The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Dengue <s> Classification of dengue using the current World Health Organization (WHO) system is not straightforward. In a large prospective study of pediatric dengue, no clinical or basic laboratory parameters clearly differentiated between children with and without dengue, although petechiae and hepatomegaly were independently associated with the diagnosis. Among the 712 dengue-infected children there was considerable overlap in the major clinical features. Mucosal bleeding was observed with equal frequency in those with dengue fever and dengue hemorrhagic fever (DHF), and petechiae, thrombocytopenia, and the tourniquet test differentiated poorly between the two diagnostic categories. Fifty-seven (18%) of 310 with shock did not fulfill all four criteria considered necessary for a diagnosis of DHF by the WHO, but use of the WHO provisional classification scheme resulted in considerable over-inflation of the DHF figures. If two separate entities truly exist rather than a continuous spectrum of disease, it is essential that some measure of capillary leak is included in any classification system, with less emphasis on bleeding and a specific platelet count. <s> BIB001 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Dengue <s> 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. ::: ::: ::: OBJECTIVES ::: To analyse the experience of clinicians in using the dengue case classification and identify challenges in applying the criteria in routine clinical practice. ::: ::: ::: METHOD ::: Systematic literature review of post-1975 English-language publications on dengue classification. ::: ::: ::: RESULTS ::: Thirty-seven papers were reviewed. Several studies had strictly applied all four WHO criteria in DHF cases; however, most clinicians reported difficulties in meeting all four criteria and used a modified classification. The positive tourniquet test representing the minimum requirement of a haemorrhagic manifestation did not distinguish between DHF and DF. In cases of DHF thrombocytopenia was observed in 8.6-96%, plasma leakage in 6-95% and haemorrhagic manifestations in 22-93%. The low sensitivity of classifying DHF could be due to failure to repeat the tests or physical examinations at the appropriate time, early intravenous fluid therapy, and lack of adequate resources in an epidemic situation and perhaps a considerable overlap of clinical manifestations in the different dengue entities. ::: ::: ::: CONCLUSION ::: A prospective multi-centre study across dengue endemic regions, age groups and the health care system is required which describes the clinical presentation of dengue including simple laboratory parameters in order to review and if necessary modify the current dengue classification. <s> BIB002
One of the most rapidly spreading mosquito-borne viral diseases in the world is dengue. The incidence of dengue has increased in the last 50 years as a result of increasing geographic expansion to new countries and to rural areas  . Annually, the World Health Organization (WHO) estimates the occurrence of 50 million dengue infections occurring and approximately 2.5 billion people facing threats of dengue since they live in dengue endemic areas  . According to the WHO 1997 guidebook of Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control, 2nd ed.  , some patients develop dengue fever (DF) in the early stage after a person is infected with the dengue virus and recover after the fever subsides, while other patients may progress on to develop dengue haemorrhagic fever (DHF). Laboratory and clinical diagnosis are used to diagnose the dengue patient. The clinical diagnosis and severity of DHF were graded from grades I to IV based on the WHO guidebook recommendation in 1997  . The WHO guidelines define Grade I as patients having a fever accompanied by nonspecific constitutional symptoms with the only haemorrhagic manifestation being a petechial rash. Grade II is defined as patients having a spontaneous bleeding from any site on their skin. Grades III and IV are known as dengue shock syndrome (DSS). Grade III is where a patient has circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV (DSS) is defined as patients having profound shock  . With the WHO 1997 dengue severity classification guideline  , many clinicians experienced several difficulties especially in the critical cases such as the DHF patients which may experience significant plasma leakage that may lead to haemorrhage and organ impairment. The decision to admit those patients to the hospital in order to monitor their plasma leakage is a great challenge due to the overlapping of present medical classification criteria for establishing the risk of dengue patients BIB001 BIB002 . On the other hand, physicians cannot decide to admit all patients because this will have an impact on the cost and quality of health care due to the high incidence of dengue in the tropics. Thus, to overcome these difficulties and to assist clinicians in determining the severity of the infection and how patients should be treated, the WHO has improved and introduced the new  guidebook which defines the dengue patients' classification according to a few levels of severity. This guideline has been approved in year 2010 and valid until year 2014. In this new guidebook, the dengue patients are no longer classified as DF and DHF, instead patients are divided into two simplified groups. They are either severe or non-severe dengue patients. The non-severe dengue patients are further classified into two subgroups: patients with warning signs and those without warning signs. In the new WHO 2009 guidebook  , the classification criteria for non-severe dengue without warning signs are fever and any two of the following: nausea/vomiting, rash, aches and pain, a positive tourniquet test, leucopoenia, and there may even be a combination of these warning signs. The warning signs for non-severe dengue with warning signs are: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation (pleural effusion/ascites), mucosal bleeding, lethargy, restlessness, liver enlargement (>2 cm), and an increase in hematocrit (HCT) concurrent with a rapid decrease in platelet count. Such patients with these warning signs require strict observation and medical intervention. Severe dengue infections are characterized by significant plasma leakage, severe bleeding, and severe involvement of organs such as the liver. This causes liver enzymes such as aspartate aminotransferase (AST), or the alanine aminotransferase (ALT) to be elevated with readings of ≥1000 units/L. Laboratory diagnosis of dengue patients is used to detect the dengue virus. Currently, a definitive diagnosis of dengue infection can be made only in the laboratory, either through virus isolation, detection of viral antigen or ribonucleic acid (RNA) present in serum or other bodily fluid, detection of antibodies present in serum, or a combination of these techniques   . At the early stage of infection, virus isolation and the detection of nucleic acid or antigen is used to make a diagnosis of dengue infection; however at the end of the acute phase of infection serological methods are more suitable  . A number of commercially rapid test kits (or coated strips) have been developed by various companies such as Korea's Standard Diagnostics, Biorad and Panbio. These kits are able to detect a combination of either antigen or antibodies  . Although rapid laboratory diagnosis is very important and highly desirable, of equal importance is the recovery rate of the patient and the patient's quality of life after recovery. To date, there is no effective vaccine or antiviral drug for dengue  . Some of the dengue patients might recover spontaneously while others face critical plasma loss that can lead to fatality  . Serology tests are not able to diagnose the micro-vascular status (micro-vascular leakage or plasma leakage) of the patient which is one of the major pathophysiological changes during dengue infection. Nevertheless the fatality of dengue disease can be reduced by close monitoring of patients to detect the onset of plasma leakage and administer prompt intravenous fluid replacement  .