Magnitude and patterns of severe Plasmodium vivax monoinfection in Vietnam: a 4-year single-center retrospective study.

Introduction: Infection with Plasmodium vivax is a recognized cause of severe malaria including deaths. The exact burden and patterns of severe P. vivax monoinfections is however still not well quantified, especially in P. vivax endemic regions. We examined the magnitude and patterns of severe malaria caused by monoinfections of P. vivax and associated predictors among patients admitted to a tertiary care center for malaria in Vietnam. Methods: A retrospective cohort study was conducted based on the patients' medical records at the Hospital for Tropical Diseases from January 2015 to December 2018. Extracted information included demographic, epidemiologic, clinical, laboratory and treatment characteristics. Results: Monoinfections with P. vivax were found in 153 (34.5, 95% CI 30.3-39.1%) patients of whom, uncomplicated and severe malaria were documented in 89.5% (137/153, 95% CI 83.7-93.5%) and 10.5% (16/153, 95% CI 6.5-16.3%), respectively. Patterns of severe malaria included jaundice (8 cases), hypoglycemia (3 cases), shock (2 cases), anemia (2 cases), and cerebral malaria (1 case). Among 153 patients, 73 (47.7%) had classic malaria paroxysm, 57 (37.3%) had >7 days of illness at the time of admission, and 40 (26.1%) were referred from other hospitals. A misdiagnosis as having other diseases from malaria cases coming from other hospitals was up to 32.5% (13/40). Being admitted to hospital after day 7th of illness (AOR = 6.33, 95% CI 1.14-35.30, p = 0.035) was a predictor of severe malaria. Severe malaria was statistically associated with longer hospital length of stay (p = 0.035). Early and late treatment failures and recrudescence were not recorded. All patients recovered completely. Discussion: This study confirms the emergence of severe vivax malaria in Vietnam which is associated with delayed hospital admission and increased hospital length of stay. Clinical manifestations of P. vivax infection can be misdiagnosed which results in delayed treatment. To meet the goal of malaria elimination by 2030, it is crucial that the non-tertiary hospitals have the capacity to quickly and correctly diagnose malaria and then provide treatment for malaria including P. vivax infections. More robust studies need to be conducted to fully elucidate the magnitude of severe P. vivax in Vietnam.

Learning meaningful latent space representations for patient risk stratification: Model development and validation for dengue and other acute febrile illness.

Background: Increased data availability has prompted the creation of clinical decision support systems. These systems utilise clinical information to enhance health care provision, both to predict the likelihood of specific clinical outcomes or evaluate the risk of further complications. However, their adoption remains low due to concerns regarding the quality of recommendations, and a lack of clarity on how results are best obtained and presented. Methods: We used autoencoders capable of reducing the dimensionality of complex datasets in order to produce a 2D representation denoted as latent space to support understanding of complex clinical data. In this output, meaningful representations of individual patient profiles are spatially mapped in an unsupervised manner according to their input clinical parameters. This technique was then applied to a large real-world clinical dataset of over 12,000 patients with an illness compatible with dengue infection in Ho Chi Minh City, Vietnam between 1999 and 2021. Dengue is a systemic viral disease which exerts significant health and economic burden worldwide, and up to 5% of hospitalised patients develop life-threatening complications. Results: The latent space produced by the selected autoencoder aligns with established clinical characteristics exhibited by patients with dengue infection, as well as features of disease progression. Similar clinical phenotypes are represented close to each other in the latent space and clustered according to outcomes broadly described by the World Health Organisation dengue guidelines. Balancing distance metrics and density metrics produced results covering most of the latent space, and improved visualisation whilst preserving utility, with similar patients grouped closer together. In this case, this balance is achieved by using the sigmoid activation function and one hidden layer with three neurons, in addition to the latent dimension layer, which produces the output (Pearson, 0.840; Spearman, 0.830; Procrustes, 0.301; GMM 0.321). Conclusion: This study demonstrates that when adequately configured, autoencoders can produce two-dimensional representations of a complex dataset that conserve the distance relationship between points. The output visualisation groups patients with clinically relevant features closely together and inherently supports user interpretability. Work is underway to incorporate these findings into an electronic clinical decision support system to guide individual patient management.

Aetiology and Potential Animal Exposure in Central Nervous System Infections in Vietnam.

An estimated 73% of emerging infections are zoonotic in origin, with animal contact and encroachment on their habitats increasing the risk of spill-over events. In Vietnam, close exposure to a wide range of animals and animal products can lead to acquisition of zoonotic pathogens, a number of which cause central nervous system (CNS) infections. However, studies show the aetiology of CNS infections remains unknown in around half of cases. We used samples and data from hospitalised patients with CNS infections, enrolled into the Vietnam Initiative on Zoonotic Infections multicentre study, to determine the association between aetiology and animal contact including those in whom the cause was unknown. Among 933 patients, a pathogen or an antibody response to it was identified in 291 (31.2%, 95% CI 28.3-34.3%). The most common pathogens were Streptococcus suis (n = 91 (9.8%, 8.0-11.9%)) and Japanese encephalitis virus (JEV) (n = 72 (7.7%, 6.1-9.7%)). Commonly reported animal contact included keeping, raising or handling (n = 364 (39.0%, 35.9-42.2%)) and handling, cooking or consuming raw meat, blood or viscera in the 2 weeks prior to symptom onset (n = 371 (39.8%, 36.6-43.0%)), with the latter most commonly from pigs (n = 343 (36.9%, 33.8-40.1%). There was no association between an unknown aetiology and exposure to animals in a multivariate logistic regression. Further testing for unknown or undetected pathogens may increase diagnostic yield, however, given the high proportion of zoonotic pathogens and the presence of risk factors, increasing public awareness about zoonoses and preventive measures can be considered.

Kinetics of neutralising antibodies against Omicron variant in Vietnamese healthcare workers after primary immunisation with ChAdOx1-S and booster with BNT162b2

We studied the development and persistence of neutralising antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs with different pre-existing immune statuses (group 1 (G1): n=21, and group 2 (G2): n=26 without and with prior breakthrough Delta variant infection, respectively). The study participants had completed primary immunisation with ChAdOx1-S and booster vaccination with BNT162b2. Neutralising antibodies were measured using a surrogate virus neutralisation assay. Of the 21 study participants in G1, neutralising antibodies against ancestral strain, Delta variant, BA.1 and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralising antibodies to the study viruses at week two post booster dose. Of the 26 study participants in G2, neutralising antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralising antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralising activities against ancestral strain and Delta variant, as compared to those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasise the importance of the first booster dose in producing cross-neutralising antibodies against Omicron variant. A second booster dose might be needed to maintain long-term protection against Omicron variant.

Immunologic Change over 72 Weeks Following Raltegravir- Versus Efavirenz-Based Therapy in HIV/HCV-Coinfected Individuals in Vietnam.

The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C virus (HCV)/HIV coinfection is incompletely understood. We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T cell activation (HLA-DR, CD38) and immune exhaustion [program cell death protein 1 (PD1), TIGIT] in HIV/HCV-coinfected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- versus efavirenz (EFV)-based therapy when used as first-time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared with those from ART-naive HIV-monoinfected and HIV-seronegative individuals. Before ART, HIV/HCV-coinfected individuals had higher levels of neopterin, sCD14, and sCD163, and increased frequencies of CD38+HLA-DR+, PD1+, and TIGIT+ CD4 and CD8 T cells compared with ART-naive HIV-monoinfected or HIV-seronegative individuals (all p < .01). Most parameters did not normalize despite 72 weeks of ART. In particular sCD163 persisted at high levels. Improvement over 72 weeks in fibrosis as assessed by FibroScan® correlated with reductions in plasma sCD163 and in the frequencies of T cell activation, single PD1+, TIGIT+, and dual PD1+TIGIT+ CD8 T cells. A nonsignificant tendency toward more favorable effects on monocyte and T cell immune activation and on T cell exhaustion were seen with RAL-compared with EFV-based therapy. The initiation of ART in HIV/HCV-coinfected individuals is associated with incomplete improvement in monocyte and T cell immune activation and exhaustion, which was associated with some corresponding improvement in liver fibrosis.

High Cure Rates for Hepatitis C Virus Genotype 6 in Advanced Liver Fibrosis With 12 Weeks Sofosbuvir and Daclatasvir: The Vietnam SEARCH Study.

BACKGROUND: Genotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis. METHODS: In this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load <500 IU/mL at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/mL received 24 weeks. Primary endpoint was sustained virological response (SVR). RESULTS: Of 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load <500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline. CONCLUSIONS: Prescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is <5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.

Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children.

The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on infections in healthy adults based on single timepoint data. Here, we analyzed the within-host evolution of 82 longitudinally sampled individuals, mostly young children, infected with A/H1N1pdm09 or A/H3N2 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous minority variants were more prevalent than synonymous ones. For A/H3N2 viruses in young children, early infection was dominated by purifying selection. As these infections progressed, nonsynonymous variants typically increased in frequency even when within-host virus titers decreased. Unlike the short-lived infections of adults where de novo within-host variants are rare, longer infections in young children allow for the maintenance of virus diversity via mutation-selection balance creating potentially important opportunities for within-host virus evolution.

Antibiotic-Resistant Gram-negative Bacteria Carriage in Healthcare Workers Working in an Intensive Care Unit.

Little is known about antibiotic-resistant Gram-negative bacteria (GNB) intestinal carriage among healthcare workers (HCWs) in Vietnam. All HCWs at a tertiary intensive care units were asked to undertake weekly rectal swabs. Among 40 participants, 65% (26/40) carried extended spectrum ß-lactamases (ESBL)/AmpC ß-lactamase-producing Escherichia coli. Two HCWs colonized with ESBL/AmpC ß-lactamase-producing Klebsiella pneumoniae. One HCW colonized with Acinetobacter baumannii. No one carried Pseudomonas spp.. A quarter (10/40) of HCWs were identified as persistent and frequent carriers. There is an urgent need to screen antibiotic-resistant GNB among HCWs and improve HCWs' hand hygiene compliance to reduce the transmission of antibiotic-resistant GNB in the hospital.

Immunogenicity of Oxford-AstraZeneca COVID-19 vaccine in Vietnamese healthcare workers

We studied the immunogenicity of Oxford-AstraZeneca vaccine in Vietnamese healthcare workers. We collected blood samples before each dose, at 14 days after each dose, and month 1 and 3 after dose 1 from each participant alongside demographics data. We measured neutralizing antibodies using a surrogate virus neutralization assay. The 554 study participants (136 males and 418 females) were aged between 22-71 years (median: 36 years). 104 and 94 out of 144 selected participants were successfully followed up at 14 days after dose 2 and 3 months after dose 1, respectively. Neutralizing antibodies increased after each dose, with the sero-conversion rate reaching 98.1% (102/104) at 14 days after dose 2. At month 3 after dose 1, neutralizing antibody levels decreased, while 94.7% (89/94) of the study participants remained seropositive. Oxford-AstraZeneca COVID-19 vaccine is immunogenic in Vietnamese healthcare workers. The requirement for a third dose warrants further research.

Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single-centre retrospective study.

BACKGROUND: Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. METHODS: Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. RESULTS: More than half (59.8%, 265/443, CI 55.1-64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1-27.4%) had severe malaria, while 7.2% (19/265, CI 4.6-10.9%) and 19.2% (51/265, CI 14.7-24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55-19.02, P < 0.001). No predictor of LTF was identified. CONCLUSIONS: Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

The natural history and transmission potential of asymptomatic SARS-CoV-2 infection

BackgroundLittle is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. MethodsWe conducted a prospective study at a quarantine centre for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. ResultsBetween March 10th and April 4th, 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. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. ConclusionsAsymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.

Duration of viral detection in throat and rectum of a patient with COVID-19

The rapid spread of coronavirus disease 2019 (COVID-19) raises concern about a global pandemic. Knowledge about the duration of viral shedding remains important for patient management and infection control. We report the duration of viral detection in throat and rectum of a COVID-19 patient treated at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Despite clinical recovery, SARS-CoV-2 RNA remained detectable by real time RT-PCR in throat and rectal swabs until day 11 and 18 of hospitalization, respectively. Because live SARS-CoV-2 has been successfully isolated from a stool sample from a COVID-19 patient in China, the results demonstrate that COVID-19 patients may remain infectious for long periods, and fecal-oral transmission may be possible. Therefore, our finding has important implications for infection control.

Researcher and study participants' perspectives of consent in clinical studies in four referral hospitals in Vietnam.

BACKGROUND: Within the research community, it is generally accepted that consent processes for research should be culturally appropriate and tailored to the context, yet researchers continue to grapple with what valid consent means within specific stakeholder groups. In this study, we explored the consent practices and attitudes regarding essential information required for the consent process within hospital-based trial communities from four referral hospitals in Vietnam. METHODS: We collected surveys from and conducted semi-structured interviews with study physicians, study nurses, ethics committee members, and study participants and family members regarding their experiences of participating in research, their perspectives toward research, and their views about various elements of the consent process. RESULTS: In our findings, we describe three interrelated themes related to the consent process: (1) words and regulation; (2) reimbursement, suspicions, and joining; and (3) responsibilities. In general, stakeholders had highly varied perspectives of nghiên cuu (Eng.: research) and researchers used varying levels of detail regarding all aspects of the study in the consent process to build trust with and/or promote potential research participants' choices about taking part in research. Findings additionally highlight how researchers felt that offering financial reimbursements in a hospital setting, where payment for services was routine, would be unfamiliar to participants and could raise suspicions about the research. Participants, however, focused their discussions on reimbursement or alternative reasons for joining the study, such as health related benefits or altruism. Finally, participants often relied on their physician to help them decide about joining a study or not. CONCLUSION: Further research is needed to understand how researchers and participants make sense of and practice consent, and how that impacts participants' decision-making about research participation. To promote valid consent within this context, it is important to engage with hospital-based trial communities as a whole. The data from this study will inform future research on consent, guide the revisions of consent related policies within our research sites and point to several larger issues surrounding researcher-participant expectations, communication, and trust.

Expert voices and equal partnerships: establishing Controlled Human Infection Models (CHIMs) in Vietnam.

The number of controlled human infection models (CHIMs) conducted worldwide has increased considerably in recent years, although few have been conducted in low and middle-income countries (LMICs), where infectious diseases have the greatest burden. Recently Oxford University Clinical Research Unit (OUCRU) in Ho Chi Minh City (HCMC) started developing CHIM research proposals motivated by the need to develop a clearer and more grounded understanding of the issues surrounding the conduct of CHIMs in LMICs. To explore initial perceptions and barriers to conducting CHIMs in Vietnam, OUCRU researchers conducted a set of key stakeholder interviews early in 2018 and held a CHIM workshop in HCMC in March 2018. This paper summarizes the discussions from the workshop and outlines a way forward for conducting CHIMs in Vietnam.

Differential prevalence and geographic distribution of hepatitis C virus genotypes in acute and chronic hepatitis C patients in Vietnam.

BACKGROUND: The highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs). METHODS: We analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5' UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS. RESULTS: 355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], (p = <0.001), while genotype 6 was significantly higher in chronic HCV mono-infected patients [(44.4% (36/81) versus 20.0% (16/80)] (p = < 0.004) compared to HIV-HCV coinfected patients. The prevalence of IL28B SNP (rs12979860) homozygous CC was 86.46% (83/96) in control individuals and was significantly higher in acutely-infected compared to chronically-infected patients [93.2 (82/88) versus 76.1% (35/46)] (p = < 0.005). CONCLUSION: HCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment naïve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6.

Clinical and aetiological study of hand, foot and mouth disease in southern Vietnam, 2013-2015: Inpatients and outpatients.

BACKGROUND: Hand, foot and mouth disease (HFMD) has been associated with large outbreaks among young children in the Asia-Pacific Region since 1997, including cases of severe illness and death. Severe illness is often associated with enterovirus A71 (EV-A71). Vietnam experienced a large sustained outbreak of 200000 hospitalized cases and over 200 deaths in 2011-12, the large majority occurring in southern Vietnam. METHODS: A prospective observational study was conducted in the outpatient clinics, infectious diseases wards, and paediatric intensive care units of the three main referral centres for the treatment of HFMD in southern Vietnam. Demographic data, basic laboratory parameters, and clinical data were recorded, and molecular diagnostic tests were performed. RESULTS: Between July 2013 and July 2015, a total of 1547 children were enrolled. Four serotypes of enterovirus A (EV-A71, Coxsackievirus (CV) A6, A10, and A16) were responsible for 1005 of 1327 diagnosed cases (75.7%). An unexpected dominance of EV-A71 was found among both inpatients and outpatients, as well as a strong association with severe illness. CV-A6 and CV-A10 emerged in Vietnam during the study period and replaced CV-A16. CV-A10 was associated with different clinical and laboratory characteristics. During admission, 119 children developed a more severe illness. It was found that children with a skin rash showed less progression of severity, but when a rash was present, a macular rash was significantly associated with an increased risk of progression. CONCLUSIONS: This study represents the most comprehensive descriptive HFMD study from Vietnam to date. Co-circulation and replacement of different serotypes has implications for vaccine development and implementation. These findings from a severely affected country add to our understanding of the presentation, progression, and aetiology of HFMD.

Molecular characterization of hepatitis B virus in Vietnam.

BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem globally. HBV genotypes and subgenotypes influence disease transmission, progression, and treatment outcome. A study was conducted among treatment naive chronic HBV patients in southern Vietnam to determine the genotypes and subgenotypes of HBV. METHODS: A prospective, exploratory study was conducted among treatment naïve chronic HBV patients attending at the Hospital for Tropical Diseases, in Ho Chi Minh City, Vietnam during 2012, 2014 and 2016. HBV DNA positive samples (systematically selected 2% of all treatment naïve chronic patients during 2012 and 2014, and 8% of all treatment naïve chronic patients during 2016) were subjected to whole genome sequencing (WGS) either by Sanger or Illumina sequencing. WGS was used to define genotype, sub-genotype, recombination, and the prevalence of drug resistance and virulence-associated mutations. RESULTS: One hundred thirty five treatment naïve chronic HBV patients including 18 from 2012, 24 from 2014, and 93 from 2016 were enrolled. Of 135 sequenced viruses, 72.6% and 27.4% were genotypes B and C respectively. Among genotype B isolates, 87.8% and 12.2% were subgenotypes B4 and B2 respectively. A G1896A mutation in the precore gene was present in 30.6% of genotype B isolates. The genotype C isolates were all subgenotype C1 and 78.4% (29/37) of them had at least one basal core promoter (BCP) mutation. A1762T and G1764 T mutations and a double mutation (A1762T and G1764 T) in the BCP region were significantly more frequent in genotype C1 isolates (p < 0.001). CONCLUSION: HBV genotype B including subgenotype B4 is predominant in southern Vietnam. However, one fourth of the chronic HBV infections were caused by subgenotype C1.

First reported cases of anti-NMDA receptor encephalitis in Vietnamese adolescents and adults.

INTRODUCTION: Anti-NMDA receptor encephalitis is increasingly recognised as an important differential diagnosis in patients with encephalitis of unknown aetiology. We report the first case series of patients diagnosed in Vietnam. METHODS: Samples of CSF from patients with presumed encephalitis but negative microbiological investigations, who exhibited dyskinesia, autonomic instability or psychosis were tested for antibodies against the NR1 subunit of the glutamate (type-NMDA) receptor using an indirect immunofluorescence assay. RESULTS: Of 99 patients admitted with all-cause encephalitis over an 18month period, 9.1% (n=9 patients, 5 female, median age 28years) had confirmed NMDAR encephalitis. All patients were admitted from one mental health hospital, and the incidence may therefore be an underestimate. Common features included reduction in speech (n=9), catatonia (n=9), convulsions (n=7), dyskinesia (n=9), rigidity (n=9) and autonomic dysfunction (n=7). Aside from a modest lymphocytic pleocytosis, routine CSF analysis was usually normal. No female patient had ovarian teratoma detected by abdominal ultrasound. Most patients were treated with high dose corticosteroids, and one patient received intravenous immunoglobulin. The median duration of hospitalization was 75days and no patient died during admission. CONCLUSIONS: Anti-NMDA receptor encephalitis is an important differential diagnosis to consider for patients presenting with acute onset psychiatric symptoms, who develop ensuing seizures, movement or autonomic disorder in Vietnam. A stronger evidence base for management and access to second line immunotherapy agents may help to reduce morbidity from this disease.

An Evidence-Based Algorithm for Early Prognosis of Severe Dengue in the Outpatient Setting.

Background: Early prediction of severe dengue could significantly assist patient triage and case management. Methods: We prospectively investigated 7563 children with ≤3 days of fever recruited in the outpatient departments of 6 hospitals in southern Vietnam between 2010 and 2013. The primary endpoint of interest was severe dengue (2009 World Health Organization Guidelines), and predefined risk variables were collected at the time of enrollment to enable prognostic model development. Results: The analysis population comprised 7544 patients, of whom 2060 (27.3%) had laboratory-confirmed dengue; nested among these were 117 (1.5%) severe cases. In the multivariate logistic model, a history of vomiting, lower platelet count, elevated aspartate aminotransferase (AST) level, positivity in the nonstructural protein 1 (NS1) rapid test, and viremia magnitude were all independently associated with severe dengue. The final prognostic model (Early Severe Dengue Identifier [ESDI]) included history of vomiting, platelet count, AST level. and NS1 rapid test status. Conclusions: The ESDI had acceptable performance features (area under the curve = 0.95, sensitivity 87% (95% confidence interval [CI], 80%-92%), specificity 88% (95% CI, 87%-89%), positive predictive value 10% (95% CI, 9%-12%), and negative predictive value of 99% (95% CI, 98%-100%) in the population of all 7563 enrolled children. A score chart, for routine clinical use, was derived from the prognostic model and could improve triage and management of children presenting with fever in dengue-endemic areas.