Building citizen science intelligence for outbreak preparedness and response: a mixed-method study in nine countries to assess knowledge, readiness and feasibility.

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.

Influenza vaccination allocation in tropical settings under constrained resources.

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.

Mosquito ageing modulates the development, virulence and transmission potential of pathogens.

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.

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

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.

Impact of antimicrobial use on abundance of antimicrobial resistance genes in chicken flocks in Vietnam.

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 ß-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.

Repeatability and timing of tropical influenza epidemics.

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.

Prevalence and Associated Factors of optrA-Positive-Enterococcus faecalis in Different Reservoirs around Farms in Vietnam.

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.

The spatio-temporal distribution of acute encephalitis syndrome and its association with climate and landcover in Vietnam.

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.

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.

Seroprotection against tetanus in southern Vietnam.

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.

Genomic epidemiological analysis of mcr-1-harboring Escherichia coli collected from livestock settings in Vietnam.

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.

Aetiology and Potential Animal Exposure in Central Nervous System Infections in Vietnam.

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.

Carriage of Plasmid-Mediated Colistin Resistance-1-Positive Escherichia coli in Humans, Animals, and Environment on Farms in Vietnam.

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.

Antimicrobial resistance in commensal Escherichia coli from humans and chickens in the Mekong Delta of Vietnam is driven by antimicrobial usage and potential cross-species transmission.

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.

A call for citizen science in pandemic preparedness and response: beyond data collection.

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.

Modelling the impact of antimicrobial use and external introductions on commensal E. coli colistin resistance in small-scale chicken farms of the Mekong delta of Vietnam.

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.

Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: An observational study.

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.

Immunogenicity of Oxford-AstraZeneca COVID-19 Vaccine in Vietnamese Health-Care Workers.

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.

Minimum inhibitory concentrations of commercial essential oils against common chicken pathogenic bacteria and their relationship with antibiotic resistance.

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.