The COVID-19 pandemic has caused millions of deaths and hundreds of millions of confirmed infections worldwide. This pandemic has prompted researchers to produce medications or vaccines to reduce or stop the progression and spread of this disease. A variety of previously licensed and marketed medications are being tested for the treatment and recurrence of SARS-CoV2, including favipiravir (Avigan). Favipiravir was recognized as an influenza antiviral drug in Japan in 2014, and has been known to have a potential in vitro activity against SARS-CoV-2, in addition to its broad therapeutic safety scope. Favipiravir was recently approved and officially used in many countries worldwide. Our review provides insights and up-to-date knowledge of the current role of favipiravir in the treatment of COVID-19 infection, focusing on preclinical and ongoing clinical trials, evidence of its efficacy against SARS-CoV-2 in COVID-19, side effects, anti-viral mechanism, and the pharmacokinetic properties of the drug in the treatment of COVID-19. Due to its teratogenic effects, favipiravir cannot be offered to expectant or pregnant mothers. The practical efficacy of such an intervention regimen will depend on its dose, treatment duration, and cost as well as difficulties in application.

Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome. Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to shed further light on the function of these cytokines in severe dengue.

Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex Immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, the multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome. Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to further investigate the function of these cytokines in severe dengue.

Immunoepidemiological studies from endemic areas have revealed age-dependent resistance correlation with increased level of IgE and decreased level of IgG4 antibodies in responses to schistosomes’ soluble worm antigen. However, there have been limited studies on analyses of major antigens that provoke IgE and IgG4 immune response during chronic stage of schistosomiasis. In this study, for the first time, immunoproteomics approach has been applied to identify S. japonicum worm antigens in liquid fractions that are recognized by IgE and IgG4 antibody using plasma from chronically infected population. ProteomeLabPF 2D fractionated 1-D and 2-D fractions of SWA antigens were screened using pooled high IgE/IgG4 reactive plasma samples by dot-blot technique. In 1-D fractions, IgE isotype was detected by fewer antigenic fractions (43.2%). The most recognized isotype was IgG3 (79.5%) followed by IgG1 (75.0%) and IgG4 (61.4%). Liquid chromatography MS/MS protein sequencing of reactive 2-D fractions revealed 18 proteins that were identified, characterized and gene ontology categories determined. 2-D fractions containing proteins such as zinc finger, RanBP2-type, domain-containing protein were strongly recognized by IgE and moderately by IgG4 whereas fractions containing proteins such as ubiquitin-conjugating enzyme and cytosolic II 5'-nucleotidase strongly recognizing by IgG subclasses (IgG1, IgG3 and IgG4) but not IgE. By this study, a simple and reproducible proteomic method has been established to identify major immunoreactive S. japonicum antigens. It is anticipated that this will stimulate further research on the immunogenicity and protective potential of proteins identified as well as discovery of novel compounds that have therapeutic importance.

The aim of this study is to collect the suggestions and recommendations of health care professionals involved in the regional palliative care program (OPTIM-study). A total of 101 multidisciplinary health care professionals who participated in the intervention program were interviewed, and 107 meaningful units were obtained from 89 valid interviews. The responses were categorized into “suggestions regardless of profession” (n=59), including “Participate in a multi-disciplinary conference to expand the network of people”, “Try to understand the situation of others”, “Seek support from others when you cannot solve the problem by yourself”, “Pursue all possibilities before giving up”, and “Do not try too hard”. As suggestions to those engaged in each profession, “Suggestions to community pharmacies” and “Suggestions to care managers” are frequently described. An examination of suggestions by the participants in the regional palliative care program could provide some insights to improve community palliative care.

The purpose of this study was to identify the greatest impact of the regional palliative care program on community health care professionals. Interviews were conducted involving 101 people who became involved in the intervention program implemented in 4 areas across Japan, and 96 valid responses were collected. The following were cited as the greatest impact: [I developed a network of people, and realized the importance of collaboration] (n＝61; “I was able to develop an interpersonal relationship” and “Now I understand the significance of collaboration”), [My knowledge and skills regarding palliative care were improved] (n＝18; “Knowledge and support helped me respond to patients with confidence” and “I have come to think that there is more to palliative care than terminal care”), [I rediscovered my role through a wide variety of experiences] (n＝10), [Both collaboration and palliative knowledge/skills meant a lot to me] (n＝4), [What I experienced in this program will help me play my role] (n＝2), and [Patients and their families became satisfied] (n＝1). The community palliative care program was most effective in facilitating collaboration, and helped participants develop knowledge and skills concerning palliative care.

In malaria endemic areas, people naturally acquire an age-related immunity to malaria. Part of this immunity involves anti-malarial specific antibodies. Acquisition of these malaria-specific antibodies depends not only on exposure to malaria parasites but also on the human genetic predisposition. CTLA-4 is a costimulatory molecule that delivers an inhibitory signal to suppress T-cell as well as B-cell responses. We investigated associations between malaria-specific antibody levels and CTLA-4 polymorphisms in 189 subjects living in a hyper-endemic area of Papua New Guinea (PNG), where both P. falciparum and P. vivax are prevalent. We determined P. falciparum⁄ P. vivax specific IgG⁄IgE levels (Pf-IgG, Pv-IgG, Pf-IgE, Pv-IgE) and polymorphisms in the CTLA-4 gene at position -1661 promoter region (A⁄G), the +49 exon 1 non-synonymous mutation (A⁄G), and the +6230 3‘-UTR (A⁄G). All quantified antibody levels were significantly higher in subjects > 5 years (n = 150) than in subjects ≤ 5 years of age (n = 39). In children ≤ 5 years old, significant associations were detected between CTLA-4 +49 (GG⁄AG vs. AA) and Pv-IgG (median 18.7 vs. 13.7 Μg⁄ml, P = 0.017) and Pv-IgE (266.6 vs. 146.5 pg⁄ml, P = 0.046). No significant difference was observed in subjects > 5 years old. These results suggest that the CTLA-4+49 polymorphism influenced Pv-IgG and Pv-IgE levels among children less than five years old in the studied population, which may regulate the age- and species-specific clinical outcomes of malaria infection.

OBJECTIVETo explore the diagnostic efficiency of circulating antigen using the TM5.28 mAB-biotin-avidin system for the detection of schistosomiasis japonica.

METHODSA mAb-biotin-avidin system was set up using a TM5.28 mAB which was prepared against a gut associated antigen of Schistosoma japonicum. Detection was performed on the sera from 50 acute schistosomiasis patients, 224 chronic patients, 49 advanced patients and 46 schistosomiasis patients who were followed up at 6 months and 12 months post treatment. In addition, 19 cases of clonorchiasis, 31 cases of paragonimiasis, 23 cases of hepatitis B and 100 healthy individuals were also included.

RESULTSThe system showed sensitivity of 83.1% and specificity of 94.0% when applied to detect chronic schistosomiasis and healthy persons respectively, while 94.0% to acute schistosomiasis. The Youden's index of the system was 0.771. The rate of cross-reaction to paragonimiasis, clonorchiasis and hepatitis B was 12.9%, 15.8% and 13.0% respectively. The rates of negative turning were 43.9% and 62.1% respectively in chronic schistosomiasis at the 6 month and 12 month intervals after treatment. Geometric mean of the OD values also decreased from 0.172 before treatment to 0.081 at 6 months and 0.068 at 12 months after treatment with a reduction rate of 60.30%. The detection rate in the heavy infected population reached a maximum of 90.0%. This was similar in moderate and light infected populations, i.e., 83.9% and 82.1%, respectively.

CONCLUSIONThe TM5.28 mAb-biotin-avidin system showed a relatively high efficiency in the diagnosis of schistosomiasis and a high negative turning rate after treatment. It is, therefore, a valuable tool for the estimation of prevalence in endemic populations, as well as individual diagnosis and for assessing the effect of chemotherapy.

Animals ; Antibodies, Helminth ; immunology ; Antibodies, Monoclonal ; immunology ; Avidin ; immunology ; Biotin ; immunology ; Cell Fusion ; Humans ; Mice ; Mice, Inbred BALB C ; Schistosomiasis japonica ; diagnosis ; immunology ; Serologic Tests