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Preventive behaviours towards influenza A(H1N1) and factors associated with the intention to take influenza A(H1N1) vaccination

Naing C, Tan RY, Soon WC, Parakh J, Sanggi SS

J Infect Public Health, 2012 Dec;5(6):412-9.
PMID: 23287612 DOI: 10.1016/j.jiph.2012.07.005

PURPOSE: (i) To determine knowledge of, and self-protecting preventive behaviours towards influenza A(H1N1) and (ii) to identify the factors influencing intention to take influenza A(H1N1) vaccination among the study population.
MATERIALS AND METHODS: This is a cross-sectional survey carried out in Mantin Town, a semi-urban area of Malaysia. A structured questionnaire consisted of sociodemographic characteristics, knowledge of pandemic influenza symptoms, mode of transmission, self-protecting preventive behaviours, and intention to receive the influenza A(H1N1)pdm09 vaccine was used for face-to-face interviews with the household members.
RESULTS: Of 230 who heard about pandemic influenza A(H1N1), 86% had misconception about mode of transmission of influenza A(H1N1)pdm09, and 52% had sufficient self-protecting behaviours. A majority (58.3%; 134/230) had intended to receive the vaccine. In the multivariate analysis, the intention to get vaccinated was significantly higher among 'those who trusted in efficacy of vaccine for prevention of influenza A(H1N1)' (p<0.001), 'those who were equipped with higher education level' (p=0.015) and 'those who worry about themselves contracting illness' (p=0.008).
CONCLUSIONS: Our findings highlight the need to scale up the community's knowledge regarding influenza A(H1N1). Recognizing the factors affecting the acceptance of vaccination documented in this study will allow decision makers to devise effective and efficient vaccination strategies.

Matched MeSH terms: Influenza, Human/prevention & control*; Influenza, Human/transmission
A case-control study of influenza vaccine effectiveness among Malaysian pilgrims attending the Haj in Saudi Arabia

Mustafa AN, Gessner BD, Ismail R, Yusoff AF, Abdullah N, Ishak I, et al.

Int J Infect Dis, 2003 Sep;7(3):210-4.
PMID: 14563225

To determine influenza vaccine effectiveness against clinically defined influenza-like illness among Malaysian pilgrims attending the Haj in Saudi Arabia.

Matched MeSH terms: Influenza, Human/prevention & control*; Influenza, Human/virology
Expression of surface-bound nonstructural 1 (NS1) protein of influenza virus A H5N1 on Lactobacillus casei strain C1

Tan TS, Syed Hassan S, Yap WB

Lett Appl Microbiol, 2017 Jun;64(6):446-451.
PMID: 28370088 DOI: 10.1111/lam.12738

The study aimed to construct a recombinant Lactobacillus casei expressing the nonstructural (NS) 1 protein of influenza A virus H5N1 on its cell wall. The NS1 gene was first amplified and fused to the pSGANC332 expression plasmid. The NS1 protein expression was carried out by Lact. casei strain C1. PCR screening and DNA sequencing confirmed the presence of recombinant pSG-NS1-ANC332 plasmid in Lact. casei. The plasmid was stably maintained (98·94 ± 1·65%) by the bacterium within the first 20 generations without selective pressure. The NS1 was expressed as a 49-kDa protein in association with the anchoring peptide. The yield was 1·325 ± 0·065 μg mg(-1) of bacterial cells. Lactobacillus casei expressing the NS1 on its cell wall was red-fluorescently stained, but the staining was not observed on Lact. casei carrying the empty pSGANC332. The results implied that Lact. casei strain C1 is a promising host for the expression of surface-bound NS1 protein using the pSGANC332 expression plasmid.
SIGNIFICANCE AND IMPACT OF THE STUDY: The study has demonstrated, for the first time, the expression of nonstructural 1 (NS1) protein of influenza A virus H5N1 on the cell wall of Lactobacillus casei using the pSGANC332 expression plasmid. Display of NS1 protein on the bacterial cell wall was evident under an immunofluorescence microscopic observation. Lactobacillus casei carrying the NS1 protein could be developed into a universal oral influenza vaccine since the NS1 is highly conserved among influenza viruses.

Matched MeSH terms: Influenza, Human/prevention & control*; Influenza, Human/virology
Fulltext The association between pre-morbid conditions and respiratory tract manifestations amongst Malaysian Hajj pilgrims

Deris ZZ, Hasan H, Ab Wahab MS, Sulaiman SA, Naing NN, Othman NH

Trop Biomed, 2010 Aug;27(2):294-300.
PMID: 20962728 MyJurnal

In a very closed and overcrowding environment, influenza transmission during Hajj season is almost inevitable. The aim of this study was to determine the association between pre-morbid conditions and influenza-like illness (ILI) amongst Hajj pilgrims. A cross-sectional study was conducted amongst Malaysian Hajj pilgrims in year 2007. Survey forms were distributed at Madinatul-Hujjaj, Jeddah and Tabung Haji Clinic, Medina, Saudi Arabia where pilgrims stay on transit before returning to Malaysia. Allergic rhinitis was significantly associated with sore throat (p=0.047), longer duration of cough (p=0.017) and runny nose (p=0.016). Pilgrims who suffered from chronic obstructive pulmonary diseases (COPD) had significant association with longer duration of cough (p=0.041) and those with diabetes mellitus had significant association with longer duration of sore throat (p=0.048). Underlying asthma was significantly associated with severe influenza like illness requiring admission to hospital for further treatment of respiratory symptoms (p=0.016). Based on these findings, we suggest those with underlying asthma should be discouraged from participating in the hajj and they should seek early treatment if they develop respiratory symptoms.

Matched MeSH terms: Influenza, Human/epidemiology; Influenza, Human/transmission
The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation

Bhowmick S, Chakravarty C, Sellathamby S, Lal SK

Arch Virol, 2017 Apr;162(4):919-929.
PMID: 27942972 DOI: 10.1007/s00705-016-3153-8

The matrix protein 2 (M2) is a spliced product of segment 7 genome of influenza A virus. Previous studies indicate its role in uncoating of the viral ribonucleoprotein complex during viral entry and in membrane scission while budding. Despite its crucial role in the viral life cycle, little is known about its subcellular distribution and dynamics. In this study, we have shown that the M2 protein is translocated from the membrane to the cytoplasm by a retrograde route via endosomes and the Golgi network. It utilizes retromer cargo while moving from the endosome to the trans-Golgi network and prevents endosome fusion with the lysosome. Further, M2 interacts with the endoplasmic-reticulum-resident AAA-ATPase p97 for its release into the cytoplasm. Our study also revealed that the M2 protein in the cellular milieu does not undergo ubiquitin-mediated proteasomal degradation. The migration of M2 through this pathway inside the infected cell suggests possible new roles that the M2 protein may have in the host cytoplasm, apart from its previously described functions.

Matched MeSH terms: Influenza, Human/metabolism; Influenza, Human/virology*
Intercontinental circulation of human influenza A(H1N2) reassortant viruses during the 2001-2002 influenza season

Xu X, Smith CB, Mungall BA, Lindstrom SE, Hall HE, Subbarao K, et al.

J Infect Dis, 2002 Nov 15;186(10):1490-3.
PMID: 12404167

Reassortant influenza A viruses bearing the H1 subtype of hemagglutinin (HA) and the N2 subtype of neuraminidase (NA) were isolated from humans in the United States, Canada, Singapore, Malaysia, India, Oman, Egypt, and several countries in Europe during the 2001-2002 influenza season. The HAs of these H1N2 viruses were similar to that of the A/New Caledonia/20/99(H1N1) vaccine strain both antigenically and genetically, and the NAs were antigenically and genetically related to those of recent human H3N2 reference strains, such as A/Moscow/10/99(H3N2). All 6 internal genes of the H1N2 reassortants examined originated from an H3N2 virus. This article documents the first widespread circulation of H1N2 reassortants on 4 continents. The current influenza vaccine is expected to provide good protection against H1N2 viruses, because it contains the A/New Caledonia/20/99(H1N1) and A/Moscow/10/99(H3N2)-like viruses, which have H1 and N2 antigens that are similar to those of recent H1N2 viruses.

Matched MeSH terms: Influenza, Human/epidemiology; Influenza, Human/virology*
Fulltext Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014

Oong XY, Ng KT, Lam TT, Pang YK, Chan KG, Hanafi NS, et al.

PLoS One, 2015;10(8):e0136254.
PMID: 26313754 DOI: 10.1371/journal.pone.0136254

Epidemiological and evolutionary dynamics of influenza B Victoria and Yamagata lineages remained poorly understood in the tropical Southeast Asia region, despite causing seasonal outbreaks worldwide. From 2012-2014, nasopharyngeal swab samples collected from outpatients experiencing acute upper respiratory tract infection symptoms in Kuala Lumpur, Malaysia, were screened for influenza viruses using a multiplex RT-PCR assay. Among 2,010/3,935 (51.1%) patients infected with at least one respiratory virus, 287 (14.3%) and 183 (9.1%) samples were tested positive for influenza A and B viruses, respectively. Influenza-positive cases correlate significantly with meteorological factors-total amount of rainfall, relative humidity, number of rain days, ground temperature and particulate matter (PM10). Phylogenetic reconstruction of haemagglutinin (HA) gene from 168 influenza B viruses grouped them into Yamagata Clade 3 (65, 38.7%), Yamagata Clade 2 (48, 28.6%) and Victoria Clade 1 (55, 32.7%). With neuraminidase (NA) phylogeny, 30 intra-clade (29 within Yamagata Clade 3, 1 within Victoria Clade 1) and 1 inter-clade (Yamagata Clade 2-HA/Yamagata Clade 3-NA) reassortants were identified. Study of virus temporal dynamics revealed a lineage shift from Victoria to Yamagata (2012-2013), and a clade shift from Yamagata Clade 2 to Clade 3 (2013-2014). Yamagata Clade 3 predominating in 2014 consisted of intra-clade reassortants that were closely related to a recent WHO vaccine candidate strain (B/Phuket/3073/2013), with the reassortment event occurred approximately 2 years ago based on Bayesian molecular clock estimation. Malaysian Victoria Clade 1 viruses carried H274Y substitution in the active site of neuraminidase, which confers resistance to oseltamivir. Statistical analyses on clinical and demographic data showed Yamagata-infected patients were older and more likely to experience headache while Victoria-infected patients were more likely to experience nasal congestion and sore throat. This study describes the evolution of influenza B viruses in Malaysia and highlights the importance of continuous surveillance for better vaccination policy in this region.

Matched MeSH terms: Influenza, Human/genetics*; Influenza, Human/epidemiology*
Fulltext Pandemic influenza A (H1N1) and its prevention: a cross sectional study on patients' knowledge, attitude and practice among patients attending primary health care clinic in Kuala Lumpur, Malaysia

Latiff LA, Parhizkar S, Zainuddin H, Chun GM, Rahiman MA, Ramli NL, et al.

Glob J Health Sci, 2012 Feb 29;4(2):95-102.
PMID: 22980156 DOI: 10.5539/gjhs.v4n2p95

The World Health Organization confirmed that the novel influenza A, H1N1 as a pandemic on 11 June 2009. After less than three months, 182 countries were affected by the pandemic accounting for about 150,000 infected cases and 3000 mortality. Successful H1N1 pandemic management strategies' shaped by making changes in health behavior. The aim of this study was to document patients' knowledge, attitudes and practices (KAP) regarding the pandemic influenza A (H1N1) and its prevention. We performed a cross-sectional study on knowledge, attitudes and practices (KAP) on preventive measures of Influenza A (H1N1) involving 322 patients attending Klinik Kesihatan Jinjang, a primary health care clinic in Kuala Lumpur, Malaysia from May 10 to 26, 2010 using a face to face interview with a structured pre-tested questionnaire. The majority of the respondents were females (56.8%), Malays (43.2%) aged between 18-27 years old (28.9%). There were significant association between knowledge on the complication of H1N1, effectiveness of the treatment, preventive measures of Influenza A (H1N1) and race (p<0.001) and educational level (p<0.001). There were also significant associations between attitude scores of these patients and their gender (p=0.03), and educational level (p=0.001). Practice scores related to H1N1 were found to be significantly associated with race (p<0.001) and educational level (p<0.001). The significant associations were observed between knowledge and attitude (p<0.001), knowledge and practices (p<0.001), as well as attitude and practices related to H1N1 (p<0.001). Knowledge has a crucial effect on patients' attitude and practice particularly in a pandemic spread. So health policy makers should attempt to disseminate information about preventive measures to community in order to improve their preventive practices during pandemics.

Matched MeSH terms: Influenza, Human/epidemiology*; Influenza, Human/prevention & control*
A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans

Chua KB, Crameri G, Hyatt A, Yu M, Tompang MR, Rosli J, et al.

Proc Natl Acad Sci U S A, 2007 Jul 03;104(27):11424-9.
PMID: 17592121

Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named "Melaka virus") isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms approximately 1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house approximately 1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans.

Matched MeSH terms: Influenza, Human/diagnosis; Influenza, Human/virology
Isolation of an influenza C virus introduced into Japan by a traveler from Malaysia

Matsuzaki Y, Sato K, Sugawara K, Takashita E, Muraki Y, Morishita T, et al.

J Clin Microbiol, 2005 Feb;43(2):993-5.
PMID: 15695727

An influenza C virus was isolated from a Japanese traveler who had visited Malaysia in April 1999. Phylogenetic analysis indicated that the genome composition of this virus was distinct from that of any other strain isolated in Japan. The possibility that a genetically unique influenza C virus was introduced into Japan by a traveler is shown.

Matched MeSH terms: Influenza, Human/epidemiology; Influenza, Human/virology*
Fulltext Molecular analysis of 2009 pandemic influenza A(H1N1) in Malaysia associated with mild and severe infections

Balraj P, Sidek H, Suppiah J, Khoo AS, Saat Z

Malays J Pathol, 2011 Jun;33(1):7-12.
PMID: 21874745 MyJurnal

The 2009 pandemic influenza A(H1N1) was first detected in Malaysia in May 2009. It quickly spread in the general population and contributed to a number of influenza-like illness. The objective of the study is to characterize genetic changes in early Malaysian isolates of mild and severe illness of the novel influenza, and to compare sequences of viruses circulating in Malaysia to those in other countries between May to September 2009. Viral isolates of 56 mild cases and 10 severe (intensive care unit or fatal) cases were sequenced for haemagglutinin (HA) and neuraminidase (NA). Genome sequencing of the viral RNA was conducted on 5 isolates (3 were from fatal cases). Highly conserved sequences with few sporadic variations were identified in HA and NA. E374K and D222N were identified in 2 viral isolates from patients with severe illness. Phylogenetic analysis showed close genetic relatedness to the vaccine strain A/California/07/09 and other isolates circulating worldwide during the same period. Sporadic variations were identified in the viral isolates, however a larger sample size is required to make associations with disease severity.

Matched MeSH terms: Influenza, Human/epidemiology*; Influenza, Human/pathology*; Influenza, Human/virology
Fulltext Monitoring of the h275y mutation in pandemic influenza A(H1N1) 2009 strains isolated in Malaysia

Suppiah J, Yusof MA, Othman KA, Saraswathy TS, Thayan R, Kasim FM, et al.

Southeast Asian J. Trop. Med. Public Health, 2011 Jan;42(1):100-4.
PMID: 21323171

The 2009 pandemic influenza A(H1N1) infection in Malaysia was first reported in May 2009 and oseltamivir was advocated for confirmed cases in postexposure prophylaxis. However, there are cases of oseltamivir-resistance reported among H1N1-positive patients in other countries. Resistance is due to substitution of histidine by tyrosine at residue 275 (H275Y) of neuraminidase (NA). In this study, we have employed Sanger sequencing method to investigate the occurrence of mutations in NA segments of 67 pandemic 2009 A(H1N1) viral isolates from Malaysian patients that could lead to probable oseltamivir resistance. The sequencing analysis did not yield mutation at residue 275 for all 67 isolates indicating that our viral isolates belong to the wild type and do not confer resistance to oseltamivir.

Matched MeSH terms: Influenza, Human/drug therapy; Influenza, Human/epidemiology; Influenza, Human/virology*
Fulltext The prevalence of acute respiratory symptoms and role of protective measures among Malaysian hajj pilgrims

Deris ZZ, Hasan H, Sulaiman SA, Wahab MS, Naing NN, Othman NH

J Travel Med, 2010 Mar-Apr;17(2):82-8.
PMID: 20412173 DOI: 10.1111/j.1708-8305.2009.00384.x

BACKGROUND: Respiratory symptoms including cough, runny nose, sore throat, and fever are the most common clinical manifestations faced by hajj pilgrims in Mecca. The aim of the study was to determine the prevalence of respiratory symptoms among Malaysian hajj pilgrims and the effect of a few protective measures taken by hajj pilgrims to reduce respiratory symptoms.
METHODS: A cross-sectional study was conducted by distributing survey forms to Malaysian hajj pilgrims at transit center before flying back to Malaysia. The recruitment of respondents to the survey was on a voluntary basis.
RESULTS: A total of 387 survey forms were available for analysis. The mean age was 50.4 +/- 11.0 years. The common respiratory symptoms among Malaysian hajj pilgrims were: cough 91.5%, runny nose 79.3%, fever 59.2%, and sore throat 57.1%. The prevalence of hajj pilgrims with triad of cough, subjective fever, and sore throat were 40.1%. The symptoms lasted less than 2 weeks in the majority of cases. Only 3.6% did not suffer from any of these symptoms. Seventy-two percent of hajj pilgrims received influenza vaccination before departure and 72.9% wore facemasks. Influenza vaccination was not associated with any of respiratory symptoms but it was significantly associated with longer duration of sore throat. Wearing masks was significantly associated with sore throat and longer duration of sore throat and fever.
CONCLUSIONS: The prevalence of respiratory symptoms was high among Malaysian hajj pilgrims and the current protective measures seemed inadequate to reduce it. Beside standardization of the term used in hajj studies, more collaborative effort should be taken to reduce respiratory symptoms. The hajj authority should prepare for the challenge of pandemic influenza by providing more healthcare facilities and implementation of more strict measures to reduce the transmission of pandemic influenza strain among hajj pilgrims.

Matched MeSH terms: Influenza, Human/epidemiology; Influenza, Human/prevention & control; Influenza, Human/transmission
Fulltext Using routine surveillance data to estimate the epidemic potential of emerging zoonoses: application to the emergence of US swine origin influenza A H3N2v virus

Cauchemez S, Epperson S, Biggerstaff M, Swerdlow D, Finelli L, Ferguson NM

PLoS Med, 2013;10(3):e1001399.
PMID: 23472057 DOI: 10.1371/journal.pmed.1001399

BACKGROUND: Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations.
METHODS AND FINDINGS: Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1-G; otherwise R can be estimated by 1-F when the case detection rate is low. In more general cases, bounds on R can still be derived.
CONCLUSIONS: We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary.

Matched MeSH terms: Influenza, Human/epidemiology*; Influenza, Human/transmission; Influenza, Human/virology*
Fulltext Chest Radiograph Findings In Novel Swine-Origin Influenza A (H1N1) Virus (S-OIV) Infection: A UKMMC Experience

Norzailin AB, Norhafizah E

Med J Malaysia, 2015 Apr;70(2):93-7.
PMID: 26162384 MyJurnal

OBJECTIVE: 1.To evaluates and recognizes findings in chest radiograph in patients with laboratory-confirmed S-OIV (H1N1) infection treated at UKMMC. 2. To evaluate whether the findings on initial chest radiographs of influenza A (H1N1) patients can help to predict the prognosis.

MATERIAL AND METHODS: Total of 109 adult patients presenting to the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) with flu-like symptoms who were positive for influenza A and these patients had underwent chest radiographs (CXR). The initial CXRs were evaluated for the pattern (consolidation, ground-glass, and reticulation), distribution, and extend of abnormality. The disease is classifies by the clinical severity (mild, moderate or severe illness) and adverse outcome (ventilated, death or recovered well).

RESULTS: The initial CXRs were normal in 56% of cases. The predominant radiographic finding was consolidation, most commonly involving the middle and lower zones (35% of cases). There is no significant association between initial CXR findings with the patient clinical outcome either fully recovered or death/ ventilated.

CONCLUSION: Normal chest radiographs is the most common radiographic finding in S-OIV (H1N1) infection and the most common abnormal lung finding is consolidation. Initial chest radiographs did not determine the patient clinical outcome and a normal initial radiograph could not exclude adverse outcome.

Matched MeSH terms: Influenza, Human
Assessment of antiviral and antibiotic combination treatment in influenza-A H1N1 induced acute kidney injury among hospitalized patients

Ishaqui AA, Khan AH, Syed Sulaiman SA, Alsultan MT, Khan I, Al Nami H

Pak J Pharm Sci, 2019 May;32(3 (Supplementary)):1225-1233.
PMID: 31326884

The aim of the study is to assess and compare the impact of antiviral drug alone and in combination with antibiotic for prevention of Influenza-A H1N1 induced acute kidney injury (AKI) in hospitalized patients. Hospitalized admitted patients with confirmed diagnosis of Influenza-A H1N1 infection were divided into two groups: group 1, which received antiviral (oseltamivir) drug alone and group 2, which received antiviral (oseltamivir) in combination with empirically prescribed antibiotic. Patients of both groups were assessed for incidences of AKI by two criteria i.e Acute Kidney Injury Network (AKIN) and RIFLE. A total of 329 patients (176 for group 1 and 153 for group 2) were enrolled. According to RIFLE criteria, 23(13%) of group 1 and 9(6%) patients of groups 2 were suffered from AKI with statistically significant difference (P<0.05). Also as per AKIN criteria, the incidence of AKI is statistically significantly difference (P<0.05) between both groups with 18(10%) patients and 6(4%) patients of group 1 and 2 respectively. Length of hospitalization was statistically less (P<0.05) in group 2 patients. The incidences of AKI in Influenza-A H1N1 treated with antiviral and antibiotic combination was statistically less as compared to patients who were given antiviral alone for treatment of influenza infection.

Matched MeSH terms: Influenza, Human
Fulltext Directly Acting Antivirals for COVID-19: Where Do We Stand?

Teoh SL, Lim YH, Lai NM, Lee SWH

Front Microbiol, 2020;11:1857.
PMID: 32849448 DOI: 10.3389/fmicb.2020.01857

The outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China in December 2019 has now become a pandemic with no approved therapeutic agent. At the moment, the genomic structure, characteristics, and pathogenic mechanisms of SARS-CoV-2 have been reported. Based upon this information, several drugs including the directly acting antivirals have been proposed to treat people with coronavirus disease 2019 (COVID-19). This rapid review aims to describe the directly acting antivirals that have been examined for use in the management of COVID-19. Searches were conducted in three electronic databases, supplemented with a search on arXiv, bioRxiv, medRxiv, ChinaXiv, ClinicalTrials.gov, and Chinese Clinical Trial Registry for studies examining the use of antivirals in COVID-19 to identify for case reports, case series, observational studies, and randomized controlled studies describing the use of antivirals in COVID-19. Data were extracted independently and presented narratively. A total of 98 studies were included, comprising of 38 published studies and 60 registered clinical trials. These drugs include the broad spectrum antivirals such as umifenovir, protease inhibitors such as lopinavir/ritonavir as well as the RNA-dependent RNA polymerase inhibitors, remdesivir, and favipiravir. Other drugs that have been used include the nucleosidase inhibitors and polymerase acidic endonuclease inhibitors which are currently approved for prevention of influenza infections. While some of the drugs appear promising in small case series and reports, more clinical trials currently in progress are required to provide higher quality evidence.

Matched MeSH terms: Influenza, Human
Fulltext Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway

Sharma S, Chatterjee A, Kumar P, Lal S, Kondabagil K

Viruses, 2020 04 15;12(4).
PMID: 32326380 DOI: 10.3390/v12040444

Micro RNAs (miRNAs) are a class of small non-coding single-stranded RNA, which play an important role in modulating host-Influenza A virus (IAV) crosstalk. The interplay between influenza and miRNA interaction is defined by a plethora of complex mechanisms, which are not fully understood yet. Here, we demonstrate that in IAV infected A549 cells, a synchronous increase was observed in the expression of mTOR up to 24 hpi and significant downregulation at 48 hpi. Additionally, NP of IAV interacts with mTOR and modulates the levels of mTOR mRNA and protein, thus regulating the translation of host cell. RNA sequencing and qPCR analysis of IAV-infected A549 cells and NP transfected cells revealed that miR-101 downregulates mTOR transcripts at later stages of infection. Ectopic expression of miR-101 mimic led to a decrease in expression of NP, a reduction in IAV titer and replication. Moreover, treatment of the cells with Everolimus, a potent inhibitor of mTOR, resulted in an increase of miR-101 transcript levels, which further suppressed the viral protein synthesis. Collectively, the data suggest a novel mechanism that IAV stimulates mTOR pathway at early stages of infection; however, at a later time-point, positive regulation of miR-101 restrains the mTOR expression, and hence, the viral propagation.

Matched MeSH terms: Influenza, Human/genetics*; Influenza, Human/metabolism*; Influenza, Human/virology*
Assessing the effects of time-dependent restrictions and control actions to flatten the curve of COVID-19 in Kazakhstan

Do TD, Gui MM, Ng KY

PeerJ, 2021;9:e10806.
PMID: 33604187 DOI: 10.7717/peerj.10806

This article presents the assessment of time-dependent national-level restrictions and control actions and their effects in fighting the COVID-19 pandemic. By analysing the transmission dynamics during the first wave of COVID-19 in the country, the effectiveness of the various levels of control actions taken to flatten the curve can be better quantified and understood. This in turn can help the relevant authorities to better plan for and control the subsequent waves of the pandemic. To achieve this, a deterministic population model for the pandemic is firstly developed to take into consideration the time-dependent characteristics of the model parameters, especially on the ever-evolving value of the reproduction number, which is one of the critical measures used to describe the transmission dynamics of this pandemic. The reproduction number alongside other key parameters of the model can then be estimated by fitting the model to real-world data using numerical optimisation techniques or by inducing ad-hoc control actions as recorded in the news platforms. In this article, the model is verified using a case study based on the data from the first wave of COVID-19 in the Republic of Kazakhstan. The model is fitted to provide estimates for two settings in simulations; time-invariant and time-varying (with bounded constraints) parameters. Finally, some forecasts are made using four scenarios with time-dependent control measures so as to determine which would reflect on the actual situations better.

Matched MeSH terms: Influenza, Human
Fulltext Knowledge, belief and barriers to adult influenza and pneumococcal vaccination among primary care doctors in Sarawak

Wong, L. K. S., Muthupalaniappen, L., Tie, S. T.

Medicine & Health, 2017;12(2):275-285.
MyJurnal

Adult influenza and pneumococcal vaccinations are grossly underutilized although there is clear benefit in reducing mortality and morbidity among those at risk. The aim of the study was to assess primary care physician’s knowledge on adult influenza and pneumococcal vaccinations, their beliefs and barriers to vaccination. A cross-sectional study using self-administered questionnaires was conducted at eight primary care centres in Kuching, Sarawak. A total of 108 primary care physicians participated in this study. Median age of participants was 29 years (IQR 4.0). The median knowledge score for influenza vaccine was 9 (IQR 3) and for pneumococcal vaccine was 8 (IQR 4). Female participants scored higher compared to their male counterparts for influenza and pneumococcal vaccines (P = 0.005 & 0.007). The highest percentage of correct responses for influenza vaccination was for side effects (75.3%) while the lowest was for contraindications (9.3%). The highest percentage of correct responses for pneumococcal vaccination was for side effects (69.1%) while the lowest was for advocated target groups (6.2%). Most participants believed that pneumococcal and influenza vaccines were safe (92.8 & 99%) and beneficial for patients (89.7 & 93.8%). Cost of influenza and pneumococcal vaccines (94.8% & 96.9%) and their availability (86.6% & 89.7%) were the main barriers to prescribing them. Primary care physicians in the public sector have moderate knowledge of both adult vaccinations. Areas of knowledge paucity and barriers need to be addressed to ensure a more comprehensive health care delivery to the aging Malaysian population.
Keywords: adult, belief, influenza vaccines, knowledge, pneumococcal vaccines

Matched MeSH terms: Influenza, Human

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