Evidence for a revised dengue case classification: A multi-centre prospective study across Southeast Asia and Latin America

Background: There has been growing concern regarding the applicability and usefulness of the current World Health Organisation (WHO) classification system for dengue. The terminology emphasises haemorrhage rather than vascular leakage as an indicator of severity, and the classification is misleading in a significant proportion of patients with shock. Methods: We recruited children and adults with suspected dengue in seven countries across Southeast Asia and Latin America. Patients were followed daily with detailed case report forms, and subsequently categorised into one of three intervention groups according to the overall level of medical and nursing support required. Using an a priori analysis plan, the clinical and laboratory profiles characteristic of these intervention categories were explored to develop a revised system based on disease severity. Results: 2259 patients were recruited between August 2006 and May 2007. A total of 230 (13%) of the 1734 laboratory confirmed patients required major intervention, with approximately 5% of patients progressing to this level of severity in hospital. Applying the current WHO system, 47/210 (22%) of patients with shock did not fulfil all criteria necessary for dengue haemorrhagic fever. We used „bottom-up“ as well as „top-down“ strategies to design a new system that takes into account clinical severity as by medical intervention category. Clinical signs and symptoms were evaluated by ROC against intervention category and a logical algorithm was used selecting or omitting candidate variables for the revised classification. Inclusion of readily discernible complications (shock and/or severe bleeding and/or severe organ dysfunction) was necessary in order to devise a revised system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. In addition several warning signs for disease progression were identified. Conclusions: Based on these results, a revised classification system comprised of two entities, „Dengue“ and „Severe Dengue“, is proposed.