The Emergence of Rotavirus G12 and the Prevalence of Enteric Viruses in Hospitalized Pediatric Diarrheal Patients in Southern Vietnam

Diarrhea is a major cause of childhood morbidity and mortality in developing countries, and the majority of infections are of viral etiology. We aimed to compare the etiological prevalence of the major enteric viruses in an urban and a rural setting in southern Vietnam. We simultaneously screened fecal specimens from 362 children in Ho Chi Minh City and Dong Thap province that were hospitalized with acute diarrhea over a 1-month-long period for four viral gastrointestinal pathogens. Rotavirus was the most common pathogen identified, but there was a differential prevalence of rotavirus and norovirus between the urban and rural locations. Furthermore, rotavirus genotyping and phylogenetic analysis again differentiated the genotypes by the sampling location. Our data show a disproportional distribution of enteric viral pathogens in urban and rural locations, and we provide evidence of continual importation of new rotavirus strains into southern Vietnam and report the emergence of rotavirus genotype G12

Physicians, Primary Caregivers and Topical Repellent: All Under-Utilised Resources in Stopping Dengue Virus Transmission in Affected Households

BACKGROUND: Primary health care facilities frequently manage dengue cases on an ambulatory basis for the duration of the patient’s illness. There is a great opportunity for specific messaging, aimed to reduce dengue virus (DENV) transmission in and around the home, to be directly targeted toward this high-risk ambulatory patient group, as part of an integrated approach to dengue management. The extent however, to which physicians understand, and can themselves effectively communicate strategies to stop focal DENV transmission around an ambulatory dengue case is unknown; the matter of patient comprehension and recollection then ensues. In addition, the effectiveness of N,N-diethyl-3-methylbenzamide (DEET)-based insect repellent in protecting dengue patients from Aedes aegypti mosquitoes’ bites has not been investigated. METHODOLOGY: A knowledge, attitude and practice (KAP) survey, focusing on the mechanisms of DENV transmission and prevention, was performed using semi-structured questionnaires. This survey was targeted towards the patients and family members providing supportive care, and physicians routinely involved in dengue patient management in Southern Vietnam. An additional clinical observational study was conducted to measure the efficacy of a widely-used 13% DEET-based insect repellent to repel Ae. aegypti mosquitoes from the forearms of dengue cases and matched healthy controls. PRINCIPAL FINDINGS: Among both the physician (n = 50) and patient (n = 49) groups there were several respondents lacking a coherent understanding of DENV transmission, leading to some inappropriate attitudes and inadequate acute preventive practices in the household. The application of insect repellent to protect patients and their relatives from mosquito bites was frequently recommended by majority of physicians (78%) participating in the survey. Nevertheless, our tested topical application of 13% DEET conferred only ~1hr median protection time from Ae. aegypti landing. This is notably shorter than that advertised on the manufacturer’s label. No differences in landing time between febrile dengue cases or matched healthy controls (n = 19 experiments) were observed. CONCLUSIONS/SIGNIFICANCE: Our study identifies missed opportunities for primary care physicians to improve public health through communication of strategies that could prevent focal dengue transmission in and around a case household. We advocate better access to more efficient communication methods for physicians and auxilliary health workers, supporting to educate those at high risk of DENV transmission. Our empirical testing of a widely-available 13% DEET-based repellent was limited in its protective efficacy against Ae. aegypti mosquito bites, and therefore DENV transmission, suggesting more frequent application is necessary to be beneficial

Hospital-acquired colonization and infections in a Vietnamese intensive care unit.

Data concerning intensive care unit (ICU)-acquired bacterial colonization and infections are scarce from low and middle-income countries (LMICs). ICU patients in these settings are at high risk of becoming colonized and infected with antimicrobial-resistant organisms (AROs). We conducted a prospective observational study at the Ho Chi Minh City Hospital for Tropical Diseases, Vietnam from November 2014 to January 2016 to assess the ICU-acquired colonization and infections, focusing on the five major pathogens in our setting: Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Klebsiella spp., Pseudomonas spp. and Acinetobacter spp., among adult patients with more than 48 hours of ICU stay. We found that 61.3% (223/364) of ICU patients became colonized with AROs: 44.2% (161/364) with rectal ESBL-producing E. coli and Klebsiella spp.; 30.8% (40/130) with endotracheal carbapenemase-producing Acinetobacter spp.; and 14.3% (52/364) with nasal methicillin-resistant S. aureus. The incidence rate of ICU patients becoming colonized with AROs was 9.8 (223/2,276) per 100 patient days. Significant risk factor for AROs colonization was the Charlson Comorbidity Index score. The proportion of ICU patients with HAIs was 23.4% (85/364), and the incidence rate of ICU patients contracting HAIs was 2.3 (85/3,701) per 100 patient days. The vascular catheterization (central venous, arterial and hemofiltration catheter) was significantly associated with hospital-acquired bloodstream infection. Of the 77 patients who developed ICU-acquired infections with one of the five specified bacteria, 44 (57.1%) had prior colonization with the same organism. Vietnamese ICU patients have a high colonization rate with AROs and a high risk of subsequent infections. Future research should focus on monitoring colonization and the development of preventive measures that may halt spread of AROs in ICU settings

Current challenges and possible solutions to improve access to care and treatment for hepatitis C infection in Vietnam: a systematic review.

BACKGROUND: Hepatitis C infection is a major public health concern in low- and middle-income countries where an estimated 71.1 million individuals are living with chronic infection. The World Health Organization (WHO) has recently released new guidance for hepatitis C virus (HCV) treatment programs, which include improving the access to new direct-acting antiviral agents. In Vietnam, a highly populated middle-income country, the seroprevalence of HCV infection is approximately 4% and multiple genotypes co-circulate in the general population. Here we review what is currently known regarding the epidemiology of HCV in Vietnam and outline options for reducing the significant burden of morbidity and mortality in our setting. METHODS: We performed a systematic review of the currently available literature to evaluate what has been achieved to date with efforts to control HCV infection in Vietnam. RESULTS: This search retrieved few publications specific to Vietnam indicating a significant gap in baseline epidemiological and public health data. Key knowledge gaps identified included an understanding of the prevalence in specific high-risk groups, characterization of circulating HCV genotypes in the population and likely response to treatment, and the extent to which HCV treatment is available, accessed and utilized. CONCLUSIONS: We conclude that there is an urgent need to perform up to date assessments of HCV disease burden in Vietnam, especially in high-risk groups, in whom incidence is high and cross infection with multiple genotypes is likely to be frequent. Coordinating renewed surveillance measures with forthcoming HCV treatment studies should initiate the traction required to achieve the WHO goal of eliminating HCV as a public health threat by 2030, at least in this region

A Multi-Center Randomized Trial to Assess the Efficacy of Gatifloxacin versus Ciprofloxacin for the Treatment of Shigellosis in Vietnamese Children

The bacterial genus Shigella is the most common cause of dysentery (diarrhea containing blood and/or mucus) and the disease is common in developing countries with limitations in sanitation. Children are most at risk of infection and frequently require hospitalization and antimicrobial therapy. The WHO currently recommends the fluoroquinolone, ciprofloxacin, for the treatment of childhood Shigella infections. In recent years there has been a sharp increase in the number of organisms that exhibit resistance to nalidixic acid (an antimicrobial related to ciprofloxacin), corresponding with reduced susceptibility to ciprofloxacin. We hypothesized that infections with Shigella strains that demonstrate resistance to nalidixic acid may prevent effective treatment with ciprofloxacin. We performed a randomized controlled trial to compare 3 day ciprofloxacin therapy with 3 days of gatifloxacin, a newer generation fluoroquinolone with greater activity than ciprofloxacin. We measured treatment failure and time to the cessation of individual disease symptoms in 249 children with dysentery treated with gatifloxacin and 245 treated with ciprofloxacin. We could identify no significant differences in treatment failure between the two groups or in time to the cessation of individual symptoms. We conclude that, in Vietnam, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute dysentery

Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial [version 2; referees: 2 approved]

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 201

Evaluation of the MODS Culture Technique for the Diagnosis of Tuberculous Meningitis

Tuberculous meningitis (TBM) is a devastating condition. The rapid instigation of appropraite chemotherapy is vital to reduce morbidity and mortality. However rapid diagnosis remains elusive; smear microscopy has extremely low sensitivity on cerebrospinal fluid (CSF) in most laboratories and PCR requires expertise with advanced infrastructure and has sensitivity of only around 60% under optimal conditions. Neither technique allows for the microbiological isolation of M. tuberculosis and subsequent drug susceptibility testing. We evaluated the recently developed microscopic observation drug susceptibility (MODS) assay format for speed and accuracy in diagnosing TBM.Two hundred and thirty consecutive CSF samples collected from 156 patients clinically suspected of TBM on presentation at a tertiary referal hospital in Vietnam were enrolled into the study over a five month period and tested by Ziehl-Neelsen (ZN) smear, MODS, Mycobacterial growth Indicator tube (MGIT) and Lowenstein-Jensen (LJ) culture. Sixty-one samples were from patients already on TB therapy for >1day and 19 samples were excluded due to untraceable patient records. One hundred and fifty samples from 137 newly presenting patients remained. Forty-two percent (n = 57/137) of patients were deemed to have TBM by clinical diagnostic and microbiological criteria (excluding MODS). Sensitivity by patient against clinical gold standard for ZN smear, MODS MGIT and LJ were 52.6%, 64.9%, 70.2% and 70.2%, respectively. Specificity of all microbiological techniques was 100%. Positive and negative predictive values for MODS were 100% and 78.7%, respectively for HIV infected patients and 100% and 82.1% for HIV negative patients. The median time to positive was 6 days (interquartile range 5-7), significantly faster than MGIT at 15.5 days (interquartile range 12-24), and LJ at 24 days (interquartile range 18-35 days) (P<0.01).We have shown MODS to be a sensitive, rapid technique for the diagnosis of TBM with high sensitivity, ease of performance and low cost (0.53 USD/sample)

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

Abstract: Background: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired “hypervirulent” strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. Methods: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool. Results: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae. Conclusions: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance—reporting full molecular profiles including STs, AMR, virulence and serotype locus information—can help standardise comparisons between sites and identify regional differences in pathogen populations

A modified Sequential Organ Failure Assessment score for dengue: development, evaluation and proposal for use in clinical trials

Background Dengue is a neglected tropical disease, for which no therapeutic agents have shown clinical efficacy to date. Clinical trials have used strikingly variable clinical endpoints, which hampers reproducibility and comparability of findings. We investigated a delta modified Sequential Organ Failure Assessment (delta mSOFA) score as a uniform composite clinical endpoint for use in clinical trials investigating therapeutics for moderate and severe dengue. Methods We developed a modified SOFA score for dengue, measured and evaluated its performance at baseline and 48 h after enrolment in a prospective observational cohort of 124 adults admitted to a tertiary referral hospital in Vietnam with dengue shock. The modified SOFA score included pulse pressure in the cardiovascular component. Binary logistic regression, cox proportional hazard and linear regression models were used to estimate association between mSOFA, delta mSOFA and clinical outcomes. Results The analysis included 124 adults with dengue shock. 29 (23.4%) patients required ICU admission for organ support or due to persistent haemodynamic instability: 9/124 (7.3%) required mechanical ventilation, 8/124 (6.5%) required vasopressors, 6/124 (4.8%) required haemofiltration and 5/124 (4.0%) patients died. In univariate analyses, higher baseline and delta (48 h) mSOFA score for dengue were associated with admission to ICU, requirement for organ support and mortality, duration of ICU and hospital admission and IV fluid use. Conclusions The baseline and delta mSOFA scores for dengue performed well to discriminate patients with dengue shock by clinical outcomes, including duration of ICU and hospital admission, requirement for organ support and death. We plan to use delta mSOFA as the primary endpoint in an upcoming host-directed therapeutic trial and investigate the performance of this score in other phenotypes of severe dengue in adults and children

Early Pandemic Influenza (2009 H1N1) in Ho Chi Minh City, Vietnam: A Clinical Virological and Epidemiological Analysis

Rogier van Doorn and colleagues analyze the initial outbreak, attempts at containment, and establishment of community transmission of pandemic H1N1 influenza in Ho Chi Minh City, Vietnam