Age-related changes in microvascular permeability: a significant factor in the susceptibility of children to shock?

Gamble, J.; Bethell, Delia; Day, Nicholas; Loc, Pham Phu; Phu, Nh H.; GARTSIDE, I. B.; Farrar, Jeremy; White, NicholasJ.

doi:10.1042/cs0980211

Cited by 75 publications

(41 citation statements)

References 12 publications

(21 reference statements)

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“…The upward shift of average age in South East Asia (Figure 3) and previous study [46]), coupled with the lower risk of DSS in older age [4], [66] could be another reason for the reduction of DSS/DHF ratio over this period. It is well known that young children have an increased risk of severe dengue infection [4], [55], probably due to a combination of timing of secondary infection, development of protective immune responses after infection with four strains [67], and increased microvascular fragility in younger children [68]. Our pooled result of 37 studies further strengthened the negative association of age with DSS.…”

Section: Discussionsupporting

confidence: 73%

Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

Huy

Giang

Duong³

et al. 2013

PLoS Negl Trop Dis

194

153

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BackgroundThe pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.Methods and FindingsPubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies.ConclusionsThe results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.

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Section: Discussionsupporting

confidence: 73%

Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

Huy

Giang

Duong³

et al. 2013

PLoS Negl Trop Dis

194

153

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“…This is a conservative assumption, as existing literature suggests that severe episodes of dengue illness in SEA affect mostly infants and children [9], [13], [73], [74], and that children are more vulnerable than adults to shock syndrome [75]. Hence, we would expect the very young to have higher death rates than the rest of the population and therefore, the economic and disease burden might be even higher.…”

Section: Discussionmentioning

confidence: 99%

Economic and Disease Burden of Dengue in Southeast Asia

2013

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BackgroundDengue poses a substantial economic and disease burden in Southeast Asia (SEA). Quantifying this burden is critical to set policy priorities and disease-control strategies.Methods and FindingsWe estimated the economic and disease burden of dengue in 12 countries in SEA: Bhutan, Brunei, Cambodia, East-Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Viet Nam. We obtained reported cases from multiple sources—surveillance data, World Health Organization (WHO), and published studies—and adjusted for underreporting using expansion factors from previous literature. We obtained unit costs per episode through a systematic literature review, and completed missing data using linear regressions. We excluded costs such as prevention and vector control, and long-term sequelae of dengue. Over the decade of 2001–2010, we obtained an annual average of 2.9 million (m) dengue episodes and 5,906 deaths. The annual economic burden (with 95% certainty levels) was US$950m (US$610m–US$1,384m) or about US$1.65 (US$1.06–US$2.41) per capita. The annual number of disability-adjusted life years (DALYs), based on the original 1994 definition, was 214,000 (120,000–299,000), which is equivalent to 372 (210–520) DALYs per million inhabitants.ConclusionDengue poses a substantial economic and disease burden in SEA with a DALY burden per million inhabitants in the region. This burden is higher than that of 17 other conditions, including Japanese encephalitis, upper respiratory infections, and hepatitis B.

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“…Age is known to influence intrinsic vascular permeability, with children demonstrating a lower threshold for leakage than adults [18]. Similarly, homeostatic mechanisms aimed at minimizing cardiovascular decompensation in the face of increased permeability are less well developed in children.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features of Dengue in a Large Vietnamese Cohort: Intrinsically Lower Platelet Counts and Greater Risk for Bleeding in Adults than Children

et al. 2012

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BackgroundAs dengue spreads to new geographical regions and the force of infection changes in existing endemic areas, a greater breadth of clinical presentations is being recognised. Clinical experience suggests that adults manifest a pattern of complications different from those observed in children, but few reports have described the age-related spectrum of disease in contemporaneous groups of patients recruited at the same geographical location.Methodology/Principal FindingsUsing detailed prospectively collected information from ongoing studies that encompass the full spectrum of hospitalised dengue cases admitted to a single hospital in southern Vietnam, we compared clinical and laboratory features, management, and outcome for 647 adults and 881 children with confirmed dengue. Signs of vascular leakage and shock were more frequent and more severe in children than adults, while bleeding manifestations and organ involvement were more common in adults. Additionally, adults experienced significantly more severe thrombocytopenia. Secondary infection but not serotype was independently associated with greater thrombocytopenia, although with a smaller effect than age-group. The effect of age-group on platelet count was also apparent in the values obtained several weeks after recovery, indicating that healthy adults have intrinsically lower counts compared to children.Conclusions/SignificanceThere are clear distinctions between adults and children in the pattern of complications seen in association with dengue infection, and these depend partly on intrinsic age-dependent physiological differences. Knowledge of such differences is important to inform research on disease pathogenesis, as well as to encourage development of management guidelines that are appropriate to the age-groups at risk.

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Age-related changes in microvascular permeability: a significant factor in the susceptibility of children to shock?

Cited by 75 publications

References 12 publications

Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

Economic and Disease Burden of Dengue in Southeast Asia

Clinical Features of Dengue in a Large Vietnamese Cohort: Intrinsically Lower Platelet Counts and Greater Risk for Bleeding in Adults than Children

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