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Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.
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ABSTRACTRat hepatitis E virus (ratHEV) is an emerging cause of acute hepatitis of zoonotic origin. Since seroprevalence studies are scarce, at-risk groups are almost unknown. Because blood-borne infections frequently occur in people with drug use, who are particularly vulnerable to infection due to lack of housing and homelessness, this population constitutes a priority in which ratHEV infection should be evaluated. Therefore, the aim of this study was to evaluate the ratHEV seroprevalence and RNA detection rate in drug users as a potential at-risk population. We designed a retrospective study involving individuals that attended drug rehabilitation centres. Exposure to ratHEV was assessed by specific antibody detection using ELISA and dot blot (DB) assay and the presence of active infection by ratHEV RNA detection using RT-qPCR. Three-hundred and forty-one individuals were included, the most of them being men (67.7%) with an average age of 45 years. A total of 17 individuals showed specific IgG antibodies against ratHEV (4.6%; 95% CI; 3.1%-7.9%). One case of active ratHEV infection was identified (0.3%; 95% CI: 0.1%-1.8%). This was a 57-year-old homeless woman with limited financial resources, who had active cocaine and heroin use via parenteral route. In conclusion, we identified a potential exposure to ratHEV among drug users. Targeted studies in drug users with proper control groups are necessary to evaluate high-risk populations and transmission routes more accurately.
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Usuários de Drogas , Vírus da Hepatite E , Hepatite E , Humanos , Pessoa de Meia-Idade , Hepatite E/epidemiologia , Hepatite E/virologia , Hepatite E/veterinária , Masculino , Feminino , Estudos Soroepidemiológicos , Adulto , Estudos Retrospectivos , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , RNA Viral/sangue , Anticorpos Anti-Hepatite/sangue , Animais , Imunoglobulina G/sangue , Adulto Jovem , RatosRESUMO
BackgroundVarious pathogens, including bacteria, fungi, parasites, and viruses can lead to meningitis. Among viruses causing meningitis, Toscana virus (TOSV), a phlebovirus, is transmitted through sandfly bites. TOSV infection may be suspected if patients with enterovirus- and herpesvirus-negative aseptic (non-bacterial) meningitis recall recent insect bites. Other epidemiological factors (season, rural area) may be considered. The broad range of possible meningitis aetiologies poses considerable diagnosis challenges. Untargeted metagenomic next-generation sequencing (mNGS) can potentially identify pathogens, which are not considered or detected in routine diagnostic panels.AimIn this retrospective, single-centre observational study, we investigated mNGS usefulness to understand the cause of meningitis when conventional approaches fail.MethodsCerebrospinal fluid (CSF) samples from patients hospitalised in southern Spain in 2015-2019 with aseptic meningitis and no aetiology found by conventional testing, were subjected to mNGS. Patients' demographic characteristics had been recorded and physicians had asked them about recent insect bites. Obtained viral genome sequences were phylogenetically analysed.ResultsAmong 23 idiopathic cases, TOSV was identified in eight (all male; median age: 39 years, range: 15-78 years). Five cases lived in an urban setting, three occurred in autumn and only one recalled insect bites. Phylogenetic analysis of TOSV segment sequences supported one intra-genotype reassortment event.ConclusionsOur study highlights the usefulness of mNGS for identifying viral pathogens directly in CSF. In southern Spain, TOSV should be considered regardless of recalling of insect bites or other epidemiological criteria. Detection of a disease-associated reassortant TOSV emphasises the importance of monitoring the spread and evolution of phleboviruses in Mediterranean countries.
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Mordeduras e Picadas de Insetos , Meningite , Vírus da Febre do Flebótomo Napolitano , Humanos , Masculino , Adulto , Vírus da Febre do Flebótomo Napolitano/genética , Filogenia , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
IMPORTANCE: This observation provides comprehensive data on the clinical correlates of both cytomegalovirus (CMV) genotypic follow-up and clinical monitoring and outcomes for two different solid organ transplantation recipients that received letermovir as secondary prophylaxis. Our study emphasizes that monitoring of CMV disease in the patient and early genotypic detection of resistance mutations are essential when using new antiviral drugs for off-label indication in patients experiencing CMV relapses or not responding to standard antiviral therapy. These cases and the bibliography reviewed can be helpful for other researchers and clinicians working in the field to optimize the use of new treatments for transplant recipients since drug-resistant CMV infection is an important emerging problem even with new developments in antiviral treatment.
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Infecções por Citomegalovirus , Transplante de Órgãos , Humanos , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/genética , Transplantados , Transplante de Órgãos/efeitos adversosRESUMO
Cytomegalovirus (CMV) infection is a major driver of accelerated immunosenescence related to CD28null T cell expansion. CMV infection and these proatherogenic T cells have been independently associated with cardiovascular disease and coronavirus disease 2019 (COVID-19) severity. We investigated the potential contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to immunosenescence and its relationship with CMV. Innate and adaptive immune subpopulations from individuals with mild or asymptomatic SARS-CoV-2 infection (mCOVID-19) and healthy donors were immunophenotyped. A significant increase in CD28nullCD57+CX3CR1+ T cell percentages (CD4+ [P ≤ .01], CD8+ [P ≤ .01], and TcRγδ (CD4-CD8-) [P ≤ .001]) was found in unnvaccinated CMV-seropositive mCOVID-19 individuals stable up to 12 months after infection. This expansion did not occur in CMV-seronegative mCOVID-19 individuals or in CMV-seropositive individuals infected after SARS-CoV-2 vaccination. There were no significant differences between mCOVID-19 and aortic stenosis groups. Thus, individuals coinfected with SARS-CoV-2 and CMV have accelerated T cell senescence, which might lead to an increased risk of cardiovascular disease.
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COVID-19 , Doenças Cardiovasculares , Infecções por Citomegalovirus , Imunossenescência , Humanos , Citomegalovirus , Linfócitos T , Vacinas contra COVID-19 , SARS-CoV-2 , Linfócitos T CD8-PositivosRESUMO
Background and aims: Persons with substance use disorder are at increased risk for hepatitis B virus (HBV) infection. Although most of them are attached to social health centers, the vaccination rate in this group is low. In this context, we designed a study to evaluate the prevalence of users of drug addiction centers (DAC) not immunized against hepatitis B and to compare the rate of vaccination against hepatitis B with the rate of immunization against SARS-Cov-2 in 2 years of follow-up. Design: Retrospective study that included individuals attended at DAC. Patients were screened at baseline (June 2020-January 2021) for HBV immunization. Individuals with HBsAb < 10 IU/mL were recommended to receive hepatitis B vaccine, during follow-up (January 2021-October 2022). At the end of follow-up, the HBV vaccination rate among candidates was determined and compared with the vaccination rate against SARS-Cov-2 in this population in the same period. Findings: A total of 325 subjects were surveyed and tested. At baseline, the 65% (211/325) of were candidates to initiate vaccination and were advisor to HBV vaccination. During the follow-up 15 individuals received at least one dose of HBV vaccine, supposing a vaccination rate of 7.2%. In the same period, 186 individuals received at least one dose against SARS-Cov-2, representing a vaccination rate of 83%. The comparison between vaccination rates reached statistically significant (p < 0.001). Conclusion: Our study manifests a low rate of immunization against HBV in DAC users, despite a high level of immunization for SARS-Cov-2 during the same period in the same population. Consequently, the lack of immunization against HVB in this population might be related with health policy issue more than to individuals linked to care and awareness. A similar approach for vaccination intended for SARS-CoV2 should be applied in high-risk population to warrant the success of immunization program against other preventable diseases such as HBV.
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COVID-19 , Hepatite B , Transtornos Relacionados ao Uso de Substâncias , Humanos , RNA Viral , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vacinação , Vacinas contra Hepatite B , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Human cytomegalovirus (HCMV) is linked to age-related diseases like cardiovascular disease, neurodegenerative conditions, and cancer. It can also cause congenital defects and severe illness in immunocompromised individuals. Accurate HCMV seroprevalence assessment is essential for public health planning and identifying at-risk individuals. This is the first HCMV seroprevalence study conducted in the general Spanish adult population in 30 years. We studied HCMV seroprevalence and HCMV IgG antibody titres in healthy adult donors (HDs) and HCMV-related disease patients from 2010 to 2013 and 2020 to 2023, categorized by sex and age. We compared our data with 1993 and 1999 studies in Spain. The current HCMV seroprevalence among HDs in Spain is 73.48%. In women of childbearing age, HCMV seroprevalence has increased 1.4-fold in the last decade. HCMV-seropositive individuals comprise 89.83% of CVD patients, 69% of SMI patients, and 70.37% of COVID-19 patients. No differences in HCMV seroprevalence or HCMV IgG antibody titres were observed between patients and HDs. A significant reduction in Spanish HCMV seroprevalence among HDs was observed in 1993. However, women of childbearing age have shown an upturn in the last decade that may denote a health risk in newborns and a change in HCMV seroprevalence trends.
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Doenças Cardiovasculares , Infecções por Citomegalovirus , Adulto , Humanos , Recém-Nascido , Feminino , Citomegalovirus , Estudos Soroepidemiológicos , Doadores de Tecidos , Anticorpos Antivirais , Imunoglobulina GRESUMO
BACKGROUND & AIM: Hepatitis E virus (HEV) was considered the only member of the Hepeviridae family with zoonotic potential. Nevertheless, this consideration has been reassessed owing to several reported cases of acute and chronic hepatitis linked to the Orthohepevirus C genus. Because the circulation of Orthohepevirus C in rodents has been described worldwide, the risk of zoonotic transmission is plausibly global. METHODS: Orthohepevirus C RNA was retrospectively evaluated in 2 cohorts of patients in Spain. The first cohort included patients with acute hepatitis without etiological diagnosis after screening for hepatotropic virus infection. The second cohort included patients diagnosed with acute HEV infection, defined as positivity for anti-HEV-IgM antibodies and/or detectable HEV RNA in serum. RESULTS: Cohort 1 comprised 169 patients (64.4% male, median age 43 years) and cohort 2 comprised 98 individuals (68.3% male, median age 45 years). Of the individuals included in Cohort 1, two (1.18%; 95% CI 0.2-3.8) had detectable Orthohepevirus C RNA in serum. In Cohort 2, of the 98 included patients, 58 showed detectable HEV RNA, while 40 only showed positivity for IgM antibodies. Among those bearing only IgM antibodies, Orthohepevirus C RNA was detected in 1 (2.5%; 95% CI 0.06-13.1) individual. All strains were consistent with genotype C1. The infection resulted in mild self-limiting acute hepatitis in 2 patients. Infection caused severe acute hepatitis in the remaining patient who died as a result of liver and renal failure. CONCLUSIONS: We described 3 cases of Orthohepevirus C in patients with acute hepatitis, resulting in the first description of this infection in Europe. The prevalence obtained in our study suggests that Orthohepevirus C could be an emerging disease in Europe. LAY SUMMARY: We describe the first cases of acute hepatitis related to rat hepatitis E virus in Europe. The prevalence found in our study suggest that rat hepatitis E virus could be considered an emerging disease in Europe.
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Vírus da Hepatite E , Hepatite E , Animais , Europa (Continente)/epidemiologia , Feminino , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Vírus da Hepatite E/genética , Humanos , Imunoglobulina M , Masculino , RNA , RNA Viral , Ratos , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
New circulating Enterovirus (EV) strains often emerge through recombination. Upsurges of recombinant non-polio enteroviruses (NPEVs) associated with neurologic manifestations such as EVA71 or Echovirus 30 (E30) are a growing public health concern in Europe. Only a few complete genomes of EVs circulating in Spain are available in public databases, making it difficult to address the emergence of recombinant EVs, understand their evolutionary relatedness and the possible implication in human disease. We have used metagenomic (untargeted) NGS to generate full-length EV genomes from CSF samples of EV-positive aseptic meningitis cases in Southern Spain between 2015 and 2018. Our analyses reveal the co-circulation of multiple Enterovirus B (EV-B) types (E6, E11, E13 and E30), including a novel E13 recombinant form. We observed a genetic turnover where emergent lineages (C1 for E6 and I [tentatively proposed in this study] for E30) replaced previous lineages circulating in Spain, some concomitant with outbreaks in other parts of Europe. Metagenomic sequencing provides an effective approach for the analysis of EV genomes directly from PCR-positive CSF samples. The detection of a novel, disease-associated, recombinant form emphasizes the importance of genomic surveillance to monitor spread and evolution of EVs.
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Enterovirus Humano B/genética , Infecções por Enterovirus/virologia , Genoma Viral , Meningite Asséptica/virologia , RNA Viral/genética , Adolescente , Adulto , Enterovirus Humano B/classificação , Enterovirus Humano B/isolamento & purificação , Infecções por Enterovirus/líquido cefalorraquidiano , Infecções por Enterovirus/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Meningite Asséptica/líquido cefalorraquidiano , Meningite Asséptica/epidemiologia , Filogenia , RNA Viral/líquido cefalorraquidiano , Análise de Sequência de DNA , Espanha/epidemiologia , Adulto JovemRESUMO
The objective was to evaluate the accuracy of a single determination of IgM antibodies for hepatitis E virus (HEV) diagnosis in patients with acute hepatitis. A prospective study included patients with suspicion of HEV infection, defined as individuals with acute hepatitis showing negative results for serological and molecular markers of other hepatitis viruses. All patients were evaluated for hepatitis E virus infection, including both IgM antibodies and viral RNA determinations. Hepatitis E virus infection was defined as positivity for any of these markers. A total of 182 patients were included in the study, of whom 68 (37.4%) were diagnosed with HEV infection. Of these, 29 (42.6%) were positive for both IgM and HEV RNA, 25 (36.8%) were positive only for IgM antibodies, and 14 (20.6%) were positive only for HEV RNA. Considering only those individuals who were positive for IgM antibodies, 54 of the 68 total cases (79.4%) could be identified, showing a percentage of false-negative individuals of 20.6%. The diagnostic algorithm of hepatitis E virus infection in patients with acute hepatitis should include the determination of both IgM antibodies and HEV RNA because single sampling for IgM antibody determination led to an important proportion of misdiagnosed cases. IMPORTANCE In immunocompetent patients with a suspicion of hepatitis E virus (HEV) infection, single IgM antibody testing is typically applied. In this prospective study, we aimed to evaluate the accuracy of three different HEV screening approaches in patients with acute hepatitis, including approaches based on IgM determination, HEV RNA detection, and the combination of both. Our study shows that any diagnostic algorithm for HEV infection in patients with acute hepatitis should be based on the determination of both markers (IgM antibodies and HEV RNA) because single sampling for IgM antibodies results in an unacceptable number of false-negative results (20%). According to our results, the determination of HEV RNA should not be limited to immunosuppressed individuals because a high proportion of cases could be misdiagnosed.
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Vírus da Hepatite E/isolamento & purificação , Hepatite E/diagnóstico , Hepatite E/imunologia , Imunoglobulina M/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , RNA ViralRESUMO
No disponible
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Quarentena/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Imobilização/efeitos adversos , Embolia Pulmonar/epidemiologia , Trombose Venosa/epidemiologia , Pandemias/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Fatores de RiscoAssuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/etiologia , Quarentena , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Controle de Infecções , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Embolia Pulmonar/epidemiologia , Fatores de Risco , Comportamento Sedentário , Espanha/epidemiologiaRESUMO
Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.
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Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Proteínas não Estruturais Virais/genética , Amidas , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Carbamatos , Ciclopropanos , Farmacorresistência Viral/genética , Feminino , Genótipo , Hepacivirus/patogenicidade , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Quinoxalinas/uso terapêutico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Espanha/epidemiologia , Sulfonamidas , Resposta Viral SustentadaRESUMO
INTRODUCTION: Prolonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought to reduce their use. The monitoring of cell immunity against CMV could be an alternative as it has shown to be useful in identifying transplant patients at low risk of infection, who could benefit from shorter prophylaxis. The aim of the CYTOCOR study is to demonstrate that the combination of a reduced prophylaxis strategy with subsequent CMV-specific immunological monitoring would allow CMV infection to be controlled in lung transplant patients as effectively as the usual strategy (prophylaxis followed by pre-emptive therapy), while reducing the side effects of antivirals due to the shorter duration of prophylaxis. METHODS AND ANALYSIS: Phase III randomised, open, multicentre, parallel, non-inferiority clinical trial to study the efficacy and safety of the combination of a prophylaxis strategy up to month +3 post-transplant followed by immuno-guided prophylaxis using the QuantiFERON-CMV technique up to month +12 post-transplant to prevent CMV disease in CMV-seropositive lung transplant recipients. This strategy will be compared with a combination of a usual prophylaxis strategy up to month +6 post-transplant followed by pre-emptive therapy up to month +12. To study the incidence of CMV disease, patients will be followed up to 18 months post-transplantation. A total of 150 patients are expected to be recruited for the study. ETHICS AND PUBLIC DISSEMINATION: The clinical trial has been approved by the Research Ethics Committees and authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS).If the hypothesis of this clinical trial is verified, the dissemination of the results could change clinical practice by increasing knowledge about the safety and efficacy of discontinuing valganciclovir prophylaxis in lung transplant recipients. TRIAL REGISTRATION NUMBER: NCT03699254.
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Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Transplante de Pulmão , Complicações Pós-Operatórias/prevenção & controle , Pré-Medicação , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Antivirais/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Citomegalovirus/imunologia , Infecções por Citomegalovirus/imunologia , Estudos de Equivalência como Asunto , Humanos , Imunidade Celular , Estudos Multicêntricos como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available. METHODS: GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12â¯weeks after treatment completion (SVR12) was recorded. RESULTS: A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin. CONCLUSIONS: In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited. LAY SUMMARY: Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.
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Anilidas/uso terapêutico , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Ciclopropanos/uso terapêutico , Farmacorresistência Viral/genética , Fluorenos/uso terapêutico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , Lactamas Macrocíclicas/uso terapêutico , Prolina/análogos & derivados , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/farmacologia , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , Estudos Prospectivos , Pirrolidinas , Retratamento , Espanha/epidemiologia , Resposta Viral Sustentada , Valina/análogos & derivados , Proteínas não Estruturais Virais/genéticaRESUMO
BackgroundReducing the burden of the hepatitis C virus (HCV) requires large-scale deployment of intervention programmes, which can be informed by the dynamic pattern of HCV spread. In Spain, ongoing transmission of HCV is mostly fuelled by people who inject drugs (PWID) infected with subtype 1a (HCV1a).AimOur aim was to map how infections spread within and between populations, which could help formulate more effective intervention programmes to halt the HCV1a epidemic in Spain.MethodsEpidemiological links between HCV1a viruses from a convenience sample of 283 patients in Spain, mostly PWID, collected between 2014 and 2016, and 1,317, 1,291 and 1,009 samples collected abroad between 1989 and 2016 were reconstructed using sequences covering the NS3, NS5A and NS5B genes. To efficiently do so, fast maximum likelihood-based tree estimation was coupled to a flexible Bayesian discrete phylogeographic inference method.ResultsThe transmission network structure of the Spanish HCV1a epidemic was shaped by continuous seeding of HCV1a into Spain, almost exclusively from North America and European countries. The latter became increasingly relevant and have dominated in recent times. Export from Spain to other countries in Europe was also strongly supported, although Spain was a net sink for European HCV1a lineages. Spatial reconstructions showed that the epidemic in Spain is diffuse, without large, dominant within-country networks.ConclusionTo boost the effectiveness of local intervention efforts, concerted supra-national strategies to control HCV1a transmission are needed, with a strong focus on the most important drivers of ongoing transmission, i.e. PWID and other high-risk populations.