Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe.

BACKGROUND & AIMS: Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. METHODS: We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS: At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS: The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY: Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).

Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.

[Mosquito allergy]. / Hyttysallergia.

Virtually all Finns are sensitized to mosquito bites already during childhood. Skin reactions caused by mosquito bites vary from rapidly appearing urticarial wheals to persistent itching papules. Allergic shock is fortunately extremely rare. The symptoms are strongest in early summer. Immediate symptoms result from proteins that get into the skin along with mosquito saliva and induce the production of IgE class antibodies by the body. The originating mechanism of delayed symptoms is unclear. Both immediate and delayed symptoms of mosquito allergy can be relieved with antihistamine drugs.

Incarceration history is associated with HIV infection among community-recruited people who inject drugs in Europe: A propensity-score matched analysis of cross-sectional studies.

AIMS: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months). MEASUREMENTS: Data on incarceration history, demographics, substance use, sexual behavior and harm reduction service use originated from cross-sectional studies among PWID in Europe. Our primary outcome was HIV status. Generalized linear mixed models and propensity-score matching were used to compare HIV status between ever- and never-incarcerated PWID. FINDINGS: Among 43 807 PWID from 82 studies surveyed (in 22 sites and 13 countries), 58.7% reported having ever been in prison and 7.16% (n = 3099) tested HIV-positive. Incarceration was associated with 30% higher odds of HIV infection [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.09-1.59]; the association between a history of incarceration and HIV infection was strongest among PWID, with the lowest estimated propensity-score for having a history of incarceration (aOR = 1.78, 95% CI = 1.47-2.16). Additionally, mainly injecting cocaine and/or opioids (aOR = 2.16, 95% CI = 1.33-3.53), increased duration of injecting drugs (per 8 years aOR = 1.31, 95% CI = 1.16-1.48), ever sharing needles/syringes (aOR = 1.91, 95% CI = 1.59-2.28) and increased income inequality among the general population (measured by the Gini index, aOR = 1.34, 95% CI = 1.18-1.51) were associated with a higher odds of HIV infection. Older age (per 8 years aOR = 0.84, 95% CI = 0.76-0.94), male sex (aOR = 0.77, 95% CI = 0.65-0.91) and reporting pharmacies as the main source of clean syringes (aOR = 0.72, 95% CI = 0.59-0.88) were associated with lower odds of HIV positivity. CONCLUSIONS: A history of incarceration appears to be independently associated with HIV infection among people who inject drugs (PWID) in Europe, with a stronger effect among PWID with lower probability of incarceration.

Dynamics of two separate but linked HIV-1 CRF01_AE outbreaks among injection drug users in Stockholm, Sweden, and Helsinki, Finland.

Detailed phylogenetic analyses were performed to characterize an HIV-1 outbreak among injection drug users (IDUs) in Stockholm, Sweden, in 2006. This study investigated the source and dynamics of HIV-1 spread during the outbreak as well as associated demographic and clinical factors. Seventy Swedish IDUs diagnosed during 2004 to 2007 were studied. Demographic, clinical, and laboratory data were collected, and the V3 region of the HIV-1 envelope gene was sequenced to allow detailed phylogenetic analyses. The results showed that the Stockholm outbreak was caused by a CRF01_AE variant imported from Helsinki, Finland, around 2003, which was quiescent until the outbreak started in 2006. Local Swedish subtype B variants continued to spread at a lower rate. The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.

Finnish HIV Quality of Care Register (FINHIV).

PURPOSE: The Finnish HIV Quality of Care Register (FINHIV) was created to: (1) estimate the number of people living with HIV (PLWH) in Finland, (2) evaluate the national level of antiretroviral medication use and viral suppression, (3) examine the change in the HIV epidemic in Finland to pinpoint issues to address and (4) enable evaluation of the health of the PLWH by combining the FINHIV data with other national healthcare data. PARTICIPANTS: The FINHIV includes all people diagnosed or being treated for HIV infection in Finland since 1984. The register was formed in 2020 by combining data from the National Infectious Diseases Register (information from time of diagnosis, data from 1984) and from the 21 HIV Clinics that treat HIV-positive patients in Finland (earliest data from 1998). The register population forms a nationwide, open cohort with yearly updates; currently it consists of 4218 PLWH (including 718 deceased) with HIV diagnosed or treated in Finland 1984-2019. Current rate of new cases is 150 cases/year. FINDINGS TO DATE: From the FINHIV data, we can confirm that Finland has reached the Joint United Nations Programme for HIV/AIDS (UNAIDS) 90-90-90 targets set for 2020, and that the proportion of virally suppressed is constant between all 21 HIV Clinics in Finland, despite their varying size. Linkage to care is estimated at 94.3% of those diagnosed. In contrast to the treatment results, more than half of the PLWH have been diagnosed at a late stage, and the proportion has increased since 2000. FUTURE PLANS: Combinations of FINHIV data with other national healthcare register data in Finland will provide further information on other aspects of the health of the PLWH in a high-resource setting (eg, comorbidities, sexual health and use of healthcare resources). Additionally, implementation of patient-reported experience and outcome measures within the FINHIV is ongoing.

Developing and Piloting a Standardized European Protocol for Hepatitis C Prevalence Surveys in the General Population (2016-2019).

Background: A robust estimate of the number of people with chronic hepatitis C virus (HCV) infection is essential for an appropriate public health response and for monitoring progress toward the WHO goal of eliminating viral hepatitis. Existing HCV prevalence studies in the European Union (EU)/European Economic Area (EEA) countries are heterogeneous and often of poor quality due to non-probability based sampling methods, small sample sizes and lack of standardization, leading to poor national representativeness. This project aimed to develop and pilot standardized protocols for undertaking nationally representative HCV prevalence surveys in the general adult population. Methods: From 2016 to 2019 a team from the Robert Koch-Institute contracted by the European Centre for Disease Prevention and Control synthesized evidence on existing HCV prevalence surveys and survey methodology and drafted a protocol. The methodological elements of the protocol were piloted and evaluated in Bulgaria, Finland and Italy, and lessons learnt from the pilots were integrated in the final protocol. An international multidisciplinary expert group was consulted regularly. Results: The protocol includes three alternative study approaches: a stand-alone survey; a "nested" survey within an existing health survey; and a retrospective testing survey approach. A decision algorithm advising which approach to use was developed. The protocol was piloted and finalized covering minimum and gold standards for all steps to be implemented from sampling, data protection and ethical issues, recruitment, specimen collection and laboratory testing options, staff training, data management and analysis and budget considerations. Through piloting, the survey approaches were effectively implemented to produce HCV prevalence estimates and the pilots highlighted the strengths and limitations of each approach and key lessons learnt were used to improve the protocol. Conclusions: An evidence-based protocol for undertaking HCV prevalence serosurveys in the general population reflecting the different needs, resources and epidemiological situations has been developed, effectively implemented and refined through piloting. This technical guidance supports EU/EEA countries in their efforts to estimate their national hepatitis C burden as part of monitoring progress toward the elimination targets.

HIV epidemiology in the Northwestern Federal District of Russia: dominance of HIV type 1 subtype A.

A rapidly advancing epidemic of HIV-1 infection has been documented among injecting drug users (IDUs) in Russia. The Northwestern Federal District was the first of the seven Russian Federal Districts involved in a drug-related HIV epidemic through an outbreak in Kaliningrad in 1996. The Northwestern Federal District has a high HIV prevalence rate having reached 252 per 100,000 by the end of 2003, exceeding the Russian average (180) by 1.4 times. The epidemic peaked in 2001. Since then the annual number of new cases has decreased, probably reflecting saturation among at least some IDU populations. However, at the same time, the heterosexual spread of HIV has become more prominent. To study the genetic epidemiology of HIV-1, samples were collected from 150 individuals covering a wide geographical area and different transmission groups in the Northwestern Federal District. Phylogenetic analysis revealed that an Eastern European subtype A HIV-1 strain similar to those reported earlier among IDUs in other regions of Russia accounted for 80% of HIV-1 infections and was the predominant subtype in six out of seven administrative territories studied both among IDUs and heterosexually infected persons. As an exception to the dominant role of the Eastern European subtype A strain, the CRF03-AB strain was found to be dominant in the city of Cherepovets located in the north central European Russian territory of Vologda Oblast. This is the first report of the CRF03-AB strain causing an outbreak outside the Kaliningrad region.

Two viral strains and a possible novel recombinant are responsible for the explosive injecting drug use-associated HIV type 1 epidemic in Estonia.

HIV-1 infection has been rare in Estonia. In 2000, an explosive epidemic among injecting drug users was detected in the Eastern border region, resulting in 3603 newly reported cases by the end of 2003. The molecular epidemiology of the outbreak was studied to establish whether the Estonian epidemic is linked to the epidemics in Eastern Europe. Over 200 newly infected individuals were prospectively sampled from June 2000 to March 2002 in a geographically representative way, with known dates of diagnosis and information of probable route of transmission. Viral regions coding for two viral gene regions were directly sequenced from plasma viral RNA and phylogenetically analyzed. In addition, a larger region coding for the entire env gene was sequenced from one sample and studied for indications of possible recombinant structure. The Estonian HIV outbreak was found to be caused by simultaneous introduction of two strains: a minor subtype A strain very similar to the Eastern European subtype A strain (approximately 8% of cases), and a second major strain (77%) found to be most closely related to the CRF06-cpx strain, previously described only from African countries. The variability in the two clusters was very low, suggesting point source introductions. Ten percent of cases seemed to be newly generated recombinants of the A and CRF06-cpx strains. Analysis of viral diversification over time revealed a rate of change within the V3 region of 0.83%/year for the CRF06-cpx strain, consistent with findings from other subtypes. Due to the relatively frequently found novel recombinant forms, the Estonian HIV-1 epidemic may allow studies of coinfection and intersubtype recombination in detail.

HIV outbreak among injecting drug users in the Helsinki region: social and geographical pockets.

BACKGROUND: Incidence of newly diagnosed HIV infections among injecting drug users (IDUs) in Helsinki rose from 0 per 100,000 inhabitants in 1997 to 2.9 in 1998 and to 11.1 in 1999. Thereafter incidence declined to 2.1 in 2003. METHODS: Data were collected from interviews with HIV-positive IDUs who attended the University Hospital in Helsinki from 1998 until 2003. We studied the sociodemographic profile and spatial distribution of IDUs who were diagnosed in the beginning of the outbreak and those diagnosed later. The indicator for the spatial differentiation within the metropolitan area is % employed males aged 25-64. RESULTS: The outbreak occurred among a marginalized population of IDUs characterized by a long history of injecting drug use (10.7 years), mean age 32 years, homelessness (66.3%), history of imprisonment (74.7%) and psychiatric hospital care (40.6%). Compared with 98 early cases diagnosed during the first 2 years until 2000, 47 recent cases diagnosed after 2001 were 4 years older, and as marginalized. Except for the city centre, both early and recent cases had been living or using drugs in the same deprived neighbourhoods with the highest unemployment rates. Up to 40% of cases in the two big geographical clusters did not have contact with the city centre, where the needle exchange services were available. CONCLUSIONS: The Finnish HIV outbreak is restricted socially to a very marginalized IDU population, and spatially to local pockets of poverty. In low prevalence countries, prevention programs should be targeted early at high-risk areas and populations.

Levocetirizine for treatment of immediate and delayed mosquito bite reactions.

People frequently experience whealing and delayed papules from mosquito bites. Various antihistamines have previously been tried for the treatment of this condition. We performed a double-blind, placebo-controlled, cross-over study with levocetirizine 5 mg and matched placebo in 30 adults who were sensitive to mosquito bites. On the third treatment day the subjects received two Aedes aegypti bites on the forearm. The size of the bite lesions and the intensity of pruritus (visual analogue scale) were measured. Bite symptoms could be analysed in 28 subjects at 15 min and in 8 subjects at 24 h. Levocetirizine decreased the size of wheals by 60% (p < 0.001) and accompanying pruritus by 62% (p < 0.001) compared with placebo. The effect of levocetirizine increased in a linear fashion with the size of wheals and was most significant in the subjects with largest bite lesions. Levocetirizine also decreased the size of 24-h bite lesions by 71% (p=0.008) and accompanying pruritus by 56% (p=0.016). These results show that prophylactic levocetirizine 5 mg is an effective treatment for both immediate and delayed mosquito bite symptoms and is especially effective in subjects with large wheals.

Tick-borne encephalitis virus infections in Lithuanian domestic animals and ticks.

In order to obtain information about the distribution of tick-borne encephalitis virus (TBEV) in Lithuania, sera of domestic animals were screened for TBEV antibodies by haemagglutination inhibition test. Samples were collected in 2001 from 423 cows, 561 goats and 118 sheep during a prophylactic examination or vaccination by a local veterinary specialist. In addition, a total of 3234 Ixodes ricinus ticks in 436 pools were collected and tested by RT-PCR for the presence of TBEV RNA (detailed analysis with genetic characterization is published separately [Han et al, J Med Virol 2005 (in press)]). Domestic animal sera from 8/18 districts were positive with an overall seropositivity of 1.7% with considerable regional differences. Sheep from the Radviliskis region had the highest seropositivity rate (16%). In comparison, the proportion of tick pools positive for TBEV-RNA was 1.38%, ranging from 1.03% in Panavezys, 3.33% in Siauliai to 16% in Radviliskis.

Molecular epidemiology of tick-borne encephalitis virus in Ixodes ricinus ticks in Lithuania.

In Lithuania, 171-645 serologically confirmed cases of tick-borne encephalitis occurred annually [Mickiene et al. (2001): Eur J Clin Microbiol Infect Dis 20:886-888] in 1993-1999, and the tick-borne encephalitis virus (TBEV) seroprevalence in the general population was found previously to be 3.0% [Juceviciene et al. (2002): J Clin Virol 25:23-27]. To assess the risk for TBEV virus infection in Lithuania and to characterize the agent a panel of 3,234 ticks combined into 436 pools [Juceviciene et al., 2005] were tested for presence of TBEV RNA by a nested RT-PCR targeting at the NS5 gene. Six pools were confirmed positive and the prevalence of the infected ticks was 0.2% (if one tick per pool [Juceviciene et al., 2005] was considered positive) and the proportion of positive tick pools was 1.4%. The prevalence of the infected ticks in the Panevezys, Siauliai, and Radviliskis regions (in central Lithuania) was 0.1%, 0.4%, and 1.7% corresponding with a higher TBE disease burden in these regions. The 252-nucleotide NS5-region amplicons, and a longer sequence (737 nucleotides) obtained from one sample from the PrM-E gene region, were sequenced. Phylogenetic analysis of the latter showed that all western type TBEV PrM-E sequences, including the Lithuanian strains, were monophyletic, showed no clustering and had very little variation. The NS5 sequences, although identical within one locality, did not show any mutations common to strains from the two Lithuanian regions, nor could any geographical clustering be found among western type TBEV strains from other areas.