ORCID Profile
0000-0002-2858-2087
Current Organisations
The Hong Kong Polytechnic University School of Nursing
,
University of Oxford
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Publisher: American Society for Microbiology
Date: 02-2019
DOI: 10.1128/AAC.01739-18
Abstract: Amphotericin B deoxycholate (DAmB) is a first-line agent for the initial treatment of talaromycosis. However, little is known about the population pharmacokinetics and pharmacodynamics of DAmB for talaromycosis.
Publisher: Public Library of Science (PLoS)
Date: 02-08-2016
Publisher: Springer Science and Business Media LLC
Date: 19-10-2018
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: F1000 Research Ltd
Date: 20-06-2018
DOI: 10.12688/WELLCOMEOPENRES.14006.2
Abstract: Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rif icin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rif icin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rif icin and isoniazid therapy.
Publisher: Public Library of Science (PLoS)
Date: 28-03-2008
Publisher: F1000 Research Ltd
Date: 20-03-2018
DOI: 10.12688/WELLCOMEOPENRES.14006.1
Abstract: Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rif icin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rif icin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rif icin and isoniazid therapy.
Publisher: Oxford University Press (OUP)
Date: 30-05-2016
DOI: 10.1093/JAC/DKW173
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2015
Publisher: Elsevier BV
Date: 10-2018
Publisher: American Society of Tropical Medicine and Hygiene
Date: 06-05-2015
Publisher: Cold Spring Harbor Laboratory
Date: 09-10-2023
Publisher: Oxford University Press (OUP)
Date: 05-04-2019
DOI: 10.1093/CID/CIZ262
Abstract: Pretreatment predictors of death from tuberculous meningitis (TBM) are well established, but whether outcome can be predicted more accurately after the start of treatment by updated clinical variables is unknown. Hence, we developed and validated models that dynamically predict mortality using time-updated Glasgow Coma Scale (GCS) and plasma sodium measurements, together with patient baseline characteristics. We included 1048 adults from 4 TBM studies conducted in southern Vietnam from 2004 to 2016. We used a landmarking approach to predict death within 120 days after treatment initiation using time-updated data during the first 30 days of treatment. Separate models were built for patients with and without human immunodeficiency virus (HIV) infection. We used the area under the receiver operating characteristic curve (AUC) to evaluate performance of the models at days 10, 20, and 30 of treatment to predict mortality by 60, 90, and 120 days. Our internal validation was corrected for overoptimism using bootstrap. We provide a web-based application that computes mortality risk within 120 days. Higher GCS indicated better prognosis in all patients. In HIV-infected patients, higher plasma sodium was uniformly associated with good prognosis, whereas in HIV-uninfected patients the association was heterogeneous over time. The bias-corrected AUC of the models ranged from 0.82 to 0.92 and 0.81 to 0.85 in HIV-uninfected and HIV-infected in iduals, respectively. The models outperformed the previously published baseline models. Time-updated GCS and plasma sodium measurements improved predictions based solely on information obtained at diagnosis. Our models may be used in practice to define those with poor prognosis during treatment.
Publisher: BMJ
Date: 06-2019
Publisher: Public Library of Science (PLoS)
Date: 06-01-2017
Publisher: eLife Sciences Publications, Ltd
Date: 28-09-2021
DOI: 10.7554/ELIFE.68929
Abstract: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with hotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential. Open label randomized controlled trial. Participants received standard care – hotericin combined with fluconazole for the first 2 weeks – or standard care plus tamoxifen 300 mg/day. The primary end point was Early Fungicidal Activity (EFA) – the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration t2/show/NCT03112031 . Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (−0.48log10 colony-forming units/mL/CSF control arm versus −0.49 tamoxifen arm, difference −0.005log10CFU/ml/day, 95% CI: −0.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation. High-dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed. The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.
Publisher: Microbiology Society
Date: 10-2015
DOI: 10.1099/JMM.0.000137
Publisher: F1000 Research Ltd
Date: 04-09-2019
DOI: 10.12688/WELLCOMEOPENRES.15408.1
Abstract: Background: Injectable interferon-based therapies have been used to treat hepatitis C virus (HCV) infection since 1991. International guidelines have now moved away from interferon-based therapy towards direct-acting antiviral (DAA) tablet regimens, because of their superior efficacy, excellent side-effect profiles, and ease of administration. Initially DAA drugs were prohibitively expensive for most healthcare systems. Access is now improving through the procurement of low-cost, generic DAAs acquired through voluntary licenses. However, HCV treatment costs vary widely, and many countries are struggling with DAA treatment scale-up. This is not helped by the limited cost data and economic evaluations from low- and middle-income countries to support HCV policy decisions. We conducted a detailed analysis of the costs of treating chronic HCV infection with interferon-based therapy in Vietnam. Understanding these costs is important for performing necessary economic evaluations of novel treatment strategies. Methods: We conducted an analysis of the direct medical costs of treating HCV infection with interferon alpha (IFN) and pegylated-interferon alpha (Peg-IFN), in combination with ribavirin, from the health sector perspective at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, in 2017. Results: The total cost of the IFN treatment regimen was estimated to range between US$1,120 and US$1,962. The total cost of the Peg-IFN treatment regimen was between US$2,156 and US$5,887. Drug expenses were the biggest contributor to the total treatment cost (54-89%) and were much higher for the Peg-IFN regimen. Conclusions: We found that treating HCV with IFN or Peg-IFN resulted in significant direct medical costs. Of concern, we found that all patients incurred substantial out-of-pocket costs, including those receiving the maximum level of support from the national health insurance programme. This cost data highlights the potential savings and importance of increased access to generic DAAs in low- and middle-income countries and will be useful within future economic evaluations.
Publisher: F1000 Research Ltd
Date: 11-09-2020
DOI: 10.12688/WELLCOMEOPENRES.15408.2
Abstract: Background: Injectable interferon-based therapies have been used to treat hepatitis C virus (HCV) infection since 1991. International guidelines have now moved away from interferon-based therapy towards direct-acting antiviral (DAA) tablet regimens, because of their superior efficacy, excellent side-effect profiles, and ease of administration. Initially DAA drugs were prohibitively expensive for most healthcare systems. Access is now improving through the procurement of low-cost, generic DAAs acquired through voluntary licenses. However, HCV treatment costs vary widely, and many countries are struggling with DAA treatment scale-up. This is not helped by the limited cost data and economic evaluations from low- and middle-income countries to support HCV policy decisions. We conducted a detailed analysis of the costs of treating chronic HCV infection with interferon-based therapy in Vietnam. Understanding these costs is important for performing necessary economic evaluations of novel treatment strategies. Methods: We conducted an analysis of the direct medical costs of treating HCV infection with interferon alpha (IFN) and pegylated-interferon alpha (Peg-IFN), in combination with ribavirin, from the health sector perspective at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, in 2017. Results: The total cost of the IFN treatment regimen was estimated to range between US$1,120 and US$1,962. The total cost of the Peg-IFN treatment regimen was between US$2,156 and US$5,887. Drug expenses were the biggest contributor to the total treatment cost (54-89%) and were much higher for the Peg-IFN regimen. Conclusions: We found that treating HCV with IFN or Peg-IFN resulted in significant direct medical costs. Of concern, we found that all patients incurred substantial out-of-pocket costs, including those receiving the maximum level of support from the national health insurance programme. This cost data highlights the potential savings and importance of increased access to generic DAAs in low- and middle-income countries and will be useful within future economic evaluations.
Publisher: Springer Science and Business Media LLC
Date: 22-06-2016
DOI: 10.1038/SREP28291
Abstract: Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging infection due to its high levels of antimicrobial resistance. Multidrug resistant A. baumannii has risen rapidly in Vietnam, where colistin is becoming the drug of last resort for many infections. In this study we generated spontaneous colistin resistant progeny (up to μg/μl) from four colistin susceptible Vietnamese isolates and one susceptible reference strain (MIC .5 μg/μl). Whole genome sequencing was used to identify single nucleotide mutations that could be attributed to the reduced colistin susceptibility. We identified six lpxACD and three pmrB mutations, the majority of which were novel. In addition, we identified further mutations in six A. baumannii genes ( vacJ , pldA , ttg2C , pheS and conserved hypothetical protein) that we hypothesise have a role in reduced colistin susceptibility. This study has identified additional mutations that may be associated with colistin resistance through novel resistance mechanisms. Our work further demonstrates how rapidly A. baumannii can generate resistance to a last resort antimicrobial and highlights the need for improved surveillance to identified A. baumannii with an extensive drug resistance profile.
Publisher: JMIR Publications Inc.
Date: 03-05-2020
Abstract: eporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel. his study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly. n offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language (R Project for Statistical Computing). The application can be run by double clicking on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested on Microsoft Windows 10 and 7 using open access ex le data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People’s Democratic Republic, Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam. e developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyze their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and CSV formats). The data files could be those exported from WHONET or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from www.amass.website/. The participating hospitals tested the application and deposited their AMR surveillance reports in an open access data repository. he AMASS is a useful tool to support the generation and sharing of AMR surveillance reports.
Publisher: Public Library of Science (PLoS)
Date: 17-08-2020
Publisher: F1000 Research Ltd
Date: 11-05-2018
DOI: 10.12688/WELLCOMEOPENRES.11558.2
Abstract: Background: Since 1962, enterovirus D68 (EV-D68) has been implicated in multiple outbreaks and sporadic cases of respiratory infection worldwide, especially in the USA and Europe with an increasing frequency between 2010 and 2014. We describe the detection, associated clinical features and molecular characterization of EV-D68 in central and southern Viet Nam between 2009 and 2015. Methods: Enterovirus/rhinovirus PCR positive respiratory or CSF s les taken from children and adults with respiratory/central nervous system infections in Viet Nam were tested by an EV-D68 specific PCR. The included s les were derived from 3 different observational studies conducted at referral hospitals across central and southern Viet Nam 2009 2015. Whole-genome sequencing was carried out using a MiSeq based approach. Phylogenetic reconstruction and estimation of evolutionary rate and recombination were carried out in BEAST and Recombination Detection Program, respectively. Results: EV-D68 was detected in 21/625 (3.4%) enterovirus/rhinovirus PCR positive respiratory s les but in none of the 15 CSF. All the EV-D68 patients were young children (age range: 11.8 – 24.5 months) and had moderate respiratory infections. Phylogenetic analysis suggested that the Vietnamese sequences clustered with those from Asian countries, of which 9 fell in the B1 clade, and the remaining sequence was identified within the A2 clade. One intra sub-clade recombination event was detected, representing the second reported recombination within EV-D68. The evolutionary rate of EV-D68 was estimated to be 5.12E -3 substitutions/site/year. Phylogenetic analysis indicated that the virus was imported into Viet Nam in 2008. Conclusions: We have demonstrated for the first time EV-D68 has been circulating at low levels in Viet Nam since 2008, associated with moderate acute respiratory infection in children. EV-D68 in Viet Nam is most closely related to Asian viruses, and clusters separately from recent US and European viruses that were suggested to be associated with acute flaccid paralysis.
Publisher: Springer Science and Business Media LLC
Date: 23-10-2019
DOI: 10.1038/S41467-019-12823-0
Abstract: Shigella sonnei increasingly dominates the international epidemiological landscape of shigellosis. Treatment options for S. sonnei are dwindling due to resistance to several key antimicrobials, including the fluoroquinolones. Here we analyse nearly 400 S. sonnei whole genome sequences from both endemic and non-endemic regions to delineate the evolutionary history of the recently emergent fluoroquinolone-resistant S. sonnei . We reaffirm that extant resistant organisms belong to a single clonal expansion event. Our results indicate that sequential accumulation of defining mutations ( gyrA -S83L, parC -S80I, and gyrA -D87G) led to the emergence of the fluoroquinolone-resistant S. sonnei population around 2007 in South Asia. This clone was then transmitted globally, resulting in establishments in Southeast Asia and Europe. Mutation analysis suggests that the clone became dominant through enhanced adaptation to oxidative stress. Experimental evolution reveals that under fluoroquinolone exposure in vitro, resistant S. sonnei develops further intolerance to the antimicrobial while the susceptible counterpart fails to attain complete resistance.
Publisher: American Society for Microbiology
Date: 29-12-2016
Abstract: To document the viral zoonotic risks in Vietnam, fecal s les were systematically collected from a number of mammals in southern Vietnam and subjected to agnostic deep sequencing. We describe here novel Vietnamese bunyavirus sequences detected in bat feces. The complete L and S segments from 14 viruses were determined.
Publisher: Elsevier BV
Date: 02-2012
Publisher: Oxford University Press (OUP)
Date: 04-2017
Publisher: Springer Science and Business Media LLC
Date: 07-06-2007
Abstract: Tuberculous meningitis (TBM) results from the haematogenous dissemination of Mycobacterium tuberculosis from the lung to the brain. Dissemination is believed to occur early during infection, before the development of adaptive immunity. Toll-like receptor 2 (TLR2) mediates recognition of M. tuberculosis and initiates the innate immune response to infection. We hypothesized that polymorphisms in the TLR2 gene influence bacterial dissemination and the development of TBM. A case-control study was designed to test the hypothesis. Cases of bacteriologically confirmed pulmonary tuberculosis (TB) (n=183) and TBM (n=175), and cord blood controls (n=389) were enrolled in Vietnam. TLR2 genotype 597CC was associated with susceptibility to TB (odds ratio (OR)=2.22, 95% confidence interval (CI): 1.23-3.99). The association was found with meningeal rather than pulmonary TB (TBM vs control, OR=3.26, 95% CI: 1.72-6.18), and was strongest when miliary TB was found on chest radiography (controls vs TBM with miliary TB, OR=5.28, 95% CI: 2.20-12.65). Furthermore, the association increased with the severity of neurologic symptoms (grade I TBM, OR=1.93, 95% CI: 0.54-6.92 grade II, OR=3.32, 95% CI: 0.84-13.2 and grade III, OR=5.70, 95% CI: 1.81-18.0). These results demonstrate a strong association of TLR2 SNP T597C with the development of TBM and miliary TB and indicate that TLR2 influences the dissemination of M. tuberculosis.
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.EJON.2012.07.010
Abstract: Notwithstanding the advances in medical treatment, childhood cancer survivors are at risk of adverse physical, psychological and social effects of the cancer treatment. The purpose of this study was to examine the impact of cancer and its treatments on the physical, psychological and social well-being of Hong Kong Chinese childhood cancer survivors. A total of 137 childhood cancer survivors (aged 9-16 years), who had their medical follow-up in an oncology out-patient clinic were invited to participate in the study. Participants were asked to respond to the standardized measures of depressive symptoms and self-esteem. Additionally, 15 participants from the group were selected for a semi-structured interview. The results revealed that more than half of the participants presented depressive symptoms. Results also found that the mean depressive symptom scores for childhood cancer survivors were statistically significant higher than those of school children without cancer (p = 0.01), while the mean self-esteem scores for the survivors were statistically significant lower (p < 0.01). Additionally, qualitative interviews indicated that cancer and its treatments have great impact on the daily life of childhood cancer survivors. The study reveals that cancer and its treatments have a great impact on the physical, psychological and social well-being of survivors. It is essential for healthcare professionals to develop appropriate interventions with the aim of promoting physical, psychological and social well-being for these children. Most importantly, it is crucial to help them develop a positive view of the impact that the cancer experience has upon their lives.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 04-2018
Publisher: Elsevier BV
Date: 2020
Publisher: Oxford University Press (OUP)
Date: 15-10-2006
DOI: 10.1086/507907
Publisher: Massachusetts Medical Society
Date: 11-10-2018
Publisher: Wiley
Date: 27-06-2023
DOI: 10.1111/JOCN.16817
Abstract: This study aimed to capture and explore family caregivers' lived experience of caring for hospitalised patients with cancer during the lockdown. The unprecedented lockdown episodes due to COVID‐19 have brought significant changes in the hospital visiting policies and caregiving practices. As part of the precautionary measures for hospital visits, the bedside companion was restricted to one caregiver for patients with cancer in Shanghai hospitals. This study adopted a descriptive phenomenological approach. Data were collected among 20 family caregivers recruited from the Oncology department of a tertiary hospital in Shanghai in May 2022, using purposive s ling method and followed by unstructured, open‐ended interviews. Colaizzi's seven‐step data analysis method was used to analyse the data to reveal the emergent themes and subthemes of the phenomenon. Four themes were generated on family caregivers' lived experience of caring for hospitalised patients with cancer during the lockdown, including (1) Feeling scared for the patient (2) Living a life feeling trapped under COVID‐19 surveillance (3) Feeling neglected and unseen (4) Growing resilience and appreciation. The lockdown exacerbated the burden of family caregivers when they cared for the hospitalised patients with cancer during the lockdown period. However, positive reframing of the lived experience facilitated their coping with the challenging situation. Findings from this study highlighted the potential proactive roles the healthcare providers could play in improving family caregivers' health and supporting them during and beyond the COVID‐19 pandemic. The study adhered to relevant EQUATOR guidelines the study was reported according to the COREQ checklist. Family caregivers of patients with cancer were involved in data collection and member‐checking of the transcripts and interpretations of their experiences.
Publisher: F1000 Research Ltd
Date: 09-01-2017
DOI: 10.12688/WELLCOMEOPENRES.10042.2
Abstract: As part of an ongoing effort to generate complete genome sequences of hand, foot and mouth disease-causing enteroviruses directly from clinical specimens, two complete coding sequences and two partial genomic sequences of human bocavirus 1 (n=3) and 2 (n=1) were co- lified and sequenced, representing the first genome sequences of human bocaviruses from Vietnam. The sequences may aid future study aiming at understanding the evolution of the virus.
Publisher: Oxford University Press (OUP)
Date: 04-05-2017
DOI: 10.1093/CID/CIX230
Publisher: eLife Sciences Publications, Ltd
Date: 27-02-2018
DOI: 10.7554/ELIFE.33478
Abstract: Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability the number of grade 3 and 4 and serious adverse events and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. 41 participants were randomised to placebo, 39 to aspirin 81 mg/day, and 40 to aspirin 1000 mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120 (76.7%) and baseline brain imaging revealed ≥1 infarct in 40/114 (35.1%) participants. The primary safety outcome occurred in 5/36 (13.9%) given placebo, and in 8/35 (22.9%) and 8/40 (20.0%) given 81 mg and 1000 mg aspirin, respectively (p=0.59). The primary efficacy outcome occurred in 11/38 (28.9%) given placebo, 8/36 (22.2%) given aspirin 81 mg, and 6/38 (15.8%) given 1000 mg aspirin (p=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (P heterogeneity = 0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32 (34.4%) events in placebo vs. 4/27 (14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000 mg p=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A 2 and upregulation of pro-resolving CSF protectins. The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial.
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 15-11-2018
DOI: 10.2807/1560-7917.ES.2018.23.46.1800590
Abstract: Since January 2018, over 53,000 hospitalisations and six deaths due to hand, foot and mouth disease (HFMD) have occurred across Vietnam with most cases from September onward. In a large tertiary referral hospital, Ho Chi Minh City, enterovirus A71 subgenogroup C4 was predominant, while B5 was only sporadically detected. The re-emergence of C4 after causing a severe HFMD outbreak with 200 deaths in 2011–12 among susceptible young children raises concern of another impending severe outbreak.
Publisher: Oxford University Press (OUP)
Date: 31-05-2018
DOI: 10.1093/CID/CIY447
Publisher: Oxford University Press (OUP)
Date: 30-08-2018
DOI: 10.1093/CID/CIY725
Publisher: Oxford University Press (OUP)
Date: 15-12-2005
DOI: 10.1086/498220
Abstract: Tuberculous meningitis occurs more commonly in human immunodeficiency virus (HIV)-infected in iduals than in HIV-uninfected in iduals, but whether HIV infection alters the presentation and outcome of tuberculous meningitis is unknown. We performed a prospective comparison of the presenting clinical features and response to treatment in 528 adults treated consecutively for tuberculous meningitis (96 were infected with HIV and 432 were uninfected with HIV) in 2 tertiary-care referral hospitals in Ho Chi Minh City, Vietnam. Logistic regression was used to model variables associated independently with HIV infection, 9-month survival, and the likelihood of having a relapse or an adverse drug event. Kaplan-Meier estimates were used to compare survival rates and times to fever clearance, coma clearance, relapse, and adverse events. HIV infection did not alter the neurological presentation of tuberculous meningitis, although additional extrapulmonary tuberculosis was more likely to occur in HIV-infected patients. The 9-month survival rate was significantly decreased in HIV-infected patients (relative risk of death from any cause, 2.91 [95% confidence interval, 2.14-3.96] P < .001), although the times to fever clearance and coma clearance and the number or timing of relapses or adverse drug events were not significantly different between the groups. HIV infection does not alter the neurological features of tuberculous meningitis but significantly reduces the survival rate.
Publisher: Springer Science and Business Media LLC
Date: 12-04-2018
Publisher: Oxford University Press (OUP)
Date: 11-09-1970
DOI: 10.1093/JAC/DKV385
Publisher: Wiley
Date: 08-2007
Abstract: Toll-like receptors (TLR) are critical mediators of the immune response to pathogens and human polymorphisms in this gene family regulate inflammatory pathways and are associated with susceptibility to infection. Lipopeptides are present in a wide variety of microbes and stimulate immune responses through TLR1/2 or TLR2/6 heterodimers. It is not currently known whether polymorphisms in TLR1 regulate the innate immune response. We stimulated human whole blood with triacylated lipopeptide, a ligand for TLR1/2 heterodimers, and found substantial inter-in idual variation in the immune response. We sequenced the coding region of TLR1 and found a non-synonymous polymorphism, I602S (base pair T1805G), that regulated signalling. In comparison to TLR1_602S, the 602I variant mediated substantially greater basal and lipopeptide-induced NF-kappaB signalling in transfected HEK293 cells. These signalling differences among TLR1 variants were also found with stimulation by extracts of Mycobacterium tuberculosis. Furthermore, in iduals with the 602II genotype produced substantially more IL-6 than those with the 602SS variant in a lipopeptide-stimulated whole-blood cytokine assay. Together, these observations demonstrate that variation in the inflammatory response to bacterial lipopeptides is regulated by a common TLR1 transmembrane domain polymorphism that could potentially impact the innate immune response and clinical susceptibility to a wide spectrum of pathogens.
Publisher: Springer Science and Business Media LLC
Date: 14-02-2018
Publisher: Wiley
Date: 04-06-2013
DOI: 10.1002/PON.3326
Abstract: There is growing concern about declining levels of physical activity in childhood cancer survivors. This study aimed to examine the effectiveness of an integrated adventure-based training and health education program in promoting changes in exercise behavior and enhancing the physical activity levels, self-efficacy, and quality of life of Hong Kong Chinese childhood cancer survivors. A randomized controlled trial, two-group pretest and repeated post-test, between-subjects design was conducted to 71 childhood cancer survivors (9- to 16-year-olds). Participants in the experimental group joined a 4-day integrated adventure-based training and health education program. Control group participants received the same amount of time and attention as the experimental group but not in such a way as to have any specific effect on the outcome measures. Participants' exercise behavior changes, levels of physical activity, self-efficacy, and quality of life were assessed at the time of recruitment, 3, 6, and 9 months after starting the intervention. Participants in the experimental group reported statistically significant differences in physical activity stages of change (p < 0.001), higher levels of physical activity (p < 0.001) and self-efficacy (p = 0.04) than those in the control group. Besides, there were statistically significant mean differences (p < 0.001) in physical activity levels (-2.6), self-efficacy (-2.0), and quality of life (-4.3) of participants in the experimental group from baseline to 9 months after starting the intervention. The integrated adventure-based training and health education program was found to be
Publisher: Springer Science and Business Media LLC
Date: 09-2013
DOI: 10.1038/NG.2744
Publisher: Oxford University Press (OUP)
Date: 15-10-2003
DOI: 10.1086/378642
Abstract: The pathogenesis of tuberculous meningitis remains unclear, and there are few data describing the kinetics of the immune response during the course of its treatment. We measured concentrations of pro- and anti-inflammatory cytokines in serial blood and cerebrospinal fluid (CSF) s les from 21 adults who were being treated for tuberculous meningitis. CSF concentrations of soluble tumor necrosis factor-alpha receptors and of matrix metalloprotein-9 and its tissue inhibitor were also measured, and blood-brain barrier permeability was assessed by the albumin and IgG partition indices. CSF concentrations of lactate, interleukin-8, and interferon-gamma were high before treatment and then decreased rapidly with antituberculosis chemotherapy. However, significant immune activation and blood-brain barrier dysfunction were still apparent after 60 days of treatment. Death was associated with high initial CSF concentrations of lactate, low numbers of white blood cells, in particular neutrophils, and low CSF glucose levels.
Publisher: American Society of Tropical Medicine and Hygiene
Date: 04-2015
Publisher: Elsevier BV
Date: 03-2018
Publisher: American Thoracic Society
Date: 03-2015
Publisher: Public Library of Science (PLoS)
Date: 23-03-2015
Publisher: Elsevier BV
Date: 04-2015
Publisher: SAGE Publications
Date: 2014
DOI: 10.33151/AJP.11.5.59
Abstract: Over 9,500 people die annually in Australia from sudden cardiac arrest, with strong evidence suggesting early high quality CPR and early counter shock being paramount for improving survival from cardiac arrest. It has also been shown that first responder programs have been able to reduce response times and increase survival rates for out-of-hospital cardiac arrest. The objective of this study was to examine data from the first seven years of an Australian out-of-hospital cardiac arrest first responder program where fire fighters provided basic life support. This study was a retrospective cohort study of all cardiac arrests attended by the Metropolitan Fire and Emergency Services Board (MFESB) as part of the Emergency Medical Response program over a seven-year period in Melbourne, Victoria, Australia. The MFESB attended 4,450 cardiac arrests. The majority of patients presented in asystole 669 (63.7%) with just 243 (23.1%) presenting in a shockable rhythm. The majority of patients in cardiac arrest were males (64.2%) and the mean age of the patients was 67.5 years. The MFESB median response time during the study period was 5.7 minutes (IQR 2.25 minutes), range of 0.15 minutes to 31.7 minutes, which remained stable over the seven years. Patients spent a median time of 4.6 minutes (0.02 seconds to 36.5 minutes) in the care of fire fighters prior to the arrival of EMS. The rhythm on handover to paramedics was asystole in 787 (75.1%) cases with no shockable rhythms. One in three (31.3%) patients received bystander CPR, with a significant rise in the rate of bystander CPR occurring over the last two years. This study demonstrated acceptable response times to cardiac arrests and a low bystander CPR rate prior to arrival of the MFESB. The incidence of a shockable rhythm on arrival of the MFESB was low with the main rhythm being asystole. The main rhythm on handover to paramedics was asystole with non-shockable rhythms. Further research is required to determine the effect on patient outcomes.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-2020
Publisher: Elsevier BV
Date: 03-2018
Publisher: Springer Science and Business Media LLC
Date: 08-2019
Publisher: Wiley
Date: 18-04-2017
DOI: 10.1111/ZPH.12362
Publisher: American Society for Microbiology
Date: 28-04-2016
Abstract: A large measles virus outbreak occurred across Vietnam in 2014. We identified and obtained complete measles virus genomes in stool s les collected from two diarrheal pediatric patients in Dong Thap Province. These are the first complete genome sequences of circulating measles viruses in Vietnam during the 2014 measles outbreak.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2015
Publisher: Wiley
Date: 09-06-2017
DOI: 10.1111/ZPH.12364
Publisher: Microbiology Society
Date: 10-2014
Abstract: Ventilator-associated pneumonia (VAP) is a serious healthcare-associated infection that affects up to 30 % of intubated and mechanically ventilated patients in intensive care units (ICUs) worldwide. The bacterial aetiology and corresponding antimicrobial susceptibility of VAP is highly variable, and can differ between countries, national provinces and even between different wards in the same hospital. We aimed to understand and document changes in the causative agents of VAP and their antimicrobial susceptibility profiles retrospectively over an 11 year period in a major infectious disease hospital in southern Vietnam. Our analysis outlined a significant shift from Pseudomonas aeruginosa to Acinetobacter spp. as the most prevalent bacteria isolated from quantitative tracheal aspirates in patients with VAP in this setting. Antimicrobial resistance was common across all bacterial species and we found a marked proportional annual increase in carbapenem-resistant Acinetobacter spp. over a 3 year period from 2008 (annual trend odds ratio 1.656, P = 0.010). We further investigated the possible emergence of a carbapenem-resistant Acinetobacter baumannii clone by multiple-locus variable number tandem repeat analysis, finding a bla OXA-23 -positive strain that was associated with an upsurge in the isolation of this pathogen. We additionally identified a single bla NDM-1 -positive A. baumannii isolate. This work highlights the emergence of a carbapenem-resistant clone of A. baumannii and a worrying trend of antimicrobial resistance in the ICU of the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.
Publisher: Frontiers Media SA
Date: 21-06-2019
Publisher: Oxford University Press (OUP)
Date: 12-12-2013
DOI: 10.1093/CID/CIT807
Publisher: F1000 Research Ltd
Date: 26-08-2202
DOI: 10.12688/WELLCOMEOPENRES.17263.2
Abstract: This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region.
Publisher: F1000 Research Ltd
Date: 05-09-2022
DOI: 10.12688/WELLCOMEOPENRES.17263.3
Abstract: This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region.
Publisher: Elsevier BV
Date: 09-2015
Publisher: F1000 Research Ltd
Date: 17-08-2120
DOI: 10.12688/WELLCOMEOPENRES.17263.1
Abstract: This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region.
Publisher: BMJ
Date: 2018
Publisher: Oxford University Press (OUP)
Date: 26-09-2017
DOI: 10.1093/CID/CIX849
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.CMI.2016.10.023
Abstract: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.
Publisher: Springer Science and Business Media LLC
Date: 09-06-2015
Publisher: MDPI AG
Date: 28-04-2022
DOI: 10.3390/W14091411
Abstract: First, this paper presents a thorough review of water quality data using a rainwater tank, categorizing the data as with and without sedimentation. Data are presented showing minimum, maximum, and mean values for the different parameters. The data measured from several sources reveal that water collected from the tank is much better than the water directly collected from the roof. In addition, to analyse the phenomena through a mathematical model, a hypothetical 5 kL rainwater tank with a 200 m2 roof was modelled with the MUSIC model. The simulations were compared with the measured water quality data from a rainwater tank in Melbourne. In general, we found that MUSIC’s simulations on the mean daily concentrations of total suspended solids (TSS) and total phosphorus (TP) are slight underestimations compared to the measured data from Melbourne. Further MUSIC simulations reveal that significant reductions in the daily maximum concentrations of TSS, TP, and total nitrogen (TN) are expected through a rainwater tank.
Publisher: Elsevier BV
Date: 04-2019
Publisher: Springer Science and Business Media LLC
Date: 07-07-2016
Publisher: Public Library of Science (PLoS)
Date: 04-10-2019
Publisher: Elsevier BV
Date: 03-2019
Publisher: Public Library of Science (PLoS)
Date: 22-09-2016
Publisher: Microbiology Society
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 02-07-2019
Publisher: Oxford University Press (OUP)
Date: 12-10-2018
Abstract: We found a high transfer ratio of anti-nontyphoidal Salmonella (NTS) antibodies from mothers to infants. Furthermore, despite a high seroincidence of NTS in infants, maternally acquired antibodies provided protection from seroconversion. Therefore, we propose prenatal immunization against NTS as a possible strategy for protecting infants from NTS disease.
Publisher: Elsevier BV
Date: 02-2020
Publisher: JMIR Publications Inc.
Date: 02-10-2020
DOI: 10.2196/19762
Abstract: Reporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel. This study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly. An offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language (R Project for Statistical Computing). The application can be run by double clicking on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested on Microsoft Windows 10 and 7 using open access ex le data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People’s Democratic Republic, Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam. We developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyze their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and CSV formats). The data files could be those exported from WHONET or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from www.amass.website/. The participating hospitals tested the application and deposited their AMR surveillance reports in an open access data repository. The AMASS is a useful tool to support the generation and sharing of AMR surveillance reports.
Publisher: Cold Spring Harbor Laboratory
Date: 02-10-2020
DOI: 10.1101/2020.10.02.20198663
Abstract: As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination c aign launches, cases and deaths are rising across the island. We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine roll-out. C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled-out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination c aign. Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact. In many settings, limited SARS-CoV-2 testing makes it difficult to estimate the true trajectory and associated burden of the virus. Non-pharmaceutical interventions (NPIs) are key tools to mitigate SARS-CoV-2 transmission. Vaccines show promise but effectiveness depends upon prioritization strategies, roll-out and uptake. This study gives evidence of the value of syndrome-based mortality as a metric, which is less dependent upon testing capacity with which to estimate transmission trends and evaluate intervention impact. NPIs implemented in Java earlier in the pandemic have substantially slowed the course of the epidemic with movement restrictions during Ramadan preventing spread to more vulnerable rural populations. Population-level immunity remains below proposed herd-immunity thresholds for the virus, though it is likely substantially higher in Jakarta. Given current levels of control, upwards trends in deaths are likely to continue in many provinces while the vaccine is scheduled to be rolled out. A key exception is Jakarta where population-level immunity may increase to a level where the epidemic begins to decline before the vaccine c aign has reached high coverage. Further relaxation of measures would lead to more rapidly progressing epidemics, depleting the eventual incremental effectiveness of the vaccine. Maintaining adherence to control measures in Jakarta may be particularly challenging if the epidemic enters a decline phase but will remain necessary to prevent a subsequent large wave. Elsewhere, higher levels of control with NPIs are likely to yield high synergistic vaccine impact.
Publisher: BMJ
Date: 08-2022
DOI: 10.1136/BMJOPEN-2021-055506
Abstract: Poverty has a detrimental influence on psychological well-being of children. Existing evidence shows that positive psychology interventions are possible to mitigate such impact. Despite criticisms that positive psychology resembles a scientific Pollyannaism that promotes overly positivity, positive psychology is not the scientific Pollyannaism that denies the difficulties and emotions that people may experience. Whereas, positive psychology acknowledges the difficulties and emotions, alongside with building up human resilience, strength and growth to face adversity. This study examined the feasibility of implementing a positive psychology intervention among Hong Kong Chinese children living in poverty. A feasibility randomised controlled trial will be conducted. A convenience s le of 120 children aged 13–17 years will be recruited from a community centre in Kwai Tsing district. Participants who are randomised into the experimental group will join a 1.5-hour workshop covering four positive psychology techniques: (1) gratitude visits/letters, (2) three good things, (3) you at your best and (4) using signature strengths. A booster intervention will be provided at 1 week. Control group participants will not receive any intervention. Assessments will be conducted at baseline and at 1-week, 1-month, 3-month and 6-month follow-ups. Descriptive statistics will be used to calculate the feasibility measures. Effect sizes on psychological outcomes (ie, self-esteem, depressive symptoms and quality of life) will be estimated by mixed between-within subjects analysis of variance using partial eta squared with poverty (yes, no) entering into the model as a factor. Ethical approval has been obtained from the Hong Kong Polytechnic University Institutional Review Broad. We will obtain parental consent as our subjects are below 18 years old. Findings from this study will be disseminated via international publications and conferences. NCT04875507 .
Publisher: Springer Science and Business Media LLC
Date: 15-12-2011
DOI: 10.1038/GENE.2011.83
Publisher: Cambridge University Press (CUP)
Date: 24-10-2017
DOI: 10.1017/S095026881700228X
Abstract: Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.
Publisher: Public Library of Science (PLoS)
Date: 22-06-2016
Publisher: F1000 Research Ltd
Date: 22-01-2019
DOI: 10.12688/WELLCOMEOPENRES.15010.1
Abstract: Background : Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with hotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest. Where unavailable, guidelines recommend treatment with hotericin and fluconazole, but this is less effective, with mortality rates of 40-50%. Faster rates of clearance of yeast from cerebrospinal fluid (CSF) are associated with better outcomes - improving the potency of antifungal therapy is likely to be an effective strategy to improve survival. Tamoxifen, a selective estrogen receptor modulator used to treat breast cancer, has anti-cryptococcal activity, appearing synergistic when combined in vitro with hotericin, and fungicidal when combined with fluconazole. It is concentrated in the brain and macrophages, off-patent, cheap and widely available. We designed a randomized trial to deliver initial efficacy and safety data for tamoxifen combined with hotericin and fluconazole. Method : A phase II, open-label, randomized (1:1) controlled trial of tamoxifen (300mg/day) combined with hotericin (1mg/kg/day) and fluconazole (800mg/day) for the first 2 weeks therapy for HIV infected or uninfected adults with cryptococcal meningitis. The study recruits at Cho Ray Hospital and the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. The primary end point is Early Fungicidal Activity (EFA-the rate of yeast clearance from CSF), over the first two weeks of treatment. 50 patients will be recruited providing ≈80% and 90% power to detect a difference in the EFA of -0.11 or -0.13 log10CFU/ml/day, respectively. Discussion: The results of the study will inform the decision to proceed to a larger trial powered to mortality. The size of effect detectable has previously been associated with reduced mortality from this devastating disease. Particular side effects of interest include QT prolongation. Trial registration : Clinicaltrials.gov NCT03112031 (11/04/2017)
Publisher: Springer Science and Business Media LLC
Date: 21-05-2018
Publisher: Public Library of Science (PLoS)
Date: 26-06-2012
Publisher: Springer Science and Business Media LLC
Date: 06-02-2014
DOI: 10.1038/GENE.2014.5
Publisher: Springer Science and Business Media LLC
Date: 14-01-2020
DOI: 10.1186/S12992-019-0539-X
Abstract: In the Mekong Delta region of Vietnam, high quantities of products containing antimicrobial are used as prophylactic and curative treatments in small-scale chicken flocks. A large number of these contain antimicrobial active ingredients (AAIs) considered of ‘critical importance’ for human medicine according to the World Health Organization (WHO). However, little is known about the retail prices of these products and variables associated with the expense on antimicrobials at farm level. Therefore, the aims of the study were: (1) to investigate the retail price of antimicrobials with regards to WHO importance criteria and (2) to quantify the antimicrobial expense incurred in raising chicken flocks. We investigated 102 randomly-selected small-scale farms raising meat chickens (100–2000 per flock cycle) in two districts in Dong Thap (Mekong Delta) over 203 flock production cycles raised in these farms. Farmers were asked to record the retail prices and amounts of antimicrobial used. A total of 214 different antimicrobial-containing products were identified. These contained 37 different AAIs belonging to 13 classes. Over half (60.3%) products contained 1 highest priority, critically important AAI, and 38.8% 1 high priority, critically important AAI. The average (farm-adjusted) retail price of a daily dose administered to a 1 kg bird across products was 0.40 cents of 1 US$ (₵) (SE ± 0.05). The most expensive products were those that included at least one high priority, critically important AAI, as well as those purchased in one of the two study districts. Farmers spent on average of ₵3.91 (SE ± 0.01) on antimicrobials per bird over the production cycle. The expense on antimicrobials in weeks with disease and low mortality was greater than on weeks with disease and high mortality, suggesting that antimicrobial use had a beneficial impact on disease outcomes ( χ 2 = 3.8 p = 0.052). Farmers generally used more expensive antimicrobials on older flocks. The retail prices of antimicrobial products used in chicken production in Mekong Delta small-scale chicken farms are very low, and not related to their relevance for human medicine. Farmers, however, demonstrated a degree of sensitivity to prices of antimicrobial products. Therefore, revising pricing policies of antimicrobial products remains a potential option to curb the use of antimicrobials of critical importance in animal production.
Publisher: Public Library of Science (PLoS)
Date: 05-12-2008
Publisher: Elsevier BV
Date: 02-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2012
Publisher: Springer Science and Business Media LLC
Date: 17-11-2016
DOI: 10.1038/GENE.2016.43
Publisher: Microbiology Society
Date: 08-2015
DOI: 10.1099/JMM.0.000100
Publisher: Elsevier BV
Date: 02-2016
Publisher: Springer Science and Business Media LLC
Date: 12-2017
DOI: 10.1038/GENE.2016.41
Publisher: Microbiology Society
Date: 04-2016
DOI: 10.1099/JMM.0.000220
Publisher: F1000 Research Ltd
Date: 20-03-2018
DOI: 10.12688/WELLCOMEOPENRES.14007.1
Abstract: Background: Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H), predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected in iduals. The primary aim of this study is to determine whether LTA4H genotype determines benefit or harm from adjunctive dexamethasone in HIV-uninfected Vietnamese adults with TBM. The secondary aim is to investigate alternative management strategies in in iduals who develop drug induced liver injury (DILI) that will enable the safe continuation of rif icin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled, multi-centre Phase III non-inferiority trial, comparing dexamethasone versus placebo for 6-8 weeks in addition to standard anti-tuberculosis treatment in HIV-uninfected patients with TBM stratified by LTA4H genotype. The primary endpoint will be death or new neurological event. The trial will enrol approximately 720 HIV-uninfected adults with a clinical diagnosis of TBM, from two hospitals in Ho Chi Minh City, Vietnam. 640 participants with CC or CT- LTA4H genotype will be randomised to either dexamethasone or placebo, and the remaining TT- genotype participants will be treated with standard-of-care dexamethasone. We will also perform a randomised comparison of three management strategies for anti-tuberculosis DILI. An identical ancillary study will also be perfomed in the linked randomised controlled trial of dexamethasone in HIV-infected adults with TBM (ACT HIV). Discussion: Previous data have shown that LTA4H genotype may be a critical determinant of inflammation and consequently of adjunctive anti-inflammatory treatment response in TBM. We will stratify dexamethasone therapy according to LTA4H genotype in HIV-uninfected adults, which may indicate a role for targeted anti-inflammatory therapy according to variation in LTA4H C/T transition. A comparison of DILI management strategies may allow the safe continuation of rif icin and isoniazid.
Publisher: Microbiology Society
Date: 12-2014
Abstract: During a hospital-based diarrhoeal disease study conducted in Ho Chi Minh City, Vietnam from 2009 to 2010, we identified four symptomatic children infected with G26P[19] rotavirus (RV) – an atypical variant that has not previously been reported in human gastroenteritis. To determine the genetic structure and investigate the origin of this G26P[19] strain, the whole genome of a representative ex le was characterized, revealing a novel genome constellation: G26–P[19]–I5–R1–C1–M1–A8–N1–T1–E1–H1. The genome segments were most closely related to porcine (VP7, VP4, VP6 and NSP1) and Wa-like porcine RVs (VP1–3 and NSP2–5). We proposed that this G26P[19] strain was the product of zoonotic transmission coupled with one or more reassortment events occurring in human and/or animal reservoirs. The identification of such strains has potential implications for vaccine efficacy in south-east Asia, and outlines the utility of whole-genome sequencing for studying RV ersity and zoonotic potential during disease surveillance.
Publisher: American Society for Microbiology
Date: 11-2006
DOI: 10.1128/JCM.01181-06
Abstract: Multidrug-resistant tuberculous meningitis is fatal without rapid diagnosis and use of second-line therapy. It is more common in human immunodeficiency virus (HIV)-positive patients. Beijing genotype strains of Mycobacterium tuberculosis are associated with drug resistance, particularly multidrug resistance, and their prevalence is increasing worldwide. The prevalence of Beijing genotype strains among Mycobacterium tuberculosis isolates from the cerebrospinal fluid of HIV-positive ( n = 35) and HIV-negative ( n = 187) patients in Ho Chi Minh City was determined. The Beijing genotype was significantly associated with HIV status (odds ratio [OR] = 2.95 [95% confidence interval {CI}, 1.38 to 6.44] P = 0.016), resistance to any drug (OR = 3.34 [95% CI, 1.87 to 5.95] P 0.001) and multidrug resistance (Fisher's exact test P = 0.001). The association of the Beijing genotype with drug resistance was independent of HIV status. This is the first report of Beijing genotype association with HIV status, which may be an association unique to tuberculous meningitis.
Publisher: Public Library of Science (PLoS)
Date: 15-02-2019
Publisher: EMBO
Date: 20-02-2015
Abstract: Multidrug‐resistant ( MDR ) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic ersity of K. pneumoniae in resource‐poor hospital settings. Through whole‐genome sequencing ( WGS ), we reconstructed an outbreak of MDR K. pneumoniae occurring on high‐dependency wards in a hospital in Kathmandu during 2012 with a case‐fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae . Using phylogenetic reconstruction and lineage‐specific PCR , our data predicted a scenario in which K. pneumoniae , circulating for 6 months before the outbreak, underwent a series of ward‐specific clonal expansions after the acquisition of genes facilitating virulence and MDR . We suggest that the early detection of a specific NDM ‐1 containing lineage in 2011 would have alerted the high‐dependency ward staff to intervene. We argue that some form of real‐time genetic characterisation, alongside clade‐specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high‐ and low‐income settings.
Publisher: MDPI AG
Date: 10-08-2020
DOI: 10.3390/ANTIBIOTICS9080499
Abstract: In the Mekong Delta of Vietnam, farmers use large quantities of antimicrobials to raise small-scale chicken flocks, often including active ingredients regarded of “critical importance’” by the World Health Organization. Due to limitations in laboratory capacity, the choice of antimicrobials normally does not follow any empirical criteria of effectiveness. The aim of this study was to highlight non-critically important antimicrobials against which chicken pathogens are likely to be susceptible as a basis for treatment guidelines. Microtiter broth dilution method was performed to determine the minimal inhibitory concentration (MIC) of 12 commonly used antimicrobials for 58 isolates, including Ornithobacterium rhinotracheale (ORT) (n = 22), Gallibacterium anatis (n = 19), and Avibacterium endocarditidis (n = 17). Unfortunately, internationally accepted breakpoints for resistance in these organisms do not exist. We drew tentative epidemiological cut-offs (TECOFFs) for those antimicrobial-pathogen combinations where MIC distributions suggested the presence of a distinct non-wild-type population. Based on the observed results, doxycycline would be the drug of choice for A.endocarditidis (11.8% presumptive non-wild type) and G. anatis infections (5.3% presumptive non-wild type). A total of 13.6% ORT isolates were non-wild type with regards to oxytetracycline, making it the drug of choice against this pathogen. This study illustrates the challenges in interpreting susceptibility testing results and the need to establish internationally accepted breakpoints for veterinary pathogens.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
Publisher: Springer Science and Business Media LLC
Date: 20-07-2017
DOI: 10.1038/S41598-017-06177-0
Abstract: Seroepidemiological studies aim to understand population-level exposure and immunity to infectious diseases. Their results are normally presented as binary outcomes describing the presence or absence of pathogen-specific antibody, despite the fact that many assays measure continuous quantities. A population’s natural distribution of antibody titers to an endemic infectious disease may include information on multiple serological states – naiveté, recent infection, non-recent infection, childhood infection – depending on the disease in question and the acquisition and waning patterns of immunity. In this study, we investigate 20,152 general-population serum s les from southern Vietnam collected between 2009 and 2013 from which we report antibody titers to the influenza virus HA1 protein using a continuous titer measurement from a protein microarray assay. We describe the distributions of antibody titers to subtypes 2009 H1N1 and H3N2. Using a model selection approach to fit mixture distributions, we show that 2009 H1N1 antibody titers fall into four titer subgroups and that H3N2 titers fall into three subgroups. For H1N1, our interpretation is that the two highest-titer subgroups correspond to recent and historical infection, which is consistent with 2009 pandemic attack rates. Similar interpretations are available for H3N2, but right-censoring of titers makes these interpretations difficult to validate.
Publisher: eLife Sciences Publications, Ltd
Date: 14-03-2016
DOI: 10.7554/ELIFE.14003
Abstract: The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31 9.7%) than gatifloxacin (15/34 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(p .001). H58 is the dominant S. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure. Clinical trial registration: ISRCTN63006567.
Publisher: Elsevier BV
Date: 05-2017
Publisher: Wiley
Date: 25-07-2016
DOI: 10.1111/MYC.12530
Abstract: Penicilliosis caused by Talaromyces marneffei is a common AIDS ‐defining illness in South and Southeast Asia. Diagnosis is based on culture which can take up to 14 days for identification, leading to treatment delay and increased mortality. We developed a TaqMan real‐time PCR assay targeting the MP 1 gene encoding an abundant cell wall protein specific to T. marneffei . The assay's performance was evaluated in MP 1 ‐containing plasmids, clinical isolates, and plasma from HIV ‐infected patients with and without penicilliosis. The assay consistently detected 10 copies of MP 1 ‐containing plasmids per reaction and 100 T. marneffei yeast cells per millilitre plasma. There were no lification with seven other Penicillium species and six other HIV ‐associated fungal pathogens tested. The assay was evaluated in 70 patients with AIDS : 50 patients with culture‐confirmed penicilliosis and 20 patients with opportunistic infections other than penicilliosis. The diagnostic sensitivity was 70.4% (19/27, 95% CI : 51.5–84.1%) and 52.2% (12/23, 95% CI : 33.0–70.8%) in plasma s les collected prior to and within 48 h of antifungal therapy respectively. The diagnostic specificity was 100% (20/20, 95% CI : 83.9–100%). This assay provides a useful tool for the rapid diagnosis of T. marneffei infection and has the potential to improve the management of patients with penicilliosis.
Publisher: Springer Science and Business Media LLC
Date: 18-10-2016
Publisher: American Society for Microbiology
Date: 04-2008
DOI: 10.1128/JCM.02180-07
Abstract: We used large sequence polymorphisms to determine the genotypes of 397 isolates of Mycobacterium tuberculosis from human immunodeficiency virus-uninfected Vietnamese adults with pulmonary ( n = 235) or meningeal ( n = 162) tuberculosis. We compared the pretreatment radiographic appearances of pulmonary tuberculosis and the presentation, response to treatment, and outcome of tuberculous meningitis between the genotypes. Multivariate analysis identified variables independently associated with genotype and outcome. A higher proportion of adults with pulmonary tuberculosis caused by the Euro-American genotype had consolidation on chest X-ray than was the case with disease caused by other genotypes ( P = 0.006). Multivariate analysis revealed that meningitis caused by the East Asian/Beijing genotype was independently associated with a shorter duration of illness before presentation and fewer cerebrospinal fluid (CSF) leukocytes. Older age, fewer CSF leukocytes, and the presence of hemiplegia (but not strain lineage) were independently associated with death or severe disability, although the East Asian/Beijing genotype was strongly associated with drug-resistant tuberculosis. The genotype of M. tuberculosis influenced the presenting features of pulmonary and meningeal tuberculosis. The association between the East Asian/Beijing lineage and disease progression and CSF leukocyte count suggests the lineage may alter the presentation of meningitis by influencing the intracerebral inflammatory response. In addition, increased drug resistance among bacteria of the East Asian/Beijing lineage might influence the response to treatment. This study suggests the genetic ersity of M. tuberculosis has important clinical consequences.
Publisher: Elsevier BV
Date: 03-2015
Publisher: Springer Science and Business Media LLC
Date: 08-09-2017
DOI: 10.1038/NRNEUROL.2017.120
Abstract: Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is h ered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood-brain barrier penetrance. The role of adjunctive anti-inflammatory, host-directed therapies - including corticosteroids, aspirin and thalidomide - has not been extensively explored. To address this deficit, two expert meetings were held in 2009 and 2015 to share findings and define research priorities. This Review summarizes historical and current research into TBM and identifies important gaps in our knowledge. We will discuss advances in the understanding of inflammation in TBM and its potential modulation vascular and hypoxia-mediated tissue injury the role of intensified antibiotic treatment and the importance of rapid and accurate diagnostics and supportive care in TBM.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 04-2019
Publisher: Oxford University Press (OUP)
Date: 13-06-2019
DOI: 10.1093/OFID/OFZ284
Abstract: Hand, foot, and mouth disease (HFMD) has become a major public health concern in the Asia-Pacific region. Knowledge of its economic burden is essential for policy makers in prioritizing the development and implementation of interventions. A multi-hospital-based study was prospectively conducted at 3 major hospitals in Ho Chi Minh City, Vietnam, during 2016–2017. Data on direct and productivity costs were collected alongside clinical information and s les and demographic information from study participants. A total of 466 patients were enrolled. Two hundred three of 466 (43.6%) patients lived in Ho Chi Minh City, and 72/466 (15.5%) had severe HFMD. An enterovirus was identified in 74% of 466 patients, with EV-A71, CV-A6, CV-A10, and CV-A16 being the most common viruses identified (236/466, 50.6%). The mean economic burden per case was estimated at US$400.80 (95% confidence interval [CI], $353.80–$448.90), of which the total direct (medical) costs accounted for 69.7%. There were considerable differences in direct medical costs between groups of patients with different clinical severities and pathogens (ie, EV-A71 vs non-EV-A71). In Vietnam, during 2016–2017, the economic burden posed by HFMD was US$90 761 749 (95% CI, $79 033 973–$103 009 756). Our findings are of public health significance because for the first time we demonstrate that HFMD causes a substantial economic burden in Vietnam, and although multivalent vaccines are required to control HFMD, effective EV-A71 vaccine could substantially reduce the burden posed by severe HFMD. The results will be helpful for health policy makers in prioritizing resources for the development and implementation of intervention strategies to reduce the burden of HFMD.
Publisher: Springer Science and Business Media LLC
Date: 05-04-2017
DOI: 10.1038/SREP45902
Abstract: The aim of the study was to examine the effects of a brief stage-matched smoking cessation intervention group compared with a control group (with usual care) in type 2 diabetes mellitus patients who smoked by randomized controlled trial. There were 557 patients, randomized either into the intervention group (n = 283) who received brief (20- minute) in idualized face-to-face counseling by trained nurses and a diabetes mellitus-specific leaflet, or a control group (n = 274) who received standard care. Patient follow-ups were at 1 week, 1 month, 3 months, 6 months, and 12 months via telephone, and assessment of smoking status from 2012 to 2014. Patients smoked an average of 14 cigarettes per day for more than 37 years, and more than 70% were in the precontemplation stage of quitting. The primary outcome showed that both the intervention and control groups had similar 7-day point-prevalence smoking abstinence (9.2% vs. 13.9% p = 0.08). The secondary outcome showed that HbA1c levels with 7.95% [63 mmol/mol] vs. 8.05% [64 mmol/mol], p = 0.49 at 12 months, respectively. There was no evidence for effectiveness in promoting the brief stage-matched smoking cessation or improving glycemic control in smokers with type 2 diabetes mellitus, particularly those in the pre-contemplation stage.
Publisher: Springer Science and Business Media LLC
Date: 22-01-2015
DOI: 10.1038/SREP07947
Abstract: Salmonella Typhi, the causative agent of typhoid fever, is a monophyletic, human-restricted bacterium that exhibits limited phenotypic variation. S . Typhi from Indonesia are a notable exception, with circulating strains expressing erse flagella antigens including H j, H d and H z66 . Hypothesizing that S . Typhi flagella plays a key role during infection, we constructed an S . Typhi fliC mutant and otherwise isogenic S . Typhi strains expressing the H j, H d , H z66 flagella antigens. Phenotyping revealed differences in flagellum structure, strain motility and immunogenicity, but not in the ability of flagellated isolates to induce TLR5 activity. Invasion assays using epithelial and macrophage cell lines revealed differences in the ability of these S . Typhi derivatives to invade cells or induce cellular restructuring in the form of ruffles. Notably, the H j variant induced substantial ruffles that were not fully dependent on the GTPases that contribute to this process. These data highlight important differences in the phenotypic properties of S . Typhi flagella variation and how they impact on the pathogenesis of S . Typhi.
Publisher: Elsevier BV
Date: 03-2007
Publisher: Elsevier BV
Date: 09-2018
Location: Hong Kong
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Guy Thwaites.