Nguyen Phu - Academia.edu (original) (raw)

Papers by Nguyen Phu

Research paper thumbnail of The integrated nutrition therapies for children with liver transplantation: an experience from Vietnam

Korean Journal of Transplantation, 2021

Background: Undernourishment was associated with the high-risk factor of post-transplantation inf... more Background: Undernourishment was associated with the high-risk factor of post-transplantation infection, mortality, mobility and length of hospital stay after pediatric liver transplant. Methods: The study described the integrated nutrition therapies for the patient by phases of transplantation. The case study was a 14-year-old girl was with primary biliary cirrhosis and gastrointestinal bleeding, esophageal varices in 108 Military Central Hospital, Vietnam. Her nutritional status was assessed by small for gestational age (SGA), BMI-forage (BAZ), and middle-upper-arm-circumference (MUAC). Results: Before the transplant, the patient's SGA was C, BAZ-1.63 SD, and MUAC 18.5 cm. She loss of appetite and anorexia. Dietitian used a combination of enteral and parenteral feeding for the patient to achieve the recommended intake. Her weight was stable until the surgery day. In the early post-transplant period, dietitians used both enteral and parenteral nutrition. The liquid diet with rice and water was applied on day 2 and day 3, 6-time per day, 50 mL each. From day 4 to day 7, she had nausea, vomit, and appetite disorder. The sum of energy was 900 kcal, with 1.7 g/kg of protein. From day 8, she felt less anorexia and vomiting. The oral nutrition increased gradually with four meals with porridge, and two formulas enriched BCAA. The total energy was 1,582.7 kcal, and she received 1.6 g/kg protein. SGA was B-level. From day 14, the intake of protein increased to 2.3 g/kg, with sources from beans, poultry, egg, fish, and vegetables. The six-meal diet was maintained (soups, rice, and formulas). From day 21, the protein diet at 2.4 g/kg was maintained. Sixty days after transplant, the liver function improved, the patient gained 37.5 kg, SGA B, BAZ-1.56 SD, and MUAC 20.0 cm. Conclusions: Nutrition management planning based on three stages of liver transplantation was essential for pediatric patients. The suitable diet with the patient's eating habits showed positive effects on liver function and improved the children's nutritional status.

Research paper thumbnail of Low Iodine Diet for Postoperative Patients with Thyroid Cancer in Vietnam

Biomedical Journal of Scientific & Technical Research, 2019

Low iodine diet and radioactive iodine therapy are required for differentiated thyroid cancer (DT... more Low iodine diet and radioactive iodine therapy are required for differentiated thyroid cancer (DTC) patients after thyroidectomy. Vietnam has inadequate data on the amounts of iodine in food. This study aims to provide the recommendation of the amount of iodine in low iodine diet and provide general instructions of low-iodine diet (LID) for Vietnamese. Result: Daily iodine intake of 50µg was recommended for low iodine diet. A two-week low iodine diet was recommended for DTC. The general instructions of restricted iodine diet: a. Restricted all type of seaweed and seafood. b. The freshwater food is acceptable. c. The maximum amount of consumption of meat is 300g per day d. The maximum amount of consumption of grains (rice) is 300g per day e. The maximum amount of consumption of fruits and vegetables is 400g per day. Conclusion: Two weeks of 50µg daily iodine intake was favored for low iodine diet. Development of Vietnamese databases on Iodine in foods is important to standardize the guideline of low-iodine dietary for Vietnamese.

Research paper thumbnail of Nghiên cứu chế biến dung dịch cao năng lượng nuôi ăn cho bệnh nhân qua ống thông dạ dày tại Bệnh viên Trung ương Quân đội 108

Tạp chí Y Dược Lâm sàng 108, Dec 1, 2022

Bệnh viện Trung ương Quân đội 108 Tóm tắt  Mục tiêu: Nghiên cứu chế biến dung dịch cao năng lượn... more Bệnh viện Trung ương Quân đội 108 Tóm tắt  Mục tiêu: Nghiên cứu chế biến dung dịch cao năng lượng nuôi ăn bệnh nhân qua ống thông dạ dày và đánh giá các tiêu chuẩn dựa trên các tiêu chí: Giá trị dinh dưỡng, hóa lý, vi sinh vật của dung dịch cao năng lượng so với sản phẩm Nutrison. Đối tượng và phương pháp: Phân tích, mô tả trên các mẫu thực phẩm có sẵn theo mùa, các thành phần của công thức dung dịch được tính theo bảng tính Excel dựa trên bảng thành phần hóa học thực phẩm Việt Nam năm 2007, kiểm nghiệm dung dịch thực tế về các chất dinh dưỡng tại Viện Dinh dưỡng Quốc gia. Kết quả: Công thức dung dịch nuôi ăn cao năng lượng tại bệnh viện Trung ương Quân đội 108, bao gồm: Gạo tẻ 120g, đậu xanh 50g, trứng gà 100g, rau xanh 100g, bột dinh dưỡng 50g, dầu ăn 6g, sữa bột 76g với tổng mức năng lượng đạt được 1020 Kcal, với đậm độ năng lượng là 1,02kcal/ml dung dịch, tỷ lệ các chất sinh năng lượng là P:L:G = 18:29:53. Kết luận: Dung dịch cao năng lượng nuôi ăn qua ống thông đảm bảo yêu cầu về mức năng lượng, giá trị dinh dưỡng, chỉ số hóa lý và vi sinh vật, an toàn vệ sinh thực phẩm so với dung dịch Nutrison, khuyến nghị Viện Dinh dưỡng và Bộ Y tế. Từ khóa: Dung dịch cao năng lượng, nuôi ăn qua ống thông dạ dày.

Research paper thumbnail of An Ultrastructural Study of the Brain in Fatal Plasmodium Falciparum Malaria

The American Journal of Tropical Medicine and Hygiene, 2003

Cerebral malaria (CM) is a major cause of death in severe Plasmodium falciparum malaria. We prese... more Cerebral malaria (CM) is a major cause of death in severe Plasmodium falciparum malaria. We present quantitative electron microscopic findings of the neuropathologic features in a prospective clinicopathologic study of 65 patients who died of severe malaria in Thailand and Vietnam. Sequestration of parasitized red blood cells (PRBCs) in cerebral microvessels was significantly higher in the brains of patients with CM compared with those with non-cerebral malaria (NCM) in all parts of the brain (cerebrum, cerebellum, and medulla oblongata). There was a hierarchy of sequestration with more in the cerebrum and cerebellum than the brain stem. When cerebral sequestration was compared with the peripheral parasitemia pre mortem, there were 26.6 times more PRBCs in the brain microvasculature than in the peripheral blood. The sequestration index was significantly higher in CM patients (median ‫ס‬ 50.7) than in NCM patients (median ‫ס‬ 6.9) (P ‫ס‬ 0.042). The degree of sequestration of P. falciparum-infected erythrocytes in cerebral microvessels is quantitatively associated with pre-mortem coma.

Research paper thumbnail of Adjunctive dexamethasone for the treatment of HIV-uninfected adults with tuberculous meningitis stratified by Leukotriene A4 hydrolase genotype (LAST ACT): Study protocol for a randomised double blind placebo controlled non-inferiority trial

Wellcome open research, 2018

Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous menin... more Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H), predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected individuals. The primary aim of this study is to determine whether LTA4H genotype determines benefit or harm from adjunctive dexamethasone in HIV-uninfected Vietnamese adults with TBM. The secondary aim is to investigate alternative management strategies in individuals who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. We will perform a parallel group, randomised (1:1), double blind, placebo-controlled, multi-centre Phase III non-inferiority trial, comparing dexamethasone versus placebo for 6-8 weeks in addition to standard anti-tuberculosis treatment in HIV-uninfected patients with TBM stratified by LTA4...

Research paper thumbnail of Improving the microbiological diagnosis of tuberculous meningitis: A prospective, international, multicentre comparison of conventional and modified Ziehl-Neelsen stain, GeneXpert, and culture of cerebrospinal fluid

The Journal of infection, Jan 12, 2018

Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests a... more Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests are insensitive. Recent reports suggest simple modifications to conventional cerebrospinal fluid (CSF) Ziehl-Neelsen (ZN) staining may greatly improve sensitivity. We sought to define the performance of modified and conventional ZN stain for TBM diagnosis. In hospitals in Vietnam, South Africa and Indonesia we conducted a prospective study of modified ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF in adults with suspected TBM. A total of 618 individuals were enrolled across 3 sites. Compared with the TBM clinical diagnostic gold standard for research (definite probable or possible TBM), sensitivity of conventional ZN and modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the difference between tests), compared with culture 31.8% and Xpert 25.1%. Using culture as a reference, sensitivities of conventional ZN, modified ZN with cytospi...

Research paper thumbnail of Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial

Trials, Jan 4, 2018

Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP... more Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam. This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admis...

Research paper thumbnail of {"__content__"=>"Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in ClinicalIsolates from Sputum, Oxidative Stress, and Iron Deficiency.", "i"=>{"__content__"=>"Mycobacterium tuberculosis"}}

Frontiers in microbiology, 2017

Mycobacteria have several unique cellular characteristics, such as multiple cell envelope layers,... more Mycobacteria have several unique cellular characteristics, such as multiple cell envelope layers, elongation at cell poles, asymmetric cell division, and accumulation of intracytoplasmic lipid inclusions, which contributes to their survival under stress conditions. However, the understanding of these characteristics in clinical() isolates and under host stress is limited. We previously reported the influence of host stress on the cell length distribution in a large set of clinicalisolates (= 158). Here, we investigate the influence of host stress on the cellular ultrastructure of few clinicalisolates (= 8) from that study. The purpose of this study is to further understand the influence of host stress on the cellular adaptations of clinicalisolates.We selected fewisolates (= 8) for analyzing the cellular ultrastructurein sputum and understress conditions by transmission electron microscopy. The cellular adaptations ofin sputum were correlated with the ultrastructure of antibiotic se...

Research paper thumbnail of Prognostic Models for 9-Month Mortality in Tuberculous Meningitis

Clinical Infectious Diseases, 2017

Background. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. ... more Background. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. Methods. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Webbased app (https://thaole.shinyapps.io/tbmapp/). Results. 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIVinfected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. Conclusions. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.

Research paper thumbnail of Central Nervous System Infection Diagnosis by Next-Generation Sequencing: A Glimpse Into the Future?

Open Forum Infectious Diseases, 2017

Japanese encephalitis virus was detected by deep sequencing for the first time in urine of a 16-y... more Japanese encephalitis virus was detected by deep sequencing for the first time in urine of a 16-year-old boy with encephalitis. Seroconversion and polymerase chain reaction analysis confirmed the metagenomics finding. Urine is useful for diagnosis of flaviviral encephalitis, whereas deep sequencing can be a panpathogen assay for the diagnosis of life-threatening infectious diseases.

Research paper thumbnail of Angiostrongylus cantonensis is an Important Cause of Eosinophilic Meningitis in Southern Vietnam

Clinical Infectious Diseases, 2017

We utilized polymerase chain reaction (PCR) to demonstrate that Angiostrongylus cantonensis was r... more We utilized polymerase chain reaction (PCR) to demonstrate that Angiostrongylus cantonensis was responsible for 67.3% of 55 cases of eosinophilic meningitis from a cohort of 1,690 adult patients with CNS infection at a tertiary hospital in southern Vietnam. Longer duration of illness, depressed consciousness, and peripheral blood eosinophilia were associated with PCR positivity.

Research paper thumbnail of Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

PloS one, 2017

Clinical trials in severe falciparum malaria require a large sample size to detect clinically mea... more Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortal...

Research paper thumbnail of Improving the radical cure of vivax malaria (IMPROV)

http://isrctn.com/, 2016

Background: Plasmodium vivax malaria is a major cause of morbidity and recognised as an important... more Background: Plasmodium vivax malaria is a major cause of morbidity and recognised as an important contributor to mortality in some endemic areas. The current recommended treatment regimen for the radical cure of P. vivax includes a schizontocidal antimalarial, usually chloroquine, combined with a 14 day regimen of primaquine. The long treatment course frequently results in poor adherence and effectiveness. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising safety. The proposed multicentre randomised clinical trial aims to provide evidence across a variety of endemic settings on the safety and efficacy of high dose short course primaquine in glucose-6-phosphate-dehydrogenase (G6PD) normal patients. Design: This study is designed as a placebo controlled, double blinded, randomized trial in four countries: Indonesia, Vietnam, Afghanistan and Ethiopia. G6PD normal patients diagnosed with vivax malaria are randomized to receive either 7 or 14 days high dose primaquine or placebo. G6PD deficient (G6PDd) patients are allocated to weekly primaquine doses for 8 weeks. All treatment is directly observed and recurrent episodes are treated with the same treatment than allocated at the enrolment episode. Patients are followed daily until completion of treatment, weekly until 8 weeks and then monthly until 1 year after initiation of the treatment. The primary endpoint is the incidence rate (per person year) of symptomatic recurrent P. vivax parasitaemia over 12 months of follow-up, for all individuals, controlling for site, comparing the 7 versus 14-day primaquine treatment arms. Secondary endpoints are other efficacy measures such as incidence risk at different time points. Further endpoints are risks of haemolysis and severe adverse events. Discussion: This study has been approved by relevant institutional ethics committees in the UK and Australia, and all participating countries. Results will be disseminated to inform P. vivax malaria treatment policy through peer-reviewed publications and academic presentations. Findings will contribute to a better understanding of the risks and benefits of primaquine which is crucial in persuading policy makers as well as clinicians of the importance of radical cure of vivax malaria, contributing to decreased transmission and a reduce parasite reservoir.

Research paper thumbnail of A Randomized Comparison of Chloroquine Versus Dihydroartemisinin-Piperaquine for the Treatment of Plasmodium vivax Infection in Vietnam

The American journal of tropical medicine and hygiene, Apr 8, 2016

A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolle... more A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolled in a prospective, open-label, randomized trial to receive either chloroquine or dihydroartemisinin-piperaquine (DHA-PPQ). The proportions of patients with adequate clinical and parasitological responses were 47% in the chloroquine arm (31 of 65 patients) and 66% in the DHA-PPQ arm (42 of 63 patients) in the Kaplan-Meier intention-to-treat analysis (absolute difference 19%, 95% confidence interval = 0-37%), thus establishing non-inferiority of DHA-PPQ. Fever clearance time (median 24 versus 12 hours, P = 0.02), parasite clearance time (median 36 versus 18 hours, P < 0.001), and parasite clearance half-life (mean 3.98 versus 1.80 hours, P…

Research paper thumbnail of LTA4H Genotype Is Associated with Susceptibility to Bacterial Meningitis but Is Not a Critical Determinant of Outcome

PLOS ONE, 2015

Adjunctive dexamethasone saves lives in the treatment of tuberculous meningitis but this response... more Adjunctive dexamethasone saves lives in the treatment of tuberculous meningitis but this response is influenced by the patient's LTA4H genotype. Despite less certain benefit, adjunctive dexamethasone is also frequently used in the treatment of pyogenic bacterial meningitis, but the influence of LTA4H genotype on outcomes has not been previously investigated. We genotyped the LTA4H promoter region SNP (rs17525495) in 390 bacterial meningitis patients and 751 population controls. rs17525495 was associated with susceptibility to bacteriologically confirmed bacterial meningitis (P = 0.01, OR 1.27 95% confidence interval [CI] 1.05-1.54) but did not influence clinical presentation, disease severity or survival following dexamethasone treatment.

Research paper thumbnail of Rapid Clinical Assessment to Facilitate the Triage of Adults with Falciparum Malaria, a Retrospective Analysis

PLoS ONE, 2014

Background: Most adults dying from falciparum malaria will die within 48 hours of their hospitali... more Background: Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. Methods: We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage. Results: If present on admission, shock, oligo-anuria, hypo-or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm's positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI) 97.8-99.9) and for survival to discharge 96.9% (95% CI 94.3-98.5). In the 712 patients receiving artesunate, the algorithm's positive predictive value for survival to 48 hours was 100% (95% CI 97.3-100) and to discharge was 98.5% (95% CI 94.8-99.8). Conclusions: Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.

Research paper thumbnail of Viral Aetiology of Central Nervous System Infections in Adults Admitted to a Tertiary Referral Hospital in Southern Vietnam over 12 Years

PLoS Neglected Tropical Diseases, 2014

Background: Central nervous system (CNS) infections are important diseases in both children and a... more Background: Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management. Methodology/Principal Findings: Study was conducted at the Hospital for Tropical Diseases in Ho Chi Minh City, a primary, secondary, and tertiary referral hospital for all southern provinces of Vietnam. Between December 1996 and May 2008, patients with CNS infections of presumed viral origin were enrolled. Laboratory diagnostics consisted of molecular and serological tests targeted at 14 meningitis/encephalitis-associated viruses. Of 291 enrolled patients, fatal outcome and neurological sequelae were recorded in 10% (28/291) and 27% (78/291), respectively. Mortality was especially high (9/19, 47%) amongst those with confirmed herpes simplex encephalitis which is attributed to the limited availability of intravenous acyclovir/valacyclovir. Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses were the most common viruses detected, responsible for 36 (12%), 19 (6.5%), 19 (6.5%) and 8 (2.7%) respectively, followed by rubella virus (6, 2%), varicella zoster virus (5, 1.7%), mumps virus (2, 0.7%), cytomegalovirus (1, 0.3%), and rabies virus (1, 0.3%). Conclusions/Significance: Viral infections of the CNS in adults in Vietnam are associated with high morbidity and mortality. Despite extensive laboratory testing, 68% of the patients remain undiagnosed. Together with our previous reports, the data confirm that Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses are the leading identified causes of CNS viral infections in Vietnam, suggest that the majority of morbidity/mortality amongst patients with a confirmed/ probable diagnosis is preventable by adequate vaccination/treatment, and are therefore of public health significance.

Research paper thumbnail of A Controlled Trial of Artemether or Quinine in Vietnamese Adults with Severe Falciparum Malaria

New England Journal of Medicine, 1996

Background Artemisinin (qinghaosu) and its derivatives are rapidly effective antimalarial drugs d... more Background Artemisinin (qinghaosu) and its derivatives are rapidly effective antimalarial drugs derived from a Chinese plant. Preliminary studies suggest that these drugs may be more effective than quinine in the treatment of severe malaria. We studied artemether in Vietnam, where Plasmodium falciparum has reduced sensitivity to quinine. Methods We conducted a randomized, doubleblind trial in 560 adults with severe falciparum malaria. Two hundred seventy-six received intramuscular quinine dihydrochloride (20 mg per kilogram of body weight followed by 10 mg per kilogram every eight hours), and 284 received intramuscular artemether (4 mg per kilogram followed by 2 mg per kilogram every eight hours). Both drugs were given for a minimum of 72 hours. Results There were 36 deaths in the artemether group (13 percent) and 47 in the quinine group (17 percent; P ϭ 0.16; relative risk of death in the patients given artemether, 0.74; 95 percent confidence interval, 0.5 to 1.11). The parasites were cleared more quickly from the blood in the artemether group (mean, 72 vs. 90 hours; P Ͻ 0.001); however, in this group fever resolved more slowly (127 vs. 90 hours, P Ͻ 0.001), the time to recovery from coma was longer (66 vs. 48 hours, P ϭ 0.003), and the hospitalization was longer (288 vs. 240 hours, P ϭ 0.005). Quinine treatment was associated with a higher risk of hypoglycemia (relative risk, 2.7; 95 percent confidence interval, 1.7 to 4.4; P Ͻ 0.001), but there were no other serious side effects in either group. Conclusions Artemether is a satisfactory alternative to quinine for the treatment of severe malaria in adults. (

Research paper thumbnail of A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria

Malaria Journal, 2013

Background: Plasma angiopoietin (Ang)-2 is associated with disease severity and mortality in adul... more Background: Plasma angiopoietin (Ang)-2 is associated with disease severity and mortality in adults and children with falciparum malaria. However the mechanism of action of the angiopoietins in fatal malaria is unclear. This study aimed to determine whether the expression of Ang-1 and Ang-2 and their receptor Tie-2 in cerebral endothelial or parenchymal cells was specific to cerebral malaria (CM), correlated with coma or other severe clinical features, and whether plasma and CSF levels of these markers correlated with the clinical and neuropathological features of severe and fatal malaria in Vietnamese adults. Methods: Immunohistochemistry was performed for Ang-1, Ang-2 and Tie-2 on post-mortem brain tissue from fatal malaria cases and controls. Quantitative ELISA for plasma and cerebrospinal fluid levels of Ang-1, Ang-2 and Tie-2 was done to compare fatal cases with surviving patients from the same study. Results: Immunohistochemistry revealed significant differences in expression in endothelial and parenchymal cells compared to controls. However there was no significant difference in expression of these markers on endothelial cells, astroglial cells or neurons between CM and non-cerebral malaria cases. Immunostaining of Ang-1, Ang-2 and Tie-2 was also not associated with Plasmodium falciparum-infected erythrocyte sequestration in the brain. However Ang-1 and Ang-2 expression in neurons was significantly correlated with the incidence of microscopic haemorrhages. Plasma levels of Ang-2 and Ang-2/Ang-1 ratio were associated with the number of severe malaria complications and were significant and independent predictors of metabolic acidosis and fatal outcome. Conclusions: The independent prognostic significance of Ang-2 and the Ang-2/Ang-1 ratio in severe malaria was confirmed, although immunohistochemistry in fatal cases did not reveal increased expression on brain endothelium in cerebral versus non-cerebral cases. Activation of the Ang-Tie-2 pathway in severe malaria is therefore related to acidosis, number of severity criteria and outcome, but is not a specific event in the brain during cerebral malaria.

Research paper thumbnail of Randomized controlled trial of artesunate or artemether in Vietnamese adults with severe falciparum malaria

Malaria Journal, 2010

Background Both artemether and artesunate have been shown to be superior to quinine for the treat... more Background Both artemether and artesunate have been shown to be superior to quinine for the treatment of severe falciparum malaria in Southeast Asian adults, although the magnitude of the superiority has been greater for artesunate than artemether. These two artemisinin derivatives had not been compared in a randomized trial. Methods A randomized double blind trial in 370 adults with severe falciparum malaria; 186 received intramuscular artesunate (2.4 mg/kg immediately followed by 1.2 mg/kg at 12 hours then 24 hours then daily) and 184 received intramuscular artemether (3.6 mg per kilogram immediately followed by 1.8 mg per kilogram daily) was conducted in Viet Nam. Both drugs were given for a minimum of 72 hours. Results There were 13 deaths in the artesunate group (7 percent) and 24 in the artemether group (13 percent); P = 0.052; relative risk of death in the patients given artesunate, 0.54; (95 percent confidence interval 0.28-1.02). Parasitaemia declined more rapidly in the ar...

Research paper thumbnail of The integrated nutrition therapies for children with liver transplantation: an experience from Vietnam

Korean Journal of Transplantation, 2021

Background: Undernourishment was associated with the high-risk factor of post-transplantation inf... more Background: Undernourishment was associated with the high-risk factor of post-transplantation infection, mortality, mobility and length of hospital stay after pediatric liver transplant. Methods: The study described the integrated nutrition therapies for the patient by phases of transplantation. The case study was a 14-year-old girl was with primary biliary cirrhosis and gastrointestinal bleeding, esophageal varices in 108 Military Central Hospital, Vietnam. Her nutritional status was assessed by small for gestational age (SGA), BMI-forage (BAZ), and middle-upper-arm-circumference (MUAC). Results: Before the transplant, the patient's SGA was C, BAZ-1.63 SD, and MUAC 18.5 cm. She loss of appetite and anorexia. Dietitian used a combination of enteral and parenteral feeding for the patient to achieve the recommended intake. Her weight was stable until the surgery day. In the early post-transplant period, dietitians used both enteral and parenteral nutrition. The liquid diet with rice and water was applied on day 2 and day 3, 6-time per day, 50 mL each. From day 4 to day 7, she had nausea, vomit, and appetite disorder. The sum of energy was 900 kcal, with 1.7 g/kg of protein. From day 8, she felt less anorexia and vomiting. The oral nutrition increased gradually with four meals with porridge, and two formulas enriched BCAA. The total energy was 1,582.7 kcal, and she received 1.6 g/kg protein. SGA was B-level. From day 14, the intake of protein increased to 2.3 g/kg, with sources from beans, poultry, egg, fish, and vegetables. The six-meal diet was maintained (soups, rice, and formulas). From day 21, the protein diet at 2.4 g/kg was maintained. Sixty days after transplant, the liver function improved, the patient gained 37.5 kg, SGA B, BAZ-1.56 SD, and MUAC 20.0 cm. Conclusions: Nutrition management planning based on three stages of liver transplantation was essential for pediatric patients. The suitable diet with the patient's eating habits showed positive effects on liver function and improved the children's nutritional status.

Research paper thumbnail of Low Iodine Diet for Postoperative Patients with Thyroid Cancer in Vietnam

Biomedical Journal of Scientific & Technical Research, 2019

Low iodine diet and radioactive iodine therapy are required for differentiated thyroid cancer (DT... more Low iodine diet and radioactive iodine therapy are required for differentiated thyroid cancer (DTC) patients after thyroidectomy. Vietnam has inadequate data on the amounts of iodine in food. This study aims to provide the recommendation of the amount of iodine in low iodine diet and provide general instructions of low-iodine diet (LID) for Vietnamese. Result: Daily iodine intake of 50µg was recommended for low iodine diet. A two-week low iodine diet was recommended for DTC. The general instructions of restricted iodine diet: a. Restricted all type of seaweed and seafood. b. The freshwater food is acceptable. c. The maximum amount of consumption of meat is 300g per day d. The maximum amount of consumption of grains (rice) is 300g per day e. The maximum amount of consumption of fruits and vegetables is 400g per day. Conclusion: Two weeks of 50µg daily iodine intake was favored for low iodine diet. Development of Vietnamese databases on Iodine in foods is important to standardize the guideline of low-iodine dietary for Vietnamese.

Research paper thumbnail of Nghiên cứu chế biến dung dịch cao năng lượng nuôi ăn cho bệnh nhân qua ống thông dạ dày tại Bệnh viên Trung ương Quân đội 108

Tạp chí Y Dược Lâm sàng 108, Dec 1, 2022

Bệnh viện Trung ương Quân đội 108 Tóm tắt  Mục tiêu: Nghiên cứu chế biến dung dịch cao năng lượn... more Bệnh viện Trung ương Quân đội 108 Tóm tắt  Mục tiêu: Nghiên cứu chế biến dung dịch cao năng lượng nuôi ăn bệnh nhân qua ống thông dạ dày và đánh giá các tiêu chuẩn dựa trên các tiêu chí: Giá trị dinh dưỡng, hóa lý, vi sinh vật của dung dịch cao năng lượng so với sản phẩm Nutrison. Đối tượng và phương pháp: Phân tích, mô tả trên các mẫu thực phẩm có sẵn theo mùa, các thành phần của công thức dung dịch được tính theo bảng tính Excel dựa trên bảng thành phần hóa học thực phẩm Việt Nam năm 2007, kiểm nghiệm dung dịch thực tế về các chất dinh dưỡng tại Viện Dinh dưỡng Quốc gia. Kết quả: Công thức dung dịch nuôi ăn cao năng lượng tại bệnh viện Trung ương Quân đội 108, bao gồm: Gạo tẻ 120g, đậu xanh 50g, trứng gà 100g, rau xanh 100g, bột dinh dưỡng 50g, dầu ăn 6g, sữa bột 76g với tổng mức năng lượng đạt được 1020 Kcal, với đậm độ năng lượng là 1,02kcal/ml dung dịch, tỷ lệ các chất sinh năng lượng là P:L:G = 18:29:53. Kết luận: Dung dịch cao năng lượng nuôi ăn qua ống thông đảm bảo yêu cầu về mức năng lượng, giá trị dinh dưỡng, chỉ số hóa lý và vi sinh vật, an toàn vệ sinh thực phẩm so với dung dịch Nutrison, khuyến nghị Viện Dinh dưỡng và Bộ Y tế. Từ khóa: Dung dịch cao năng lượng, nuôi ăn qua ống thông dạ dày.

Research paper thumbnail of An Ultrastructural Study of the Brain in Fatal Plasmodium Falciparum Malaria

The American Journal of Tropical Medicine and Hygiene, 2003

Cerebral malaria (CM) is a major cause of death in severe Plasmodium falciparum malaria. We prese... more Cerebral malaria (CM) is a major cause of death in severe Plasmodium falciparum malaria. We present quantitative electron microscopic findings of the neuropathologic features in a prospective clinicopathologic study of 65 patients who died of severe malaria in Thailand and Vietnam. Sequestration of parasitized red blood cells (PRBCs) in cerebral microvessels was significantly higher in the brains of patients with CM compared with those with non-cerebral malaria (NCM) in all parts of the brain (cerebrum, cerebellum, and medulla oblongata). There was a hierarchy of sequestration with more in the cerebrum and cerebellum than the brain stem. When cerebral sequestration was compared with the peripheral parasitemia pre mortem, there were 26.6 times more PRBCs in the brain microvasculature than in the peripheral blood. The sequestration index was significantly higher in CM patients (median ‫ס‬ 50.7) than in NCM patients (median ‫ס‬ 6.9) (P ‫ס‬ 0.042). The degree of sequestration of P. falciparum-infected erythrocytes in cerebral microvessels is quantitatively associated with pre-mortem coma.

Research paper thumbnail of Adjunctive dexamethasone for the treatment of HIV-uninfected adults with tuberculous meningitis stratified by Leukotriene A4 hydrolase genotype (LAST ACT): Study protocol for a randomised double blind placebo controlled non-inferiority trial

Wellcome open research, 2018

Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous menin... more Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H), predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected individuals. The primary aim of this study is to determine whether LTA4H genotype determines benefit or harm from adjunctive dexamethasone in HIV-uninfected Vietnamese adults with TBM. The secondary aim is to investigate alternative management strategies in individuals who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. We will perform a parallel group, randomised (1:1), double blind, placebo-controlled, multi-centre Phase III non-inferiority trial, comparing dexamethasone versus placebo for 6-8 weeks in addition to standard anti-tuberculosis treatment in HIV-uninfected patients with TBM stratified by LTA4...

Research paper thumbnail of Improving the microbiological diagnosis of tuberculous meningitis: A prospective, international, multicentre comparison of conventional and modified Ziehl-Neelsen stain, GeneXpert, and culture of cerebrospinal fluid

The Journal of infection, Jan 12, 2018

Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests a... more Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests are insensitive. Recent reports suggest simple modifications to conventional cerebrospinal fluid (CSF) Ziehl-Neelsen (ZN) staining may greatly improve sensitivity. We sought to define the performance of modified and conventional ZN stain for TBM diagnosis. In hospitals in Vietnam, South Africa and Indonesia we conducted a prospective study of modified ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF in adults with suspected TBM. A total of 618 individuals were enrolled across 3 sites. Compared with the TBM clinical diagnostic gold standard for research (definite probable or possible TBM), sensitivity of conventional ZN and modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the difference between tests), compared with culture 31.8% and Xpert 25.1%. Using culture as a reference, sensitivities of conventional ZN, modified ZN with cytospi...

Research paper thumbnail of Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial

Trials, Jan 4, 2018

Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP... more Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam. This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admis...

Research paper thumbnail of {"__content__"=>"Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in ClinicalIsolates from Sputum, Oxidative Stress, and Iron Deficiency.", "i"=>{"__content__"=>"Mycobacterium tuberculosis"}}

Frontiers in microbiology, 2017

Mycobacteria have several unique cellular characteristics, such as multiple cell envelope layers,... more Mycobacteria have several unique cellular characteristics, such as multiple cell envelope layers, elongation at cell poles, asymmetric cell division, and accumulation of intracytoplasmic lipid inclusions, which contributes to their survival under stress conditions. However, the understanding of these characteristics in clinical() isolates and under host stress is limited. We previously reported the influence of host stress on the cell length distribution in a large set of clinicalisolates (= 158). Here, we investigate the influence of host stress on the cellular ultrastructure of few clinicalisolates (= 8) from that study. The purpose of this study is to further understand the influence of host stress on the cellular adaptations of clinicalisolates.We selected fewisolates (= 8) for analyzing the cellular ultrastructurein sputum and understress conditions by transmission electron microscopy. The cellular adaptations ofin sputum were correlated with the ultrastructure of antibiotic se...

Research paper thumbnail of Prognostic Models for 9-Month Mortality in Tuberculous Meningitis

Clinical Infectious Diseases, 2017

Background. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. ... more Background. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. Methods. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Webbased app (https://thaole.shinyapps.io/tbmapp/). Results. 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIVinfected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. Conclusions. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.

Research paper thumbnail of Central Nervous System Infection Diagnosis by Next-Generation Sequencing: A Glimpse Into the Future?

Open Forum Infectious Diseases, 2017

Japanese encephalitis virus was detected by deep sequencing for the first time in urine of a 16-y... more Japanese encephalitis virus was detected by deep sequencing for the first time in urine of a 16-year-old boy with encephalitis. Seroconversion and polymerase chain reaction analysis confirmed the metagenomics finding. Urine is useful for diagnosis of flaviviral encephalitis, whereas deep sequencing can be a panpathogen assay for the diagnosis of life-threatening infectious diseases.

Research paper thumbnail of Angiostrongylus cantonensis is an Important Cause of Eosinophilic Meningitis in Southern Vietnam

Clinical Infectious Diseases, 2017

We utilized polymerase chain reaction (PCR) to demonstrate that Angiostrongylus cantonensis was r... more We utilized polymerase chain reaction (PCR) to demonstrate that Angiostrongylus cantonensis was responsible for 67.3% of 55 cases of eosinophilic meningitis from a cohort of 1,690 adult patients with CNS infection at a tertiary hospital in southern Vietnam. Longer duration of illness, depressed consciousness, and peripheral blood eosinophilia were associated with PCR positivity.

Research paper thumbnail of Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

PloS one, 2017

Clinical trials in severe falciparum malaria require a large sample size to detect clinically mea... more Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortal...

Research paper thumbnail of Improving the radical cure of vivax malaria (IMPROV)

http://isrctn.com/, 2016

Background: Plasmodium vivax malaria is a major cause of morbidity and recognised as an important... more Background: Plasmodium vivax malaria is a major cause of morbidity and recognised as an important contributor to mortality in some endemic areas. The current recommended treatment regimen for the radical cure of P. vivax includes a schizontocidal antimalarial, usually chloroquine, combined with a 14 day regimen of primaquine. The long treatment course frequently results in poor adherence and effectiveness. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising safety. The proposed multicentre randomised clinical trial aims to provide evidence across a variety of endemic settings on the safety and efficacy of high dose short course primaquine in glucose-6-phosphate-dehydrogenase (G6PD) normal patients. Design: This study is designed as a placebo controlled, double blinded, randomized trial in four countries: Indonesia, Vietnam, Afghanistan and Ethiopia. G6PD normal patients diagnosed with vivax malaria are randomized to receive either 7 or 14 days high dose primaquine or placebo. G6PD deficient (G6PDd) patients are allocated to weekly primaquine doses for 8 weeks. All treatment is directly observed and recurrent episodes are treated with the same treatment than allocated at the enrolment episode. Patients are followed daily until completion of treatment, weekly until 8 weeks and then monthly until 1 year after initiation of the treatment. The primary endpoint is the incidence rate (per person year) of symptomatic recurrent P. vivax parasitaemia over 12 months of follow-up, for all individuals, controlling for site, comparing the 7 versus 14-day primaquine treatment arms. Secondary endpoints are other efficacy measures such as incidence risk at different time points. Further endpoints are risks of haemolysis and severe adverse events. Discussion: This study has been approved by relevant institutional ethics committees in the UK and Australia, and all participating countries. Results will be disseminated to inform P. vivax malaria treatment policy through peer-reviewed publications and academic presentations. Findings will contribute to a better understanding of the risks and benefits of primaquine which is crucial in persuading policy makers as well as clinicians of the importance of radical cure of vivax malaria, contributing to decreased transmission and a reduce parasite reservoir.

Research paper thumbnail of A Randomized Comparison of Chloroquine Versus Dihydroartemisinin-Piperaquine for the Treatment of Plasmodium vivax Infection in Vietnam

The American journal of tropical medicine and hygiene, Apr 8, 2016

A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolle... more A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolled in a prospective, open-label, randomized trial to receive either chloroquine or dihydroartemisinin-piperaquine (DHA-PPQ). The proportions of patients with adequate clinical and parasitological responses were 47% in the chloroquine arm (31 of 65 patients) and 66% in the DHA-PPQ arm (42 of 63 patients) in the Kaplan-Meier intention-to-treat analysis (absolute difference 19%, 95% confidence interval = 0-37%), thus establishing non-inferiority of DHA-PPQ. Fever clearance time (median 24 versus 12 hours, P = 0.02), parasite clearance time (median 36 versus 18 hours, P < 0.001), and parasite clearance half-life (mean 3.98 versus 1.80 hours, P…

Research paper thumbnail of LTA4H Genotype Is Associated with Susceptibility to Bacterial Meningitis but Is Not a Critical Determinant of Outcome

PLOS ONE, 2015

Adjunctive dexamethasone saves lives in the treatment of tuberculous meningitis but this response... more Adjunctive dexamethasone saves lives in the treatment of tuberculous meningitis but this response is influenced by the patient's LTA4H genotype. Despite less certain benefit, adjunctive dexamethasone is also frequently used in the treatment of pyogenic bacterial meningitis, but the influence of LTA4H genotype on outcomes has not been previously investigated. We genotyped the LTA4H promoter region SNP (rs17525495) in 390 bacterial meningitis patients and 751 population controls. rs17525495 was associated with susceptibility to bacteriologically confirmed bacterial meningitis (P = 0.01, OR 1.27 95% confidence interval [CI] 1.05-1.54) but did not influence clinical presentation, disease severity or survival following dexamethasone treatment.

Research paper thumbnail of Rapid Clinical Assessment to Facilitate the Triage of Adults with Falciparum Malaria, a Retrospective Analysis

PLoS ONE, 2014

Background: Most adults dying from falciparum malaria will die within 48 hours of their hospitali... more Background: Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. Methods: We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage. Results: If present on admission, shock, oligo-anuria, hypo-or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm's positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI) 97.8-99.9) and for survival to discharge 96.9% (95% CI 94.3-98.5). In the 712 patients receiving artesunate, the algorithm's positive predictive value for survival to 48 hours was 100% (95% CI 97.3-100) and to discharge was 98.5% (95% CI 94.8-99.8). Conclusions: Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.

Research paper thumbnail of Viral Aetiology of Central Nervous System Infections in Adults Admitted to a Tertiary Referral Hospital in Southern Vietnam over 12 Years

PLoS Neglected Tropical Diseases, 2014

Background: Central nervous system (CNS) infections are important diseases in both children and a... more Background: Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management. Methodology/Principal Findings: Study was conducted at the Hospital for Tropical Diseases in Ho Chi Minh City, a primary, secondary, and tertiary referral hospital for all southern provinces of Vietnam. Between December 1996 and May 2008, patients with CNS infections of presumed viral origin were enrolled. Laboratory diagnostics consisted of molecular and serological tests targeted at 14 meningitis/encephalitis-associated viruses. Of 291 enrolled patients, fatal outcome and neurological sequelae were recorded in 10% (28/291) and 27% (78/291), respectively. Mortality was especially high (9/19, 47%) amongst those with confirmed herpes simplex encephalitis which is attributed to the limited availability of intravenous acyclovir/valacyclovir. Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses were the most common viruses detected, responsible for 36 (12%), 19 (6.5%), 19 (6.5%) and 8 (2.7%) respectively, followed by rubella virus (6, 2%), varicella zoster virus (5, 1.7%), mumps virus (2, 0.7%), cytomegalovirus (1, 0.3%), and rabies virus (1, 0.3%). Conclusions/Significance: Viral infections of the CNS in adults in Vietnam are associated with high morbidity and mortality. Despite extensive laboratory testing, 68% of the patients remain undiagnosed. Together with our previous reports, the data confirm that Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses are the leading identified causes of CNS viral infections in Vietnam, suggest that the majority of morbidity/mortality amongst patients with a confirmed/ probable diagnosis is preventable by adequate vaccination/treatment, and are therefore of public health significance.

Research paper thumbnail of A Controlled Trial of Artemether or Quinine in Vietnamese Adults with Severe Falciparum Malaria

New England Journal of Medicine, 1996

Background Artemisinin (qinghaosu) and its derivatives are rapidly effective antimalarial drugs d... more Background Artemisinin (qinghaosu) and its derivatives are rapidly effective antimalarial drugs derived from a Chinese plant. Preliminary studies suggest that these drugs may be more effective than quinine in the treatment of severe malaria. We studied artemether in Vietnam, where Plasmodium falciparum has reduced sensitivity to quinine. Methods We conducted a randomized, doubleblind trial in 560 adults with severe falciparum malaria. Two hundred seventy-six received intramuscular quinine dihydrochloride (20 mg per kilogram of body weight followed by 10 mg per kilogram every eight hours), and 284 received intramuscular artemether (4 mg per kilogram followed by 2 mg per kilogram every eight hours). Both drugs were given for a minimum of 72 hours. Results There were 36 deaths in the artemether group (13 percent) and 47 in the quinine group (17 percent; P ϭ 0.16; relative risk of death in the patients given artemether, 0.74; 95 percent confidence interval, 0.5 to 1.11). The parasites were cleared more quickly from the blood in the artemether group (mean, 72 vs. 90 hours; P Ͻ 0.001); however, in this group fever resolved more slowly (127 vs. 90 hours, P Ͻ 0.001), the time to recovery from coma was longer (66 vs. 48 hours, P ϭ 0.003), and the hospitalization was longer (288 vs. 240 hours, P ϭ 0.005). Quinine treatment was associated with a higher risk of hypoglycemia (relative risk, 2.7; 95 percent confidence interval, 1.7 to 4.4; P Ͻ 0.001), but there were no other serious side effects in either group. Conclusions Artemether is a satisfactory alternative to quinine for the treatment of severe malaria in adults. (

Research paper thumbnail of A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria

Malaria Journal, 2013

Background: Plasma angiopoietin (Ang)-2 is associated with disease severity and mortality in adul... more Background: Plasma angiopoietin (Ang)-2 is associated with disease severity and mortality in adults and children with falciparum malaria. However the mechanism of action of the angiopoietins in fatal malaria is unclear. This study aimed to determine whether the expression of Ang-1 and Ang-2 and their receptor Tie-2 in cerebral endothelial or parenchymal cells was specific to cerebral malaria (CM), correlated with coma or other severe clinical features, and whether plasma and CSF levels of these markers correlated with the clinical and neuropathological features of severe and fatal malaria in Vietnamese adults. Methods: Immunohistochemistry was performed for Ang-1, Ang-2 and Tie-2 on post-mortem brain tissue from fatal malaria cases and controls. Quantitative ELISA for plasma and cerebrospinal fluid levels of Ang-1, Ang-2 and Tie-2 was done to compare fatal cases with surviving patients from the same study. Results: Immunohistochemistry revealed significant differences in expression in endothelial and parenchymal cells compared to controls. However there was no significant difference in expression of these markers on endothelial cells, astroglial cells or neurons between CM and non-cerebral malaria cases. Immunostaining of Ang-1, Ang-2 and Tie-2 was also not associated with Plasmodium falciparum-infected erythrocyte sequestration in the brain. However Ang-1 and Ang-2 expression in neurons was significantly correlated with the incidence of microscopic haemorrhages. Plasma levels of Ang-2 and Ang-2/Ang-1 ratio were associated with the number of severe malaria complications and were significant and independent predictors of metabolic acidosis and fatal outcome. Conclusions: The independent prognostic significance of Ang-2 and the Ang-2/Ang-1 ratio in severe malaria was confirmed, although immunohistochemistry in fatal cases did not reveal increased expression on brain endothelium in cerebral versus non-cerebral cases. Activation of the Ang-Tie-2 pathway in severe malaria is therefore related to acidosis, number of severity criteria and outcome, but is not a specific event in the brain during cerebral malaria.

Research paper thumbnail of Randomized controlled trial of artesunate or artemether in Vietnamese adults with severe falciparum malaria

Malaria Journal, 2010

Background Both artemether and artesunate have been shown to be superior to quinine for the treat... more Background Both artemether and artesunate have been shown to be superior to quinine for the treatment of severe falciparum malaria in Southeast Asian adults, although the magnitude of the superiority has been greater for artesunate than artemether. These two artemisinin derivatives had not been compared in a randomized trial. Methods A randomized double blind trial in 370 adults with severe falciparum malaria; 186 received intramuscular artesunate (2.4 mg/kg immediately followed by 1.2 mg/kg at 12 hours then 24 hours then daily) and 184 received intramuscular artemether (3.6 mg per kilogram immediately followed by 1.8 mg per kilogram daily) was conducted in Viet Nam. Both drugs were given for a minimum of 72 hours. Results There were 13 deaths in the artesunate group (7 percent) and 24 in the artemether group (13 percent); P = 0.052; relative risk of death in the patients given artesunate, 0.54; (95 percent confidence interval 0.28-1.02). Parasitaemia declined more rapidly in the ar...