Is there any association between body mass index and severity of dengue infection?

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 (%) (aß=0.09; 95% CI 0.01 to 0.16), but not with platelet count (x103/µL) (aß=-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.

Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries.

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. METHOD/DESIGN: This is a prospective multi-centre observational study aiming to enrol 7-8000 participants aged ≥ 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later. DISCUSSION: Data from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for "Integrated Management of Childhood Illness" used in dengue-endemic countries. TRIAL REGISTRATION: NCT01550016. Registration Date: March 7, 2012.

Comparing the usefulness of the 1997 and 2009 WHO dengue case classification: a systematic literature review.

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.

Differential expression of aldolase, alpha tubulin and thioredoxin peroxidase in peripheral blood mononuclear cells from dengue fever and dengue hemorrhagic fever patients.

We determined the differential expression levels of proteins in peripheral blood mononuclear cells of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Proteins were subjected to two-dimensional electrophoresis, mass spectrometry and Western blot analysis. We identified 8 proteins that were 2-fold or more up-regulated in patients compared to healthy control, three of which, aldolase, thioredoxin peroxidase and alpha tubulin, were related to dengue infection. Both thioredoxin peroxidase and alpha tubulin were over-expressed 4.9 and 3.3 times respectively in DHF compared to DF patients while aldolase was up-regulated 2.2 times in DF compared to DHF patients. Alpha tubulin and thioredoxin peroxidase have the potential to be utilized as biomarkers for DHF.

The use of two-dimension electrophoresis to identify serum biomarkers from patients with dengue haemorrhagic fever.

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.

Cross-reactive T-cell responses to the nonstructural regions of dengue viruses among dengue fever and dengue hemorrhagic fever patients in Malaysia.

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.

Bloodstream infection in children.

OBJECTIVE: To establish the definitions of bloodstream infection (BSI) in children for the purposes of identifying BSI for early therapy, enrollment in sepsis trials, and epidemiology and surveillance studies. METHODS: Generalized medical literature search using various combinations of the terms "bloodstream infection," "children," and "sepsis." RESULTS: The medical literature is sparse on these topics; therefore, these recommendations are adapted from guidelines designed for adults. BSI overlaps with other areas of sepsis, such as catheter-related BSI, which will be covered separately. This discussion focuses on BSI of unknown origin, also known as primary BSI. CONCLUSION: 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.