Chronological, geographical, and seasonal trends of human cases of avian influenza A (H5N1) in Vietnam, 2003-2014: a spatial analysis.

BACKGROUND: Human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to occur in Southeast Asia. The objective of this study was to identify when and where human H5N1 cases have occurred in Vietnam and how the situation has changed from the beginning of the H5N1 outbreaks in 2003 through 2014, to assist with implementing methods of targeted disease management. METHODS: We assessed the disease clustering and seasonal variation of human H5N1 cases in Vietnam to evaluate the geographical and monthly timing trends. The clustering of H5N1 cases and associated mortality were examined over three time periods: the outbreak period (2003-2005), the post-outbreak (2006-2009), and the recent period (2010-2014) using the flexibly shaped space-time scan statistic. The most likely cases to co-cluster and the elevated risks for incidence and mortality were assessed via calculation of the relative risk (RR). The H5N1 case seasonal variation was analysed as the cyclic trend in incidence data using Roger's statistical test. RESULTS: Between 2003 and 2005, H5N1 cases (RR: 2.15, p = 0.001) and mortality (RR: 2.49, p = 0.021) were significantly clustered in northern Vietnam. After 2010, H5N1 cases tended to occur on the border with Cambodia in the south, while H5N1 mortality clustered significantly in the Mekong delta area (RR: 6.62, p = 0.002). A significant seasonal variation was observed (p < 0.001), with a higher incidence of morbidity in December through April. CONCLUSIONS: These findings indicate that clinical preparedness for H5N1 in Vietnam needs to be strengthened in southern Vietnam in December-April.

Clinical and microbiological evaluation of ventilator-associated pneumonia in an intensive care unit in Vietnam.

Background: The increasing incidence of multidrug-resistant Gram-negative bacteria causing ventilator-associated pneumonia (VAP) is a global concern. A better understanding of the epidemiology of VAP in Southeast Asia is essential to optimise treatments and patient outcomes. Methods: VAP epidemiology in an intensive care unit in Vietnam was investigated. A prospective cohort study was conducted. Patients who were ventilated for >48 hours, diagnosed with VAP, and had a positive respiratory culture between October 2015 and March 2017 were included. Whole-genome sequencing (WGS) was performed on Acinetobacter baumannii isolates. Results: We identified 125 patients (137 episodes) with VAP from 1,699 admissions. Twelve patients had 2 VAP episodes. The median age was 60 years (interquartile range: 48-70), and 68.8% of patients were male. Diabetes mellitus was the most frequent comorbidity (N=35, 28%). Acinetobacter baumannii was most frequently isolated in the first VAP episode (N=84, 67.2%) and was multiply resistant to meropenem, levofloxacin, and amikacin. The 30-day mortality rate was 55.2% (N=69) and higher in patients infected with A. baumannii (N=52, 65%). WGS results suggested a complex spread of multiple clones. Conclusions: In an intensive care unit in Vietnam, VAP due to A. baumannii had a high mortality rate, and A. baumannii and K. pneumoniae were multidrug resistant, with carbapenem resistance of 97% and 70%, respectively.

Evidence of widespread endemic populations of highly multidrug resistant Klebsiella pneumoniae in hospital settings in Hanoi, Vietnam: a prospective cohort study.

BACKGROUND: Patients with prolonged hospitalisation have a significant risk of carriage of and subsequent infection with extended spectrum ß-lactamase (ESBL)-producing and carbapenemase-producing Klebsiella pneumoniae. However, the distinctive roles of the community and hospital environments in the transmission of ESBL-producing or carbapenemase-producing K pneumoniae remain elusive. We aimed to investigate the prevalence and transmission of K pneumoniae within and between the two tertiary hospitals in Hanoi, Viet Nam, using whole-genome sequencing. METHODS: We did a prospective cohort study of 69 patients in intensive care units (ICUs) from two hospitals in Hanoi, Viet Nam. Patients were included if they were aged 18 years or older, admitted for longer than the mean length of stay in their ICU, and cultured K pneumoniae from their clinical samples. Longitudinally collected samples from patients (collected weekly) and the ICU environment (collected monthly) were cultured on selective media, and whole-genome sequences from K pneumoniae colonies analysed. We did phylogenetic analyses and correlated phenotypic antimicrobial susceptibility testing with genotypic features of K pneumoniae isolates. We constructed transmission networks of patient samples, relating ICU admission times and locations with genetic similarity of infecting K pneumoniae. FINDINGS: Between June 1, 2017, and Jan 31, 2018, 69 patients were in the ICUs and eligible for inclusion, and a total of 357 K pneumoniae isolates were cultured and successfully sequenced. 228 (64%) of K pneumoniae isolates carried between two and four different ESBL-encoding and carbapenemase-encoding genes, with 164 (46%) isolates carrying genes encoding both, with high minimum inhibitory concentrations. We found a novel co-occurrence of blaKPC-2 and blaNDM-1 in 46·6% of samples from the globally successful ST15 lineage. Despite being physically and clinically separated, the two hospitals shared closely related strains carrying the same array of antimicrobial resistance genes. INTERPRETATION: These results highlight the high prevalence of ESBL-positive carbapenem-resistant K pneumoniae in ICUs in Viet Nam. Through studying K pneumoniae ST15 in detail, we showed how important resistance genes are contained within these strains that are carried broadly by patients entering the two hospitals directly or through referral. FUNDING: Medical Research Council Newton Fund, Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Genomic characterisation of multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii in two intensive care units in Hanoi, Viet Nam: a prospective observational cohort study.

BACKGROUND: Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam. METHODS: A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018. Clinical and environmental samples were cultured on selective media, characterised with MALDI TOF mass spectrometry, and sequenced with Illumina. Phylogenies based on the de-novo assemblies (SPAdes) were constructed with MAFFT (PARsnp), Gubbins, and RAxML. Resistance genes were detected with Abricate against the US National Center for Biotechnology Information database. FINDINGS: 3153 Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A baumannii (global clone 2, sequence types ST2 and ST571) and K pneumoniae (ST15, ST16, ST656, ST11, and ST147) isolates. Isolation from stool was most common with E coli (87·0%) followed by K pneumoniae (62·5%). Of the E coli, 85·0% carried a blaCTX-M variant, while 81·8% of K pneumoniae isolates carried blaNDM (54·4%), or blaKPC (45·1%), or both. Transmission analysis with single nucleotide polymorphisms identified 167 clusters involving 251 (68%) of 369 patients, in some cases involving patients from both ICUs. There were no clear differences between the lineages or AMR genes recovered between the two ICUs. INTERPRETATION: This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission before ICU admission in other health-care settings or in the community. FUNDING: UK Medical Research Council Newton Fund, Viet Nam Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and UK National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Prevalence and Factors Associated with Psychological Problems of Healthcare Workforce in Vietnam: Findings from COVID-19 Hotspots in the National Second Wave.

Adopting a cross-sectional study design, we aimed to examine the prevalence of psychological problems in different healthcare workers during the COVID-19 pandemic in the hospitals in these COVID-19 hotspots (Da Nang city and Quang Nam province) and to explore the socioeconomic and COVID-19 control-related factors that are associated with various psychological problems. A total of 611 healthcare workers were included in the final analysis from 1 August 2020 to 31 August 2020. The prevalence of anxiety, depression, insomnia, and overall psychological problems was 26.84%, 34.70%, 34.53%, and 46.48%, respectively. The prevalence rates of anxiety were approximately equal amongst the groups of healthcare workers, and moderate-to-severe anxiety was the most common in physicians (11.11%). The prevalence of depression was the highest in nurses (38.65%) and moderate-to-severe depression was mainly found in physicians (11.81%). The prevalence rates of insomnia were 34.03% in physicians, 36.20% in nurses, and 31.21% in technicians; in particular, the rate of moderate-to-severe insomnia was higher in physicians and nurses compared to technicians. The prevalence of overall moderate-to-severe psychological problems was the highest among physicians (14.58%), followed by nurses (12.58%) and technicians (9.22%). Statistically significant associated factors of current psychological problems were the occupations of physicians or nurses, less than 1 year of experience, university education, living with 4-5 people, reporting 1000-5000 m distance between home and workplace, participating in the COVID-19 control for less than 1 week, being under social isolation at home, being affected a lot by the community, reporting inadequate equipment in current workplace conditions, frequently working in the department directly in contact with the COVID-19 patients, and feeling anxious, stressed, or sad about current works. Present findings can provide valuable evidence for the policymakers and managers to adopt supportive, encouraging, motivational, protective, training, and educational interventions into healthcare workforce in other parts of Vietnam.

Tuberculosis-induced acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation.

Tuberculosis (TB) is a rare but known cause of acute respiratory distress syndrome (ARDS) with a high mortality. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) may be an alternative option for treating TB-induced ARDS. However, the literature on TB-induced ARDS treated with VV-ECMO is limited and the most of them were prolonged therapy. We report on a-48-year-old man with TB-induced ARDS who was successfully treated by short-term use of VV-ECMO (5 days). He was developed symptoms and hospitalized with severe dyspnea in a local hospital for 3 days before admission to our hospital. At the time when he was transferred to our hospital, his chest computed tomography showed bilateral, diffuse and consolidative shadows all over the lungs, the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) was 50 mmHg, and respiratory system compliance was 12.5 mL/cmH2O. Two days after admission, Mycobacterium tuberculosis was detected by a sputum smear examination and he was diagnosed with TB-induced ARDS. VV-ECMO support was then initiated with administration of anti-TB drugs and systemic corticosteroid treatment. On the 4thday of ECMO support, his PaO2/FiO2 increased to 400 mmHg and lung compliance increased to 45 mL/cmH2O. He was weaned from ECMO on the 5th day of ECMO support and was extubated at the 8th day. He was discharged from hospital on the 47th hospitalized day and continued anti-TB medication at home. VV-ECMO is effective for TB-induced ARDS even in short-term administration if progression of ARDS is rapid.

Clinical epidemiology and mortality on patients with acute respiratory distress syndrome (ARDS) in Vietnam.

BACKGROUND: The clinical epidemiology and disease prognosis in patients with acute respiratory distress syndrome (ARDS) have not yet been fully elucidated in Vietnam. METHODS: We conducted a retrospective observational study at a national tertiary hospital in Hanoi, Vietnam. Participants were adult patients (age ≥18 years) who were admitted and diagnosed with ARDS during 2015-2017. Data on patients' general and clinical conditions, radiographic findings, ventilator settings, gas exchange, and treatment methods were collected and compared between survivors and non-survivors. Risk factors for mortality were assessed using logistic regression analysis. RESULTS: Among 126 eligible patients with ARDS admitted to the central tertiary hospital in Vietnam, we observed high mortality (57.1%). Of the total patients, 91.3% were transferred from local hospitals with a diagnosis of severe pneumonia and then diagnosed with ARDS at the central hospital. At the time of admission, 53.2% of patients had severe ARDS, 37.3% had moderate ARDS, and 9.5% had mild ARDS. The mean (standard deviation) sequential organ failure assessment (SOFA) score was 9.5 (3.4) in non-survivors and 7.4 (3.4) in survivors (p = 0.002). Although there was no significant difference in PaO2/FiO2 on admission between non-survivors and survivors, that on day 3 after admission was significantly different (p = 0.002). Logistic regression revealed that PaO2/FiO2 on day 3 [odds ratio (OR), 1.010; 95% confidence interval (CI), 1.003-1.017], length of stay in a local hospital before admission to the central hospital (OR, 1.122; 95% CI, 1.042-1.210) due to stable condition, and SOFA score on Day 1 (OR, 0.842; 95% CI, 0.708-1.002) were independent factors in patient survival. CONCLUSIONS: Patients with ARDS admitted the central tertiary hospital had severe illness and high mortality. Most patients were transferred from local hospitals. Improvements in human, medical, and sociological resources in local will contribute to reducing the mortality of ARDS in Vietnam.

Ventilator-associated respiratory infection in a resource-restricted setting: impact and etiology.

BACKGROUND: Ventilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available. METHODS: We conducted a prospective observational study in four Vietnamese ICUs to assess the incidence and impact of VARI. Patients ≥ 16 years old and expected to be mechanically ventilated > 48 h were enrolled in the study and followed daily for 28 days following ICU admission. RESULTS: Four hundred fifty eligible patients were enrolled over 24 months, and after exclusions, 374 patients' data were analyzed. A total of 92/374 cases of VARI (21.7/1000 ventilator days) were diagnosed; 37 (9.9%) of these met ventilator-associated pneumonia (VAP) criteria (8.7/1000 ventilator days). Patients with any VARI, VAP, or VARI without VAP experienced increased hospital and ICU stay, ICU cost, and antibiotic use (p < 0.01 for all). This was also true for all VARI (p < 0.01 for all) with/without tetanus. There was no increased risk of in-hospital death in patients with VARI compared to those without (VAP HR 1.58, 95% CI 0.75-3.33, p = 0.23; VARI without VAP HR 0.40, 95% CI 0.14-1.17, p = 0.09). In patients with positive endotracheal aspirate cultures, most VARI was caused by Gram-negative organisms; the most frequent were Acinetobacter baumannii (32/73, 43.8%) Klebsiella pneumoniae (26/73, 35.6%), and Pseudomonas aeruginosa (24/73, 32.9%). 40/68 (58.8%) patients with positive cultures for these had carbapenem-resistant isolates. Patients with carbapenem-resistant VARI had significantly greater ICU costs than patients with carbapenem-susceptible isolates (6053 USD (IQR 3806-7824) vs 3131 USD (IQR 2108-7551), p = 0.04) and after correction for adequacy of initial antibiotics and APACHE II score, showed a trend towards increased risk of in-hospital death (HR 2.82, 95% CI 0.75-6.75, p = 0.15). CONCLUSIONS: VARI in a resource-restricted setting has limited impact on mortality, but shows significant association with increased patient costs, length of stay, and antibiotic use, particularly when caused by carbapenem-resistant bacteria. Evidence-based interventions to reduce VARI in these settings are urgently needed.

Polymyxin-B-immobilized-fiber column hemoperfusion with oseltamivir treatment for ARDS due to influenza H1N1/09.

Acute respiratory distress syndrome (ARDS) is one of the severe complications of influenza H1N1/09 infection, resulting in high mortality. Effective treatment strategies for ARDS are needed. This report presents two cases of ARDS due to influenza in Vietnam. Both cases were similar in terms of starting symptoms, the rapid progression to ARDS, and the treatment strategy, direct hemoperfusion with a polymyxin-B-immobilized fiber column (PMX-DHP) and oseltamivir. However, the clinical course of disease and the outcomes were different. For case 1, treatment was initiated on day 4 following the onset of hypoxemia due to ARDS. Symptoms improved rapidly after treatment and the patient was discharged on day 12. For case 2, treatment was initiated on day 9 after the onset of symptoms. Despite intensive therapy, the patient died on day 18. In conclusion, treatment with PMX-DHP and oseltamivir is effective on ARDS due to influenza but only if initiated early.

The efficacy and nephrotoxicity associated with colistin use in an intensive care unit in Vietnam: Use of colistin in a population of lower body weight.

BACKGROUND: There has been a growing need for colistin as a key drug for the treatment of MDR-GNB infection. Information on colistin use in Asian population is limited. METHODS: A retrospective observational study was conducted to assess the efficacy and nephrotoxicity in critically ill adult patients who received intravenous colistin for MDR-GNB infection in the intensive care unit (ICU) at Bach Mai Hospital in Hanoi, Vietnam. Colistin was administered according to the dosing guideline that was based on pharmacokinetic, pharmacodynamic and toxicodynamic principles, adjusted by body weight and creatinine clearance. RESULTS: Twenty-eight eligible patients were included. The mean patient age was 60±20.4 years. The mean body weight was 53±8.6kg. The mean daily dose of colistin was 4.1±1.6 MIU, and the mean cumulative dose of colistin was 48.2±22.8 MIU. Colistin therapies were classified as clinically effective in 19 (67.9%) cases. Six (21.4%) patients developed nephrotoxicity during the study period according to RIFLE criteria. CONCLUSION: A personalized dosing protocol of colistin was effective, with low nephrotoxicity, among critically ill Vietnamese patients with low body weight. Further studies are warranted for assessing the efficacy and toxicity in a larger cohort.

Clinical preparedness for severe pneumonia with highly pathogenic avian influenza A (H5N1): experiences with cases in Vietnam.

BACKGROUND: Avian influenza A (H5N1) in human presents a global pandemic threat, and preparedness is urgently required in high-risk countries. METHODS: A retrospective chart review was conducted on 8 patients with H5N1 infection (aged 2-30 years; 3 fatal) who were hospitalized in Bach Mai Hospital (BMH), Vietnam, or in affiliated hospitals with consultation by physicians in BMH between 2007 and 2010. Demographic background, chest radiographs, and clinical and laboratory data were evaluated to determine the critical issues in relation to clinical outcomes. Treatment of 4 patients with acute respiratory distress syndrome (ARDS) (2 fatal) was assessed for renal replacement therapy using continuous hemodiafiltration (CHDF), polymyxin B-immobilized (PMX) hemoperfusion, or their combination. RESULTS: Patients had direct contact with dead/sick poultry infected with H5N1 virus or lived in areas where H5N1 poultry outbreaks had been reported at the same time as their illness. Time to initiation of oseltamivir from symptom onset was 2-6 days for survivors and 7-9 days for non-survivors. All patients except one had infiltrative shadows on chest radiographs on admission. Patients with delayed treatment developed ARDS. Renal replacement therapy contributed to patient survival, with improvement of oxygenation and a dramatic decrease in serum cytokine levels if initiated earlier. CONCLUSIONS: Understanding local H5N1 poultry outbreaks and chest radiography assist early diagnosis and initiation of antiviral treatment. Developing a network among local and tertiary care hospitals can reduce the time to initiation of treatment. CHDF and PMX hemoperfusion are possible candidates for effective treatment of ARDS with H5N1 if applied earlier.