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We tested pre-pandemic (2015-2019) plasma samples from 148 Vietnamese children, and 100 Vietnamese adults at high risk of zoonotic infections, for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive. The data thus demonstrated that there was no evidence of prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietnam. Future studies should look at pre-existing B cell and T cell memory in pre-pandemic samples in Vietnam, which might further shed light on the pathogenesis of the infection.

We studied the immunogenicity of the Oxford-AstraZeneca vaccine in health-care workers of a major infectious diseases hospital in Vietnam. We measured neutralizing antibodies before and 14 days after each dose, and at day 28 and month 3 after dose 1. A total of 554 workers (136 men and 418 women; age range, 22–71 years; median age, 36 years) participated with the study. Of the 144 participants selected for follow-up after dose 1, 104 and 94 gave blood for antibody measurement at weeks 6 and 8, and at month 3 after dose 1, respectively. The window time between the two doses was 6 weeks. At baseline, none had detectable neutralizing antibodies. After dose 1, the proportion of participants with detectable neutralizing antibodies increased from 27.3% (151 of 554) at day 14 to 78.0% (432 of 554) at day 28. Age correlated negatively with the development and the levels of neutralizing antibodies. However, at day 28, these differences were less profound, and women had a greater seroconversion rate and greater levels of neutralizing antibodies than men. After dose 2, these age and gender associations were not observable. In addition, the proportion of study participants with detectable neutralizing antibodies increased from 70.2% (73 of 104) before dose 2 (week 6, after dose 1) to 98.1% (102 of 104) 14 days later. At month 3, neutralizing antibodies decreased and 94.7% (89 of 94) of the study participants remained seropositive. The Oxford-AstraZeneca COVID-19 vaccine is immunogenic in Vietnamese health-care workers. These data are critical to informing the deployment of the COVID-19 vaccine in Vietnam and in Southeast Asia, where vaccination coverage remains inadequate.

BackgroundLittle is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsWe conducted a prospective study at a quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals.ResultsBetween 10 March and 4 April 2020, 14 000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13 (43%) never had symptoms and 17 (57%) were symptomatic. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 [62%] vs 17/17 [100%]; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 [64%] in the asymptomatic group and 13 of 16 [81%] in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P ConclusionsAsymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.

Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate chloroquine as a potential therapeutic for the treatment of hospitalised people with COVID-19. We hypothesise that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid decline of viral load in throat/nose swabs. This viral attenuation should be associated with improved patient outcomes. Method: The study will start with a 10-patient prospective observational pilot study following the same entry and exclusion criteria as for the randomized trial and undergoing the same procedures. The main study is an open label, randomised, controlled trial with two parallel arms of standard of care (control arm) versus standard of care with 10 days of chloroquine (intervention arm) with a loading dose over the first 24 hours, followed by 300mg base orally once daily for nine days. The study will recruit patients in three sites in Ho Chi Minh City, Vietnam: the Hospital for Tropical Diseases, the Cu Chi Field Hospital, and the Can Gio COVID hospital. The primary endpoint is the time to viral clearance from throat/nose swab, defined as the time following randomization until the midpoint between the last positive and the first of the negative throat/nose swabs. Viral presence will be determined using RT-PCR to detect SARS-CoV-2 RNA. Discussion: The results of the study will add to the evidence-based guidelines for management of COVID-19. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19. Trial registration: Clinicaltrials.gov NCT04328493 31/03/2020

BackgroundOne hundred days after SARS-CoV-2 was first reported in Vietnam on January 23rd, 270 cases have been confirmed, with no deaths. We describe the control measures used by the Government and their relationship with imported and domestically-acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control.MethodsClinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of Government control measures, including numbers of tests and quarantined individuals, were captured by Vietnam’s National Steering Committee for COVID-19 response. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of pre-symptomatic transmission events and time-varying reproduction numbers.FindingsAfter the first confirmed case on January 23rd, the Vietnamese Government initiated mass communications measures, case-contact tracing, mandatory 14-day quarantine, school and university closures, and progressive flight restrictions. A national lockdown was implemented between April 1st and 22nd. Around 200 000 people were quarantined and 266 122 RT-PCR tests conducted. Population mobility decreased progressively before lockdown. 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. 21 developed severe disease, with no deaths. The serial interval was 3.24 days, and 27.5% (95% confidence interval, 15.7%-40.0%) of transmissions occurred pre-symptomatically. Limited transmission amounted to a maximum reproduction number of 1.15 (95% confidence interval, 0.37-2.36). No community transmission has been detected since April 15th.InterpretationVietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact-tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial pre-symptomatic transmission.FundingThe Vietnam Ministry of Health and Wellcome Trust, UK.Research in contextEvidence before this studyVietnam was one of the first countries outside of China to detect imported and human-to-human transmitted SARS-CoV-2 within its borders. Yet, as of May 1st, a total of only 270 cases have been confirmed, no deaths have occurred, and no community transmission has been detected since April 15th despite intensive screening, tracing and testing. We did a PubMed database search to identify studies investigating COVID-19 response in Vietnam using the terms “Vietnam”, “COVID-19”, and “SARS-CoV-2”. All relevant articles were evaluated. Studies describe cases of COVID-19 and their management, aspects of the government response from newspapers and online government sources, but there are no previous reports using national data to describe and investigate the national epidemic and the impact of control measures cases over time.Added value of this studyWe used data from the National Steering Committee for COVID-19 response to give a comprehensive account of the first 100 days of the SARS-CoV-2 epidemic in Vietnam, including case numbers and their symptomatology, the estimated reproductive number by week, and their relation to the multiple control measures instituted by the Vietnam Government over time. We show two distinctive features of Vietnam’s response. First, the Government took rapid actions to restrict international flights, closed schools and universities, and instituted meticulous case-contact tracing and quarantining from late January, well before these measures were advised by WHO. Second, they placed mass communication, education, and the identification, serial testing, and 14-day quarantine of all direct contacts of cases, regardless of symptom development, at the heart of the response. The value of strict contact-tracing and quarantine is supported by the high proportion of asymptomatic cases (43%) and imported cases (60%), and evidence for substantial pre-symptomatic transmission.Implications of all the available evidenceVietnam has had remarkable success in controlling the emergence of SARS-CoV-2. Our report provides a complete picture of the control of SARS-CoV-2 in Vietnam, with lessons for other Governments seeking to extend national SARS-CoV-2 control or prevent future epidemics. Our findings shows the importance of acting early, before the virus becomes established in the community, and before the case numbers overwhelm systems of case-contact tracing and mass quarantine. They also demonstrate the value of effective mass communication in rapidly educating the public in infection prevention measures and providing real-time information on the state of the epidemic.

In Vietnam, there are no accurate data on tetanus incidence to allow assessment of disease burden or vaccination program efficacy. We analyzed age structure of 786 tetanus cases admitted to a tertiary referral center in Vietnam for three separate years during an 18-year period to examine the impact of tetanus prevention programs, namely the Expanded Program on Immunization (EPI) and the Maternal and Neonatal Tetanus (MNT) initiative. Most cases were born before the initiation of EPI. Median age increased from 33 (interquartile range: 20-52) in 1994, to 46 (32-63) in 2012 (P < 0.001). Birth-year distribution was unchanged, indicating the same birth cohorts presented with tetanus in 1994, 2003, and 2012. Enzyme-linked immunosorbent assay measurements in 90 men and 90 women covered by MNT but not EPI showed 73.3% (95% confidence interval [CI]: 62.9-82.1%) of women had anti-tetanus antibody compared with 24.4% (95% CI: 15.9-34.7%) of men, indicating continued tetanus vulnerability in older men in Vietnam.

Background Ventilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available. Methods We conducted a prospective observational study in four Vietnamese ICUs to assess the incidence and impact of VARI. Patients ≥ 16 years old and expected to be mechanically ventilated > 48 h were enrolled in the study and followed daily for 28 days following ICU admission. Results Four hundred fifty eligible patients were enrolled over 24 months, and after exclusions, 374 patients’ data were analyzed. A total of 92/374 cases of VARI (21.7/1000 ventilator days) were diagnosed; 37 (9.9%) of these met ventilator-associated pneumonia (VAP) criteria (8.7/1000 ventilator days). Patients with any VARI, VAP, or VARI without VAP experienced increased hospital and ICU stay, ICU cost, and antibiotic use (p

Background: Neonatal tetanus continues to occur in many resource-limited settings but there are few data regarding long-term neurological outcome from the disease, especially in settings with critical care facilities. Methods: We assessed long-term outcome following neonatal tetanus in infants treated in a pediatric intensive care unit in southern Vietnam. Neurological and neurodevelopmental testing was performed in 17 survivors of neonatal tetanus and 18 control children from the same communities using tools previously validated in Vietnamese children. Results: The median age of children assessed was 36 months. Eight neonatal tetanus survivors and 9 community control cases aged < 42 months were tested using the Bayley III Scales of Infant and Toddler Development (Bayley III-VN) and 8 neonatal tetanus survivors and 9 community controls aged ≥42 months were tested using the Movement Assessment Battery for Children. No significant reductions in growth indices or neurodevelopmental scores were shown in survivors of neonatal tetanus compared to controls although there was a trend towards lower scores in neonatal tetanus survivors. Neurological examination was normal in all children except for two neonatal tetanus survivors with perceptive deafness and one child with mild gross motor abnormality. Neonatal tetanus survivors who had expienced severe disease (Ablett grade ≥ 3) had lower total Bayley III-VN scores than those with mild disease (15 (IQR 14–18) vs 24 (IQR 19–27), p = 0.05) with a significantly lower cognitive domain score (3 (IQR 2–6) severe disease vs 7 (IQR 7–8) mild disease, p = 0.02). Conclusions: Neonatal tetanus is associated with long-term sequelae in those with severe disease. In view of these findings, prevention of neonatal tetanus should remain a priority.

Healthcare-associated pneumonia (HCAP) is a common complication in patients with severe tetanus. Nursing tetanus patients in a semi-recumbent body position could reduce the incidence of HCAP. In a randomised controlled trial we compared the occurrence of HCAP in patients with severe tetanus nursed in a semi-recumbent (30°) or supine position. A total of 229 adults and children (aged ≥1 year) with severe tetanus admitted to hospital in Vietnam, were randomly assigned to a supine (n = 112) or semi-recumbent (n = 117) position. For patients maintaining their assigned positions and in hospital for > 48. h there was no significant difference between the two groups in the frequency of clinically suspected pneumonia [22/106 (20.8%) vs 26/104 (25.0%); p = 0.464], pneumonia rate/1000 intensive care unit days (13.9 vs 14.6; p = 0.48) and pneumonia rate/1000 ventilated days (39.2 vs 38.1; p = 0.72). Mortality in the supine patients was 11/112 (9.8%) compared with 17/117 (14.5%) in the semi-recumbent patients (p = 0.277). The overall complication rate [57/112 (50.9%) vs 76/117 (65.0%); p = 0.03] and need for tracheostomy [51/112 (45.5%) vs 69/117 (58.9%); p = 0.04) was greater in semi-recumbent patients. Semi-recumbent body positioning did not prevent the occurrence of HCAP in severe tetanus patients. [Clinical Trials.gov Identifier: NCT01331252]. © 2011 Royal Society of Tropical Medicine and Hygiene.

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.

Highlights • Large contemporary case-series in a setting of improved critical care facilities. • Analysis of variables, some not analysed in previous studies/meta-analyses. • Age and weight were associated with a poor outcome. • Delay in admission to hospital and leukocytosis were also associated with a poor outcome., Summary Objectives Most data regarding the prognosis in neonatal tetanus originate from regions where limited resources have historically impeded management. It is not known whether recent improvements in critical care facilities in many low- and middle-income countries have affected indicators of a poor prognosis in neonatal tetanus. We aimed to determine the factors associated with worse outcomes in a Vietnamese hospital with neonatal intensive care facilities. Methods Data were collected from 107 cases of neonatal tetanus. Clinical features on admission were analyzed against mortality and a combined endpoint of ‘death or prolonged hospital stay’. Results Multivariable analysis showed that only younger age (odds ratio (OR) for mortality 0.69, 95% confidence interval (CI) 0.48–0.98) and lower weight (OR for mortality 0.06, 95% CI 0.01–0.54) were significantly associated with both the combined endpoint and death. A shorter period of onset (OR 0.94, 95% CI 0.88–0.99), raised white cell count (OR 1.17, 95% CI 1.02–1.35), and time between first symptom and admission (OR 3.77, 95% CI 1.14–12.51) were also indicators of mortality. Conclusions Risk factors for a poor outcome in neonatal tetanus in a setting with critical care facilities include younger age, lower weight, delay in admission, and leukocytosis.

Ventilator-associated pneumonia (VAP) is a serious healthcare-associated infection that affects up to 30 % of intubated and mechanically ventilated patients in intensive care units (ICUs) worldwide. The bacterial aetiology and corresponding antimicrobial susceptibility of VAP is highly variable, and can differ between countries, national provinces and even between different wards in the same hospital. We aimed to understand and document changes in the causative agents of VAP and their antimicrobial susceptibility profiles retrospectively over an 11 year period in a major infectious disease hospital in southern Vietnam. Our analysis outlined a significant shift from Pseudomonas aeruginosa to Acinetobacter spp. as the most prevalent bacteria isolated from quantitative tracheal aspirates in patients with VAP in this setting. Antimicrobial resistance was common across all bacterial species and we found a marked proportional annual increase in carbapenem-resistant Acinetobacter spp. over a 3 year period from 2008 (annual trend; odds ratio 1.656, P = 0.010). We further investigated the possible emergence of a carbapenem-resistant Acinetobacter baumannii clone by multiple-locus variable number tandem repeat analysis, finding a bla OXA-23-positive strain that was associated with an upsurge in the isolation of this pathogen. We additionally identified a single bla NDM-1-positive A. baumannii isolate. This work highlights the emergence of a carbapenem-resistant clone of A. baumannii and a worrying trend of antimicrobial resistance in the ICU of the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

Clostridium tetani is the etiologic agent of the muscle-spasming disease tetanus. Despite an effective vaccine, tetanus is an ongoing problem in some developing countries. Diagnosis by bacterial culture is not done because it is generally unnecessary and the entry of route of the bacteria can be inapparent. We attempted to isolate and evaluate C. tetani from the wounds of 84 patients with tetanus. We effectively isolated C. tetani from 45 patients. All strains tested positive by polymerase chain reaction for the gene encoding tetanus neurotoxin. Antimicrobial susceptibilities were determined by disc diffusion and E-test. All C. tetani isolates were susceptible to penicillin and metronidazole but resistant to co-trimoxazole. Despite treatment with high doses of penicillin, C. tetani was isolated after 16 days of intravenous penicillin in two cases. These data show that the intravenous route for penicillin may be inadequate for clearing the infection and emphasizes wound debridement in the treatment of tetanus.

Antimicrobial-resistant pathogenic members of theEnterobacteriaceaeare a well-defined global problem. We hypothesized that one of the main reservoirs of dissemination of antimicrobial resistance genes in Vietnam is non-pathogenic intestinal flora, and sought to isolate antimicrobial-resistant organisms from hospitalized patients and non-hospitalized healthy individuals in Ho Chi Minh City. The results identified substantial faecal carriage of gentamicin-, ceftazidime- and nalidixic acid-resistant members of theEnterobacteriaceaein both hospitalized patients and non-hospitalized healthy individuals. A high prevalence of quinolone resistance determinants was identified, particularly theqnrSgene, in both community- and hospital-associated strains. Furthermore, the results demonstrated that a combination of quinolone resistance determinants can confer resistance to nalidixic acid and ciprofloxacin, even in the apparent absence of additional chromosomal resistance mutations in wild-type strains and laboratory strains with transferred plasmids. These data suggest that intestinal commensal organisms are a significant reservoir for the dissemination of plasmid-mediated quinolone resistance in Ho Chi Minh City.

Unvaccinated individuals throughout the world are vulnerable to tetanus, but there are few data regarding the impact of focused vaccination programmes and modern intensive care facilities on the disease, particularly in the developing world. The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam admitted 2422 patients with tetanus aged > or =1 year between April 1993 and December 2002, during which time vaccine coverage and treatment facilities improved. The proportion of children < or =10 years old admitted with tetanus fell from 11.1 to 5.6% over the 10 year period (P = 0.002). The proportion of women aged 20-40 years fell from 10.1 to 1.2% (P < 0.001). Mortality rates fell from a maximum of 27.81% in 1994 to 10.04% in 2002 (P < 0.001). Thus, a marked reduction in tetanus incidence has occurred in age groups specifically targeted by the national vaccination programme. However, tetanus continues to be a major cause of morbidity and mortality in individuals outside the target population. Improved intensive care facilities, such as mechanical ventilation and low-cost infection control procedures are associated with a significant reduction in mortality.