scholarly journals State of the Art, Unresolved Issues, and Future Research Directions in the Fight against Hepatitis C Virus: Perspectives for Screening, Diagnostics of Resistances, and Immunization

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Cecilia Trucchi ◽  
Andrea Orsi ◽  
Cristiano Alicino ◽  
Laura Sticchi ◽  
Giancarlo Icardi ◽  
...  

Hepatitis C virus (HCV) still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. New generation of direct-acting antiviral agents (DAAs) has been recently introduced in clinical practice promising to cure HCV and to overcome the issues related to the interferon-based therapies. However, the emergence of drug resistance and the suboptimal activity of DAAs therapies against diverse HCV genotypes have been observed, determining treatment failure and hampering an effective control of HCV spread worldwide. Moreover, these treatments remain poorly accessible, particularly in low-income countries. Finally, effective screening strategy is crucial to early identifying and treating all HCV chronically infected patients. For all these reasons, even though new drugs may contribute to impacting HCV spread worldwide a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally, with the ultimate goal of its eradication. Advances in molecular vaccinology, together with a strong financial, political, and societal support, will enable reaching this fundamental success in the coming years. In this comprehensive review, the state of the art about these major topics in the fight against HCV and the future of research in these fields are discussed.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1350
Author(s):  
Shukun Wei ◽  
Xiaoyou Hu ◽  
Lingyu Du ◽  
Linlin Zhao ◽  
Hongjuan Xue ◽  
...  

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Several classes of compounds, such as amantadine and rimantadine have been testified for p7 inhibition. However, the efficacies of these compounds are not high. Here, we screened some novel p7 inhibitors with amantadine scaffold for the inhibitor development. The dissociation constant (Kd) of 42 ARD-series compounds were determined by nuclear magnetic resonance (NMR) titrations. The efficacies of the two best inhibitors, ARD87 and ARD112, were further confirmed using viral production assay. The binding mode analysis and binding stability for the strongest inhibitor were deciphered by molecular dynamics (MD) simulation. These ARD-series compounds together with 49 previously published compounds were further analyzed by molecular docking. Key pharmacophores were identified among the structure-similar compounds. Our studies suggest that different functional groups are highly correlated with the efficacy for inhibiting p7 of HCV, in which hydrophobic interactions are the dominant forces for the inhibition potency. Our findings provide guiding principles for designing higher affinity inhibitors of p7 as potential anti-HCV drug candidates.





Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 463
Author(s):  
Mohammed Majam ◽  
Alex Fischer ◽  
Elena Ivanova Reipold ◽  
Naleni Rhagnath ◽  
Vanessa Msolomba ◽  
...  

Only 20% of people with hepatitis C virus (HCV) know their status. In low-income countries diagnosis is under 10%. Self-testing for HCV antibodies (HCVST) could expand the coverage of HCV testing services. Currently, there are no stringent regulatory authority (SRA) approved HCVSTs, therefore lay-user usability of three prototype kits was assessed. This was a cross-sectional observational study conducted with 171 (CareStart n = 60, Bioline n = 52, First Response n = 59) participants. Participants were given one of the three HCVST kits with only instructions for use (IFU) and asked to perform the test in front of a professional trained in rapid diagnostic tests (RDT). Usability indices were calculated based on the correctness of performing each step of the product-specific process followed by contrived results interpretation and a post-test interview. The usability index was 93.9% for CareStart, 90.7% for Bioline and 94.9% for First Response. Most errors were on incorrect handwashing, sample collection and transfer to the test device. An average of 93.1% of contrived results were correctly interpreted, with most errors related to interpreting invalid results. Most participants (n = 167) stated they would visit a clinic after a positive result. With negative results, nearly half (28/60 (46.7%)) stated they should condomize, while just over two-thirds of participants that used Bioline (35/52 (67.3%)) and First Response (38/59 (64.4%)) said they should re-test. Most participants (n = 162) found the devices easy to use. Participants liked that self-testing was fast, private and convenient, however there were some confusion with IFU steps and pictures, finger-pricking with the lancet, collecting blood after the finger-prick, and transferring the sample/buffer. Prototype HCVST kits exhibit high usability and result interpretation by lay-users, and should be considered for SRA approval.



Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 491
Author(s):  
Sona Jain ◽  
Wanessa Santana ◽  
Silvio S. Dolabella ◽  
André L. S. Santos ◽  
Eliana B. Souto ◽  
...  

Leishmaniasis is one of the deadliest neglected tropical diseases affecting 12–15 million people worldwide, especially in middle- and low-income countries. Rapid and accurate diagnosis of the disease is important for its adequate management and treatment. Several techniques are available for the diagnosis of leishmaniasis. Among these, parasitological and immunological tests are most widely used. However, in most cases, the utilized diagnostic techniques are not good enough, showing cross-reactivity and reduced accuracy. In recent years, many new methods have been reported with potential for improved diagnosis. This review focuses on the diagnosis of Leishmania exploring the biosensors and nanotechnology-based options for their detection. New developments including the use of nanomaterials as fluorophores, fluorescence quenchers as reducing agents and as dendrimers for signal improvement and amplification, together with the use of aptamers to replace antibodies are described. Future research opportunities to overcome the current limitations on the available diagnostic approaches are also discussed.



2020 ◽  
Vol 43 (8) ◽  
pp. 418-425
Author(s):  
Maria Isabel Guzman Ramos ◽  
Mercedes Manzano-García ◽  
M. de las Aguas Robustillo-Cortés ◽  
Juan Antonio Pineda ◽  
Ramón Morillo-Verdugo


Author(s):  
Giorgia Gon ◽  
Abdunoor M. Kabanywanyi ◽  
Petri Blinkhoff ◽  
Simon Cousens ◽  
Stephanie J. Dancer ◽  
...  

Abstract Background Healthcare associated infections (HAI) are estimated to affect up to 15% of hospital inpatients in low-income countries (LICs). A critical but often neglected aspect of HAI prevention is basic environmental hygiene, particularly surface cleaning and linen management. TEACH CLEAN is an educational intervention aimed at improving environmental hygiene. We evaluated the effectiveness of this intervention in a pilot study in three high-volume maternity and newborn units in Dar es Salaam, Tanzania. Methods This study design prospectively evaluated the intervention as a whole, and offered a before-and-after comparison of the impact of the main training. We measured changes in microbiological cleanliness [Aerobic Colony Counts (ACC) and presence of Staphylococcus aureus] using dipslides, and physical cleaning action using gel dots. These were analysed with descriptive statistics and logistic regression models. We used qualitative (focus group discussions, in-depth interviews, and semi-structured observation) and quantitative (observation checklist) tools to measure why and how the intervention worked. We describe these findings across the themes of adaptation, fidelity, dose, reach and context. Results Microbiological cleanliness improved during the study period (ACC pre-training: 19%; post-training: 41%). The odds of cleanliness increased on average by 1.33 weekly during the pre-training period (CI = 1.11–1.60), and by 1.08 (CI = 1.03–1.13) during the post-training period. Cleaning action improved only in the pre-training period. Detection of S. aureus on hospital surfaces did not change substantially. The intervention was well received and considered feasible in this context. The major pitfalls in the implementation were the limited number of training sessions at the hospital level and the lack of supportive supervision. A systems barrier to implementation was lack of regular cleaning supplies. Conclusions The evaluation suggests that improvements in microbiological cleanliness are possible using this intervention and can be sustained. Improved microbiological cleanliness is a key step on the pathway to infection prevention in hospitals. Future research should assess whether this bundle is cost-effective in reducing bacterial and viral transmission and infection using a rigorous study design.



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