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1.
J Infect Dis ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976562

RESUMO

BACKGROUND: Men and women with a migration background comprise an increasing proportion of incident human immunodeficiency virus (HIV) cases across Western Europe. METHODS: To characterize sources of transmission in local transmission chains, we used partial HIV consensus sequences with linked demographic and clinical data from the opt-out AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort of people with HIV in the Netherlands and identified phylogenetically and epidemiologically possible HIV transmission pairs in Amsterdam. We interpreted these in the context of estimated infection dates, and quantified population-level sources of transmission to foreign-born and Dutch-born Amsterdam men who have sex with men (MSM) within Amsterdam transmission chains. RESULTS: We estimate that Dutch-born MSM were the predominant sources of infections among all Amsterdam MSM who acquired their infection locally in 2010-2021, and among almost all foreign-born Amsterdam MSM subpopulations. Stratifying by 2-year intervals indicated time trends in transmission dynamics, with a majority of infections originating from foreign-born MSM since 2016, although uncertainty ranges remained wide. CONCLUSIONS: Native-born MSM have predominantly driven HIV transmissions in Amsterdam in 2010-2021. However, in the context of rapidly declining incidence in Amsterdam, the contribution from foreign-born MSM living in Amsterdam is increasing, with some evidence that most local transmissions have been from foreign-born Amsterdam MSM since 2016.

2.
Transfusion ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963400

RESUMO

BACKGROUND: Less discriminatory donor selection policies for men who have sex with men (MSM) may impact transfusion safety in terms of higher residual risks for known transfusion-transmitted infections (TTIs), increased vulnerability toward new TTIs that are also transmitted via sex, and HIV infections masked by pre-exposure prophylaxis (PrEP). STUDY DESIGN AND METHODS: TTI trends in Dutch donors were studied over a 13-year period (2011-2023), characterized by successive relaxations of MSM deferral criteria. Structured posttest counseling was performed to determine risk factors in TTI-positive donors. PrEP drug levels were measured in 9977 donations from male donors living in urban areas and in 67 donors with active or resolved syphilis. RESULTS: HIV incidence (from 5.8 to 1.5 per 1,000,000 donor years (DY)) and HBV incidence (from 12.4 to 4.5 per 1,000,000 DY) in Dutch donors decreased with less stringent MSM deferral criteria, while syphilis prevalence (from 26.4 to 44.1 per 100,000 new donors) and syphilis incidence (from 18.3 to 46.3 per 1,000,000 DY) increased over time. The proportion of MSM-related syphilis rose from 2% to 32% in new donors and from 12% to 27% in repeat donors. PrEP was detected in 2 of 9977 (0.02%) donations from male donors living in urban areas, and in 1 of 39 (2.6%) male donors with syphilis. DISCUSSION: To date, phasing out donor deferral for MSM had no significant impact on transfusion safety in the Netherlands. However, rising syphilis rates and (recent) PrEP use in the blood donor population, albeit rare, suggest an influx of donors with higher sexual risk profiles and requires intensified TTI surveillance in donors.

3.
Vox Sang ; 119(4): 388-401, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38270352

RESUMO

BACKGROUND AND OBJECTIVES: Until recently, gay, bisexual and other men who have sex with men (MSM) were deferred from donating blood for 3-12 months since the last male-to-male sexual contact. This MSM deferral has been discontinued by several high-income countries (HIC) that now perform gender-neutral donor selection. MATERIALS AND METHODS: An international symposium (held on 20-04-2023) gathered experts from seven HICs to (1) discuss how this paradigm shift might affect the mitigation strategies for transfusion-transmitted infections and (2) address the challenges related to gender-neutral donor selection. RESULTS: Most countries employed a similar approach for implementing a gender-neutral donor selection policy: key stakeholders were consulted; the transition was bridged by time-limited deferrals; donor compliance was monitored; and questions or remarks on anal sex and the number and/or type of sexual partners were often added. Many countries have now adopted a gender-neutral approach in which questions on pre- and post-exposure prophylaxis for human immunodeficiency virus (HIV) have been added (or retained, when already in place). Other countries used mitigation strategies, such as plasma quarantine or pathogen reduction technologies for plasma and/or platelets. CONCLUSION: The experience with gender-neutral donor selection has been largely positive among the countries covered herein and seems to be acceptable to stakeholders, donors and staff. The post-implementation surveillance data collected so far appear reassuring with regards to safety, although longer observation periods are necessary. The putative risks associated with HIV antiretrovirals should be further investigated.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Humanos , Masculino , Feminino , Homossexualidade Masculina , Seleção de Pacientes , Infecções por HIV/epidemiologia , Doadores de Sangue , Comportamento Sexual , Seleção do Doador
4.
Vox Sang ; 119(7): 745-751, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38516962

RESUMO

BACKGROUND AND OBJECTIVES: Nucleic acid-amplification testing (NAT) is used for screening blood donations/donors for blood-borne viruses. We reviewed global viral NAT characteristics and NAT-yield confirmatory testing used by blood operators. MATERIALS AND METHODS: NAT characteristics and NAT-yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion-Transmitted Infectious Diseases. Reported characteristics are presented herein. RESULTS: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini-pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT-yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow-up sample. CONCLUSION: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT-yields, potentially benefitting blood operators seeking to implement NAT.


Assuntos
Doadores de Sangue , Técnicas de Amplificação de Ácido Nucleico , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Infecções Transmitidas por Sangue , Seleção do Doador/métodos
5.
Vox Sang ; 119(4): 315-325, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38390819

RESUMO

BACKGROUND AND OBJECTIVES: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion-transmitted infections. This project reviewed NAT for screening blood donations globally. MATERIALS AND METHODS: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion-transmitted Infectious Diseases (ISBT WP-TTID), was distributed through ISBT WP-TTID members. Data were analysed using descriptive statistics. RESULTS: Forty-three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT-positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT-positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT-positivity rate was higher in first-time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). CONCLUSION: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT.


Assuntos
Hepatite B , Ácidos Nucleicos , Reação Transfusional , Infecção por Zika virus , Zika virus , Humanos , Doação de Sangue , Doadores de Sangue , Hepatite B/diagnóstico , Vírus da Hepatite B/genética , Técnicas de Amplificação de Ácido Nucleico
6.
Entropy (Basel) ; 25(8)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37628168

RESUMO

Bayesian state and parameter estimation are automated effectively in a variety of probabilistic programming languages. The process of model comparison on the other hand, which still requires error-prone and time-consuming manual derivations, is often overlooked despite its importance. This paper efficiently automates Bayesian model averaging, selection, and combination by message passing on a Forney-style factor graph with a custom mixture node. Parameter and state inference, and model comparison can then be executed simultaneously using message passing with scale factors. This approach shortens the model design cycle and allows for the straightforward extension to hierarchical and temporal model priors to accommodate for modeling complicated time-varying processes.

7.
Transfusion ; 62(6): 1241-1250, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35502143

RESUMO

BACKGROUND: To better balance the safety of the blood supply and the inclusion of men who have sex with men (MSM), further improvements are needed to the risk management strategy employed in the Netherlands to reduce transfusion-transmissible infections (TTIs). A gender-neutral individual risk assessment could provide a solution by determining donor eligibility based on sexual behaviors known to increase the risk of TTIs. Our objective is to estimate the proportion of blood donors that would be deferred by such an assessment, as well as their discomfort answering such questions. STUDY DESIGN AND METHODS: Two surveys were distributed in May 2020 to assess sexual behavior in blood donors in the last 4, 6, and 12 months, as well as their discomfort reporting such information. A combination of both surveys measured the extent to which discomfort was associated with reporting sexual behavior. A high-risk sexual behavior pattern was defined as having had multiple sexual partners and having engaged in anal sex, without consistent condom use. RESULTS: Of all 2177 participating whole blood donors, 0.8% report engaging in high-risk sexual behaviors over the last 4 months and would therefore be ineligible to donate. When accounting for the additional proportion of donors that reported such questions would stop them from donating, 2.0% and 3.2% of female and male donors, respectively, would be lost. DISCUSSION: Gender-neutral eligibility criteria based on high-risk sexual behaviors may reduce the overall number of eligible donors in the Netherlands, but could make blood donation more accessible to a broader group of donors.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Doadores de Sangue , Segurança do Sangue , Seleção do Doador , Feminino , Homossexualidade Masculina , Humanos , Masculino , Países Baixos , Medição de Risco , Comportamento Sexual
8.
Bioethics ; 36(8): 840-848, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35656585

RESUMO

Blood service organizations employ various ways to ensure transfusion blood safety, including the testing of all donations for transfusion-transmissible infections (TTI) and the exclusion of donors who are at increased risk of a recent infection. As some TTIs are more common among men who have sex with men (MSM), many jurisdictions (temporarily) defer the donation of blood by sexually active MSM. This boils down to a categorical exclusion of a large group solely on the basis of their sexual orientation, which is seen as unduly discriminatory and stigmatizing. Blood service organizations in the U.K. and the Netherlands have recently changed their deferral policies for MSM. The problem of the MSM deferral involves a conflict between fundamental rights: the right of MSM to equal treatment and the right to health of the recipients of blood and blood products. We distinguish and discuss three broad alternative options to the current categorical deferral of MSM donations: (1) completely abandoning donor selection on the basis of sexual behavior, (2) individual risk assessment of the sexual activities of each potential donor, and (3) individual risk assessment of the sexual activities of MSM only. The new U.K. policy falls within the second category, and the new Dutch policy is in the third category. We argue that each approach comes with moral costs but that the most reasonable option is different from the policies of both the U.K. and the Netherlands.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Doadores de Sangue , Segurança do Sangue/efeitos adversos , Feminino , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual
9.
J Infect Dis ; 223(2): 206-213, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535237

RESUMO

BACKGROUND: Recent advances in CRISPR-based diagnostics suggest that DETECTR, a combination of reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) and subsequent Cas12 bystander nuclease activation by amplicon-targeting ribonucleoprotein complexes, could be a faster and cheaper alternative to quantitative reverse-transcription polymerase chain reaction (qRT-PCR) without sacrificing sensitivity and/or specificity. METHODS: In this study, we compare DETECTR with qRT-PCR to diagnose coronavirus disease 2019 on 378 patient samples. Patient sample dilution assays suggest a higher analytical sensitivity of DETECTR compared with qRT-PCR; however, this was not confirmed in this large patient cohort, where we report 95% reproducibility between the 2 tests. RESULTS: These data showed that both techniques are equally sensitive in detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) providing additional value of DETECTR to the currently used qRT-PCR platforms. For DETECTR, different guide ribonucleic acids can be used simultaneously to obviate negative results due to mutations in N-gene. Lateral flow strips, suitable as a point-of-care test, showed a 100% correlation to the high-throughput DETECTR assay. More importantly, DETECTR was 100% specific for SARS-CoV-2 relative to other human coronaviruses. CONCLUSIONS: Because there is no need for specialized equipment, DETECTR could be rapidly implemented as a complementary technically independent approach to qRT-PCR thereby increasing the testing capacity of medical microbiological laboratories and relieving the existent PCR platforms for routine non-SARS-CoV-2 diagnostic testing.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , SARS-CoV-2/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Testes Imediatos , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Padrões de Referência , Reprodutibilidade dos Testes , SARS-CoV-2/genética
10.
Clin Infect Dis ; 72(12): e1056-e1063, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33289036

RESUMO

BACKGROUND: It is unclear whether unrestricted access and high uptake of direct-acting antivirals (DAAs) is sufficient to eliminate hepatitis C virus (HCV) in high-risk populations such as men who have sex with men (MSM). This study presents historic trends and current dynamics of HCV transmission among MSM in Amsterdam based on sequence data collected between 1994 and 2019. METHODS: Hypervariable region 1 sequences of 232 primary HCV infections and 56 reinfections were obtained from 244 MSM in care in Amsterdam. Maximum-likelihood phylogenies were constructed for HCV genotypes separately, and time-scaled phylogenies were constructed using a Bayesian coalescent approach. Transmission clusters were determined by Phydelity and trends in the proportion of unclustered sequences over time were evaluated using logistic regression. RESULTS: Seventy-six percent (218/288) of sequences were part of 21 transmission clusters and 13 transmission pairs. Transmission cluster sizes ranged from 3 to 44 sequences. Most clusters were introduced between the late 1990s and early 2010s and no new clusters were introduced after 2012. The proportion of unclustered sequences of subtype 1a, the most prevalent subtype in this population, fluctuated between 0% and 20% in 2009-2012, after which an increase occurred from 0% in 2012 to 50% in 2018. CONCLUSIONS: The proportion of external introductions of HCV infections among MSM in Amsterdam has recently increased, coinciding with high DAA uptake. Frequent international transmission events will likely complicate local microelimination efforts. Therefore, international collaboration combined with international scale-up of prevention, testing, and treatment of HCV infections (including reinfections) is warranted, in particular for local microelimination efforts.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Minorias Sexuais e de Gênero , Antivirais/uso terapêutico , Teorema de Bayes , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Homossexualidade Masculina , Humanos , Masculino
11.
Clin Infect Dis ; 73(3): 460-467, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-32459339

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at high risk of hepatitis C virus (HCV) reinfection following clearance of HCV, but risk factors specifically for reinfection have never been comprehensively assessed. METHODS: Using data from a prospective observational cohort study among HIV-positive MSM with an acute HCV infection (MOSAIC), the incidence of HCV reinfection following spontaneous clearance or successful treatment was assessed. A univariable Bayesian exponential survival model was used to identify risk factors associated with HCV reinfection. RESULTS: In total, 122 HIV-positive MSM who had a spontaneously cleared or successfully treated HCV infection between 2003 and 2017 were included. During a median follow-up of 1.4 years (interquartile range [IQR] 0.5-3.8), 34 HCV reinfections were observed in 28 patients. The incidence of HCV reinfection was 11.5/100 person-years and among those with reinfection, median time to reinfection was 1.3 years (IQR 0.6-2.7). HCV reinfection was associated with receptive condomless anal intercourse, sharing of sex toys, group sex, anal rinsing before sex, ≥10 casual sex partners in the last 6 months, nadir CD4 cell count <200 cells/mm3, and recent CD4 cell count <500 cells/mm3. CONCLUSIONS: Incidence of HCV reinfection was high and strongly associated with sexual risk behavior, highlighting the need for interventions to reduce risk behavior and prevent HCV reinfections among HIV-positive MSM.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C , Minorias Sexuais e de Gênero , Teorema de Bayes , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/epidemiologia , Homossexualidade Masculina , Humanos , Incidência , Masculino , Estudos Prospectivos , Reinfecção , Assunção de Riscos , Comportamento Sexual
12.
Neural Comput ; 33(10): 2710-2735, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34280254

RESUMO

Active inference (ActInf) is an emerging theory that explains perception and action in biological agents in terms of minimizing a free energy bound on Bayesian surprise. Goal-directed behavior is elicited by introducing prior beliefs on the underlying generative model. In contrast to prior beliefs, which constrain all realizations of a random variable, we propose an alternative approach through chance constraints, which allow for a (typically small) probability of constraint violation, and demonstrate how such constraints can be used as intrinsic drivers for goal-directed behavior in ActInf. We illustrate how chance-constrained ActInf weights all imposed (prior) constraints on the generative model, allowing, for example, for a trade-off between robust control and empirical chance constraint violation. Second, we interpret the proposed solution within a message passing framework. Interestingly, the message passing interpretation is not only relevant to the context of ActInf, but also provides a general-purpose approach that can account for chance constraints on graphical models. The chance constraint message updates can then be readily combined with other prederived message update rules without the need for custom derivations. The proposed chance-constrained message passing framework thus accelerates the search for workable models in general and can be used to complement message-passing formulations on generative neural models.


Assuntos
Teorema de Bayes , Probabilidade
13.
Transfusion ; 61(7): 2116-2124, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33899233

RESUMO

BACKGROUND: In the Netherlands, blood donor screening for hepatitis B virus (HBV) consists of HBsAg screening since the 1970s, HBV DNA minipool testing (MP-NAT) since 2008, and anti-HBc screening since 2011. Anti-HBc reactivity causes deferral only if anti-HBs titers are <200 IU/mL, or when anti-HBc was acquired during follow-up. STUDY DESIGN AND METHODS: Over 5.5 million donations from 582,459 Dutch donors were screened for HBV DNA, HBsAg, anti-HBc, and, if anti-HBc positive, also for anti-HBs. The added value, expressed as the yield of (potentially) infectious and/or recent HBV infections versus unnecessary donor loss, was evaluated for each of the three HBV screening tests. RESULTS: HBV donor screening identified 89 HBV-infected donors with at least two reactive HBV markers (MP-NAT, HBsAg and/or anti-HBc). Single HBV-marker yield was: 5 MP-NAT-only, 0 HBsAg-only, and 20 anti-HBc-only donors. In addition, anti-HBc screening yielded 1,067 potentially infectious donors at risk for occult HBV infection (OBI). In total, 4,126 (0.71%) donors were anti-HBc-reactive at first-time screening, and 1,098 (0.19%) seroconverted during follow-up. Anti-HBc-related donor loss was limited to 2,627 (0.45%) donors using anti-HBs titers and two-strike programs. Donor loss due to MP-NAT and HBsAg screening was extremely low: 0 and 128 donors, respectively. CONCLUSION: HBV donor screening could be limited to MP-NAT and anti-HBc screening. MP-NAT and anti-HBc improved blood safety by intercepting infectious donations from donors with recent infection or OBI, while HBsAg did not. Unnecessary donor loss related to anti-HBc screening is substantial but does not endanger the continuity of the blood supply.


Assuntos
Doadores de Sangue , Segurança do Sangue , Seleção do Doador , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B/prevenção & controle , Técnicas de Amplificação de Ácido Nucleico , Viremia/sangue , Adulto , DNA Viral/sangue , Hepatite B/sangue , Hepatite B/diagnóstico , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Países Baixos , Procedimentos Desnecessários , Viremia/diagnóstico , Viremia/virologia
14.
Vox Sang ; 116(10): 1084-1093, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33835513

RESUMO

BACKGROUND AND OBJECTIVES: Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. MATERIALS AND METHODS: Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody-positive donations and nucleic acid testing (NAT)-only-positive donations was broken down according to first-time or repeat donor status, along with the relevant denominators. RESULTS: There is a modest correlation between HIV prevalence among first-time donors and HIV prevalence in the general population. However, rates of HIV-positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT-only-positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. CONCLUSION: Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low.


Assuntos
Doadores de Sangue , Infecções por HIV , Brasil , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , Prevalência
15.
Entropy (Basel) ; 23(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202913

RESUMO

Accurate evaluation of Bayesian model evidence for a given data set is a fundamental problem in model development. Since evidence evaluations are usually intractable, in practice variational free energy (VFE) minimization provides an attractive alternative, as the VFE is an upper bound on negative model log-evidence (NLE). In order to improve tractability of the VFE, it is common to manipulate the constraints in the search space for the posterior distribution of the latent variables. Unfortunately, constraint manipulation may also lead to a less accurate estimate of the NLE. Thus, constraint manipulation implies an engineering trade-off between tractability and accuracy of model evidence estimation. In this paper, we develop a unifying account of constraint manipulation for variational inference in models that can be represented by a (Forney-style) factor graph, for which we identify the Bethe Free Energy as an approximation to the VFE. We derive well-known message passing algorithms from first principles, as the result of minimizing the constrained Bethe Free Energy (BFE). The proposed method supports evaluation of the BFE in factor graphs for model scoring and development of new message passing-based inference algorithms that potentially improve evidence estimation accuracy.

16.
J Hepatol ; 72(5): 855-864, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31862485

RESUMO

BACKGROUND & AIMS: HCV has emerged as a sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). We evaluated HCV incidence and its risk factors among HIV-negative MSM using HIV pre-exposure prophylaxis (PrEP). METHODS: Participants of the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. Participants used daily or event-driven PrEP and could switch regimens during follow-up. We calculated incidence rates (IRs) for overall HCV infection and separately for primary and re-infection. A univariable Bayesian exponential survival model was used to identify risk factors associated with incident HCV infection. The HCV NS5B gene fragment (709 bp) was sequenced and compared to HCV isolates from HIV-positive MSM and other risk groups (n = 419) using phylogenetic analysis. RESULTS: Among 350 participants contributing 653.6 person-years (PYs), we detected 15 HCV infections in 14 participants (IR = 2.30/100PY). There were 8 primary infections (IR = 1.27/100PY) and 7 re-infections (IR = 27.8/100PY). IR was 2.71/100PY in daily and 1.15/100PY in event-driven PrEP users. Factors associated with incident HCV infection were higher number of receptive condomless anal sex acts with casual partners (posterior hazard ratio [HR] 1.57 per ln increase; 95% credibility interval [CrI] 1.09-2.20), anal STI (posterior HR 2.93; 95% CrI 1.24-7.13), injecting drug use (posterior HR 4.69; 95% CrI 1.61-12.09) and sharing straws when snorting drugs (posterior HR 2.62; 95% CrI 1.09-6.02). We identified robust MSM-specific HCV clusters of subtypes 1a, 4d, 2b and 3a, which included MSM with and without HIV. CONCLUSIONS: HIV-negative MSM using PrEP are at risk of incident HCV infection, while identified risk factors are similar to those in HIV-positive MSM. Regular HCV testing is needed, especially for those with a previous HCV infection and those reporting risk factors. LAY SUMMARY: We report that hepatitis C virus infections are frequently acquired among HIV-negative men who have sex with men (MSM) using pre-exposure prophylaxis to prevent HIV infection. New infections occurred more frequently in those reporting receptive anal sex without using condoms, having an anal sexually transmitted infection, injecting drugs, and sharing straws when snorting drugs. The viruses found in HIV-negative men using pre-exposure prophylaxis are genetically similar to those in HIV-positive men, but not in other hepatitis C risk groups, suggesting that (sexual) transmission is occurring between HIV-positive MSM and HIV-negative MSM using pre-exposure prophylaxis. CLINICAL TRIAL NUMBER: Dutch trial registration number NTR5411.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , HIV , Hepacivirus/genética , Hepatite C/epidemiologia , Homossexualidade Masculina , Profilaxia Pré-Exposição/métodos , Reinfecção/epidemiologia , Pessoas Transgênero , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Feminino , Seguimentos , Genótipo , Hepatite C/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/genética , Fatores de Risco , Comportamento Sexual , Sexo sem Proteção
17.
Clin Infect Dis ; 68(6): 1001-1008, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30052873

RESUMO

BACKGROUND: Deferral of men who have sex with men (MSM) from blood donation is highly debated. We therefore investigated their suitability to donate blood. METHODS: We compared the antibody prevalence of 10 sexually and transfusion-transmissible infections (TTIs) among 583 MSM and 583 age-matched repeat male blood donors. MSM were classified as low risk (lr) or medium-to-high risk (hr) based on self-reported sexual behavior and as qualified or unqualified using Dutch donor deferral criteria. Infection pressure (IP) was defined as the number of antibody-reactive infections, with class A infections (human immunodeficiency virus-1/2, hepatitis B virus, hepatitis C virus, human T-cell lymphotropic virus-1/2, syphilis) given double weight compared to class B infections (cytomegalovirus, herpes simplex virus-1/2, human herpesvirus 8, hepatitis E virus, parvovirus B19). RESULTS: Donors had a lower median IP than qualified lr-MSM and qualified hr-MSM (2 [interquartile range {IQR}, 1-2] vs 3 [IQR, 2-4]; P < .001). Low IP was found in 76% of donors, 39% of qualified lr-MSM, and 27% of qualified hr-MSM. The prevalence of class A infections did not differ between donors and qualified lr-MSM but was significantly higher in qualified hr-MSM and unqualified MSM. Recently acquired class A infections were detected in hr-MSM only. Compared to blood donors, human herpesviruses were more prevalent in all MSM groups (P < .001). CONCLUSIONS: IP correlates with self-reported risk behavior among MSM. Although lr-MSM might form a low threat for blood safety with regard to class A infections, the high seroprevalence of human herpesviruses in lr-MSM warrants further investigation.


Assuntos
Doadores de Sangue , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/psicologia , Homossexualidade Masculina , Influência dos Pares , Adulto , Doadores de Sangue/psicologia , Coinfecção , Doenças Transmissíveis/transmissão , Homossexualidade Masculina/psicologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Fatores de Risco , Assunção de Riscos , Comportamento Sexual
18.
Transfusion ; 59(8): 2575-2583, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31228271

RESUMO

BACKGROUND: In the Netherlands, needle-related events (NREs) including tattoos, piercings, and acupuncture are a reason for temporary blood donor deferral. This study aims to evaluate whether donors with recent NREs had a higher risk of transfusion-transmissible infections (TTIs) compared to donors without recent NREs. STUDY DESIGN AND METHODS: Data from 2006 through 2015 on all blood donation attempts in the Netherlands were collected. Multivariate regression models (for repeated measurements) were used to assess the associations between recent NREs and the acquisition of TTIs. Posttest counseling data were used to determine the most likely risk factor in TTI-positive new and repeat donors. RESULTS: Recent NREs were documented in 97,518 out of 9,266,036 (1.1%) donation attempts; 14,097 (14.5%) NREs resulted in NRE-based donor deferral. Recent NREs reported pre-donation were not associated with an increased risk for TTIs. A total of 29 out of 287 TTI-positive donors (11 repeat donors, 18 new donors) reported a recent NRE pre- and/or post-donation. Recent NREs, all needle-stick injuries, were the likely route of transmission in 12 out of 287 (4.2%) of TTI-positive donors. The donor health questionnaire (DHQ) identified only 1 out of 12 TTI-linked NREs. Non-return after NRE deferral, any deferral, or no deferral was 24, 15, and 5%, respectively. DISCUSSION: Recent tattoos, body piercings, or acupuncture were not associated with an increased risk for TTIs in Dutch donors. Given the lower return rates of donors following a temporary NRE-based deferral, we advocate ending blood donor deferral policies for acupuncture, tattooing, and body piercings, but not needle-stick injuries, in countries where these practices can be considered safe.


Assuntos
Terapia por Acupuntura , Doadores de Sangue , Transfusão de Sangue , Piercing Corporal , Inquéritos e Questionários , Tatuagem , Reação Transfusional/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Risco
20.
Sex Transm Infect ; 93(5): 368-373, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27789574

RESUMO

The number of infectious disease outbreaks and the number of unique pathogens responsible have significantly increased since the 1980s. HIV-positive men who have sex with men (MSM) are a vulnerable population with regards to the introduction, spread and clinical consequences of (newly introduced) STIs. After the introduction of combination antiretroviral treatment (cART), the incidence of sexually acquired hepatitis C virus (HCV) infection and human papillomavirus (HPV)-induced anal cancers have significantly increased among HIV-positive MSM. The introduction and expansion of HCV is the result of increased sexual risk behaviour and sexually acquired mucosal trauma within large interconnected networks of HIV-positive MSM in particular. With the availability of cART, postexposure and pre-exposure prophylaxis (PEP and PrEP) and direct-acting antivirals (DAAs) for HCV, less concern for HIV and HCV might require a new approach to develop effective behavioural intervention strategies among MSM. The marked rise in HPV-induced anal cancers can be ascribed to the long-term immunologic defects in an ageing population affected by HIV. More evidence with regards to effective treatment options for anal dysplastic lesions and the usefulness of anal malignancy screening programmes is urgently needed. Most anal cancers in the future generation of HIV-positive MSM could be prevented with the inclusion of boys in addition to girls in current HPV vaccination programmes.


Assuntos
Doenças do Ânus/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Hepatite C/epidemiologia , Homossexualidade Masculina , Infecções por Papillomavirus/epidemiologia , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Canal Anal/virologia , Doenças do Ânus/etiologia , Doenças do Ânus/prevenção & controle , Doenças do Ânus/virologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/prevenção & controle , Neoplasias do Ânus/virologia , Doenças Transmissíveis Emergentes/virologia , Infecções por HIV/complicações , Infecções por HIV/transmissão , Infecções por HIV/virologia , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Hepatite C/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Profilaxia Pré-Exposição , Fatores de Risco , Doenças Virais Sexualmente Transmissíveis/complicações , Doenças Virais Sexualmente Transmissíveis/tratamento farmacológico , Doenças Virais Sexualmente Transmissíveis/transmissão
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