History

Fact Explanation
Exposure to mosquito bite Dengue fever is caused by an RNA virus which has 4 serotypes named dengue virus type 1 to type 4. Infection with one serotype provides life-long immunity against that particular serotype, and partial immunity against other serotypes. When a person who is immune to one serotype gets infected with another serotype, the risk of developing severe dengue is high. After the incubation period, febrile phase starts which is followed by the critical phase and recovery phase. [6,7] However these sequence of events might not be present in all patients with dengue. Some patients may not enter the critical phase and some remain asymptomatic. [8]
Symptoms during the febrile period Fever is preceded by the prodromal symptoms (chills, erythematous diffuse skin rash and facial flushing). [2] Infants and young children may present with mild fever but adults usually present with rapidly rising fever often more than 39°C. Nausea and or vomiting are common associations of fever. During the febrile period patients often complain of severe retro-orbital headache, arthralgia, myalgia and fatigue. [2] Petechiae, bruising and macular or maculopapular erythematous skin rash can develop during the febrile phase. [4,6]
Symptoms during the critical phase During the critical phase plasma leaking and hemorrhagic manifestations occur and it happens around the time of defervescence (roughly 4-5 days after the onset of fever and lasts about 48 hours). [2,5,6] Cutaneous bleeding and mucosal bleeding (hemoptysis, melena, vaginal bleeding, and epistaxis) manifest during this phase. [2,3,6] Dengue shock syndrome can occur during this phase. [6] Severe dengue is a deadly consequence of dengue fever that can occur during the critical phase, and it is the cumulative effect of plasma leak, respiratory failure, severe hemorrhage, and multi organ failure. Patients often complain of severe abdominal pain, persistent vomiting, hematemesis, gum bleeding, rapid breathing, fatigue and restlessness. [7]
Symptoms during the recovery phase Patients often complain of rapid improvement of the symptoms. Cutaneous manifestations include asymptomatic or itchy maculopapular rash. Fatigue may remain even after the recovery period in adults and may last about several weeks. [6]
Risk factors A recent history of travel to an endemic area and presence of diagnosed patients with dengue fever in the near vicinity and living in an environment with lot of mosquito breeding sites are risk factors. [1]
References
  1. ALI M, WAGATSUMA Y, EMCH M, BREIMAN RF. Use of a geographic information system for defining spatial risk for dengue transmission in Bangladesh: role for Aedes albopictus in an urban outbreak. Am J Trop Med Hyg [online] 2003 Dec, 69(6):634-40 [viewed 24 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/14740881
  2. THOMAS EA, JOHN M, KANISH B. MUCOCUTANEOUS MANIFESTATIONS OF DENGUE FEVER Indian J Dermatol [online] 2010, 55(1):79-85 [viewed 24 May 2014] Available from: doi:10.4103/0019-5154.60359
  3. Dengue fever in Indonesia. World Health Organization. [online] [viewed 24 May 2014] Available from: http://www.who.int/csr/don/2004_02_26a/en/index.html
  4. THOMAS EA, JOHN M, BHATIA A. Cutaneous manifestations of dengue viral infection in Punjab (north India). Int J Dermatol [online] 2007 Jul, 46(7):715-9 [viewed 24 May 2014] Available from: doi:10.1111/j.1365-4632.2007.03298.x
  5. RICHARDS AL, BAGUS R, BASO SM, FOLLOWS GA, TAN R, GRAHAM RR, SANDJAJA B, CORWIN AL, PUNJABI N. The first reported outbreak of dengue hemorrhagic fever in Irian Jaya, Indonesia. Am J Trop Med Hyg [online] 1997 Jul, 57(1):49-55 [viewed 24 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9242317
  6. SIMMONS CAMERON P., FARRAR JEREMY J., VAN VINH CHAU NGUYEN, WILLS BRIDGET. Dengue. N Engl J Med [online] 2012 April, 366(15):1423-1432 [viewed 25 May 2014] Available from: doi:10.1056/NEJMra1110265
  7. Dengue and severe dengue. World health organization. [online] [viewed 25 May 2014] Available from: http://www.who.int/mediacentre/factsheets/fs117/en/
  8. GARCíA G, SIERRA B, PéREZ AB, AGUIRRE E, ROSADO I, GONZALEZ N, IZQUIERDO A, PUPO M, DANAY DíAZ DR, SáNCHEZ L, MARCHECO B, HIRAYAMA K, GUZMáN MG. Asymptomatic Dengue Infection in a Cuban Population Confirms the Protective Role of the RR Variant of the Fc?RIIa Polymorphism Am J Trop Med Hyg [online] 2010 Jun, 82(6):1153-1156 [viewed 25 May 2014] Available from: doi:10.4269/ajtmh.2010.09-0353

Examination

Fact Explanation
Febrile phase As the name implies patients are febrile and can have mild hemorrhagic manifestations like, petechiae and skin bruising. [1,6] Hepatomegaly, the most valuable indicator of hepatic involvement in dengue fever is detected during the febrile phase and often associated with jaundice. [4,5] Lymphadenopathy occurs due to viral replication within the lymph nodes. [3]
Signs during the critical phase Patients are usually afebrile. Plasma leaking reduces the circulatory volume and patients develop tachycardia, narrow pulse pressure hypotension, cold blotchy skin congested peripheries, and central cyanosis occurs with circulatory collapse. [4] Plasma leaking results in pleural effusions and ascites. [4] Petechiae, epistaxis, and gingival bleeding are cutaneous manifestations. [1,2] Tourniquet test usually becomes positive during the hemorrhagic phase. Although positive tourniquet test only suggests dengue fever a negative test cannot exclude the possibility of dengue. [7] Tender hepatomegaly is still present during the critical phase as well. [6]
Signs during the recovery phase A maculopapular skin rash and desquamation of the skin lesions are seen during the recovery phase. [6]
References
  1. THOMAS EA, JOHN M, KANISH B. MUCOCUTANEOUS MANIFESTATIONS OF DENGUE FEVER Indian J Dermatol [online] 2010, 55(1):79-85 [viewed 24 May 2014] Available from: doi:10.4103/0019-5154.60359
  2. Dengue fever in Indonesia. World Health Organization. [online] [viewed 24 May 2014] Available from: http://www.who.int/csr/don/2004_02_26a/en/index.html
  3. RAZA FAIZ AHMED, et al. Demographic and Clinico-Epidemiological Features of Dengue Fever in Faisalabad, Pakistan. PLoS ONE [online] 2014 March [viewed 24 May 2014] Available from: doi:10.1371/journal.pone.0089868
  4. GURUGAMA P, GARG P, PERERA J, WIJEWICKRAMA A, SENEVIRATNE SL. DENGUE VIRAL INFECTIONS Indian J Dermatol [online] 2010, 55(1):68-78 [viewed 24 May 2014] Available from: doi:10.4103/0019-5154.60357
  5. JAGADISHKUMAR K, JAIN P, MANJUNATH VG, UMESH L. Hepatic Involvement in Dengue Fever in Children Iran J Pediatr [online] 2012 Jun, 22(2):231-236 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446077
  6. SIMMONS CAMERON P., FARRAR JEREMY J., VAN VINH CHAU NGUYEN, WILLS BRIDGET. Dengue. N Engl J Med [online] 2012 April, 366(15):1423-1432 [viewed 25 May 2014] Available from: doi:10.1056/NEJMra1110265
  7. MAYXAY M, et al. Predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection in adults Trop Med Int Health [online] 2011 Jan, 16(1):127-133 [viewed 25 May 2014] Available from: doi:10.1111/j.1365-3156.2010.02641.x

Differential Diagnoses

Fact Explanation
Viral fever [1] Most children and infants present with non-specific symptoms and fever resembling more common viral fever. Chikungunya fever have rapid onset of symptoms and a shorter febrile period. [2,4] Koplik's spots which appear during the prodromal phase are pathognomonic of measles. [1] Rubella, Roseola infantum, infectious mononucleosis, typhoid fever, leptospirosis are other infective causes presenting with fever and rash. [1] Infection with enterovirus, adenovirus, malaria, viral hepatitis, rickettsial diseases, and bacterial sepsis should also be considered. [5]
Scarlet fever Another differential diagnosis for fever with rash. Skin rash appears after 12 hours to 2days of onset of fever and become generalized within few hours. [1]
Kawasaki disease Often high spiking fever is prolonged and should be suspected in patients with bilateral non-suppurative conjunctivitis, red cracked lips, “strawberry tongue”, peeling of the skin from fingertips and polymorphic macular, maculopapular or urticarial rash. [3]
Infective exanthems Skin manifestations of dengue fever may mimic bacterial or viral exanthems. [1]
References
  1. THOMAS EA, JOHN M, KANISH B. MUCOCUTANEOUS MANIFESTATIONS OF DENGUE FEVER Indian J Dermatol [online] 2010, 55(1):79-85 [viewed 24 May 2014] Available from: doi:10.4103/0019-5154.60359
  2. NIMMANNITYA S, HALSTEAD SB, COHEN SN, MARGIOTTA MR. Dengue and chikungunya virus infection in man in Thailand, 1962-1964. I. Observations on hospitalized patients with hemorrhagic fever. Am J Trop Med Hyg [online] 1969 Nov, 18(6):954-71 [viewed 24 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/5355242
  3. D ELEFTHERIOU, M LEVIN, D SHINGADIA, R TULLOH, NJ KLEIN, PA BROGAN. Management of Kawasaki disease. Arch Dis Child [online] 2014;99:74-83. [viewed 24 May 2014] Available from: http://adc.bmj.com/content/99/1/74.full
  4. STAPLES J. ERIN, BREIMAN ROBERT F., POWERS ANN M.. Chikungunya Fever: An Epidemiological Review of a Re‐Emerging Infectious Disease. CLIN INFECT DIS [online] 2009 September, 49(6):942-948 [viewed 24 May 2014] Available from: doi:10.1086/605496
  5. SIMMONS CAMERON P., FARRAR JEREMY J., VAN VINH CHAU NGUYEN, WILLS BRIDGET. Dengue. N Engl J Med [online] 2012 April, 366(15):1423-1432 [viewed 25 May 2014] Available from: doi:10.1056/NEJMra1110265

Investigations - for Diagnosis

Fact Explanation
Full blood count Thrombocytopenia and leucopenia are seen in full blood count. In some patients platelet count can be normal. Packed cell volume is raised in dengue hemorrhagic fever. [1,3]
Reverse transcription (RT)-PCR Detects the dengue antigen and enables the diagnosis within 2 to 7 days of illness. [2]
Enzyme-linked immunosorbent assay (ELISA) ELISA can detect antibodies against dengue virus. Ig M type indicates an acute infection and Ig G type indicates a secondary infection. [5] ELISA is also useful in detecting E/M antigen and the NS1 antigen up to 9days from the onset of symptoms. [2,4]
References
  1. GURUGAMA P, GARG P, PERERA J, WIJEWICKRAMA A, SENEVIRATNE SL. DENGUE VIRAL INFECTIONS Indian J Dermatol [online] 2010, 55(1):68-78 [viewed 24 May 2014] Available from: doi:10.4103/0019-5154.60357
  2. SHU PY, HUANG JH. Current Advances in Dengue Diagnosis Clin Diagn Lab Immunol [online] 2004 Jul, 11(4):642-650 [viewed 25 May 2014] Available from: doi:10.1128/CDLI.11.4.642-650.2004
  3. POTTS JA, ROTHMAN AL. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations Trop Med Int Health [online] 2008 Nov, 13(11):1328-1340 [viewed 25 May 2014] Available from: doi:10.1111/j.1365-3156.2008.02151.x
  4. CHATERJI S, ALLEN JC JR, CHOW A, LEO YS, OOI EE. Evaluation of the NS1 Rapid Test and the WHO Dengue Classification Schemes for Use as Bedside Diagnosis of Acute Dengue Fever in Adults Am J Trop Med Hyg [online] 2011 Feb 4, 84(2):224-228 [viewed 25 May 2014] Available from: doi:10.4269/ajtmh.2011.10-0316
  5. SIMMONS CAMERON P., FARRAR JEREMY J., VAN VINH CHAU NGUYEN, WILLS BRIDGET. Dengue. N Engl J Med [online] 2012 April, 366(15):1423-1432 [viewed 25 May 2014] Available from: doi:10.1056/NEJMra1110265

Investigations - Fitness for Management

Fact Explanation
Liver function test Hepatic transaminases are elevated and the liver function can be deranged. Acute liver failure can occur with multi organ dysfunction syndrome. [1,2]
Renal function test Assessment of the renal function is important as acute renal failure is a complication of severe dengue. [3]
References
  1. GURUGAMA P, GARG P, PERERA J, WIJEWICKRAMA A, SENEVIRATNE SL. DENGUE VIRAL INFECTIONS Indian J Dermatol [online] 2010, 55(1):68-78 [viewed 24 May 2014] Available from: doi:10.4103/0019-5154.60357
  2. JAGADISHKUMAR K, JAIN P, MANJUNATH VG, UMESH L. Hepatic Involvement in Dengue Fever in Children Iran J Pediatr [online] 2012 Jun, 22(2):231-236 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446077
  3. LEE IK, LIU JW, YANG KD. Clinical characteristics, risk factors, and outcomes in adults experiencing dengue hemorrhagic fever complicated with acute renal failure. Am J Trop Med Hyg [online] 2009 Apr, 80(4):651-5 [viewed 24 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19346394

Investigations - Followup

Fact Explanation
Full blood count Full blood count should be repeated at least once a day to detect the progression of the disease. Platelet count is considered as the surrogate marker to monitor the disease progress. Platelet count drops rapidly during the febrile phase and the lowest value is recorded during the critical phase. Platelet count less than 100,000/μL indicates impending dengue hemorrhagic fever or dengue shock syndrome. [9] Hemoconcentration occurs in the critical phase due to plasma leaking. So the packed cell volume rises. 20% or more rise in packed cell volume from the baseline value is diagnostic of dengue hemorrhagic fever. [2] With those clues in full blood count, evidence of fluid leakage (pleural effusion, pericardial effusion, ascites) should be looked for. Rising platelet counts indicates end of the critical phase and entering in to the recovery phase.
Ultrasound scan Enables detection of hepatomegaly, pleural effusions, pericardial effusions and ascites in dengue hemorrhagic fever. [5]
Chest X-ray Detect pleural effusions. But this is inferior to ultrasound scan in detecting pleural effusions. [6,7] Often lateral decubitus chest X-ray can detect small pleural effusions than an erect chest X-ray film. [9]
Serum electrolytes Acute renal failure is a known complication of dengue hemorrhagic fever and dengue shock syndrome, but this is uncommon. [1]
Coagulation studies Disseminated intravascular coagulation is a complication associated with dengue shock syndrome (DSS). [2] Prothrombin time prolongs in the presence of hepatic involvement. [3]
Hepatic transaminases Elevated in hepatic involvement. [2,3]
Serum bilirubin Can be increased due to hepatic involvement. [3]
Serum albumin Low in dengue shock syndrome. [3]
Fibrin degradation products Elevated in disseminated intra-vascular coagulation. [4]
Blood grouping and cross matching Platelet transfusion may be needed in severe thrombocytopenia. [8]
References
  1. LEE IK, LIU JW, YANG KD. Clinical characteristics, risk factors, and outcomes in adults experiencing dengue hemorrhagic fever complicated with acute renal failure. Am J Trop Med Hyg [online] 2009 Apr, 80(4):651-5 [viewed 24 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19346394
  2. GURUGAMA P, GARG P, PERERA J, WIJEWICKRAMA A, SENEVIRATNE SL. DENGUE VIRAL INFECTIONS Indian J Dermatol [online] 2010, 55(1):68-78 [viewed 24 May 2014] Available from: doi:10.4103/0019-5154.60357
  3. JAGADISHKUMAR K, JAIN P, MANJUNATH VG, UMESH L. Hepatic Involvement in Dengue Fever in Children Iran J Pediatr [online] 2012 Jun, 22(2):231-236 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446077
  4. MITRAKUL C, POSHYACHINDA M, FUTRAKUL P, SANGKAWIBHA N, AHANDRIK S. Hemostatic and platelet kinetic studies in dengue hemorrhagic fever. Am J Trop Med Hyg [online] 1977 Sep, 26(5 Pt 1):975-84 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/907057
  5. SANTHOSH VR, PATIL PRASHANTHG, SRINATH MG, KUMAR ASHOK, ARCHANA M, JAIN ADITI. Sonography in the Diagnosis and Assessment of Dengue Fever. J Clin Imaging Sci [online] 2014 December [viewed 25 May 2014] Available from: doi:10.4103/2156-7514.129260
  6. BALASUBRAMANIAN S, JANAKIRAMAN L, KUMAR SS, MURALINATH S, SHIVBALAN S. A reappraisal of the criteria to diagnose plasma leakage in dengue hemorrhagic fever. Indian Pediatr [online] 2006 Apr, 43(4):334-9 [viewed 24 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16651672
  7. ZAKI SA. Pleural Effusion and Ultrasonography in Dengue Fever Indian J Community Med [online] 2011, 36(2):163 [viewed 24 May 2014] Available from: doi:10.4103/0970-0218.84140
  8. TANTAWICHIEN T. Dengue fever and dengue haemorrhagic fever in adolescents and adults. Paediatr Int Child Health [online] 2012 May:22-7 [viewed 24 May 2014] Available from: doi:10.1179/2046904712Z.00000000049
  9. RAJAPAKSE S, RODRIGO C, RAJAPAKSE A. Treatment of dengue fever Infect Drug Resist [online] :103-112 [viewed 25 May 2014] Available from: doi:10.2147/IDR.S22613

Management - General Measures

Fact Explanation
Health education Preventive measures of dengue include destroying mosquito breeding sites and use of mosquito repellents and nets to avoid bitten by the mosquitoes. [1,2,3] Patients with dengue should be advised to take adequate rest and fluid intake. Patients should be warned not to take non-steroidal anti-inflammatory drugs for fever especially during outbreaks. [3] Patients can be managed as an out patient during the febrile period and they should be advised to seek immediate health care if they develop dehydration, any bleeding manifestations or if there is no symptom improvement with the settlement of fever. [4]
Fluid management Fluid management is the mainstay of treatment. Patients who are in the febrile phase can be managed with oral hydration. But regular monitoring is necessary for the early detection of entering in to the critical phase. [4] Once the critical period is over patient can be asked to take oral fluid with no restriction. [5]
Antipyeritics Paracitamol is the drug of choice and non-steroidal anti-inflammatory drugs are contraindicated. [3]
References
  1. KHORMI HM, KUMAR L. Assessing the risk for dengue fever based on socioeconomic and environmental variables in a geographical information system environment. Geospat Health [online] 2012 May, 6(2):171-6 [viewed 24 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22639119
  2. HEUKELBACH J, DE OLIVEIRA FA, KERR-PONTES LR, FELDMEIER H. Risk factors associated with an outbreak of dengue fever in a favela in Fortaleza, north-east Brazil. Trop Med Int Health [online] 2001 Aug, 6(8):635-42 [viewed 24 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11555429
  3. Dengue. Centers for Disease Control and Prevention. [online] [viewed 25 May 2014] Available from: http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/dengue
  4. KALAYANAROOJ S. Clinical Manifestations and Management of Dengue/DHF/DSS Trop Med Health [online] 2011 Dec, 39(4 Suppl):83-87 [viewed 25 May 2014] Available from: doi:10.2149/tmh.2011-S10
  5. RAJAPAKSE S, RODRIGO C, RAJAPAKSE A. Treatment of dengue fever Infect Drug Resist [online] :103-112 [viewed 25 May 2014] Available from: doi:10.2147/IDR.S22613

Management - Specific Treatments

Fact Explanation
Fluid management during the critical period (in the absence of shock) Patients usually need intravenous fluids during the critical phase. The total fluid requirement (both oral and intravenous) for the 48 hours of critical period is, the sum of maintenance fluid requirement for 24 hours and the fluid deficit, 50 mL/kg calculated up to 50kg of maximum body weight. This amount is to be spread over the critical period, as excessive and injudicious fluid administration can lead to fluid overload and pulmonary edema. Signs of fluid overload (puffy eyes, pulmonary edema) should be cautiously looked for during this period. Sometimes in severe dengue patients need blood transfusions to maintain the intravascular volume. If the hematocrit continue to fall despite adequate fluid replacement, either internal bleeding or end of the critical period should be suspected (As the recovery phase begins extravasated fluid is reabsorbed in to the intravascular compartment, so the hematocrit drops). Cross-matched whole blood should be transfused if significant bleeding (more than 300 ml) develops. Transfusion of platelets is indicated if platelet counts are very low. [1,2]
Fluid management in dengue shock In the presence of dengue shock fluid boluses (20 mL/kg) should be administered until the blood pressure is recordable. Crystalloids are preferred for the initial fluid resuscitation and colloids (dextran) should be used as the second line choice if the blood pressure is not responding to crystalloids. [1,2,3] After patient recovers from the shock the rest of the calculated fluid volume should be administrated not exceeding that.
References
  1. RAJAPAKSE S, RODRIGO C, RAJAPAKSE A. Treatment of dengue fever Infect Drug Resist [online] :103-112 [viewed 25 May 2014] Available from: doi:10.2147/IDR.S22613
  2. KALAYANAROOJ S. Clinical Manifestations and Management of Dengue/DHF/DSS Trop Med Health [online] 2011 Dec, 39(4 Suppl):83-87 [viewed 25 May 2014] Available from: doi:10.2149/tmh.2011-S10
  3. WILLS BRIDGET A., DUNG NGUYEN M., LOAN HA T., TAM DONG T.H., THUY TRAN T.N., MINH LE T.T., DIET TRAN V., HAO NGUYEN T., CHAU NGUYEN V., STEPNIEWSKA KASIA, WHITE NICHOLAS J., FARRAR JEREMY J.. Comparison of Three Fluid Solutions for Resuscitation in Dengue Shock Syndrome. N Engl J Med [online] 2005 September, 353(9):877-889 [viewed 25 May 2014] Available from: doi:10.1056/NEJMoa044057