HCV reinfection and superinfection. RESULTS: Multiple HCV infections were detected in 23/59 (39%) seroconverters; 7 had HCV reinfections, 14 were superinfected, and 2 had reinfection followed by superinfection. At the moment of HCV reinfection, 7/9 seroconverters were HIV-negative: persistent HCV reinfection developed in both HIV-positive cases but also in 4/7 HIV-negative cases. In total, we identified 93 different HCV infections, varying from 1 to 4 infections per seroconverter. Multiple HCV infections were observed in 10/24 seroconverters with spontaneous HCV clearance (11 reinfections, 3 superinfections) and in 13/35 seroconverters without viral clearance (20 superinfections). CONCLUSIONS: HCV reinfection and superinfection are common among actively injecting drug users. This might further complicate the development of an effective HCV vaccine.