Lucy Chai See Lum

Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever

Background  The current World Health Organisation (WHO) classification of dengue includes two distinct entities: dengue fever (DF) and dengue haemorrhagic fever (DHF)/dengue shock syndrome; it is largely based on pediatric cases in Southeast Asia. Dengue has extended to different tropical areas and older age groups. Variations from the original description of dengue manifestations are being reported.

Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia.

Background: This study was designed to evaluate the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) against culture-confirmed influenza in children 12 to <36 months of age during 2 consecutive influenza seasons at multiple sites in Asia. Methods: In year 1, 3174 children 12 to <36 months of age were randomized to receive 2 doses of CAIV-T (n = 1900) or placebo (n = 1274) intranasally ≥28 days apart. In year 2, 2947 subjects were rerandomized to receive 1 dose of CAIV-T or placebo. Results: Mean age at enrollment was 23.5 ± 7.4 months. In year 1, efficacy of CAIV-T compared with placebo was 72.9% [95% confidence interval (CI): 62.8–80.5%] against antigenically similar influenza subtypes, and 70.1% (95% CI: 60.9–77.3%) against any strain. In year 2, revaccination with CAIV-T demonstrated significant efficacy against antigenically similar (84.3%; 95% CI: 70.1–92.4%) and any (64.2%; 95% CI: 44.2–77.3%) influenza strains. In year 1, fever, runny nose/nasal congestion, decreased activity and appetite, and use of fever medication were more frequent with CAIV-T after dose 1. Runny nose/nasal congestion after dose 2 (year 1) and dose 3 (year 2) and use of fever medication after dose 3 (year 2) were the only other events reported significantly more frequently in CAIV-T recipients. Conclusions: CAIV-T was well tolerated and effective in preventing culture-confirmed influenza illness over multiple and complex influenza seasons in young children in Asia.

Multicentre prospective study on dengue classification in four South-east Asian and three Latin American countries

Objective  To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence‐based classification that would better reflect clinical severity.

Towards a global dengue research agenda.

Dengue is the most rapidly advancing vector-borne disease with an estimated 50 million dengue infections occurring annually. As a result of major demographic changes rapid urbanization on a massive scale global travel and environmental change the world - particularly the tropical world - faces enormous challenges from emerging infectious diseases. Dengue epitomizes these challenges. In the early years of the 21st century we are collectively failing to meet the threat posed by dengue as the disease spreads unabated and almost 40% of the worlds population now live at risk of contracting it. Because of the rapidly increasing public health importance of dengue the 2002 World Health Assembly Resolution (WHA55.17) urged greater commitment among Member States and WHO to dengue control; of particular significance is the 2005 Revision of the International Health Regulations (WHA58.3) which includes dengue fever as an example of a disease that may constitute an international public health emergency. (excerpt)

Cytokine expression profile of dengue patients at different phases of illness.

Background Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease. Methods and Findings Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study. Conclusions The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.

Editorial: Towards a global dengue research agenda

Dengue is the most rapidly advancing vector-borne disease with an estimated 50 million dengue infections occurring annually. As a result of major demographic changes rapid urbanization on a massive scale global travel and environmental change the world - particularly the tropical world - faces enormous challenges from emerging infectious diseases. Dengue epitomizes these challenges. In the early years of the 21st century we are collectively failing to meet the threat posed by dengue as the disease spreads unabated and almost 40% of the worlds population now live at risk of contracting it. Because of the rapidly increasing public health importance of dengue the 2002 World Health Assembly Resolution (WHA55.17) urged greater commitment among Member States and WHO to dengue control; of particular significance is the 2005 Revision of the International Health Regulations (WHA58.3) which includes dengue fever as an example of a disease that may constitute an international public health emergency. (excerpt)

Impact of 24 hour critical care physician staffing on case-mix adjusted mortality in paediatric intensive care

The 24 h availability of intensive care consultants (intensivists) has been shown to improve outcomes in adult intensive care units (ICU) in the UK. We tested whether such availability would improve standardised mortality ratios when compared to out-of-hours cover by general paediatricians in the paediatric ICU setting of a medium-income developing country. The standardised mortality ratio (SMR) improved significantly from 1.57 (95%CI 1.25-1.95) with non-specialist care to 0.88 (95%CI 0.63-1.19) with intensivist care (rate ratio 0.56, 95% CI 0.47-0.67). Mortality odds ratio decreased by 0.234, 0.246 and 0.266 in the low, moderate and high-risk patients. 24 h availability of intensivists was associated with improved outcomes and use of resources in paediatric intensive care in a developing country.

Preventive transfusion in dengue shock syndrome–is it necessary?

We compared 53 patients with Dengue shock syndrome (DSS) who received preventive transfusions with 53 who did not. Significant differences in the development of pulmonary edema and length of hospitalization (P<.05) and none in hemorrhage (P=.136) were observed. Preventive transfusions did not produce sustained improvements in the coagulation status in DSS.

Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children

Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).

Dengue-associated adult respiratory distress syndrome

In dengue shock syndrome, an acute increase in capillary permeability results in leakage of plasma into the interstitial space. Pleural effusion is commonly seen in dengue shock syndrome. We report three cases of dengue-associated adult respiratory distress syndrome (ARDS) in children, in all of whom dengue haemorrhagic fever, presenting with grade 3 or grade 4 dengue shock syndrome with disseminated intravascular coagulopathy, was confirmed. The criteria for the diagnosis of ARDS were based on the expanded definition of ARDS by Murray et al. Treatment consisted of fluid resuscitation, correction of coagulopathy and mechanical ventilation. All three children had multi-organ impairment, but it was more severe in the two who died. The one survivor was well at discharge.