Clinical evaluation of AI-assisted muscle ultrasound for monitoring muscle wasting in ICU patients.

Muscle ultrasound has been shown to be a valid and safe imaging modality to assess muscle wasting in critically ill patients in the intensive care unit (ICU). This typically involves manual delineation to measure the rectus femoris cross-sectional area (RFCSA), which is a subjective, time-consuming, and laborious task that requires significant expertise. We aimed to develop and evaluate an AI tool that performs automated recognition and measurement of RFCSA to support non-expert operators in measurement of the RFCSA using muscle ultrasound. Twenty patients were recruited between Feb 2023 and July 2023 and were randomized sequentially to operators using AI (n = 10) or non-AI (n = 10). Muscle loss during ICU stay was similar for both methods: 26 ± 15% for AI and 23 ± 11% for the non-AI, respectively (p = 0.13). In total 59 ultrasound examinations were carried out (30 without AI and 29 with AI). When assisted by our AI tool, the operators showed less variability between measurements with higher intraclass correlation coefficients (ICCs 0.999 95% CI 0.998-0.999 vs. 0.982 95% CI 0.962-0.993) and lower Bland Altman limits of agreement (± 1.9% vs. ± 6.6%) compared to not using the AI tool. The time spent on scans reduced significantly from a median of 19.6 min (IQR 16.9-21.7) to 9.4 min (IQR 7.2-11.7) compared to when using the AI tool (p < 0.001). AI-assisted muscle ultrasound removes the need for manual tracing, increases reproducibility and saves time. This system may aid monitoring muscle size in ICU patients assisting rehabilitation programmes.

The seroincidence of childhood Shigella sonnei infection in Ho Chi Minh City, Vietnam.

BACKGROUND: Shigella sonnei is a pathogen of growing global importance as a cause of diarrhoeal illness in childhood, particularly in transitional low-middle income countries (LMICs). Here, we sought to determine the incidence of childhood exposure to S. sonnei infection in a contemporary transitional LMIC population, where it represents the dominant Shigella species. METHODS: Participants were enrolled between the age of 12-36 months between June and December 2014. Baseline characteristics were obtained through standardized electronic questionnaires, and serum samples were collected at 6-month intervals over two years of follow-up. IgG antibody against S. sonnei O-antigen (anti-O) was measured using an enzyme-linked immunosorbent assay (ELISA). A four-fold increase in ELISA units (EU) with convalescent IgG titre >10.3 EU was taken as evidence of seroconversion between timepoints. RESULTS: A total of 3,498 serum samples were collected from 748 participants; 3,170 from the 634 participants that completed follow-up. Measures of anti-O IgG varied significantly by calendar month (p = 0.03). Estimated S. sonnei seroincidence was 21,451 infections per 100,000 population per year (95% CI 19,307-23,834), with peak incidence occurring at 12-18 months of age. Three baseline factors were independently associated with the likelihood of seroconversion; ever having breastfed (aOR 2.54, CI 1.22-5.26), history of prior hospital admission (aOR 0.57, CI 0.34-0.95), and use of a toilet spray-wash in the household (aOR 0.42, CI 0.20-0.89). CONCLUSIONS: Incidence of S. sonnei exposure in Ho Chi Minh City is substantial, with significant reduction in the likelihood of exposure as age increases beyond 2 years.

Genome evolution of dengue virus serotype 1 under selection by Wolbachia pipientis in Aedes aegypti mosquitoes.

The introgression of antiviral strains of Wolbachia into Aedes aegypti mosquito populations is a public health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of Wolbachia and undermine this approach. Here, we established a serial-passage system to investigate the evolution of DENV in Ae. aegypti mosquitoes infected with the wMel strain of Wolbachia. Using this system, we report on virus genetic outcomes after twenty passages of serotype 1 of DENV (DENV-1). An amino acid substitution, E203K, in the DENV-1 envelope protein was more frequently detected in the consensus sequence of virus populations passaged in wMel-infected Ae. aegypti than wild-type counterparts. Positive selection at residue 203 was reproducible; it occurred in passaged virus populations from independent DENV-1-infected patients and also in a second, independent experimental system. In wild-type mosquitoes and human cells, the 203K variant was rapidly replaced by the progenitor sequence. These findings provide proof of concept that wMel-associated selection of virus populations can occur in experimental conditions. Field-based studies are needed to explore whether wMel imparts selective pressure on DENV evolution in locations where wMel is established.

Applying artificial intelligence and digital health technologies, Viet Nam.

Problem: Direct application of digital health technologies from high-income settings to low- and middle-income countries may be inappropriate due to challenges around data availability, implementation and regulation. Hence different approaches are needed. Approach: Within the Viet Nam ICU Translational Applications Laboratory project, since 2018 we have been developing a wearable device for individual patient monitoring and a clinical assessment tool to improve dengue disease management. Working closely with local staff at the Hospital for Tropical Diseases, Ho Chi Minh City, we developed and tested a prototype of the wearable device. We obtained perspectives on design and use of the sensor from patients. To develop the assessment tool, we used existing research data sets, mapped workflows and clinical priorities, interviewed stakeholders and held workshops with hospital staff. Local setting: In Viet Nam, a lower middle-income country, the health-care system is in the nascent stage of implementing digital health technologies. Relevant changes: Based on patient feedback, we are altering the design of the wearable sensor to increase comfort. We built the user interface of the assessment tool based on the core functionalities selected by workshop attendees. The interface was subsequently tested for usability in an iterative manner by the clinical staff members. Lessons learnt: The development and implementation of digital health technologies need an interoperable and appropriate plan for data management including collection, sharing and integration. Engagements and implementation studies should be conceptualized and conducted alongside the digital health technology development. The priorities of end-users, and understanding context and regulatory landscape are crucial for success.

Clinical benefit of AI-assisted lung ultrasound in a resource-limited intensive care unit.

BACKGROUND: Interpreting point-of-care lung ultrasound (LUS) images from intensive care unit (ICU) patients can be challenging, especially in low- and middle- income countries (LMICs) where there is limited training available. Despite recent advances in the use of Artificial Intelligence (AI) to automate many ultrasound imaging analysis tasks, no AI-enabled LUS solutions have been proven to be clinically useful in ICUs, and specifically in LMICs. Therefore, we developed an AI solution that assists LUS practitioners and assessed its usefulness in  a low resource ICU. METHODS: This was a three-phase prospective study. In the first phase, the performance of four different clinical user groups in interpreting LUS clips was assessed. In the second phase, the performance of 57 non-expert clinicians with and without the aid of a bespoke AI tool for LUS interpretation was assessed in retrospective offline clips. In the third phase, we conducted a prospective study in the ICU where 14 clinicians were asked to carry out LUS examinations in 7 patients with and without our AI tool and we interviewed the clinicians regarding the usability of the AI tool. RESULTS: The average accuracy of beginners' LUS interpretation was 68.7% [95% CI 66.8-70.7%] compared to 72.2% [95% CI 70.0-75.6%] in intermediate, and 73.4% [95% CI 62.2-87.8%] in advanced users. Experts had an average accuracy of 95.0% [95% CI 88.2-100.0%], which was significantly better than beginners, intermediate and advanced users (p < 0.001). When supported by our AI tool for interpreting retrospectively acquired clips, the non-expert clinicians improved their performance from an average of 68.9% [95% CI 65.6-73.9%] to 82.9% [95% CI 79.1-86.7%], (p < 0.001). In prospective real-time testing, non-expert clinicians improved their baseline performance from 68.1% [95% CI 57.9-78.2%] to 93.4% [95% CI 89.0-97.8%], (p < 0.001) when using our AI tool. The time-to-interpret clips improved from a median of 12.1 s (IQR 8.5-20.6) to 5.0 s (IQR 3.5-8.8), (p < 0.001) and clinicians' median confidence level improved from 3 out of 4 to 4 out of 4 when using our AI tool. CONCLUSIONS: AI-assisted LUS can help non-expert clinicians in an LMIC ICU improve their performance in interpreting LUS features more accurately, more quickly and more confidently.

A combination of annual and nonannual forces drive respiratory disease in the tropics.

Background: It is well known that influenza and other respiratory viruses are wintertime-seasonal in temperate regions. However, respiratory disease seasonality in the tropics remains elusive. In this study, we aimed to characterize the seasonality of influenza-like illness (ILI) and influenza virus in Ho Chi Minh City (HCMC), Vietnam. Methods: We monitored the daily number of ILI patients in 89 outpatient clinics from January 2010 to December 2019. We collected nasal swabs and tested for influenza from a subset of clinics from May 2012 to December 2019. We used spectral analysis to describe the periodicities in the system. We evaluated the contribution of these periodicities to predicting ILI and influenza patterns through lognormal and gamma hurdle models. Findings: During ten years of community surveillance, 66,799 ILI reports were collected covering 2.9 million patient visits; 2604 nasal swabs were collected 559 of which were PCR-positive for influenza virus. Both annual and nonannual cycles were detected in the ILI time series, with the annual cycle showing 8.9% lower ILI activity (95% CI: 8.8%-9.0%) from February 24 to May 15. Nonannual cycles had substantial explanatory power for ILI trends (ΔAIC = 183) compared to all annual covariates (ΔAIC = 263). Near-annual signals were observed for PCR-confirmed influenza but were not consistent along in time or across influenza (sub)types. Interpretation: Our study reveals a unique pattern of respiratory disease dynamics in a tropical setting influenced by both annual and nonannual drivers. Timing of vaccination campaigns and hospital capacity planning may require a complex forecasting approach.

Urinary catecholamine excretion, cardiovascular variability, and outcomes in tetanus.

Severe tetanus is characterized by muscle spasm and cardiovascular system disturbance. The pathophysiology of muscle spasm is relatively well understood and involves inhibition of central inhibitory synapses by tetanus toxin. That of cardiovascular disturbance is less clear, but is believed to relate to disinhibition of the autonomic nervous system. The clinical syndrome of autonomic nervous system dysfunction (ANSD) seen in severe tetanus is characterized principally by changes in heart rate and blood pressure which have been linked to increased circulating catecholamines. Previous studies have described varying relationships between catecholamines and signs of ANSD in tetanus, but are limited by confounders and assays used. In this study, we aimed to perform detailed characterization of the relationship between catecholamines (adrenaline and noradrenaline), cardiovascular parameters (heart rate and blood pressure) and clinical outcomes (ANSD, mechanical ventilation required, and length of intensive care unit stay) in adults with tetanus, as well as examine whether intrathecal antitoxin administration affected subsequent catecholamine excretion. Noradrenaline and adrenaline were measured by ELISA from 24-h urine collections taken on day 5 of hospitalization in 272 patients enrolled in a 2 × 2 factorial-blinded randomized controlled trial in a Vietnamese hospital. Catecholamine results measured from 263 patients were available for analysis. After adjustment for potential confounders (i.e., age, sex, intervention treatment, and medications), there were indications of non-linear relationships between urinary catecholamines and heart rate. Adrenaline and noradrenaline were associated with subsequent development of ANSD, and length of ICU stay.

Direct Medical Costs of Tetanus, Dengue, and Sepsis Patients in an Intensive Care Unit in Vietnam.

Background: Critically ill patients often require complex clinical care by highly trained staff within a specialized intensive care unit (ICU) with advanced equipment. There are currently limited data on the costs of critical care in low-and middle-income countries (LMICs). This study aims to investigate the direct-medical costs of key infectious disease (tetanus, sepsis, and dengue) patients admitted to ICU in a hospital in Ho Chi Minh City (HCMC), Vietnam, and explores how the costs and cost drivers can vary between the different diseases. Methods: We calculated the direct medical costs for patients requiring critical care for tetanus, dengue and sepsis. Costing data (stratified into different cost categories) were extracted from the bills of patients hospitalized to the adult ICU with a dengue, sepsis and tetanus diagnosis that were enrolled in three studies conducted at the Hospital for Tropical Diseases in HCMC from January 2017 to December 2019. The costs were considered from the health sector perspective. The total sample size in this study was 342 patients. Results: ICU care was associated with significant direct medical costs. For patients that did not require mechanical ventilation, the median total ICU cost per patient varied between US$64.40 and US$675 for the different diseases. The costs were higher for patients that required mechanical ventilation, with the median total ICU cost per patient for the different diseases varying between US$2,590 and US$4,250. The main cost drivers varied according to disease and associated severity. Conclusion: This study demonstrates the notable cost of ICU care in Vietnam and in similar LMIC settings. Future studies are needed to further evaluate the costs and economic burden incurred by ICU patients. The data also highlight the importance of evaluating novel critical care interventions that could reduce the costs of ICU care.

Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial.

BACKGROUND: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection. METHODS: In a 2  × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed. FINDINGS: 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66-1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75-1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths. INTERPRETATION: We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration. FUNDING: The Wellcome Trust.

The compensatory reserve index predicts recurrent shock in patients with severe dengue.

BACKGROUND: Dengue shock syndrome (DSS) is one of the major clinical phenotypes of severe dengue. It is defined by significant plasma leak, leading to intravascular volume depletion and eventually cardiovascular collapse. The compensatory reserve Index (CRI) is a new physiological parameter, derived from feature analysis of the pulse arterial waveform that tracks real-time changes in central volume. We investigated the utility of CRI to predict recurrent shock in severe dengue patients admitted to the ICU. METHODS: We performed a prospective observational study in the pediatric and adult intensive care units at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Patients were monitored with hourly clinical parameters and vital signs, in addition to continuous recording of the arterial waveform using pulse oximetry. The waveform data was wirelessly transmitted to a laptop where it was synchronized with the patient's clinical data. RESULTS: One hundred three patients with suspected severe dengue were recruited to this study. Sixty-three patients had the minimum required dataset for analysis. Median age was 11 years (IQR 8-14 years). CRI had a negative correlation with heart rate and moderate negative association with blood pressure. CRI was found to predict recurrent shock within 12 h of being measured (OR 2.24, 95% CI 1.54-3.26), P < 0.001). The median duration from CRI measurement to the first recurrent shock was 5.4 h (IQR 2.9-6.8). A CRI cutoff of 0.4 provided the best combination of sensitivity and specificity for predicting recurrent shock (0.66 [95% CI 0.47-0.85] and 0.86 [95% CI 0.80-0.92] respectively). CONCLUSION: CRI is a useful non-invasive method for monitoring intravascular volume status in patients with severe dengue.

Cost-Effectiveness of Amphotericin B Deoxycholate Versus Itraconazole for Induction Therapy of Talaromycosis in Human Immunodeficiency Virus-Infected Adults in Vietnam.

BACKGROUND: Talaromycosis (penicilliosis) is an invasive fungal infection and a major cause of human immunodeficiency virus (HIV)-related deaths in Southeast Asia. Guidelines recommend induction therapy with amphotericin B deoxycholate; however, treatment with itraconazole has fewer toxic effects, is easier to administer, and is less expensive. Our recent randomized controlled trial in Vietnam found that amphotericin B was superior to itraconazole with respect to 6-month mortality. We undertook an economic evaluation alongside this trial to determine whether the more effective treatment is cost-effective. METHODS: Resource use, direct and indirect costs, and health and quality-of-life outcomes (measured using quality-adjusted life-years [QALYs]) were evaluated for 405 trial participants from 2012 to 2016. Both a Vietnamese health service and a broader societal costing perspective were considered. Mean costs and QALYs were combined to calculate the within-trial cost-effectiveness of amphotericin vs itraconazole from both perspectives. RESULTS: From a Vietnamese health service perspective, amphotericin increases costs but improves health outcomes compared to itraconazole, at a cost of $3013/QALY gained. The probability that amphotericin is cost-effective at a conventional (World Health Organization CHOICE) threshold of value for money is 46%. From a societal perspective, amphotericin is cost-reducing and improves outcomes compared to itraconazole, and is likely to be a cost-effective strategy at any value for money threshold greater than $0. CONCLUSIONS: Our analysis indicates that induction therapy with amphotericin is a cost-effective treatment strategy for HIV-infected adults diagnosed with talaromycosis in Vietnam. These results provide the evidence base for health care providers and policy makers to improve access to and use of amphotericin.

Antibiotic-Resistant Gram-negative Bacteria Carriage in Healthcare Workers Working in an Intensive Care Unit / 감염과화학요법

Little is known about antibiotic-resistant Gram-negative bacteria (GNB) intestinal carriage among healthcare workers (HCWs) in Vietnam. All HCWs at a tertiary intensive care units were asked to undertake weekly rectal swabs. Among 40 participants, 65% (26/40) carried extended spectrum β-lactamases (ESBL)/AmpC β-lactamase-producing Escherichia coli. Two HCWs colonized with ESBL/AmpC β-lactamase-producing Klebsiella pneumoniae. One HCW colonized with Acinetobacter baumannii. No one carried Pseudomonas spp.. A quarter (10/40) of HCWs were identified as persistent and frequent carriers. There is an urgent need to screen antibiotic-resistant GNB among HCWs and improve HCWs' hand hygiene compliance to reduce the transmission of antibiotic-resistant GNB in the hospital.

Antibiotic-Resistant Gram-negative Bacteria Carriage in Healthcare Workers Working in an Intensive Care Unit / 감염과화학요법

Little is known about antibiotic-resistant Gram-negative bacteria (GNB) intestinal carriage among healthcare workers (HCWs) in Vietnam. All HCWs at a tertiary intensive care units were asked to undertake weekly rectal swabs. Among 40 participants, 65% (26/40) carried extended spectrum β-lactamases (ESBL)/AmpC β-lactamase-producing Escherichia coli. Two HCWs colonized with ESBL/AmpC β-lactamase-producing Klebsiella pneumoniae. One HCW colonized with Acinetobacter baumannii. No one carried Pseudomonas spp.. A quarter (10/40) of HCWs were identified as persistent and frequent carriers. There is an urgent need to screen antibiotic-resistant GNB among HCWs and improve HCWs' hand hygiene compliance to reduce the transmission of antibiotic-resistant GNB in the hospital.

The Natural History and Transmission Potential of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Little is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a prospective study at a quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. RESULTS: Between 10 March and 4 April 2020, 14 000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13 (43%) never had symptoms and 17 (57%) were symptomatic. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 [62%] vs 17/17 [100%]; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 [64%] in the asymptomatic group and 13 of 16 [81%] in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P < .001 for difference over the first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit SARS-CoV-2 to 4 contacts. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.

Multiple Wolbachia strains provide comparative levels of protection against dengue virus infection in Aedes aegypti.

The insect bacterium Wolbachia pipientis is being introgressed into Aedes aegypti populations as an intervention against the transmission of medically important arboviruses. Here we compare Ae. aegypti mosquitoes infected with wMelCS or wAlbB to the widely used wMel Wolbachia strain on an Australian nuclear genetic background for their susceptibility to infection by dengue virus (DENV) genotypes spanning all four serotypes. All Wolbachia-infected mosquitoes were more resistant to intrathoracic DENV challenge than their wildtype counterparts. Blocking of DENV replication was greatest by wMelCS. Conversely, wAlbB-infected mosquitoes were more susceptible to whole body infection than wMel and wMelCS. We extended these findings via mosquito oral feeding experiments, using viremic blood from 36 acute, hospitalised dengue cases in Vietnam, additionally including wMel and wildtype mosquitoes on a Vietnamese nuclear genetic background. As above, wAlbB was less effective at blocking DENV replication in the abdomen compared to wMel and wMelCS. The transmission potential of all Wolbachia-infected mosquito lines (measured by the presence/absence of infectious DENV in mosquito saliva) after 14 days, was significantly reduced compared to their wildtype counterparts, and lowest for wMelCS and wAlbB. These data support the use of wAlbB and wMelCS strains for introgression field trials and the biocontrol of DENV transmission. Furthermore, despite observing significant differences in transmission potential between wildtype mosquitoes from Australia and Vietnam, no difference was observed between wMel-infected mosquitoes from each background suggesting that Wolbachia may override any underlying variation in DENV transmission potential.

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

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.

Dynamic Prediction of Death in Patients With Tuberculous Meningitis Using Time-updated Glasgow Coma Scale and Plasma Sodium Measurements.

BACKGROUND: Pretreatment predictors of death from tuberculous meningitis (TBM) are well established, but whether outcome can be predicted more accurately after the start of treatment by updated clinical variables is unknown. Hence, we developed and validated models that dynamically predict mortality using time-updated Glasgow Coma Scale (GCS) and plasma sodium measurements, together with patient baseline characteristics. METHODS: We included 1048 adults from 4 TBM studies conducted in southern Vietnam from 2004 to 2016. We used a landmarking approach to predict death within 120 days after treatment initiation using time-updated data during the first 30 days of treatment. Separate models were built for patients with and without human immunodeficiency virus (HIV) infection. We used the area under the receiver operating characteristic curve (AUC) to evaluate performance of the models at days 10, 20, and 30 of treatment to predict mortality by 60, 90, and 120 days. Our internal validation was corrected for overoptimism using bootstrap. We provide a web-based application that computes mortality risk within 120 days. RESULTS: Higher GCS indicated better prognosis in all patients. In HIV-infected patients, higher plasma sodium was uniformly associated with good prognosis, whereas in HIV-uninfected patients the association was heterogeneous over time. The bias-corrected AUC of the models ranged from 0.82 to 0.92 and 0.81 to 0.85 in HIV-uninfected and HIV-infected individuals, respectively. The models outperformed the previously published baseline models. CONCLUSIONS: Time-updated GCS and plasma sodium measurements improved predictions based solely on information obtained at diagnosis. Our models may be used in practice to define those with poor prognosis during treatment.