Seroepidemiology and Carriage of Diphtheria in Epidemic-Prone Area and Implications for Vaccination Policy, Vietnam.

In 2019, a community-based, cross-sectional carriage survey and a seroprevalence survey of 1,216 persons 1-55 years of age were conducted in rural Vietnam to investigate the mechanism of diphtheria outbreaks. Seroprevalence was further compared with that of an urban area that had no cases reported for the past decade. Carriage prevalence was 1.4%. The highest prevalence, 4.5%, was observed for children 1-5 years of age. Twenty-seven asymptomatic Coerynebacterium diphtheriae carriers were identified; 9 carriers had tox gene-bearing strains, and 3 had nontoxigenic tox gene-bearing strains. Child malnutrition was associated with low levels of diphtheria toxoid IgG, which might have subsequently increased child carriage prevalence. Different immunity patterns in the 2 populations suggested that the low immunity among children caused by low vaccination coverage increased transmission, resulting in symptomatic infections at school-going age, when vaccine-induced immunity waned most. A school-entry booster dose and improved infant vaccination coverage are recommended to control transmissions.

Association of pneumococcal carriage in infants with the risk of carriage among their contacts in Nha Trang, Vietnam: A nested cross-sectional survey.

BACKGROUND: Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam. METHODS AND FINDINGS: In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant's carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly. CONCLUSIONS: In this study, we observed that cross-sectional contact and infection studies could help identify pneumococcal transmission routes and that preschool-age children may be the largest reservoir for pneumococcal transmission to infants in Nha Trang, Vietnam.

Investigating COVID-19 transmission in a tertiary hospital in Hanoi, Vietnam using social network analysis.

OBJECTIVES: In March 2020, a COVID-19 outbreak in a major referral hospital in Hanoi, Vietnam led to 7664 patients and staff being sent into lockdown for 2 weeks, and more than 52,200 persons across 49 provinces being quarantined. We assessed SARS-CoV-2 transmission patterns during this to-date largest hospital outbreak in Vietnam using social network analysis (SNA). METHODS: We constructed a directed relational network and calculated network metrics for 'degree', 'betweenness', 'closeness' and 'eigenvector' centrality to understand individual-level transmission patterns. We analysed network components and modularity to identify sub-network structures with disproportionately big effects. RESULTS: We detected 68 connections between 46 confirmed cases, of whom 27 (58.7%) were ancillary support staff, 7 (15.2%) caregivers, 6 (13%) patients and 2 (4.4%) nurses. Among the 10 most important cases selected by each SNA network metric, transmission dynamics clustered in 17 cases, of whom 12 (70.6%) cases were ancillary support staff. Ancillary support staff also constituted 71.1% of cases in the dominant sub-network and 68.8% of cases in the three largest sub-communities. CONCLUSIONS: We identified non-clinical ancillary support staff, who are responsible for room service and food distribution in hospital wards in Vietnam, as a group with disproportionally big impacts on transmission dynamics during this outbreak. Our findings call for a holistic approach to nosocomial outbreak prevention and response that includes both clinical and non-clinical hospital staff. Our work also shows the potential of SNA as a complementary outbreak investigation method to better understand infection patterns in hospitals and similar settings.

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

What are the most effective community-based antimicrobial stewardship interventions in low- and middle-income countries? A narrative review.

Antimicrobial resistance (AMR) is a major global issue and antimicrobial stewardship is central to tackling its emergence. The burden of AMR disproportionately impacts low- and middle-income countries (LMICs), where capacity for surveillance and management of resistant pathogens is least developed. Poorly regulated antibiotic consumption in the community is a major driver of AMR, especially in LMICs, yet community-based interventions are neglected in stewardship research, which is often undertaken in high-income settings and/or in hospitals. We reviewed the evidence available to researchers and policymakers testing or implementing community-based antimicrobial stewardship strategies in LMICs. We critically appraise that evidence, deliver recommendations and identify outstanding areas of research need. We find that multifaceted, education-focused interventions are likely most effective in our setting. We also confirm that the quality and quantity of community-based stewardship intervention research is limited, with research on microbiological, clinical and economic sustainability most urgently needed.

Timeliness of contact tracing among flight passengers during the COVID-19 epidemic in Vietnam.

BACKGROUND: International air travel plays an important role in the global spread of SARS-CoV-2, and tracing of close contacts is an integral part of the public health response to COVID-19. We aimed to assess the timeliness of contact tracing among airline passengers arriving in Vietnam on flights containing COVID-19 cases and investigated factors associated with timeliness of contact tracing. METHODS: We included data from 2228 passengers on 22 incoming flights between 2 and 19 March 2020. Contact tracing duration was assessed separately for the time between the date of index case confirmation and date of contact tracing initiation (interval I), and the date of contact tracing initiation and completion (interval II). We used log-rank tests and multivariable Poisson regression models to identify factors associated with timeliness. RESULTS: The median duration of interval I and interval II was one (IQR: 1-2) and 3 days (IQR: 2-5), respectively. The contact tracing duration was shorter for passengers from flights where the index case was identified through mandatory testing directly upon arrival (median = 4; IQR: 3-5) compared to flights with index case detection through self-presentation at health facilities after arrival (median = 7; IQR: 5-8) (p-value = 0.018). Cumulative hazards for successful tracing were higher for Vietnamese nationals compared to non-Vietnamese nationals (p < 0.001). CONCLUSIONS: Contact tracing among flight passengers in the early stage of the COVID-19 epidemic in Vietnam was timely though delays occurred on high workload days. Mandatory SARS-CoV-2 testing at arrival may reduce contact tracing duration and should be considered as an integrated screening tool for flight passengers from high-risk areas when entering low-transmission settings with limited contact tracing capacity. We recommend a standardized risk-based contact tracing approach for flight passengers during the ongoing COVID-19 epidemic.

Severe Acute Respiratory Syndrome Coronavirus 2 Shedding by Travelers, Vietnam, 2020.

We analyzed 2 clusters of 12 patients in Vietnam with severe acute respiratory syndrome coronavirus 2 infection during January-February 2020. Analysis indicated virus transmission from a traveler from China. One asymptomatic patient demonstrated virus shedding, indicating potential virus transmission in the absence of clinical signs and symptoms.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

The Effect of Maternal Pertussis Immunization on Infant Vaccine Responses to a Booster Pertussis-Containing Vaccine in Vietnam.

BACKGROUND: Maternal vaccination with an acellular pertussis (aP)-containing vaccine is a recommended strategy in a growing number of industrialized countries, to protect young infants from disease. Little is known on the effect of this strategy in low- and middle-income countries. Following a previous report on the effect of adding a pertussis and diphtheria component to the tetanus vaccination program in pregnant women in Vietnam, we report on infant immune responses to a booster aP vaccine dose in this randomized controlled clinical trial. METHODS: Thirty infants of Tdap (tetanus, diphtheria, and acellular pertussis)-vaccinated pregnant women and 37 infants of women vaccinated with a tetanus-only vaccine received a fourth aP-containing vaccine dose in the second year of life. Blood was taken 1 month after the fourth infant dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT), and diphtheria toxoid (DT) were measured using commercially available enzyme-linked immunosorbent assays (ELISA). RESULTS: One month after the booster dose, significantly lower antibody titers were measured in the Tdap group for anti-TT IgG (P < .001) only. Anti-DT IgG, anti-PT IgG, anti-Prn IgG, and anti-FHA IgG antibody titers were comparable for both groups. A rise in antibody concentrations was elicited for all (except DT) antigens after boosting. CONCLUSIONS: The present results indicate that the blunting of infant pertussis responses induced by maternal immunization, measured after a primary series of aP vaccines, was resolved with the booster aP vaccine dose. These results add to the evidence for national and international decision makers on maternal immunization as a vaccination strategy for protection of young infants against infectious diseases.

Mycobacterium tuberculosis lineages and anti-tuberculosis drug resistance in reference hospitals across Viet Nam.

BACKGROUND: Mycobacterium tuberculosis, the tuberculosis (TB) pathogen, despite a low level of genetic diversity, has revealed a high variety of biological and epidemiological characteristics linked to their lineages, such as transmissibility, fitness and propensity to acquire drug resistance. This has important implications for the epidemiology of TB. We conducted this first countrywide cross-sectional study to identify the prevalent M. tuberculosis lineages and to assess their epidemiological associations and their relation to drug resistance. The study was conducted among isolates acquired in reference hospitals across Vietnam. Isolates with drug susceptibility testing profiles were identified for their lineages by spoligotyping. Logistic regression was used to investigate the association of M. tuberculosis lineages with location, age and sex of the patients and drug resistance levels. RESULTS: Results showed that the most prevalent lineage was Beijing (55.4 %), followed by EAI (27.5 %), T (6.4 %), LAM (1.3 %), Haarlem (1 %) and Zero type (0.3 %). The proportion of Beijing isolates in the North (70.4 %) and the South (68 %) was higher than in the Centre (28 %) (OR = 1.7 [95 % CI: 1.4-2.0], p < 0.0001), whereas the proportion of EAI isolates in the North (7.1 %) and the South (17 %) was much lower compared with the Centre (59 %) (OR = 0.5 [95 % CI: 0.4-0.6], p < 0.0001). Overall, Beijing isolates were the most likely to be drug-resistant and EAI isolates were the least likely to be drug-resistant, except in the South of Vietnam where EAI is also highly drug-resistant. The proportion of Beijing isolates was significantly higher (p < 0.01), and the proportion of EAI isolates was significantly lower (p < 0.05) in younger patients. The proportion of drug-resistance was higher in isolates collected from male patients and from patients in the middle age groups. CONCLUSIONS: The findings suggest ongoing replacement of EAI lineage, which is mainly more drug-susceptible with highly drug-resistant Beijing lineage in all studied regions of Vietnam. Male patients of working ages should be the focus for better control to prevent the emergence of drug-resistant TB.

Cost of rotavirus diarrhea for programmatic evaluation of vaccination in Vietnam.

BACKGROUND: Rotavirus is the most common etiology of diarrhea-associated hospitalizations and clinic visits in Vietnamese children < 5 years old. To estimate the economic burden of rotavirus-associated formal healthcare encounters, an economic study was conducted. METHODS: A cost-of-illness study was performed from a societal perspective. Data were collected from children below the age of five years who presented to a clinic or hospital with symptoms of acute gastroenteritis (AGE). Patient-specific information on resource use and cost was obtained through caregiver interviews and medical chart review. Costs are presented in 2014 US dollar ($). RESULTS: A total of 557 children with symptoms of AGE were enrolled from March through June 2009, with mean age of 16.5 months. Of the 340 outpatients and 217 admitted patients enrolled, 41 % tested rotavirus positive. It was found that, from a societal perspective, the mean total cost of AGE was $175. Costs of patients with and without rotavirus were $217 and $158, respectively. From multiple regression analysis, it was found that rotavirus infection, patient age and receiving oral rehydration solution before visiting health facility had significant effect on the costs. CONCLUSIONS: This study clearly demonstrated substantial economic burden of AGE including rotavirus disease. They were significantly greater than the previously reported cost estimates in Vietnam. These updated costs of illness result in more favorable vaccine cost-effectiveness than in previous economic evaluations.

Increase in human immunodeficiency virus and syphilis prevalence and incidence among men who have sex with men, vietnam 2015 - 2020.

INTRODUCTION: We assessed trends in HIV and syphilis prevalence, HIV incidence, related risk factors, and preventive behaviors among men who have sex with men (MSM) in Vietnam from 2015 to 2020. METHODS: Data originated from the HIV Sentinel Surveillance Plus system, which sampled MSM at venues and hotspots in seven of Vietnam's 63 provinces in 2015, 2016, 2018, and 2020 (N = 1100-1445 per year; ∼150-300 per province per year). RESULTS: HIV prevalence estimates increased from 6.6% (95% CI 4.5-9.6) in 2015 to 13.8% (95% CI 10.5-18.2, p = .001 for trend) in 2020 overall, and separately in An Giang, Can Tho, Hai Phong, and Khanh Hoa provinces but not in Ho Chi Minh City, Hanoi, or Kien Giang. Syphilis prevalence increased from 2.7% (95% CI 1.4-5.1) in 2015 to 12.6% (95% CI 8.7-18.0) in 2020 overall (p < .001 for trend), and separately in An Giang, Can Tho, and Hai Phong provinces but not in Ho Chi Minh City or Kien Giang. We calculated time-at-risk from first anal sex to first HIV-positive or last HIV-negative test to estimate HIV incidence. Estimated HIV incidence suggested increasing rates of seroconversion from 1.36 per 100 person-years experienced by participants in 2015 to 2.61 per 100 person-years among participants in 2020 (hazard ratio per year 1.13, 95% CI 1.08-1.18, p < .001). There was a statistically significant increase in HIV testing, STI testing, and receipt of free condoms over the period (p < .05 for trend), and a statistically significant decrease in amphetamine use (p = .043 for trend). CONCLUSIONS: Despite prevention efforts and improvements in some risk indicators, consecutive cross-sectional sampling results provide evidence of increasing incidence of HIV and syphilis among MSM in Vietnam, especially outside the major cities. Aggressive HIV prevention and treatment services can be expanded while conducting deeper investigations into the causes of these increases.

Sero and Carriage Epidemiology of Pertussis in Urban and Rural Regions in Vietnam.

The underestimation of the pertussis burden prompted our study to investigate the prevalence of recent pertussis infection, its associated factors, and antibody titer changes in the same individuals in Vietnam. Two cross-sectional surveys were conducted in Nha Trang in 2017 and Quang Ngai in 2019, representing high- and low-vaccine-coverage areas, respectively. Serum anti-pertussis toxin immunoglobulin-G (anti-PT IgG) ≥ 62.5 IU/mL by ELISA indicated infection in the previous 12 months. In Nha Trang, the participants of the 2017 survey were followed up in 2019. Logistic regression was used to determine the odds ratios for the characteristics associated with anti-PT IgG ≥ 62.5. The age-stratified prevalence in patients aged >2 years ranged from 2.1% (age 26-35) to 9.6% (3-5) in Nha Trang (2017) and from 7.2% (age 26-35) to 11.4% (6-15) in Quang Ngai. The prevalence tended to be higher in Quang Ngai across all age groups. Cough, recent antibiotic use, and smoking in Nha Trang were positively associated with an anti-PT IgG of ≥62.5, and having been diagnosed with pertussis and persistent cough with paroxysms/whoop in Quang Ngai were positively associated with an anti-PT IgG of ≥62.5. No nasopharyngeal swabs were positive for Bordetella pertussis using real-time PCR. The geometric mean of the IgG titer ratio from 2019 to 2017 was 1.45 in the paired samples. This study emphasizes Bordetella pertussis circulation across all age groups in both low- and high-vaccine-coverage settings in Vietnam, underscoring the need for continuous and standardized surveillance for a comprehensive understanding of its epidemiology.

Pre-existing cross-reactive neutralizing activity against SARS-CoV-2 and seasonal coronaviruses prior to the COVID-19 pandemic (2014-2019) with limited immunity against recent emerging SARS-CoV-2 variants, Vietnam.

OBJECTIVES: SARS-CoV-2 transmission and epidemic potential is related to the population's immunity levels. As such, assessing different regions' preexisting immune responses to SARS-CoV-2 is important to understand the transmission potential of emerging SARS-CoV-2 variants. DESIGN: In 975 serum samples from Vietnam (2014 to 2019), anti-SARS-CoV-2 Immunoglobulin G levels were determined by enzyme-linked immunosorbent assay. Plaque reduction neutralization test (PRNT) was performed using Wuhan strain and variants of concern (VOCs). Cross-reactivity was confirmed by analyzing B-cell receptor (BCR) repertoire sequences and identifying BCR repertoire sequences-derived T-cell epitopes. RESULTS: Overall, 20.9% (n = 76/364) and 9.2% (n = 7) demonstrated SARS-CoV-2 neutralizing activity (PRNT50) against the Wuhan and Alpha strain, respectively. Neutralizing activity against Beta, Gamma, and Delta strains was absent (PRNT50<5) in all samples. Cross-reactive epitopes against SARS-CoV-2 and other coronavirus spike proteins were detected in the N-terminal domain, S2, and receptor-binding domain regions. CONCLUSIONS: Following BCR and major histocompatibility complex analysis, T-cell receptor-recognized epitope motif (TREM) among pathogenic coronaviruses and coronaviruses spike proteins were the top TREM peptide, suggesting that pre-existing immunity against SARS-CoV-2 in Vietnam was due to exposure to common cold coronaviruses. With limited immunity against emerging VOCs, further monitoring, and control of the epidemic, along with COVID-19 vaccine programs against VOCs, are necessary.

Respiratory syncytial virus: co-infection and paediatric lower respiratory tract infections.

Comprehensive population-based data on the role of respiratory viruses in the development of lower respiratory tract infections (LRTIs) remain unclear. We investigated the incidence and effect of single and multiple infections with respiratory viruses on the risk of LRTIs in Vietnam. Population-based prospective surveillance and a case-control study of hospitalised paediatric patients with acute respiratory infection (ARI) were conducted from April 2007 through to March 2010. Healthy controls were randomly recruited from the same community. Nasopharyngeal samples were collected and tested for 13 respiratory viruses using multiplex PCRs. 1992 hospitalised ARI episodes, including 397 (19.9%) with LRTIs, were enrolled. Incidence of hospitalised LRTIs among children aged <24 months was 2171.9 per 100 000 (95% CI 1947.9-2419.7). The majority of ARI cases (60.9%) were positive for at least one virus. Human rhinovirus (24.2%), respiratory syncytial virus (20.1%) and influenza A virus (12.0%) were the most common and 9.5% had multiple-viral infections. Respiratory syncytial virus and human metapneumovirus infections independently increased the risk of LRTIs. Respiratory syncytial virus further increased the risk, when co-infected with human rhinovirus, human metapneumovirus and parainfluenza virus-3 but not with influenza A virus. The case-control analysis revealed that respiratory syncytial virus and influenza A virus increased the risk of ARI hospitalisation but not human rhinovirus. Respiratory syncytial virus is the leading pathogen associated with risk of ARI hospitalisation and LRTIs in Vietnam.

Incidence of radiologically-confirmed pneumonia and Haemophilus influenzae type b carriage before Haemophilus influenzae type b conjugate vaccine introduction in Central Vietnam.

OBJECTIVES: To determine the incidence of radiologically-confirmed pneumonia (RCP) and Haemophilus influenzae type b (Hib) carriage in central Vietnam as a baseline data before Hib conjugate vaccine introduction. STUDY DESIGN: In the context of ongoing population-based prospective, hospitalized acute respiratory infection surveillance study, a cross-sectional Hib carriage study was conducted among 1000 children < 5 years of age living in NhaTrang, Vietnam in June 2010, 1 month before the nationwide introduction of Hib conjugate vaccine in Vietnam. RESULTS: The incidence of RCP hospitalizations among children < 5 years of age was 3.3 per 1000 children. The highest incidence was observed among children 12-23 month age group (8.3 per 1000). Haemophilus influenzae carriage was detected in 37% of the children and Hib carriage rate was 3%. Eighty-two percent of the Haemophilus influenzae had TEM ß-lactamase resistance gene. The presence of 6 or more family members was associated with an increased rate of Hib carriage (P = .04). CONCLUSIONS: Incidence of RCP and Hib carriage in this cross-sectional survey are lower compared with other studies. Continued surveillance for invasive Hib disease and sequential Hib carriage surveys are needed to support future assessments of the impact of Hib conjugate vaccine in Vietnam.

Evaluation of the effect of reduced-dose pneumococcal conjugate vaccine schedules on vaccine serotype carriage in children and their caretakers in a naïve population in Vietnam: Protocol for a cluster randomized non-inferiority trial.

Introduction: The WHO currently recommends giving pneumococcal conjugate vaccines (PCVs) as three doses - either three doses in infancy with Pentavalent vaccine (3p+0), or two doses in infancy followed by a booster around 12 months (2p+1). However, their high price is a barrier to introduction and sustainability in low and middle-income countries. We hypothesize that a schedule with a single priming and a booster dose (1p+1) may maintain similar levels of protection for the community by sustaining herd immunity, once circulation of vaccine types has been controlled. Methods and analysis: We will conduct a cluster randomized trial with four intervention arms (1p+1, 0p+1, 2p+1, 3p+0) and three unvaccinated clusters in the 27 communes of Nha Trang, central Vietnam. A PCV catch-up vaccination campaign to all children under three years of age will be performed at the start of the trial. The primary endpoint is non-inferiority of the1p+1 schedule if compared to the WHO standard 2p+1 and 3p+0 schedules in reducing vaccine serotype carriage prevalence in infants. We will also explore impact of 0p+1 schedule. A baseline and annual pneumococcal carriage surveys of 6480 participants per survey covering infants, toddlers and their mothers will be conducted. Ethics and dissemination: Ethical approvals were obtained from the ethical review committees of Institute of Tropical Medicine, Nagasaki University (151203149-2) and the Ministry of Health, Vietnam (1915/QD-BYT). The results, interpretation and conclusions will be presented at national and international conferences, and published in peer-reviewed open access journals. Trial registration number: NCT02961231.

Molecular Epidemiology of Streptococcus pneumoniae Detected in Hospitalized Pediatric Acute Respiratory Infection Cases in Central Vietnam.

Streptococcus pneumoniae is the major bacterial pathogen causing high pneumonia morbidity and mortality in children <5 years of age. This study aimed to determine the molecular epidemiology of S. pneumoniae detected among hospitalized pediatric ARI cases at Khanh Hoa General Hospital, Nha Trang, Vietnam, from October 2015 to September 2016 (pre-PCV). We performed semi-quantitative culture to isolate S. pneumoniae. Serotyping, antimicrobial susceptibility testing, resistance gene detection and multi-locus sequence typing were also performed. During the study period, 1300 cases were enrolled and 413 (31.8%) S. pneumoniae were isolated. School attendance, age <3 years old and prior antibiotic use before admission were positively associated with S. pneumoniae isolation. Major serotypes were 6A/B (35.9%), 19F (23.7%) and 23F (12.7%), which accounted for 80.3% of vaccine-type pneumococci. High resistance to Clarithromycin, Erythromycin and Clindamycin (86.7%, 85%, 78.2%) and the mutant drug-resistant genes pbp1A (98.1%), pbp2b (98.8%), pbp2x (99.6%) ermB (96.6%) and mefA (30.3%) were detected. MLST data showed high genetic diversity among the isolates with dominant ST 320 (21.2%) and ST 13223 (19.3%), which were mainly found in Vietnam. Non-typeables accounted for most of the new STs found in the study. Vaccine-type pneumococcus and macrolide resistance were commonly detected among hospitalized pediatric ARI cases.

A decade of human metapneumovirus in hospitalized children with acute respiratory infection: molecular epidemiology in central Vietnam, 2007-2017.

Human metapneumovirus (hMPV) can cause severe acute respiratory infection (ARI). We aimed to clarify the clinical and molecular epidemiological features of hMPV. We conducted an ARI surveillance targeting hospitalized children aged 1 month to 14 years in Nha Trang, Vietnam. Nasopharyngeal swabs were tested for respiratory viruses with PCR. We described the clinical characteristics of hMPV patients in comparison with those with respiratory syncytial virus (RSV) and those with neither RSV nor hMPV, and among different hMPV genotypes. Among 8822 patients, 278 (3.2%) were hMPV positive, with a median age of 21.0 months (interquartile range: 12.7-32.5). Among single virus-positive patients, hMPV cases were older than patients with RSV (p < 0.001) and without RSV (p = 0.003). The proportions of clinical pneumonia and wheezing in hMPV patients resembled those in RSV patients but were higher than in non-RSV non-hMPV patients. Seventy percent (n = 195) were genotyped (A2b: n = 40, 20.5%; A2c: n = 99, 50.8%; B1: n = 37, 19%; and B2: n = 19, 9.7%). The wheezing frequency was higher in A2b patients (76.7%) than in those with other genotypes (p = 0.033). In conclusion, we found a moderate variation in clinical features among hMPV patients with various genotypes. No seasonality was observed, and the multiple genotype co-circulation was evident.

A Birth Cohort Follow-Up Study on Congenital Zika Virus Infection in Vietnam.

We assessed the development, sensory status, and brain structure of children with congenital Zika virus (ZIKV) infection (CZI) at two years and preschool age. CZI was defined as either ZIKV RNA detection or positive ZIKV IgM and neutralization test in the cord or neonatal blood. Twelve children with CZI born in 2017-2018 in Vietnam, including one with Down syndrome, were assessed at 23-25.5 months of age, using Ages and Stages Questionnaire (ASQ-3), ASQ:Social-Emotional (ASQ:SE-2), Modified Checklist for Autism in Toddlers, automated auditory brainstem response (AABR), and Spot Vision Screener (SVS). They underwent brain CT and MRI. They had detailed ophthalmological examinations, ASQ-3, and ASQ:SE-2 at 51-62 months of age. None had birthweight or head circumference z-score < -3 except for the one with Down syndrome. All tests passed AABR (n = 10). No ophthalmological problems were detected by SVS (n = 10) and detailed examinations (n = 6), except for a girl's astigmatism. Communication and problem-solving domains in a boy at 24 months, gross-motor area in a boy, and gross-motor and fine-motor areas in another boy at 59-61 months were in the referral zone. Brain CT (n = 8) and MRI (n = 6) revealed no abnormalities in the cerebrum, cerebellum, or brainstem other than cerebellar hypoplasia with Down syndrome. The CZI children were almost age-appropriately developed with no brain or eye abnormalities. Careful and longer follow-up is necessary for children with CZI.