Study on the co-infection of children with severe community-acquired pneumonia.

BACKGROUD: Pneumonia is one of the leading causes of death in children under 5 years old. Viruses have historically been the most common cause of community-acquired pneumonia in children. Co-infections in severe pneumonia are more concern by clinicians. METHOD: It was a perspective and descriptive study. Real-time polymerase chain reaction (RT-PCR) is a modern test that was used to detect many new pathogens, including microbiological co-infections. RT-PCR technique was used in this study to investigate the causes of severe pneumonia. RESULTS: Through the analysis of nasopharyngeal aspiration samples from 95 children with severe community-acquired pneumonia, the positive RT-PCR rate was 90.5%. Viral-bacterial co-infection accounted for the highest proportion (43.1%), followed by bacterial co-infection (33.7%), viral infection (7.4%), bacterial infection (6.3%) and the remaining 9.5% was unknown. In the co-infections groups, the five main bacteria species detected by PCR were Streptococcus pneumoniae, Haemophilus influenzae, MRSA, Moraxella catarrhalis and Mycoplasma pneumoniae. CONCLUSION: Antibiotic treatment should focus on detected microbes in cases of severe pneumonia for having a good result.

A dengue outbreak on a floating village at Cat Ba Island in Vietnam.

BACKGROUND: A dengue outbreak in an ecotourism destination spot in Vietnam, from September to November 2013, impacted a floating village of fishermen on the coastal island of Cat Ba. The outbreak raises questions about how tourism may impact disease spread in rural areas. METHODS: Epidemiological data were obtained from the Hai Phong Preventive Medical Center (PMC), including case histories and residential location from all notified dengue cases from this outbreak. All household addresses were geo-located. Knox test, a spatio-temporal analysis that enables inference dengue clustering constrained by space and time, was performed on the geocoded locations. From the plasma available from two patients, positive for Dengue serotype 3 virus (DENV3), the Envelope (E) gene was sequenced, and their genetic relationships compared to other E sequences in the region. RESULTS: Of 192 dengue cases, the odds ratio of contracting dengue infections for people living in the floating villages compared to those living on the island was 4.9 (95 % CI: 3.6-6.7). The space-time analyses on 111 geocoded dengue residences found the risk of dengue infection to be the highest within 4 days and a radius of 20 m of a given case. Of the total of ten detected clusters with an excess risk greater than 2, the cluster with the highest number of cases was in the floating village area (24 patients for a total duration of 31 days). Phylogenetic analysis revealed a high homology of the two DENV3 strains (genotype III) from Cat Ba with DENV3 viruses circulating in Hanoi in the same year (99.1 %). CONCLUSIONS: Our study showed that dengue transmission is unlikely to be sustained on Cat Ba Island and that the 2013 epidemic likely originated through introduction of viruses from the mainland, potentially Hanoi. These findings suggest that prevention efforts should be focused on mainland rather than on the island.

Antibiotic resistance determination using Enterococcus faecium whole-genome sequences: a diagnostic accuracy study using genotypic and phenotypic data.

BACKGROUND: DNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining antibiotic resistance by detecting genetic determinants associated with decreased antibiotic susceptibility. Here, we aimed to assess and improve the accuracy of antibiotic resistance determination from Enterococcus faecium genomes for diagnosis and surveillance purposes. METHODS: In this retrospective diagnostic accuracy study, we first conducted a literature search in PubMed on Jan 14, 2021, to compile a catalogue of genes and mutations predictive of antibiotic resistance in E faecium. We then evaluated the diagnostic accuracy of this database to determine susceptibility to 12 different, clinically relevant antibiotics using a diverse population of 4382 E faecium isolates with available whole-genome sequences and in vitro culture-based AST phenotypes. Isolates were obtained from various sources in 11 countries worldwide between 2000 and 2018. We included isolates tested with broth microdilution, Vitek 2, and disc diffusion, and antibiotics with at least 50 susceptible and 50 resistant isolates. Phenotypic resistance was derived from raw minimum inhibitory concentrations and measured inhibition diameters, and harmonised primarily using the breakpoints set by the European Committee on Antimicrobial Susceptibility Testing. A bioinformatics pipeline was developed to process raw sequencing reads, identify antibiotic resistance genetic determinants, and report genotypic resistance. We used our curated database, as well as ResFinder, AMRFinderPlus, and LRE-Finder, to assess the accuracy of genotypic predictions against phenotypic resistance. FINDINGS: We curated a catalogue of 228 genetic markers involved in resistance to 12 antibiotics in E faecium. Very accurate genotypic predictions were obtained for ampicillin (sensitivity 99·7% [95% CI 99·5-99·9] and specificity 97·9% [95·8-99·0]), ciprofloxacin (98·0% [96·4-98·9] and 98·8% [95·9-99·7]), vancomycin (98·8% [98·3-99·2] and 98·8% [98·0-99·3]), and linezolid resistance (after re-testing false negatives: 100·0% [90·8-100·0] and 98·3% [97·8-98·7]). High sensitivity was obtained for tetracycline (99·5% [99·1-99·7]), teicoplanin (98·9% [98·4-99·3]), and high-level resistance to aminoglycosides (97·7% [96·6-98·4] for streptomycin and 96·8% [95·8-97·5] for gentamicin), although at lower specificity (60-90%). Sensitivity was expectedly low for daptomycin (73·6% [65·1-80·6]) and tigecycline (38·3% [27·1-51·0]), for which the genetic basis of resistance is not fully characterised. Compared with other antibiotic resistance databases and bioinformatic tools, our curated database was similarly accurate at detecting resistance to ciprofloxacin and linezolid and high-level resistance to streptomycin and gentamicin, but had better sensitivity for detecting resistance to ampicillin, tigecycline, daptomycin, and quinupristin-dalfopristin, and better specificity for ampicillin, vancomycin, teicoplanin, and tetracycline resistance. In a validation dataset of 382 isolates, similar or improved diagnostic accuracies were also achieved. INTERPRETATION: To our knowledge, this work represents the largest published evaluation to date of the accuracy of antibiotic susceptibility predictions from E faecium genomes. The results and resources will facilitate the adoption of whole-genome sequencing as a tool for the diagnosis and surveillance of antimicrobial resistance in E faecium. A complete characterisation of the genetic basis of resistance to last-line antibiotics, and the mechanisms mediating antibiotic resistance silencing, are needed to close the remaining sensitivity and specificity gaps in genotypic predictions. FUNDING: Wellcome Trust, UK Department of Health, British Society for Antimicrobial Chemotherapy, Academy of Medical Sciences and the Health Foundation, Medical Research Council Newton Fund, Vietnamese Ministry of Science and Technology, and European Society of Clinical Microbiology and Infectious Disease.

Antibiotic resistance of Streptococcus pneumoniae in Vietnamese children with severe pneumonia: a cross-sectional study.

Background: Streptococcus pneumoniae is the most common bacterium that causes community-acquired pneumonia (CAP) in children. The rate of S. pneumoniae resistance to antibiotics is increasing, particularly in patients with severe CAP. Therefore, the level of antibiotic resistance of S. pneumoniae causing severe CAP in Vietnamese children requires regular monitoring. Methods: This was a cross-sectional descriptive study. Nasopharyngeal aspiration specimens from children were cultured, isolated, and examined for S. pneumoniae. Bacterial strains were assessed for antimicrobial susceptibility, and the minimum inhibitory concentration (MIC) was determined. Results: Eighty-nine strains of S. pneumoniae were isolated from 239 children with severe CAP. The majority of isolates were completely non-susceptible to penicillin (1.1% intermediate, 98.9% resistant) and highly resistant to erythromycin (96.6%) and clarithromycin (88.8%); the rate of resistance to ceftriaxone was 16.9%, with the proportion of intermediate resistance at 46.0%; 100% of strains were susceptible to vancomycin and linezolid. For most antibiotics, MIC50 and MIC90 were equal to the resistance threshold according to the Clinical and Laboratory Standards Institute 2021; penicillin had an eight-fold increase in MIC90 (64 mg/L) and ceftriaxone had a 1.5-fold increase in MIC90 (6 mg/L). Conclusion: Streptococcus pneumoniae isolates described in this study were resistant to many antibiotics. Penicillin should not be the first-line antibiotic of choice, and ceftriaxone at an enhanced dose should be used instead.

Antimicrobial susceptibility testing results from 13 hospitals in Viet Nam: VINARES 2016-2017.

OBJECTIVE: To analyse data from 2016-17 from a hospital-based antimicrobial resistance surveillance with national coverage in a network of hospitals Viet Nam. METHODS: We analysed data from 13 hospitals, 3 less than the dataset from the 2012-13 period. Identification and antimicrobial susceptibility testing data from the clinical microbiology laboratories from samples sent in for routine diagnostics were used. Clinical and Laboratory Standards Institute 2018 guidelines were used for antimicrobial susceptibility testing interpretation. WHONET was used for data entry, management and analysis. RESULTS: 42,553 deduplicated isolates were included in this analysis; including 30,222 (71%) Gram-negative and 12,331 (29%) Gram-positive bacteria. 8,793 (21%) were from ICUs and 7,439 (18%) isolates were from invasive infections. Escherichia coli and Staphylococcus aureus were the most frequently detected species with 9,092 (21%) and 4,833 isolates (11%), respectively; followed by Klebsiella pneumoniae (3,858 isolates - 9.1%) and Acinetobacter baumannii (3,870 isolates - 9%). Bacteria were mainly isolated from sputum (8,798 isolates - 21%), blood (7,118 isolates - 17%) and urine (5,202 isolates - 12%). Among Gram-positives 3,302/4,515 isolates (73%) of S. aureus were MRSA; 99/290 (34%) of Enterococcus faecium were resistant to vancomycin; and 58% (663/1,136) of Streptococcus pneumoniae proportion were reduced susceptible to penicillin. Among Gram-negatives 59% (4,085/6,953) and 40% (1,186/2,958) of E. coli and K. pneumoniae produced ESBL and 29% (376/1,298) and 11% (961/8,830) were resistant to carbapenems, respectively. 79% (2855/3622) and 45% (1,514/3,376) of Acinetobacter spp. and Pseudomonas aeruginosa were carbapenem resistant, respectively. 88% (804/911) of Haemophilus influenzae were ampicillin resistant and 18/253 (7%) of Salmonella spp. and 7/46 (15%) of Shigella spp. were resistant to fluoroquinolones. The number of isolates from which data were submitted in the 2016-2017 period was twice as high as in 2012-2013. AMR proportions were higher in 2016-2017 for most pathogen-antimicrobial combinations of interest including imipenem-resistant A. baumannii, P. aeruginosa and Enterobacterales. CONCLUSIONS: The data show alarmingly high and increasing resistant proportions among important organisms in Viet Nam. AMR proportions varied across hospital types and should be interpreted with caution because existing sampling bias and missing information on whether isolates were community or hospital acquired. Affordable and scalable ways to adopt a sample- or case-based approach across the network should be explored and clinical data should be integrated to help provide more accurate inferences of the surveillance data.

Associated Factors with Perceived Fear of COVID-19 among Vietnamese Hospital Healthcare Workers during Fourth Wave of the COVID-19 Pandemic: Policy Implications for Interconnected and Social- and Personal-Based Health Support.

(1) Background: The present study measures the fear of COVID-19 among hospital healthcare workers and identifies several factors associated with increasing fear of COVID-19. (2) Methods: A cross-sectional, hospital-based survey was conducted on healthcare workforce recruited from the National Hospital of Tropical Diseases from 1 October 2021 and 20 October 2021. We selected the participants who have been directly involved in diagnosing, treating, or providing nursing care to patients with COVID-19. The primary data was collected via sending the invitation directly to the participants, utilizing structured self-completed questionnaires. The seven-item fear of COVID-19 scale was used to measure the data. The responses of 208 hospital healthcare workers were included in the final analysis. (3) Results: Total score of COVID-19 fear was 19.62 (SD = 5.22). The COVID-19 fear score of 7 items ranged from 2.38 (SD = 0.83) to 3.21 (SD = 0.96). The lowest and highest scores were the item 'My hands become clammy when I think about Corona' and the item 'I am most afraid of corona' was the highest, respectively. Linear regression of the COVID-19 fear showed that the factors positively correlated with the fear of COVID-19 among hospital healthcare workers were: being influenced by the community (p = 0.001), feeling at very high risk of COVID-19 (p = 0.03), and experiencing traumatic stress with an academic event (p = 0.042). (4) Conclusions: Although these findings merit further elaboration, these preliminary findings suggest relatively great fear of the COVID-19 pandemic among Vietnamese hospital healthcare workers and that social and personal connections are necessary for maintaining the mental wellbeing.

Depression, Anxiety and Associated Factors among Frontline Hospital Healthcare Workers in the Fourth Wave of COVID-19: Empirical Findings from Vietnam.

(1) Background: This study aims to assess the magnitude of, and factors associated with, depression and anxiety among Vietnamese frontline hospital healthcare workers in the fourth wave of COVID-19; (2) Methods: A hospital based cross-sectional study was carried out within two weeks, October 2020, at a central COVID-19 treatment hospital. Depression and anxiety were measured with PHQ-9 and GAD-7, respectively. Bivariate and multivariate logistic regression analysis were applied to recognize variables related to depression and anxiety, respectively; (3) Results: Among 208 frontline hospital healthcare workers, overall prevalence of depressive symptoms, anxiety symptoms, and both symptoms of depression and anxiety was 38.94%, 25.48% and 24.04%, respectively, in healthcare workers. In a reduced model after using multivariate stepwise logistic regression, age (OR = 0.9, p = 0.001), marital status (OR = 7.84, p = 0.027), profession (OR = 0.39, p = 0.028), having experienced traumatic stress following a work event (OR = 46.24, p < 0.001), feeling at very high risk for COVID-19 (OR = 0.02, p < 0.04), and affected by workplace conditions (OR = 5.36, p < 0.001) were associated with the symptoms of depression. With regard to symptoms of anxiety, single status (OR: 12.18, p = 0.002), being medical technician (OR: 68.89, p < 0.001), alcohol use (OR: 6.83, p = 0.014), using pain relief medications (OR: 25.50, p = 0.047), having experienced traumatic stress following a family event (OR: 130.32, p = 0.001), having experienced traumatic stress following a work event (OR: 181.55, p = 0.002), reporting at very high risk for COVID-19 (OR: 29.64, p = 0.011), treating moderate (OR: 6.46, p = 0.038) and severe (OR: 18.96, p = 0.004) COVID-19 patients, and being significantly affected by the community (OR: 6.33, p = 0.003) were increased risk factors for the symptoms of anxiety. Meanwhile, those living with 4-5 people (OR: 0.15, p = 0.011), specializing in infectious disease (OR: 0.13, p = 0.044)/resuscitation and emergency medicine (OR: 0.04, p = 0.046), and having knowledge preparation before participating in COVID-19 (OR: 0.008, p = 0.014) were less associated with the symptoms of anxiety; (4) Conclusions: There was a relatively high prevalence among Vietnamese hospital healthcare workers exhibiting symptoms of depression and anxiety during the ongoing pandemic. Greater attention to training in psychological skills should be suggested for those belonging to a younger age group, being single/widowed/divorced, treating moderate and severe COVID-19 patients, feeling at very high risk for COVID-19, being significantly affected a lot the community or workplace conditions, or experiencing traumatic stress following a family/work event in the past week.

Multiple routes of hepatitis C virus transmission among injection drug users in Hai Phong, Northern Vietnam.

To identify hepatitis C virus (HCV) transmission routes among injection drug users in Northern Vietnam, plasma samples were collected from 486 drug users in Hai Phong. Plasma viral RNA was extracted from 323 (66.5%) samples that were positive for anti-HCV antibodies. Portions of the HCV 5'-untranslated (5'UTR)-Core and NS5B genes were amplified by reverse-transcriptase polymerase chain reaction, sequenced directly, and genotyped in 194 and 195 specimens, respectively. Both regions were genotyped in 137 specimens. In the 5'UTR-Core region, genotype 6a was predominant (32.5%), followed by genotype 1a (23.7%), genotype 1b (20.6%), and genotype 6e (14.4%). In the NS5B region, genotype 1a was predominant (42.6%), followed by genotype 1b (24.1%), genotype 6a (14.4%), genotype 3b (7.2%), and genotype 6e (5.1%). Of the 137 specimens with both regions genotyped, 23 (16.8%) showed discordant genotyping results between the two regions, suggesting possible recombination and/or dual infection. Phylogenetic analysis revealed close associations between Hai Phong strains and strains from Southern China: the Yunnan province for genotype 3b; the Guangxi province for genotype 6e; the USA for genotype 1a; and Southern Vietnam for genotypes 1a and 6e. The human immunodeficiency virus (HIV) infection rate among HCV-infected injection drug users was 52.6-55.4% and did not differ significantly by HCV genotype. Most drug users infected with HIV-1 [98.8% (171/173)] were co-infected with HCV. These results suggest multiple routes of HCV transmission among injection drug users in Northern Vietnam that may also be HIV transmission routes.

Antimicrobial susceptibility testing and antibiotic consumption results from 16 hospitals in Viet Nam: The VINARES project 2012-2013.

OBJECTIVE: To establish a hospital-based surveillance network with national coverage for antimicrobial resistance (AMR) and antibiotic consumption in Viet Nam. METHODS: A 16-hospital network (Viet Nam Resistance: VINARES) was established and consisted of national and provincial-level hospitals across the country. Antimicrobial susceptibility testing results from routine clinical diagnostic specimens and antibiotic consumption data in Defined Daily Dose per 1000 bed days (DDD/1000 patient-days) were prospectively collected and analysed between October 2012 and September 2013. RESULTS: Data from a total of 24 732 de-duplicated clinical isolates were reported. The most common bacteria were: Escherichia coli (4437 isolates, 18%), Klebsiella spp. (3290 isolates, 13%) and Acinetobacter spp. (2895 isolates, 12%). The hospital average antibiotic consumption was 918 DDD/1000 patient-days. Third-generation cephalosporins were the most frequently used antibiotic class (223 DDD/1000 patient-days, 24%), followed by fluoroquinolones (151 DDD/1000 patient-days, 16%) and second-generation cephalosporins (112 DDD/1000 patient-days, 12%). Proportions of antibiotic resistance were high: 1098/1580 (69%) Staphylococcus aureus isolates were methicillin-resistant (MRSA); 115/344 isolates (33%) and 90/358 (25%) Streptococcus pneumoniae had reduced susceptibility to penicillin and ceftriaxone, respectively. A total of 180/2977 (6%) E. coli and 242/1526 (16%) Klebsiella pneumoniae were resistant to imipenem, respectively; 602/1826 (33%) Pseudomonas aeruginosa were resistant to ceftazidime and 578/1765 (33%) to imipenem. Of Acinetobacter spp. 1495/2138 (70%) were resistant to carbapenems and 2/333 (1%) to colistin. CONCLUSIONS: These data are valuable in providing a baseline for AMR among common bacterial pathogens in Vietnamese hospitals and to assess the impact of interventions.

Limited geographic distribution of the novel cyclovirus CyCV-VN.

A novel cyclovirus, CyCV-VN, was recently identified in cerebrospinal fluid (CSF) from patients with central nervous system (CNS) infections in central and southern Vietnam. To explore the geographic distribution of this novel virus, more than 600 CSF specimens from patients with suspected CNS infections in northern Vietnam, Cambodia, Nepal and The Netherlands were screened for the presence of CyCV-VN but all were negative. Sequence comparison and phylogenetic analysis between CyCV-VN and another novel cyclovirus recently identified in CSF from Malawian patients indicated that these represent distinct cycloviral species, albeit phylogenetically closely related. The data suggest that CyCV-VN has a limited geographic distribution within southern and central Vietnam. Further research is needed to determine the global distribution and diversity of cycloviruses and importantly their possible association with human disease.

Severe pandemic H1N1 2009 infection is associated with transient NK and T deficiency and aberrant CD8 responses.

BACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired.

Immunological and viral determinants of dengue severity in hospitalized adults in Ha Noi, Viet Nam.

BACKGROUND: The relationships between the infecting dengue serotype, primary and secondary infection, viremia and dengue severity remain unclear. This cross-sectional study examined these interactions in adult patients hospitalized with dengue in Ha Noi. METHODS AND FINDINGS: 158 patients were enrolled between September 16 and November 11, 2008. Quantitative RT-PCR, serology and NS1 detection were used to confirm dengue infection, determine the serotype and plasma viral RNA concentration, and categorize infections as primary or secondary. 130 (82%) were laboratory confirmed. Serology was consistent with primary and secondary infection in 34% and 61%, respectively. The infecting serotype was DENV-1 in 42 (32%), DENV-2 in 39 (30%) and unknown in 49 (38%). Secondary infection was more common in DENV-2 infections (79%) compared to DENV-1 (36%, p<0.001). The proportion that developed dengue haemorrhagic fever (DHF) was 32% for secondary infection compared to 18% for primary infection (p = 0.14), and 26% for DENV-1 compared to 28% for DENV-2. The time until NS1 and plasma viral RNA were undetectable was shorter for DENV-2 compared to DENV-1 (p≤0.001) and plasma viral RNA concentration on day 5 was higher for DENV-1 (p = 0.03). Plasma viral RNA concentration was higher in secondary infection on day 5 of illness (p = 0.046). We didn't find an association between plasma viral RNA concentration and clinical severity. CONCLUSION: Dengue is emerging as a major public health problem in Ha Noi. DENV-1 and DENV-2 were the prevalent serotypes with similar numbers and clinical presentation. Secondary infection may be more common amongst DENV-2 than DENV-1 infections because DENV-2 infections resulted in lower plasma viral RNA concentrations and viral RNA concentrations were higher in secondary infection. The drivers of dengue emergence in northern Viet Nam need to be elucidated and public health measures instituted.