Spatial clusters of human and livestock anthrax define high-risk areas requiring intervention in Lao Cai Province, Vietnam 1991-2022.

Anthrax, a widespread zoonosis in low and middle-income countries with low disease awareness and insufficient livestock vaccination coverage, has been known in Lao Cai Province in northern Vietnam for years before its apparent absence in 2009, which requires investigation as this infection is frequently reported from neighbouring provinces and countries. We aimed to describe the seasonal patterns of anthrax (1991-2008), compare livestock anthrax vaccine coverage to disease occurrence (1991- 2022), and delineate the high-risk areas to inform local disease surveillance in the province. We illustrated the seasonal pattern of anthrax and provided a comparison between livestock vaccine coverage and disease occurrence by purely spatial SaTScan (Poisson model, 25% population at risk) to detect spatial clusters of human and livestock anthrax using population derived from zonal statistics routines. The number of cases, crude cumulative incidence, and spatial clusters of human and livestock anthrax were mapped in QGIS. Results indicate peak anthrax incidence from May to October. Buffalo, domestic cattle, and horses accounted for 75% of total animal cases. Horse anthrax was more common in Lao Cai than in its neighbours and often occurred in years with human mortality. Vaccination covered less than 30% of the livestock population. We found an apparent pattern where anthrax was controlled from 1998-2003 with higher vaccine coverage (>20%) and identified spatial clusters of human and livestock anthrax in Muong Khuong, Bao Thang, and Bac Ha districts of Lao Cai. The local public health and veterinary agencies are recommended to revisit the high-risk areas and communicate with neighbouring provinces for a regional approach to anthrax surveillance and control.

Spatial epidemiology of human anthrax in Son La province, Vietnam, 2003-2022.

AIMS: Anthrax is reported with frequency but poorly understood in Southeast Asian countries including Vietnam. In Vietnam, anthrax surveillance is national. However, case detection, prevention, and control are implemented locally at the provincial level. Here, we describe the epidemiological characteristics, identify spatial clusters of human anthrax, and compare the variation in livestock anthrax vaccine coverage to disease incidence in humans and livestock using historical data in Son La province, Vietnam (2003-2020). METHODS AND RESULTS: Most human cases occurred between April and September. Most of the patients were male, aged 15-54 years old. The human cases were mainly reported by public district hospitals. There was a delay between disease onset and hospitalization of ~5 days. We identified spatial clusters of high-high incidence communes in the northern communes of the province using the local Moran's I statistic. The vaccine coverage sharply decreased across the study period. The province reported sporadic human anthrax outbreaks, while animal cases were only reported in 2005 and 2022. CONCLUSIONS: These results suggest underreporting for human and livestock anthrax in the province. Intersectoral information sharing is needed to aid livestock vaccination planning, which currently relies on reported livestock cases. The spatial clusters identify areas for targeted surveillance and livestock vaccination, while the seasonal case data suggest prioritizing vaccination campaigns for February or early March ahead of the April peak. A regional approach for studying the role of livestock trading between Son La and neighbouring provinces in anthrax occurrence is recommended.

Spatial analysis of human and livestock anthrax in Lai Chau province, Vietnam (2004-2021).

Anthrax is reported globally with varying disease intensity and seasonality among countries. In Vietnam, anthrax epidemiology and ecology remain understudied. We used historical data of human and livestock anthrax from 2004 to 2021 in Lai Chau province, to identify spatial clusters of human and livestock anthrax, describe epidemiological characteristics, and compare livestock anthrax vaccine coverage to human and livestock disease incidence. Local Moran's I (LISA) using spatial Bayes smoothed commune-level cumulative incidence (per 10,000) for the study period, epidemiological descriptive statistics, livestock vaccine coverage data, and annual incidence rates (per 10,000) at provincial level were used. LISA identified a human anthrax hotspot (high-high) in the southeast which did not overlap spatially with livestock anthrax hotspots in southeastern and northeastern communes. Most human cases were male, aged 15-59 years, handled sick animals, and/or consumed contaminated meat. Almost all cases were reported by grassroot health facilities with a delay of 6.3 days between exposure and case notification to the national surveillance system. 80 % of human cases were reported from June-October. The increase in disease incidence occurred shortly after livestock anthrax vaccine coverage decreased. This study informs vaccination strategy and targeted surveillance and control measures in newly identified high-risk areas and seasons of anthrax.

Spatial and phylogenetic patterns reveal hidden infection sources of Bacillus anthracis in an anthrax outbreak in Son La province, Vietnam.

Bacillus anthracis, the bacterial cause of anthrax, is a zoonosis affecting livestock and wildlife often spilling over into humans. In Vietnam, anthrax has been nationally reportable since 2015 with cases occurring annually, mostly in the northern provinces. In April 2022, an outbreak was reported in Son La province following the butchering of a water buffalo, Bubalus bubalis. A total of 137 humans from three villages were likely exposed to contaminated meat from the animal. Early epidemiological investigations suggested a single animal was involved in all exposures. Five B. anthracis isolates were recovered from human clinical cases along with one from the buffalo hide, another from associated maggots, and one from soil at the carcass site. The isolates were whole genome sequenced, allowing global, regional, and local molecular epidemiological analyses of the outbreak strains. All recovered B. anthracis belong to the A.Br.001/002 lineage based on canonical single nucleotide polymorphism analysis (canSNP). Although not previously identified in Vietnam, this lineage has been identified in the nearby countries of China, India, Indonesia, Thailand, as well as Australia. A twenty-five marker multi-locus variable number tandem repeat analysis (MLVA-25) was used to investigate the relationship between human, soil, and buffalo strains. Locally, four MLVA-25 genotypes were identified from the eight isolates. This level of genetic diversity is unusual for the limited geography and timing of cases and differs from past literature using MLVA-25. The coupled spatial and phylogenetic data suggest this outbreak originated from multiple, likely undetected, animal sources. These findings were further supported by local news reports that identified at least two additional buffalo deaths beyond the initial animal sampled in response to the human cases. Future outbreak response should include intensive surveillance for additional animal cases and additional molecular epidemiological traceback to identify pathogen sources.

Shift from a Zero-COVID strategy to a New-normal strategy for controlling SARS-COV-2 infections in Vietnam.

The aim of this study is to analyse the changing patterns in the transmission of COVID-19 in relation to changes in Vietnamese governmental policies, based on epidemiological data and policy actions in a large Vietnamese province, Bac Ninh, in 2021. Data on confirmed cases from January to December 2021 were collected, together with policy documents. There were three distinct periods of the COVID-19 pandemic in Bac Ninh province during 2021. During the first period, referred to as the 'Zero-COVID' period (01/04-07/04/2021), there was a low population vaccination rate, with less than 25% of the population receiving its first vaccine dose. Measures implemented during this period focused on domestic movement restrictions, mask mandates, and screening efforts to control the spread of the virus. The subsequent period, referred to as the 'Transition' period (07/05-10/22/2021), witnessed a significant increase in population vaccination coverage, with 80% of the population receiving their first vaccine dose. During this period, several days passed without any reported COVID-19 cases in the community. The local government implemented measures to manage domestic actions and reduce the time spent in quarantine, and encouraged home quarantining for the close contacts of cases with COVID-19. Finally, the 'New-normal' stage (10/23-12/31/2021), during which the population vaccination coverage with a second vaccine dose increased to 70%, and most of the mandates for the prevention and control of COVID-19 were reduced. In conclusion, this study highlights the importance of governmental policies in managing and controlling the transmission of COVID-19 and provides insights for developing realistic and context-specific strategies in similar settings.

Assessing the robustness of COVID-19 vaccine efficacy trials: systematic review and meta-analysis, January 2023.

BackgroundVaccines play a crucial role in the response to COVID-19 and their efficacy is thus of great importance.AimTo assess the robustness of COVID-19 vaccine efficacy (VE) trial results using the fragility index (FI) and fragility quotient (FQ) methodology.MethodsWe conducted a Cochrane and PRISMA-compliant systematic review and meta-analysis of COVID-19 VE trials published worldwide until 22 January 2023. We calculated the FI and FQ for all included studies and assessed their associations with selected trial characteristics using Wilcoxon rank sum tests and Kruskal-Wallis H tests. Spearman correlation coefficients and scatter plots were used to quantify the strength of correlation of FIs and FQs with trial characteristics.ResultsOf 6,032 screened records, we included 40 trials with 54 primary outcomes, comprising 909,404 participants with a median sample size per outcome of 13,993 (interquartile range (IQR): 8,534-25,519). The median FI and FQ was 62 (IQR: 22-123) and 0.50% (IQR: 0.24-0.92), respectively. FIs were positively associated with sample size (p < 0.001), and FQs were positively associated with type of blinding (p = 0.023). The Spearman correlation coefficient for FI with sample size was moderately strong (0.607), and weakly positive for FI and FQ with VE (0.138 and 0.161, respectively).ConclusionsThis was the largest study on trial robustness to date. Robustness of COVID-19 VE trials increased with sample size and varied considerably across several other important trial characteristics. The FI and FQ are valuable complementary parameters for the interpretation of trial results and should be reported alongside established trial outcome measures.

Incidence and Spatial distribution of Human and Livestock Anthrax in Cao Bang Province, Vietnam (2004-2020).

Specific knowledge on the distribution of anthrax, a zoonosis caused by Bacillus anthracis, in Southeast Asia, including Vietnam, remains limited. In this study, we describe disease incidence and spatial distribution of human and livestock anthrax using spatially smoothed cumulative incidence from 2004 to 2020 in Cao Bang province, Vietnam. We employed the zonal statistics routine a geographic information system (GIS) using QGIS, and spatial rate smoothing using spatial Bayes smoothing in GeoDa. Results showed higher incidence of livestock anthrax compared with human anthrax. We also identified co-occurrence of anthrax in humans and livestock in northwestern districts and the province center. Livestock anthrax vaccine coverage was <6% and not equally distributed among the districts of Cao Bang province. We provide implications for future studies and recommend improving disease surveillance and response through data sharing between human and animal health sectors.

Informing One Health Anthrax Surveillance and Vaccination Strategy from Spatial Analysis of Anthrax in Humans and Livestock in Ha Giang Province, Vietnam (1999-2020).

Anthrax, caused by Bacillus anthracis, has a nearly global distribution but is understudied in Southeast Asia, including Vietnam. Here, we used historical data from 1999 to 2020 in Ha Giang, a province in northern Vietnam. The objectives were to describe the spatiotemporal patterns and epidemiology of human and livestock anthrax in the province and compare livestock vaccine coverage with human and livestock anthrax incidence. Annual incidence rates (per 10,000) for humans, buffalo/cattle, and goats were used to explore anthrax patterns and for comparison with livestock annual vaccine variations. A data subset describes anthrax epidemiology in humans by gender, age, source of infection, type of anthrax, admission site, and season. Zonal statistics and SaTScan were used to identify spatial and space-time clusters of human anthrax. SaTScan revealed space-time clusters in 1999, 2004, and 2007-2008 in the province, including in the northeastern, eastern, and western areas. Most human anthrax was reported between July and October. Most patients were male, aged 15-59 years, who had handled sick animals and/or consumed contaminated meat. High case-fatality rates were reported with gastrointestinal or respiratory cases. Our data suggest that vaccination in buffalo and cattle reduces the disease burden in humans and vaccinated animals but does not reduce the incidence in unvaccinated animals (goats). This study identified spatial areas of high risk for anthrax and can inform One Health surveillance and livestock vaccination planning in contextual settings similar to Ha Giang province.

Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children.

The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on infections in healthy adults based on single timepoint data. Here, we analyzed the within-host evolution of 82 longitudinally sampled individuals, mostly young children, infected with A/H1N1pdm09 or A/H3N2 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous minority variants were more prevalent than synonymous ones. For A/H3N2 viruses in young children, early infection was dominated by purifying selection. As these infections progressed, nonsynonymous variants typically increased in frequency even when within-host virus titers decreased. Unlike the short-lived infections of adults where de novo within-host variants are rare, longer infections in young children allow for the maintenance of virus diversity via mutation-selection balance creating potentially important opportunities for within-host virus evolution.

Epidemiological and molecular characteristics of a measles outbreak in northern Vietnam, 2013-2014.

BACKGROUND: A nationwide measles outbreak occurred in Vietnam between 2013 and 2014. OBJECTIVES: To provide an overview on the 2013-2014 measles outbreak in northern Vietnam using epidemiological and molecular analysis of the measles virus (MeV). STUDY DESIGN: Epidemiological information was collected from all suspected cases of measles/rubella. Serum and/or throat swabs were collected for laboratory confirmation of measles. MeV genomes were detected and sequenced for phylogenetic analysis. RESULTS: A total of 9577 confirmed measles cases were reported in northern Vietnam with an incidence rate of 116.4/1,000,000 population. Of these, approximately 76.3% had unvaccinated or unknown vaccination history and 55.7% were under five years old. The outbreak started in a minority population from the mountainous area bordering Lao PDR and China and exploded in high-density population areas. Molecular analysis of MeV revealed co-circulation of genotypes H1 and D8, with H1 as the predominant strain, and divided into two clusters: cluster 1, sharing high similarity with those detected in China and Lao PDR, and cluster 2, circulating locally with unidentified origin. The minor D8 strains belonged to the D8-Frankfurt cluster. CONCLUSION: The outbreak originated in and spread from a population with limited access to vaccines. Molecular analysis revealed co-circulation of MeVs with three different origins during the outbreak. This is the first report to provide an overview of the 2013-2014 measles outbreak in northern Vietnam, demonstrating the need for vaccination strategies against measles that are tailored to local conditions with enhanced molecular surveillance to achieve measles elimination.

Successful containment of a flight-imported COVID-19 outbreak through extensive contact tracing, systematic testing and mandatory quarantine: Lessons from Vietnam.

BACKGROUND: The importation of SARS-CoV-2 through air travel poses substantial risks to generate new COVID-19 outbreaks. Timely contact tracing is particularly crucial to limit onwards transmission in settings without established community transmission. METHODS: We conducted an in-depth analysis of the response to a big flight-associated COVID-19 outbreak in Vietnam in March 2020 that involved contact tracing, systematic testing and strict quarantine up to third generation contacts. RESULTS: 183 primary contacts from the flight as well as 1000 secondary and 311 third generation contacts were traced, tested, and quarantined across 15 provinces across Vietnam. The protracted confirmation of the index case at 3 days and 19 h after arrival resulted in isolation/quarantine delays of 6.8 days (IQR 6.3-6.8) and 5.8 days (IQR 5.8-7.0) for primary and secondary cases, respectively, which generated 84.0 and 26.4 person-days of community exposure from primary and secondary cases, respectively. Nevertheless, only 5 secondary cases occurred. CONCLUSIONS: A large flight-related COVID-19 cluster was successfully contained through timely, systematic and comprehensive public health responses despite delayed index case identification. Multiagency collaboration and pre-established mechanisms are crucial for low and middle income countries like Vietnam to limit community transmission after COVID-19 importation through air travel.

Sero-Prevalence Surveillance to Predict Vaccine-Preventable Disease Outbreaks; A Lesson from the 2014 Measles Epidemic in Northern 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.

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

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

H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance.

Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.

Social contact patterns in Vietnam and implications for the control of infectious diseases.

BACKGROUND: The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam. METHODS AND FINDINGS: A diary based survey of social contact patterns was conducted in a household-structured community cohort in North Vietnam in 2007. We used generalized estimating equations to model the number of contacts while taking into account the household sampling design, and used weighting to balance the household size and age distribution towards the Vietnamese population. We recorded 6675 contacts from 865 participants in 264 different households and found that mixing patterns were assortative by age but were more homogenous than observed in a recent European study. We also observed that physical contacts were more concentrated in the home setting in Vietnam than in Europe but the overall level of physical contact was lower. A model of individual versus household vaccination strategies revealed no difference between strategies in the impact on R(0). CONCLUSIONS AND SIGNIFICANCE: This work is the first to estimate contact patterns relevant to the spread of infections transmitted from person to person by non-sexual routes in a developing country setting. The results show interesting similarities and differences from European data and demonstrate the importance of context specific data.