Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.     

Specifics of chronic fatigue syndrome coping strategies identified in a French flash survey during the COVID-19 containment

The COVID-19 pandemic has focused health systems on supporting patients affected by this virus. Meanwhile in the community, many other contained patients could only use self-care strategies, especially in countries that have set up a long and strict containment such as France. The study aimed to compare coping strategies deployed by patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS; a poorly recognised syndrome) to those with better known and referenced chronic conditions. An online flash survey was conducted during the containment period in partnership with French Patients Organizations including ME/CFS national association. Therefore, ‘Brief COPE’ version of Lazarus and Folkman's Ways of Coping Check List has been adapted to the specificity of the containment. The survey was e-distributed in France from 15 April to 11 May 2020. Differences of coping strategies were analyzed using Wilcoxon–Mann–Withney test. Amongst 637 responses, 192 were complete, presenting a wide variety of diseases, including 93 ME/CFS. The latter have significantly different coping strategies than recognised diagnosed diseases patients: similar uses of emotion focused coping but less uses of seek social support and problem-focused copings. In conclusion, coping strategies are different for those who deal with the daily experience of ME/CFS, highly disabling chronic condition with diagnostic ambiguity, low degree of medical and social recognition and without treatment. Better understanding of those strategies is needed to provide the means for health promotion researchers, managers and clinicians, to accompany those patients.     

Improving health care for disabled people in COVID-19 and beyond: Lessons from Australia and England

COVID-19 has exacerbated pre-existing difficulties children and adults with disability face accessing quality health care. Some people with disability are at greater risk of contracting COVID-19 because they require support for personal care and are unable to physically distance, e.g. those living in congregate settings. Additionally, some people with disability have health conditions that put them at higher risk of poor outcomes if they become infected. Despite this, governments have been slow to recognise, and respond to, the unique and diverse health care needs of people with disability during COVID-19. While some countries, including Australia, have improved access to high-quality health care for people with disability others, like England, have failed to support their citizens with disability. In this Commentary we describe the health care responses of England and Australia and make recommendations for rapidly improving health care for people with disability in the pandemic and beyond.     

Covid-19 Pandemic: Resumption of Orthopedic Care and Medical Education

Covid-19 is a respiratory disease caused by coronavirus 2 (SARS-CoV-2) first identified in Wuhan, China (December 2019). The disease rapidly crossed the barrier of countries, continents and spread globally. Non-pharmaceutical measures such as social distancing, face mask, frequent hand washing and use of sanitizer remained the best available option to prevent the spread of disease. OPD, IPD admissions, elective O. Ts were curtailed. Orthopedic care was only limited to emergency and semi-urgent procedures like necrotizing fasciitis, open fracture, and compartment syndrome. These measures were taken to preserve infrastructure and manpower to manage covid-19 pandemic. The children were thought to have a low susceptibility to covid-19 as compared to an adult. Deferring the patient during pandemic has led to high orthopedic disease burden, morbidity and disease-related sequelae, hence elective care must be resumed with modified hospital infrastructure. Resumption of elective/emergent orthopedic care should be slow, phasic and strategic, much similar to unlocking. Cases must be stratified depending on covid status and severity. Dedicated O.Ts with neutral/negative pressure and HEPA filter for covid positive and suspected patients are to be used. All symptomatic and suspected patients should be investigated for covid-19 by RT-PCR, blood counts and CT scan. Regional anaesthesia should be preferred to General anaesthesia. Power drill/saw/burr/pulse lavage should be minimized to avoid aerosol generation. Postoperatively continuous surveillance and monitoring to be done for covid related symptoms. Medical institutes rapidly shifted to the online mode of education. Blended learning (virtual & physical) and imparting skills have to be continued in post covid phase with equitable distribution of teaching hours to students of different years.     

Special surgical approaches during peri-COVID-19 pandemic: Robotic and transanal minimally invasive surgery

During the peri-coronavirus disease 2019 pandemic, the need of special care has raised, not only for our patients but also for health care workers. These needs are different regarding the procedure and the approach performed. This is a dynamic review in the use of robotics and transanal approaches for colorectal diseases. We searched PubMed and KSREvidence.com for studies related to coronavirus disease and robotic surgery/transanal mesorectal excision/transanal surgery(primary and systematic reviews). From 147 results in PubMed, 11 were selected for full text screening, and 11 were included in this paper. From 3 results in KSREvidence, no relevant systematic reviews were identified. We also checked the references in identified papers for further relevant studies. European Society of Coloproctology guidelines were including as part of the recommendations available. Robotic and transanal MIS can be performed safely during the pandemic, but particular characteristics of these procedure need to be taken into consideration.     

Quantification of SARS-CoV-2 spike and nucleocapsid proteins using isotope dilution tandem mass spectrometry

The emergence and subsequent global outbreak of the novel coronavirus SARS-CoV-2 prompted our laboratory to launch efforts to develop methods for SARS-CoV-2 antigen detection and quantification. We present an isotope dilution mass spectrometry method (IDMS) for rapid and accurate quantification of the primary antigens, spike and nucleocapsid proteins. This IDMS method utilizes liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze sample tryptic digests for detection and quantification of selected conserved peptides of SARS-CoV-2 spike and nucleocapsid proteins. The IDMS method has the necessary attributes to be successfully utilized for accurate quantification in SARS-CoV-2 protein-based vaccines and as targets of rapid diagnostic tests. Absolute quantification was achieved by quantifying and averaging 5 peptides for spike protein (3 peptides in the S1 subunit and 2 peptides in the S2 subunit) and 4 peptides for nucleocapsid protein. The overall relative standard deviation of the method was 3.67% for spike protein and 5.11% for nucleocapsid protein. IDMS offers speed (5 h total analysis time), sensitivity (LOQ; 10 fmol/µL) and precision for quantification of SARS-CoV-2 spike and nucleocapsid proteins.     

Estimating the number of averted illnesses and deaths as a result of vaccination against an influenza pandemic in nine low- and middle-income countries

BackgroundDuring the 2009 influenza A(H1N1)pdm09 pandemic, 77 countries received donated monovalent A(H1N1)pdm09 vaccine through the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative. However, 47% did not receive their first shipment until after the first wave of virus circulation, and 8% did not receive their first shipment until after the WHO declared the end of the pandemic. Arguably, these shipments were too late into the pandemic to have a substantial effect on virus transmission or disease burden during the first waves of the pandemic.ObjectivesIn order to evaluate the potential benefits of earlier vaccine availability, we estimated the number of illnesses and deaths that could be averted during a 2009-like influenza pandemic under five different vaccine-availability timing scenarios.MethodsWe adapted a model originally developed to estimate annual influenza morbidity and mortality burden averted through US seasonal vaccination and ran it for five vaccine availability timing scenarios in nine low- and middle-income countries that received donated vaccine.ResultsAmong nine study countries, we estimated that the number of averted cases was 61–216,197 for actual vaccine receipt, increasing to 2,914–283,916 had vaccine been available simultaneously with the United States.ConclusionsEarlier delivery of vaccines can reduce influenza case counts during a simulated 2009-like pandemic in some low- and middle-income countries. For others, increasing the number of cases and deaths prevented through vaccination may be dependent on factors other than timely initiation of vaccine administration, such as distribution and administration capacity.     

Individual-level factors associated with COVID-19 vaccine acceptance among U.S. patients with cancer

IntroductionVaccine hesitancy in the wake of the COVID-19 pandemic is a major public health concern in the US. Cancer patients are especially vulnerable to adverse COVID-19 outcomes and require targeted prevention efforts against COVID-19.MethodsWe used longitudinal survey data from patients seen at Moffitt Cancer Center to identify attitudes, beliefs, and sociodemographic factors associated with COVID-19 vaccination acceptance among cancer patients. Patients with confirmed invasive cancer diagnosis through Cancer Registry data were asked about vaccine acceptance through the question “Now that a COVID-19 vaccine is available, are you likely to get it?” and dichotomized into high accepters (already received it, would get it when available) and low accepters (waiting for a doctor to recommend it, waiting until more people received it, not likely to get it).ResultsMost patients (86.8% of 5,814) were high accepters of the COVID-19 vaccine. High accepters had more confidence in the effectiveness and safety of the vaccine than low accepters. Multivariable logistic regression showed older individuals (70–89 vs.18–49: OR:2.57, 95% CI:1.33–4.86), those with greater perceived severity of COVID-19 infection (very serious vs. not at all serious: OR:2.55, 95% CI:1.76–3.70), practicing more risk mitigation behaviors (per one standard deviation OR:1.75, 95% CI:1.57–1.95), and history of receiving the flu shot versus not (OR:6.56, 95% CI:5.25–8.20) had higher odds of vaccine acceptance. Individuals living with more than one other person (vs. alone: OR: 0.53, 95% CI: 0.35, 0.79) and those who were more socioeconomically disadvantaged (per 10 percentile points: OR: 0.89, 95 %CI: 0.85, 0.93) had lower odds of reporting vaccine acceptance.ConclusionMost patients with cancer have or would receive the COVID-19 vaccine. Those who are less likely to accept the vaccine have more concerns regarding effectiveness and side effects, are younger, more socioeconomically disadvantaged, and have lower perceptions of COVID-19 severity.     

广东省增城市一起登革热爆发的调查

2002年8～9月增城市石滩镇和沙庄街相继爆发登革热。流行时间从8月9日至10月18日,发病136例,男性53例,女性83例,男女发病差异具有极显著意义(X~3=13.24,P<0.01);发病年龄最小2岁,最大77岁,以青壮年发病居多;农民发病最多,民工其次,学生再次。症状主要有畏寒、头痛、疲乏、全身肌肉酸痛、食欲不振、恶心呕吐和腹部不适。体征主要有发热、皮疹(多数在热退时出现,为充血性“斑丘疹”,出疹部位多在四肢和躯干,呈对称性分布),少数患者有出血倾向如鼻衄、便血、齿龈血等。患者末梢血白细胞和血小板计数普遍下降。采集急性期患者血清进行登革病毒IgM抗体检测,阳性率为71.83％,经PCR分型鉴定为登革Ⅰ型病毒。