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1.  Comparison of subset selection methods in linear regression in the context of health-related quality of life and substance abuse in Russia 
Automatic stepwise subset selection methods in linear regression often perform poorly, both in terms of variable selection and estimation of coefficients and standard errors, especially when number of independent variables is large and multicollinearity is present. Yet, stepwise algorithms remain the dominant method in medical and epidemiological research.
Performance of stepwise (backward elimination and forward selection algorithms using AIC, BIC, and Likelihood Ratio Test, p = 0.05 (LRT)) and alternative subset selection methods in linear regression, including Bayesian model averaging (BMA) and penalized regression (lasso, adaptive lasso, and adaptive elastic net) was investigated in a dataset from a cross-sectional study of drug users in St. Petersburg, Russia in 2012–2013. Dependent variable measured health-related quality of life, and independent correlates included 44 variables measuring demographics, behavioral, and structural factors.
In our case study all methods returned models of different size and composition varying from 41 to 11 variables. The percentage of significant variables among those selected in final model varied from 100 % to 27 %. Model selection with stepwise methods was highly unstable, with most (and all in case of backward elimination: BIC, forward selection: BIC, and backward elimination: LRT) of the selected variables being significant (95 % confidence interval for coefficient did not include zero). Adaptive elastic net demonstrated improved stability and more conservative estimates of coefficients and standard errors compared to stepwise. By incorporating model uncertainty into subset selection and estimation of coefficients and their standard deviations, BMA returned a parsimonious model with the most conservative results in terms of covariates significance.
BMA and adaptive elastic net performed best in our analysis. Based on our results and previous theoretical studies the use of stepwise methods in medical and epidemiological research may be outperformed by alternative methods in cases such as ours. In situations of high uncertainty it is beneficial to apply different methodologically sound subset selection methods, and explore where their outputs do and do not agree. We recommend that researchers, at a minimum, should explore model uncertainty and stability as part of their analyses, and report these details in epidemiological papers.
Electronic supplementary material
The online version of this article (doi:10.1186/s12874-015-0066-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4553217  PMID: 26319135
Bayesian model selection; Penalized least squares; Stepwise regression; Linear regression; Subset selection; Quality of life; Substance abuse; HIV; Russia
3.  Association between HIV-1 tropism and CCR5 human haplotype E in a Caucasian population 
The influence of the diversity of CCR5 on HIV susceptibility and disease progression has been clearly demonstrated but how the variability of this gene influences the HIV tropism is poorly understood. We investigated whether CCR5 haplotypes are associated with HIV tropism in a Caucasian population.
We evaluated 161 HIV-positive subjects in a cross-sectional study. CCR5 haplotypes were derived after genotyping nine CCR2-CCR5 polymorphisms. The HIV subtype was determined by phylogenetic analysis using the Maximum Likelihood method and viral tropism by the genotypic tropism assay (geno2pheno). Associations between CCR5 haplotypes and viral tropism were determined using logistic regression analyses. Samples from 500 blood donors were used to evaluate the representativeness of HIV-positives in terms of CCR5 haplotype distribution.
The distribution of CCR5 haplotypes was similar in HIV-positive subjects and blood donors. The majority of viruses (93.8%) belonged to HIV-1 CRF06_cpx; 7.5% were X4, and the remaining were R5 tropic. X4 tropic viruses were overrepresented among people with CCR5 human haplotype E (HHE) compared to those without this haplotype (13.0% vs 1.4%; p=0.006). People possessing CCR5 HHE had eleven times increased odds (OR=11.00; 95% CI 1.38 to 87.38) of having X4 tropic viruses than those with non-HHE. After adjusting for antiretroviral therapy (ARV), neither the presence of HHE nor the use of ARV were associated with X4 tropic viruses.
Our results suggest that CCR5 HHE as well as ARV treatment might be associated with the presence of HIV-1 X4 tropic viruses.
PMCID: PMC4146654  PMID: 24508837
CCR5; X4 tropic viruses; intravenous drug users
4.  Screening for genital chlamydia infection 
This is the protocol for a review and there is no abstract. The objectives are as follows:
To assess the effects and safety of chlamydia screening in pregnant and non-pregnant women and in men, compared with standard care, on chlamydia transmission and on complications of infection.
PMCID: PMC4459401
5.  Genital Chlamydia Prevalence in Europe and Non-European High Income Countries: Systematic Review and Meta-Analysis 
PLoS ONE  2015;10(1):e0115753.
Accurate information about the prevalence of Chlamydia trachomatis is needed to assess national prevention and control measures.
We systematically reviewed population-based cross-sectional studies that estimated chlamydia prevalence in European Union/European Economic Area (EU/EEA) Member States and non-European high income countries from January 1990 to August 2012. We examined results in forest plots, explored heterogeneity using the I2 statistic, and conducted random effects meta-analysis if appropriate. Meta-regression was used to examine the relationship between study characteristics and chlamydia prevalence estimates.
We included 25 population-based studies from 11 EU/EEA countries and 14 studies from five other high income countries. Four EU/EEA Member States reported on nationally representative surveys of sexually experienced adults aged 18–26 years (response rates 52–71%). In women, chlamydia point prevalence estimates ranged from 3.0–5.3%; the pooled average of these estimates was 3.6% (95% CI 2.4, 4.8, I2 0%). In men, estimates ranged from 2.4–7.3% (pooled average 3.5%; 95% CI 1.9, 5.2, I2 27%). Estimates in EU/EEA Member States were statistically consistent with those in other high income countries (I2 0% for women, 6% for men). There was statistical evidence of an association between survey response rate and estimated chlamydia prevalence; estimates were higher in surveys with lower response rates, (p = 0.003 in women, 0.018 in men).
Population-based surveys that estimate chlamydia prevalence are at risk of participation bias owing to low response rates. Estimates obtained in nationally representative samples of the general population of EU/EEA Member States are similar to estimates from other high income countries.
PMCID: PMC4304822  PMID: 25615574
6.  Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users 
TLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection.
Materials and methods
A total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay.
The TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors – 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p = 0.037 and 80% vs. 53%; p = 0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR = 0.29, 95% CI = 0.09–0.90). This association remained significant (OR = 0.25, 95% CI = 0.07–0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use).
The TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.
PMCID: PMC4001117  PMID: 23962581
TLR3; Leu412Phe; Intravenous drug users; Highly exposed HIV seronegatives
7.  Provision of chlamydia testing, and training of primary health care staff about chlamydia testing, across four European countries 
BMC Public Health  2014;14:1147.
The objectives of this study were to describe and compare chlamydia testing provided by general practitioners (GPs) in four selected European countries with well-developed primary health care systems and high reported chlamydia rates; we aimed to compare contrasting countries where chlamydia testing is provided by GPs (England, Sweden) with countries where primary care chlamydia testing is absent or very limited (France, Estonia).
For data generation a structured questionnaire was developed and secondary data sources were searched. The questionnaire developed by the research team allowed a systematic approach to analysing chlamydia care (including testing in general practice) and the gathering of relevant data.
There were no significant differences in the burden of the disease or the type of general practice care provision in the study countries. In all four countries, testing for chlamydia (with nucleic acid amplification test, NAAT) is available in the public sector, a substantial proportion (>60%) of young people aged 16–25 years visit their general practitioner (GP) annually, and reimbursement for chlamydia testing costs to the relevant parties (GPs in England, Sweden and Estonia; and patients in France) by the national health insurance system or its equivalent.
In countries where chlamydia testing is provided by GPs (England, Sweden) a national strategy or plan on STI control that specifically mentions chlamydia was in force, chlamydia care guidelines for GPs were in place and STI management was more firmly established in the GP residency training curriculum, either formally (England) or informally (Sweden), than in the other countries.
Future research on the effectiveness of chlamydia screening (also in the context of general practice care) and program provision should reflect national needs and the prevention of complications.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-1147) contains supplementary material, which is available to authorized users.
PMCID: PMC4240879  PMID: 25374092
Chlamydia; Testing; Training; General practice; Europe
8.  Developing an adherence support intervention for patients on antiretroviral therapy in the context of the recent IDU-driven HIV/AIDS epidemic in Estonia 
AIDS care  2013;25(7):863-873.
There is limited data on and experience with interventions for antiretroviral therapy (ART) adherence support for patients on ART in Eastern Europe. We sought to identify a feasible adherence support intervention for delivery amongst HIV-positive adults receiving care in Estonia, where the HIV/AIDS epidemic has been mainly concentrated among injection drug users. Our application of intervention mapping strategies used existing literature, formative research and multidisciplinary team input to produce a brief clinic-based intervention entitled the Situated Optimal Adherence Intervention Estonia (sOAI Estonia) which uses both Next-Step Counseling and Information-Motivation-Behavioral Skills Model approach to facilitate integration of ART into the context and demands of daily life. We present the intervention development process, the resulting sOAI Estonia approach, and describe a randomized controlled trial which is underway to evaluate the intervention (results due in spring 2013).
PMCID: PMC3651786  PMID: 23391132
ART; HAART; adherence; intervention
9.  Non-cancer morbidity among Estonian Chernobyl cleanup workers: a register-based cohort study 
BMJ Open  2014;4(5):e004516.
To examine non-cancer morbidity in the Estonian Chernobyl cleanup workers cohort compared with the population sample with special attention to radiation-related diseases and mental health disorders.
Register-based cohort study.
An exposed cohort of 3680 men (cleanup workers) and an unexposed cohort of 7631 men (population sample) were followed from 2004 to 2012 through the Population Registry and Health Insurance Fund database.
Morbidity in the exposed cohort compared with the unexposed controls was estimated in terms of rate ratio (RR) with 95% CIs using Poisson regression models.
Elevated morbidity in the exposed cohort was found for diseases of the nervous system, digestive system, musculoskeletal system, ischaemic heart disease and for external causes. The most salient excess risk was observed for thyroid diseases (RR=1.69; 95% CI 1.38 to 2.07), intentional self-harm (RR=1.47; 95% CI 1.04 to 2.09) and selected alcohol-related diagnoses (RR=1.25; 95% CI 1.12 to 1.39). No increase in morbidity for stress reactions, depression, headaches or sleep disorders was detected.
No obvious excess morbidity consistent with biological effects of radiation was seen in the exposed cohort, with the possible exception of benign thyroid diseases. Increased alcohol-induced morbidity may reflect alcohol abuse, and could underlie some of the higher morbidity rates. Mental disorders in the exposed cohort were probably under-reported. The future challenge will be to study mental and physical comorbidities in the Chernobyl cleanup workers cohort.
PMCID: PMC4024594  PMID: 24833681
alcohol-induced disorders; Chernobyl nuclear accident; Estonia; MENTAL HEALTH; morbidity; radiation effects
10.  Socio-demographic factors, health risks and harms associated with early initiation of injection among people who inject drugs in Tallinn, Estonia: evidence from cross-sectional surveys 
To explore socio-demographic factors, health risks and harms associated with early initiation of injecting (before age 16) among injecting drug users (IDUs) in Tallinn, Estonia.
IDUs were recruited using respondent driven sampling methods for two cross-sectional interviewer-administered surveys (in 2007 and 2009). Bivariate and multivariate logistic regression analysis was used to identify factors associated with early initiation versus later initiation.
A total of 672 current IDUs reported the age when they started to inject drugs; the mean was 18 years, and about a quarter of the sample (n=156) reported early initiation into injecting drugs. Factors significantly associated in multivariate analysis with early initiation were being female, having a lower educational level, being unemployed, shorter time between first drug use and injecting, high-risk injecting (sharing syringes and paraphernalia, injecting more than once a day), involvement in syringe exchange attendance and getting syringes from outreach workers, and two-fold higher risk of HIV seropositivity.
Our results document significant adverse health consequences (including higher risk behaviour and HIV seropositivity) associated with early initiation into drug injecting and emphasize the need for comprehensive prevention programs and early intervention efforts targeting youth at risk. Our findings suggest that interventions designed to delay the age of starting drug use, including injecting drug use, can contribute to reducing risk behaviour and HIV prevalence among IDUs.
PMCID: PMC3566328  PMID: 23036651
Adolescents; injecting drug use; risk behaviour; Eastern Europe; Respondent Driven Sampling; HIV
11.  Non-fatal injuries resulting in activity limitations in Estonia—risk factors and association with the incidence of chronic conditions and quality of life: a retrospective study among the population aged 20–79 
BMJ Open  2013;3(7):e002695.
Evidence about the health and quality-of-life outcomes of injuries is obtained mainly from follow-up studies of surviving trauma patients; population-based studies are rarer, in particular for countries in Eastern Europe. This study examines the incidence, prevalence and social variation in non-fatal injuries resulting in activity limitations and outcomes of injuries in Estonia.
A retrospective population-based study.
7855 respondents of the face-to-face interviews of the second round of the Estonian Family and Fertility Survey conducted between 2004 and 2005 based on the nationally representative probability sample (n=11 192) of the resident population of Estonia aged 20–79.
Primary and secondary outcome measures
The cumulative incidence and prevalence of injuries leading to activity limitations was estimated. Survival models were applied to analyse variations in the injury risk across sociodemographic groups. The association between injuries and the development of chronic conditions and quality of life was examined using survival and logistic regression models.
10% (95% CI 9.4 to 10.7) of the population aged 20–79 had experienced injuries leading to activity limitations; the prevalence of activity limitations due to injuries was 4.4% (95% CI 3.9% to 4.9%). Significant differences in injury risk were associated with gender, education, employment, marital status and nativity. Limiting injury was associated with a doubling of the likelihood of having chronic conditions (adjusted HR 1.97, 95% CI 1.58 to 2.46). Injury exhibited a statistically significant negative association with most quality-of-life measures. Although reduced, these effects persisted after recovery from activity limitations.
Substantial variation in injury risk across population groups suggests potential for prevention. Men and workers in manual occupations constitute major target groups for injury prevention in Estonia. The association of injury with the development of chronic conditions and reduced quality of life warrants further investigation.
PMCID: PMC3731728  PMID: 23901024
non-fatal injuries; activity limitations; chronic conditions; quality of life; life course epidemiology
12.  CCR5 Haplotypes Influence HCV Serostatus in Caucasian Intravenous Drug Users 
PLoS ONE  2013;8(7):e70561.
Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia.
Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2–CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5.
Compared to IDUs seronegative for both HCV and HIV (HCV−/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+were 92% and 82%, respectively, less likely to possess the CCR5-HHG*1 haplotype, after controlling for co-variates (Padjusted = 1.89×10−4 and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG*1 haplotype pairs. Approximately 25% and<10% of HCV−/HIV- IDUs and HCV−/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype.
Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs.
PMCID: PMC3723663  PMID: 23936229
13.  The epidemiological and economic impact of a quadrivalent human papillomavirus (hpv) vaccine in Estonia 
BMC Infectious Diseases  2013;13:304.
This analysis assessed the epidemiological and economic impact of quadrivalent human papillomavirus (HPV4: 6/11/16/18) vaccination in Estonia.
A dynamic transmission model was used to assess the epidemiological and economic impact of the routine vaccination of 12-year-old girls with a HPV4 vaccine in preventing cervical cancer, cervical intraepithelial neoplasia (CIN) grades 1, 2 and 3 and genital warts.
The model projected that at year 100, HPV4 vaccination would lead to a reduction of HPV 16/18 related cervical cancer incidence and deaths by over 97% and the incidence of HPV 6/11 related genital warts among Estonian women and men by over 94% and 81%, respectively. The incremental cost-effectiveness ratio of the HPV4 vaccination strategy was € 4,889 per QALY gained over a time horizon of 100 years.
Routine vaccination of 12-year-old girls with HPV4 vaccine appears to be cost-effective in Estonia, in addition to providing both short term and long term health gains.
PMCID: PMC3706227  PMID: 23819789
HPV; Vaccine; Cost effectiveness; Screening; Cervical cancer; Genital warts; Estonia
14.  Multiple routes of drug administration and HIV risk among injecting drug users 
This study assesses relationships between drug administration routes and HIV serostatus, drug-use and sexual behaviors among current injecting drug users (IDUs) in Tallinn, Estonia. We recruited 350 IDUs for a cross-sectional risk behavior survey. Adjusted odds ratios (AORs) were calculated to explore injection risk behavior, sexual behavior and HIV serostatus associated with multiple route use. Focus groups explored reasons why injectors might use non-injecting routes of administration. Those reporting multiple drug administration routes were less likely to be HIV seropositive (AOR 0.49; 95%CI 0.25-0.97), had almost twice the odds of having more than one sexual partner (AOR 1.90; 95%CI 1.01-3.60) and of reporting having sexually transmitted diseases (AOR 2.38; 95%CI 1.02-5.59).
IDUs who engage in non-injecting drug use may be reducing their risk of acquiring HIV though sharing injection equipment, but if infected may be a critical group for sexual transmission of HIV to people who do not inject drugs.
PMCID: PMC3289756  PMID: 22116012
Injecting drug use; HIV; Risk behavior; Illicit drug use; Sexual risk behaviors
15.  Assessing non-response to a mailed health survey including self-collection of biological material 
Background: Collection of biological material via mailed health surveys is an emerging trend. This study was conducted to assess non-response bias in a study of sexually transmitted infection utilizing self-collected, home-obtained specimens. Methods: Data from a nationwide administrative database on health care utilization together with data from a research study were used. The research study was an outreach screening programme including home-obtained, participant-collected, mail-delivered testing for Chlamydia trachomatis. A random sample of 1690 persons aged 18–35 years from the population registry was selected. Study materials (specimen collection kit, informed consent, questionnaire) were mailed in three waves. Results: The first mailing yielded a response rate of 18.5% (n = 259), the second 10.1% (n = 141) and the third 11.4% (n = 160). Women were more likely to respond than men, and responders were less likely to have had medical care in the past year and more likely to have had a prior sexually transmitted infection than non-responders. Chlamydia trachomatis infection rates tended to be higher in early responders. Late responders appeared more like non-responders in terms of demographic factors, health care utilization patterns and potential disease status. Conclusion: Non-response in a health survey including biological material self-collection warrants research as it may differ from non-response in general health questionnaires.
PMCID: PMC3139099  PMID: 20457781
Chlamydia; epidemiologic study; participant collected specimen; participation
16.  Estonia at the Threshold of the Fourth Decade of the AIDS Era in Europe 
This article describes the trends of HIV/AIDS and related conditions in Estonia during the past decade (2000–2009), with special focus on the potential for epidemic transition. Key transmission determinants and major risk groups are examined and problems and barriers to fighting HIV/AIDS with possible applications in prevention and control are described. Estonian routine data sources and published literature were reviewed, supplemented with information from personal communication with physicians and public health specialists. For comparative European data, international HIV/AIDS and drug addiction surveillance documents, administrative data, and published literature were reviewed. In Eastern Europe (including Estonia) the predominant HIV transmission mode is injection drug use (IDU), closely followed by heterosexual transmission, an increasing risk factor for new cases. Although the contribution of cases acquired by sexual contact with high-risk partners such as IDUs is not known, characteristics of the sexual networks of IDUs may be important in determining the evolution of the HIV/AIDS epidemics in the region. In Estonia, despite major gaps in available data, the HIV/AIDS epidemic is still presumably confined to IDUs (and probably, to their sexual partners). In Eastern Europe, young women in IDU–non-IDU partnerships engaging in unprotected sex potentially serve as a bridge to the general population, yet knowledge of and research into the population characteristics and potential magnitude of bridging are limited. In Estonia, as in other Eastern European countries, HIV prevention and harm reduction initiatives should be tailored not only to the predominantly male HIV-positive IDU population, but also to their noninfected non-IDU female sexual partners.
PMCID: PMC3180763  PMID: 21142588
17.  Self-reported activity limitations among the population aged 20–79 in Estonia: a cross-sectional study 
Background: Along with population ageing, limitations in activities of daily living constitute a rising health-related burden in demographically advanced countries. The present study aims to assess the prevalence of self-reported activity limitations derived from chronic conditions and social variation of limitations in the subgroups of the population aged 20–79 years in Estonia. Methods: A cross-sectional study employs data from the second round of the Estonian Family and Fertility Survey, a national project in the framework of Gender and Generation Programme. The target population covers age groups of 20–79 years. A nationally representative probability sample was drawn from the 2000 population census. Face-to-face interviews (n = 7855) were conducted in 2004–05. Results: The estimated prevalence of activity limitations with chronic conditions is 18.5% (95% CI 17.6–19.4) and the prevalence of severe limitations is 10.6% (95% CI 9.9–11.3) among the population. The logistic regression model shows significant differences in activity limitations associated with age, educational attainment and marital status. Conclusions: Judging from our results and the EU structural indicators on health, the prevalence of activity limitations derived from chronic conditions is comparatively high in Estonia. The measures to prevent activity limitations and disability should receive a higher priority in Estonia.
PMCID: PMC3106285  PMID: 20129929
activity limitations; chronic conditions; disability; Eastern Europe; Estonia; social variation
18.  Expanded syringe exchange programs and reduced HIV infection among new injection drug users in Tallinn, Estonia 
BMC Public Health  2011;11:517.
Estonia has experienced an HIV epidemic among intravenous drug users (IDUs) with the highest per capita HIV prevalence in Eastern Europe. We assessed the effects of expanded syringe exchange programs (SEP) in the capital city, Tallinn, which has an estimated 10,000 IDUs.
SEP implementation was monitored with data from the Estonian National Institute for Health Development. Respondent driven sampling (RDS) interview surveys with HIV testing were conducted in Tallinn in 2005, 2007 and 2009 (involving 350, 350 and 327 IDUs respectively). HIV incidence among new injectors (those injecting for < = 3 years) was estimated by assuming (1) new injectors were HIV seronegative when they began injecting, and (2) HIV infection occurred at the midpoint between first injection and time of interview.
SEP increased from 230,000 syringes exchanged in 2005 to 440,000 in 2007 and 770,000 in 2009. In all three surveys, IDUs were predominantly male (80%), ethnic Russians (>80%), and young adults (mean ages 24 to 27 years). The proportion of new injectors decreased significantly over the years (from 21% in 2005 to 12% in 2009, p = 0.005). HIV prevalence among all respondents stabilized at slightly over 50% (54% in 2005, 55% in 2007, 51% in 2009), and decreased among new injectors (34% in 2005, 16% in 2009, p = 0.046). Estimated HIV incidence among new injectors decreased significantly from 18/100 person-years in 2005 and 21/100 person-years in 2007 to 9/100 person-years in 2009 (p = 0.026).
In Estonia, a transitional country, a decrease in the HIV prevalence among new injectors and in the numbers of people initiating injection drug use coincided with implementation of large-scale SEPs. Further reductions in HIV transmission among IDUs are still required. Provision of 70 or more syringes per IDU per year may be needed before significant reductions in HIV incidence occur.
PMCID: PMC3146432  PMID: 21718469
19.  Enhanced tuberculosis case detection among substitution treatment patients: a randomized controlled trial 
BMC Research Notes  2011;4:192.
Historically, HIV, TB (tuberculosis) and illegal drug treatment services in Estonia have been developed as vertical structures. Related health care services are often provided by different health care institutions and in different locations. This may present obstacles for vulnerable groups, such as injecting drug users (IDU), to access the needed services. We conducted a small scale randomized controlled trial to evaluate a case management intervention aimed at increasing TB screening and treatment entry among IDUs referred from a methadone drug treatment program in Jõhvi, North-Eastern Estonia.
Of the 189 potential subjects, 112 (59%) participated. HIV prevalence was 86% (n = 96) and 7.4% (n = 8) of participants were interferon gamma release assay (IGRA) positive (6.5% were both HIV and IGRA-positive, n = 7). Overall, 44% of participants (n = 49) attended TB clinic, 17 (30%) from control group and 32 (57%) from case management group (p = 0.004). None of the participants were diagnosed with TB. In a multivariate model, those randomized to case management group were more likely to access TB screening services.
These findings demonstrate the urgent need for scaling up TB screening among IDUs and the value of more active approach in referring substitution treatment patients to TB services.
Trial registration NCT01290081
PMCID: PMC3138461  PMID: 21676222
20.  CCL3L1 copy number is a strong genetic determinant of HIV seropositivity in Caucasian intravenous drug users 
The Journal of infectious diseases  2010;201(5):730-739.
A high copy number of CCL3L1, the most potent HIV-suppressive chemokine, associates with reduced HIV susceptibility. Whether CCL3L1 influences acquisition of multiple blood-borne infections (HCV, HIV-1, HBV) that occurs commonly among intravenous drug users (IDUs) is unknown.
We determined CCL3L1 copy number by real-time PCR among 374 Caucasian IDUs from Estonia of whom 285 were HCV-positive, 208 HIV+, 177 HCV+/HIV+, and 57 HCV−/HIV−.
In univariate and multivariate analyses, HCV and HBV seropositivity, and duration of IDU each strongly predicted HIV seropositivity. A high CCL3L1 copy number (>2) associated with a 80% reduced risk of acquiring HIV, after adjusting for age, gender, HCV/HBV status, CCR5-Δ32 polymorphism and IDU duration (OR=0.20; 95% CI=0.09–0.45). By contrast, CCL3L1 gene dose did not influence HCV seropositivity. Among HCV+ IDUs, there was a 3.5-fold over- and 65% under-representation of a high CCL3L1 copy number among HCV+/HIV− and HCV+/HIV+ subjects, respectively.
Among IDUs exposed heavily to HCV/HIV, CCL3L1 copy number is a major determinant of HIV seropositivity, but not HCV seropositivity. The contrasting distribution of a protective high CCL3L1 copy number among HCV+/HIV− vs HCV+/HIV+ IDUs may reflect that HIV preferentially selects for subjects with a low CCL3L1 gene dose.
PMCID: PMC2836481  PMID: 20095832
chemokine copy number; HIV; HCV; IDU
21.  Evaluating Recruitment among Female Sex Workers and Injecting Drug Users at Risk for HIV Using Respondent-driven Sampling in Estonia 
Few recent publications have highlighted theoretical and methodological challenges using respondent-driven sampling (RDS). To explore why recruitment with RDS may work in some populations and not in others, we assess the implementation of RDS to recruit female sex workers (FSWs) and injection drug users (IDUs) into a human immunodeficiency virus biological and risk behavior survey in Tallinn, Estonia. Recruitment of FSWs was slower and more challenging than that of IDUs. The IDU study recruited 350 participants within 7 weeks, while the FSW study recruited 227 participants over 28 weeks. Implementation modifications that did not negatively impact key RDS theoretical and methodological requirements were used to improve recruitment during the FSW study. We recommend that all RDS studies include a formative research process to involve the participation of target populations and key persons associated with these populations in the study planning and throughout the implementation processes to improve recruitment from the outset and to respond to poor recruitment during data collection.
PMCID: PMC2845833  PMID: 20131018
Injecting drug users; Female sex workers; Respondent-driven sampling; HIV; Estonia
22.  Should Pharmacists have a Role in Harm Reduction Services for IDUs? A Qualitative Study in Tallinn, Estonia 
Despite the high number of injecting drug users (IDUs) in Estonia, little is known about involving pharmacies into human immunodeficiency virus (HIV) prevention activities and potential barriers. Similarly, in other Eastern European countries, there is a need for additional sources for clean syringes besides syringe exchange programmes (SEPs), but data on current practices relating to pharmacists’ role in harm reduction strategies is scant. Involving pharmacies is especially important for several reasons: they have extended hours of operation and convenient locations compared to SEPs, may provide access for IDUs who have avoided SEPs, and are a trusted health resource in the community. We conducted a series of focus groups with pharmacists and IDUs in Tallinn, Estonia, to explore their attitudes toward the role of pharmacists in HIV prevention activities for IDUs. Many, but not all, pharmacists reported a readiness to sell syringes to IDUs to help prevent HIV transmission. However, negative attitudes toward IDUs in general and syringe sales to them specifically were identified as important factors restricting such sales. The idea of free distribution of clean syringes or other injecting equipment and disposal of used syringes in pharmacies elicited strong resistance. IDUs stated that pharmacies were convenient for acquiring syringes due to their extended opening hours and local distribution. IDUs were positive toward pharmacies, although they were aware of stigma from pharmacists and other customers. They also emphasized the need for distilled water and other injection paraphernalia. In conclusion, there are no formal or legislative obstacles for providing HIV prevention services for IDUs at pharmacies. Addressing negative attitudes through educational courses and involving pharmacists willing to be public health educators in high drug use areas would improve access for HIV prevention services for IDUs.
PMCID: PMC2791822  PMID: 19921542
Injecting drug users; Pharmacists; Harm reduction services
23.  The HIV prevention needs of injection drug users in Estonia 
To assess the relationships between HIV transmission risk behaviours, HIV serostatus and knowledge of HIV serostatus among active injection drug users (IDUs) residing in Tallinn, Estonia, we conducted HIV testing and administered a standardized interview to 266 participants reporting recent injection drug use. In total, 45% were HIV positive, and of those, 39% knew their HIV serostatus. Those who knew their HIV-positive serostatus were less likely to report giving someone else their needle after they used it (9%) than were HIV-negative participants (23%) and those who were HIV positive but unaware of their HIV-positive serostatus (25%). There were no statistically significant differences in unprotected sex or other drug use behaviours between the groups. Most participants reported that HIV can be transmitted through sharing needles (98%) and unprotected sexual activity (93%). Prevention needs of IDUs in this area include increasing the rates of HIV testing and implementing effective programmes to reduce sexual and drug use risk behaviours.
PMCID: PMC2925653  PMID: 17609027
HIV; substance abuse; intravenous; sexual behaviour; Baltic states
24.  Atypical Genital Herpes: Report of Five Cases 
Manifestations of human genital herpes virus (HSV) infection are not limited to the typical cluster of genital lesions. Here we present 5 case histories suggestive to clinically atypical genital herpes (HSV detected with the polymerase chain reaction) collected in 2001 from a private outpatient clinic specializing in dermatological and venereal diseases. The clinical presentations included mucopurulent cervicitis, haemorrhagic cystitis, recurrent urethritis, and lower hack pain.
PMCID: PMC2925659  PMID: 15000557
25.  High prevalence of blood-borne virus infections and high-risk behaviour among injecting drug users in Tallinn, Estonia 
The HIV epidemic in Estonia is rapidly expanding, and injection drug users (IDUs) are the major risk group contributing to the expansion. A convenience sample of 159 IDUs visiting syringe-exchange programmes (SEPs) was selected to quantify the association of HIV-risk behaviours and blood-borne infections. A high prevalence of HIV, hepatitis B core antibody (HBVcore), hepatitis B surface antigen (HbsAg) and hepatitis C virus antibodies (56, 85.1, 21.3, and 96.2%, respectively) was associated with high-risk injections, unsafe sexual behaviour and alcohol abuse. These findings emphasize the importance of evidence-based secondary prevention among the HIV-infected, especially given the uncertain sustainability of antiretroviral and substance abuse treatments.
PMCID: PMC2925660  PMID: 17326862
injection drug use; HIV; HBV; HCV; high-risk behaviour; Estonia

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