Hao Chung

• Doctor of Philosophy
• PostDoc Position at Oxford University Clinical Research Unit

Background/Objective: Hirschsprung-associated enterocolitis (HAEC) can occur before and after surgery, increasing the complication rates, hospital stay, and treatment costs. This study aims to determine the incidence of preoperative and postoperative Hirschsprung-associated enterocolitis HAEC and the related risk factors. Methods: This study is a p...

Hirschsprung-associated enterocolitis (HAEC) can occur before and after surgery, increasing the complication rates, hospital stay, and treatment costs. Objective: This study aims to determine the incidence of preoperative and postoperative Hirschsprung-associated enterocolitis HAEC and the related risk factors. Methods: A prospective cohort study w...

Hypervirulent Klebsiella pneumoniae (hvKp) is a significant cause of severe invasive infections in Vietnam, yet data on its epidemiology, population structure and dynamics are scarce. We screened hvKp isolates from patients with bloodstream infections (BSIs) at a tertiary infectious diseases hospital in Vietnam and healthy individuals, followed by...

Infectious diarrhoeal diseases remain a substantial health burden in young children in low- and middle-income countries. The disease and its variable treatment options significantly alter the gut microbiome, which may affect clinical outcomes and overall gut health. Antibiotics are often prescribed, but their impact on the gut microbiome during rec...

Salmonella enterica serotype 1,4,[5],12:i:- (Typhimurium monophasic variant) of sequence type (ST) 34 has emerged as the predominant pandemic genotype in recent decades. Despite increasing reports of resistance to antimicrobials in Southeast Asia, Salmonella ST34 population structure and evolution remained understudied in the region. Here we perfor...

Background: Routine placement of a drain for complicated appendicitis is one of the approaches to reduce postoperative complication. In a resource-limited hospital where radiologist-directed monitoring is not feasible, drainage is beneficial for complication follow-up. Nevertheless, emerging studies indicated drainage did not significantly impact o...

Linezolid is an antibiotic of last resort for the treatment of infections caused by Gram-positive bacteria, including vancomycin-resistant enterococci. Enterococcus faecalis, a member of enterococci, is a significant pathogen in nosocomial infections. E. faecalis resistance to linezolid is frequently related to the presence of optrA, which is often...

Salmonella enterica serotype 4,[5],12,i:- (Typhimurium monophasic variant) of sequence type (ST) 34 has emerged as the predominant pandemic genotype in recent decades. Despite increasing reports of resistance to antimicrobials in Southeast Asia, Salmonella ST34 population structure and evolution remained understudied in the region. Here we performe...

Perturbations in the gut microbiome have been associated with colorectal cancer (CRC), with the colonic overabundance of Fusobacterium nucleatum shown as the most consistent marker. Despite its significance in the promotion of CRC, genomic studies of Fusobacterium is limited. We enrolled 43 Vietnamese CRC patients and 25 participants with non-cance...

Conventional disease surveillance for shigellosis in developing country settingsrelies on serotyping and low-resolution molecular typing, which fails to contextualise the evolutionary history of the genus. Here, we interrogated a collection of 1,804 Shigella whole genome sequences from organisms isolated in four continental Southeast Asian countrie...

Despite the widespread implementation of sanitation, immunization and appropriate treatment, infectious diarrheal diseases still inflict a great health burden to children living in low resource settings. Conventional microbiology research in diarrhea have focused on the pathogen’s biology and pathogenesis, but initial enteric infections could trigg...

Perturbations in the gut microbiome have been linked to the promotion and prognosis of colorectal cancer (CRC), with the colonic overabundance of Fusobacterium nucleatum shown as the most consistent marker. Despite the increasing health burden inflicted by CRC in low- and middle-income countries like Vietnam, the CRC-specific microbiome in these po...

Shigella flexneri serotype 6 is an understudied cause of diarrhoeal diseases in developing countries, and has been proposed as one of the major targets for vaccine development against shigellosis. Despite being named as S. flexneri , Shigella flexneri serotype 6 is phylogenetically distinct from other S. flexneri serotypes and more closely related...

Bifidobacterium pseudocatenulatum is a beneficial member of the human gut microbiota. The organism can modulate inflammation and has probiotic potential, but its characteristics are largely strain dependent and associated with distinct genomic and biochemical features.

Antimicrobials are a key group of therapeutic agents. Given the animal/human population density and high antimicrobial consumption rate in Southeast Asia, the region is a focal area for monitoring antimicrobial resistance (AMR). Hypothesizing that the gastrointestinal tract of healthy individuals in Vietnam is a major source of AMR genes that may b...

Bifidobacterium pseudocatenulatum is a member of the human gut microbiota, and has previously been used as a probiotic to improve gut integrity and reduce inflammatory responses. We showed previously that B. pseudocatenulatum was significantly depleted during dysenteric diarrhea, suggesting the organism may aid in recovery from diarrhea. Here, in o...

Conventional disease surveillance for shigellosis in developing country settings relies on serotyping and low-resolution molecular typing, which fails to contextualise the evolutionary history of the genus. Here, we interrogated a collection of 1,804 Shigella whole genome sequences from organisms isolated in four continental Southeast Asian countri...

The emergence of carbapenem resistance in Klebsiella pneumoniae represents a major global public health concern. Nosocomial outbreaks caused by multidrug-resistant K. pneumoniae are commonly reported to result in high morbidity and mortality due to limited treatment options. Between October 2019 and January 2020, two concurrent high-mortality nosoc...

Pre-existing colonization with Staphylococcus aureus or Klebsiella pneumoniae has been found to increase the risk of infection in intensive care patients. We previously conducted a longitudinal study to characterize colonization of these two organisms in patients admitted to intensive care in a hospital in southern Vietnam. Here, using genomic and...

Background Shigella is a major diarrheal pathogen for which there is presently no vaccine. Whole genome sequencing provides the ability to predict and derive novel antigens for use as vaccines. Here, we aimed to identify novel immunogenic Shigella antigens that could serve as Shigella vaccine candidates, either alone, or when conjugated to Shigella...

Nontyphoidal Salmonella (NTS) are among the most common aetiological agents of diarrhoeal diseases worldwide and have become the most commonly detected bacterial pathogen in children hospitalised with diarrhoea in Vietnam. Aiming to better understand the epidemiology, serovar distribution, antimicrobial resistance (AMR), and clinical manifestation...

Antimicrobial resistance (AMR) has been identified by the World Health Organization (WHO) as one of the ten major threats to global health. Advances in technology, including whole-genome sequencing, have provided new insights into the origin and mechanisms of AMR. However, our understanding of the short-term impact of antimicrobial pressure and res...

Despite the sporadic detection of fluoroquinolone-resistant Shigella in Asia in the early 2000s and the subsequent global spread of ciprofloxacin-resistant (cipR) Shigella sonnei from 2010, fluoroquinolones remain the recommended therapy for shigellosis1–7. The potential for cipR S. sonnei to develop resistance to alternative second-line drugs may...

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 evolu...

The global dissemination of a ciprofloxacin-resistant (cipR) S. sonnei clone outlines the mobility of this important agent of diarrheal disease, and threatens the utility of ciprofloxacin as a first-line antimicrobial for shigellosis. Here, we aimed to track the emergence of cipR S. sonnei in Vietnam to understand how novel antimicrobial resistant...

Purpose: Antimicrobial-resistant bacterial infections in low- and middle-income countries (LMICs) are a well-established global health issue. We aimed to assess the prevalence of and epidemiological factors associated with the carriage of ciprofloxacin- and ceftriaxone-resistant Escherichia coli and associated resistance genes in a cohort of 498 h...

Purpose of review: Diarrhoea is a major global health problem, and recent studies have confirmed Shigella as a major contributor to this burden. Here, we review recent advances in Shigella research; focusing on their epidemiology, pathogenesis, antimicrobial resistance, and the role of the gut microbiome during infection. Recent findings: Enhanc...

Shigella are ranked among the most prevalent aetiologies of diarrhoeal disease worldwide, disproportionately affecting young children in developing countries and high-risk communities in developed settings. Antimicrobial treatment, most commonly with fluoroquinolones, is currently recommended for Shigella infections to alleviate symptoms and contro...

Infection by Shigella spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment, however antimicrobial resistance in Shigella spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian Shigella isolate...

Genetic and environmental factors shape host susceptibility to infection, but how and how rapidly environmental variation might alter the susceptibility of mammalian genotypes remains unknown. Here, we investigate the impacts of seminatural environments upon the nematode susceptibility profiles of inbred C57BL/6 mice. We hypothesized that natural e...

Albumin, total protein, and leptin levels in blood between infected and uninfected mice across all environments at 3 weeks and 4 weeks p.i. (A) Plasma albumin, total protein, and leptin levels in uninfected and infected mice across all environments at 3 weeks p.i. Sample sizes: Uninfected Lab mice: N = 2; Infected Lab mice: N = 8; Uninfected Short-...

Supporting information. (DOC)

Trichuris muris worm burdens and worm biomass in C57BL/6 mice residing in laboratory versus outdoor environments at 4 weeks p.i. (A) Worm burdens and (B) worm biomass from infected C57BL/6 mice residing in laboratory and outdoor environments at 4 weeks p.i. Lab: N = 7, Short-term Wild: N = 7, Long-term Wild: N = 8. Box centers show the medians, and...

Differences in the relative abundance of LPMC and MLN cytokines in mice living in laboratory and outdoor environments at 4 weeks p.i. (A) Proportion of CD4+ cells that are producing IL-13, IFNγ, IL-4, IL-10, IL-17, and TNFα in LPMCs of mice residing in laboratory and outdoor environments at 4 weeks p.i. Sample sizes: Uninfected Lab mice: N = 3; Inf...

Cytokine production in LPMCs of infected C57BL/6 and STAT6-/- mice residing outdoors for the short term. Proportion of CD4+ cells that are producing IL-4, IL-10, IL-17, and TNFα from LPMCs of infected C57BL/6 (N = 4) and STAT6-/- (N = 5) mice residing outdoors for the short term. Data on cytokine-positive lamina propria cells were log(x+1) transfor...

Effects of environmental variation and infection on host weight over time. Body weight in grams lost/gained over the course of the experiment from uninfected and infected mice residing in laboratory and outdoor environments. Data are means ± standard error mean. https://doi.org/10.5061/dryad.h9g697r. (TIF)

Outdoor environments alter the microbial and fungal communities of the gut. (A) Taxa summary plots at the phylum level showing the microbiota composition of individual Lab mice (N = 47) compared to Long-term Wild (N = 28) mice, which had been residing outdoors for two weeks. The Lab group includes both Lab and Short-term Wild mice, as both groups w...

Differences in the relative abundance of LPMC and MLN cytokines in mice living in laboratory and outdoor environments at 3 weeks p.i. (A) Representative gating strategy for CD4+ and CD8+ cytokine analyses from LPMCs of a laboratory mouse. (B) Proportion of CD4+ cells that are producing IL-4, IL-10, IL-17, and TNFα in LPMCs from mice residing in lab...

Statistical table showing blood albumin, total protein, and leptin levels at 3 weeks and 4 weeks p.i. Two-way ANOVA results for plasma albumin (g/dl), total protein (g/dl), and leptin (pg/ml) levels at 3 weeks and 4 weeks p.i., with location and infection as main factors. Nutritional data were log(x+1) transformed to meet assumptions of analysis. W...

Statistical table showing the alpha diversity of 16S microbiota data for fecal samples collected at 3 weeks and 4 weeks p.i. Two-way ANOVA results showing the alpha diversity as represented by the Shannon index of microbiota data for fecal samples at 3 weeks and 4 weeks p.i. When the interaction term is not significant, the main effect results come...

Statistical table showing LPMC and MLN cytokine production at 3 weeks and 4 weeks p.i. Two-way ANOVA results for CD4+ and CD8+ LPMC and MLN cytokine production at 3 weeks and 4 weeks p.i. with location and infection as main factors. Data on cytokine-positive lamina propria cells and in vitro cytokine secretion were log(x+1) transformed to meet assu...

Alterations in the composition, diversity, and density of the fecal microbiota with high-dose Trichuris muris infection. (A) Log2 fold change of OTUs that differ between infected and uninfected mice residing in laboratory and outdoor environments at 4 weeks p.i. using DESeq2. Data shown have been filtered to include OTUs that have a log2 fold chang...

Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiologi...

Background: Probiotics are the most frequently prescribed treatment for children hospitalized with diarrhea in Vietnam. We were in uncertain of the benefits of probiotics for the treatment of acute watery diarrhea in Vietnamese children. Methods: We conducted a double blind, placebo-controlled, randomized trial of children hospitalized with acut...

Background: Antimicrobial resistance is a major issue in the Shigellae, particularly as a specific multidrug-resistant (MDR) lineage of Shigella sonnei (lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment for Shigella infections. However, ciprofloxacin-resistant S. sonnei are being increasingly isolated in Asia and...

Objectives The objective of this study was to assess the presence of mcr-1 in Shigella sonnei isolated in Vietnam. Methods WGS data were analysed for the presence of the mcr-1 gene sequence. The association of mcr-1 with a plasmid was assessed by PCR and by conjugation. Results Through genome sequencing we identified a plasmid-associated inactive...

Shigella spp. are some of the key pathogens responsible for the global burden of diarrhoeal disease. These facultative intracellular bacteria belong to the family Enterobacteriaceae, together with other intestinal pathogens, such as Escherichia coli and Salmonella spp. The genus Shigella comprises four different species, each consisting of several...

Background Antimicrobial resistance is a major issue in the Shigellae , particularly as a specific multidrug resistant (MDR) lineage of Shigella sonnei (lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment for Shigella infections. However, ciprofloxacin resistant S. sonnei are being increasingly isolated in Asia, and...

The mcr-1 gene, which confers resistance against the last-resort antimicrobial colistin, was recently discovered in Enterobacteriaceae circulating in China. Through genome sequencing we identified a plasmid-associated inactive form of mcr-1 in a 2008 Vietnamese isolate of Shigella sonnei. The plasmid was conjugated into E. coli and mcr-1 was activa...

Objectives: We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and...

Shigella sonnei is a major contributor to the global burden of diarrhoeal disease, generally associated with dysenteric diarrhoea in developed countries but also emerging in developing countries. The reason for the recent success of S. sonnei is unknown, but is likely catalysed by its ability to acquire resistance against multiple antimicrobials. B...

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity 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...

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity 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...