The 1997 and 2009 WHO dengue case classifications were compared in a systematic review with 12 eligible studies (4 prospective). Ten expert opinion articles were used for discussion. For the 2009 WHO classification studies show: when determining severe dengue sensitivity ranges between 59–98% (88%/98%: prospective studies), specificity between 41–99% (99%: prospective study) - comparing the 1997 WHO classification: sensitivity 24.8–89.9% (24.8%/74%: prospective studies), specificity: 25%/100% (100%: prospective study). The application of the 2009 WHO classification is easy, however for (non-severe) dengue there may be a risk of monitoring increased case numbers. Warning signs validation studies are needed. For epidemiological/pathogenesis research use of the 2009 WHO classification, opinion papers show that ease of application, increased sensitivity (severe dengue) and international comparability are advantageous; 3 severe dengue criteria (severe plasma leakage, severe bleeding, severe organ manifestation) are useful research endpoints. The 2009 WHO classification has clear advantages for clinical use, use in epidemiology is promising and research use may at least not be a disadvantage.

Background: The burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course.

BackgroundThe human leukocyte antigen alleles have been implicated as probable genetic markers in predicting the susceptibility and/or protection to severe manifestations of dengue virus (DENV) infection. In this present study, we aimed to investigate for the first time, the genotype variants of HLA Class 1(-A and -B) of DENV infected patients against healthy individuals in Malaysia.Methodology/Principal FindingsThis study was carried out with 92 dengue disease patients and 95 healthy controls from three different ethnic groups (Malay, Chinese and Indian) in Malaysia. All patients with clinical and laboratory confirmation of DENV infection were typed for the HLA-A and B loci, using polymerase chain reaction-sequence specific primer techniques. In our total population, a significant increase for HLA-B*53 (P = 0.042, Pc = 1.008) allele and a significant decrease for A*03 (P = 0.015, Pc = 0.18, OR = 5.23, 95% CI = 1.19–23.02) and B*18 (P = 0.017, Pc = 0.408) alleles were noted in DHF patients as compared to healthy donors. We also observed that in the Malay DHF patients, allele B*13 (P = 0.049, Pc = 1.176, OR = 0.18, 95% CI = 0.03–0.90) was present at a significantly higher frequency in this population while allele HLA-B*18 (P = 0.024, Pc = 0.576) was seen to be negatively associated with DHF.Conclusions/SignificanceThese are the first findings on genetic polymorphisms in our population and we conclude that: (1) In our total population, HLA-B*53 probably involve in disease susceptibility, while the HLA-A*03 and HLA-B*18 may confer protection from progression to severe disease; (2) In the Malay population, HLA-B*13 and B*18 are probably associated in disease susceptibility and protection, respectively. These results could furnish as a valuable predictive tool to identify ethnically different individuals at risk and/or protection from severe forms of DENV infection and would provide valuable informations for the design of future dengue vaccine.

Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas in the world. Attempts to develop effective vaccines have been hampered by the lack of understanding of the pathogenesis of the disease and the absence of suitable experimental models for dengue viral infection. The magnitude of T-cell responses has been reported to correlate with dengue disease severity. Sixty Malaysian adults with dengue viral infections were investigated for their dengue virus-specific T-cell responses to 32 peptides antigens from the structural and nonstructural regions from a dengue virus isolate. Seventeen different peptides from the C, E, NS2B, NS3, NS4A, NS4B, and NS5 regions were found to evoke significant responses in a gamma interferon enzyme-linked immunospot (ELISPOT) assay of samples from 13 selected patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). NS3 and predominantly NS3 422-431 were found to be important T-cell targets. The highest peaks of T-cell responses observed were in responses to NS3 422-431 and NS5 563-571 in DHF patients. We also found almost a sevenfold increase in T-cell response in three DHF patients compared to three DF patient responses to peptide NS3 422-431 . A large number of patients' T cells also responded to the NS2B 97-106 region. The ELISPOT analyses also revealed high frequencies of T cells that recognize both serotype-specific and cross-reactive dengue virus antigens in patients with DHF.

Dengue infection is a major public health problem affecting millions of people living in tropical countries. With no suitable vaccines and specific antiviral drugs, treatment for dengue is usually symptomatic and supportive. Early diagnosis and recognition of severe disease is therefore crucial for better management of the patient. Two-dimension electrophoresis was used to identify disease-associated proteins that can be used for diagnosis and as drug targets for treatment. Two markers, identified by mass spectrometry analysis as alpha1-antitrypsin and NS1 proteins were found to be upregulated in dengue fever (DF; n=10) and dengue haemorrhagic fever (DHF; n=10) patients compared with healthy individuals (n=8). Both alpha1-antitrypsin and NS1 proteins were overexpressed two-fold in DHF patients compared with DF patients. Our study suggests that alpha1-antitrypsin and NS1 protein could be used as biomarkers as early indicators of DHF risk among patients with suspected dengue infection.

A BSI is the presence of a pathogen in the blood. Its clinical significance should be determined by the presence of the host response as defined by the modified criteria for systemic inflammatory response syndrome SIRS in children or a clinically recognizable syndrome. Definitions of BSI for the purposes of sepsis trials may differ from those for epidemiologic or surveillance studies.

Pediatric Intensive Care Units (PICUs) provide multidisciplinary care to critically ill children and their families. Grief is present throughout the trajectory of illness and can peak around the time of death or non-death losses. The objective of this study was to assess how PICUs around the world implement grief and bereavement care (GBC) as part of an integrated model of care. This is a multicenter cross-sectional, prospective survey study. Questionnaires with multiple-choice and open-ended questions focusing on unit infrastructure, personnel, policies, limited patient data, and practices related to GBC for families and health care professionals (HCPs) were completed by on-site researchers, who were HCPs on the direct care of patients. PICU fulfillment of GBC goals was evaluated using a custom scoring based on indicators developed by the Initiative for Pediatric Palliative Care (IPPC). We compared average total and individual items fulfillment scores according to the respective country's World Bank income. Patient characteristics and details of unit infrastructure were also evaluated as potential predictors of total GBC fulfillment scores. Statistical analysis included multilevel generalized linear models (GLM) with a Gaussian distribution adjusted by child age/gender and clustering by center, using high income countries (HICs) as the comparative reference. Additionally, we applied principals of content analysis to analyze and summarize open-ended answers to contextualize qualitative data. The study included 34 PICUs from 18 countries: high-income countries (HICs): 32.4%, upper middle-income countries (UMICs): 44.1%, low middle-income and low-income countries (LMI/LICs): 23.5%. All groups reported some compliance with GBC goals; no group reported perfect fulfillment. We found statistically significant differences in GBC fulfillment scores between HICs and UMICs (specifically, HCP grief support), and between HICs and LMICs (specifically, family grief support and HCP grief support). PICUs world-wide provide some GBC, independent of income, but barriers include lack of financial support, time, and training, overall unit culture, presence of a palliative care consultation service, and varying cultural perceptions of child death. Disparities in GBC for families and HCPs exist and were related to the native countries' income level. Identifying barriers to support families and HCPs, can lead to opportunities of improving GBC in PICUs world-wide.

Background Dengue, an acute infectious disease caused by a flavivirus, is a threat to global health. There is sparse evidence exploring obesity and the development of more severe dengue cases in adults. With increasing prevalence of obesity in areas with a high risk of dengue infection, obesity may increase the burden and mortality related to dengue infection. Our study aimed to determine the association between obesity and the development of more severe dengue infection in primary healthcare settings and whether these associations were modified by dengue fever phase. Methods A cohort study was conducted among laboratory-confirmed dengue patients aged >18 y in the central region of Peninsular Malaysia from May 2016 to November 2017. We collected demographic, clinical history, physical examination and laboratory examination information using a standardized form. Dengue severity (DS) was defined as either dengue with warning signs or severe dengue. Participants underwent daily follow-up, during which we recorded their vital signs, warning signs and full blood count results. Incidence of DS was modeled using mixed-effects logistic regression. Changes in platelet count and hematocrit were modeled using mixed-effects linear regression. The final multivariable models were adjusted for age, gender, ethnicity and previous dengue infection. Results A total of 173 patients were enrolled and followed up. The mean body mass index (BMI) was 37.4±13.75 kg/m2. The majority of patients were Malay (65.9%), followed by Chinese (17.3%), Indian (12.7%) and other ethnic groups (4.1%). A total of 90 patients (52.0%) were male while 36 patients (20.8%) had a previous history of dengue infection. BMI was significantly associated with DS (adjusted OR=1.17; 95% CI 1.04 to 1.34) and hematocrit (%) (aβ=0.09; 95% CI 0.01 to 0.16), but not with platelet count (x103/µL) (aβ=−0.01; 95% CI −0.84 to 0.81). In the dose response analysis, we found that as BMI increases, the odds of DS, hematocrit levels and platelet levels increase during the first phase of dengue fever. Conclusion Higher BMI and higher hematocrit levels were associated with higher odds of DS. Among those with high BMI, the development of DS was observed during phase one of dengue fever instead of during phase two. These novel results could be used by clinicians to help them risk-stratify dengue patients for closer monitoring and subsequent prevention of severe dengue complications.