Dengue virus infection is more and more acknowledged as one of the world’s major escalating problems. Dengue is prevalent in most tropical and subtropical countries. To solve this problem, pharmacists need to understand the epidemiology, risk factors, clinical spectrum, diagnosis, management, prevention, and novel avenues of dengue.
Dengue is the most frequent origin of arboviral infection. Four dengue (DEN) virus serotypes are, known as DEN-1, DEN-2, DEN-3, and DEN-4. They fit into the genus Flavivirus, family unit Flaviviridae having approximately 70 viruses [
Lack of effective mosquito control is a third major factor in areas where dengue is widespread [
In short, lack of resources for vector-borne infectious disease prevention and control, demographic and communal changes, and changes in public health policy have all contributed to amplifying happening dengue activity, the expansion of hyperendemicity, and the appearance of epidemic DHF.
Dengue hemorrhagic fever (DHF) is a critical sign of dengue, which is more frequent after a secondary infection with dengue virus. Cost effective vaccine and drugs are considered necessary for the prevention and control of dengue.
Alteration in the dengue epidemiology escorts to problems with the use of the presented WHO classification. Symptomatic dengue virus infections were grouped into three categories: undifferentiated fever, dengue fever (DF) and dengue hemorrhagic fever (DHF). DHF had more classified into four severity grades, with grades III and IV being defined as dengue shock syndrome (DSS) [
For clinical care efficient and accurate diagnosis of dengue is of primary importance (i.e. Early recognition of severe cases, case authentication and differential diagnosis with other infectious diseases), surveillance actions, outbreak control, pathogenesis, academic research, vaccine development, and clinical trials.
Criteria for dengue | Warning signs | Criteria for severe dengue |
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Probable dengue ・ live in/travel to dengue endemic area. ・ Fever and 2 of the following criteria: ・ Nausea, vomiting ・ Rash ・ Aches and pains ・ Tourniquet test + ve ・ Leukopenia ・ Any warning sign Laboratory-confirmed dengue (Important when no sign of plasma leakage) | ・ Abdominal pain or tenderness ・ Persistent vomiting ・ Clinical fluid accumulation ・ Mucosal bleeding ・ Lethargy, restlessness ・ Liver enlargement > 2 cm ・ Laboratory: ↑ in HCT ・ Concurrent with rapid ↓ in platelet count *(Requiring strict observation and medical intervention) | Severe plasma leakage leading to: ・ Shock (DSS) ・ Fluid accumulation with respiratory distress Severe bleeding As evaluated by clinician Severe organ involvement ・ Liver: AST/ALT > 1000 ・ CNS: Impaired consciousness ・ Heart and other organs as well |
Dengue virus causes a systemic and dynamic disease which has a wide clinical spectrum that includes both severe and non-severe clinical features [
Severe dengue is defined by one or more of the following:
1) Plasma leakage that may lead to shock (dengue shock) and/or fluid accumulation, with or without respiratory distress, and/or
2) Severe bleeding
3) Severe organ impairment
If the patient is from an area of dengue risk presenting with fever of 2 - 7 days plus any of the following manifestations severe dengue should be considered:
1) Plasma leakage supported by such as: high or progressively rising haematocrit; pleural effusions or ascites; circulatory compromise or shock (tachycardia, cold and clammy extremities, capillary refill time greater than three seconds, weak or untraceable pulse, narrow pulse pressure or, in late shock, recordable blood pressure).
2) Significant bleeding
3) Altered level of consciousness (lethargy or restlessness, coma, convulsions)
4) Severe gastrointestinal involvement (constant vomiting, growing or intense abdominal pain, jaundice
5) Severe organ destruction (acute liver failure, acute renal failure encephalopathy or encephalitis, or other unusual manifestations, cardiomyopathy) or other curious manifestations.
For effective programmed management important activities are regular monitoring of the delivery of dengue prevention and control services and evaluation of the impact of interventions. Appropriate indicators should be
Febrile phase | Critical phase | Recovery phase |
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・ Dehydration ・ High fever ・ Neurological disturbances ・ Febrile seizures in young children | ・ Shock from plasma leakage ・ Severe hemorrhage ・ Organ impairment | ・ Hypervolemia (only if intravenous fluid therapy has been excessive and/or has extended into this period) |
A stepwise approach to the management of dengue |
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Step I. Overall assessment I.1 History, including information on symptoms, past medical and family history I.2 Physical examination, including full physical and mental assessment I.3 Investigation, including routine laboratory and dengue-specific laboratory Step II. Diagnosis II.1 Assessment of disease phase and severity Step III. Management III.1 Disease notification III.2 Management decisions. Depending on the clinical manifestations and other circumstances. Patients may: ¾ Be sent home ¾ Be referred for in-hospital management ¾ Require emergency treatment and urgent referral |
recognized to measure the advancement of execution, with output and outcome indicators.
The pharmacist should play a key role in good clinical practices to ensure rational treatment to the dengue patient as given in
Vector control and personal protection from the bites of infected mosquitoes are currently possible key prevention
Activity | Good practice | Bad practice |
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Environmental management | Determining local ecology of immature stages as a basis for choosing the most appropriate interventions Integrating dengue control with sanitation, solid waste disposal, water supply services and other vector and pest control programs | Investing disproportionately in chemical control methods when affordable and more sustainable environmental management solutions are available. Responding primarily to outbreaks and not investing in sustained vector control measures. |
Chemical control | Using insecticides judiciously | Using chemical control methods without Evaluating efficacy and cost-effectiveness, and Without monitoring local vector susceptibility. |
Municipal services | Intersectoral collaboration on urban development or renewal to minimize the availability of larval habitats of dengue vectors and vectors of other diseases | Social marketing of larvicides for water-storage containers, with consequent low coverage rates. |
Entomological monitoring and surveillance | Monitoring of vector populations to target Control in time and space and to provide feedback for program adjustment | Generating routine entomological surveillance data that are not analyzed or utilized in a timely and efficient manner for management decision-making. |
Good clinical practice | Bad clinical practice | |
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1 | Assessment and follow-up of patients with non-severe dengue and careful instruction of warning signs to watch out for | Sending patients with non-severe dengue home with no follow-up and inadequate instructions |
2 | Administration of paracetamol for high fever if the patient is uncomfortable | Administration of acetylsalicylic acid (aspirin) or ibuprofen |
3 | Obtaining a hematocrit level before and after fluid boluses | Not knowing when hematocrit levels are taken with respect to fluid therapy |
4 | Clinical assessment of the hemodynamic status before and after each fluid bolus | No clinical assessment of patient with respect to fluid therapy |
5 | Interpretation of hematocrit levels in the context of fluid administered and hemodynamic assessment | Interpretation of hematocrit levels independent of clinical status |
6 | Administration of intravenous fluids for repeated vomiting or a high or rapidly rising hematocrit | Administration of intravenous fluids to any patient with non-severe dengue |
7 | Use of isotonic intravenous fluids for severe dengue | Use of hypotonic intravenous fluids for severe dengue |
8 | Giving intravenous fluid volume just sufficient to maintain effective circulation during the period of plasma leakage for severe dengue | Excessive or prolonged intravenous fluid administration for severe dengue |
9 | Avoiding intramuscular injections in dengue patients | Giving intramuscular injections to dengue patients |
10 | Intravenous fluid rate and frequency of monitoring and hematocrit measurement adjusted according to the patient’s condition | Fixed intravenous fluid rate and unchanged frequency of monitoring and hematocrit measurement during entire hospitalization for severe dengue |
11 | Close monitoring of blood glucose, i.e. tight glycemic control | Not monitoring blood glucose, unaware of the hyperglycemic effect on osmotic diuresis and confounding hypervolemia |
12 | Discontinuation or reducing fluid therapy once hemodynamic status stabilizes | Continuation and no review of intravenous fluid therapy once hemodynamic status stabilizes |
of dengue. But, the development of drugs and vaccines has the potential to revolutionize this. For an anti-dengue drug and vaccines, there are various requirements. Oral route of administration, frequency of dosing of once per day, stability in the face of heat and humidity, a long shelf-life, and small/reasonable cost of goods and ease of formulation to permit a reasonably priced product should be included in the minimal target drug profile [