Age-time-specific transmission of hand-foot-and-mouth disease enterovirus serotypes in Vietnam: A catalytic model with maternal immunity.

Hand, foot and mouth disease (HFMD) is highly prevalent in the Asia Pacific region, particularly in Vietnam. To develop effective interventions and efficient vaccination programs, we inferred the age-time-specific transmission patterns of HFMD serotypes enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) in Ho Chi Minh City, Vietnam from a case data collected during 2013-2018 and a serological survey data collected in 2015 and 2017. We proposed a catalytic model framework with good adaptability to incorporate maternal immunity using various mathematical functions. Our results indicate the high-level transmission of CV-A6 and CV-A10 which is not obvious in the case data, due to the variation of disease severity across serotypes. Our results provide statistical evidence supporting the strong association between severe illness and CV-A6 and EV-A71 infections. The HFMD dynamic pattern presents a cyclical pattern with large outbreaks followed by a decline in subsequent years. Additionally, we identify the age group with highest risk of infection as 1-2 years and emphasise the risk of future outbreaks as over 50% of children aged 6-7 years were estimated to be susceptible to CV-A16 and EV-A71. Our study highlights the importance of multivalent vaccines and active surveillance for different serotypes, supports early vaccination prior to 1 year old, and points out the potential utility for vaccinating children older than 5 years old in Vietnam.

A novel diagnostic model for tuberculous meningitis using Bayesian latent class analysis.

BACKGROUND: Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of a gold standard. Current microbiological tests lack sensitivity and clinical diagnostic approaches are subjective. We therefore built a diagnostic model that can be used before microbiological test results are known. METHODS: We included 659 individuals aged [Formula: see text] years with suspected brain infections from a prospective observational study conducted in Vietnam. We fitted a logistic regression diagnostic model for TBM status, with unknown values estimated via a latent class model on three mycobacterial tests: Ziehl-Neelsen smear, Mycobacterial culture, and GeneXpert. We additionally re-evaluated mycobacterial test performance, estimated individual mycobacillary burden, and quantified the reduction in TBM risk after confirmatory tests were negative. We also fitted a simplified model and developed a scoring table for early screening. All models were compared and validated internally. RESULTS: Participants with HIV, miliary TB, long symptom duration, and high cerebrospinal fluid (CSF) lymphocyte count were more likely to have TBM. HIV and higher CSF protein were associated with higher mycobacillary burden. In the simplified model, HIV infection, clinical symptoms with long duration, and clinical or radiological evidence of extra-neural TB were associated with TBM At the cutpoints based on Youden's Index, the sensitivity and specificity in diagnosing TBM for our full and simplified models were 86.0% and 79.0%, and 88.0% and 75.0% respectively. CONCLUSION: Our diagnostic model shows reliable performance and can be developed as a decision assistant for clinicians to detect patients at high risk of TBM. Diagnosis of tuberculous meningitis is hampered by the lack of gold standard. We developed a diagnostic model using latent class analysis, combining confirmatory test results and risk factors. Models were accurate, well-calibrated, and can support both clinical practice and research.

Determination of Methanol, Acetaldehyde, and Ethyl Acetate in Thousand Folds of Ethanol Sample by Headspace Gas Chromatography with Mass Spectrometry.

Alcohol beverages have been widely consumed in several parts of the world. In this study, volatile organic compounds in alcoholic beverages including acetaldehyde, ethyl acetate, methanol, and higher ethanol were investigated and evaluated using a headspace gas chromatograph equipped with a mass spectrometer. This study evaluated the suitability of the chromatographic system, linearity, limit of detection, and limit of quantification, accuracy, and precision of the single and simultaneous determination of acetaldehyde, ethyl acetate, and methanol in thousand folds of ethanol. Results showed that the acetaldehyde concentration in local beer samples and local manual product liqueur samples ranged from 4.65 to 13.22 mg/L and from 5.55 to 75.96 mg/L, respectively, but in local industrial product liqueur samples, acetaldehyde was not detected. Methanol was only detected in a few local beer samples and locally manually produced liqueur samples within low concentrations. Ethyl acetate was only detected in all local beer samples, but it was not present in local industrial product liqueur samples.

Ultrasonic spray pyrolysis synthesis of TiO2/Al2O3 microspheres with enhanced removal efficiency towards toxic industrial dyes.

Developing low-cost and highly effective adsorbent materials to decolorate wastewater is still challenging in the industry. In this study, TiO2-modified Al2O3 microspheres with different TiO2 contents were produced by spray pyrolysis, which is rapid and easy to scale up. Results reveal that the modification of γ-Al2O3 with TiO2 reduced the crystallite size of Al2O3 and generated more active sites in the composite sample. The as-synthesized Al2O3-TiO2 microspheres were applied to remove anionic methyl orange (MO) and cationic rhodamine B (RB) dyes in an aqueous solution using batch and continuous flow column sorption processes. Results show that the Al2O3 microspheres modified with 15 wt% of TiO2 exhibited the maximum adsorbing capacity of ∼41.15 mg g-1 and ∼32.28 mg g-1 for MO and RB, respectively, exceeding the bare γ-Al2O3 and TiO2. The impact of environmental complexities on the material's reactivity for the organic pollutants was further delineated by adjusting the pH and adding coexisting ions. At pH ∼5.5, the TiO2/Al2O3 microspheres showed higher sorption selectivity towards MO. In the continuous flow column removal, the TiO2/Al2O3 microspheres achieved sorption capacities of ∼31 mg g-1 and ∼19 mg g-1 until the breakthrough point for MO and RB, respectively. The findings reveal that TiO2-modified Al2O3 microspheres were rapidly prepared by spray pyrolysis, and they effectively treated organic dyes in water in batch and continuous flow removal processes.

Seroprotection against tetanus in southern Vietnam.

BACKGROUND: Ongoing tetanus cases and sporadic outbreaks of vaccine-preventable diseases associated with routine vaccination programmes remain problems in many low and middle-income countries, including Vietnam. With no human-to-human transmission or natural immunity, tetanus antibody levels indicate both individual risk of tetanus and gaps in vaccination programmes. METHODS: To investigate gaps in immunity to tetanus in Vietnam, a country with a historically high level of tetanus vaccination coverage, tetanus antibodies were measure by ELISA from samples selected from a long-term serum bank, established for the purposes of general-population seroepidemiological investigations in southern Vietnam. Samples were selected from 10 provinces, focussing on age-groups targeted by national vaccination programmes for infants and pregnant women (Expanded Programme on Immunization, EPI, and Maternal and Neonatal Tetanus, MNT). RESULTS: Antibodies were measured from a total of 3864 samples. Highest tetanus antibody concentrations occurred in children under 4 years old, over 90 % of whom had protective levels. Approximately 70 % of children aged 7-12 years had protective antibody concentrations although there was variation among provinces. For infants and children, there were no significant differences in tetanus protection between males and females, but for adults aged 20-35 years, in five of the ten provinces surveyed, protection against tetanus was higher in females (p < 0.05) who are eligible for booster doses under the MNT programme. In seven of ten provinces, antibody concentrations were inversely related to age (p < 0.01) and protection of older individuals was generally low. CONCLUSION: Widespread immunity to tetanus toxoid is seen in infants and young children consistent with the high coverage rates reported for diptheria tetanus toxoid and pertussis (DTP) in Vietnam. However, the lower antibody concentrations seen in older children and men suggest reduced immunity to tetanus in populations not targeted by EPI and MNT programmes.

Kinetics of Neutralizing Antibodies against Omicron Variant in Vietnamese Healthcare Workers after Primary Immunization with ChAdOx1-S and Booster Immunization with BNT162b2.

We studied the development and persistence of neutralizing 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, including group 1 (G1, N = 21) and group 2 (G2; N = 26) without and with breakthrough Delta variant infection before booster immunization, respectively). The study participants had completed primary immunization with ChAdOx1-S and booster vaccination with BNT162b2. Neutralizing antibodies were measured using a surrogate virus neutralization assay. Of the 21 study participants in G1, neutralizing 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 neutralizing antibodies to the study viruses at week 2 post booster dose. Of the 26 study participants in G2, neutralizing 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, neutralizing antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralizing activities against ancestral strain and Delta variant compared with those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasize the importance of the first booster dose in producing cross-neutralizing antibodies against Omicron variant. A second booster to maintain long-term vaccine effectiveness against the currently circulating variants merits further research.

Immunogenicity of Oxford-AstraZeneca COVID-19 Vaccine in Vietnamese Health-Care Workers.

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

Influence of Strongyloides stercoralis Coinfection on the Presentation, Pathogenesis, and Outcome of Tuberculous Meningitis.

BACKGROUND: Helminth infections may modulate the inflammatory response to Mycobacterium tuberculosis and influence disease presentation and outcome. Strongyloides stercoralis is common among populations with high tuberculosis prevalence. Our aim was to determine whether S. stercoralis coinfection influenced clinical presentation, cerebrospinal fluid (CSF) inflammation, and outcome from tuberculous meningitis (TBM). METHODS: From June 2017 to December 2019, 668 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817 and NCT03100786), underwent pretreatment S. stercoralis testing by serology, stool microscopy, and/or stool polymerase chain reaction. Comparisons of pretreatment TBM severity, CSF inflammation (including cytokines), and 3-month clinical end points were performed in groups with or without active S. stercoralis infection. RESULTS: Overall, 9.4% participants (63 of 668) tested positive for S. stercoralis. Active S. stercoralis infection was significantly associated with reduced pretreatment CSF neutrophil counts (median [interquartile range], 3/µL [0-25/µL] vs 14 /µL [1-83/µL]; P = .04), and with reduced CSF interferon É£, interleukin 2, and tumor necrosis factor α concentrations (11.4 vs 56.0 pg/mL [P = .01], 33.1 vs 54.5 pg/mL [P = .03], and 4.5 vs 11.9 pg/mL [P = .02], respectively), compared with uninfected participants. Neurological complications by 3 months were significantly reduced in participants with active S. stercoralis infection compared with uninfected participants (3.8% [1 of 26] vs 30.0% [33 of 110], respectively; P = .01). CONCLUSIONS: S. stercoralis coinfection may modulate the intracerebral inflammatory response to M. tuberculosis and improve TBM clinical outcomes.

Wearable devices for remote monitoring of hospitalized patients with COVID-19 in Vietnam.

Patients with severe COVID-19 disease require monitoring with pulse oximetry as a minimal requirement. In many low- and middle- income countries, this has been challenging due to lack of staff and equipment. Wearable pulse oximeters potentially offer an attractive means to address this need, due to their low cost, battery operability and capacity for remote monitoring. Between July and October 2021, Ho Chi Minh City experienced its first major wave of SARS-CoV-2 infection, leading to an unprecedented demand for monitoring in hospitalized patients. We assess the feasibility of a continuous remote monitoring system for patients with COVID-19 under these circumstances as we implemented 2 different systems using wearable pulse oximeter devices in a stepwise manner across 4 departments.

An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam.

BACKGROUND: Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited. METHODS: We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing. FINDINGS: Between 11th-25th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8-33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.002). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms. INTERPRETATION: Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals. FUNDING: Wellcome and NIH/NIAID.

Absence of SARS-CoV-2 antibodies in pre-pandemic plasma from children and adults in Vietnam.

We tested pre-pandemic (2015--2019) plasma samples from 148 Vietnamese children and 100 Vietnamese adults at high risk of zoonotic infections for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive. The data thus demonstrated no evidence of prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietnam. No pre-existing cross-reactivity might explain Vietnam success of COVID-19 control.

Coxsackievirus A16 in Southern Vietnam.

Background: Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies. Materials and Methods: From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis. Results: Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96-31.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases. Conclusion: We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2-3 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development.

The Role of the Gastrointestinal Tract in Toxigenic Clostridium tetani Infection: A Case-Control Study.

Tetanus arises from wound contamination with Clostridium tetani, but approximately one fifth of patients have no discernable entry wound. Clostridium tetani is culturable from animal feces, suggesting the gastrointestinal tract could be an endogenous reservoir or direct-entry portal, but human data are lacking. In this study of 101 Vietnamese adults with tetanus and 29 hospitalized control subjects, admission stool samples were cultured for C. tetani. Anti-tetanus toxin antibodies were measured by ELISA. Clostridium tetani toxigenicity was evaluated using polymerase chain reaction and sequencing. Toxigenic C. tetani was cultured from stool samples in 50 of 100 (50%) tetanus cases and 12 of 28 (42.9%) control subjects (P = 0.50), and stool samples of 44 of 85 (52.4%) tetanus cases with clinically identified wounds compared with 6 of 15 (47.6%) patients without clinically identified wounds (P = 0.28). Nine of 12 (75%) control subjects with toxigenic C. tetani in their stool samples lacked protective antibody concentrations. These findings fail to show evidence of an association between gastrointestinal C. tetani and tetanus infection, but emphasize the importance of increasing vaccination coverage.

Redondoviridae: High Prevalence and Possibly Chronic Shedding in Human Respiratory Tract, But No Zoonotic Transmission.

Redondoviridae is a recently discovered DNA virus family consisting of two species, vientovirus and brisavirus. Here we used PCR amplification and sequencing to characterize redondoviruses in nasal/throat swabs collected longitudinally from a cohort of 58 individuals working with animals in Vietnam. We additionally analyzed samples from animals to which redondovirus DNA-positive participants were exposed. Redondoviruses were detected in approximately 60% of study participants, including 33% (30/91) of samples collected during episodes of acute respiratory disease and in 50% (29/58) of baseline samples (with no respiratory symptoms). Vientovirus (73%; 24/33) was detected more frequently in samples than brisaviruses (27%; 9/33). In the 23 participants with at least 2 redondovirus-positive samples among their longitudinal samples, 10 (43.5%) had identical redondovirus replication-gene sequences detected (sampling duration: 35-132 days). We found no identical redondovirus replication genes in samples from different participants, and no redondoviruses were detected in 53 pooled nasal/throat swabs collected from domestic animals. Phylogenetic analysis described no large-scale geographical clustering between viruses from Vietnam, the US, Spain, and China, indicating that redondoviruses are highly genetically diverse and have a wide geographical distribution. Collectively, our study provides novel insights into the Redondoviridae family in humans, describing a high prevalence, potentially associated with chronic shedding in the respiratory tract with lack of evidence of zoonotic transmission from close animal contacts. The tropism and potential pathogenicity of this viral family remain to be determined.

The Application of Sample Pooling for Mass Screening of SARS-CoV-2 in an Outbreak of COVID-19 in Vietnam.

We sampled nasal-pharyngeal throat swabs from 96,123 asymptomatic individuals at risk of SARS-CoV-2 infection, and generated 22,290 pools at collection, each containing samples from two to seven individuals. We detected SARS-CoV-2 in 24 pools, and confirmed the infection in 32 individuals after resampling and testing of 104 samples from positive pools. We completed the testing within 14 days. We would have required 64 days to complete the screening for the same number of individuals if we had based our testing strategy on individual testing. There was no difference in cycle threshold (Ct) values of pooled and individual samples. Thus, compared with individual sample testing, our approach did not compromise PCR sensitivity, but saved 77% of the resources. The present strategy might be applicable in settings, where there are shortages of reagents and the disease prevalence is low, but the demand for testing is high.

Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam.

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children's hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Automating the Generation of Antimicrobial Resistance Surveillance Reports: Proof-of-Concept Study Involving Seven Hospitals in Seven Countries.

BACKGROUND: Reporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel. OBJECTIVE: This study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly. METHODS: An offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language (R Project for Statistical Computing). The application can be run by double clicking on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested on Microsoft Windows 10 and 7 using open access example data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People's Democratic Republic, Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam. RESULTS: We developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyze their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and CSV formats). The data files could be those exported from WHONET or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from https://www.amass.website/. The participating hospitals tested the application and deposited their AMR surveillance reports in an open access data repository. CONCLUSIONS: The AMASS is a useful tool to support the generation and sharing of AMR surveillance reports.

A multi centre randomized open label trial of chloroquine for the treatment of adults with SARS-CoV-2 infection in Vietnam.

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