WHO Dengue Classification Research Articles

1376. A Retrospective Analysis of Intravenous Fluid Therapy Practice at Hospital Admission for Adults with Dengue

Abstract Background Dengue epidemics in Asia was almost exclusively a childhood disease but recently dengue in adults have become increasingly prevalent. Yet intravenous fluid replacement (IVFR), the main supportive therapy for dengue, was developed for pediatric dengue. Evidence-based guidance for fluid replacement, especially for older adults with concomitant chronic diseases that both increases risk of severe dengue and complicate fluid replacement, is lacking. We retrospectively analyzed the use of IVFR in adult dengue patients at admission to a tertiary hospital. Methods Medical records of patients diagnosed with dengue (confirmed by rapid NS1 kit or laboratory confirmation of RT-PCR, NS1 or IgM) from January 2020 to December 2022 were analyzed. Recovery phase was defined as fever defervescence for >12 hours with rising platelet count. Appropriateness of IVFR was based on disease severity according to the 2009 WHO dengue classification scheme. Results Preliminary analysis of the first 30 patients found an almost equal number of males (47%) and females. The median age was 52.5 years (range 15.0-83.0). 20 patients had at least one comorbidity with hyperlipidemia (33%), hypertension (23%) and ischemic heart disease (10%) being the most common. Average time from onset to presentation was 4.3 days (95% CI: 3.8-4.9). 16 (53%) met the WHO classification scheme as requiring IVFR at admission; 4 hypotension, 5 acute kidney injury (AKI), 2 hypotension with AKI, 4 hemoconcentration, 1 AKI with hemoconcentration. Of these 16, one also had altered mental status and another had hemophagocytic lymphohistiocytosis-like presentation. Despite 47% having uncomplicated dengue, all patients had IVFR at admission. Total fluid volume administered during hospitalization varied across the population and fluctuated daily for each patient, with 8 patients receiving IVFR beyond the recovery phase. One developed fluid overload while another had IV cannula-related thrombophlebitis. There was no mortality. Conclusion Preliminary findings of our on-going study suggest excessive use of IVFR and the lack of standardization possibly contributed to two iatrogenic complications. We call for development of evidence-based protocol on fluid management in older dengue patients. Disclosures All Authors: No reported disclosures

To find out role of serum ferritin levels as an early predictor of severity of dengue-an observational study

Background: Ferritin is an acute-phase reactant and highly expressed by cells of the reticulo-endothelial system in response to infection and inflammation. Hyperferritinaemia is a hallmark of diseases characterized by extensive immune activation such as malignancy or viral infection, including dengue. Aims and Objectives: To find out if serum ferritin levels can predict the severity of dengue early. Material and Methods: Study design: This was a single centre, prospective observational study done on 50 patients with positive NS1Ag or dengue antibody serology Ig-M and are admitted in Paediatric ward or in Paediatric ICU during study period (December 2019 - May 2021) in tertiary care centre, Karad. Enrolled patients underwent serum ferritin level analysis at time of admission. Serum ferritin levels were later compared with the severity of the dengue disease (According to WHO dengue classification 2009). Statistical Analysis: Data was analyzed using computer software, SPSS-v21, DeLong et al (1988) and Binomial exact. Data was expressed in frequency and percentage as well as mean and standard deviation. A p<0.05 was taken as significant.

Cytokine Signature of Dengue Patients at Different Severity of the Disease

Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

Clinical manifestations of primary and secondary dengue in Paraguay and its relation to virus serotype.

Dengue virus (DENV) infection is currently a major cause of morbidity in the world, and its incidence has mainly increased during the last years in Latin America, including Paraguay. The objective of this study was to compare the clinical and laboratory findings of dengue and assess whether the serotype is a risk factor for severity. We included patients ≤ 15 years old hospitalized with dengue at the Institute of Tropical Medicine, from Paraguay, from 2007 to 2018. Patients were classified according to the 2009 WHO dengue classification guidelines and were stratified by serotype into three groups according to the hospitalization period: the 2007 epidemic (DENV-3), the 2012-2013 epidemic (DENV-2) and the 2016-2018 epidemic (DENV-1). Of 784 children hospitalized for dengue, 50 cases (6.3%) were caused by DENV-3, 471 (60%) by DENV-2, and 263 (33.5%) by DENV-1. Myalgias and headache were associated with DENV-3 cases and abdominal pain was associated with DENV-2 cases. Bleeding was observed mainly in DENV-1 and 2 cases. Patients with DENV-2 infections experienced more severe disease, required fluid expansion more frequently, and exhibited more often shock and admission in the ICU. Secondary cases of dengue were more severe that primary cases. Patients with infection by DENV-2 had longer hospital stays (5.1 ± 2.8 days) when compared to DENV-3 o DENV-1 infection cases (2.9 ± 1.6 days and 4.36 ± 2.7 days, respectively) (p < 0.05). The DENV serotype has a profound impact on the clinical manifestations and severity of dengue. DENV-2 infections were associated more frequently to requirement of fluid expansion, shock, and longer hospital stay.

Classification of dengue cases in Southwest India based on the WHO systems—a retrospective analysis

The WHO dengue classification 1997 was revised in 2009 and the revised classification system has now been in use for the past decade. This study was carried out to compare the 1997 and revised classifications in assessing the severity of dengue infection among all age groups during a dengue outbreak in southwest India. This retrospective cross-sectional study was carried out including serologically confirmed dengue cases. A total of 1033 dengue cases were classified on the basis of the 1997 WHO classification and 2009 revised classification. The statistical analysis was carried out using SPSS 15.0 for Windows (SPSSTM Inc, Chicago, IL, USA). Both the 1997 and revised WHO classifications were applied to 1033 confirmed dengue cases, including 692 males (67%) and 341 females (33%). The median age of the study participants was 23 years (IQR 10-33), including 112 (10.8%) children at and below the age of 5 years. The level of agreement between the two systems of classification was poor (kappa=0.143, 0.055-0.198, p-value <0.001). A greater sensitivity and specificity of the revised classification was observed in comparison with the 1997 WHO classification. In the context of changing dengue epidemiology and geographical expansion, the revised classification is helpful in the identification of severe cases, facilitating timely management.

Definitions for warning signs and signs of severe dengue according to the WHO 2009 classification: Systematic review of literature.

Since warning signs and signs of severe dengue are defined differently between studies, we conducted a systematic review on how researchers defined these signs. We conducted an electronic search in Scopus to identify relevant articles, using key words including dengue, "warning signs," "severe dengue," and "classification." A total of 491 articles were identified through this search strategy and were subsequently screened by 2 independent reviewers for definitions of any of the warning or severe signs in the 2009 WHO dengue classification. We included all original articles published in English after 2009, classifying dengue by the 2009 WHO classification or providing the additional definition or criterion of warning signs and severity (besides the information of 2009 WHO). Analysis of the extracted data from 44 articles showed wide variations among definitions and cutoff values used by physicians to classify patients diagnosed with dengue infection. The establishment of clear definitions for warning signs and severity is essential to prevent unnecessary hospitalization and harmonizing the interpretation and comparability of epidemiological studies dedicated to dengue infection.

Management of dengue in Australian travellers: a retrospective multicentre analysis.

To describe the epidemiology, clinical and laboratory features and outcomes of dengue in returned Australian travellers, applying the revised WHO dengue classification (2009) to this population. Retrospective case series analysis of confirmed dengue cases hospitalised at one of four Australian tertiary hospitals, January 2012 - May 2015. Clinical features, laboratory findings and outcomes of patients with dengue; dengue classification according to 2009 WHO guidelines. 208 hospitalised patients (median age, 32 years; range, 4-76 years) were included in the study. Dengue was most frequently acquired in Indonesia (94 patients, 45%) and Thailand (40, 19%). The most common clinical features were fever (98% of patients) and headache (76%). 84 patients (40%) met the WHO criteria for dengue with warning signs, and one the criteria for severe dengue; the most common warning signs were mucosal bleeding (44 patients, 21%) and abdominal pain (43, 21%). Leukopenia (176 patients, 85%), thrombocytopenia (133, 64%), and elevated liver enzyme levels (154, 76%) were the most common laboratory findings. 46 patients (22%) had serological evidence of previous exposure to dengue virus. WHO guidelines were documented as a management benchmark in ten cases (5%); 46 patients (22%) received non-steroidal anti-inflammatory drugs (NSAIDs). A significant proportion of returning Australian travellers hospitalised for dengue have unrecognised warning signs of severe disease. Many received NSAIDs, which can increase the risk of haemorrhage in dengue. As travel to Asia from Australia continues to increase, it is vital for averting serious outcomes that clinicians can recognise and manage dengue.

Factors Associated with the Time of Admission among Notified Dengue Fever Cases in Region VIII Philippines from 2008 to 2014.

In cases of Dengue fever, late hospital admission can lead to treatment delay and even death. In order to improve early disease notification and management, it is essential to investigate the factors affecting the time of admission of Dengue cases. This study determined the factors associated with the time of admission among notified Dengue cases. The study covered the period between 2008 and 2014 in Region VIII, Philippines. The factors assessed were age, sex, hospital sector, hospital level, disease severity based on the 1997 WHO Dengue classification, and period of admission (distinguishing between the 2010 Dengue epidemic and non-epidemic time). We analysed secondary data from the surveillance of notified Dengue cases. We calculated the association through chi-square test, ordinal logistic regression and linear regression at p value < 0.05. The study included 16,357 admitted Dengue cases. The reported cases included a majority of children (70.09%), mild cases of the disease (64.00%), patients from the public sector (69.82%), and non-tertiary hospitals (62.76%). Only 1.40% of cases had a laboratory confirmation. The epidemic period in 2010 comprised 48.68% of all the admitted cases during this period. Late admission was more likely among adults than children (p<0.05). The severe type of the disease was more likely to be admitted late than the mild type (p<0.05). Late admission was also more likely in public hospitals than in private hospitals (p<0.05); and within tertiary level hospitals than non-tertiary hospitals (p<0.05). Late admission was more likely during the non-epidemic period than the 2010 epidemic period (p<0.05). A case fatality rate of 1 or greater was significantly associated with children, severe diseases, tertiary hospitals and public hospitals when admitted late (p<0.05). Data suggests that early admission among child cases was common in Region VIII. This behavior is encouraging, and should be continued. However, further study is needed on the late admission among tertiary, public hospitals and non-epidemic period with reference to the quality of care, patient volume, out of pocket expense, and accessibility We recommend the consistent use of the 2009 WHO Dengue guidelines in order to standardize the admission criteria and time across hospitals.

Meta-Analysis of Dengue Severity during Infection by Different Dengue Virus Serotypes in Primary and Secondary Infections.

IntroductionDengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and has gained much attention. Thus, this review compared the percentage of severe cases of both primary and secondary infections with different serotypes of dengue virus.MethodsData related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords “(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)”, according to the MESH terms suggested by PUBMED and OVID.ResultsApproximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22–53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64–80.89, 4–14 studies, n = 668–3,149, I2 = 14.77–96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47–40.24, 5–8 studies, n = 642–2,530, I2 = 76.93–97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86–54.58, 9 studies, n = 674–2,278, I2 = 55.74–88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4 from the SEA region were discovered to be more highly associated with secondary infection compared to other serotypes (95% CI, 72.01–96.32, 9–12 studies, n = 671–2,863, I2 = 25.01–96.75%).ConclusionThis study provides evidence that the presence of certain serotypes, including primary infection with DENV-3 from the SEA region and secondary infection with DENV-2, DENV-3, and DENV-4 also from the SEA region, as well as DENV-2 and DENV-3 from non SEA regions, increased the risk of severe dengue infections. Thus, these serotypes are worthy of special consideration when making clinical predictions upon the severity of the infection.Systematic Review RegistrationPROSPERO CRD42015026093 (http://www.crd.york.ac.uk/PROSPERO)

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

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. We followed suspected dengue cases daily in seven countries across South-east Asia and Latin America and then categorised them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre-defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not. A total of 2259 patients were recruited during 2006-2007 and 230 (13%) of the 1734 laboratory-confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue haemorrhagic fever. However, no three-tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression. Based on these results, a revised classification system comprised of two entities, 'Dengue' and 'Severe Dengue', was proposed and has now been incorporated into the new WHO guidelines.

The WHO dengue classification and case definitions: time for a reassessment

Dengue is the most prevalent mosquito-borne viral disease in people. It is caused by four dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus, and transmitted by Aedes aegypti mosquitoes. Infection provides life-long immunity against the infecting viral serotype, but not against the other serotypes. Although most of the estimated 100 million dengue virus infections each year do not come to the attention of medical staff, of those that do, the most common clinical manifestation is non-specific febrile illness or classic dengue fever.