Risultati per: Papilloma virus

Annals of Internal Medicine, Volume 176, Issue 5, May 2023.

Il 20 maggio 1983 su Science la prima descrizione apre alla cura dell’Aids

Approximately 250 million people worldwide are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogues (NAs) as the mainstay of antiviral therapy efficiently suppress viraemia, normalise liver enzymes and prevent progression of liver disease, however, they do not reduce hepatitis B surface antigen (HBsAg) levels in the majority of patients. HBsAg is an important component of the HBV satellite virus hepatitis D virus (HDV). It allows HBV and HDV viral entry through the interaction of its preS1 domain with the cell receptor sodium taurocholate cotransporting polypeptide (NTCP). Irrespective of antiviral treatment, patients with chronic HBV infection are thus at persistent risk of HDV superinfection. HDV superinfection leads to chronic HBV/HDV infection in the majority of patients and is associated with fast progression to liver cirrhosis.1 Even after the conditional approval of the HBV/HDV entry inhibitor bulevirtide (BLV) in Europe in 2020, treatment options for HBV/HDV infection are limited:…

Objective
Chronic HBV/HDV infections are a major cause of liver cancer. Current treatments can only rarely eliminate HBV and HDV. Our previously developed preS1-HDAg immunotherapy could induce neutralising antibodies to HBV in vivo and raise HBV/HDV-specific T-cells. Here, we further investigate if a heterologous prime-boost strategy can circumvent T-cell tolerance and preclude HDV superinfection in vivo.

Design
A DNA prime-protein boost strategy was evaluated for immunogenicity in mice and rabbits. Its ability to circumvent T-cell tolerance was assessed in immunocompetent hepatitis B surface antigen (HBsAg)-transgenic mice. Neutralisation of HBV and HDV was evaluated both in vitro and in immunodeficient human-liver chimeric mice upon adoptive transfer.

Results
The prime-boost strategy elicits robust HBV/HDV-specific T-cells and preS1-antibodies that can effectively prevent HBV and HDV (co-)infection in vitro and in vivo. In a mouse model representing the chronic HBsAg carrier state, active immunisation primes high levels of preS1-antibodies and HDAg-specific T-cells. Moreover, transfer of vaccine-induced antibodies completely protects HBV-infected human-liver chimeric mice from HDV superinfection.

Conclusion
The herein described preS1-HDAg immunotherapy is shown to be immunogenic and vaccine-induced antibodies are highly effective at preventing HBV and HDV (super)infection both in vitro and in vivo. Our vaccine can complement current and future therapies for the control of chronic HBV and HDV infection.

Objectives
Pakistan has a hepatitis C virus (HCV) infection prevalence of 6%–9% and aims to achieve World Health Organisation (WHO) targets for elimination of HCV by the year 2030. We aim to evaluate the potential cost-effectiveness of a reference laboratory-based (centralised laboratory testing; CEN) confirmatory testing approach versus a molecular near-patient point-of-care (POC) confirmatory approach to screen the general population for HCV in Pakistan.

Study design
We used a decision tree-analytic model from a governmental (formal healthcare sector) perspective.

Study setting
Individuals were assumed to be initially screened with an anti-HCV test at home, followed by POC nucleic acid test (NAT) at nearby district hospitals or followed by NAT at centralised laboratories.

Participants
We included the general testing population for chronic HCV in Pakistan.

Intervention
Screening with an anti-HCV antibody test (Anti-HCV) followed by either POC NAT (Anti-HCV-POC), or reference laboratory NAT (Anti-HCV-CEN), was compared, using data from published literature and the Pakistan Ministry of Health.

Measures
Outcome measures included: number of HCV infections identified per year, percentage of individuals correctly classified, total costs, average costs per individual tested, and cost-effectiveness (assessed as cost per additional HCV infection identified). Sensitivity analysis was also performed.

Results
At a national level (25 million annual screening tests), the Anti-HCV-CEN strategy would identify 142 406 more HCV infections in 1 year and increase correct classification of individuals by 0.57% compared with the Anti-HCV-POC strategy. The total annual cost of HCV testing was reduced using the Anti-HCV-CEN strategy by US$7.68 million (US$0.31/person). Thus, incrementally, the Anti-HCV-CEN strategy costs less and identifies more HCV infections than Anti-HCV-POC. The incremental difference in HCV infections identified was most sensitive to the probability of loss to follow-up (for POC confirmatory NAT).

Conclusions
Anti-HCV-CEN would provide the best value for money when scaling up HCV testing in Pakistan.

Si riunisce la quindicesima riunione del Comitato di emergenza per il Covid-19 che potrebbe rappresenta un passo decisivo verso la derubricazione dell’emergenza

This case report describes a 37-year-old man with a 1-week history of a genital nodule that rapidly ulcerated and with concomitant fever 2 days after anal intercourse.

New England Journal of Medicine, Ahead of Print.

Attesa per luglio l’approvazione definitiva della Commissione Ue

A hundred years ago the existence of viruses was unknown. The beginning of knowledge of this group of infectious agents indeed goes back only a half century. It is not yet fifty years since Beijerinck established that the infectious agent of tobacco mosaic disease is filtrable and called it a “contagious living fluid” and since Loeffler and Frosch identified the first ascertained virus disease of animals, foot-and-mouth disease. In the decade or so which followed a small number of other plant and animal diseases were identified as of virus origin. Among these were yellow fever, rabies, vaccinia-variola and poliomyelitis. But while the boundaries of knowledge regarding virus diseases widened gradually from this beginning, it was not until shortly after the first World War that the advances became rapid. This new period was ushered in by the discovery that bacteria, the outstanding partners of viruses in causing infections, are themselves victims of a virus disease. At first there was some uncertainty as to whether this disease, bacteriophagy or the Twort-d’Herelle phenomenon, could be classified along with other then known virus diseases. It was viewed with caution by many. The precise nature of the agent responsible became the subject of warm debate, and one might ask today how much d’Herelle’s staunch advocacy of bacteriophage as a living “ultramicrobe” had to do with the acceleration of interest in viruses which took root in the early twenties. Certainly bacteriophagy afforded an opportunity to study a virus disease under relatively simple and inexpensive conditions and still affords a favored approach to some of the unsolved problems in the virus field.

Objectives
To assess the seroprevalence of herpes simplex virus (HSV) types 1 and 2 in patients infected with HIV in Nigeria.

Design
Cross-sectional design from January to June 2019.

Setting
Federal Teaching Hospital, Ebonyi State, Nigeria.

Participants
A total of 276 patients with HIV were analysed using ELISA method for the presence of HSV-1 and HSV-2 specific IgG antibodies.

Outcomes
Fisher’s exact test was used to determine the association between the seroprevalence of HSV and demographic variables (statistically significant=p value ≤0.05).

Results
Totally, 212 (76.8%) and 155 (56.2%) patients with HIV were seropositive for HSV-1 and HSV-2 IgG antibodies, respectively. The seroprevalence of HSV-1 was significantly higher than the HSV-2 in patients with HIV (p value 0.05). The seroprevalence of HSV-1 was significantly higher in the singles (87.4%, 90/103) than the married patients with HIV (p=0.001). However, HSV-2 seroprevalence was significantly higher in the married patients with HIV (63.6%, 110/173) (p=0.001).

Conclusions
Prevalence of 76.8% for HSV-1 and 56.2% for HSV-2 among patients with HIV was seen. The HSV-1 was significantly higher in the singles while HSV-2 seroprevalence was significantly higher in the married patients with HIV with HSV-1 and HSV-2 coinfection rate of 7.6%. This study became very imperative to provide an important insight into the hidden dynamics of HSV infections.

Memory CD4 T cells generated after infection with OC43, a common cold coronavirus, also exhibited an immune response against SARS-CoV-2 in early childhood, according to results from 2- and 6-year-old children and adults who did not have antibodies against the novel coronavirus and from a group of adults who had recovered from COVID-19. By age 2 years, many children had antibodies against OC43; by age 6, the reactivity of the CD4 T cells had peaked and then declined in adulthood.

Objectives
Hepatitis C virus (HCV) poses a global public health threat. Prisons are a focus of prevention efforts due to high infection burdens. Expedition of treatment for incarcerated people is critical, as many are short-term sentenced. We evaluated point-of-care (PoC) HCV RNA testing in a maximum-security Scottish prison and assessed its impact on transition to treatment. We also evaluated costs and determinants of implementation.

Design
Mixed-methods evaluation of a single-centre care pathway pilot using National Health Service (NHS) data from 2018 to 2021. Descriptive statistics and survival analysis were undertaken. Cost analysis was assessed from a provider perspective. Healthcare staff participated in semistructured interviews and thematic analysis with a deductive approach was undertaken to identify implementation determinants.

Setting
A large maximum-security Scottish prison health centre administered by the NHS.

Participants
296 incarcerated NHS patients (all men) and six NHS staff members (two men and four women).

Interventions
HCV testing using the Cepheid GeneXpert platform with Xpert HCV VL Fingerstick assay.

Outcome measures
The main outcome was survival (in days) from HCV test to treatment initiation. Secondary outcomes were cost-per-cure obtained and implementation determinants.

Results
During the pilot, 167 Xpert tests were administered, with an 84% completion rate, and treatment transition was superior for those who received it (p=0.014). Where PoC tests were administered, shorter survival to treatment was observed (19 vs 33 days: adjusted HR (aHR) 1.91 (1.03–3.55), p=0.040; 19 vs 50 days; aHR 3.76 (1.67–8.46), p=0.001). PoC was costlier than conventional testing. In qualitative analysis, most facilitators were observed among characteristics of individual domain while most barriers were noted in the inner setting.

Conclusions
Integrating PoC HCV RNA diagnosis into nurse-led HCV care in a maximum-security prison health centre shortens survival to HCV treatment. However, there are cost implications to this approach and multiple determinants that impact on implementation should be addressed.

Objectives
A major goal of curative hepatitis B virus (HBV) treatments is the reduction or inactivation of intrahepatic viral covalently closed circular DNA (cccDNA). Hence, precise cccDNA quantification is essential in preclinical and clinical studies. Southern blot (SB) permits cccDNA visualisation but lacks sensitivity and is very laborious. Quantitative PCR (qPCR) has no such limitations but inaccurate quantification due to codetection of viral replicative intermediates (RI) can occur. The use of different samples, preservation conditions, DNA extraction, nuclease digestion methods and qPCR strategies has hindered standardisation. Within the ICE-HBV consortium, available and novel protocols for cccDNA isolation and qPCR quantification in liver tissues and cell cultures were compared in six laboratories to develop evidence-based guidance for best practices.

Design
Reference material (HBV-infected humanised mouse livers and HepG2-NTCP cells) was exchanged for cross-validation. Each group compared different DNA extraction methods (Hirt extraction, total DNA extraction with or without proteinase K treatment (+PK/–PK)) and nuclease digestion protocols (plasmid-safe ATP-dependent DNase (PSD), T5 exonuclease, exonucleases I/III). Samples were analysed by qPCR and SB.

Results
Hirt and –PK extraction reduced coexisting RI forms. However, both cccDNA and the protein-free relaxed circular HBV DNA (pf-rcDNA) form were detected by qPCR. T5 and Exo I/III nucleases efficiently removed all RI forms. In contrast, PSD did not digest pf-rcDNA, but was less prone to induce cccDNA overdigestion. In stabilised tissues (eg, Allprotect), nucleases had detrimental effects on cccDNA.

Conclusions
We present here a comprehensive evidence-based guidance for optimising, controlling and validating cccDNA measurements using available qPCR assays.

Hanno causato a 22 decessi e 50 trapianti di fegato. La conferma da tre studi su Nature