Measuring the impact of an integrated bite case management program on the detection of canine rabies cases in Vietnam.

Introduction: Dog-mediated rabies is enzootic in Vietnam, resulting in at least 70 reported human deaths and 500,000 human rabies exposures annually. In 2016, an integrated bite cases management (IBCM) based surveillance program was developed to improve knowledge of the dog-mediated rabies burden in Phu Tho Province of Vietnam. Methods: The Vietnam Animal Rabies Surveillance Program (VARSP) was established in four stages: (1) Laboratory development, (2) Training of community One Health workers, (3) Paper-based-reporting (VARSP 1.0), and (4) Electronic case reporting (VARSP 2.0). Investigation and diagnostic data collected from March 2016 to December 2019 were compared with historical records of animal rabies cases dating back to January 2012. A risk analysis was conducted to evaluate the probability of a rabies exposure resulting in death after a dog bite, based on data collected over the course of an IBCM investigation. Results: Prior to the implementation of VARSP, between 2012 and 2015, there was an average of one rabies investigation per year, resulting in two confirmed and two probable animal rabies cases. During the 46 months that VARSP was operational (2016 - 2019), 1048 animal investigations were conducted, which identified 79 (8%) laboratory-confirmed rabies cases and 233 (22%) clinically-confirmed(probable) cases. VARSP produced a 78-fold increase in annual animal rabies case detection (one cases detected per year pre-VARSP vs 78 cases per year under VARSP). The risk of succumbing to rabies for bite victims of apparently healthy dogs available for home quarantine, was three deaths for every 10,000 untreated exposures. Discussion: A pilot IBCM model used in Phu Tho Province showed promising results for improving rabies surveillance, with a 26-fold increase in annual case detection after implementation of a One Health model. The risk for a person bitten by an apparently healthy dog to develop rabies in the absence of rabies PEP was very low, which supports the WHO recommendations to delay PEP for this category of bite victims, when trained animal assessors are available and routinely communicate with the medical sector. Recent adoption of an electronic IBCM system is likely to expedite adoption of VARSP 2.0 to other Provinces and improve accuracy of field decisions and data collection.

A systematic study towards evolutionary and epidemiological dynamics of currently predominant H5 highly pathogenic avian influenza viruses in Vietnam.

This study aimed to elucidate virus, host and environmental dynamics of Vietnamese H5 highly pathogenic avian influenza viruses (HPAIVs) during 2014-2017. Epidemiologically, H5 HPAIVs were frequently detected in apparently healthy domestic and Muscovy ducks and therefore these are preferred species for H5 HPAIV detection in active surveillance. Virologically, clade 2.3.2.1c and 2.3.4.4 H5 HPAIVs were predominant and exhibited distinct phylogeographic evolution. Clade 2.3.2.1c viruses clustered phylogenetically in North, Central and South regions, whilst clade 2.3.4.4 viruses only detected in North and Central regions formed small groups. These viruses underwent diverse reassortment with existence of at least 12 genotypes and retained typical avian-specific motifs. These H5 HPAIVs exhibited large antigenic distance from progenitor viruses and commercial vaccines currently used in poultry. Bayesian phylodynamic analysis inferred that clade 2.3.2.1c viruses detected during 2014-2017 were likely descended from homologous clade viruses imported to Vietnam previously and/or preexisting Chinese viruses during 2012-2013. Vietnamese clade 2.3.4.4 viruses closely shared genetic traits with contemporary foreign spillovers, suggesting that there existed multiple transboundary virus dispersals to Vietnam. This study provides insights into the evolution of Vietnamese H5 HPAIVs and highlights the necessity of strengthening control measures such as, preventive surveillance and poultry vaccination.

Complete Genome Sequence of O/VN1/2014, a Foot-and-Mouth Disease Virus of Serotype O Isolated in Vietnam in 2014.

In this article, we report the complete genome sequence of foot-and-mouth disease virus (FMDV) strain O/VN1/2014 isolated in Vietnam (Lao Cai) in 2014. The virus belongs to serotype O, topotype South East Asia (SEA), and genotype Mya-98 (O/SEA/Mya-98). It is the latest complete genome information for the genotype O/SEA/Mya-98 in Vietnam since 2009.

Antigenic characterization of highly pathogenic avian influenza A(H5N1) viruses with chicken and ferret antisera reveals clade-dependent variation in hemagglutination inhibition profiles.

Highly pathogenic avian influenza (HPAI) A(H5N1) viruses pose a significant economic burden to the poultry industry worldwide and have pandemic potential. Poultry vaccination against HPAI A(H5N1) viruses has been an important component of HPAI control measures and has been performed in Vietnam since 2005. To systematically assess antigenic matching of current vaccines to circulating field variants, we produced a panel of chicken and ferret antisera raised against historical and contemporary Vietnamese reference viruses representing clade variants that were detected between 2001 and 2014. The antisera were used for hemagglutination inhibition (HI) assays to generate data sets for analysis by antigenic cartography, allowing for a direct comparison of results from chicken or ferret antisera. HI antigenic maps, developed with antisera from both hosts, revealed varying patterns of antigenic relationships and clustering of viruses that were dependent on the clade of viruses analyzed. Antigenic relationships between existing poultry vaccines and circulating field viruses were also aligned with in vivo protection profiles determined by previously reported vaccine challenge studies. Our results establish the feasibility and utility of HPAI A(H5N1) antigenic characterization using chicken antisera and support further experimental and modeling studies to investigate quantitative relationships between genetic variation, antigenic drift and correlates of poultry vaccine protection in vivo.

Influenza A Viruses of Swine (IAV-S) in Vietnam from 2010 to 2015: Multiple Introductions of A(H1N1)pdm09 Viruses into the Pig Population and Diversifying Genetic Constellations of Enzootic IAV-S.

Active surveillance of influenza A viruses of swine (IAV-S) involving 262 farms and 10 slaughterhouses in seven provinces in northern and southern Vietnam from 2010 to 2015 yielded 388 isolates from 32 farms; these viruses were classified into H1N1, H1N2, and H3N2 subtypes. Whole-genome sequencing followed by phylogenetic analysis revealed that the isolates represented 15 genotypes, according to the genetic constellation of the eight segments. All of the H1N1 viruses were entirely A(H1N1)pdm09 viruses, whereas all of the H1N2 and H3N2 viruses were reassortants among 5 distinct ancestral viruses: H1 and H3 triple-reassortant (TR) IAV-S that originated from North American pre-2009 human seasonal H1, human seasonal H3N2, and A(H1N1)pdm09 viruses. Notably, 93% of the reassortant IAV-S retained M genes that were derived from A(H1N1)pdm09, suggesting some advantage in terms of their host adaptation. Bayesian Markov chain Monte Carlo analysis revealed that multiple introductions of A(H1N1)pdm09 and TR IAV-S into the Vietnamese pig population have driven the genetic diversity of currently circulating Vietnamese IAV-S. In addition, our results indicate that a reassortant IAV-S with human-like H3 and N2 genes and an A(H1N1)pdm09 origin M gene likely caused a human case in Ho Chi Minh City in 2010. Our current findings indicate that human-to-pig transmission as well as cocirculation of different IAV-S have contributed to diversifying the gene constellations of IAV-S in Vietnam. IMPORTANCE: This comprehensive genetic characterization of 388 influenza A viruses of swine (IAV-S) isolated through active surveillance of Vietnamese pig farms from 2010 through 2015 provides molecular epidemiological insight into the genetic diversification of IAV-S in Vietnam after the emergence of A(H1N1)pdm09 viruses. Multiple reassortments among A(H1N1)pdm09 viruses and enzootic IAV-S yielded 14 genotypes, 9 of which carried novel gene combinations. The reassortants that carried M genes derived from A(H1N1)pdm09 viruses became predominant, replacing those of the IAV-S that had been endemic in Vietnam since 2011. Notably, one of the novel reassortants likely caused a human case in Vietnam. Given that Vietnam is the second-largest pig-producing country in Asia, continued monitoring of IAV-S is highly important from the viewpoints of both the swine industry and human public health.

Effect of herd size on subclinical infection of swine in Vietnam with influenza A viruses.

BACKGROUND: Influenza A viruses of swine (IAV-S) cause acute and subclinical respiratory disease. To increase our understanding of the etiology of the subclinical form and thus help prevent the persistence of IAV-S in pig populations, we conducted active virologic surveillance in Vietnam, the second-largest pig-producing country in Asia, from February 2010 to December 2013. RESULTS: From a total of 7034 nasal swabs collected from clinically healthy pigs at 250 farms and 10 slaughterhouses, we isolated 172 IAV-S from swine at the weaning and early-fattening stages. The isolation rate of IAV-S was significantly higher among pigs aged 3 weeks to 4.5 months than in older and younger animals. IAV-S were isolated from 16 large, corporate farms and 6 family-operated farms from among the 250 farms evaluated. Multivariate logistic regression analysis revealed that "having more than 1,000 pigs" was the most influential risk factor for IAV-S positivity. Farms affected by reassortant IAV-S had significantly larger pig populations than did those where A(H1N1)pdm09 viruses were isolated, thus suggesting that large, corporate farms serve as sites of reassortment events. CONCLUSIONS: We demonstrate the asymptomatic circulation of IAV-S in the Vietnamese pig population. Raising a large number of pigs on a farm has the strongest impact on the incidence of subclinical IAV-S infection. Given that only some of the corporate farms surveyed were IAV-S positive, further active monitoring is necessary to identify additional risk factors important in subclinical infection of pigs with IAV-S in Vietnam.

Genetic and antigenic characterization of H5, H6 and H9 avian influenza viruses circulating in live bird markets with intervention in the center part of Vietnam.

A total of 3,045 environmental samples and oropharyngeal and cloacal swabs from apparently healthy poultry have been collected at three live bird markets (LBMs) at which practices were applied to reduce avian influenza (AI) virus transmission (intervention LBMs) and six conventional LBMs (non-intervention LBMs) in Thua Thien Hue province in 2014 to evaluate the efficacy of the intervention LBMs. The 178 AI viruses, including H3 (19 viruses), H4 (2), H5 (8), H6 (30), H9 (114), and H11 (5), were isolated from domestic ducks, muscovy ducks, chickens, and the environment. The prevalence of AI viruses in intervention LBMs (6.1%; 95% CI: 5.0-7.5) was similar to that in non-intervention LBMs (5.6%; 95% CI: 4.5-6.8; χ(2)=0.532; df=1; P=0.53) in the study area. Eight H5N6 highly pathogenic avian influenza (HPAI) viruses were isolated from apparently healthy ducks, muscovy ducks, and an environmental sample in an intervention LBM. The hemagglutinin genes of the H5N6 HPAI viruses belonged to the genetic clade 2.3.4.4, and the antigenicity of the H5N6 HPAI viruses differed from the H5N1 HPAI viruses previously circulating in Vietnam. Phylogenetic and antigenic analyses of the H6 and H9 viruses isolated in both types of LBMs revealed that they were closely related to the viruses isolated from domestic birds in China, Group II of H6 viruses and Y280 lineage of H9 viruses. These results indicate that the interventions currently applied in LBMs are insufficient to control AI. A risk analysis should be conducted to identify the key factors contributing to AI virus prevalence in intervention LBMs.

Complete Genome Sequence of a Foot-and-Mouth Disease Virus of Serotype A Isolated from Vietnam in 2013.

The complete genome sequence of a foot-and-mouth disease virus (FMDV) found in an isolate collected in northern Vietnam in 2013 appears to be closely related to a genetic cluster formed with isolates from China, Mongolia, and Russia in 2013. All of these are classified to fall within the Sea-97 lineage, for which little complete genome data are available.

Genetic evolution of H5 highly pathogenic avian influenza virus in domestic poultry in Vietnam between 2011 and 2013.

In spite of highly pathogenic avian influenza H5N1 vaccination campaigns for domestic poultry, H5N1 viruses continue to circulate in Vietnam. To estimate the prevalence of avian influenza virus in Vietnam, surveillance was conducted between November 2011 and February 2013. Genetic analysis of 312 highly pathogenic avian influenza H5 viruses isolated from poultry in Vietnam was conducted and possible genetic relationships with strains from neighboring countries were investigated. As previously reported, phylogenetic analysis of the avian influenza virus revealed two H5N1 HPAI clades that were circulating in Vietnam. Clade 1.1, related to Cambodian strains, was predominant in the southern provinces, while clade 2.3.2.1 viruses were predominant in the northern and central provinces. Sequence analysis revealed evidence of active genetic evolution. In the gene constellation of clade 2.3.2.1, genotypes A, B, and B(II) existed during the 2011/2012 winter season. In June 2012, new genotype C emerged by reassortment between genotype A and genotype B(II), and this genotype was predominant in 2013 in the northern and central provinces. Interestingly, enzootic Vietnamese clade 2.3.2.1C H5 virus subsequently reassorted with N2, which originated from wild birds, to generate H5N2 highly pathogenic avian influenza, which was isolated from duck in the northeast region. This investigation indicated that H5N1 outbreaks persist in Vietnam and cause genetic reassortment with circulating viruses. It is necessary to strengthen active influenza surveillance to eradicate highly pathogenic avian influenza viruses and sever the link between highly pathogenic avian influenza and other circulating influenza viruses.

Geographical distribution of low pathogenic avian influenza viruses of domestic poultry in Vietnam and their genetic relevance with Asian isolates.

From the avian influenza virus (AIV) outbreaks and market surveillances in Vietnam during November 2011 and March 2012, a total of 196 AIV were isolated. Although H5N1 highly pathogenic avian influenza (HPAI) was the most prevalent subtype in Vietnam, 57 low pathogenic avian influenza (LPAI) viruses were identified from mainly domestic ducks and some chickens. Of note, various subtypes of LPAI viruses were isolated from domestic ducks in Vietnam: H3 (n = 16), H4 (n = 4), H6 (n = 24), H7 (n = 1), and H9 (n = 10). Geographically, the LPAI viruses were identified in different regions of Vietnam. Phylogenetic analysis of HA and NA genes in LPAIV in Vietnam showed that some H3 (group I) and H4 subtypes AIV clustered with the viruses of several Asian isolates from domestic poultry and wild birds. However, the H6, H9, and some H3 (group II and III) subtypes AIV were closely related to isolates from domestic poultry in Southern China. In addition, whereas the N2 and N6 subtypes AIV belonged to the Eurasian lineage, the N8 subtype AIV was classified to be both of Eurasian and American lineage. These findings revealed that the regional trade and wild birds play a key role transmission of LPAIV in domestic ducks in Vietnam. Further surveillance at the intercountry level is needed to understand the epidemiology of these viruses and to cope with emergence of novel AIV types.