Addo-Yobo E.,University of Ghana |
Anh D.D.,National Institute of Hygiene and Epidemiology |
El-Sayed H.F.,Suez Canal University |
Fox L.M.,Boston University |
And 5 more authors.
Tropical Medicine and International Health | Year: 2011
Objective A recent randomized clinical trial demonstrated home-based treatment of WHO-defined severe pneumonia with oral amoxicillin was equivalent to hospital-based therapy and parenteral antibiotics. We aimed to determine whether this finding is generalizable across four countries. Methods Multicentre observational study in Bangladesh, Egypt, Ghana and Vietnam between November 2005 and May 2008. Children aged 3-59months with WHO-defined severe pneumonia were enrolled at participating health centres and managed at home with oral amoxicillin (80-90mg/kg per day) for 5days. Children were followed up at home on days 1, 2, 3 and 6 and at a facility on day 14 to look for cumulative treatment failure through day 6 and relapse between days 6 and 14. Results Of 6582 children screened, 873 were included, of whom 823 had an outcome ascertained. There was substantial variation in presenting characteristics by site. Bangladesh and Ghana had fever (97%) as a more common symptom than Egypt (74%) and Vietnam (66%), while in Vietnam, audible wheeze was more common (49%) than at other sites (range 2-16%). Treatment failure by day 6 was 9.2% (95% CI: 7.3-11.2%) across all sites, varying from 6.4% (95% CI: 3.1-9.8%) in Ghana to 13.2% (95% CI: 8.4-18.0%) in Vietnam; 2.7% (95% CI: 1.5-3.9%) of the 733 children well on day 6 relapsed by day 14. The most common causes of treatment failure were persistence of lower chest wall indrawing (LCI) at day 6 (3.8%; 95% CI: 2.6-5.2%), abnormally sleepy or difficult to wake (1.3%; 95% CI: 0.7-2.3%) and central cyanosis (1.3%; 95% CI: 0.7-2.3%). All children survived and only one adverse drug reaction occurred. Treatment failure was more frequent in young infants and those presenting with rapid respiratory rates. Conclusions Clinical treatment failure and adverse event rates among children with severe pneumonia treated at home with oral amoxicillin did not substantially differ across geographic areas. Thus, home-based therapy of severe pneumonia can be applied to a wide variety of settings. © 2011 Blackwell Publishing Ltd.
Anders K.L.,University of Oxford |
Anders K.L.,Monash University |
Nguyen N.M.,University of Oxford |
Van Thuy N.T.,University of Oxford |
And 7 more authors.
BMC Public Health | Year: 2013
Background: In Ho Chi Minh City, Vietnam, more than one-third of admissions to the two paediatric hospitals are attributable to four infectious syndromes: dengue, diarrhoeal disease, acute respiratory infection, and hand, foot and mouth disease. We have established a large prospective birth cohort study to investigate individual, environmental, virological, and immunological determinants of infection and disease in infants. Specific research questions are focused on the role of maternal antibody in protection against infection in infancy, and the adaptive immune response to vaccination and natural infection. This paper presents the cohort design, methods, and baseline characteristics of the participants enrolled in the first two years. Methods/design. Women are enrolled prior to delivery at one hospital in each of two catchment areas: an urban district in central HCMC, and a mixed urban/rural district in the Mekong Delta 150 km southwest of HCMC. Infants are enrolled within 3 days of birth, and maternal and cord blood samples are collected. Routine blood samples and data on growth, health status and vaccinations are collected from infants at scheduled visits at 4, 9 and 12 months. Clinical data and specimens are collected from infants presenting at a study clinic, or admitted to hospital, with any of the the four infectious syndromes of interest. Discussion. In four years since since the study began in July 2009, >6400 infants have been enrolled, and enrolment is ongoing. Attrition is low: 84% of participants have completed the full 12-month follow-up period. Baseline characteristics of the first 4300 enrollees are presented here. We have demonstrated the feasibility of establishing a large prospective study of infectious diseases in infancy in a resource-limited setting, with minimal loss to follow-up. Our linked socio-demographic, clinical and laboratory data will help elucidate the viral aetiology and epidemiology of common infectious diseases of infancy, and can inform the implemention of existing and future vaccines. This study furthermore provides a platform to which additional endpoints could be added in the future. © 2013 Anders et al.; licensee BioMed Central Ltd.
Khor C.C.,Genome Institute of Singapore |
Khor C.C.,National University of Singapore |
Chau T.N.B.,University of Oxford |
Pang J.,Genome Institute of Singapore |
And 29 more authors.
Nature Genetics | Year: 2011
Hypovolemic shock (dengue shock syndrome (DSS)) is the most common life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P meta = 4.41 × 10 -11, per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P meta = 3.08 × 10 -10, per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue. © 2011 Nature America, Inc. All rights reserved.
PubMed | Childrens Hospital No 1, Childrens Hospital No 2, Dong Nai Childrens Hospital, Hospital for Tropical Diseases and 4 more.
Type: | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2016
Early prediction of severe dengue could significantly assist patient triage and case management METHODS: We prospectively investigated 7563 children with 3 days of fever recruited in the outpatient departments of six hospitals in southern Vietnam between 2010 and 2013. The primary endpoint of interest was severe dengue (2009 WHO Guidelines) and pre-defined risk variables were collected at the time of enrolment to enable prognostic model development.The analysis population comprised 7544 patients, of whom 2060 (27.3%) had laboratory-confirmed dengue and nested amongst these were 117 (1.5%) severe cases. In the multivariate logistic model a history of vomiting, lower platelet count, elevated aspartate aminotransferase (AST), positivity in the NS1 rapid test and viremia magnitude were all independently associated with severe dengue. The final prognostic model (Early Severe Dengue identifier- ESDI) included history of vomiting, platelet count, AST level and NS1 rapid test status.The ESDI had acceptable performance features (AUC=0.95, sensitivity 87% (95%CI: 80-92%), specificity 88% (95%CI: 87-89%), positive predictive value 10% (95%CI: 9-12%), negative predictive value of 99.8% (95%CI: 99.6-99.9%)) in the population of all 7563 enrolled children. A score-chart, for routine clinical use, was derived from the prognostic model and could improve triage and management of children presenting with fever in dengue endemic areas.
PubMed | Hung Vuong Hospital, Childrens Hospital No 1, Dong Thap Hospital, University of Melbourne and 5 more.
Type: | Journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases | Year: 2015
Previous studies indicate a high burden of diarrhoeal disease in Vietnamese children, however longitudinal community-based data on burden and aetiology are limited. The findings from a large, prospective cohort study of diarrhoeal disease in infants in southern Vietnam are presented herein.Infants were enrolled at birth in urban Ho Chi Minh City and a semi-rural district in southern Vietnam, and followed for 12 months (n=6706). Diarrhoeal illness episodes were identified through clinic-based passive surveillance, hospital admissions, and self-reports.The minimum incidence of diarrhoeal illness in the first year of life was 271/1000 infant-years of observation for the whole cohort. Rotavirus was the most commonly detected pathogen (50% of positive samples), followed by norovirus (24%), Campylobacter (20%), Salmonella (18%), and Shigella (16%). Repeat infections were identified in 9% of infants infected with rotavirus, norovirus, Shigella, or Campylobacter, and 13% of those with Salmonella infections.The minimum incidence of diarrhoeal disease in infants in both urban and semi-rural settings in southern Vietnam was quantified prospectively. A large proportion of laboratory-diagnosed disease was caused by rotavirus and norovirus. These data highlight the unmet need for a rotavirus vaccine in Vietnam and provide evidence of the previously unrecognized burden of norovirus in infants.
PubMed | Victoria University of Melbourne, Childrens Hospital No 1, Childrens Hospital No 2, Dong Nai Childrens Hospital and 6 more.
Type: Clinical Trial | Journal: PLoS neglected tropical diseases | Year: 2015
Dengue is the commonest arboviral disease of humans. An early and accurate diagnosis of dengue can support clinical management, surveillance and disease control and is central to achieving the World Health Organisation target of a 50% reduction in dengue case mortality by 2020.5729 children with fever of <72 hrs duration were enrolled into this multicenter prospective study in southern Vietnam between 2010-2012. A composite of gold standard diagnostic tests identified 1692 dengue cases. Using statistical methods, a novel Early Dengue Classifier (EDC) was developed that used patient age, white blood cell count and platelet count to discriminate dengue cases from non-dengue cases.The EDC had a sensitivity of 74.8% (95%CI: 73.0-76.8%) and specificity of 76.3% (95%CI: 75.2-77.6%) for the diagnosis of dengue. As an adjunctive test alongside NS1 rapid testing, sensitivity of the composite test was 91.6% (95%CI: 90.4-92.9%).We demonstrate that the early diagnosis of dengue can be enhanced beyond the current standard of care using a simple evidence-based algorithm. The results should support patient management and clinical trials of specific therapies.
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.
Cheng H.-J.,National Cheng Kung University |
Luo Y.-H.,National Cheng Kung University |
Wan S.-W.,National Cheng Kung University |
Lin C.-F.,Taipei Medical University |
And 8 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2015
We have previously shown that anti-dengue virus nonstructural protein 1 (anti-DENV NS1) antibodies cross-react with endothelial cells, and several autoantigens have been identified. This study shows that the antibody levels against these self-proteins are higher in sera from patients with dengue hemorrhagic fever (DHF) than those in control sera. Anti-protein disulfide isomerase (PDI) and anti-heat shock protein 60 (anti-HSP60) IgM levels correlated with both anti-endothelial cells and anti-DENV NS1 IgM titers. A cross-reactive epitope on the NS1 amino acid residues 311-330 (P311-330) had been predicted. We further found that there were higher IgM and IgG levels against P311-330 in DHF patients' sera than those in the control sera. In addition, correlations were observed between anti-PDI with anti-P311-330 IgM and IgG levels, respectively. Therefore, our results indicate that DENV NS1 P311-330 is a major epitope for cross-reactive antibodies to PDI on the endothelial cell surface, which may play an important role in DENV infection-induced autoimmunity. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene.
Hung N.T.,Childrens Hospital No 1
Paediatrics and International Child Health | Year: 2012
Dengue is a serious public health problem worldwide. Dengue shock syndrome (DSS), the severe form of dengue fever, can cause death within 12-24 hours if appropriate treatment is not promptly administered. For patients with DSS and the 30% of non-shocked dengue patients who require intravenous fluid therapy, a range of solutions is available for plasma volume support. Crystalloid solutions, such as normal 0.9% saline or Ringer's lactate, are the ones most commonly used. In severe cases, colloid solutions may be administered for their greater osmotic effect, although they carry a greater risk of adverse events. This paper summarises the key clinical data, comparing fluid regimens in children with severe dengue, and concludes that the majority of patients with DSS can be treated successfully with isotonic crystalloid solutions. If a colloid is thought necessary, a medium-molecular-weight preparation that combines good initial plasma volume support with good intravascular persistence and an acceptable side-effect profile is optimal. Further research should aim to determine whether there are benefits to early treatment with colloids, and which colloid solution is most effective for resuscitation of DSS patients. © W. S. Maney & Son Ltd 2012.
PubMed | Childrens Hospital No 1
Type: Journal Article | Journal: PloS one | Year: 2013
Enterovirus 71 (EV71) frequently causes fatal infections in young children in Asia. In 2011, EV71 epidemics occurred in southern Vietnam. We conducted genetic and antigenic analysis of the EV71 isolates and found that 94% of them were genotype C4a related to two lineages circulating in China and 6% were genotype C5 which have circulated in Vietnam since 2003. Antigenic variants were not detected. EV71 vaccines are being developed. Longitudinal enterovirus surveillance data are critical to formulate vaccination policy in Vietnam.