Transient Introgression of Wolbachia into Aedes aegypti Populations Does Not Elicit an Antibody Response to Wolbachia Surface Protein in Community Members.

Wolbachia is an endosymbiotic bacterium that can restrict the transmission of human pathogenic viruses by Aedes aegypti mosquitoes. Recent field trials have shown that dengue incidence is significantly reduced when Wolbachia is introgressed into the local Ae. aegypti population. Female Ae. aegypti are anautogenous and feed on human blood to produce viable eggs. Herein, we tested whether people who reside on Tri Nguyen Island (TNI), Vietnam developed antibodies to Wolbachia Surface Protein (WSP) following release of Wolbachia-infected Ae. aegypti, as a measure of exposure to Wolbachia. Paired blood samples were collected from 105 participants before and after mosquito releases and anti-WSP titres were measured by ELISA. We determined no change in anti-WSP titres after ~30 weeks of high levels of Wolbachia-Ae. aegypti on TNI. These data suggest that humans are not exposed to the major Wolbachia surface antigen, WSP, following introgression of Wolbachia-infected Ae. aegypti mosquitoes.

The first community outbreak of COVID-19 in Viet Nam: description and lessons learned.

OBJECTIVE: At the time of this study, the prevention of novel coronavirus disease 2019 (COVID-19) relied solely on nonpharmaceutical interventions. Implementation of these interventions is not always optimal and, consequently, several cases were imported into non-epidemic areas and led to large community outbreaks. This report describes the characteristics of the first community outbreak of COVID-19 in Viet Nam and the intensive preventive measures taken in response. METHODS: Cases were detected and tested for SARS-CoV-2 by real-time reverse transcriptase polymerase chain reaction. Contact tracing and active surveillance were conducted to identify suspected cases and individuals at risk. Clinical symptoms were recorded using a standardized questionnaire. RESULTS: In Vinh Phuc province from 20 January to 3 March 2020, there were 11 confirmed cases among 158 suspected cases and 663 contacts. Nine of the confirmed cases (81.8%) had mild symptoms at the time of detection and two (18.2%) were asymptomatic; none required admission to an intensive care unit. Five prevention and control measures were implemented, including quarantining a community of 10 645 individuals for 20 days. The outbreak was successfully contained as of 13 February 2020. DISCUSSION: In the absence of specific interventions, the intensive use of combined preventive measures can mitigate the spread of COVID-19. The lessons learned may be useful for other communities.

Increasing HIV prevalence and injection drug use among men who have sex with men in Ho Chi Minh City, Vietnam.

Vietnam has been conducting HIV/sexually transmitted infection (STI) integrated bio-behavioral surveillance surveys on men who have sex with men (MSM) as well as other key populations since 2005. Although HIV prevalence in the Vietnamese general population remains below 1%, it is expected to be much higher among MSM.Data on HIV prevalence and sexual and drug use behaviors were collected from MSM in Ho Chi Minh City (HCMC) in 2006 (n = 397), 2009 (n = 399) and 2013 (n = 350) using respondent-driven sampling. Eligible participants were males, aged ≥15 years who reported having manual, oral, or anal sexual activity with males in the past year and lived, worked or socialized in HCMC.HIV seroprevalence among MSM was 5.8% in 2006, 16.1% in 2009 and 12.1% in 2013 and prevalence of at least one STI (syphilis, gonorrhea and/or chlamydia infection) was 11.4% in 2006 and 15.6% in 2009 (no data for 2013). Significant, but small, increasing trends were found for MSM who reported ever testing and receiving results for HIV and for HIV prevalence. No significant changes for condom use, injecting and non-injecting drug use, or and receipt of free condoms were observed.Although a small percentage of MSM reported injecting drugs, HIV was positively associated with ever injecting drugs. Programs targeting MSM should include screening and treatment for injection drug use to most effectively control the HIV/AIDS epidemic among MSM in HCMC.

Plans for Nationwide Serosurveillance Network in Vietnam.

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

Viral load suppression and acquired HIV drug resistance in adults receiving antiretroviral therapy in Viet Nam: results from a nationally representative survey.

OBJECTIVE: The purpose of this survey was to estimate the prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Viet Nam using a nationally representative sampling method. METHODS: The survey was conducted between May and August 2014 using a two-stage cluster design. Sixteen ART clinics were selected using probability proportional to proxy size sampling, and patients receiving ART for at least 36 months were consecutively enrolled. Epidemiological information and blood specimens were collected for HIV-1 VL and HIVDR testing; HIVDR was defined by the Stanford University HIVDR algorithm. RESULTS: Overall, 365 eligible individuals were recruited with a mean age of 38.2 years; 68.4% were men. The mean time on ART was 75.5 months (95% confidence interval [CI]: 69.0-81.9 months), and 93.7% of the patients were receiving non-nucleoside reverse transcriptase inhibitor-based regimens. Of the 365 individuals, 345 (94.7%, 95% CI: 64.1-99.4%) had VL below 1000 copies/mL and 19 (4.6%, 95% CI: 2.8--7.5) had HIVDR mutations. DISCUSSION: Our nationally representative survey found a high level of VL suppression and a low prevalence of HIVDR among individuals who received ART for at least 36 months in Viet Nam. Continued surveillance for HIVDR is important for evaluating and improving HIV programs.

Mycobacterium tuberculosis Drug Resistance and Transmission among Human Immunodeficiency Virus-Infected Patients in Ho Chi Minh City, Vietnam.

Vietnam has a high burden of tuberculosis (TB) and multidrug-resistant (MDR) TB, but drug resistance patterns and TB transmission dynamics among TB/human immunodeficiency virus (HIV) coinfected patients are not well described. We characterized 200 Mycobacterium tuberculosis isolates from TB/HIV coinfected patients diagnosed at the main TB referral hospital in Ho Chi Minh City, Vietnam. Phenotypic drug susceptibility testing (DST) for first-line drugs, spoligotyping, and 24-locus mycobacterial interspersed repetitive unit (MIRU-24) analysis was performed on all isolates. The 24-locus mycobacterial interspersed repetitive unit clusters and MDR isolates were subjected to whole genome sequencing (WGS). Most of the TB/HIV coinfected patients were young (162/174; 93.1% aged < 45 years) males (173; 86.5% male). Beijing (98; 49.0%) and Indo-Oceanic (70; 35.0%) lineage strains were most common. Phenotypic drug resistance was detected in 84 (42.0%) isolates, of which 17 (8.5%) were MDR; three additional MDR strains were identified on WGS. Strain clustering was reduced from 84.0% with spoligotyping to 20.0% with MIRU-24 typing and to 13.5% with WGS. Whole genome sequencing identified five additional clusters, or members of clusters, not recognized by MIRU-24. In total, 13 small (two to three member) WGS clusters were identified, with less clustering among drug susceptible (2/27; 7.4%) than among drug-resistant strains (25/27; 92.6%). On phylogenetic analysis, strains from TB/HIV coinfected patients were interspersed among strains from the general community; no major clusters indicating transmission among people living with HIV were detected. Tuberculosis/HIV coinfection in Vietnam was associated with high rates of drug resistance and limited genomic evidence of ongoing M. tuberculosis transmission among HIV-infected patients.

Efficacy of Communication Training of Community Health Workers on Service Delivery to People Who Inject Drugs in Vietnam: A Clustered Randomized Trial.

OBJECTIVES: To evaluate the efficacy of an intervention targeted to commune health workers (CHWs) who deliver services to people who inject drugs (PWID) in Vietnam. METHODS: From 2014 to 2016, we conducted a cluster randomized controlled trial of 300 CHWs and 900 PWID in 60 communes in 2 provinces of Vietnam. Intervention CHWs participated in training sessions to enhance their communication skills. Trained CHWs were asked to deliver individual sessions to PWID. We assessed the outcomes at baseline and at 3-, 6-, 9-, and 12-month follow-ups. RESULTS: Intervention CHWs showed greater improvement in provider-client interactions than did control CHWs at all follow-ups (range of difference = 3.33-5.18; P < .001). Intervention CHWs showed greater reduction in negative attitudes toward PWID at the 12-month follow-up (mean ±SD = 1.75 ±0.50; P < .001). PWID in the intervention group exhibited greater improvement in drug avoidance than did those in the control group from the 6-month follow-up on (range of difference = 1.21-1.65; P < .001). We observed no intervention effect on heroin use as measured by urinalysis. CONCLUSIONS: This intervention targeting CHWs could lead to desired outcomes for both CHWs and PWID. ClinicalTrials.gov: NCT0213092.1.

Epidemiological, Serological, and Virological Features of Dengue in Nha Trang City, Vietnam.

Vietnam is endemic for dengue. We conducted a series of retrospective and prospective studies to characterize the epidemiology of dengue and population mobility patterns in Nha Trang city, Vietnam, with a view to rational design of trials of community-level interventions. A 10-year time series of dengue case notifications showed pronounced interannual variability, as well as spatial heterogeneity in ward-level dengue incidence (median annual coefficient of variation k = 0.47). Of 451 children aged 1-10 years enrolled in a cross-sectional serosurvey, almost one-third had evidence of a past dengue virus (DENV) infection, with older children more likely to have a multitypic response indicative of past exposure to ≥ 1 serotype. All four DENV serotypes were detected in hospitalized patients during 8 months of sampling in 2015. Mobility data collected from 1,000 children and young adults via prospective travel diaries showed that, although all ages spent approximately half of their daytime hours (5:00 am-9:00 pm) at home, younger age groups (≤ 14 years) spent a significantly greater proportion of their time within 500 m of home than older respondents. Together these findings inform the rational design of future trials of dengue preventive interventions in this setting by identifying 1) children < 7 years as an optimal target group for a flavivirus-naive serological cohort, 2) children and young adults as the predominant patient population for a study with a clinical end point of symptomatic dengue, and 3) substantial spatial and temporal variations in DENV transmission, with a consequent requirement for a trial to be large enough and of long enough duration to overcome this heterogeneity.

Highly Pathogenic Avian Influenza A(H5N1) Viruses at the Animal-Human Interface in Vietnam, 2003-2010.

Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance.

Drug resistance and Mycobacterium tuberculosis strain diversity in TB/HIV co-infected patients in Ho Chi Minh city, Vietnam.

BACKGROUND: Mycobacterium tuberculosis strain diversity and drug resistance among people living with human immunodeficiency virus (HIV) in Vietnam have not been described previously. METHODS: We examined M. tuberculosis isolates from TB/HIV co-infected patients in Ho Chi Minh City, Vietnam. Drug susceptibility testing (DST), spoligotyping and 24-locus Mycobacterial Interspersed Repetitive Unit (MIRU-24 typing) were performed, and the rpoB, katG, inhA and inhA promoter, rpsL, rrs and embB genes were sequenced in all drug resistant isolates identified. RESULTS: In total, 84/200 (42.0%) strains demonstrated "any drug resistance"; 17 (8.5%) were multi-drug resistant (MDR). Streptomycin resistance was present in 80 (40.0%) isolates; 95.2% (80/84) with "any drug resistance" and 100% with MDR. No rifampicin monoresistance was detected. Of the rifampicin resistant strains 16/18 (88.9%) had mutations in the 81-bp Rifampicin Resistance Defining Region (RRDR) of the rpoB gene. Isoniazid resistance was mostly associated with Ser315Thr mutations in the katG gene (15/17; 88.2%). Beijing (49.0%) and East African Indian (EAI) lineage strains (35.0%; 56/70 EAI-5) were most common. CONCLUSION: TB/HIV co-infection in Vietnam was associated with high rates of TB drug resistance, although we were unable to differentiate new from retreatment cases.

Valine/isoleucine variants drive selective pressure in the VP1 sequence of EV-A71 enteroviruses.

BACKGROUND: In 2011-2012, Northern Vietnam experienced its first large scale hand foot and mouth disease (HFMD) epidemic. In 2011, a major HFMD epidemic was also reported in South Vietnam with fatal cases. This 2011-2012 outbreak was the first one to occur in North Vietnam providing grounds to study the etiology, origin and dynamic of the disease. We report here the analysis of the VP1 gene of strains isolated throughout North Vietnam during the 2011-2012 outbreak and before. METHODS: The VP1 gene of 106 EV-A71 isolates from North Vietnam and 2 from Central Vietnam were sequenced. Sequence alignments were analyzed at the nucleic acid and protein level. Gene polymorphism was also analyzed. A Factorial Correspondence Analysis was performed to correlate amino acid mutations with clinical parameters. RESULTS: The sequences were distributed into four phylogenetic clusters. Three clusters corresponded to the subgenogroup C4 and the last one corresponded to the subgenogroup C5. Each cluster displayed different polymorphism characteristics. Proteins were highly conserved but three sites bearing only Isoleucine (I) or Valine (V) were characterized. The isoleucine/valine variability matched the clusters. Spatiotemporal analysis of the I/V variants showed that all variants which emerged in 2011 and then in 2012 were not the same but were all present in the region prior to the 2011-2012 outbreak. Some correlation was found between certain I/V variants and ethnicity and severity. CONCLUSIONS: The 2011-2012 outbreak was not caused by an exogenous strain coming from South Vietnam or elsewhere but by strains already present and circulating at low level in North Vietnam. However, what triggered the outbreak remains unclear. A selective pressure is applied on I/V variants which matches the genetic clusters. I/V variants were shown on other viruses to correlate with pathogenicity. This should be investigated in EV-A71. I/V variants are an easy and efficient way to survey and identify circulating EV-A71 strains.

Estimating False-Recent Classification for the Limiting-Antigen Avidity EIA and BED-Capture Enzyme Immunoassay in Vietnam: Implications for HIV-1 Incidence Estimates.

Laboratory tests that can distinguish recent from long-term HIV infection are used to estimate HIV incidence in a population, but can potentially misclassify a proportion of long-term HIV infections as recent. Correct application of an assay requires determination of the proportion false recents (PFRs) as part of the assay characterization and for calculating HIV incidence in a local population using a HIV incidence assay. From April 2009 to December 2010, blood specimens were collected from HIV-infected individuals attending nine outpatient clinics (OPCs) in Vietnam (four from northern and five from southern Vietnam). Participants were living with HIV for ≥1 year and reported no antiretroviral (ARV) drug treatment. Basic demographic data and clinical information were collected. Specimens were tested with the BED capture enzyme immunoassay (BED-CEIA) and the Limiting-antigen (LAg)-Avidity EIA. PFR was estimated by dividing the number of specimens classified as recent by the total number of specimens; 95% confidence intervals (CI) were calculated. Specimens that tested recent had viral load testing performed. Among 1,813 specimens (north, n = 942 and south, n = 871), the LAg-Avidity EIA PFR was 1.7% (CI: 1.2-2.4) and differed by region [north 2.7% (CI: 1.8-3.9) versus south 0.7% (CI: 0.3-1.5); p = .002]. The BED-CEIA PFR was 2.3% (CI: 1.7-3.0) and varied by region [north 3.4% (CI: 2.4-4.7) versus south 1.0% (CI: 0.5-1.2), p < .001]. Excluding specimens with an undetectable VL, the LAg-Avidity EIA PFR was 1.2% (CI: 0.8-1.9) and the BED-CEIA PFR was 1.7% (CI: 1.2-2.4). The LAg-Avidity EIA PFR was lower than the BED-CEIA PFR. After excluding specimens with an undetectable VL, the PFR for both assays was similar. A low PFR should facilitate the implementation of the LAg-Avidity EIA for cross-sectional incidence estimates in Vietnam.

Modeling the impact of rubella vaccination in Vietnam.

Supported by GAVI Alliance, measles-rubella vaccination was introduced in Vietnam in 2014, involving a mass campaign among 1-14 year olds and routine immunization of children aged 9 months. We explore the impact on the incidence of Congenital Rubella Syndrome (CRS) during 2013-2050 of this strategy and variants involving women aged 15-35 years. We use an age and sex-structured dynamic transmission model, set up using recently-collected seroprevalence data from Central Vietnam, and also consider different levels of transmission and contact patterns. If the serological profile resembles that in Central Vietnam, the planned vaccination strategy could potentially prevent 125,000 CRS cases by 2050 in Vietnam, despite outbreaks predicted in the meantime. Targeting the initial campaign at 15-35 year old women with or without children aged 9 months-14 years led to sustained reductions in incidence, unless levels of ongoing transmission were medium-high before vaccination started. Assumptions about contact greatly influenced predictions if the initial campaign just targeted 15-35 year old women and/or levels of ongoing transmission were medium-high. Given increased interest in rubella vaccination, resulting from GAVI Alliance funding, the findings are relevant for many countries.

Seasonality of absolute humidity explains seasonality of influenza-like illness in Vietnam.

BACKGROUND: Experimental and ecological studies have shown the role of climatic factors in driving the epidemiology of influenza. In particular, low absolute humidity (AH) has been shown to increase influenza virus transmissibility and has been identified to explain the onset of epidemics in temperate regions. Here, we aim to study the potential climatic drivers of influenza-like illness (ILI) epidemiology in Vietnam, a tropical country characterized by a high diversity of climates. We specifically focus on quantifying and explaining the seasonality of ILI. METHODS: We used 18 years (1993-2010) of monthly ILI notifications aggregated by province (52) and monthly climatic variables (minimum, mean, maximum temperatures, absolute and relative humidities, rainfall and hours of sunshine) from 67 weather stations across Vietnam. Seasonalities were quantified from global wavelet spectra, using the value of the power at the period of 1 year as a measure of the intensity of seasonality. The 7 climatic time series were characterized by 534 summary statistics which were entered into a regression tree to identify factors associated with the seasonality of AH. Results were extrapolated to the global scale using simulated climatic times series from the NCEP/NCAR project. RESULTS: The intensity of ILI seasonality in Vietnam is best explained by the intensity of AH seasonality. We find that ILI seasonality is weak in provinces experiencing weak seasonal fluctuations in AH (annual power <17.6), whereas ILI seasonality is strongest in provinces with pronounced AH seasonality (power >17.6). In Vietnam, AH and ILI are positively correlated. CONCLUSIONS: Our results identify a role for AH in driving the epidemiology of ILI in a tropical setting. However, in contrast to temperate regions, high rather than low AH is associated with increased ILI activity. Fluctuation in AH may be the climate factor that underlies and unifies the seasonality of ILI in both temperate and tropical regions. Alternatively, the mechanism of action of AH on disease transmission may be different in cold-dry versus hot-humid settings.

An outbreak of influenza A(H1N1)pdm09 virus in a primary school in Vietnam.

BACKGROUND: Despite school pupils being at greatest risk during the 2009 influenza pandemic there are limited data on outbreaks of influenza A(H1N1)pdm09 in primary schools in South-East Asia. This prospective cohort study describes an outbreak of influenza A(H1N1)pdm09 in a primary school in rural Vietnam. FINDINGS: In total 103 cases of influenza-like illness were found among the 407 pupils in the primary school. Ten of these were laboratory confirmed cases of influenza A(H1N1)pdm09 virus. The overall attack rate (AR) was 25% (103/407), and was highest (41%) in grade 4 pupils, where the outbreak started. All cases in the outbreak presented with a mild and self-limiting illness, acute respiratory symptoms and fever. Public health interventions to contain the outbreak could explain the lower attack rates in other grades. Ill pupils were asked to stay at home. Oseltamivir was not given to pupils and the school did not close during the outbreak. The last detected case occurred 12 days following identification of the first case. CONCLUSIONS: This is the first report of an outbreak of influenza A(H1N1)pdm09 among pupils in a primary school in Vietnam. High attack rates in Grade 4 pupils suggest shared activities contributed to transmission. The public health response using non-pharmaceutical measures may have played a role in ending the outbreak.

Region-wide synchrony and traveling waves of dengue across eight countries in Southeast Asia.

Dengue is a mosquito-transmitted virus infection that causes epidemics of febrile illness and hemorrhagic fever across the tropics and subtropics worldwide. Annual epidemics are commonly observed, but there is substantial spatiotemporal heterogeneity in intensity. A better understanding of this heterogeneity in dengue transmission could lead to improved epidemic prediction and disease control. Time series decomposition methods enable the isolation and study of temporal epidemic dynamics with a specific periodicity (e.g., annual cycles related to climatic drivers and multiannual cycles caused by dynamics in population immunity). We collected and analyzed up to 18 y of monthly dengue surveillance reports on a total of 3.5 million reported dengue cases from 273 provinces in eight countries in Southeast Asia, covering ∼ 10(7) km(2). We detected strong patterns of synchronous dengue transmission across the entire region, most markedly during a period of high incidence in 1997-1998, which was followed by a period of extremely low incidence in 2001-2002. This synchrony in dengue incidence coincided with elevated temperatures throughout the region in 1997-1998 and the strongest El Niño episode of the century. Multiannual dengue cycles (2-5 y) were highly coherent with the Oceanic Niño Index, and synchrony of these cycles increased with temperature. We also detected localized traveling waves of multiannual dengue epidemic cycles in Thailand, Laos, and the Philippines that were dependent on temperature. This study reveals forcing mechanisms that drive synchronization of dengue epidemics on a continental scale across Southeast Asia.

Practices around the use of masks and respirators among hospital health care workers in 3 diverse populations.

A cross-sectional survey was conducted in 89 secondary- and tertiary-level hospitals in 3 countries, and samples of masks and respirators were also collected and examined. Results showed varied practices around the use of masks and respirators, which are probably influenced by the available resources and local recommendations. Nonstandardized practices are common in low-resource settings, which may be placing health care workers at risk.

Brief behavioural surveys in routine HIV sentinel surveillance: a new tool for monitoring the HIV epidemic in Viet Nam.

In this report we describe a new approach in HIV sentinel surveillance that was piloted in Viet Nam in 2009 and is currently being rolled out in all provinces. It comprises a brief behavioural questionnaire added to the HIV sentinel surveillance surveys conducted routinely among people who inject drugs, female sex workers and men who have sex with men. Timely reporting of data from this system has resulted in improvements to HIV prevention efforts for most at-risk populations.