Phan Tu Qui

Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia.

Avian influenza A (H5N1) viruses cause severe disease in humans, but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis. Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity. To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment.

Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: a randomized, placebo-controlled trial.

Use of oral prednisolone for 3 days during the early acute phase of dengue virus infection appears to be safe, but did not reduce the rate of development of shock or other recognized complications of dengue in this randomized, placebo-controlled trial.

Clinical Characteristics of Dengue Shock Syndrome in Vietnamese Children: A 10-Year Prospective Study in a Single Hospital

We present the clinical features, management, and outcomes for 1719 Vietnamese children with dengue shock syndrome enrolled in a 10-year prospective study in a single center, to provide the first comprehensive description of this increasingly important disorder.

Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges

In early 2012, doctors in Cambodia noticed high numbers of infants and young children presenting with a severe and unusual illness. The striking features of the disease were an initial encephalitic presentation followed by a rapidly fatal destructive alveolar pneumonia, alarming experienced clinicians. Between April and July 2012 a total of 78 children were affected, 54 of whom died. Enterovirus 71 (EV71) was identified as the causative organism, possibly aggravated by malnutrition and uncontrolled use of steroids.1 EV71 is one of the pathogens associated with hand, foot and mouth disease (HFMD). It was responsible for large HFMD outbreaks in Taiwan (1.5 million cases) and Malaysia (Sarawak, 2628 cases) in the late 1990s. In 2008 and 2011 large outbreaks were also described in China (490 000 cases) and Vietnam (110 000 cases).2 The recent Cambodian outbreak further demonstrates the emergence and spread of serious EV71 related disease in the South-East Asian region over the last two decades. The clinical syndrome of fever with oral ulcers and exanthema on the hands and feet of young children was first observed in 1957 in New Zealand. The term ‘Hand, foot and mouth disease’ was first used the following year.3 HFMD is mostly caused by EVs belonging to the species Enterovirus A (consisting of Coxsackie viruses A 2–8, 10, 12, 14, 16 and EVs 71, 76 and 89–92). EV71 is thought to have evolved from Coxsackie virus A16 around 1940,4 subsequently diverging into three lineages, A, B and C. Lineages B and C are further divided into five sublineages, with B4, B5, C4 and C5 the dominant sublineages identified in recent years in South-East Asia. Although genetically different, all lineages and sublineages represent one serotype of EV71. HFMD is typically a benign self-limiting illness observed among young children and infants. Outbreaks are often …

A successful antimicrobial regime for Chromobacterium violaceum induced bacteremia

BackgroundChromobacterium violaceum is a proteobacterium found in soil and water in tropical regions. The organism rarely causes infection in humans, yet can cause a severe systemic infection by entering the bloodstream via an open wound.Case presentationWe recently identified a case of severe bacteremia caused by Chromobacterium violaceum at the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. Here, we describe how rapid microbiological identification and a combination of antimicrobials was used to successfully treat this life threatening infection in a four-year-old child.ConclusionsThis case shows the need for rapid diagnosis when there is the suspicion of a puncture wound contaminated with water and soil in tropical regions. We suggest that the aggressive antimicrobial combination used here is considered when this infection is suspected.

Phylodynamics of Enterovirus A71-Associated Hand, Foot, and Mouth Disease in Viet Nam

ABSTRACT Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia. IMPORTANCE EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study, we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus.

A generic assay for whole-genome amplification and deep sequencing of enterovirus A71.

Enterovirus A71 (EV-A71) has emerged as the most important cause of large outbreaks of severe and sometimes fatal hand, foot and mouth disease (HFMD) across the Asia-Pacific region. EV-A71 outbreaks have been associated with (sub)genogroup switches, sometimes accompanied by recombination events. Understanding EV-A71 population dynamics is therefore essential for understanding this emerging infection, and may provide pivotal information for vaccine development. Despite the public health burden of EV-A71, relatively few EV-A71 complete-genome sequences are available for analysis and from limited geographical localities. The availability of an efficient procedure for whole-genome sequencing would stimulate effort to generate more viral sequence data. Herein, we report for the first time the development of a next-generation sequencing based protocol for whole-genome sequencing of EV-A71 directly from clinical specimens. We were able to sequence viruses of subgenogroup C4 and B5, while RNA from culture materials of diverse EV-A71 subgenogroups belonging to both genogroup B and C was successfully amplified. The nature of intra-host genetic diversity was explored in 22 clinical samples, revealing 107 positions carrying minor variants (ranging from 0 to 15 variants per sample). Our analysis of EV-A71 strains sampled in 2013 showed that they all belonged to subgenogroup B5, representing the first report of this subgenogroup in Vietnam. In conclusion, we have successfully developed a high-throughput next-generation sequencing-based assay for whole-genome sequencing of EV-A71 from clinical samples.

Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants

Highlights • Large contemporary case-series in a setting of improved critical care facilities.• Analysis of variables, some not analysed in previous studies/meta-analyses.• Age and weight were associated with a poor outcome.• Delay in admission to hospital and leukocytosis were also associated with a poor outcome.

Neonatal Tetanus in Vietnam: Comprehensive Intensive Care Support Improves Mortality

We report a 66% reduction in neonatal tetanus mortality after introducing a new management bundle integrating antibiotic therapy, muscle relaxation and invasive monitoring. The latter allowed rapid detection of autonomic instability which was treated with magnesium sulphate. This is the first report of its use in neonatal tetanus.

Skin dendritic cell and T cell activation associated with dengue shock syndrome

The pathogenesis of severe dengue remains unclear, particularly the mechanisms underlying the plasma leakage that results in hypovolaemic shock in a small proportion of individuals. Maximal leakage occurs several days after peak viraemia implicating immunological pathways. Skin is a highly vascular organ and also an important site of immune reactions with a high density of dendritic cells (DCs), macrophages and T cells. We obtained skin biopsies and contemporaneous blood samples from patients within 24 hours of onset of dengue shock syndrome (DSS), and from healthy controls. We analyzed cell subsets by flow cytometry, and soluble mediators and antibodies by ELISA; the percentage of migratory CD1a+ dermal DCs was significantly decreased in the DSS patients, and skin CD8+ T cells were activated, but there was no accumulation of dengue-specific antibodies. Inflammatory monocytic cells were not observed infiltrating the skin of DSS cases on whole-mount histology, although CD14dim cells disappeared from blood.