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Malaria is one of the most common mosquito-borne diseases widespread in tropical and subtropical regions, causing thousands of deaths every year in the world. In a previous paper, we formulated an age-structured model containing three structural variables: (i) the chronological age of human and mosquito populations, (ii) the time since they are infected, and (iii) humans waning immunity (i.e. the progressive loss of protective antibodies after recovery). In the present paper, we expand the analysis of this age-structured model and focus on the derivation of entomological and epidemiological results commonly used in the literature, following the works of Smith and McKenzie. We generalize their results to the age-structured case. In order to quantify the impact of neglecting structuring variables such as chronological age, we assigned values from the literature to our model parameters. While some parameters values are readily accessible from the literature, at least those about the human population, the parameters concerning mosquitoes are less commonly documented and the values of a number of them (e.g. mosquito survival in the presence or in absence of infection) can be discussed extensively. Our analysis, informed by parameter values from the literature, demonstrates that overlooking those structural variables of human and mosquito populations may result in inaccurate epidemiological predictions and suboptimal control strategies. We highlight the epidemiological implications of these findings and emphasize the necessity of considering age structure in future malaria control programs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The experimental validation of theoretical predictions is a crucial step in demonstrating the predictive power of a model. While quantitative validations are common in infectious diseases epidemiology, experimental microbiology primarily focuses on the evaluation of a qualitative match between model predictions and experiments. In this study, we develop a method to deepen the quantitative validation process with a polymorphic viral population. We analyse the data from an experiment carried out to monitor the evolution of the temperate bacteriophage λ spreading in continuous cultures of Escherichia coli . This experimental work confirmed the influence of the epidemiological dynamics on the evolution of transmission and virulence of the virus. A variant with larger propensity to lyse bacterial cells was favoured in emerging epidemics (when the density of susceptible cells was large), but counter-selected when most cells were infected. Although this approach qualitatively validated an important theoretical prediction, no attempt was made to fit the model to the data nor to further develop the model to improve the goodness of fit. Here, we show how theoretical analysis-including calculations of the selection gradients-and model fitting can be used to estimate key parameters of the phage life cycle and yield new insights on the evolutionary epidemiology of the phage λ . First, we show that modelling explicitly the infected bacterial cells which will eventually be lysed improves the fit of the transient dynamics of the model to the data. Second, we carry out a theoretical analysis that yields useful approximations that capture at the onset and at the end of an epidemic the effects of epidemiological dynamics on selection and differentiation across distinct life stages of the virus. Finally, we estimate key phenotypic traits characterizing the two strains of the virus used in our experiment such as the rates of prophage reactivation or the probabilities of lysogenization. This study illustrates the synergy between experimental, theoretical, and statistical approaches; and especially how interpreting the temporal variation in the selection gradient and the differentiation across distinct life stages of a novel variant is a powerful tool to elucidate the evolutionary epidemiology of emerging infectious diseases., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Influenza virus seasonality, synchronicity, and vaccine supply differ substantially between temperate and tropical settings, and optimal vaccination strategy may differ on this basis. Many national vaccine recommendations focus on high-risk groups, elderly populations, and healthcare workers despite previous analyses demonstrating broad benefits to vaccinating younger high-contact age groups. In this study, we parameterized an age-structured nonseasonal asynchronous epidemiological model of influenza virus transmission for a tropical low-income setting. We evaluated timing and age allocation of vaccines across vaccine supplies ranging from 10 to 90% using decade-based age groups. Year-round vaccination was beneficial when compared with more concentrated annual vaccine distribution. When targeting a single age group for vaccine prioritization, maximum vaccine allocation to the 10-19 high-contact age group minimized annual influenza mortality for all but one vaccine supply. When evaluating across all possible age allocations, optimal strategies always allocated a plurality of vaccines to school-age children (10-19). The converse, however, was not true as not all strategies allocating a plurality to children aged 10-19 minimized mortality. Allocating a high proportion of vaccine supply to the 10-19 age group is necessary but not sufficient to minimize annual mortality as distribution of remaining vaccine doses to other age groups also needs to be optimized. Strategies focusing on indirect benefits (vaccinating children) showed higher variance in mortality outcomes than strategies focusing on direct benefits (vaccinating the elderly). However, the indirect benefit approaches showed a lower mean mortality and a lower minimum mortality than vaccination focused on the elderly., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Measles remains a major public health burden worldwide. Parents often hesitate to vaccinate children with chronic diseases. We investigated the association between the percentage of vaccination and chronic diseases and explore hospital infections' role in the 2017-2019 measles outbreak across northern Vietnam provinces., Methods: A total of 2,064 children aged 0-15 years old admitted for measles to the National Children's Hospital during the outbreak were included in the study. Demographic information, clinical characteristics, vaccination statuses and laboratory examination were extracted from electronic medical records, vaccination records, or interviews with parents when other sources were unavailable., Results: The incidence rate that provincial hospitals sent to the National Children's Hospital was proportional to the population density of their provinces of residence. Early nosocomial transmission of measles was observed before community-acquired cases emerged in many provinces. Among patients aged over 18 months, those with chronic diseases had a proportion of vaccination of 9.4%, lower than patients without chronic diseases at 32.4%. Unvaccinated patients had a higher proportion of hospital-acquired infections with aOR = 2.42 (1.65-3.65), p < 0.001 relative to vaccinated patients. The proportion of hospital-acquired infections was higher among children with chronic diseases compared to those without, with aOR = 3.81 (2.90-5.02), p < 0.001., Conclusion: Measles spread in healthcare settings prior to community cases that occurred in several provinces. We recommend enhancing hospital infection control by increasing staff training and improving early detection and isolation during non-outbreak periods. Measles patients with chronic diseases exhibited lower proportions of vaccination and faced a higher risk of hospital-acquired infections. It is crucial to establish comprehensive vaccination guidelines and enhance parental awareness regarding the significance and safety of measles vaccination to protect these vulnerable individuals., (© 2024. The Author(s).)

Hypervirulent Klebsiella pneumoniae (hvKp) is a significant cause of severe invasive infections in Vietnam, yet data on its epidemiology, population structure and dynamics are scarce. We screened hvKp isolates from patients with bloodstream infections (BSIs) at a tertiary infectious diseases hospital in Vietnam and healthy individuals, followed by whole genome sequencing and plasmid analysis. Among 700 BSI-causing Kp strains, 100 (14.3%) were hvKp. Thirteen hvKp isolates were identified from 350 rectal swabs of healthy adults; none from 500 rectal swabs of healthy children. The hvKp isolates were genetically diverse, encompassing 17 sequence types (STs), predominantly ST23, ST86 and ST65. Among the 113 hvKp isolates, 14 (12.6%) carried at least one antimicrobial resistance (AMR) gene, largely mediated by IncFII, IncR, and IncA/C plasmids. Notably, the acquisition of AMR conjugative plasmids facilitated horizontal transfer of the non-conjugative virulence plasmid between K. pneumoniae strains. Phylogenetic analysis demonstrated hvKp isolates from BSIs and human carriage clustered together, suggesting a significant role of intestinal carriage in hvKp transmission. Enhanced surveillance is crucial to understand the factors driving intestinal carriage and hvKp transmission dynamics for informing preventive measures. Furthermore, we advocate the clinical use of our molecular assay for diagnosing hvKp infections to guide effective management., (© 2024. The Author(s).)

Introduction: Citizen science (CS) is an emerging approach in public health to harness the collective intelligence of individuals to augment traditional scientific efforts. However, citizens' viewpoint, especially the hard-to-reach population, is lacking in current outbreak-related literature. We aim to understand the awareness, readiness and feasibility of outbreak-related CS, including digitally enabled CS, in low-income and middle-income countries., Methods: This mixed-method study was conducted in nine countries between October 2022 and June 2023. Recruitment through civil society targeted the general population, marginalised/indigenous groups, youth and community health workers. Participants (aged ≥18 years) completed a quantitative survey, and a subset participated in focus group discussions (FGDs)., Results: 2912 participants completed the survey and 4 FGDs were conducted in each country. Incorporating participants' perspectives, CS is defined as the practice of active public participation, collaboration and communication in all aspects of scientific research to increase public knowledge, create awareness, build trust and facilitate information flow between citizens, governments and scientists. In Bangladesh, Indonesia, the Philippines, Cameroon and Kenya, majority were unaware of outbreak-related CS. In India and Uganda, majority were aware but unengaged, while in Nepal and Zimbabwe, majority participated in CS before. Engagement approaches should consider different social and cultural contexts, while addressing incentivisation, attitudes and practicality factors. Overall, 76.0% expressed interest in digital CS but needed training to build skills and confidence. Digital CS was perceived as convenient, safer for outbreak-related activities and producing better quality and quantity of data. However, there were concerns over non-inclusion of certain groups, data security and unclear communication., Conclusion: CS interventions need to be relatable and address context-specific factors influencing CS participation. Digital CS has the potential to facilitate collaboration, but capacity and access issues must be considered to ensure inclusive and sustainable engagement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Influenza virus seasonality, synchronicity, and vaccine supply differ substantially between temperate and tropical settings, and optimal vaccination strategy may differ on this basis. Most national vaccine recommendations focus on high-risk groups, elderly populations, and healthcare workers despite previous analyses demonstrating broad benefits to vaccinating younger high-contact age groups. Here, we parameterized an age-structured non-seasonal asynchronous epidemiological model of influenza virus transmission for a tropical low-income setting. We evaluated timing and age allocation of vaccines across vaccine supplies ranging from 10% to 90% using decade-based age groups. Year-round vaccination was beneficial when comparing to vaccination strategies focused on a particular time of year. When targeting a single age-group for vaccine prioritization, maximum vaccine allocation to the 10-19 high-contact age group minimized annual influenza mortality for all but one vaccine supply. When evaluating across all possible age allocations, optimal strategies always allocated a plurality of vaccines to school-age children (10-19). The converse however was not true as not all strategies allocating a plurality to children aged 10-19 minimized mortality. Allocating a high proportion of vaccine supply to the 10-19 age group is necessary but not sufficient to minimize annual mortality as distribution of remaining vaccine doses to other age groups also needs to be optimized. Strategies focusing on indirect benefits (vaccinating children) showed higher variance in mortality outcomes than strategies focusing on direct benefits (vaccinating the elderly). However, the indirect benefit approaches showed lower mean mortality and lower minimum mortality than vaccination focused on the elderly.

Host age variation is a striking source of heterogeneity that can shape the evolution and transmission dynamic of pathogens. Compared with vertebrate systems, our understanding of the impact of host age on invertebrate-pathogen interactions remains limited. We examined the influence of mosquito age on key life-history traits driving human malaria transmission. Females of Anopheles coluzzii , a major malaria vector, belonging to three age classes (4-, 8- and 12-day-old), were experimentally infected with Plasmodium falciparum field isolates. Our findings revealed reduced competence in 12-day-old mosquitoes, characterized by lower oocyst/sporozoite rates and intensities compared with younger mosquitoes. Despite shorter median longevities in older age classes, infected 12-day-old mosquitoes exhibited improved survival, suggesting that the infection might act as a fountain of youth for older mosquitoes specifically. The timing of sporozoite appearance in the salivary glands remained consistent across mosquito age classes, with an extrinsic incubation period of approximately 13 days. Integrating these results into an epidemiological model revealed a lower vectorial capacity for older mosquitoes compared with younger ones, albeit still substantial owing to extended longevity in the presence of infection. Considering age heterogeneity provides valuable insights for ecological and epidemiological studies, informing targeted control strategies to mitigate pathogen transmission.

Introduction: It is well known that influenza and other respiratory viruses are wintertime-seasonal in temperate regions. However, respiratory disease seasonality in the tropics is less well understood. In this study, we aimed to characterise the seasonality of influenza-like illness (ILI) and influenza virus in Ho Chi Minh City, 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 periodic signals in the system. We evaluated the contribution of these periodic signals to predicting ILI and influenza patterns through lognormal and gamma hurdle models., Results: During 10 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% to 9.0%) from February 24 to May 15. Nonannual cycles had substantial explanatory power for ILI trends (ΔAIC=183) compared with all annual covariates (ΔAIC=263) in lognormal regression. Near-annual signals were observed for PCR-confirmed influenza but were not consistent over time or across influenza (sub)types. The explanatory power of climate factors for ILI and influenza virus trends was weak., Conclusion: Our study reveals a unique pattern of respiratory disease dynamics in a tropical setting influenced by both annual and nonannual drivers, with influenza dynamics showing near-annual periodicities. Timing of vaccination campaigns and hospital capacity planning may require a complex forecasting approach., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: We investigated longitudinally Vietnamese small-scale chicken flocks in order to characterize changes in antimicrobial resistance gene (ARG) content over their life cycle, and the impact of antimicrobial use (AMU) on an intervention consisting of veterinary advice provision., Methods: AMU data and faecal samples were collected from 83 flocks (25 farms) at day-old, mid- and late-production (∼4 month cycle). Using high-throughput real-time PCR, samples were investigated for 94 ARGs. ARG copies were related to 16S rRNA and ng of DNA (ngDNA). Impact of AMU and ARGs in day-olds was investigated by mixed-effects models., Results: Flocks received a mean (standard error, SE) animal daily dose (ADD) of 736.7 (83.0) and 52.1 (9.9) kg in early and late production, respectively. Overall, ARGs/16S rRNA increased from day-old (mean 1.47; SE 0.10) to mid-production (1.61; SE 0.16), further decreasing in end-production (1.60; SE 0.1) (all P  > 0.05). In mid-production, ARGs/16S rRNA increased for aminoglycosides, phenicols, sulphonamides and tetracyclines, decreasing for polymyxins β-lactams and genes that confer resistance to mutiple classes (multi-drug resistance) (MDR). At end-production, aminoglycoside resistance decreased and polymyxin and quinolone resistance increased (all P  < 0.05). Results in relation to ngDNA gave contradictory results. Neither AMU nor ARGs in day-olds had an impact on subsequent ARG abundance. The intervention resulted in 74.2% AMU reduction; its impact on ARGs depended on whether ARGs/ngDNA (+14.8%) or ARGs/16S rRNA metrics (-10.7%) ( P  > 0.05) were computed., Conclusions: The flocks' environment (contaminated water, feed and residual contamination) is likely to play a more important role in transmission of ARGs to flocks than previously thought. Results highlight intriguing differences in the quantification of ARGs depending on the metric chosen., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Much of the world experiences influenza in yearly recurring seasons, particularly in temperate areas. These patterns can be considered repeatable if they occur predictably and consistently at the same time of year. In tropical areas, including southeast Asia, timing of influenza epidemics is less consistent, leading to a lack of consensus regarding whether influenza is repeatable. This study aimed to assess repeatability of influenza in Vietnam, with repeatability defined as seasonality that occurs at a consistent time of year with low variation. We developed a mathematical model incorporating parameters to represent periods of increased transmission and then fitted the model to data collected from sentinel hospitals throughout Vietnam as well as four temperate locations. We fitted the model for individual (sub)types of influenza as well as all combined influenza throughout northern, central, and southern Vietnam. Repeatability was evaluated through the variance of the timings of peak transmission. Model fits from Vietnam show high variance (sd = 64-179 days) in peak transmission timing, with peaks occurring at irregular intervals and throughout different times of year. Fits from temperate locations showed regular, annual epidemics in winter months, with low variance in peak timings (sd = 32-57 days). This suggests that influenza patterns are not repeatable or seasonal in Vietnam. Influenza prevention in Vietnam therefore cannot rely on anticipation of regularly occurring outbreaks., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Servadio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Acute encephalitis syndrome (AES) differs in its spatio-temporal distribution in Vietnam with the highest incidence seen during the summer months in the northern provinces. AES has multiple aetiologies, and the cause remains unknown in many cases. While vector-borne disease such as Japanese encephalitis and dengue virus and non-vector-borne diseases such as influenza and enterovirus show evidence of seasonality, associations with climate variables and the spatio-temporal distribution in Vietnam differs between these. The aim of this study was therefore to understand the spatio-temporal distribution of, and risk factors for AES in Vietnam to help hypothesise the aetiology., Methods: The number of monthly cases per province for AES, meningitis and diseases including dengue fever; influenza-like-illness (ILI); hand, foot, and mouth disease (HFMD); and Streptococcus suis were obtained from the General Department for Preventive Medicine (GDPM) from 1998-2016. Covariates including climate, normalized difference vegetation index (NDVI), elevation, the number of pigs, socio-demographics, JEV vaccination coverage and the number of hospitals were also collected. Spatio-temporal multivariable mixed-effects negative binomial Bayesian models with an outcome of the number of cases of AES, a combination of the covariates and harmonic terms to determine the magnitude of seasonality were developed., Results: The national monthly incidence of AES declined by 63.3% over the study period. However, incidence increased in some provinces, particularly in the Northwest region. In northern Vietnam, the incidence peaked in the summer months in contrast to the southern provinces where incidence remained relatively constant throughout the year. The incidence of meningitis, ILI and S. suis infection; temperature, relative humidity with no lag, NDVI at a lag of one month, and the number of pigs per 100,000 population were positively associated with the number of cases of AES in all models in which these covariates were included., Conclusions: The positive correlation of AES with temperature and humidity suggest that a number of cases may be due to vector-borne diseases, suggesting a need to focus on vaccination campaigns. However, further surveillance and research are recommended to investigate other possible aetiologies such as S. suis or Orientia tsutsugamushi., (© 2023. The Author(s).)

Linezolid is an antibiotic of last resort for the treatment of infections caused by Gram-positive bacteria, including vancomycin-resistant enterococci. Enterococcus faecalis , a member of enterococci, is a significant pathogen in nosocomial infections. E. faecalis resistance to linezolid is frequently related to the presence of optrA, which is often co-carried with fex , phenicol exporter genes, and erm genes encoding macrolide resistance. Therefore, the common use of antibiotics in veterinary might promote the occurrence of optrA in livestock settings. This is a cross-sectional study aiming to investigate the prevalence of optrA positive E. faecalis (OPEfs) in 6 reservoirs in farms in Ha Nam province, Vietnam, and its associated factors and to explore genetic relationships of OPEfs isolates. Among 639 collected samples, the prevalence of OPEfs was highest in flies, 46.8% (51/109), followed by chickens 37.3% (72/193), dogs 33.3% (17/51), humans 18.7% (26/139), wastewater 16.4% (11/67) and pigs 11.3%, (14/80). The total feeding area and total livestock unit of the farm were associated with the presence of OPEfs in chickens, flies, and wastewater. Among 186 OPEfs strains, 86% were resistant to linezolid. The presence of optrA was also related to the resistant phenotype against linezolid and levofloxacin of E. faecalis isolates. Close genotypic relationships identified by Pulsed Field Gel Electrophoresis between OPEfs isolates recovered from flies and other reservoirs including chickens, pigs, dogs, and wastewater suggested the role of flies in the transmission of antibiotic-resistant pathogens. These results provided warnings of linezolid resistance although it is not used in livestock.

Background: Ongoing tetanus cases and sporadic outbreaks of vaccine-preventable diseases associated with routine vaccination programmes remain problems in many low and middle-income countries, including Vietnam. With no human-to-human transmission or natural immunity, tetanus antibody levels indicate both individual risk of tetanus and gaps in vaccination programmes., Methods: To investigate gaps in immunity to tetanus in Vietnam, a country with a historically high level of tetanus vaccination coverage, tetanus antibodies were measure by ELISA from samples selected from a long-term serum bank, established for the purposes of general-population seroepidemiological investigations in southern Vietnam. Samples were selected from 10 provinces, focussing on age-groups targeted by national vaccination programmes for infants and pregnant women (Expanded Programme on Immunization, EPI, and Maternal and Neonatal Tetanus, MNT)., Results: Antibodies were measured from a total of 3864 samples. Highest tetanus antibody concentrations occurred in children under 4 years old, over 90 % of whom had protective levels. Approximately 70 % of children aged 7-12 years had protective antibody concentrations although there was variation among provinces. For infants and children, there were no significant differences in tetanus protection between males and females, but for adults aged 20-35 years, in five of the ten provinces surveyed, protection against tetanus was higher in females (p < 0.05) who are eligible for booster doses under the MNT programme. In seven of ten provinces, antibody concentrations were inversely related to age (p < 0.01) and protection of older individuals was generally low., Conclusion: Widespread immunity to tetanus toxoid is seen in infants and young children consistent with the high coverage rates reported for diptheria tetanus toxoid and pertussis (DTP) in Vietnam. However, the lower antibody concentrations seen in older children and men suggest reduced immunity to tetanus in populations not targeted by EPI and MNT programmes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Louise Thwaites reports financial support was provided by Wellcome Trust. OUCRU affiliated authors reports financial support was provided by Wellcome Trust., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

An estimated 73% of emerging infections are zoonotic in origin, with animal contact and encroachment on their habitats increasing the risk of spill-over events. In Vietnam, close exposure to a wide range of animals and animal products can lead to acquisition of zoonotic pathogens, a number of which cause central nervous system (CNS) infections. However, studies show the aetiology of CNS infections remains unknown in around half of cases. We used samples and data from hospitalised patients with CNS infections, enrolled into the Vietnam Initiative on Zoonotic Infections multicentre study, to determine the association between aetiology and animal contact including those in whom the cause was unknown. Among 933 patients, a pathogen or an antibody response to it was identified in 291 (31.2%, 95% CI 28.3-34.3%). The most common pathogens were Streptococcus suis (n = 91 (9.8%, 8.0-11.9%)) and Japanese encephalitis virus (JEV) (n = 72 (7.7%, 6.1-9.7%)). Commonly reported animal contact included keeping, raising or handling (n = 364 (39.0%, 35.9-42.2%)) and handling, cooking or consuming raw meat, blood or viscera in the 2 weeks prior to symptom onset (n = 371 (39.8%, 36.6-43.0%)), with the latter most commonly from pigs (n = 343 (36.9%, 33.8-40.1%). There was no association between an unknown aetiology and exposure to animals in a multivariate logistic regression. Further testing for unknown or undetected pathogens may increase diagnostic yield, however, given the high proportion of zoonotic pathogens and the presence of risk factors, increasing public awareness about zoonoses and preventive measures can be considered., (© 2022. The Author(s).)

Livestock has been implicated as a reservoir for antimicrobial resistance (AMR) genes that can spread to humans when antimicrobials are used in animals for food production to treat clinical diseases and prevent and control common disease events. In Vietnam, mcr-1 -harboring Escherichia coli (MCRPEC) strains have been isolated from humans, animals (chickens, pigs, and dogs) feces, flies, foods, and the environment (rainwater, well water, and irrigation water) in communities and from clinical specimens in hospitals. The relationship between levels of AMR in livestock and its occurrence in humans is complex and is driven by many factors. We conducted whole genome sequencing of MCRPEC to analyze the molecular epidemiological characteristics, history, and relatedness of 50 isolates obtained in 2019 from different reservoirs in farms and markets in Ha Nam province, Vietnam. 34 sequence types (STs) with 3 new STs were identified in multilocus sequence typing analysis: ST12945 and ST12946 from chicken feces, and ST12947 from flies. The AMR phenotypes of 50 MCRPEC isolates were as follows: ampicillin (100%, 50/50), cefotaxime (10%, 5/50), gentamicin (60%, 30/50), amikacin (8%, 4/50), meropenem (6%, 3/50), ceftazidime (18%, 9/50), colistin (24%, 12/50) and ciprofloxacin (80%, 40/50). All 50 MCRPEC isolates were identified as MDR. 100% (50/50) isolates carried AMR genes, ranging from 5 to 22 genes. The most prevalent plasmid replicon types carrying mcr-1 were IncP-1 (17/37, 45.9%), IncX4 (7/37, 18.9%), and IncHI2/IncHI2A (6/37, 16.2%). These data suggest that the epidemiology of the mcr-1 gene is mostly determined by plasmid spreading instead of clonal dissemination of MCRPE strains. The co-occurrence of several STs such as ST10, ST48, ST155, ST206, ST2705 in various sample types, joined to the higher prevalence of a few types of Inc plasmids, confirms the dissemination of the mcr-1 carrying plasmids in E. coli clones established in livestock. 5 over 8 STs identified in flies (ST206, ST2705, ST155, ST10, and ST48) suggested the fly contribution in the transmission of AMR bacteria in environments. These popular STs also occur in human samples and 100% of the human samples were positive for the mcr-1 gene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nguyen, Ngo, Tran, Vu, Le, Tran, Pham, Nguyen, Tran, Nguyen, Nguyen, Tran, Dang, Bañuls, Choisy, van Doorn, Suzuki and Tran.)

This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Choisy M et al.)

Colistin is a critically important antimicrobial for human medicine, and colistin-resistant Escherichia coli are commonly found in poultry and poultry products in Southeast Asia. Here, we aim at disentangling the within-farm and outside-farm drivers of colistin resistance in small-scale chicken farms of the Mekong delta of Vietnam. Nineteen Vietnamese chicken farms were followed up along a whole production cycle, during which weekly antimicrobial use data were recorded. At the beginning, middle and end of each production cycle, commensal E. coli samples from birds were collected, pooled and tested for colistin resistance. Twelve models were fitted to the data using an expectation-maximization algorithm and compared. We further tested the spatial clustering of the occurrence of resistance importations from external sources using the local Moran's I statistic. In the best model, colistin resistance in E. coli from chickens was found to be mostly affected by importations of resistance, and, to a lesser extent, by the use of antimicrobials in the last 1.73 weeks [0.00; 2.90], but not by the use of antimicrobials in day-olds, nor their colistin resistance carriage from hatchery. The occurrence of external source importations proved to be sometimes spatially clustered, suggesting a role of local environmental sources of colistin resistance., (© 2022 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)

This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Choisy M et al.)

Plasmid-Mediated Colistin Resistance 1 (mcr-1) was first reported in 2015 and is a great concern to human health. In this study, we investigated the prevalence of mcr-1 and mcr-1-positive Escherichia coli (MCRPEC) and the association in infection status among various reservoirs connected to livestock. The study was conducted in 70 poultry and swine farms in a commune in Ha Nam province, northern Vietnam. Samples were collected from farmers, food animals, domestic animals, and farm environments (flies and wastewater) for polymerase chain reaction (PCR) screening for mcr-1 gene and species identification of PCR positive isolates. Among 379 obtained mcr-1 positives isolates, Escherichia coli was the major identified, varying from 50% (2/4) in dog feces to 100% (31/31) in humans feces isolates. The prevalence of MCRPEC was 14.4% (20/139), 49.7% (96/193), 31.3% (25/80), 36.7% (40/109), 26.9% (18/67), and 3.9% (2/51) in humans, chickens, pigs, flies, wastewater, and dogs, respectively. The study identified association between MCRPEC infection status in humans and flies (OR = 3.4), between flies and chickens (OR = 5.3), and between flies and pigs (OR = 9.0). Farmers' age and farm livestock unit were also associated factors of MCRPEC infection status in humans (OR = 5.1 and 1.05, respectively). These findings bring new knowledge on antibiotic resistance in livestock setting and important suggestions on potential role of flies in the transmission of mcr-1 resistance gene.

The COVID-19 pandemic has underlined the need to partner with the community in pandemic preparedness and response in order to enable trust-building among stakeholders, which is key in pandemic management. Citizen science, defined here as a practice of public participation and collaboration in all aspects of scientific research to increase knowledge and build trust with governments and researchers, is a crucial approach to promoting community engagement. By harnessing the potential of digitally enabled citizen science, one could translate data into accessible, comprehensible and actionable outputs at the population level. The application of citizen science in health has grown over the years, but most of these approaches remain at the level of participatory data collection. This narrative review examines citizen science approaches in participatory data generation, modelling and visualisation, and calls for truly participatory and co-creation approaches across all domains of pandemic preparedness and response. Further research is needed to identify approaches that optimally generate short-term and long-term value for communities participating in population health. Feasible, sustainable and contextualised citizen science approaches that meaningfully engage affected communities for the long-term will need to be inclusive of all populations and their cultures, comprehensive of all domains, digitally enabled and viewed as a key component to allow trust-building among the stakeholders. The impact of COVID-19 on people's lives has created an opportune time to advance people's agency in science, particularly in pandemic preparedness and response., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate phenotypic antimicrobial resistance (AMR) in relation to antimicrobial use (AMU) and potential inter-species transmission among Escherichia coli from humans and chickens located in the same households in the Mekong Delta of Vietnam., Methods: We collected data on AMU and faecal swabs from humans ( N  = 426) and chickens ( N  = 237) from 237 small-scale farms. From each sample, one E. coli strain was isolated and tested for its susceptibility against 11 antimicrobials by Sensititre AST. The association between AMR and AMU was investigated by logistic regression modelling. Using randomization, we compared the degree of similarity in AMR patterns between human and chicken E. coli from the same farms compared with isolates from different farms., Results: The AMU rate was ∼19 times higher in chickens (291.1 per 1000 chicken-days) than in humans (15.1 per 1000 person-days). Isolates from chickens also displayed a higher prevalence of multidrug resistance (63.3%) than those of human origin (55.1%). AMU increased the probability of resistance in isolates from human (ORs between 2.1 and 5.3) and chicken (ORs between 1.9 and 4.8). E. coli from humans and chickens living on same farms had a higher degree of similarity in their AMR patterns than isolates from humans and chicken living on different farms., Conclusions: We demonstrated the co-influence of AMU and potential transmission on observed phenotypic AMR patterns among E. coli isolates from food-producing animals and in-contact humans. Restricting unnecessary AMU alongside limiting interspecies contact (i.e. increasing hygiene and biocontainment) are essential for reducing the burden of AMR., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Over 10-years of whole-genome sequencing (WGS) of Mycobacterium tuberculosis in Birmingham presents an opportunity to explore epidemiological trends and risk factors for transmission in new detail., Methods: Between 1st January 2009 and 15th June 2019, we obtained the first WGS isolate from every patient resident in a postcode district covered by Birmingham's centralised tuberculosis service. Data on patients' sex, country of birth, social risk-factors, anatomical locus of disease, and strain lineage were collected. Poisson harmonic regression was used to assess seasonal variation in case load and a mixed-effects multivariable Cox proportionate hazards model was used to assess risk factors for a future case arising in clusters defined by a 5 single nucleotide polymorphism (SNP) threshold, and by 12 SNPs in a sensitivity analysis., Findings: 511/1653 (31%) patients were genomically clustered with another. A seasonal variation in diagnoses was observed, peaking in spring, but only among clustered cases. Risk-factors for a future clustered case included UK-birth (aHR=2·03 (95%CI 1·35-3·04), p  < 0·001), infectious (pulmonary/laryngeal/miliary) tuberculosis (aHR=3·08 (95%CI 1·98-4·78), p  < 0·001), and M. tuberculosis lineage 3 (aHR=1·91 (95%CI 1·03-3·56), p  = 0·041) and 4 (aHR=2·27 (95%CI 1·21-4·26), p  = 0·011), vs. lineage 1. Similar results pertained to 12 SNP clusters, for which social risk-factors were also significant (aHR 1·72 (95%CI 1·02-2·93), p  = 0·044). There was marked heterogeneity in transmission patterns between postcode districts., Interpretation: There is seasonal variation in the diagnosis of genomically clustered, but not non-clustered, cases. Risk factors for clustering include UK-birth, infectious forms of tuberculosis, and infection with lineage 3 or 4., Funding: Wellcome Trust, MRC, UKHSA., Competing Interests: No authors declare any conflict of interests., (© 2022 The Author(s).)

Aims: We investigated the antibacterial effect of seven essential oils (EOs) and one EO-containing liquid phytogenic solution marketed for poultry and pigs ('Product A') on chicken pathogens, as well as the relationship between minimum inhibitory concentration (MIC) in EOs and antibiotics commonly administered to chicken flocks in the Mekong Delta (Vietnam)., Methods and Results: Micellar extracts from oregano (Origanum vulgare), cajeput (Melaleuca leucadendra), garlic (Allium sativum), black pepper (Piper nigrum), peppermint (Mentha × piperita L.), tea tree (Melaleuca alternifolia), cinnamon (Cinnamomum zeylanicum) EOs and Product A were investigated for their MIC against Avibacterium endocarditidis (N = 10), Pasteurella multocida (N = 7), Ornitobacterium rhinotracheale (ORT) (N = 10), Escherichia coli (N = 10) and Gallibacterium anatis (N = 10). Cinnamon EO had the lowest median MIC across strains (median 0.5 mg/ml [IQR, interquartile range 0.3-2.0 mg/ml]), followed by Product A (3.8 mg/ml [1.9-3.8 mg/ml]), oregano EO (30.4 mg/ml [7.6-60.8 mg/ml]) and garlic 63.1 mg/ml [3.9 to >505.0 mg/ml]. Peppermint, tea tree, cajeput and pepper EOs had all MIC ≥219 mg/ml. In addition, we determined the MIC of the 12 most commonly used antibiotics in chicken flocks in the area. After accounting for pathogen species, we found an independent, statistically significant (p < 0.05) positive correlation between MIC of 10 of 28 (35.7%) pairs of EOs. For 67/96 (69.8%) combinations of EOs and antibiotics, the MICs were correlated. Of all antibiotics, doxycycline was positively associated with the highest number of EOs (peppermint, tea tree, black pepper and cajeput, all p < 0.05). For cinnamon, the MICs were negatively correlated with the MICs of 11/12 antimicrobial tested (all except colistin)., Conclusions: Increases in MIC of antibiotics generally correlates with increased tolerance to EOs. For cinnamon EO, however, the opposite was observed., Significance and Impact of the Study: Our results suggest increased antibacterial effects of EOs on multi-drug resistant pathogens; cinnamon EO was particularly effective against bacterial poultry pathogens., (© 2021 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.)

We studied the immunogenicity of the Oxford-AstraZeneca vaccine in health-care workers of a major infectious diseases hospital in Vietnam. We measured neutralizing antibodies before and 14 days after each dose, and at day 28 and month 3 after dose 1. A total of 554 workers (136 men and 418 women; age range, 22-71 years; median age, 36 years) participated with the study. Of the 144 participants selected for follow-up after dose 1, 104 and 94 gave blood for antibody measurement at weeks 6 and 8, and at month 3 after dose 1, respectively. The window time between the two doses was 6 weeks. At baseline, none had detectable neutralizing antibodies. After dose 1, the proportion of participants with detectable neutralizing antibodies increased from 27.3% (151 of 554) at day 14 to 78.0% (432 of 554) at day 28. Age correlated negatively with the development and the levels of neutralizing antibodies. However, at day 28, these differences were less profound, and women had a greater seroconversion rate and greater levels of neutralizing antibodies than men. After dose 2, these age and gender associations were not observable. In addition, the proportion of study participants with detectable neutralizing antibodies increased from 70.2% (73 of 104) before dose 2 (week 6, after dose 1) to 98.1% (102 of 104) 14 days later. At month 3, neutralizing antibodies decreased and 94.7% (89 of 94) of the study participants remained seropositive. The Oxford-AstraZeneca COVID-19 vaccine is immunogenic in Vietnamese health-care workers. These data are critical to informing the deployment of the COVID-19 vaccine in Vietnam and in Southeast Asia, where vaccination coverage remains inadequate.

The relationship between age and seroprevalence can be used to estimate the annual attack rate of an infectious disease. For pathogens with multiple serologically distinct strains, there is a need to describe composite exposure to an antigenically variable group of pathogens. In this study, we assay 24,402 general-population serum samples, collected in Vietnam between 2009 to 2015, for antibodies to eleven human influenza A strains. We report that a principal components decomposition of antibody titer data gives the first principal component as an appropriate surrogate for seroprevalence; this results in annual attack rate estimates of 25.6% (95% CI: 24.1% - 27.1%) for subtype H3 and 16.0% (95% CI: 14.7% - 17.3%) for subtype H1. The remaining principal components separate the strains by serological similarity and associate birth cohorts with their particular influenza histories. Our work shows that dimensionality reduction can be used on human antibody profiles to construct an age-seroprevalence relationship for antigenically variable pathogens., (© 2021. The Author(s).)

Background: Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited., Methods: We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing., Findings: Between 11 th -25 th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8-33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.002). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms., Interpretation: Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals., Funding: Wellcome and NIH/NIAID., Competing Interests: All authors declare no competing interests., (© 2021 The Author(s).)

This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Choisy M et al.)

Background  COVID-19 was first detected in Wuhan, China, in 2019 and spread worldwide within a few weeks. The COVID-19 epidemic started to gain traction in France in March 2020. Subnational hospital admissions and deaths were then recorded daily and served as the main policy indicators. Concurrently, mobile phone positioning data have been curated to determine the frequency of users being colocalized within a given distance. Contrarily to individual tracking data, these can be a proxy for human contact networks between subnational administrative units. Methods  Motivated by numerous studies correlating human mobility data and disease incidence, we developed predictive time series models of hospital incidence between July 2020 and April 2021. We added human contact network analytics, such as clustering coefficients, contact network strength, null links or curvature, as regressors. Findings  We found that predictions can be improved substantially (by more than 50%) at both the national level and the subnational level for up to 2 weeks. Our subnational analysis also revealed the importance of spatial structure, as incidence in colocalized administrative units improved predictions. This original application of network analytics from colocalization data to epidemic spread opens new perspectives for epidemic forecasting and public health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Development of antimicrobial use (AMU) surveillance systems in humans and animals is a priority for many low- and middle-income countries; however accurate estimations are hampered by a diversity of animal production systems and metrics. The Mekong Delta region of Vietnam is a 'hotspot' of antimicrobial resistance and is home to a high density of humans and animal populations., Objectives: To measure and compare AMU using different metrics (standing population, biomass and population correction unit) in the Mekong Delta, and to explore the potential of field-based data collection methods in the design of AMU surveillance systems., Methods: We collected AMU data from humans and animals (chickens, ducks, Muscovy ducks, pigs) from 101 small-scale farms in the Mekong Delta over a fixed period (90 days in humans, 7 days in animals)., Results: Humans used 7.1 DDD kg , or 175.9 mg of antimicrobial active ingredients (AAIs) per kg of standing body mass annually; animals consumed 60.9 ADD kg or 1324 mg. In the Mekong Delta humans represented 79.3% of the total body mass but consumed 29.6% of AAIs by weight. AAIs regarded of critical importance by WHO represented 56.9% and 50.2% of doses consumed by animals and humans, respectively., Conclusions: Using a One Health approach, we show that AMU can potentially be estimated from cross-sectional surveys, although results are hypothetical due to small sample size and are sensitive to the chosen population denominator. The methodology proposed here can potentially be scaled up be applied to design AMU surveillance in low-resource settings, allowing AMU reduction efforts to be focused on particular animal species., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Antimicrobials are extensively used both prophylactically and therapeutically in poultry production. Despite this, there are little data on the effect of antimicrobial use (AMU) on disease incidence rate and per cent mortality. We investigated the relationships between AMU and disease and between AMU and mortality using data from a large (n = 322 flocks) cohort of small-scale chicken flocks in the Mekong Delta, Vietnam, that were followed longitudinally from day old to slaughter (5,566 observation weeks). We developed a parameterized algorithm to emulate a randomized control trial from observational data by categorizing the observation weeks into 'non-AMU', 'prophylactic AMU' and 'therapeutic AMU'. To evaluate the prophylactic AMU effect, we compared the frequencies of clinical signs in 'non-AMU' and 'prophylactic AMU' periods. To analyse therapeutic AMU, we compared weekly per cent mortality between the weeks of disease episodes before and after AMU. Analyses were stratified by clinical signs (4) and antimicrobial classes (13). Prophylactic AMU never reduced the probability of disease, and some antimicrobial classes such as lincosamides, amphenicols and penicillins increased the risk. The risk of diarrhoea consistently increased with prophylactic AMU. Therapeutic AMU often had an effect on mortality, but the pattern was inconsistent across the combinations of antimicrobial classes and clinical signs with 14/29 decreasing and 11/29 increasing the per cent weekly mortality. Lincosamides, methenamines and cephalosporins were the only three antimicrobial classes that always decreased the mortality when used therapeutically. Results were robust respective to the parameters values of the weeks categorization algorithm. This information should help support policy efforts and interventions aiming at reducing AMU in animal production., (© 2021 The Authors. Zoonoses and Public Health published by Wiley-VCH.)

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.

Background: One hundred days after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Vietnam on 23 January, 270 cases were confirmed, with no deaths. We describe the control measures used by the government and their relationship with imported and domestically acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control., Methods: Clinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of government control measures, including numbers of tests and quarantined individuals, were analyzed. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of presymptomatic transmission events and time-varying reproduction numbers., Results: A national lockdown was implemented between 1 and 22 April. Around 200 000 people were quarantined and 266 122 reverse transcription polymerase chain reaction (RT-PCR) tests conducted. Population mobility decreased progressively before lockdown. In total, 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. The serial interval was 3.24 days, and 27.5% (95% confidence interval [CI], 15.7%-40.0%) of transmissions occurred presymptomatically. Limited transmission amounted to a maximum reproduction number of 1.15 (95% CI, .·37-2.·36). No community transmission has been detected since 15 April., Conclusions: Vietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial presymptomatic transmission., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

A cluster of severe acute respiratory syndrome coronavirus 2 infections in Danang, Vietnam, began July 25, 2020, and resulted in 551 confirmed cases and 35 deaths as of February 2021. We analyzed 26 sequences from this cluster and identified a novel shared mutation in nonstructural protein 9, suggesting a single introduction into Vietnam.

Antimicrobials are included in commercial animal feed rations in many low- and middle-income countries (LMICs). We measured antimicrobial use (AMU) in commercial feed products consumed by 338 small-scale chicken flocks in the Mekong Delta of Vietnam, before a gradual nationwide ban on prophylactic use of antimicrobials (including in commercial feeds) to be introduced in the country over the coming five years. We inspected the labels of commercial feeds and calculated amounts of antimicrobial active ingredients (AAIs) given to flocks. We framed these results in the context of overall AMU in chicken production, and highlighted those products that did not comply with Government regulations. Thirty-five of 99 (35.3%) different antimicrobial-containing feed products included at least one AAI. Eight different AAIs (avilamycin, bacitracin, chlortetracycline, colistin, enramycin, flavomycin, oxytetracycline, virginamycin) belonging to five classes were identified. Brooding feeds contained antimicrobials the most (60.0%), followed by grower (40.9%) and finisher feeds (20.0%). Quantitatively, chlortetracycline was consumed most (42.2 mg/kg SEM ±0.34; 50.0% of total use), followed by enramycin (18.4 mg/kg SEM ±0.03, 21.8%), bacitracin (16.4 mg/kg SEM ±0.20, 19.4%) and colistin (6.40 mg/kg SEM ± 4.21;7.6%). Other antimicrobials consumed were virgianamycin, avilamycin, flavomycin and oxytetracycline (each ≤0.50 mg/kg). Antimicrobials in commercial feeds were more commonly given to flocks in the earlier part of the production cycle. A total of 10 (9.3%) products were not compliant with existing Vietnamese regulation (06/2016/TT-BNNPTNT) either because they included a non-authorised AAI (4), had AAIs over the permitted limits (4), or both (2). A number of commercial feed formulations examined included colistin (polymyxin E), a critically important antimicrobial of highest priority for human medicine. These results illustrate the challenges for effective implementation and enforcement of restrictions of antimicrobials in commercial feeds in LMICs. Results from this study should help encourage discussion about policies on medicated feeds in LMICs., Competing Interests: The authors have declared that no competing interests exist.

In an epidemic, individuals can widely differ in the way they spread the infection depending on their age or on the number of days they have been infected for. In the absence of pharmaceutical interventions such as a vaccine or treatment, non-pharmaceutical interventions (e.g. physical or social distancing) are essential to mitigate the pandemic. We develop an original approach to identify the optimal age-stratified control strategy to implement as a function of the time since the onset of the epidemic. This is based on a model with a double continuous structure in terms of host age and time since infection. By applying optimal control theory to this model, we identify a solution that minimizes deaths and costs associated with the implementation of the control strategy itself. We also implement this strategy for three countries with contrasted age distributions (Burkina-Faso, France, and Vietnam). Overall, the optimal strategy varies throughout the epidemic, with a more intense control early on, and depending on host age, with a stronger control for the older population, except in the scenario where the cost associated with the control is low. In the latter scenario, we find strong differences across countries because the control extends to the younger population for France and Vietnam 2 to 3 months after the onset of the epidemic, but not for Burkina Faso. Finally, we show that the optimal control strategy strongly outperforms a constant uniform control exerted over the whole population or over its younger fraction. This improved understanding of the effect of age-based control interventions opens new perspectives for the field, especially for age-based contact tracing., Competing Interests: The authors have declared that no competing interests exist.

Dengue outbreaks have regularly been recorded in Lao People's Democratic Republic (PDR) since the first detection of the disease in 1979. In 2012, an integrated arbovirus surveillance network was set up in Lao PDR and an entomological surveillance has been implemented since 2016 in Vientiane Capital. Here, we report a study combining epidemiological, phylogenetic, and entomological analyzes during the largest DENV-4 epidemic ever recorded in Lao PDR (2015-2019). Strikingly, from 2015 to 2019, we reported the DENV-4 emergence and spread at the country level after two large epidemics predominated by DENV-3 and DENV-1, respectively, in 2012-2013 and 2015. Our data revealed a significant difference in the median age of the patient infected by DENV-4 compared to the other serotypes. Phylogenetic analysis demonstrated the circulation of DENV-4 Genotype I at the country level since at least 2013. The entomological surveillance showed a predominance of Aedes aegypti compared to Aedes albopictus and high abundance of these vectors in dry and rainy seasons between 2016 and 2019, in Vientiane Capital. Overall, these results emphasized the importance of an integrated approach to evaluate factors, which could impact the circulation and the epidemiological profile of dengue viruses, especially in endemic countries like Lao PDR.

Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.

Background: Tuberculosis (TB) is a major global health burden, with an estimated quarter of the world's population being infected. The World Health Organization (WHO) launched the "End TB Strategy" in 2014 emphasising knowing the epidemic. WHO ranks Vietnam 12th in the world of high burden countries. TB spatial and temporal patterns have been observed globally with evidence of Vitamin D playing a role in seasonality. We explored the presence of temporal and spatial clustering of TB in Vietnam and their determinants to aid public health measures., Methods: Data were collected by the National TB program of Vietnam from 2010 to 2015 and linked to the following datasets: socio-demographic characteristics; climatic variables; influenza-like-illness (ILI) incidence; geospatial data. The TB dataset was aggregated by province and quarter. Descriptive time series analyses using LOESS regression were completed per province to determine seasonality and trend. Harmonic regression was used to determine the amplitude of seasonality by province. A mixed-effect linear model was used with province and year as random effects and all other variables as fixed effects., Results: There were 610,676 cases of TB notified between 2010 and 2015 in Vietnam. Heat maps of TB incidence per quarter per province showed substantial temporal and geospatial variation. Time series analysis demonstrated seasonality throughout the country, with peaks in spring/summer and troughs in autumn/winter. Incidence was consistently higher in the south, the three provinces with the highest incidence per 100,000 population were Tay Ninh, An Giang and Ho Chi Minh City. However, relative seasonal amplitude was more pronounced in the north. Mixed-effect linear model confirmed that TB incidence was associated with time and latitude. Of the demographic, socio-economic and health related variables, population density, percentage of those under 15 years of age, and HIV infection prevalence per province were associated with TB incidence. Of the climate variables, absolute humidity, average temperature and sunlight were associated with TB incidence., Conclusion: Preventative public health measures should be focused in the south of Viet Nam where incidence is highest. Vitamin D is unlikely to be a strong driver of seasonality but supplementation may play a role in a package of interventions.

In the Mekong Delta region of Vietnam, small-scale chicken farming is common. However, high levels of disease or mortality in such flocks impair economic development and challenge the livelihoods of many rural households. We investigated 61 diseased small-scale flocks (122 chickens) for evidence of infection with 5 bacteria, 4 viruses, and helminths. Serological profiles (ELISA) were also determined against 6 of these pathogens. The aims of this study were the following: (1) to investigate the prevalence of different pathogens and to compare the probability of detection of bacterial pathogens using PCR and culture; (2) to investigate the relationship between detection of organisms in birds' tissues and the observed morbidity and mortality, as well as their antibody profile; and (3) to characterize risk factors for infection with specific viral or bacterial pathogens. We used PCR to test for viral (viruses causing infectious bronchitis [IB], highly pathogenic avian influenza [HPAI], Newcastle disease, and infectious bursal disease [IBD]) and bacterial pathogens (Mycoplasma gallisepticum, Pasteurella multocida, Avibacterium paragallinarum, and Ornithobacterium rhinotracheale [ORT]). The latter two were also investigated in respiratory tissues by conventional culture. Colisepticemic Escherichia coli was investigated by liver or spleen culture. In 49 of 61 (80.3%) flocks, at least one bacterial or viral pathogen was detected, and in 29 (47.5%) flocks, more than one pathogen was detected. A. paragallinarum was detected in 62.3% flocks, followed by M. gallisepticum (26.2%), viruses causing IBD (24.6%) and IB (21.3%), septicemic E. coli (14.8%), ORT (13.1%), and HPAI viruses (4.9%). Of all flocks, 67.2% flocks were colonized by helminths. Mortality was highest among flocks infected with HPAI (100%, interquartile range [IQR]: 81.6-100%) and lowest with flocks infected with ORT (5.3%, IQR: 1.1-9.0%). The results indicated slight agreement (kappa ≤ 0.167) between detection by PCR and culture for both A. paragallinarum and ORT, as well as between the presence of cestodes and ORT infection (kappa = 0.317). Control of A. paragallinarum, viruses causing HPAI, IBD, and IB, M. gallisepticum, and gastrointestinal helminths should be a priority in small-scale flocks., (Copyright © 2019. Published by Elsevier Inc.)

The accurate assessment of antimicrobial use (AMU) requires relating quantities of active ingredients (AAIs) with population denominators. These data can be used to prioritize potential sources of selective pressure for antimicrobial resistance and to establish reduction targets. Here, we estimated AMU in Vietnam (human population 93.4 M in 2015), and compared it with European Union (EU) data (population 511.5 M in 2014). We extrapolated AMU data on each key animal species and humans from different published sources to calculate overall AMU (in tonnes) in Vietnam. We then compared these data with published statistics on AMU in the European Union (EU). A total of 3838 t of antimicrobials were used in Vietnam, of which 2751 (71.7%) corresponded to animal use, and the remainder (1086 t; 28.3%) to human AMU. This equates to 261.7 mg and 247.3 mg per kg of human and animal biomass, compared with 122.0 mg and 151.5 mg in the EU. The greatest quantities of antimicrobials (in decreasing order) were used in pigs (41.7% of total use), humans (28.3%), aquaculture (21.9%) and chickens (4.8%). Combined AMU in other species accounted for < 1.5%. These results are approximate and highlight the need to conduct targeted surveys to improve country-level estimates of AMU., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

In recent years, serosurveillance has gained momentum as a way of determining disease transmission and immunity in populations, particularly with respect to vaccine-preventable diseases. At the end of 2017, the Oxford University Clinical Research Unit and the National Institute of Hygiene and Epidemiology held a meeting in Vietnam with national policy makers, researchers, and international experts to discuss current seroepidemiologic projects in Vietnam and future needs and plans for nationwide serosurveillance. This report summarizes the meeting and the plans that were discussed to set up nationwide serosurveillance in Vietnam.

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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chicken is, among farmed species, the target of the highest levels of antimicrobial use (AMU). There are considerable knowledge gaps on how and when antimicrobials are used in commercial small-scale chicken farms. These shortcomings arise from cross-sectional study designs and poor record keeping practiced by many such farmers. Furthermore, there is a large diversity of AMU metrics, and it is not clear how these metrics relate to each other. We performed a longitudinal study on a cohort of small-scale chicken farms ( n = 102) in the Mekong Delta (Vietnam), an area regarded as a hotspot of AMU, from October 2016 to May 2018. We collected data on all medicine products administered to 203 flocks with the following aims: (1) to describe types and quantities of antimicrobial active ingredients (AAIs) used; (2) to describe critical time points of AMU; and (3) to compare AMU using three quantitative metrics: (a) weight of AAIs related to bird weight at the time of treatment (mg/kg at treatment); (b) weight of AAIs related to weight of birds sold (mg/kg sold); and (c) "treatment incidence" (TI), or the number of daily doses per kilogram of live chicken [Vietnamese animal daily dose (ADDvetVN)] per 1,000 days. Antimicrobials contained in commercial feed, administered by injection ( n = N = 6), or antimicrobials for human medicine ( n = N = 16) were excluded. A total of 236 products were identified, containing 42 different AAIs. A total of 76.2% products contained AAIs of "critical importance" according to the World Health Organization (WHO). On average, chickens consumed 791.8 (SEM ±16.7) mg/kg at treatment, 323.4 (SEM ±11.3) mg/kg sold, and the TI was 382.6 (SEM ±5.5) per 1,000 days. AMU was more common early in the production cycle and was highly skewed, with the upper 25% quantile of flocks accounting for 60.7% of total AMU. The observed discrepancies between weight- and dose-based metrics were explained by differences in the strength of AAIs, mortality levels, and the timing of administration. Results suggest that in small-scale chicken production, AMU reduction efforts should preferentially target the early (brooding) period, which is when birds are most likely to be exposed to antimicrobials, whilst restricting access to antimicrobials of critical importance for human medicine.

Background: Antimicrobials are used by poultry farmers in Vietnam as a tool to treat and prevent infectious diseases. We aimed to determine the fraction of disease episodes likely to remain untreated due to the administration of antimicrobials on non-susceptible pathogens in chicken flocks in the Mekong Delta of Vietnam. Weekly data on antimicrobial use and clinical signs were collected from 88 randomly chosen chicken flocks over 124 full production cycles (i.e. time between restocking flocks with day-old chicks and sale for slaughter). A naïve Bayes model was trained to infer the probabilities of disease episodes having been caused by each of 24 pathogens, given the observed clinical sign profile, and expert knowledge on their relative incidence., Results: A total of 224 disease episodes were observed, of which 44.8% were attributed to viruses (95% CI 31.1-58.4%), 54.6% (CI 40.4-68.7%) to bacteria, and 0.6% (CI 0-1.7%) to a protozoan (Eimeria spp.). Antimicrobials were more frequently administered on weeks with disease than on weeks without disease (43.3% vs. 17.8%; p < 0.001). A median of 2 [IQR 0-4] antimicrobials were used by episode. The choice of specific antimicrobials was independent on whether the flocks had disease clinical signs or not. Antimicrobials were not used in 30.3% of the episodes. The overall probability that episodes were not effectively treated was 74.2, and 53.7% when discounting cases where the inferred aetiology is viral. Considering only episodes where antimicrobials were given, these probabilities were 57.4 and 23.8% respectively., Conclusions: This study highlights untargeted use of antimicrobials on small-scale Vietnamese chicken farms, as well as the limitations of antimicrobials as effective tools to control infectious diseases.

Raising chickens in small-scale flocks following all-in-all-out management is common in the Mekong Delta of Vietnam. These flocks represent an intermediate category between backyard and intensive (industrial) farming systems. However, little is known about the occurrence and burden of disease and/or mortality in such flocks, and their potential association with antimicrobial usage (AMU). We investigated mortality, disease and weekly antimicrobial use (AMU) in 124 cycles of meat chicken flocks raised in 88 farms in the Mekong Delta of Vietnam (with a median cycle duration of 18 weeks [inter-quartile range IQR 17-20]). We visited each farm 4 times per cycle to review data collected weekly by the farmers on clinical signs, mortality, and AMU. The overall probability of disease and AMU were 0.31 (95% CI 0.29-0.32) and 0.26 (95% CI 0.24-0.28), respectively. The average weekly incidence of mortality was 2.6 (95% CI 2.2-3.0) per 100 birds. Both the probabilities of a flock experiencing disease and mortality, as well as of using antimicrobials decreased with the flock's age. However, mortality peaked at the 5-10 week period. The only significant explanatory factors associated with presence of disease was the stage of production ≥5 weeks (protective) (OR ≤ 0.51). Factors independently associated with AMU (p < 0.05) were: (1) Number of chickens (log) (OR=1.46), (2) Stage of production ≥5 weeks (OR≤0.67) (protective), (3) Cao Lanh district (OR=2.23), (4) Density of veterinary drug shops at commune level (log) (OR=1.58), and (5) Disease in flocks (OR=1.80). Factors independently associated with overall increased weekly incidence of mortality (p < 0.05) were: (1) High level of education attainment (secondary education or higher) (Hazard rate Ratio [HR]=1.70), (2) number of chickens (log) (HR=1.39), and (3) Stage of production >5 weeks (HR≤2.14). In flocks reporting disease, AMU significantly reduced the incidence of mortality (HR=0.90). These results confirm an exceptionally high mortality in chicken flocks in the area, jeopardizing the profitability and sustainability of these small-scale farming systems. The data also suggest an association between nearby access to antimicrobials and AMU, and a high correlation of AMU over consecutive cycles. The atomized farming landscape of the Mekong Delta, the high incidence of disease and mortality, and the unrestricted and easy access to antimicrobials present major challenges to the implementation of policies aimed at AMU reductions., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Rickettsioses are endemic to Vietnam; however, only a limited number of clinical studies have been performed on these vectorborne bacteria. We conducted a prospective hospital-based study at 2 national referral hospitals in Hanoi to describe the clinical characteristics of scrub typhus and murine typhus in northern Vietnam and to assess the diagnostic applicability of quantitative real-time PCR assays to diagnose rickettsial diseases. We enrolled 302 patients with acute undifferentiated fever and clinically suspected rickettsiosis during March 2015-March 2017. We used a standardized case report form to collect clinical information and laboratory results at the time of admission and during treatment. We confirmed scrub typhus in 103 (34.1%) patients and murine typhus in 12 (3.3%) patients. These results highlight the need for increased emphasis on training for healthcare providers for earlier recognition, prevention, and treatment of rickettsial diseases in Vietnam.

Background: During the first half of 2014, a severe outbreak of measles occurred in northern Vietnam, causing 15 033 confirmed cases and 146 deaths., Methods: To evaluate the population-level seroprevalence of protection against measles in the period before the outbreak, we made use of an existing age-stratified serum bank, collected over the year before the outbreak, between November 2012 and December 2013, from 4 sites across the country (Hanoi, Hue, Dak Lak, and Ho Chi Minh City). Data from the UNICEF's Multiple Indicator Clustered Surveys (MICS), carried out in Vietnam during the first quarter of 2014, were used to assess the vaccine coverage in 6 ecological regions of Vietnam., Results: Results revealed a large discrepancy between levels of protection, as estimated from the serology and vaccine coverage estimated by UNICEF's MICS. Variation in seroprevalence across locations and age groups corresponded with reported numbers of measles cases, most of which were among the 0-2-year-old age group and in the northern part of the country., Conclusions: Our study presents a strong case in favor of a serosurveillance sentinel network that could be used to proactively tune vaccination policies and other public health interventions.