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    linus Olson

    Objectives Carbapenemase-producing Enterobacterales (CPE) are high priority targets of global antimicrobial surveillance. Herein, we determined the colonization rate of CPE on admission to intensive care units in Vientiane, Lao PDR in... more
    Objectives Carbapenemase-producing Enterobacterales (CPE) are high priority targets of global antimicrobial surveillance. Herein, we determined the colonization rate of CPE on admission to intensive care units in Vientiane, Lao PDR in August-September 2019. Methods Data regarding clinical conditions, infection control, and antibiotic usage were collected during admission. Rectal swab samples (n = 137) collected during admission were inoculated to selective chromogenic agars, followed by confirmatory tests for extended-spectrum beta-lactamases and carbapenemases. All CPE isolates were sequenced on Illumina (HiSeq2500), reads assembled using SPAdes 3.13, and the draft genomes used to query a database (https://www.genomicepidemiology.org) for resistome, plasmid replicons, and sequence types (ST). Optical DNA mapping (ODM) was used to characterize plasmids and to determine location of resistance genes. Minimum spanning tree was generated using the Bacterial Isolate Genome Sequence datab...
    BackgroundThe quality of neonatal resuscitation after delivery needs to be improved to reach the Sustainable Development Goals 3.2 (reducing neonatal deaths to <12/1,000 live newborns) by the year 2030. Studies have emphasized the... more
    BackgroundThe quality of neonatal resuscitation after delivery needs to be improved to reach the Sustainable Development Goals 3.2 (reducing neonatal deaths to <12/1,000 live newborns) by the year 2030. Studies have emphasized the importance of correctly performing the basic steps of resuscitation including stimulation, heart rate assessment, ventilation, and thermal control. Recordings with video cameras have previously been shown to be one way to identify performance practices during neonatal resuscitation.MethodsA description of a low-cost delivery room set up for video recording of neonatal resuscitation. The technical setup includes rechargeable high-definition cameras with two-way audio, NeoBeat heart rate monitors, and the NeoTapAS data collection tools for iPad with direct data export of data for statistical analysis. The setup was field tested at Mulago National Referral Hospital, Kampala, Uganda, and Phu San Hanoi Hospital, Hanoi, Vietnam.ResultsThe setup provided highl...
    Additional file 5: Fig. S5. The genetic relatedness based on single-nucleotide polymorphisms (SNPs) of 8 carbapenem-resistant Klebsiella pneumoniae (CRKP) belonging to ST334 collected from faecal samples from patients at the study... more
    Additional file 5: Fig. S5. The genetic relatedness based on single-nucleotide polymorphisms (SNPs) of 8 carbapenem-resistant Klebsiella pneumoniae (CRKP) belonging to ST334 collected from faecal samples from patients at the study hospital was illustrated in a phylogenetic tree. The closest distances between these clusters are denoted by the closest related inter-cluster relatives as indicated along the vertical line. The maximum number of SNPs along the clusters indicate the largest distance between two isolates in the indicated cluster.
    Background Vietnam and Southeast Asia are hotspots for antimicrobial resistance; however, little is known on the prevalence of carriage of carbapenem resistance in non-hospitalized humans and in animals. Carbapenem-resistant... more
    Background Vietnam and Southeast Asia are hotspots for antimicrobial resistance; however, little is known on the prevalence of carriage of carbapenem resistance in non-hospitalized humans and in animals. Carbapenem-resistant Enterobacteriaceae (CRE), particularly Escherichia coli (CREC) and Klebsiella pneumoniae (CRKP) and also Acinetobacter baumannii (CRAB) are emerging threats worldwide. Methods We investigated healthy humans (n = 652), chickens (n = 237), ducks (n = 150) and pigs (n = 143) in 400 small-scale farms in the Mekong Delta of Vietnam. Samples (rectal swabs, faecal swabs) were investigated for carriage of CRE/CRAB and were further characterized phenotypically and genotypically. Results In the Mekong Delta of Vietnam, the prevalence of CRE isolates in human rectal swabs was 0.6%, including 4 CREC and 1 CRKP. One pig was infected with CREC (prevalence 0.7%). CRAB was isolated from chickens (n = 4) (prevalence 2.1%) and one duck (prevalence 0.7%). CRKP was isolated from a ...
    Supplemental material, Supplementary_data_1 for Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam by Linh Vu Phuong Dang, Hung Viet Pham, Thanh Thi Dinh, Phuong Thi Vu, Lam Van... more
    Supplemental material, Supplementary_data_1 for Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam by Linh Vu Phuong Dang, Hung Viet Pham, Thanh Thi Dinh, Phuong Thi Vu, Lam Van Nguyen, Hai Thanh Le, Mattias Larsson and Linus Olson in Therapeutic Advances in Infectious Disease
    Objectives To assess if admission screening for Carbapenem Resistant Enterobacteriaceae (CRE) and cohort care can reduce CRE acquisition (CRE colonization during hospital stay), Hospital Acquired Infections (HAI), hospital-stay,... more
    Objectives To assess if admission screening for Carbapenem Resistant Enterobacteriaceae (CRE) and cohort care can reduce CRE acquisition (CRE colonization during hospital stay), Hospital Acquired Infections (HAI), hospital-stay, mortality, and costs in three Intensive Care Units (ICU’s) at the Vietnamese National Children’s Hospital. Method CRE screening using rectal swabs and ChromIDCarbas elective culture at admission and if CRE negative, once weekly. Patients were treated in cohorts based on CRE colonization status. Results CRE colonization at baseline point-prevalence screening was 76.9% (103/134). Of 941 CRE screened at admission, 337 (35.8%) were CREpos. 694 patients met inclusion criteria. The 244 patients CRE negative at admission and screened > 2 times were stratified in 8 similar size groups (periods), based on time of admission. CRE acquisition decreased significant (OR − 3.2, p < 0.005) from 90% in period 2 (highest) to 48% in period 8 (last period). Patients with ...
    OBJECTIVES The carbapenemase-encoding gene blaNDM-1 has been reported in Vietnam over the last ten years, and blaNDM-producing Enterobacteriaceae are now silently and rapidly spreading. A key factor behind dissemination of blaNDM-1 are... more
    OBJECTIVES The carbapenemase-encoding gene blaNDM-1 has been reported in Vietnam over the last ten years, and blaNDM-producing Enterobacteriaceae are now silently and rapidly spreading. A key factor behind dissemination of blaNDM-1 are plasmids, mobile genetic elements that commonly carry antibiotic resistance genes and spread via conjugation. Here, we characterized the diversity of blaNDM-1-encoding plasmids from neonates at a large Vietnamese hospital . METHODS 18 fecal Klebsiella pneumoniae and Klebsiella quasipneumoniae isolates collected from 16 neonates at a large pediatric hospital in Vietnam were studied with optical DNA mapping (ODM) and next-generation sequencing (NGS). We identified the plasmid(s) carrying blaNDM-1 by combining ODM with Cas9 restriction. By comparing the plasmids between isolates, we could investigate if the same plasmid was present in different patients. RESULTS Although the same plasmid was found among some isolates, ODM confirmed that there were at least 10 different plasmids encoding blaNDM-1 among the 18 isolates collected from 16 neonates, suggesting a large plasmid diversity. The ODM results were in large agreement with the NGS data. Interestingly, some isolates had two distinct plasmids encoding blaNDM-1, which could be readily detected with ODM. Thus far, the coexistence of different plasmids carrying the same carbapenem resistance gene in an isolate encoding blaNDM-1 has rarely been reported, likely due to limitations in existing plasmid characterization techniques. CONCLUSIONS Our results show that the plasmids encoding blaNDM-1 in this cohort were very diverse, suggesting a similar picture in the Vietnamese society. The study also highlights important aspects of the usefulness of ODM for plasmid analysis.
    Received: 18/4/2021 The study aims to describe the current status of HIV infection and some factors related to the common syndromes/ diseases in HIV-infected children aged 10-15 years received ARV treatment at the Vietnam national... more
    Received: 18/4/2021 The study aims to describe the current status of HIV infection and some factors related to the common syndromes/ diseases in HIV-infected children aged 10-15 years received ARV treatment at the Vietnam national children’s hospital in 2020. A descriptive cross-sectional study was performed on 187 patients, the average age was 12.84 ± 1.65 years, the male/ female ratio was 1.2/1. Maternal transmission of HIV was the main mode of transmission (over 90%). The rate of patients infected with HIV > 1 year is 98.93%. This is also the rate of patients with ARV treatment time > 1 year. Before treatment ARV, the most recognized opportunistic infections, are Wasting syndrome caused by HIV infection (11.22%) and tuberculosis (9.63%). At the time of the study, the first clinical stage accounted for the main proportion (97.86%), the viral load below the detection threshold (81.3%), the number of T-CD4 cells ≥ 500 (82.9%), 1st line therapy is mainly used for treatment (80....
    Background The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is a growing problem globally, particularly in low- to middle-income countries (LMICs). Previous studies have shown high rates of CRE colonisation among... more
    Background The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is a growing problem globally, particularly in low- to middle-income countries (LMICs). Previous studies have shown high rates of CRE colonisation among patients at hospitals in LMICs, with increased risk of hospital-acquired infections. Methods We isolated carbapenem-resistant Klebsiella pneumoniae (CRKP) from faecal samples collected in 2017 from patients at admission and discharge at a Vietnamese neonatal intensive care unit (NICU). 126 CRKP were whole-genome sequenced. The phylogenetic relationship between the isolates and between clinical CRKP isolates collected in 2012–2018 at the same hospital were investigated. Results NDM-type carbapenemase-(61%) and KPC-2-encoding genes (41%) were the most common carbapenem resistance genes observed among the admission and discharge isolates. Most isolates (56%) belonged to three distinct clonal clusters of ST15, carrying blaKPC-2, blaNDM-1 and blaNDM-4, ...
    Mục tiêu: Mô tả chất lượng cuộc sống (CLCS) và một số yếu tố liên quan ở trẻ vị thành niên 10-15 tuổi nhiễm HIV đang điều trị ARV ngoại trú tại Bệnh viện Nhi trung ương. Đối tượng và phương pháp: Nghiên cứu cắt ngang được thực hiện trên... more
    Mục tiêu: Mô tả chất lượng cuộc sống (CLCS) và một số yếu tố liên quan ở trẻ vị thành niên 10-15 tuổi nhiễm HIV đang điều trị ARV ngoại trú tại Bệnh viện Nhi trung ương. Đối tượng và phương pháp: Nghiên cứu cắt ngang được thực hiện trên 190 trẻ từ 10-15 tuổi nhiễm HIV đang được quản lý điều trị ARV ngoại trú tại Bệnh viện Nhi trung ương từ 6-12/2020. CLCS được đánh giá bằng công cụ PedsQL 4.0 với 23 câu hỏi liên quan đến 4 lĩnh vực về thể chất, tình cảm, xã hội và học tập. Điểm số càng cao tương ứng với CLCS càng tốt. Kết quả: Điểm trung bình CLCS chung 72,2; về sức khỏe thể chất 80,3; sức khỏe tâm lý xã hội 75,6; xã hội 82,2; cảm xúc 76,3; và học tập 68,3. Tỷ lệ CLCS tốt tính chung là 56,8%; về sức khỏe thể chất 67,9%; sức khỏe tâm lý xã hội 57,4%; về xã hội 73,2%, cảm xúc 57,9% và học tập 45,3%. Trẻ thuộc các hộ gia đình nghèo, trẻ có NCS có học vấn thấp (từ THCS trở xuống) và trẻ có thời gian từ nhà đến phòng khám từ 60 phút trở lên có CLCS thấp hơn (p<0,05). Kết luận: Trẻ vị ...
    To assess a cost‐effective in‐house selective plate formula for actively screening carbapenem‐resistant Enterobacteriaceae (CRE).
    Background: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective... more
    Background: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the gag gene, particularly the important functional binding domains in relation to treatment outcomes. Methods: HIV-infected children enrolled and treated at Vietnam National Children’s Hospital were recruited in the study. A total of 25 gag sequences were generated and used to construct phylogenetic trees and aligned with a reference sequence comparing 17 functional domains. Results: We found that all patients in a treatment failure (TF) group belonged to one cluster of the phylogenetic tree. In addition, the rate of mutations was significantly higher in TF compared with a treatment success (TS) group, specifically the PIP2 recognition motif, and the nucleocapsid basic and zinc motif 2 domains...
    AimTo evaluate whether phase‐changing material can be used for therapeutic hypothermia of asphyxiated newborns in low‐resource settings.MethodsProspective interventional study of asphyxiated term infants fulfilling criteria for... more
    AimTo evaluate whether phase‐changing material can be used for therapeutic hypothermia of asphyxiated newborns in low‐resource settings.MethodsProspective interventional study of asphyxiated term infants fulfilling criteria for hypothermia treatment at Vietnam National Children's Hospital from September 2014 to September 2016. Hypothermia was induced within 6 hours after birth and maintained for 72 hours by a phase‐changing material mattress with melting point of 32°C. Rectal temperature was continuously measured, and deviations from target temperature range 33.5‐34.5°C were recorded.ResultsIn total 52 infants (mean gestational age 39.3 ± 1.1 weeks) included and cooled, the median temperature at initiation of cooling was 35.3 (IQR 34.5‐35.9)°C. The median time to reach target temperature was 2.5 (IQR 2‐3) hours. The mean temperature during the cooling phase was 33.95 ± 0.2°C. Throughout the cooling phase, the target temperature range (33.5‐34.5°C) was maintained more than 80% of...
    Background:HIV is characterized by high levels of genetic variability, including increased numbers of heterogeneous sequences of the envelope region. Therefore, studying genetic variability of HIV in relation to viral replication might... more
    Background:HIV is characterized by high levels of genetic variability, including increased numbers of heterogeneous sequences of the envelope region. Therefore, studying genetic variability of HIV in relation to viral replication might facilitate prognosis of disease progression.Methods:The study was designed as cross-sectional; data and samples of participants collected and analyzed env genes were obtained from 23 children enrolled by Vietnam National Children’s Hospital.Results:Substantial mutations in the C2 region were found in patients with high levels of viral replication while changes in the C3 region were mostly found in patients with low viral load. In the V1 region, we found profound amino acid modifications in patients with low HIV viral loads in contrast to the V2 sequence, where we identified single point mutations in patients with increased HIV viral load. The V3 region was relatively homogeneous, while profound deletions in the V4 region were detected in patients with...
    Background Carbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection... more
    Background Carbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC). Methods A point prevalence survey (PPS) with screening for colonization with CRE was conducted on 2233 patients admitted to neonatal, pediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of fecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome. Results A total of 1165 (52%) patients were colonized with CRE...
    ObjectiveTo gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on... more
    ObjectiveTo gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR).DesignA web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns.Setting39 NNUs from 12 countries.PatientsAny neonate admitted to one of the participating NNUs.InterventionsThis was an observational cohort study.ResultsThe number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <...
    Resistance among Klebsiella pneumoniae to the last resort antibiotics carbapenems and colistin is increasing worldwide. In this study, we used whole-genome sequencing to determine the colistin resistance mechanisms in clinical isolates of... more
    Resistance among Klebsiella pneumoniae to the last resort antibiotics carbapenems and colistin is increasing worldwide. In this study, we used whole-genome sequencing to determine the colistin resistance mechanisms in clinical isolates of carbapenem- and colistin-resistant K. pneumoniae from Vietnam. Alterations in the regulatory gene mgrB, via mutations and insertion sequence transpositions, was found in 30 of 31 isolates, emphasizing the importance of this resistance mechanism in colistin-resistant K. pneumoniae.
    A carbapenemase-producing colistin-resistant Klebsiella oxytoca isolate was recovered from a blood culture of a female patient without previous report of risk factors to obtain multidrug-resistant Gram-negative bacilli. A combination of... more
    A carbapenemase-producing colistin-resistant Klebsiella oxytoca isolate was recovered from a blood culture of a female patient without previous report of risk factors to obtain multidrug-resistant Gram-negative bacilli. A combination of biochemical and molecular methods was used to identify the resistance mechanism of this isolate. Carbapenemase production was mediated by Verona integron-encoded metallo-β-lactamase (VIM)-2. Colistin resistance was not due to plasmid- borne mcr-1 gene, but we found an integration of IS5-like sequence in the mgrB gene of K. oxytoca. This gene is known to be an important regulator of the PhoPQ two-component system, and the disruption of this gene is most likely the cause of lipid A modification resulting in colistin resistance of our isolate. To the best of our knowledge this constitutes the first report of a carbapenemase-producing K. oxytoca with colistin resistance, a case that demonstrates the limited treatment options for infections with multidrug...
    Hypothermia can reduce neurodevelopmental disabilities in asphyxiated newborn infants. However, the optimal cooling temperature for neuroprotection is not well defined. We studied the effects of transient piglet brain hypoxic ischemia... more
    Hypothermia can reduce neurodevelopmental disabilities in asphyxiated newborn infants. However, the optimal cooling temperature for neuroprotection is not well defined. We studied the effects of transient piglet brain hypoxic ischemia (HI) on transcriptional activity of eight genes and if mRNA level alterations could be counteracted by whole body cooling to 35, 33.5 or 30 °C. BDNF mRNA was globally upregulated by the insult, and none of the cooling temperatures counteracted this change. In contrast, MANF mRNA was downregulated, and these changes were modestly counteracted in different brain regions by hypothermic treatment at 33.5 °C, while 30 °C aggravated the MANF mRNA loss. MAP2 mRNA was markedly downregulated in all brain regions except striatum, and cooling to 33.5 °C modestly counteract this downregulation in the cortex cerebri. There was a tendency for GFAP mRNA levels in core, but not mantle regions to be downregulated and for these changes to be modestly counteracted by cooling to 33.5 or 35 °C. Cooling to 30 °C caused global GFAP mRNA decrease. HSP70 mRNA tended to become upregulated by HI and to be more pronounced in cortex and CA1 of hippocampus during cooling to 33.5 °C. We conclude that HI causes alterations of mRNA levels of many genes in superficial and deep piglet brain areas. Some of these changes may be beneficial, others detrimental, and lowering body temperature partly counteracts some, but not all changes. There may be general differences between core and mantle regions, as well as between the different cooling temperatures for protection. Comparing the three studied temperatures, cooling to 33.5 °C, appears to provide the best cooling temperature compromise.
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    Background: Induced mild hypothermia is an emerging therapy that has been shown to reduce the combined outcome of death or severe neurodevelopmental disabilities in asphyxiated full‐term infants if started within 6 h after birth.Aim: To... more
    Background: Induced mild hypothermia is an emerging therapy that has been shown to reduce the combined outcome of death or severe neurodevelopmental disabilities in asphyxiated full‐term infants if started within 6 h after birth.Aim: To study the feasibility and safety of inducing hypothermia in asphyxiated infants already at the referring hospital by stopping active warming.Methods: Temperatures during passive induction of hypothermia were prospectively collected from transported asphyxiated infants.Results: Between December 2006 and April 2008, 37 infants of the total birth cohort of 40 350 fulfilled the criteria for hypothermia treatment. Eighteen of 34 infants treated with induced hypothermia were outborn. The rectal temperatures of the infants were 33.0–36.4°C before transport and 31.0–36.5°C on arrival. Six of the infants had a sub‐therapeutic (<33.0°C) rectal temperature on arrival.Conclusion: Passive induction of hypothermia by turning off active warming devices is possib...