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51 result(s) for "Boonnak, Kobporn"
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Genetic characteristics and epidemiology of influenza and respiratory syncytial viruses associated with acute respiratory infections in Thailand
Background Influenza and respiratory syncytial virus (RSV) are significant contributors to acute respiratory infections and play a substantial role in seasonal morbidity. This study sought to elucidate the clinical characteristics, seasonal trends, and genetic evolution of circulating influenza and RSV strains in Thailand during the period from 2022 to 2023. Methods Nasopharyngeal swabs were obtained from 113 patients presenting with respiratory symptoms. Laboratory confirmation identified 57 cases of influenza and 25 cases of RSV infections. Clinical and demographic data were subjected to analysis. The hemagglutinin ( HA ) and attachment glycoprotein ( G ) genes from representative strains of influenza and RSV viruses were sequenced to facilitate phylogenetic and amino acid analyses. Results Influenza cases were predominantly observed in younger adults aged 18–35 years, whereas RSV infections were distributed evenly across various age groups and were more prevalent among females. The clinical manifestations of influenza included cough, nasal congestion, sore throat, and myalgia. In contrast, RSV cases were associated with vomiting, pneumonia, bronchitis, and elevated rates of respiratory distress. The most prevalent influenza subtype was A/H3N2, accounting for 63.2% of cases, followed by A/H1N1 and B/Victoria. RSV-B was more prevalent than RSV-A, with a prevalence rate of 64.0%. The A/H3N2 strains exhibited divergence from the vaccine strain A/Darwin/9/2021, characterised by notable amino acid substitutions. Conversely, A/H1N1 strains remained closely aligned with the vaccine strains. The B/Victoria strains were categorised under the subclade V1A.3a.2 and consistently demonstrated a deletion of three amino acids in the HA gene. RSV-A isolates were identified as belonging to genotype ON1, while RSV-B isolates were classified under genotype BA9, both displaying characteristic duplications and substitutions. Conclusion This study elucidates significant distinctions in the epidemiology and clinical outcomes of influenza and RSV in Thailand during 2022–2023. Influenza, particularly the A/H3N2 subtype, was more prevalent among younger adults and exhibited genetic divergence from the recommended vaccine strain, highlighting the necessity for continuous surveillance to inform vaccine updates. Conversely, RSV affected individuals across various age groups and was associated with more severe respiratory complications, with RSV-B being predominant. The genetic profiles of influenza and RSV strains, including amino acid substitutions and lineage-specific deletions or duplications, offer valuable insights into viral evolution and immune evasion. Collectively, these findings underscore the importance of integrated clinical and molecular surveillance to inform vaccine strain selection, enhance diagnostic accuracy, and bolster public health preparedness against seasonal respiratory pathogens.
A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses
Trichinella spiralis can modulate host immune responses to retain a suitable environment for its long-term survival. Incidentally, the parasite elicits regulatory effects through immunomodulatory molecule release, which can suppress host inflammation and may be used for the treatment of unrelated inflammatory diseases in someday. Here we identified and characterized a novel T. spiralis cystatin (TsCstN), which inhibits inflammation mediated by LPS-treated macrophages.Proteins contained in the excretory-secretory (ES) product of muscle-stage T. spiralis (ES-L1) were fractionated, and each was treated with mouse bone marrow-derived macrophages (mBMDMs) before LPS stimulation. The fractions that exhibited high immunomodulatory property by decreasing pro-inflammatory cytokines or increasing anti-inflammatory cytokines were identified by mass spectrometry. Incidentally, the conserved hypothetical protein (Tsp_04814) was selected for further characterization as it presented the most significant MS score. An annotation of Tsp_04814 using protein structural homology comparison suggested that it has high structural similarity to human cystatin E/M (TM score 0.690). The recombinant T. spiralis novel cystatin (rTsCstN) was expressed in Escherichia coli at a molecular weight of approximately 13 kDa. Mouse anti-rTsCstN polyclonal antibody (pAb) could detect native TsCstN in crude worm antigens (CWA) and ES-L1 and be predominantly localized in the stichosome and subcuticular cells. rTsCstN inhibited cysteine proteases in vitro, especially cathepsin L, at an optimal pH of 6. Besides, rTsCstN could be internalized into mBMDMs, which were mostly distributed in the cytoplasm and lysosome both before and after LPS stimulation. To evaluate the rTsCstN immunomodulatory properties on mBMDMs, rTsCstN was incubated with mBMDM before LPS stimulation; this demonstrated that rTsCstN suppressed pro-inflammatory cytokine production and MHC class II expression.T. spiralis L1-derived TsCstN was characterized as a novel cysteine protease inhibitor. The protein elicits an anti-inflammatory property by suppressing pro-inflammatory cytokines and interfering with the antigen presentation process through depletion of MHC class II expression.
Characterization of neutralizing versus binding antibody and T cell responses to varicella-zoster virus in the elderly
Age-related immune changes increase the risk of herpes zoster (HZ) caused by varicella-zoster virus (VZV) reactivation. Understanding immune responses to VZV is crucial for reducing the burden of HZ in aging populations. Due to the limited availability of data regarding the VZV immune profiles of elderly individuals, particularly in developing countries, more comprehensive immunological investigations are warranted. A total of 213 participants aged ≥ 60 years were included in this study. VZV-neutralizing antibodies (NAb) and glycoprotein-binding antibodies (BAb) were quantified. Furthermore, VZV-specific T cell subsets and their functionality were evaluated using flow cytometry. Elderly individuals demonstrated a high VZV seropositivity rate of 98.6%, exceeding that of the younger adults. Interestingly, VZV-BAb increased, whereas the proportion of NAb decreased with age, with a significantly lower proportion in the elderly aged ≥ 70 years. The elderly showed decreased naïve T cells and accumulated VZV-specific aged T cells; central memory and effector memory CD4 + and CD8 + T cells, and terminal effector memory CD8 + T cells; with elevated expression of senescence and exhaustion markers, indicating functional impairment. Nonetheless, VZV-specific functional T cells; percentages of VZV-specific interferon-γ-secreting CD4 + and CD8 + T cells; were not diminished. These findings provide insights into aging VZV immune profiles, which will facilitate the development of age-specific HZ vaccination policies.
Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge
New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppression of the hemagglutinin signal sequence, with the corresponding H1N1 and H5N1 cold-adapted ( ca ) live attenuated influenza virus vaccines in mice and ferrets. Administration of two doses of H1 or H5 S-FLU vaccines protected mice and ferrets from lethal challenge with homologous, heterologous, and heterosubtypic influenza viruses, and two doses of S-FLU and ca vaccines yielded comparable effects. Importantly, when ferrets immunized with one dose of H1 S-FLU or ca vaccine were challenged with the homologous H1N1 virus, the challenge virus failed to transmit to naive ferrets by the airborne route. S-FLU technology can be rapidly applied to any emerging influenza virus, and the promising preclinical data support further evaluation in humans. IMPORTANCE Influenza viruses continue to represent a global public health threat, and cross-protective vaccines are needed to prevent seasonal and pandemic influenza. Currently licensed influenza vaccines are based on immunity to the hemagglutinin protein that is highly variable. However, T cell responses directed against highly conserved viral proteins contribute to clearance of the virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses. In this study, two nonreplicating pseudotyped influenza virus vaccines were compared with their corresponding live attenuated influenza virus vaccines, and both elicited robust protection against homologous and heterosubtypic challenge in mice and ferrets, making them promising candidates for further evaluation in humans. Influenza viruses continue to represent a global public health threat, and cross-protective vaccines are needed to prevent seasonal and pandemic influenza. Currently licensed influenza vaccines are based on immunity to the hemagglutinin protein that is highly variable. However, T cell responses directed against highly conserved viral proteins contribute to clearance of the virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses. In this study, two nonreplicating pseudotyped influenza virus vaccines were compared with their corresponding live attenuated influenza virus vaccines, and both elicited robust protection against homologous and heterosubtypic challenge in mice and ferrets, making them promising candidates for further evaluation in humans.
Altered Moesin and Actin Cytoskeleton Protein Rearrangements Affect Transendothelial Permeability in Human Endothelial Cells upon Dengue Virus Infection and TNF-α Treatment
It has been hypothesized that the host, viral factors, and secreted cytokines (especially TNF-α) play roles in the pathogenesis of secondary dengue infections. Mass spectrometry-based proteomic screening of cytoskeleton fractions isolated from human endothelial (EA.hy926) cells upon dengue virus (DENV) infection and TNF-α treatment identified 450 differentially altered proteins. Among them, decreased levels of moesin, actin stress fiber rearrangements, and dot-like formations of vinculin were observed with western blot analyses and/or immunofluorescence staining (IFA). In vitro vascular permeability assays using EA.hy926 cells, seeded on collagen-coated transwell inserts, showed low levels of transendothelial electrical resistance in treated cells. The synergistic effects of DENV infection and TNF-α treatment caused cellular permeability changes in EA.hy926 cells, which coincided with decreasing moesin levels and the production of abnormal organizations of actin stress fibers and vinculin. Functional studies demonstrated moesin overexpression restored transendothelial permeability in DENV/TNF-α-treated EA.hy926 cells. The present study improves the understanding of the disruption mechanisms of cytoskeleton proteins in enhancing vascular permeability during DENV infection and TNF-α treatment. The study also suggests that these disruption mechanisms are major factors contributing to vascular leakage in severe dengue patients.
Probable Person-to-Person Transmission of Avian Influenza A (H5N1)
This investigation was conducted in Thailand after a young girl and her mother died from acute viral pneumonia and an aunt with whom the girl had lived also had severe viral pneumonia. Samples from the mother and aunt were positive for avian influenza (H5N1) infection. In this cluster of avian influenza infection, two of the patients had had no exposure to ill birds, suggesting that person-to-person transmission occurred. During the first months of 2004, outbreaks of highly pathogenic avian influenza caused by influenza A (H5N1) virus were recognized in eight Asian countries. 1 , 2 The poultry outbreaks receded and then reappeared in July in five countries, with human cases recognized in Vietnam and Thailand. 3 As of November 11, 2004, there had been 44 documented human infections and 32 deaths (mortality, 73 percent), sparking fears that this lethal pathogen might cause a pandemic. Since the first avian influenza outbreak, in 1997, 4 there has been concern that the influenza A (H5N1) virus might either mutate and adapt to allow efficient transmission . . .
Virological, Serological and Clinical Analysis of Chikungunya Virus Infection in Thai Patients
From 2018 to 2020, the Chikungunya virus (CHIKV) outbreak re-emerged in Thailand with a record of more than 10,000 cases up until the end of 2020. Here, we studied acute CHIKV-infected patients who had presented to the Bangkok Hospital for Tropical Diseases from 2019 to 2020 by assessing the relationship between viral load, clinical features, and serological profile. The results from our study showed that viral load was significantly high in patients with fever, headache, and arthritis. We also determined the neutralizing antibody titer in response to the viral load in patients, and our data support the evidence that an effective neutralizing antibody response against the virus is important for control of the viral load. Moreover, the phylogenetic analysis revealed that the CHIKV strains we studied belonged to the East, Central, and Southern African (ECSA) genotype, of the Indian ocean lineage (IOL), and possessed E1-K211E and E1-I317V mutations. Thus, this study provides insight for a better understanding of CHIKV pathogenesis in acute infection, along with the genomic diversity of the current CHIKV strains circulating in Thailand.
Analysis of the serum proteome profile of wild stump-tailed macaques (Macaca arctoides) seropositive for Zika virus antibodies in Thailand
Zika virus (ZIKV) is a member of the Flaviviridae virus family and poses a significant global health concern. ZIKV is transmitted by Aedes mosquitoes, and it has been implicated in various neurological conditions associated with fetal brain development. ZIKV has two transmission cycles: a sylvatic cycle in which nonhuman primates are infected via arboreal mosquito bites, and an interhuman (urban) cycle in which the virus is transmitted among primates by Aedes mosquitoes. ZIKV was first discovered in wild macaques, and the danger posed by the virus is increased due to the close proximity between humans and wild animals in modern society. However, data regarding the extent and role of infection in nonhuman primates are limited. Thus, there is an urgent need for improved surveillance, diagnostic methods, and public health interventions to effectively combat ZIKV transmission and its associated health impacts in Southeast Asia. In this study, we used a proteomics and bioinformatics approach to profile serum proteins in wild stump-tailed macaques seropositive for neutralizing antibodies against ZIKV. A total of 9,532 total proteins were identified, and 338 differentially expressed proteins were identified between naïve and seropositive animals. A total of 52 important proteins were used to construct a serum proteomic profile. These 52 important proteins were associated with immune and inflammatory responses (36.54%), neurological damage (23.08%), viral activities (21.15%), the apoptosis signaling pathway (9.61%), and other pathways (9.61%). Our proteomic profile identified proteins that inhibit the apoptosis pathway, intracellular resource competition with the virus, and neurological damage due to ZIKV and the host immune and defense responses.
Mimicking platelet indices in patients with malaria and dengue hemorrhagic fever: characteristics and clinical applications
Background Although platelet indices are routinely available using automated blood cell counters, the clinical applications of these parameters for malaria and dengue hemorrhagic fever (DHF) have not been substantially implemented. We conducted this study to investigate the potential role of platelet indices as a prognostic marker in adult patients with Plasmodium vivax malaria, Plasmodium falciparum malaria, and DHF admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. Methods We enrolled 219 eligible patients, comprising 96 with P. falciparum malaria, 71 with P. vivax malaria, and 52 with DHF. We evaluated the study groups’ baseline clinical features and alterations of platelet indices during the first 4 days of admission. Results Upon admission, the initial laboratory findings showed no statistically significant difference in platelet count (PC), plateletcrit (PCT), or platelet distribution width (PDW) between patients with P. vivax and P. falciparum ; however, mean platelet volume (MPV) was significantly higher in patients with P. falciparum . Comparisons of the initial platelet indices in malaria and DHF showed that only PC and PCT were significantly lower in DHF. Although MPV in DHF tended to be lower than in malaria, a statistically significant difference was observed only with P. falciparum . Moreover, the results also showed no significant alterations in the platelet indices among the study groups during the first 4 days of admission. Conclusions and recommendations Clinical presentations of DHF and malaria are nonspecific and may overlap with other common tropical diseases. Alterations of initial platelet indices may be investigated in P. vivax and P. falciparum malaria mimicking DHF. Although a significant reduction in PC and PCT in DHF might be a clue for differential diagnosis of malaria, the use of MPV and PDW might be impractical. We suggest that appropriate laboratory diagnoses for malaria and dengue infections are still needed for the differential diagnosis of acute febrile patients who have a risk of malaria or dengue infections. To clarify the clinical utility of platelet indices in patients with dengue and malaria, further studies are required that particularly include patients with different severities, geographical areas, and levels of health care settings.
A Serosurvey of Japanese Encephalitis Virus in Monkeys and Humans Living in Proximity in Thailand
Japanese encephalitis virus (JEV) is a member of the Flaviviridae family and one of Asia’s most common causes of encephalitis. JEV is a zoonotic virus that is transmitted to humans through the bite of infected mosquitoes of the Culex species. While humans are dead-end hosts for the virus, domestic animals such as pigs and birds are amplification hosts. Although JEV naturally infected monkeys have been reported in Asia, the role of non-human primates (NHPs) in the JEV transmission cycle has not been intensively investigated. In this study, we demonstrated neutralizing antibodies against JEV in NHPs (Macaca fascicularis) and humans living in proximity in two provinces located in western and eastern Thailand by using Plaque Reduction Neutralization Test (PRNT). We found a 14.7% and 5.6% seropositive rate in monkeys and 43.7% and 45.2% seropositive rate in humans living in west and east Thailand, respectively. This study observed a higher seropositivity rate in the older age group in humans. The presence of JEV neutralizing antibodies in NHPs that live in proximity to humans shows the occurrence of natural JEV infection, suggesting the endemic transmission of this virus in NHPs. According to the One Health concept, regular serological studies should be conducted especially at the animal–human interface.