Displaying publications 1 - 20 of 104 in total

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  1. Ong NH, Chua CL, Liew JWK, Wan Sulaiman WY, Chan YF, Sam IC, et al.
    Acta Trop, 2020 Aug;208:105472.
    PMID: 32389451 DOI: 10.1016/j.actatropica.2020.105472
    Zika virus (ZIKV) is a mosquito-borne flavivirus with global impact since 2015. Although ZIKV was first isolated from Aedes aegypti in Malaysia in 1965, not much is known about the competency of Malaysian Ae. aegypti to ZIKV. To date only 9 cases of ZIKV have been reported in Malaysia despite the abundance of mosquito vectors. This study aimed to determine the susceptibility of Ae. aegypti to ZIKV, and the impact of sequential infections in Ae. aegypti mosquitoes with DENV serotype 2 (DENV-2) followed by ZIKV. Field-caught urban Ae. aegypti were orally challenged with a Martinique strain of ZIKV, and midgut, head/thorax and saliva were collected at 3, 7 and 14 days post-infection (dpi). At 14 dpi, ZIKV-exposed mosquitoes had infection and dissemination rates of 59% (n=10/17) and 90% (n=9/10), respectively. Average titres of 3.9 and 4.4 log pfu infectious ZIKV were recovered in midgut and head/thorax, respectively. In sequential infection, prior exposure of Ae. aegypti to DENV did not affect the subsequent ZIKV infection in head/thorax albeit with a low sample size. In conclusion, Malaysian urban Ae. aegypti is susceptible to the contemporary Asian lineage of ZIKV. The established and continuous DENV circulation in Ae. aegypti did not suppress ZIKV emergence in Malaysia. Other factors contributing to low level of ZIKV circulation in Malaysia remain to be explored.
  2. Tan CW, Chan YF, Quah YW, Poh CL
    Antiviral Res, 2014 Jul;107:35-41.
    PMID: 24769243 DOI: 10.1016/j.antiviral.2014.04.004
    Enterovirus 71 (EV-71) infections are generally manifested as mild hand, foot and mouth disease, but have been reported to cause severe neurological complications with high mortality rates. Treatment options remain limited due to the lack of antivirals. Octaguanidinium-conjugated morpholino oligomers (vivo-MOs) are single-stranded DNA-like antisense agents that can readily penetrate cells and reduce gene expression by steric blocking of complementary RNA sequences. In this study, inhibitory effects of three vivo-MOs that are complementary to the EV-71 internal ribosome entry site (IRES) and the RNA-dependent RNA polymerase (RdRP) were tested in RD cells. Vivo-MO-1 and vivo-MO-2 targeting the EV-71 IRES showed significant viral plaque reductions of 2.5 and 3.5 log10PFU/ml, respectively. Both vivo-MOs reduced viral RNA copies and viral capsid expression in RD cells in a dose-dependent manner. In contrast, vivo-MO-3 targeting the EV-71 RdRP exhibited less antiviral activity. Both vivo-MO-1 and 2 remained active when administered either 4h before or within 6h after EV-71 infection. Vivo-MO-2 exhibited antiviral activities against poliovirus (PV) and coxsackievirus A16 but vivo-MO-1 showed no antiviral activities against PV. Both the IRES-targeting vivo-MO-1 and vivo-MO-2 inhibit EV-71 RNA translation. Resistant mutants arose after serial passages in the presence of vivo-MO-1, but none were isolated against vivo-MO-2. A single T to C substitution at nucleotide position 533 was sufficient to confer resistance to vivo-MO-1. Our findings suggest that IRES-targeting vivo-MOs are good antiviral candidates for treating early EV-71 infection, and vivo-MO-2 is a more favorable candidate with broader antiviral spectrum against enteroviruses and are refractory to antiviral resistance.
  3. Tan CW, Sam IC, Chong WL, Lee VS, Chan YF
    Antiviral Res, 2017 07;143:186-194.
    PMID: 28457855 DOI: 10.1016/j.antiviral.2017.04.017
    Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log10 PFU viral reduction with IC50value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
  4. Pang YK, Ismail AI, Chan YF, Cheong A, Chong YM, Doshi P, et al.
    BMC Infect Dis, 2021 Jul 05;21(1):644.
    PMID: 34225647 DOI: 10.1186/s12879-021-06360-9
    BACKGROUND: Available data on influenza burden across Southeast Asia are largely limited to pediatric populations, with inconsistent findings.

    METHODS: We conducted a multicenter, hospital-based active surveillance study of adults in Malaysia with community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute exacerbation of asthma (AEBA), who had influenza-like illness ≤10 days before hospitalization. We estimated the rate of laboratory-confirmed influenza and associated complications over 13 months (July 2018-August 2019) and described the distribution of causative influenza strains. We evaluated predictors of laboratory-confirmed influenza and severe clinical outcomes using multivariate analysis.

    RESULTS: Of 1106 included patients, 114 (10.3%) were influenza-positive; most were influenza A (85.1%), with A/H1N1pdm09 being the predominant circulating strain during the study following a shift from A/H3N2 from January-February 2019 onwards. In multivariate analyses, an absence of comorbidities (none versus any comorbidity [OR (95%CI), 0.565 (0.329-0.970)], p = 0.038) and of dyspnea (0.544 (0.341-0.868)], p = 0.011) were associated with increased risk of influenza positivity. Overall, 184/1106 (16.6%) patients were admitted to intensive care or high-dependency units (ICU/HDU) (13.2% were influenza positive) and 26/1106 (2.4%) died (2.6% were influenza positive). Males were more likely to have a severe outcome (ICU/HDU admission or death).

    CONCLUSIONS: Influenza was a significant contributor to hospitalizations associated with CAP, AECOPD and AEBA. However, it was not associated with ICU/HDU admission in this population. Study registration, NMRR ID: NMRR-17-889-35,174.

  5. Khor CS, Sam IC, Hooi PS, Quek KF, Chan YF
    BMC Pediatr, 2012;12:32.
    PMID: 22429933 DOI: 10.1186/1471-2431-12-32
    Viral respiratory tract infections (RTI) are relatively understudied in Southeast Asian tropical countries. In temperate countries, seasonal activity of respiratory viruses has been reported, particularly in association with temperature, while inconsistent correlation of respiratory viral activity with humidity and rain is found in tropical countries. A retrospective study was performed from 1982-2008 to investigate the viral etiology of children (≤ 5 years old) admitted with RTI in a tertiary hospital in Kuala Lumpur, Malaysia.
  6. Kandiah N, Ong PA, Yuda T, Ng LL, Mamun K, Merchant RA, et al.
    CNS Neurosci Ther, 2019 02;25(2):288-298.
    PMID: 30648358 DOI: 10.1111/cns.13095
    BACKGROUND: The Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer's disease (AD).

    METHODS: To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence-based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease.

    RESULTS: Key randomized trials and robust meta-analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761® versus placebo in patients with mild-to-moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk-benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta-analyses have not supported this association.

    CONCLUSIONS: The Expert Group foresee an important role for EGb 761® , used alone or as an add-on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.

  7. Kandiah N, Chan YF, Chen C, Dasig D, Dominguez J, Han SH, et al.
    CNS Neurosci Ther, 2021 Feb;27(2):149-162.
    PMID: 33352000 DOI: 10.1111/cns.13536
    BACKGROUND: Mild cognitive impairment (MCI) is a neurocognitive state between normal cognitive aging and dementia, with evidence of neuropsychological changes but insufficient functional decline to warrant a diagnosis of dementia. Individuals with MCI are at increased risk for progression to dementia; and an appreciable proportion display neuropsychiatric symptoms (NPS), also a known risk factor for dementia. Cerebrovascular disease (CVD) is thought to be an underdiagnosed contributor to MCI/dementia. The Ginkgo biloba extract, EGb 761® , is increasingly being used for the symptomatic treatment of cognitive disorders with/without CVD, due to its known neuroprotective effects and cerebrovascular benefits.

    AIMS: To present consensus opinion from the ASian Clinical Expert group on Neurocognitive Disorders (ASCEND) regarding the role of EGb 761® in MCI.

    MATERIALS & METHODS: The ASCEND Group reconvened in September 2019 to present and critically assess the current evidence on the general management of MCI, including the efficacy and safety of EGb 761® as a treatment option.

    RESULTS: EGb 761® has demonstrated symptomatic improvement in at least four randomized trials, in terms of cognitive performance, memory, recall and recognition, attention and concentration, anxiety, and NPS. There is also evidence that EGb 761® may help delay progression from MCI to dementia in some individuals.

    DISCUSSION: EGb 761® is currently recommended in multiple guidelines for the symptomatic treatment of MCI. Due to its beneficial effects on cerebrovascular blood flow, it is reasonable to expect that EGb 761® may benefit MCI patients with underlying CVD.

    CONCLUSION: As an expert group, we suggest it is clinically appropriate to incorporate EGb 761® as part of the multidomain intervention for MCI.

  8. Ng KT, Oong XY, Lim SH, Chook JB, Takebe Y, Chan YF, et al.
    Clin Infect Dis, 2018 07 02;67(2):261-268.
    PMID: 29385423 DOI: 10.1093/cid/ciy063
    Background: Rhinovirus (RV) is one of the main viral etiologic agents of acute respiratory illnesses. Despite the heightened disease burden caused by RV, the viral factors that increase the severity of RV infection, the transmission pattern, and seasonality of RV infections remain unclear.

    Methods: An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014.

    Results: The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P < .001) was observed, from 883 viral copies/µL at 1-2 days after symptom onset to 312 viral copies/µL at 3-4 days and 158 viral copies/µL at 5-7 days, before declining to 35 viral copies/µL at ≥8 days. In comparison with RV-A (median VL, 217 copies/µL) and RV-B (median VL, 275 copies/µL), RV-C-infected subjects produced higher VL (505 copies/µL; P < .001). Importantly, higher RV VL (median, 348 copies/µL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P = .017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate.

    Conclusions: Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV.

  9. Chiam CW, Chan YF, Loong SK, Yong SS, Hooi PS, Sam IC
    Diagn Microbiol Infect Dis, 2013 Oct;77(2):133-7.
    PMID: 23886793 DOI: 10.1016/j.diagmicrobio.2013.06.018
    Quantitative real-time polymerase chain reaction (qRT-PCR) is useful for diagnosis and studying virus replication. We developed positive- and negative-strand qRT-PCR assays to detect nsP3 of chikungunya virus (CHIKV), a positive-strand RNA alphavirus that causes epidemic fever, rash, and arthritis. The positive- and negative-strand qRT-PCR assays had limits of quantification of 1 and 3 log10 RNA copies/reaction, respectively. Compared to a published E1 diagnostic assay using 30 laboratory-confirmed clinical samples, the positive-strand nsP3 qRT-PCR assay had higher R(2) and efficiency and detected more positive samples. Peak viral load of 12.9 log(10) RNA copies/mL was reached on day 2 of illness, and RNA was detectable up to day 9, even in the presence of anti-CHIKV IgM. There was no correlation between viral load and persistent arthralgia. The positive-strand nsP3 assay is suitable for diagnosis, while the negative-strand nsP3 assay, which uses tagged primers to increase specificity, is useful for study of active viral replication kinetics.
  10. Sam IC, Kahar-Bador M, Chan YF, Loong SK, Mohd Nor Ghazali F
    Diagn Microbiol Infect Dis, 2008 Dec;62(4):437-9.
    PMID: 18842374 DOI: 10.1016/j.diagmicrobio.2008.07.016
    The 1st 9 clinical isolates of multisensitive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) from Malaysia carry SCCmec type IV and predominantly cause skin and soft-tissue infections. Seven were classified as nosocomially acquired. There was considerable clonal diversity, with both pandemic and novel multilocus sequence types detected. CA-MRSA rates appear to be increasing in our hospital, warranting close surveillance.
  11. Chan YF, AbuBaker S
    Emerg Infect Dis, 2004 Aug;10(8):1468-70.
    PMID: 15496251
    Hand, foot and mouth disease (HFMD) is a common illness of infants and young children <10 years of age. It is characterized by fever, ulcers in the oral cavity, and rashes with blisters that appear on the palm and sole. The most common causal agents of HFMD are coxsackievirus A16 (CV-A16) and human enterovirus 71 (HEV71), but other enteroviruses, including CV-A5 and CV-A10, can also cause it. When caused by CV-A16 infection, it is usually a mild disease, and patients normally recover without requiring any special medical attention.
  12. Sam IC, Chua CL, Rovie-Ryan JJ, Fu JY, Tong C, Sitam FT, et al.
    Emerg Infect Dis, 2015 Sep;21(9):1683-5.
    PMID: 26291585 DOI: 10.3201/eid2109.150439
  13. Chua CL, Chan YF, Andu ESGS, Rovie-Ryan JJ, Sitam FT, Verasahib K, et al.
    Emerg Infect Dis, 2019 02;25(2):374-376.
    PMID: 30666941 DOI: 10.3201/eid2502.180258
    We tested a sample of 234 wild long-tailed macaques (Macaca fascicularis) trapped in Peninsular Malaysia in 2009, 2010, and 2016 for Zika virus RNA and antibodies. None were positive for RNA, and only 1.3% were seropositive for neutralizing antibodies. Long-tailed macaques are unlikely to be reservoirs for Zika virus in Malaysia.
  14. Hsieh CF, Jheng JR, Lin GH, Chen YL, Ho JY, Liu CJ, et al.
    Emerg Microbes Infect, 2020 Dec;9(1):1194-1205.
    PMID: 32397909 DOI: 10.1080/22221751.2020.1767512
    Enterovirus A71 (EV-A71), a positive-stranded RNA virus of the Picornaviridae family, may cause neurological complications or fatality in children. We examined specific factors responsible for this virulence using a chemical genetics approach. Known compounds from an anti-EV-A71 herbal medicine, Salvia miltiorrhiza (Danshen), were screened for anti-EV-A71. We identified a natural product, rosmarinic acid (RA), as a potential inhibitor of EV-A71 by cell-based antiviral assay and in vivo mouse model. Results also show that RA may affect the early stage of viral infection and may target viral particles directly, thereby interfering with virus-P-selectin glycoprotein ligand-1 (PSGL1) and virus-heparan sulfate interactions without abolishing the interaction between the virus and scavenger receptor B2 (SCARB2). Sequencing of the plaque-purified RA-resistant viruses revealed a N104K mutation in the five-fold axis of the structural protein VP1, which contains positively charged amino acids reportedly associated with virus-PSGL1 and virus-heparan sulfate interactions via electrostatic attraction. The plasmid-derived recombinant virus harbouring this mutation was confirmed to be refractory to RA inhibition. Receptor pull-down showed that this non-positively charged VP1-N104 is critical for virus binding to heparan sulfate. As the VP1-N104 residue is conserved among different EV-A71 strains, RA may be useful for inhibiting EV-A71 infection, even for emergent virus variants. Our study provides insight into the molecular mechanism of virus-host interactions and identifies a promising new class of inhibitors based on its antiviral activity and broad spectrum effects against a range of EV-A71.
  15. Tan CW, Huan Hor CH, Kwek SS, Tee HK, Sam IC, Goh ELK, et al.
    Emerg Microbes Infect, 2019;8(1):426-437.
    PMID: 30898036 DOI: 10.1080/22221751.2019.1590130
    The emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon antagonist rather than an entry receptor, the exact entry mechanism remains unresolved. Here we report that cell surface sialic acid plays an important role in ZIKV infection. Removal of cell surface sialic acid by neuraminidase significantly abolished ZIKV infection in Vero cells and human induced-pluripotent stem cells-derived neural progenitor cells. Furthermore, knockout of the sialic acid biosynthesis gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase resulted in significantly less ZIKV infection of both African and Asian lineages. Huh7 cells deficient in α2,3-linked sialic acid through knockout of ST3 β-galactoside-α2,3-sialyltransferase 4 had significantly reduced ZIKV infection. Removal of membrane-bound, un-internalized virus with pronase treatment revealed the role of sialic acid in ZIKV internalization but not attachment. Sialyllactose inhibition studies showed that there is no direct interaction between sialic acid and ZIKV, implying that sialic acid could be mediating ZIKV-receptor complex internalization. Identification of α2,3-linked sialic acid as an important host factor for ZIKV internalization provides new insight into ZIKV infection and pathogenesis.
  16. Tee HK, Zainol MI, Sam IC, Chan YF
    Expert Rev Anti Infect Ther, 2021 06;19(6):733-747.
    PMID: 33183118 DOI: 10.1080/14787210.2021.1851194
    Introduction: Hand, foot, and mouth disease caused by enterovirus A71 (EV-A71) is more frequently associated with neurological complications and deaths compared to other enteroviruses.Areas covered: The authors discuss current understanding of the neuropathogenesis of EV-A71 based on various clinical, human, and animal model studies. The authors discuss the important advancements in virus entry, virus dissemination, and neuroinvasion. The authors highlight the role of host immune system, host genetic factors, viral quasispecies, and heparan sulfate in EV-A71 neuropathogenesis.Expert opinion: Comparison of EV-A71 with EV-D68 and PV shows similarity in primary target sites and dissemination to the central nervous system. More research is needed to understand cellular tropisms, persistence of EV-A71, and other possible invasion routes. EV-A71 infection has varied clinical manifestations which may be attributed to multiple receptors usage. Future development of antivirals and vaccines should target neurotropic enteroviruses. Repurposing drug and immunomodulators used in combination could reduce the severity of EV-A71 infection. Only a few drugs have been tested in clinical trials, and in the absence of antiviral and vaccines (except China), active virus surveillance, good hand hygiene, and physical distancing should be advocated. A better understanding of EV-A71 neuropathogenesis is critical for antiviral and multivalent vaccines development.
  17. Khaw YS, Chan YF, Jafar FL, Othman N, Chee HY
    Front Microbiol, 2016;7:543.
    PMID: 27199901 DOI: 10.3389/fmicb.2016.00543
    Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5' and 3' non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63-81% among themselves and 63-96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection.
  18. Vythilingam I, Sam JI, Chan YF, Khaw LT, Sulaiman WY
    Front Microbiol, 2016;7:1452.
    PMID: 27679623 DOI: 10.3389/fmicb.2016.01452
    Zika virus (ZIKV) has now become a global public health concern. The vectors for ZIKV are Aedes aegypti and A. albopictus. Both these mosquitoes are predominant in Southeast Asia and are also responsible for the spread of other arboviral diseases like dengue virus and chikungunya virus. The incidence of dengue has been increasing over the years and this is of concern to public health workers. Simple laboratory tools for the detection of ZIKV is also lacking. In the absence of drugs and vaccine for these arboviral diseases, vector control is the main option for surveillance and control. Aedes larval surveys have been the hallmark of dengue control along with larviciding and fogging when cases are reported. However, we need new paradigms and options for control of these vectors. The current situation in Southeast Asia clearly proves that effective strategies for vector control need to be proactive and not reactive. This will be the way forward to control epidemics of these diseases inclusive of ZIKV until a vaccine becomes available.
  19. Leifels M, Khalilur Rahman O, Sam IC, Cheng D, Chua FJD, Nainani D, et al.
    ISME Commun, 2022;2(1):107.
    PMID: 36338866 DOI: 10.1038/s43705-022-00191-8
    The human population has doubled in the last 50 years from about 3.7 billion to approximately 7.8 billion. With this rapid expansion, more people live in close contact with wildlife, livestock, and pets, which in turn creates increasing opportunities for zoonotic diseases to pass between animals and people. At present an estimated 75% of all emerging virus-associated infectious diseases possess a zoonotic origin, and outbreaks of Zika, Ebola and COVID-19 in the past decade showed their huge disruptive potential on the global economy. Here, we describe how One Health inspired environmental surveillance campaigns have emerged as the preferred tools to monitor human-adjacent environments for known and yet to be discovered infectious diseases, and how they can complement classical clinical diagnostics. We highlight the importance of environmental factors concerning interactions between animals, pathogens and/or humans that drive the emergence of zoonoses, and the methodologies currently proposed to monitor them-the surveillance of wastewater, for example, was identified as one of the main tools to assess the spread of SARS-CoV-2 by public health professionals and policy makers during the COVID-19 pandemic. One-Health driven approaches that facilitate surveillance, thus harbour the potential of preparing humanity for future pandemics caused by aetiological agents with environmental reservoirs. Via the example of COVID-19 and other viral diseases, we propose that wastewater surveillance is a useful complement to clinical diagnosis as it is centralized, robust, cost-effective, and relatively easy to implement.
  20. Chan YF, Sam IC, AbuBakar S
    Infect Genet Evol, 2010 Apr;10(3):404-12.
    PMID: 19465162 DOI: 10.1016/j.meegid.2009.05.010
    Human enterovirus 71 (EV-71) is genotyped for molecular epidemiological investigation mainly using the two structural genes, VP1 and VP4. Based on these, EV-71 is divided into three genotypes, A, B and C, and within the genotypes B and C, there are further subgenotypes, B1-B5 and C1-C5. Classification using these genes is useful but gives incomplete phylogenetic information. In the present study, the phylogenetic relationships amongst all the known EV-71 and human enterovirus A (HEV-A) isolates with complete genome sequences were examined. A different tree topology involving EV-71 isolates of subgenotypes, C4 and B5 was obtained in comparison to that drawn using VP1. The nucleotide sequence divergence of the C4 isolates was 18.11% (17-20%) when compared to other isolates of subgenotype C. However, this positions the C4 isolates within the cut-off divergence value of 17-22% used to designate the virus genotypes. Hence, it is proposed here that C4 should be designated as a new genotype D. In addition, the subgenotype B5 isolates had an average nucleotide divergence of only 6.14% (4-8%) when compared to other subgenotype B4 isolates. This places the B5 isolates within the subgenotype B4. It is proposed here that the B5 isolates to be redesignated as B4. With the newly proposed genotype D and inclusion of subgenotype B5 within B4, the average nucleotide divergence between genotypes was 18.99% (17-22%). Inter- and intra-subgenotype average divergences were 12.02% (10-14%) and 3.92% (1-10%), respectively. A phylogenetic tree built using the full genome sequences is robust as it takes into consideration changes in the sequences of both the structural and non-structural genes. Similar nucleotide similarities, however, were obtained if only VP1 and 3D RNA polymerase genes were used. Furthermore, addition of 3D RNA polymerase sequences will also show recombination events. Hence, in the absence of full genome sequences, it is proposed here that a combination of VP1 and 3D RNA polymerase gene sequences be used for initial genotyping of EV-71 isolates.
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