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The Omicron variant caused a surge of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Viet Nam in early 2022, signalling community transmission. We report on active whole-genome sequencing surveillance of positive SARS-CoV-2 samples collected at that time in northern Viet Nam from international arrivals and community clusters. We used an amplicon protocol developed with 14 polymerase chain reaction products and the Illumina iSeq 100 platform. Overall, 213 nasopharyngeal or throat swabs were analysed, of which 172 samples were identified with the Omicron variant. Of these, 80 samples were collected from community cases in February 2022, among which 59 samples were sublineage BA.2 and one sample was the recombinant XE variant. Our results indicated that Omicron had replaced Delta as the dominant variant in a very short period of time and that continuously conducting active whole-genome sequencing surveillance is necessary in monitoring the evolution and genomic diversity of SARS-CoV-2 in Viet Nam.

The respiratory syncytial virus is a major cause of acute respiratory tract infection in young children. However, molecular characteristics analysis was not as much of its’ burden, especially in developing countries as well as Viet Nam. Therefore, we performed molecular evolutionary analyses of the G gene of RSV-A sequences which were collected from pediatric severe acute respiratory infection patients in north Viet Nam from 2017–2020. The Bayesian Markov Chain Monte Carlo method was used to conduct phylogenetic analyses and a time scale for evolution. We also calculated population dynamics, estimated the natural selection pressure and potential N-glycosylation sites. The results indicated the majority of study sequences were classified into the ON1 genotype. There were three strains belonging to the non-ON1 genotype with p-distance = 0.048. Besides, even though most of the Vietnamese sequences were identified as ON1 genotype, all of them had no 72-nucleotide duplication in the second hypervariable region of the G gene. The molecular evolutionary rate of the RSV-A G gene in northern Viet Nam was estimated to be 1.32 × 10− 3 substitutions/site/year. Each year, the shifts of the N-glycosylation pattern within the G gene of Vietnamese sequences were observed. Moreover, five amino acid substitution sites were related to positive selection pressure. These results were the first report of the molecular evolution of the RSV-A G gene detected in Viet Nam after 2015.

Background: Vietnam implemented various public health interventions such as contact tracing and testing, mandatory quarantine, and lockdowns in response to coronavirus disease 2019 (COVID-19). However, the effects of these measures on the epidemic remain unclear. Methods: This article describes the public health interventions in relation to COVID-19 incidence. Maximum likelihood estimations were used to assess containment delays (time between symptom onset and start of isolation) and multivariable regression was employed to identify associated factors between interventions and COVID-19 incidence. The effective reproductive numbers (Rt) were calculated based on transmission pairs. Results: Interventions were introduced periodically in response to the epidemic. Overall, 817 (55.4%) among 1474 COVID-19 cases were imported. Based on a serial interval of 8.72 ± 5.65 days, it was estimated that Rt decreased to below 1 (lowest at 0.02, 95% CI 0–0.12) during periods of strict border control and contact tracing, and increased ahead of new clusters. The main method to detect cases shifted over time from passive notification to active case-finding at immigration or in lockdown areas, with containment delays showing significant differences between modes of case detection. Conclusions: A combination of early, strict, and consistently implemented interventions is crucial to control COVID-19. Low-middle income countries with limited capacity can contain COVID-19 successfully using non-pharmaceutical interventions.

Background: Viet Nam confirmed its first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on 23 January 2020 among travellers from Wuhan, China, and experienced several clusters of community transmission until September. Viet Nam implemented an aggressive testing, isolation, contact tracing and quarantine strategy in response to all laboratory-confirmed cases. We report the results of SARS-CoV-2 testing during the first half of 2020 in northern Viet Nam. Methods: Between January and May 2020, 15 650 upper respiratory tract specimens were collected from 14 470 suspected cases and contacts in northern Viet Nam. All were tested for SARS-CoV-2 by real-time RT-PCR. Individuals with positive specimens were tested every three days until two tests were negative. Positive specimens from 81 individuals were cultured. Results: Among 14 470 tested individuals, 158 (1.1%) cases of SARS-CoV-2 infection were confirmed; 89 were imported and 69 were associated with community transmission. Most patients (122, 77%) had negative results after two tests, while 11 and 4 still tested positive when sampled a third and fourth time, respectively. SARS-CoV-2 was isolated from 29 of 81 specimens (36%) with a cycle threshold (Ct) value 30 and negative cultures. Conclusion: Early, widespread testing for SARS-CoV-2 in northern Viet Nam identified very few cases, which, when combined with other aggressive strategies, may have dramatically contained the epidemic. We observed rapid viral clearance and very few positive results after clearance. Large-scale molecular diagnostic testing is a critical part of early detection and containment of COVID-19 in Viet Nam and will remain necessary until vaccination is widely implemented.

Antimicrobial resistance (AMR) is a global public health concern for both clinical and veterinary medicine. Rodent feces are one of the major infectious sources of zoonotic pathogens including AMR bacteria. So far, there are limited studies reported focused on Escherichia coli isolated in rodent feces from rural and suburban areas in Vietnam. In this study, we investigated the prevalence of antimicrobial resistance in E. coli isolated from feces samples of 144 urban rodents caught in Hanoi, Vietnam. A total of 59 AMR E. coli was isolated from urban rodents of which 42 were multidrug-resistant (MDR) isolates (resistance to at least three classes of antimicrobial agents), four were extended-spectrum β-lactamase (ESBL) producing isolates and five were colistin-resistant isolates. The highest prevalence of the resistance was against ampicillin (79.7%: 47/59), followed by tetracycline (78.0%: 46/59), nalidixic acid (67.8%: 40/59), sulfamethoxazole-trimethoprim (59.3%: 35/59), chloramphenicol (45.8%: 27/59), ciprofloxacin (44.1%: 26/59), cefotaxime (30.5%: 18/59), cefodizime (23.7%: 14/59), amoxicillin-clavulanate (22.0%: 13/59), and gentamicin (22.0%: 13/59). With regard to the virulence genes associated with diarrheagenic E. coli (DEC), only aaiC gene found in one AMR isolate. In general, the use of antimicrobials does not aim to treat rodents except for companion animals. However, our findings show the carriage of AMR and MDR E. coli in urban rodents and highlight the potential risk of rodents in Hanoi acting as a reservoir of transferable MDR E. coli, including ESBL-producing, colistin-resistant E. coli, and virulence-associated with DEC.

Leptospirosis is a zoonotic disease that is caused by pathogenic spirochaetes of Leptospira spp. and it has become a public health concern in urban localities in the tropics. Rats are important reservoir animals for the transmission of leptospirosis in urban areas. Leptospirosis is considered endemic in Vietnam. However, information on the causative Leptospira genotypes and serotypes in the country is limited. We investigated the carrier status of Leptospira spp. in rats captured in Hanoi by culturing and DNA detection. Isolates were characterized using a serological method and multiple-locus variable-number tandem repeat analysis (MLVA). We captured 144 rats (1 Rattus argentiventer, 135 R. norvegicus, and 8 R. rattus) and obtained 17 L. interrogans, determined by rrs sequencing, from R. norvegicus (12.6%). Sixteen of the isolates were serogroup Bataviae. Five of the 16 isolates exhibited an MLVA type identical to that of the serovar Bataviae reference strain Van Tienen, while there were nine repeats for the other 11 isolates at VNTR31 compared with the reference strain. The remaining isolate grew poorly, and we were unable to determine its serogroup. However, it had an MLVA type matching those of serogroup Pomona strains isolated from R. norvegicus in Japan. Three different flaB sequences were detected in 23 out of 81 R. norvegicus kidney tissue samples (28.4%) using nested PCR followed by DNA sequencing. Two of the sequences were identical with those of serogroups Bataviae and Pomona, and no strain with another sequence was detected in the present study. The present study reveals a high prevalence rate of L. interrogans among R. norvegicus in Hanoi, Vietnam, indicating a potential risk of rat-borne leptospirosis in the area. The present study also demonstrates that a fastidious L. interrogans strain circulates among rats and that molecular detection is crucial in facilitating the accurate determination of reservoir animals.

Dengue virus (DENV) replication between mosquito and human hosts is hypothesized to be associated with viral determinants that interact in a differential manner between hosts. However, the understanding of inter-host viral determinants that drive DENV replication and growth between hosts is limited. Through the use of clinical isolates, we identified an amino acid variation of Ala, Met and Val at position 116 of DENV-1 NS4B. While the proportion of virus with the NS4B-116V variant remained constantly high in serial passages in a mosquito cell line, populations of the NS4B-116M and NS4B-116A variants became dominant after serial passages in mammalian cell lines. Using recombinant DENV-1 viruses, the Val to Ala or Met alteration at position NS4B-116 (rDENV-1-NS4B-116A and rDENV-1-NS4B-116M) resulted in enhanced virus growth in human cells in comparison to the clone with Val at NS4B-116 (rDENV-1-NS4B-116V). However, the reverse phenomenon was observed in a mosquito cell line. Additionally, in a human cell line, differential levels of IFN-α/β and IFN-stimulated gene expressions (IFIT3, IFI44L, OAS1) suggested that the enhanced viral growth was dependent on the ability of the NS4B protein to hamper host IFN response during the early phase of infection. Overall, we identified a novel and critical viral determinant at the pTMD3 of NS4B region that displayed differential effects on DENV replication and fitness in human and mosquito cell lines. Taken together, the results suggest the importance of the NS4B protein in virus replication and adaptation between hosts.

The database of the Global Influenza B Study was created by collecting surveillance datasets from each of the participating countries. These national datasets are owned by the participating countries, and thus cannot be shared publicly. Researchers interested in obtaining the country-specific datasets may contact the individuals listed below for further details regarding data access.Argentina (Santa Fe Province): Gabriela Kusznierz (labconi@yahoo.com.ar)Australia: Kate Pennington (kate.pennington@health.gov.au)Bhutan: Sonam Wangchuk (swangchuk@health.gov.bt)Brazil: Cláudio Maierovitch Pessanha Henriques (claudio.henriques@saude.gov.br)Cameroon: Guy Vernet (vernet@pasteur-yaounde.org)Chile: Rodrigo Fasce (rfasce@ispch.cl)China: Feng Luzhao (fenglz@chinacdc.cn)Costa Rica: Alexey W. Clara (wclara@cdc.gov)Ecuador: Alfredo Bruno (alfredobruno@yahoo.es)El Salvador: Alexey W. Clara (wclara@cdc.gov)England: Maria Zambon (maria.zambon@phe.gov.uk)Guatemala: Alexey W. Clara (wclara@cdc.gov)Honduras: Alexey W. Clara (wclara@cdc.gov)Indonesia: Herman Kosasih (hermaninarespond@gmail.com)Italy: Caterina Rizzo (caterina.rizzo@iss.it)Ivory Coast: Herve A. Kadjo (hervekadjo@pasteur.ci)Kazakhstan: Gulzhan Muratbayeva (hnv2@cdc.gov)Kenya: Joshua Mott (zud9@cdc.gov)Madagascar: Jean-Michel Heraud (jmheraud@pasteur.mg)Morocco: Amal Barakat (amal.barakat@yahoo.fr)New Zealand: Sue Huang (sue.huang@esr.cri.nz)Nicaragua: Alexey W. Clara (wclara@cdc.gov)Panama: Alexey W. Clara (wclara@cdc.gov)Portugal: Ana Paula Rodrigues (ana.rodrigues@insa.min-saude.pt)Singapore: Vernon Lee (vernonljm@hotmail.com)South Africa: Cheryl Cohen (cherylc@nicd.ac.za)Turkey: Meral Akcay Ciblak (ciblakm@yahoo.com)Ukraine: Alla Mironenko (miralla@ukr.net)Viet Nam: Le Thi Quinh Mai (lom9@hotmail.com); International audience; BACKGROUND:Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases).METHODS:For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity.RESULTS:The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I2>90%) for most sRIRs. The variations of countries' geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play.CONCLUSIONS:These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.

Japanese encephalitis virus (JEV) is classified into 5 genotypes (GI, GII, GIII, GIV, and GV), and the GI and GIII strains are the most widely distributed in JE endemic areas. In recent years, GV JEV has been detected in China and Korea, suggesting that GV JEV may invade other JE endemic areas, including Vietnam, and that more attention should be paid to the JEV strains circulating in these areas. In this study, we investigated the neutralization ability of the sera collected from 22 Vietnamese patients with JE who lived in northern Vietnam against the GI and GV JEV strains. In most cases, the ratios of the titer against GV to that against GI (GV:GI) were equal to or less than 1:4. However, the titer against GV JEV was equivalent (1:1) to that against GI JEV in only a few cases, and no serum had a ratio higher than 1:1. Thus, our results did not show convincing evidence that GV JEV was emerging in northern Vietnam in 2014.

The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 2.3.2.1 and clade 2.3.4 strains isolated from 2008–2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new insight into the human adaptation of AI viruses and help in avian influenza virus risk assessment.

Journal of Clinical Virology, 66, pp.24-26; 2015

Background. The pathogenesis of influenza A virus subtype H5N1 (hereafter, “H5N1”) infection in humans is not completely understood, although hypercytokinemia is thought to play a role. We previously reported that most H5N1 viruses induce high cytokine responses in human macrophages, whereas some H5N1 viruses induce only a low level of cytokine production similar to that induced by seasonal viruses. Methods. To identify the viral molecular determinants for cytokine induction of H5N1 viruses in human macrophages, we generated a series of reassortant viruses between the high cytokine inducer A/Vietnam/UT3028II/03 clone 2 (VN3028IIcl2) and the low inducer A/Indonesia/UT3006/05 (IDN3006) and evaluated cytokine expression in human macrophages. Results. Viruses possessing the acidic polymerase (PA) gene of VN3028IIcl2 exhibited high levels of hypercytokinemia-related cytokine expression in human macrophages, compared with IDN3006, but showed no substantial differences in viral growth in these cells. Further, the PA gene of VN3028IIcl2 conferred enhanced virulence in mice. Conclusions. These results demonstrate that the PA gene of VN3028IIcl2 affects cytokine production in human macrophages and virulence in mice. These findings provide new insights into the cytokine-mediated pathogenesis of H5N1 infection in humans.

Erratum in - Correction: Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination? PLoS One. 2016 May 2;11(5):e0155089. doi: 10.1371/journal.pone.0155089. Introduction: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with 80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate. The Global Influenza B Study is supported by an unrestricted research grant from Sanofi Pasteur. info:eu-repo/semantics/publishedVersion

Highly pathogenic H5N1 avian influenza viruses have caused infection in humans, with a high mortality rate, since 1997. While the pathogenesis of this infection is not completely understood, hypercytokinaemia and alveolar macrophages are thought to play a role. To gain further insight into the cytokine-mediated pathogenesis of this infection in humans, we measured various cytokines produced by primary human macrophages infected with H5N1, pandemic H1N1 or seasonal influenza viruses. We found that many cytokines were produced at higher levels on infection with the H5N1 strains tested compared with seasonal influenza viruses. Interestingly, the extent of cytokine induction varied among the H5N1 strains and did not correlate with replicative ability in macrophages. Further, a pandemic H1N1 virus induced higher levels of several cytokines compared with seasonal viruses and some H5N1 strains. Our results demonstrate that high cytokine induction is not a universal feature of all H5N1 viruses.

Like the histidine-to-tyrosine substitution at position 274 in neuraminidase (NA H274Y), an asparagine-to-serine mutation at position 294 in this protein (NA N294S) confers oseltamivir resistance to highly pathogenic H5N1 influenza A viruses. However, unlike viruses with the NA H274Y mutation, the properties of viruses possessing NA N294S are not well understood. Here, we assessed the effect of the NA N294S substitution on the replication and pathogenicity of human H5N1 viruses and on the efficacy of the NA inhibitors oseltamivir and zanamivir in mouse and ferret models. Although NA N294S-possessing H5N1 viruses were attenuated in mice and ferrets compared to their oseltamivir-sensitive counterparts, one of the infected ferrets died from systemic infection, demonstrating the potential lethality in ferrets of oseltamivir-resistant H5N1 viruses with the NA N294S substitution. The efficacy of oseltamivir, but not that of zanamivir, against an NA N294S-possessing virus was substantially impaired both in ferrets and in vitro . These results demonstrate the considerable pathogenicity of NA N294S substitution-possessing H5N1 viruses and underscore the importance of monitoring the emergence of the NA N294S mutation in circulating H5N1 viruses.

We designed a new set of primers for reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) to specifically amplify the HA gene of avian influenza viruses subtype H5N1. By testing nine H5N1 virus strains and 41 clinical samples collected in Northern Vietnam, we found that the new primers showed higher sensitivity and specificity than the previously published RT-LAMP primers and were comparable to the RT-PCR method currently recommended by WHO. These results suggest that our RT-LAMP assay may be a better choice as a diagnostic tool for current H5N1 influenza virus infection., Tropical Medicine and Health, 39(1), pp.3-7; 2011

A novel influenza (H1N1) virus caused an influenza pandemic in 2009, while highly pathogenic H5N1 avian influenza viruses have continued to infect humans since 1997. Influenza, therefore, remains a serious health threat. Currently, neuraminidase (NA) inhibitors are the mainstay for influenza therapy; however, drug-resistant mutants of seasonal H1N1 and H5N1 viruses have emerged highlighting the need for alternative therapeutic approaches. One such approach is antibody immunotherapy. Here, we show that the monoclonal antibody C179, which recognizes a neutralizing epitope common among H1, H2, H5, and H6 hemagglutinins (HAs), protected mice from a lethal challenge with various H5N1 and pandemic (H1N1) 2009 viruses when administered either intraperitoneally or intranasally. The protective efficacy of intranasally inoculated C179 was comparable to that of intraperitoneal administration. Our results suggest that direct administration of this anti-influenza antibody to viral replication sites is an effective strategy for prophylaxis and therapy.

Simple and rapid diagnosis of influenza is useful for making treatment decisions in the clinical setting. Although many influenza rapid diagnostic tests (IRDTs) are available for the detection of seasonal influenza virus infections, their sensitivity for other viruses, such as H5N1 viruses and the recently emerged swine origin pandemic (H1N1) 2009 virus, remains largely unknown. Here, we examined the sensitivity of 20 IRDTs to various influenza virus strains, including H5N1 and 2009 pandemic H1N1 viruses. Our results indicate that the detection sensitivity to swine origin H1N1 viruses varies widely among IRDTs, with some tests lacking sufficient sensitivity to detect the early stages of infection when the virus load is low.

Avian influenza A viruses (IAVs) and human 1918, 1957, and 1968 pandemic IAVs all have neuraminidases (NAs) that are stable at low pH sialidase activity, yet most human epidemic IAVs do not. We examined the pH stability of H5N1 highly pathogenic avian IAV (HPAI) NAs and identified amino acids responsible for conferring stability at low pH. We found that, unlike other avian viruses, most H5N1 IAVs isolated since 2003 had NAs that were unstable at low pH, similar to human epidemic IAVs. These H5N1 viruses are thus already human virus-like and, therefore, have the frequent infections of humans., Highlights ▸ All neuraminidases (NAs) of avian influenza A viruses (IAVs) are stable at low pH. ▸ Human 1918, 1957, and 1968 pandemic IAVs also have NAs that are stable at low pH. ▸ Most human epidemic IAVs have NAs that are unstable at low pH. ▸ The NAs of most H5N1 IAVs isolated since 2003 are unstable at low pH. ▸ Instability of H5N1 IAV NAs at low pH might explain frequent human infections.