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Fulltext Complete genome analysis and characterization of neurotropic dengue virus 2 cosmopolitan genotype isolated from the cerebrospinal fluid of encephalitis patients

Ngwe Tun MM, Muthugala R, Nabeshima T, Soe AM, Dumre SP, Rajamanthri L, et al.

PLoS One, 2020;15(6):e0234508.
PMID: 32555732 DOI: 10.1371/journal.pone.0234508

Dengue virus (DENV) infection remains a major public health concern in many parts of the world, including Southeast Asia and the Americas. Sri Lanka experienced its largest dengue outbreak in 2017. Neurological symptoms associated with DENV infection have increasingly been reported in both children and adults. Here, we characterize DENV type 2 (DENV-2) strains, which were isolated from cerebrospinal fluid (CSF) and/or serum of patients with dengue encephalitis. Acute serum and CSF samples from each patient were subjected to dengue-specific non-structural protein 1 (NS1) antigen test, IgM and IgG enzyme-linked immunosorbent assay (ELISA), virus isolation, conventional and real-time polymerase chain reaction (PCR), and next-generation sequencing (NGS). Among the 5 dengue encephalitis patients examined, 4 recovered and 1 died. DENV-2 strains were isolated from serum and/or CSF samples of 3 patients. The highest viral genome levels were detected in the CSF and serum of the patient who succumbed to the illness. A phylogenetic tree revealed that the DENV-2 isolates belonged to a new clade of cosmopolitan genotype and were genetically close to strains identified in China, South Korea, Singapore, Malaysia, Thailand, and the Philippines. According to the NGS analysis, greater frequencies of nonsynonymous and synonymous mutations per gene were identified in the nonstructural genes. The full genomes of serum- and CSF-derived DENV-2 from the same patient shared 99.7% similarity, indicating that the virus spread across the blood-brain barrier. This is the first report to describe neurotropic DENV-2 using whole-genome analysis and to provide the clinical, immunological, and virological characteristics of dengue encephalitis patients during a severe dengue outbreak in Sri Lanka in 2017.
Unusual, neurological and severe dengue manifestations during the outbreak in Sri Lanka, 2017

Ngwe Tun MM, Muthugala R, Nabeshima T, Rajamanthri L, Jayawardana D, Attanayake S, et al.

J Clin Virol, 2020 04;125:104304.
PMID: 32145478 DOI: 10.1016/j.jcv.2020.104304

BACKGROUND: Sri Lanka experienced its largest dengue outbreak in 2017 with more than 185,000 dengue cases including at least 250 fatalities.
OBJECTIVES: Our study aimed to characterize the clinical, immunological and virological features of confirmed dengue patients in Sri Lanka during the outbreak in 2017 when unusual manifestations of severe dengue were observed.
STUDY DESIGN: Sera from 295 patients who were admitted to Teaching Hospital Kandy, Kandy, Sri Lanka between March 2017- January 2018 were subjected to NS1 antigen, IgM and IgG ELISAs, virus isolation, conventional and real time RT-PCR and next generation sequencing.
RESULTS: Primary and secondary infections were detected in 48.5 % and 51.5 % of the study population, respectively. Two hundred twenty five DENV strains were isolated (219 DENV-2, one DENV-3, two DENV-4, two mixed infections of DENV-2 and -3 and one mixed infection of DENV-2 and -4). Unusual and severe manifestations such as encephalitis, encephalopathy, liver failure, kidney failure, myocarditis, Guillain-Barré syndrome and multi-organ failure were noted in 44 dengue patients with 11 deaths. The viraemia levels in patients with primary infection and unusual manifestations were significantly higher compared to those in patients with secondary infection. A new clade of DENV-2 Cosmopolitan genotype strains was observed with the strains closely related to those from China, Malaysia, Indonesia, Singapore and Taiwan.
CONCLUSIONS: The new clade of DENV-2 cosmopolitan genotype observed in Sri Lanka in 2017 caused an unprecedented, severe dengue outbreak. The emergence of DENV-3 and DENV-4 in the 2017 outbreak might cause future outbreaks in Sri Lanka.
Fulltext Universal checklist for COVID-19 control measures: consensus via a Delphi method

Sharma A, U V, Dong V, Raut A, Tawfik GM, Ng SJ, et al.

Clin Med (Lond), 2021 Mar;21(Suppl 2):25-26.
PMID: 34078684 DOI: 10.7861/clinmed.21-2-s25
Fulltext SARS-CoV-2 Omicron and its current known unknowns: A narrative review

Le TTB, Vasanthakumaran T, Thi Hien HN, Hung IC, Luu MN, Khan ZA, et al.

Rev Med Virol, 2023 Jan;33(1):e2398.
PMID: 36150052 DOI: 10.1002/rmv.2398

The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.
Fulltext Study Protocol for a Global Survey: Awareness and Preparedness of Hospital Staff Against Coronavirus Disease (COVID-19) Outbreak

Qarawi ATA, Ng SJ, Gad A, Luu MN, Al-Ahdal TMA, Sharma A, et al.

Front Public Health, 2021;9:580427.
PMID: 34277529 DOI: 10.3389/fpubh.2021.580427

Background: The outbreak of Coronavirus disease (COVID-19) caused by a novel coronavirus (named SARS-CoV-2) has gained attention globally and has been recognized as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to the rapidly increasing number of deaths and confirmed cases. Health care workers (HCWs) are vulnerable to this crisis as they are the first frontline to receive and manage COVID-19 patients. In this multicenter multinational survey, we aim to assess the level of awareness and preparedness of hospital staff regarding COVID-19 all over the world. Methods: From February to March 2020, the web-based or paper-based survey to gather information about the hospital staff's awareness and preparedness in the participants' countries will be carried out using a structured questionnaire based on the United States Centers for Disease Control and Prevention (CDC) checklist and delivered to participants by the local collaborators for each hospital. As of March 2020, we recruited 374 hospitals from 58 countries that could adhere to this protocol as approved by their Institutional Review Boards (IRB) or Ethics Committees (EC). Discussion: The awareness and preparedness of HCWs against COVID-19 are of utmost importance not only to protect themselves from infection, but also to control the virus transmission in healthcare facilities and to manage the disease, especially in the context of manpower lacking and hospital overload during the pandemic. The results of this survey can be used to inform hospitals about the awareness and preparedness of their health staff regarding COVID-19, so appropriate policies and practice guidelines can be implemented to improve their capabilities of facing this crisis and other future pandemic-prone diseases.
Fulltext Awareness and preparedness of healthcare workers against the first wave of the COVID-19 pandemic: A cross-sectional survey across 57 countries

Huy NT, Chico RM, Huan VT, Shaikhkhalil HW, Uyen VNT, Qarawi ATA, et al.

PLoS One, 2021;16(12):e0258348.
PMID: 34936646 DOI: 10.1371/journal.pone.0258348

BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave.
METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training.
RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a 'great-extent-of-confidence' in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors.
INTERPRETATION: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type.
Fulltext Anxiety and its risk factors among non-Japanese residents living in Japan undergoing COVID-19 situation: A cross-sectional survey

Luu MN, Imoto A, Matsuo Y, Huy NT, Qarawi A, Alhady STM, et al.

PLoS One, 2024;19(3):e0280144.
PMID: 38489310 DOI: 10.1371/journal.pone.0280144

INTRODUCTION: In the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic.
METHODS: A web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation. The State-Trait Anxiety Inventory assessed the level of anxiety-State (STAI-S) scores prorated from its six-item version. The multivariable logistic regression using the Akaike Information Criterion (AIC) method was performed to identify the associated factors of anxiety among participants.
RESULTS: From January to March 2021, we collected 392 responses. A total of 357 valid responses were analyzed. 54.6% of participants suffered from clinically significant anxiety (CSA). In multivariable logistic model analysis, the CSA status or the high level of anxiety was associated with three factors, including having troubles/difficulties in learning or working, decreased sleep duration, and decreased overall physical health (p<0.05).
CONCLUSION: Our study suggests several possible risk factors of anxiety among non-Japanese residents living in Japan undergoing the COVID-19 pandemic, including the troubles or difficulties in learning or working, the decrease in sleep duration, and the decrease in overall physical health.