Antiviral options and therapeutics against influenza: history, latest developments and future prospects.

Drugs and chemotherapeutics have helped to manage devastating impacts of infectious diseases since the concept of 'magic bullet'. The World Health Organization estimates about 650,000 deaths due to respiratory diseases linked to seasonal influenza each year. Pandemic influenza, on the other hand, is the most feared health disaster and probably would have greater and immediate impact on humanity than climate change. While countermeasures, biosecurity and vaccination remain the most effective preventive strategies against this highly infectious and communicable disease, antivirals are nonetheless essential to mitigate clinical manifestations following infection and to reduce devastating complications and mortality. Continuous emergence of the novel strains of rapidly evolving influenza viruses, some of which are intractable, require new approaches towards influenza chemotherapeutics including optimization of existing anti-infectives and search for novel therapies. Effective management of influenza infections depend on the safety and efficacy of selected anti-infective in-vitro studies and their clinical applications. The outcomes of therapies are also dependent on understanding diversity in patient groups, co-morbidities, co-infections and combination therapies. In this extensive review, we have discussed the challenges of influenza epidemics and pandemics and discoursed the options for anti-viral chemotherapies for effective management of influenza virus infections.

Clinical and Diagnostic Findings of Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy in the COVID-19 Era.

BACKGROUND: Growing evidence suggests an association between the infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and eye disorders. The aim of this review was to analyze the clinical presentation and diagnostic features of acute macular neuroretinopathy (AMN) and paracentral acute middle maculopathy (PAMM) associated with COVID-19 infection. The features are then compared with previous reports regarding these retinal disorders, to recognize possible specific characteristics and to assess the role of multimodal ophthalmic imaging. SUMMARY: A literature search was performed by consulting PubMed, Scopus, and Embase. The following terms were searched: "(COVID-19 OR SARS-CoV-2 OR coronavirus) AND ([acute macular neuroretinopathy] OR [paracentral acute middle maculopathy])." Inclusion criteria were as follows: (1) publication date from January 31, 2020 to January 31, 2022; (2) English language; (3) original research or case report; (4) free full-text availability.Optical coherence tomography (OCT) findings in AMN patients were hyper-reflectivity (HR) of the outer plexiform layer, of the outer nuclear layer, and ellipsoid or interdigitation zones (EZ and IZ, respectively) disruption. In most cases, the presence of HR and EZ/IZ abnormalities resulted combined. When performed, OCT angiography (OCTA) identified attenuation of signal of the deep capillary plexus (DCP). The most common OCT finding in PAMM was an alteration of the inner nuclear layer, associated with other areas of HR, while no signs of EZ/IZ disruption were detected. When performed, OCTA showed the attenuation of signal of both the DCP and the superficial capillary plexus. KEY MESSAGES: In this review, we reported a case series of AMN and PAMM in patients with a previous or concomitant infection from SARS-CoV-2. The microvascular changes in these cases are highlighted by the OCTA scans. Even if we are far from the determination of a direct link between COVID-19 and these retinal disorders, we could hypothesize that the vascular alterations associated with SARS-CoV-2 infection could be a possible risk factor for both AMN and PAMM.

PI3K/Akt/Nrf2 mediated cellular signaling and virus-host interactions: latest updates on the potential therapeutic management of SARS-CoV-2 infection.

The emergence and re-emergence of viral diseases, which cause significant global mortality and morbidity, are the major concerns of this decade. Of these, current research is focused majorly on the etiological agent of the COVID-19 pandemic, SARS-CoV-2. Understanding the host response and metabolic changes during viral infection may provide better therapeutic targets for the proper management of pathophysiological conditions associated with SARS-CoV-2 infection. We have achieved control over most emerging viral diseases; however, a lack of understanding of the underlying molecular events prevents us from exploring novel therapeutic targets, leaving us forced to witness re-emerging viral infections. SARS-CoV-2 infection is usually accompanied by oxidative stress, which leads to an overactive immune response, the release of inflammatory cytokines, increasing lipid production, and also alterations in the endothelial and mitochondrial functions. PI3K/Akt signaling pathway confers protection against oxidative injury by various cell survival mechanisms including Nrf2-ARE mediated antioxidant transcriptional response. SARS-CoV-2 is also reported to hijack this pathway for its survival within host and few studies have suggested the role of antioxidants in modulating the Nrf2 pathway to manage disease severity. This review highlights the interrelated pathophysiological conditions associated with SARS-CoV-2 infection and the host survival mechanisms mediated by PI3K/Akt/Nrf2 signaling pathways that can help ameliorate the severity of the disease and provide effective antiviral targets against SARS-CoV-2.

Safety of a quadrivalent influenza vaccine in Vietnamese healthy subjects aged 6 months and older.

Quadrivalent influenza vaccines (QIVs) provide protection against the two influenza A viruses (H1N1 and H3N2) and both co-circulating influenza B lineages. QIVs have been found safe, immunogenic, and efficacious in several phase III clinical trials. Here we assess the safety of QIV after vaccination in Vietnamese infants, children, and adults. Participants (n = 228) were asked to report any solicited adverse events (AEs) occurring within 7 days, unsolicited non-serious AEs occurring within 28 days post-vaccination, and serious adverse events (SAEs) at any time during the study. The study was completed by 224 participants (97.4%). Thirty-one children (39.7%) aged 6 - 35 months, 32 children (40.0%) aged 3 - 8 years, 2 participants (9.0%) aged 9 - 17 years, 5 participants (17.9%) aged 18 - 60 years, and 3 participants (15.0%) aged ≥60 years reported ≥1 solicited reaction within 7 days following vaccination. The most frequent-solicited AEs were injection-site tenderness or pain, appetite loss, fever, and abnormal crying in 6 - 35 month-olds, and fever, headache, and myalgia in other age groups. No severe-unsolicited AEs or vaccine-related SAEs were reported. These results suggest that QIV is well tolerated across age groups in Vietnam, and can be safely used to protect the Vietnamese population against influenza and its potentially serious complications.

A review of COVID-19 vaccines in development: 6 months into the pandemic.

The advent of the COVID-19 pandemic and the dynamics of its spread is unprecedented. Therefore, the need for a vaccine against the virus is huge. Researchers worldwide are working around the clock to find a vaccine. Experts estimate that a fast-tracked vaccine development process could speed a successful candidate to market in approximately 12-18 months. The objective of this review was to describe the coronavirus vaccines candidates in development and the important considerations. The review was conducted through a thematic analysis of the literature on COVID-19 vaccines in development. It only included data until the end of June 2020, 6 months after the emergence of the COVID-19. Different approaches are currently used to develop COVID-19 vaccines from traditional live-attenuated, inactivated, subunit vaccines, to more novel technologies such as DNA or mRNA vaccines. The race is on to find both medicines and vaccines for the COVID-19 pandemic. As with drugs, vaccine candidates go through pre-clinical testing first before they go through the three phases of clinical trials in humans. Of the over 130 vaccine candidates, 17 are in clinical trials while others are expected to move to clinical testing after the animal studies.

Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections.

Several viruses cause pulmonary infections due to their shared tropism with cells of the respiratory tract. These respiratory problems due to viral infection become a public health concern due to rapid transmission through air/aerosols or via direct-indirect contact with infected persons. In addition, the cross-species transmission causes alterations to viral genetic makeup thereby increasing the risk of emergence of pathogens with new and more potent infectivity. With the introduction of effective nucleic acid-based technologies, post translational gene silencing (PTGS) is being increasingly used to silence viral gene targets and has shown promising approach towards management of many viral infections. Since several host factors are also utilized by these viruses during various stages of infection, silencing these host factors can also serve as promising therapeutic tool. Several nucleic acid-based technologies such as short interfering RNAs (siRNA), antisense oligonucleotides, aptamers, deoxyribozymes (DNAzymes), and ribozymes have been studied and used against management of respiratory viruses. These therapeutic nucleic acids can be efficiently delivered through the airways. Studies have also shown efficacy of gene therapy in clinical trials against respiratory syncytial virus (RSV) as well as models of respiratory diseases including severe acute respiratory syndrome (SARS), measles and influenza. In this review, we have summarized some of the recent advancements made in the area of nucleic acid based therapeutics and highlighted the emerging roles of nucleic acids in the management of some of the severe respiratory viral infections. We have also focused on the methods of their delivery and associated challenges.

The emerging influenza virus threat: status and new prospects for its therapy and control.

Influenza A viruses (IAVs) are zoonotic pathogens that cause yearly outbreaks with high rates of morbidity and fatality. The virus continuously acquires point mutations while circulating in several hosts, ranging from aquatic birds to mammals, including humans. The wide range of hosts provides influenza A viruses greater chances of genetic re-assortment, leading to the emergence of zoonotic strains and occasional pandemics that have a severe impact on human life. Four major influenza pandemics have been reported to date, and health authorities worldwide have shown tremendous progress in efforts to control epidemics and pandemics. Here, we primarily discuss the pathogenesis of influenza virus type A, its epidemiology, pandemic potential, current status of antiviral drugs and vaccines, and ways to effectively manage the disease during a crisis.

Cost-effectiveness of two-dose human papillomavirus vaccination in Singapore.

INTRODUCTION: Cervical cancer is the tenth most common cancer and the eighth most frequent cause of death among women in Singapore. As human papillomavirus (HPV) infection is the necessary cause of cervical cancer, the risk of cervical cancer can be substantially reduced through vaccination. This study was conducted to evaluate the cost-effectiveness of two-dose HPV vaccination as part of a national vaccination programme for 12-year-old girls in Singapore, from the perspective of the healthcare payer. METHODS: A lifetime Markov cohort model was used to evaluate the cost-effectiveness of introducing the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v) to the current cervical screening programme in Singapore. Furthermore, the cost-effectiveness of the AS04-HPV-16/18v was compared with the HPV-6/11/16/18 vaccine (4vHPV). Model inputs were derived from local data, where possible, and validated by clinical experts in Singapore. RESULTS: Introduction of the AS04-HPV-16/18v in Singapore was shown to prevent 137 cervical cancer cases and 48 cervical cancer deaths when compared with screening alone. This resulted in an incremental cost-effectiveness ratio of SGD 12,645 per quality-adjusted life year (QALY) gained, which is cost-effective according to the World Health Organization threshold for Singapore. When discounted at 3%, AS04-HPV-16/18v was dominant over 4vHPV, with cost savings of SGD 80,559 and 28 additional QALYs gained. In the one-way sensitivity analysis, AS04-HPV-16/18v remained cost-effective compared with screening alone and dominant compared with 4vHPV. CONCLUSION: AS04-HPV-16/18v is the most cost-effective choice for reducing the burden of cervical cancer through universal mass vaccination for 12-year-old girls in Singapore.

Literature review of the epidemiology of influenza B disease in 15 countries in the Asia-Pacific region.

Influenza control strategies focus on the use of trivalent influenza vaccines containing two influenza A virus subtypes and one of the two circulating influenza type B lineages (Yamagata or Victoria). Mismatches between the vaccine B lineage and the circulating lineage have been regularly documented in many countries, including those in the Asia-Pacific region. We conducted a literature review with the aim of understanding the relative circulation of influenza B viruses in Asia-Pacific countries. PubMed and Western Pacific Region Index Medicus were searched for relevant articles on influenza type B published since 1990 in English language for 15 Asia-Pacific countries. Gray literature was also accessed. From 4834 articles identified, 121 full-text articles were analyzed. Influenza was reported as an important cause of morbidity in the Asia-Pacific region, affecting all age groups. In all 15 countries, influenza B was identified and associated with between 0% and 92% of laboratory-confirmed influenza cases in any one season/year. Influenza type B appeared to cause more illness in children aged between 1 and 10 years than in other age groups. Epidemiological data for the two circulating influenza type B lineages remain limited in several countries in the Asia-Pacific, although the co-circulation of both lineages was seen in countries where strain surveillance data were available. Mismatches between circulating B lineages and vaccine strains were observed in all countries with available data. The data suggest that a shift from trivalent to quadrivalent seasonal influenza vaccines could provide additional benefits by providing broader protection.

[Innovations in vaccinology: challenge and opportunities for Africa]. / Innovations en vaccinologie: enjeux et perspectives pour l'Afrique.

Immunization is undoubtedly one of the most effective and most cost-effective health interventions. Vaccines continue to revolutionize our ability to prevent diseases and improve health. With all the technological advances, we are able to extend the benefits of vaccines to more people and to provide better protection from life-threatening infectious diseases. Nevertheless, thanks to the unceasing implementation of novel microbial strains on a worldwide basis, research in vaccinology must innovate continuously. African countries have made great progress in increasing routine immunization coverage rates and in introducing newly developed vaccines. New types of vaccines associated with vectorization, administration and specific licensing tools as well as with adjuvants designed to finely modulate immune responses are expected to be achieved in the near future. African countries need to work to develop a regional approach to respond effectively to the many challenges. Providing better information, implementing healthcare personnel vaccinology training programs and well targeted research projects are the keys to future achievements in the field.

Innovations en vaccinologie: enjeux et perspectives pour l'Afrique

La vaccination est incontestablement l'une des interventions de santé publique les plus efficaces et les plus rentables qui soient. Les vaccins continuent de révolutionner notre capacité à prévenir les maladies et à améliorer la santé. Avec toutes les avancées technologiques, nous sommes en mesure d'étendre les avantages des vaccins à plus de gens et de fournir une meilleure protection contre les maladies infectieuses mortelles. Toutefois, avec le développement incessant de nouvelles souches microbiennes à travers le monde, la recherche en vaccinologie se doit d'innover continuellement. D'énormes progrès ont été réalisés pour améliorer la couverture vaccinale et introduire de nouveaux vaccins en Afrique. De nouveaux types de vaccins associés à des outils de vectorisation, d'administration et de délivrance spécifiques mais aussi des adjuvants susceptibles de moduler finement la réponse immunitaire sont attendus dans le futur. En Afrique, il est nécessaire de développer une approche régionale afin de répondre efficacement aux nombreux défis. Une meilleure information, la formation des personnels de santé en vaccinologie et des recherches bien ciblées sont les clés des futurs accomplissements dans le domaine

Zika: what we know and don't know.

Since the initial reports of a link between Zika and microcephaly, researchers across the world began working toward understanding the virus. In a short amount of time, Zika has become a household name, prompting worldwide concern. The virus is spread rapidly by mosquito bites. We currently do not have a vaccine for Zika. But with the recent findings, vaccine companies are mobilizing their resources to expedite efforts to shave years off the typical decade-long process of vaccine development.

Neonatal infections: Case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

Maternal vaccination is an important area of research and requires appropriate and internationally comparable definitions and safety standards. The GAIA group, part of the Brighton Collaboration was created with the mandate of proposing standardised definitions applicable to maternal vaccine research. This study proposes international definitions for neonatal infections. The neonatal infections GAIA working group performed a literature review using Medline, EMBASE and the Cochrane collaboration and collected definitions in use in neonatal and public health networks. The common criteria derived from the extensive search formed the basis for a consensus process that resulted in three separate definitions for neonatal blood stream infections (BSI), meningitis and lower respiratory tract infections (LRTI). For each definition three levels of evidence are proposed to ensure the applicability of the definitions to different settings. Recommendations about data collection, analysis and presentation are presented and harmonized with the Brighton Collaboration and GAIA format and other existing international standards for study reporting.

Vaccination Against Tuberculosis With Whole-Cell Mycobacterial Vaccines.

Live attenuated and killed whole-cell vaccines (WCVs) offer promising vaccination strategies against tuberculosis. A number of WCV candidates, based on recombinant bacillus Calmette-Guerin (BCG), attenuated Mycobacterium tuberculosis, or related mycobacterial species are in various stages of preclinical or clinical development. In this review, we discuss the vaccine candidates and key factors shaping the development pathway for live and killed WCVs and provide an update on progress.

A review of the surveillance systems of influenza in selected countries in the tropical region.

Influenza viruses cause annual epidemics of respiratory tract disease that affect all age groups. Many developing countries do not have an influenza surveillance system or adequate laboratory capacity for virus detection. The objective of this study was to describe the influenza surveillance systems in the different countries in the tropics and to identify outstanding research needs. A questionnaire was designed and sent to 52 NICs and MoHs in the different countries in tropical Asia and Africa to gather information on the surveillance systems, sentinel sites, specimen and data collection, and laboratory testing. Replies were received from 32 NICs and MoHs (61.5% response)--17 were located in tropical Asia and 15 in Africa. There are 20 WHO recognized NICs in tropical Asia and 14 in tropical Africa, all with virus isolation and polymerase chain reaction (PCR) testing capacity. Of the Asian countries, only Hong Kong and Singapore reported that the patient population from the sites represents the broader community. In tropical Africa, only Senegal has sentinel sites distributed all over the country contributing to the geographic representativeness of the surveillance system. The rest of the countries in Africa have just established their influenza surveillance system in the past decade and are working toward geographic expansion of the ILI and SARI sites. Limited laboratory capacity or infrastructure to perform influenza surveillance makes difficult to justify the importance of influenza vaccine or other influenza control measures as a strategy for improving population health in the tropical region.