Pasteur Institute in Ho Chi Minh City

Ho Chi Minh City, Vietnam

Pasteur Institute in Ho Chi Minh City

Ho Chi Minh City, Vietnam

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Hadinegoro S.R.,University of Indonesia | Arredondo-Garcia J.L.,Instituto Nacional Of Pediatria | Capeding M.R.,Institute of Tropical Medicine | Deseda C.,Caribbean Travel Medicine Clinic | And 19 more authors.
New England Journal of Medicine | Year: 2015

Background: A candidate tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries. We report the results of long-term follow-up interim analyses and integrated efficacy analyses. Methods: We are assessing the incidence of hospitalization for virologically confirmed dengue as a surrogate safety end point during follow-up in years 3 to 6 of two phase 3 trials, CYD14 and CYD15, and a phase 2b trial, CYD23/57. We estimated vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15. Results: Follow-up data were available for 10,165 of 10,275 participants (99%) in CYD14 and 19,898 of 20,869 participants (95%) in CYD15. Data were available for 3203 of the 4002 participants (80%) in the CYD23 trial included in CYD57. During year 3 in the CYD14, CYD15, and CYD57 trials combined, hospitalization for virologically confirmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group. Pooled relative risks of hospitalization for dengue were 0.84 (95% confidence interval [CI], 0.56 to 1.24) among all participants, 1.58 (95% CI, 0.83 to 3.02) among those under the age of 9 years, and 0.50 (95% CI, 0.29 to 0.86) among those 9 years of age or older. During year 3, hospitalization for severe dengue, as defined by the independent data monitoring committee criteria, occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group. Pooled rates of efficacy for symptomatic dengue during the first 25 months were 60.3% (95% CI, 55.7 to 64.5) for all participants, 65.6% (95% CI, 60.7 to 69.9) for those 9 years of age or older, and 44.6% (95% CI, 31.6 to 55.0) for those younger than 9 years of age. Conclusions: Although the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term follow-up, the risk among children 2 to 16 years of age was lower in the vaccine group than in the control group. Copyright © 2015 Massachusetts Medical Society.


PubMed | Childrens Hospital No 1, Korean International Vaccine Institute, Hospital for Tropical Diseases, Pasteur Institute in Ho Chi Minh City and 4 more.
Type: Journal Article | Journal: PLoS neglected tropical diseases | Year: 2016

Ho Chi Minh City and Bangkok are highly dengue endemic. The extent to which disease patterns are attributable to local versus regional dynamics remains unclear. To address this gap we compared key transmission parameters across the locations.We used 2003-2009 age-stratified case data to inform catalytic transmission models. Further, we compared the spatial clustering of serotypes within each city. We found that annual case numbers were highly consistent across the two cities (correlation of 0.77, 95% CI: 0.74-0.79) as was the annual force of infection (correlation of 0.57, 95% CI: 0.46-0.68). Serotypes were less similar with serotype-specific correlations ranging from 0.65 for DENV1 to -0.14 for DENV4. Significant spatial clustering of serotypes was observed in HCMC at distances <500m, similar to previous observations from Bangkok.Dengue dynamics are comparable across these two hubs. Low correlation in serotype distribution suggests that similar built environments, vector populations and climate, rather than viral flow drives these observations.


Huy N.T.,Nagasaki University | Thao N.T.H.,Childrens Hospital | Ha T.T.N.,Pasteur Institute in Ho Chi Minh City | Lan N.T.P.,Pasteur Institute in Ho Chi Minh City | And 9 more authors.
Critical Care | Year: 2013

Introduction: Mortality from dengue infection is mostly due to shock. Among dengue patients with shock, approximately 30% have recurrent shock that requires a treatment change. Here, we report development of a clinical rule for use during a patient's first shock episode to predict a recurrent shock episode.Methods: The study was conducted in Center for Preventive Medicine in Vinh Long province and the Children's Hospital No. 2 in Ho Chi Minh City, Vietnam. We included 444 dengue patients with shock, 126 of whom had recurrent shock (28%). Univariate and multivariate analyses and a preprocessing method were used to evaluate and select 14 clinical and laboratory signs recorded at shock onset. Five variables (admission day, purpura/ecchymosis, ascites/pleural effusion, blood platelet count and pulse pressure) were finally trained and validated by a 10-fold validation strategy with 10 times of repetition, using a logistic regression model.Results: The results showed that shorter admission day (fewer days prior to admission), purpura/ecchymosis, ascites/pleural effusion, low platelet count and narrow pulse pressure were independently associated with recurrent shock. Our logistic prediction model was capable of predicting recurrent shock when compared to the null method (P < 0.05) and was not outperformed by other prediction models. Our final scoring rule provided relatively good accuracy (AUC, 0.73; sensitivity and specificity, 68%). Score points derived from the logistic prediction model revealed identical accuracy with AUCs at 0.73. Using a cutoff value greater than -154.5, our simple scoring rule showed a sensitivity of 68.3% and a specificity of 68.2%.Conclusions: Our simple clinical rule is not to replace clinical judgment, but to help clinicians predict recurrent shock during a patient's first dengue shock episode. © 2013 Huy et al.; licensee BioMed Central Ltd.


Nguyen N.T.B.,Institute of Hygiene and Public Health in Ho Chi Minh City | Pham H.V.,Vietnam Field Epidemiology Training Program | Hoang C.Q.,Vietnam Field Epidemiology Training Program | Nguyen T.M.,Children Hospital | And 5 more authors.
BMC Infectious Diseases | Year: 2014

Background: In 2011, a large outbreak of hand, foot and mouth disease (HFMD) in Vietnam resulted in 113,121 children seeking medical attention, of whom170 died. Understanding the epidemiology of fatal HFMD may improve treatment and help targeting prevention activities for vulnerable populations. We describe epidemiological and clinical characteristics of children who died from HFMD in Vietnam in 2011.Methods: Clinical data were obtained through reviewing medical records of the deaths occurring from January through December 2011 in all hospitals in Vietnam. Hospitals reported any deaths among patients with laboratory-confirmed enterovirus (EV) infection to the Ministry of Health. Data were extracted from the national database.Results: Of the 169 deaths reviewed for whom records were available, 87% were 3-year-old or younger, 69% were male, 18% attended daycare, 89% lived in Southern Vietnam, and 85% of the deaths occurred between May-October 2011. One hundred thirty (77%) cases sought treatment in a hospital within three days of onset of illness. Symptoms at admission included fever (98%), myoclonus (66%), vomiting (53%), oral ulcers (50%) and vesicular erythema (50%). One hundred six (75%) cases had leukocytosis and 91 (54%) had hyperglycemia. One hundred three (61%) tested positive for EV, of which 84 (82%) were positive for EV71.Conclusions: Deaths associated with HFMD occurred throughout 2011 among males three years or younger who were cared for at home. The HFMD control program should focus on interventions at the household level. Clinicians should be alerted to symptoms suggestive of severe HFMD including fever, myoclonus, vomiting, oral ulcers and vesicles with high white blood cell count especially in young children. © 2014 Nguyen et al.; licensee BioMed Central Ltd.


Mangione J.N.A.,Nagasaki University | Mangione J.N.A.,Leiden University | Huy N.T.,Nagasaki University | Lan N.T.P.,Pasteur Institute in Ho Minh City | And 10 more authors.
Tropical Medicine and Health | Year: 2014

Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome. Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to shed further light on the function of these cytokines in severe dengue. © 2014 by The Japanese Society of Tropical Medicine.


Minard G.,University Claude Bernard Lyon 1 | Tran F.H.,University Claude Bernard Lyon 1 | Van V.T.,University Claude Bernard Lyon 1 | Goubert C.,CNRS Biometry and Evolutionary Biology Laboratory | And 5 more authors.
Frontiers in Microbiology | Year: 2015

The Asian tiger mosquito Aedes albopictus is one of the most significant pathogen vectors of the twenty-first century. Originating from Asia, it has invaded a wide range of eco-climatic regions worldwide. The insect-associated microbiota is now recognized to play a significant role in host biology. While genetic diversity bottlenecks are known to result from biological invasions, the resulting shifts in host-associated microbiota diversity has not been thoroughly investigated. To address this subject, we compared four autochthonous Ae. albopictus populations in Vietnam, the native area of Ae. albopictus, and three populations recently introduced to Metropolitan France, with the aim of documenting whether these populations display differences in host genotype and bacterial microbiota. Population-level genetic diversity (microsatellite markers and COI haplotype) and bacterial diversity (16S rDNA metabarcoding) were compared between field-caught mosquitoes. Bacterial microbiota from the whole insect bodies were largely dominated by Wolbachia pipientis. Targeted analysis of the gut microbiota revealed a greater bacterial diversity in which a fraction was common between French and Vietnamese populations. The genus Dysgonomonas was the most prevalent and abundant across all studied populations. Overall genetic diversities of both hosts and bacterial microbiota were significantly reduced in recently established populations of France compared to the autochthonous populations of Vietnam. These results open up many important avenues of investigation in order to link the process of geographical invasion to shifts in commensal and symbiotic microbiome communities, as such shifts may have dramatic impacts on the biology and/or vector competence of invading hematophagous insects. © 2015 Minard, Tran, Van, Goubert, Bellet, Lambert, Kim, Thuy, Mavingui and Valiente Moro.


Kume A.,Obihiro University of Agriculture and Veterinary Medicine | Kume A.,Gifu University | Anh D.T.M.,Obihiro University of Agriculture and Veterinary Medicine | Anh D.T.M.,Pasteur Institute in Ho Chi Minh City | And 4 more authors.
Malaria Journal | Year: 2016

Background: Artemisinin-based combination therapy (ACT) has been adopted as national policy for the first-line treatment in large number of malaria-endemic regions. However, artemisinin-resistant parasites have emerged and are spreading, with slow-cleaning parasites being reported in patients treated with ACT. It means that more parasites are exposed to the partner drug alone and the risk of developing resistant parasites against the partner drug is increasing. Therefore, the development of a new method to enhance the effect of artemisinin is required. In this study, the potential effect of probucol as a combination drug of dihydroartemisinin (DHA), an artemisinin derivative, was examined. Methods: C57BL/6 J mice infected with Plasmodium yoelii XL-17 were treated with probucol and/or DHA. The mice were fed with a probucol mixed diet from 2 weeks before infection and through infection period. DHA was injected to mice three to 5 days post infection once a day. In addition, 0.5 % (w/w) probucol was mixed with vitamin E supplemented diet (800 mg/kg) and fed to mice infected with P. yoelii XL-17 to examine the mechanisms of probucol on murine malaria. Furthermore, 8-OHdG, a biomarker of oxidized DNA, was detected in infected red blood cells (iRBC) taken from infected mice by immunofluorescent staining. Results: With dose-dependent manner, both probucol and DHA decreased parasitaemia and increased survival rate of mice infected with P. yoelii XL-17. A significantly larger amount of 8-OHdG was detected in iRBC taking from probucol-treated mice than control mice. In addition, a large amount of vitamin E supplementation eliminated the effect of probucol against P. yoelii XL-17 infection and lowered the effect of probucol on host plasma vitamin E concentration. The effective doses for probucol and DHA were 0.5 % and 30 mg/kg, respectively, in each single treatment. While the combination treatment of 0.25 % probucol and 7.5 mg/kg DHA was effective in all mice from P. yoelii XL-17 infection. Conclusion: This study demonstrated that probucol has some impact on malaria by oxidative stress through the induction of host plasma vitamin E deficiency. Moreover, the effective dose of DHA on malaria was decreased by prophylactic treatment of probucol. This finding indicates that probucol might be a candidate for a prophylactic treatment drug to enhance the effect of DHA. © 2016 The Author(s).


Ohba S.-Y.,Nagasaki University | Ohba S.-Y.,Kyoto University | Huynh T.T.,Pasteur Institute in Ho Chi Minh City | Kawada H.,Nagasaki University | And 5 more authors.
Journal of Vector Ecology | Year: 2011

Residents of Vietnam living in areas with water shortages and/or poor tap water maintain water storage containers, such as jars, in and around their domiciles in order to store water used in daily life. Although these water jars are known to be important breeding sources of the Aedes mosquito, use of chemical larvicides in such containers is legally prohibited in Vietnam. In this study, we identified the dominant mosquito insect predators in water jars in and around residences located in Tan Chanh, Long An, southern Vietnam. Of 3,646 Heteroptera collected from such jars, Corixidae (Micronecta spp.) and Veliidae (Microvelia spp.) were revealed to be the dominant predators. Polymerase chain reaction (PCR) analysis revealed that 40% of Micronecta and 12% of Veliidae had Aedes aegypti-positive reactions, indicating that these two dominant Heteroptera are important predators of Ae. aegypti. Our results suggest that aquatic Heteroptera may be an important mosquito control agent in addition to the currently used copepods. © 2011 The Society for Vector Ecology.


Xuan L.T.T.,Hanoi Medical University | Van Hau P.,Pasteur Institute in Ho Chi Minh City | Thu D.T.,Hanoi Medical University | Toan D.T.T.,Hanoi Medical University
Global Health Action | Year: 2014

Background: Dengue fever (DF) is a vector-borne disease that is sensitive to weather and climate variability. To date, however, this relationship in coastal northern Vietnam has not been well documented. Objectives: This paper aims to examine the associations between meteorological variables and dengue incidence in Haiphong, Vietnam, over the period 2008-2012. Methods: Monthly data on dengue incidence from all commune health stations and hospitals of Haiphong (with a total population of ~1.8 million) were obtained in accordance with the WHO's recommendations over a 5-year period (2008-2012). Temperature, rainfall, and humidity were recorded as monthly averages by local meteorological stations. The association between ecologic weather variables and dengue cases was assessed using a Poisson regression model. The estimation of regression parameters was based on the method of maximum likelihood using the R program package. Results: From 2008 through 2012, 507 cases of dengue were reported. The risk of dengue was increased by sevenfold during the September-December period compared with other months over the period 2008-2012.DF cases in Haiphong were correlated with rainfall and humidity. In themultivariable Poisson regression model, an increased risk of dengue was independently associated with months with a higher amount of rainfall (RR=1.06; 95% CI 1.00-1.13 per 50 mm increase) and higher humidity (RR=1.05; 95% CI 1.02-1.08 per 1% increase). Conclusion: These data suggest that rainfall and relative humidity could be used as ecological indicators of dengue risk in Haiphong. Intensified surveillance and disease control during periods with high rainfall and humidity are recommended. This study may provide baseline information for identifying potential long-term effects and adaptation needs of global climate change on dengue in the coming decades. © 2014 Cecilia Fernbrant et al.


PubMed | Hanoi Medical University and Pasteur Institute in Ho Chi Minh City
Type: | Journal: Global health action | Year: 2014

Dengue fever (DF) is a vector-borne disease that is sensitive to weather and climate variability. To date, however, this relationship in coastal northern Vietnam has not been well documented.This paper aims to examine the associations between meteorological variables and dengue incidence in Haiphong, Vietnam, over the period 2008-2012.Monthly data on dengue incidence from all commune health stations and hospitals of Haiphong (with a total population of ~1.8 million) were obtained in accordance with the WHOs recommendations over a 5-year period (2008-2012). Temperature, rainfall, and humidity were recorded as monthly averages by local meteorological stations. The association between ecologic weather variables and dengue cases was assessed using a Poisson regression model. The estimation of regression parameters was based on the method of maximum likelihood using the R program package.From 2008 through 2012, 507 cases of dengue were reported. The risk of dengue was increased by sevenfold during the September-December period compared with other months over the period 2008-2012. DF cases in Haiphong were correlated with rainfall and humidity. In the multivariable Poisson regression model, an increased risk of dengue was independently associated with months with a higher amount of rainfall (RR=1.06; 95% CI 1.00-1.13 per 50 mm increase) and higher humidity (RR=1.05; 95% CI 1.02-1.08 per 1% increase).These data suggest that rainfall and relative humidity could be used as ecological indicators of dengue risk in Haiphong. Intensified surveillance and disease control during periods with high rainfall and humidity are recommended. This study may provide baseline information for identifying potential long-term effects and adaptation needs of global climate change on dengue in the coming decades.

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