Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonosis caused by SFTS virus (SFTSV). In addition to tick bites, animal-to-human transmission of SFTSV has been ...reported, but little is known about feline SFTSV infection. In this study, we analyzed data on 187 cats with suspected SFTS to identify biomarkers for SFTS diagnosis and clinical outcome. Body weight, red and white blood cell and platelet counts, and serum aspartate aminotransferase and total bilirubin levels were useful for SFTS diagnosis, whereas alanine aminotransferase, aspartate aminotransferase and serum SFTSV RNA levels were associated with clinical outcome. We developed a scoring model to predict SFTSV infection. In addition, we performed a phylogenetic analysis to reveal the relationship between disease severity and viral strain. This study provides comprehensive information on feline SFTS and could contribute to the protection of cat owners, community members, and veterinarians from the risk of cat-transmitted SFTSV infection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2019 has led to a global health crisis. Mutations of the SARS-CoV-2 genome have impeded the development ...of effective therapeutics and vaccines against SARS-CoV-2. Natural products are important for discovering therapeutics to treat the 2019 coronavirus disease (COVID-19). In the present study, we investigated the antiviral activity of herbal drug extracts from Polygala Root, Areca, and Quercus Bark and natural compounds derived from herbal drug such as baicalin and glabridin, with IC
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values of 9.5 µg/ml, 1.2 µg/ml, 5.4 µg/ml, 8.8 µM, and 2.5 µM, respectively, against SARS CoV-2 infection in vitro. Certain herbal drug extracts and natural compounds were found to inhibit viral RNA levels and infectious titers of SARS-CoV-2 in a dose-dependent manner. Furthermore, viral protein analyses showed that herbal drug extracts and natural compounds effectively inhibited SARS-CoV-2 in the various entry treatments. Our study revealed that three herbal drugs are good candidates for further in vivo and clinical studies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to global public health. The emergence of SARS-CoV-2 ...variants is a significant concern regarding the continued effectiveness of vaccines and antiviral therapeutics. Thus, natural products such as foods, drinks, and other compounds should be investigated for their potential to treat COVID-19. Here, we examined the
in vitro
antiviral activity against SARS-CoV-2 of various polyethylene terephthalate (PET)-bottled green Japanese teas and tea compounds. Six types of PET-bottled green tea were shown to inhibit SARS-CoV-2 at half-maximal inhibitory concentrations (IC
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) of 121- to 323-fold dilution. Our study revealed for the first time that a variety of PET-bottled Japanese green tea drinks inhibit SARS-CoV-2 infection in a dilution-dependent manner. The tea compounds epigallocatechin gallate (EGCG) and epicatechin gallate showed virucidal activity against SARS-CoV-2, with IC
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values of 6.5 and 12.5 µM, respectively. The investigated teas and tea compounds inactivated SARS-CoV-2 in a dose-dependent manner, as demonstrated by the viral RNA levels and infectious titers. Furthermore, the green teas and EGCG showed significant inhibition at the entry and post-entry stages of the viral life cycle and inhibited the activity of the SARS-CoV-2 3CL-protease. These findings indicate that green tea drinks and tea compounds are potentially useful in prophylaxis and COVID-19 treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chikungunya virus (CHIKV) infection is a re-emerging arboviral disease with no approved vaccine, although numerous options are in development. Before vaccine implementation, disease burden, affected ...age group, and hospitalization rate information should be documented. In 2019, a sizeable outbreak of the East Central South African genotype of CHIKV occurred in Myanmar, and during this period, a cross-sectional study was conducted in two regions, Mandalay and Yangon, to examine the molecular and seropositivity rate of the CHIKV infection. The participants (1124) included dengue-suspected pediatric patients, blood donors, and healthy volunteers, who were assessed using molecular assays (quantitative real-time RT-PCR), serological tests (anti-CHIKV IgM capture and IgG indirect enzyme-linked immunosorbent assays), and neutralization tests. The tests confirmed the following positivity rates: 11.3% (127/1124) for the molecular assay, 12.4% (139/1124) for the anti-CHIKV IgM Ab, 44.5% (500/1124) for the anti-CHIKV IgG Ab, and 46.3% (520/1124) for the CHIKV neutralizing Ab. The highest rate for the molecular test occurred with the dengue-suspected pediatric patients. The seroprevalence rate through natural infection was higher in the healthy volunteers and blood donors than that in the pediatric patients. The results of this study will help stakeholders determine the criteria for choosing appropriate recipients when a CHIKV vaccine is introduced in Myanmar.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Dengue fever, caused by the mosquito-borne dengue virus (DENV), has been endemic in Myanmar since 1970 and it has become a significant public health burden. It is crucial that circulating DENV ...strains are identified and monitored, and that their transmission efficiency and association with disease severity is understood. In this study, we analyzed DENV-1, DENV-2, DENV-3, and DENV-4 serotypes in 1235 serum samples collected in Myanmar between 2017 and 2019. Whole-genome sequencing of DENV-1–4 demonstrated that most DENV-1–4 strains had been circulating in Myanmar for several years. We also identified the emergence of DENV-3 genotype-I in 2017 samples, which persisted through 2018 and 2019. The emergence of the strain coincided with a period of increased DENV-3 cases and marked changes in the serotype dynamics. Nevertheless, we detected no significant differences between serum viral loads, disease severity, and infection status of individuals infected with different DENV serotypes during the 3-year study. Our results not only identify the spread of a new DENV-3 genotype into Yangon, Myanmar, but also support the importance of DENV evolution in changing the epidemic dynamics in endemic regions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In search of a mouse model for use in evaluating dengue vaccines, we assessed A129 mice that lacked IFN-α/β receptors, rendering them susceptible to dengue virus (DENV) infection. To our knowledge, ...no reports have evaluated dengue vaccine efficiency using A129 mice. A129 mice were given a single intraperitoneal (IP) or subcutaneous (SC) injection of the vaccine, Dengvaxia. After 14 days of immunization via the IP or SC injection of Dengvaxia, the A129 mice exhibited notably elevated levels of anti-DENV immunoglobulin G and neutralizing antibodies (NAb) targeting all four DENV serotypes, with DENV-4 displaying the highest NAb levels. After challenge with DENV-2, Dengvaxia and mock-immunized mice survived, while only the mock group exhibited signs of morbidity. Viral genome levels in the serum and tissues (excluding the brain) were considerably lower in the immunized mice compared to those in the mock group. The SC administration of Dengvaxia resulted in lower viremia levels than IP administration did. Therefore, given that A129 mice manifest dengue-related morbidity, including viremia in the serum and other tissues, these mice represent a valuable model for investigating novel dengue vaccines and antiviral drugs and for exploring dengue pathogenesis.
Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the ...emergence of new genotypes and serotype shifting. To understand the genomic and viral characteristics of DENV-infected patients, we conducted a cross-sectional descriptive study among pediatric patients admitted at the 550-bedded Mandalay Children Hospital during the 2018 DEN endemic season. We conducted virus isolation, serological tests, viremia level measurement, and whole-genome sequencing. Among the 202 serum samples, we detected 85 samples with DENV (46 DENV-1, 10 DENV-3, 26 DENV-4 and three multiple serotype co-infections) via reverse transcription quantitative/real-time PCR (RT-qPCR), and we obtained 49 DENV isolates (31 DENV-1, 10 DENV-3 and 8 DEN-4). We did not detect DENV-2 in this study. The viral genome levels in serum did not differ significantly among virus serotypes, infection status (primary versus secondary) and disease severity. Based on the phylogenetic analysis, we identified DENV-1 genotype-1, DENV-4 genotype-1 and DENV-3 genotype-3 and genotype-1 which was detected for the first time. Next-generation sequencing analysis revealed greater frequencies of nonsynonymous and synonymous mutations per gene in the nonstructural genes. Moreover, mutation rates were also higher among DENV-1. In conclusion, there was an increasing trend of DENV-3 cases during DENV endemic season in 2018 with the first detection of the genotype 1. However, DENV-1 has remained the predominant serotype in this study area since 2013, and we identified stop codon mutations in the DENV-1 genome. This report is the first to feature a complete genome analysis of the strains of DENV-3 and DENV-4 circulating among pediatric patients in Myanmar. This study highlighted the importance of annual surveillance for a better understanding of the molecular epidemiology of DENVs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Myanmar is an endemic country for the Japanese encephalitis virus (JEV), and the SA-14-14-2 live-attenuated JEV vaccine was first introduced as a catch-up vaccination campaign in 2017. To determine ...the effectiveness of vaccination by means of neutralizing antibody titers against JEV, a cross-sectional descriptive study was conducted among five to 15-year-old monastic school children in Mandalay, Myanmar. A total of 198 students who had received vaccines were recruited, and single-time investigation of anti-JEV IgG and neutralizing antibodies against wild-type JEV were determined using anti-JEV IgG ELISA and plaque reduction neutralization tests (PRNT50). All students 100% (198/198) showed positive results on the anti-JEV IgG ELISA, and 87% (172/198) of the students had neutralizing antibodies against JEV six months after immunization. The geometric mean titers of both IgG antibodies and neutralizing antibodies increased with the participants’ age groups, and statistically significant differences in anti-JEV IgG titers were noted across age groups. In this study, we could not investigate the persistence of neutralizing antibodies as only single-time blood collection was done. This study, which is the first report of JEV vaccination among children in Myanmar, showed similar neutralizing antibody production rates among vaccinated individuals as did studies in other countries.
The dengue virus (DENV) has been endemic in Myanmar since 1970, causing outbreaks every 2-3 years. DENV infection symptoms range from mild fever to lethal hemorrhage. Clinical biomarkers must be ...identified to facilitate patient risk stratification in the early stages of infection. We analyzed 45 cytokines and other factors in serum samples from the acute phase of DENV infection (within 3-5 days of symptom onset) from 167 patients in Yangon, Myanmar, between 2017 and 2019. All of the patients tested positive for serum DENV nonstructural protein 1 antigen (NS1 Ag); 78.4% and 62.9% were positive for immunoglobulin M (IgM) and G (IgG), respectively; and 18.0%, 19.8%, and 11.9% tested positive for serotypes 1, 3, and 4, respectively. Although the DENV-4 viral load was significantly higher than those of DENV-1 or DENV-3, disease severity was not associated with viral load or serotype. Significant correlations were identified between disease severity and CCL5, SCF, PDGF-BB, IL-10, and TNF-α levels; between NS1 Ag and SCF, CCL5, IFN-α, IL-1α, and IL-22 levels; between thrombocytopenia and IL-2, TNF-α, VEGF-D, and IL-6 levels; and between primary or secondary infection and IL-2, IL-6, IL-31, IL-12p70, and MIP-1β levels. These circulating factors may represent leading signatures in acute DENV infections, reflecting the clinical outcomes in the dengue endemic region, Myanmar.
In 2017, Sri Lanka experienced its largest dengue epidemic and reported severe and unusual presentations of dengue with high morbidity. This outbreak was associated with the reemergence of dengue ...virus-2 (DENV-2), with the responsible strain identified as a variant of the previously circulating DENV-2 cosmopolitan genotype. In this study, we characterized the DENV-2 cosmopolitan genotype from patients during this epidemic. Also, we identified host factors that contributed to the severity of dengue infection in patients infected with this particular virus. Ninety-one acute serum samples from patients at the National Hospital in Kandy were randomly selected. Of these, 40.2% and 48.9% were positive for dengue IgM and IgG, respectively. NS1 antigen levels were significantly higher in primary infections. The severe dengue (SD) and dengue with warning signs (DWWS) groups exhibited significantly higher viral genome and infectivity titers than the dengue without warning signs (DWoWS) group. The highest viremia level was observed in SD patients. As for host cytokine response, interferon α (IFN-α) levels were significantly higher in the DWoWS group than in the DWWS and SD groups, whereas interleukin (IL)-12p40 and tumor necrosis factor α (TNF-α) levels in SD patients were significantly higher than in the other two groups. The TNF-α, IL-4, and monocyte chemoattractant protein-1 concentrations were positively correlated with NS1 antigen levels. From whole-genome analysis, NS4 had the highest frequency of amino acid variants, followed by the E gene. Our study suggests that viremia levels and immune responses contributed to SD outcomes, and these findings may help in identifying an effective therapeutic strategy against SD infection.
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