Systems-level multi-omics characterization provides novel molecular insights into indomethacin toxicity.

The mechanism of indomethacin toxicity at the systemic level is largely unknown. In this study, multi-specimen molecular characterization was conducted in rats treated with three doses of indomethacin (2.5, 5, and 10 mg/kg) for 1 week. Kidney, liver, urine, and serum samples were collected and analyzed using untargeted metabolomics. The kidney and liver transcriptomics data (10 mg indomethacin/kg and control) were subjected to a comprehensive omics-based analysis. Indomethacin exposure at 2.5 and 5 mg/kg doses did not cause significant metabolome changes, whereas considerable alterations in the metabolic profile compared to the control were induced by a dose of 10 mg/kg. Decreased levels of metabolites and an increased creatine level in the urine metabolome indicated injury to the kidney. The integrated omics analysis in both liver and kidney revealed an oxidant-antioxidant imbalance due to an excess of reactive oxygen species, likely originating from dysfunctional mitochondria. Specifically, indomethacin exposure induced changes in metabolites related to the citrate cycle, cell membrane composition, and DNA synthesis in the kidney. The dysregulation of genes related to ferroptosis and suppression of amino acid and fatty acid metabolism were evidence of indomethacin-induced nephrotoxicity. In conclusion, a multi-specimen omics investigation provided important insights into the mechanism of indomethacin toxicity. The identification of targets that ameliorate indomethacin toxicity will enhance the therapeutic utility of this drug.

Predictive Value of Preoperative Diffusion Tensor Imaging for Evaluating Postoperative Outcomes of Supratentorial Glioma in the Motor Function Area.

Objective: This study aimed to assess the predictive value of preoperative diffusion tensor imaging (DTI) data for surgical outcomes of patients with supratentorial glioma in the motor function area. Patients and Methods: This is a retrospective study of 43 patients receiving navigation-guided surgery for histopathologically demonstrated supratentorial glioma in the motor function area. All patients underwent preoperative 3 Tesla magnetic resonance imaging examinations with conventional and DTI sequences. Data on preoperative imaging and pre- and postoperative clinical characteristics of patients were retrospectively collected. Univariate and multivariate linear regressions were applied to analyze the relationships between preoperative parameters and pre- and postoperative muscle strength and the Karnofsky Performance Status (KPS) score. Results: Fourteen patients had low-grade gliomas and 29 had high-grade gliomas. Although the corticospinal tract (CST) score did not differ significantly between tumor grades, edema and deviation were common in low-grade gliomas (64.3%), while destroyed and infiltrated lesions were common in high-grade gliomas (58.6%). Muscle strength improved after surgery in the deviated tract group (40%) more than in the infiltrated tract group (33.3%). Two independent indices, preoperative muscle strength (p = 0.000) and glioma-to-CST distance (p = 0.001), were linearly related to postoperative muscle strength. The preoperative KPS score was the only indicator that affected the postoperative KPS score (p = 0.000). Conclusion: DTI should be considered in surgical management of supratentorial gliomas in the motor function area to determine the appropriate surgical strategy and predict the nature of the tumor and postoperative motor function.

Two novel CD40LG gene mutations causing X-linked hyper IgM syndrome in Vietnamese patients.

The X-linked hyper IgM syndrome is a primary immunodeficiency disorder (PID) due to mutations in the CD40LG gene. Hyper IgM syndrome is characterized by the absence or decreased levels of IgG and IgA and normal or elevated IgM levels in serum. Affected patients become susceptible to infections such as pneumonia, diarrhea, and skin ulcer types. Hematopoietic stem cell transplantation is the only treatment currently available and ideally performed before the age of 10 years. Early, accurate diagnosis will contribute to the effective treatment for patients with hyper IgM. The patients from different Vietnamese families who have been diagnosed with hyper IgM at The Allergy, Immunology and Rheumatology Department, Vietnam National Hospital Pediatrics, were performed a genetic analysis using whole exome sequencing. The mutations were confirmed by the Sanger sequencing method in patients and their families. The influence of the mutations was predicted with the in silico analysis tools: PROVEAN, SIFT, PolyPhen-2, and MutationTaster. In this study, two novel mutations (p.Thr254fs and p.Leu138Phe) in the CD40LG gene were found in Vietnamese patients with X-linked hyper IgM syndrome. Our results contribute to the general understanding of the etiology of the disease and can help diagnose the different forms of PID.

Frequency and distribution of HLA-DQB1 alleles from 2076 cord blood samples of the Vietnamese cohort.

Human leucocyte antigen (HLA) alleles are very diverse and characterized by ethnicity. To date, information about the frequencies and distributions of HLA alleles among the Vietnamese population is still limited. In this study, HLA-DQB1 alleles of 2076 cord blood units from individuals belonging to Vietnam's Kinh ethnic people were genotyped using Luminex-based polymerase chain reaction sequence-specific oligonucleotide. The results of the study demonstrated that there were 23 alleles on the locus HLA-DQB1. Among those, there were six alleles with high frequencies of over 5%, including DQB1* 03:01 (35.9%), DQB1* 05:01 (12.8%), DQB1* 03:03 (12.2%); DQB1* 06:01 (7.20%), DQB1* 05:02 (6.62%) and DQB1* 02:01 (5.30%) and five rare alleles with low frequencies of below 0.1%. More importantly, this study for the first time reported the presence of two new rare alleles including DQB1* 01:01 and DQB1* 01:02. Conclusively, this study provided significant information about HLA-DQB1 alleles for further investigations and clinical applications.

Allele and Haplotype Frequencies of HLA-A, -B, -C, and -DRB1 Genes in 3,750 Cord Blood Units From a Kinh Vietnamese Population.

The frequencies and diversities of human leukocyte antigen (HLA) alleles and haplotypes are representative of ethnicities. Matching HLA alleles is essential for many clinical applications, including blood transfusion, stem cell transplantation, and tissue/organ transplantation. To date, the information about the frequencies and distributions of HLA alleles and haplotypes among the Kinh Vietnamese population is limited because of the small sample size. In this study, more than 3,750 cord blood units from individuals belonging to the Kinh Vietnamese population were genotyped using PCR sequence-specific oligonucleotide (PCR-SSO) for HLA testing. The results of the study demonstrated that the most frequently occurring HLA-A, -B, -C, and -DRB1 alleles were A*11:01 (25%), A*24:02 (12.3%), A*02:01 (11.2); A*03:03 (8.95%), A*02:03 (7.81%), A*29:01 (7.03%); B*15:02 (15.1%), B*46:01 (10.7%), B*58:01 (7.65%), B*38:02 (7.29%); C*08:01 (17.2), C*07:02 (16.2%), C*01:02 (15.2), C*03:02 (8.3%), C*15:05 (6.13); DRB1*12:02 (31.0%), DRB1*09:01 (10.47%), DRB1*15:02 (7.54%); DRB1*07:01 (6.68%), DRB1*10:01 (6.63%), respectively, with the highest allele diversity level observed in locus B (93 alleles). The most frequent haplotypes of two-locus combinations of HLA-A-B, HLA-A-C, HLA-A-DRB1, HLA-B-C, HLA-B-DRB1, and HLA-C-DRB1 haplotypes were A*11:01-B*15:02 (7.63%), A*11:01-C*08:01 (7.98%), A*11:01-DRB1*12:02 (10.56%), B*15:02-C*08:01 (14.0%), B*15:02-DRB1*12:02 (10.47%), and C*08:01-DRB1*12:02 (11.38%), respectively. In addition, the most frequent haplotypes of three- and four-locus sets of HLA-A-B-C, HLA-A-B-DRB1, HLA-A-C-DRB1, HLA-B-C-DRB1, and HLA-A-B-C-DRB1 were A*11:01-B*15:02-C*08:01 (7.57%), A*11:01-B*15:02-DRB1*12:02 (5.39%), A*11:01-C*08:01-DRB1*12:02 (5.54%), B*15:02-C*08:01-DRB1*12:02 (10.21%), and A*11:01-B*15:02-C*08:01-DRB1*12:02 (5.45%), respectively. This study provides critical information on the frequencies and distributions of HLA alleles and haplotypes in the Kinh Vietnamese population, accounting for more than 85% of Vietnamese citizens. It paves the way to establish an umbilical cord blood bank for cord blood transplantation programs in Vietnam.

Primary intraventricular gliosarcoma on MRI: A challenging diagnosis.

Gliosarcoma (GS) is an uncommon central nervous system tumor with several characteristics of a malignant neoplasm and poor prognosis. The majority of GS reports describe a predilection for the cerebral hemispheres, and cases of intraventricular GS are extremely rare, with only a few reported. In addition, intraventricular GS has not been associated with any unique radiographic or clinical features, which can result in misdiagnosis as other intraventricular tumor types. In this report, we present the case of a 32-year-old woman with GS in the trigone of the lateral ventricle and provide a retrospective review of similar, previously reported cases.

Data on cerebral palsy in Vietnam will inform clinical practice and policy in low and middle-income countries.

PURPOSE: To document known risk factors, clinical severity, associated impairments and rehabilitation status of children presenting with cerebral palsy (CP) to the National Children's Hospital (NCH) in Hanoi, Vietnam. MATERIALS AND METHODS: Active prospective ascertainment of cases of CP presenting between June and November 2017 to the NCH using surveillance modelled on the Paediatric Active Enhanced Disease Surveillance system in Australia. RESULTS: Data were collected on 765 children with CP (mean age: 2 years 7 months (SD 2 y 6 mo). Mean age at diagnosis was 1 year 8 months (SD 1 y 9 mo). Children predominantly had spastic CP (95.2%, n = 729), most were quadriplegic (69.6%, n = 532) and 60.3% (n = 454) were Gross Motor Functional Classification System level III-V. Of the children 76.2% (n = 583) had one/more associated impairments. 36.3% (n = 276) had presumed perinatal asphyxia, 26.5% (n = 202) were preterm. Physiotherapy (94.3%, n = 663) was the most common form of intervention used. Only 2.6% (n = 12) of the children who would have benefitted from assistive devices had wheelchairs. CONCLUSION: We established hospital-based surveillance of CP in Hanoi and confirmed a high burden and severity of CP with potentially preventable risk factors. These data will inform clinician training and health policy and identify need for evidence-based care and assistive devices.IMPLICATIONS FOR REHABILITATIONWe identified a high number of children with severe forms of cerebral palsy (CP) in Hanoi, Vietnam through hospital-based surveillance.There is an urgent need for clinician training and access to and use of evidence-based interventions including assistive technology.This study will inform local capacity building and health policy for improved diagnosis and care of children with CP in Vietnam and other low and middle-income countries.

Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout.

Allopurinol (ALP) is commonly used as a drug for gout treatment. However, ALP is known to cause cutaneous adverse reactions (CARs) in patients. The HLA-B*58:01 allele is considered a biomarker of severe CAR (SCAR) in patients with gout, with symptoms of Stevens Johnson syndrome, and with toxic epidermal necrolysis. However, in patients with gout and mild cutaneous adverse drug reactions (MCARs), the role of HLA-allele polymorphisms has not been thoroughly investigated. In this study, 50 samples from ALP-tolerant patients and ALP-induced MCARs patients were genotyped in order to examine the polymorphisms of their HLA-A and HLA-B alleles. Our results showed that the frequencies of HLA-A*02:01/HLA-A*24:02 and HLA-A*02:01/HLA-A*29:01, the dual haplotypes in HLA-A, in patients with ALP-induced MCARs were relatively high, at 33.3% (7/21), which was HLA-B*58:01-independent, while the frequency of these dual haplotypes in the HLA-A locus in ALP-tolerant patients was only 3.45% (1/29). The HLA-B*58:01 allele was detected in 38% (8/21) of patients with ALP-induced MCARs, and in 3.45% (1/29) of ALP-tolerant patients. Notably, although HLA-B*58:01 may be a cause for the occurrence of MCARs in patients with gout, this correlation was not as strong as that previously reported in patients with SCAR. In conclusion, in addition to the HLA-B*58:01 allele, the presence of the dual haplotypes of HLA-A*02:01/HLA-A*24:02 and/or HLA-A*02:01/HLA-A*29:01 in the HLA-A locus may also play an important role in the appearance of ALP-induced MCARs in the Vietnamese population. The obtained primary data may contribute to the development of suitable treatments for patients with gout not only in Vietnam but also in other Asian countries.

Nutritional Status of Children with Cerebral Palsy-Findings from Prospective Hospital-Based Surveillance in Vietnam Indicate a Need for Action.

BACKGROUND: Lack of evidence on the burden and risk factors for malnutrition among children with cerebral palsy (CP) in Vietnam limits evidence-based interventions. We aimed to define the nutritional status of children with CP in Vietnam. MATERIALS AND METHODS: The study utilized data from active prospective hospital-based surveillance modelled on the Pediatric Active Enhanced Disease Surveillance system. Children (0-18 years) with CP attending the National Children's Hospital Hanoi, Vietnam between June-November 2017 were included. Data on demographic, clinical and rehabilitation status were collected following detailed neurodevelopmental assessment. Anthropometric measurements were taken. Nutritional status was determined using the World Health Organization guideline. RESULTS: Of 765 children (the mean (SD) age was 2.6 (2.5) years; 35.8% were female), 28.9% (n = 213) were underweight and 29.0% (n = 214) stunted. The odds of underweight were significantly higher among children aged >5 years and/or having a monthly family income of <50 USD. Underweight and/or stunting was high among children with quadriplegia (81%, n = 60 and 84.5%, n = 87) and/or Gross Motor Functional Classification System (GMFCS) level IV-V (62.5%, n = 45 and 67.0%, n = 67). Nearly one-third of intellectually impaired and more than half of hearing-impaired children were underweight and/or stunted. CONCLUSIONS: Poor economic status and increased motor severity increased vulnerability to malnutrition. Our findings will inform nutritional rehabilitation programs among these vulnerable children.

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice.

Radiotherapy side-effects present serious problems in cancer treatment. Melanin, a natural polymer with low toxicity, is considered as a potential radio-protector; however, its application as an agent against irradiation during cancer treatment has still received little attention. In this study, nanomelanin particles were prepared, characterized and applied in protecting the spleens of tumor-bearing mice irradiated with X-rays. These nanoparticles had sizes varying in the range of 80-200 nm and contained several important functional groups such as carboxyl (-COO), carbonyl (-C=O) and hydroxyl (-OH) groups on the surfaces. Tumor-bearing mice were treated with nanomelanin at a concentration of 40 mg/kg before irradiating with a single dose of 6.0 Gray of X-ray at a high dose rate (1.0 Gray/min). Impressively, X-ray caused mild splenic fibrosis in 40% of nanomelanin-protected mice, whereas severe fibrosis was observed in 100% of mice treated with X-ray alone. Treatment with nanomelanin also partly rescued the volume and weight of mouse spleens from irradiation through promoting the transcription levels of splenic Interleukin-2 (IL-2) and Tumor Necrosis Factor alpha (TNF-α). More interestingly, splenic T cell and dendritic cell populations were 1.91 and 1.64-fold higher in nanomelanin-treated mice than those in mice which received X-ray alone. Consistently, the percentage of lymphocytes was also significantly greater in blood from nanomelanin-treated mice. In addition, nanomelanin might indirectly induce apoptosis in tumor tissues via activation of TNF-α, Bax, and Caspase-3 genes. In summary, our results demonstrate that nanomelanin protects spleens from X-ray irradiation and consequently enhances immunoactivity in tumor-bearing mice; therefore, we present nanomelanin as a potential protector against damage from radiotherapy in cancer treatment.

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.

Protocol for hospital based-surveillance of cerebral palsy (CP) in Hanoi using the Paediatric Active Enhanced Disease Surveillance mechanism (PAEDS-Vietnam): a study towards developing hospital-based disease surveillance in Vietnam.

INTRODUCTION: The epidemiology, pathogenesis, management and outcomes of cerebral palsy (CP) in low-income and middle-income countries including Vietnam are unknown because of the lack of mechanisms for standardised collection of data. In this paper, we outline the protocol for developing a hospital-based surveillance system modelled on the Paediatric Active Enhanced Disease Surveillance (PAEDS) system in Australia. Using PAEDS-Vietnam we will define the aetiology, motor function and its severity, associated impairments, and nutritional and rehabilitation status of children with CP in Hanoi, Vietnam. These essential baseline data will inform future health service planning, health professional education and training, and family support. METHODS AND ANALYSIS: This is a hospital-based prospective surveillance of children with CP presenting to the rehabilitation, neurology and general paediatric services at the National Children's Hospital and St Paul Hospital in Hanoi. We will use active, prospective daily case-finding for all children with CP aged <18 years who are hospitalised or present to outpatient departments. Following parental consent, data will be collected using a modified version of the Australian Cerebral Palsy Register questionnaire. The data collection form has been developed in consultation with local and international experts and translated into Vietnamese. Information collected will include demographics, maternal health and birth history, type and severity of CP, known risk factors for CP, and nutrition, immunisation, education and rehabilitation status. ETHICS AND DISSEMINATION: This study was approved by the Hanoi Medical University Institutional Review Board (decision no 1722) and The University of Sydney Human Research Ethics Committee (approval no 2016/456). Establishment of PAEDS-Vietnam will enable hospital-based surveillance of CP for the first time in Vietnam. It will identify preventable causes of CP, patient needs and service gaps, and facilitate early diagnosis and intervention. Study findings will be disseminated through local and international conferences and peer-reviewed publications.

Molecular analysis of pyrazinamide resistance in Mycobacterium tuberculosis in Vietnam highlights the high rate of pyrazinamide resistance-associated mutations in clinical isolates.

Pyrazinamide (PZA) is a key antibiotic in current anti-tuberculosis regimens. Although the WHO has stressed the urgent need to obtain data on PZA resistance, in high tuberculosis burden countries, little is known about the level of PZA resistance, the genetic basis of such resistance or its link with Mycobacterium tuberculosis families. In this context, this study assessed PZA resistance through the molecular analysis of 260 Vietnamese M. tuberculosis isolates. First-line drug susceptibility testing, pncA gene sequencing, spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing were performed. Overall, the pncA mutation frequency was 38.1% (99 out of 260 isolates) but was higher than 72% (89 out of 123 isolates) in multidrug and quadruple-drug resistant isolates. Many different pncA mutations (71 types) were detected, of which 55 have been previously described and 50 were linked to PZA resistance. Among the 16 novel mutations, 14 are likely to be linked to PZA resistance because of their mutation types or codon positions. Genotype analysis revealed that PZA resistance can emerge in any M. tuberculosis cluster or family, although the mutation frequency was the highest in Beijing family isolates (47.7%, 62 out of 130 isolates). These data highlight the high rate of PZA resistance-associated mutations in M. tuberculosis clinical isolates in Vietnam and bring into question the use of PZA for current and future treatment regimens of multidrug-resistant tuberculosis without PZA resistance testing.

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.

Mycobacterium tuberculosis: ecology and evolution of a human bacterium.

Some species of the Mycobacterium tuberculosis complex (MTBC), particularly Mycobacterium tuberculosis, which causes human tuberculosis (TB), are the first cause of death linked to a single pathogen worldwide. In the last decades, evolutionary studies have much improved our knowledge on MTBC history and have highlighted its long co-evolution with humans. Its ability to remain latent in humans, the extraordinary proportion of asymptomatic carriers (one-third of the entire human population), the deadly epidemics and the observed increasing level of resistance to antibiotics are proof of its evolutionary success. Many MTBC molecular signatures show not only that these bacteria are a model of adaptation to humans but also that they have influenced human evolution. Owing to the unbalance between the number of asymptomatic carriers and the number of patients with active TB, some authors suggest that infection by MTBC could have a protective role against active TB disease and also against other pathologies. However, it would be inappropriate to consider these infectious pathogens as commensals or symbionts, given the level of morbidity and mortality caused by TB.

Surveillance of congenital rubella syndrome (CRS) in tertiary care hospitals in Hanoi, Vietnam during a rubella epidemic.

OBJECTIVE: To describe the epidemiology and clinical features of congenital rubella syndrome (CRS) in Hanoi, Vietnam. METHODS: Prospective surveillance of CRS between May 2011 and March 2012 in Hanoi, Vietnam. CRS burden was assessed by clinical examination and collection of serum samples from infants in neonatology, cardiology and pediatric departments of two tertiary care hospitals in Hanoi. All infants born during the study period with clinical manifestations of CRS and seropositivity (IgM) for rubella were included in this study. RESULTS: During the surveillance period 113 infants were identified with confirmed CRS (clinical features and positive rubella IgM). Their mean age at diagnosis was 38.4 days (range 1-152 days) and 61% were female. Clinical manifestations of CRS included low birth weight<2500 g (86.0%), congenital heart disease (63.7%), hearing impairment (63.7%) and ophthalmological abnormalities (46.9%). Other clinical features at birth included: thrombocytopenia (85.0%), neonatal purpura (74.3%), splenomegaly (63.7%), hepatomegaly (62.8%) and blueberry muffin rash (61.1%). Among the mothers of infants with confirmed CRS none had received a rubella vaccine in the past and 88.4% gave a history of rubella contact during the pregnancy under study. In most cases (84.1%) maternal infection occurred in the first trimester. During the surveillance period the estimated annual incidence of CRS was 1.13/1000 live births (95% CI 0.92-1.34). CONCLUSIONS: These preliminary baseline data show a high burden of CRS in Hanoi, Vietnam and the urgent need for universal vaccination. Surveillance to determine and monitor the national burden of CRS is essential.