Diagnosis and Management of Dengue Fever in Children Ashlesha Kaushik, Carol Pineda and Helen Kest Pediatr. Rev.

2010;31;e28-e35 DOI: 10.1542/pir.31-4-e28

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pedsinreview.aappublications.org/cgi/content/full/31/4/e28

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1979. Pediatrics in Review is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2010 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.

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Article

infectious diseases

Diagnosis and Management of Dengue Fever in Children

Ashlesha Kaushik, MD,* Carol Pineda, MD,* Helen Kest, MD, MPH, CPH

Objectives
1. 2. 3. 4.

After completing this article, readers should be able to:

Describe the epidemiology and clinical spectrum of dengue viral infections. Recognize when to consider dengue in the differential diagnosis of acute fever. Discuss the diagnosis and management of this common tropical illness. Identify other diseases that can mimic dengue viral infections.

Author Disclosure Drs Kaushik, Pineda, and Kest have disclosed no nancial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/ investigative use of a commercial product/ device.

Case 1 Presentation
A 17-year-old Hispanic girl presents with a 5-day history of temperature of 39.4C to 40.5C and a 4-day history of severe bifrontal and intermittent headaches. She also has a 3-day history of malaise, generalized body aches, and mild epigastric pain. On the day of admission, she develops a dark reddish-purple, nonpruritic, and nonblanching rash over her arms and thighs and is brought to the emergency department. There is no cough, sore throat, vomiting, or diarrhea. She denies illicit drug use, tick exposure, sexual activity, or allergies. On physical examination, the girl appears alert, oriented, and in no acute distress. Her temperature is 38.5C, heart rate is 119 beats/min, respiratory rate is 18 breaths/min, and blood pressure is 130/68 mm Hg (90th to 95th percentile). Capillary rell time is less than 2 seconds. A petechial rash is present over her arms and anterior thighs. She has mild epigastric tenderness, with no rebound tenderness, guarding, hepatosplenomegaly, or masses. Tourniquet test is positive. Kernig and Brudzinski signs are negative. The remainder of the physical examination ndings are normal. Her white blood cell count is 3.5 103/mcL (3.5 10 9/L) with 59% neutrophils, 33% lymphocytes, 6% monocytes, and 1% eosinophils; hemoglobin is 13.4 g/dL (134 g/L); hematocrit is 39.6% (0.396); platelet count is 126 103/mcL (126 10 9/L); and erythrocyte sedimentation rate is 13 mm/hour. The electrolytes, urinalysis, and coagulation prole are normal. The stool is negative for blood. Liver function test results include a protein concentration of 6.9 g/dL (69 g/L), albumin of 4 g/dL (40 g/L), aspartate aminotransferase of 39 U/L, alanine aminotransferase of 18 U/L, alkaline phosphatase of 103 U/L, total bilirubin of 0.9 mg/dL (15.4 mcmol/L), and direct bilirubin of 0.3 mg/dL (5.1 mcmol/L). Thick and thin smears are negative for malarial parasites. The patient is admitted for monitoring, and intravenous hydration is started. On additional questioning, she states that she had returned from the Dominican Republic yesterday. Additional serum testing reveals the diagnosis of classic dengue fever. Viral serology reveals a dengue virus immunoglobin M (IgM) enzyme-linked immunosorbent assay (ELISA) titer of 4.93 (negative, 1.11) and dengue virus IgG ELISA titer of 9.69 (negative, 1.11). Platelet counts and hematocrit values are monitored every day. On the second hospital day, her platelet count declines to 96 10 3/mcL (96 10 9/L) with no evidence of bleeding. The counts increase to 109 10 3/mcL (109 10 9/L) on the third hospital day and 121 10 3/mcL (121 10 9/L) on the following day. Her hematocrit value remains stable at 40% (0.40). Three days after hospitalization, the fever resolves, the patient has stable vital signs, and she is discharged.

Case 2 Presentation
A 15-year-old boy who has a 5-day history of a temperature of 39.0C to 39.5C with chills and severe pain in both legs is admitted to the hospital for evaluation. Three days ago, he developed

*Department of Pediatrics, St Josephs Childrens Hospital, Patterson, NJ. Division of Pediatric Infectious Disease, Department of Pediatrics, St. Josephs Childrens Hospital, Patterson, NJ. e28 Pediatrics in Review Vol.31 No.4 April 2010

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nausea, headache, myalgias, and severe fatigue. He denies any vomiting, somnolence, abdominal pain, or neck pain. Findings on past and family histories are unremarkable. Physical examination reveals a tired-looking adolescent who has a temperature of 39.4C, heart rate of 95 beats/ min, respiratory rate of 16 breaths/min, and blood pressure of 120/70 mm Hg (75th to 90th percentile). No neck stiffness, rash, or lesions are apparent. After the blood pressure cuff is removed, he develops petechiae all over his antecubital fossa. He has shotty cervical lymphadenopathy. All other physical ndings are normal. Initial laboratory results reveal a white blood cell count of 3.6 103/mcL (3.6 10 9/L) with 55% neutrophils, 29% bands, 14% lymphocytes, and 10% monocytes; hemoglobin of 15.7 g/dL (157 g/L); hematocrit of 42.2% (0.422); and platelet count of 87 103/mcl (87 10 9/L). Electrolytes and brinogen values are normal. Prothrombin time is 15.2 seconds, international normalized ratio (INR) is 1.2, and activated partial thromboplastin time is 41.2 seconds. D-dimers are 3.3 mcg/mL (normal, 0.50 mcg/mL). Thick and thin smears for malarial parasites are negative. Liver function tests include a total protein of 6.2 g/dL (62 g/L), albumin of 3.4 g/dL (34 g/L), aspartate aminotransferase of 587 U/L, alanine aminotransferase of 412 U/L, alkaline phosphatase of 157 U/L, total bilirubin of 1 mg/dL (17.1 mcmol/L), and direct bilirubin of 0.2 mg/dL (3.4 mcmol/L). Additional questioning reveals that the boy had been in the Dominican Republic for 2 weeks and returned the day his fever started. He is admitted with a diagnosis of suspected dengue hemorrhagic fever. Viral studies sent on admission reveal an acute-phase dengue virus IgM ELISA titer of 1.8 (negative, 1.11) and a dengue virus IgG ELISA titer of 8.8 (negative, 1.11). On the second hospital day, he has one episode of vomiting containing blood. Laboratory results reveal a platelet count of 37 103/mcL (37 10 9/L), prothrombin time of 16.2 seconds, INR of 1.2, and partial thromboplastin time of 42.9 seconds. On the third hospital day, due to another episode of hematemesis and a low platelet count of 21 103/mcL (21 10 9/L), he receives a platelet transfusion. On the same day, he develops diarrhea and mild lower abdominal tenderness. He has a hemoglobin of 18.3 g/dL (183 g/L) and hematocrit of 52.6% (0.53), which is a 20% increase from the baseline. Liver function tests yield normal results except for an albumin of 3.1 g/dL (31 g/L). Ultrasonography of the abdomen shows normal results, and stool examination for parasites and culture produces negative results. Serum amylase and lipase values are normal. On the fth hospital day, the diarrhea subsides and the patient

is afebrile. By the sixth hospital day, the child is feeling better and has stable vital signs. His hematocrit and platelet counts have improved, and he is discharged the following day.

Case 3 Presentation
An 11-year-old Hispanic boy develops a temperature of 39.1C with diarrhea. Two days later, the diarrhea subsides, but he develops severe abdominal pain and vomiting, becomes increasingly lethargic, and is brought to the emergency department. His parents state that he has been complaining of severe back pain and headache. They deny any medication use, previous hospitalization, or tick bites. Physical examination reveals a sick-looking boy who is somnolent but arousable. His temperature is 40.0C, heart rate is 140 beats/min, respiratory rate is 26 breaths/min, blood pressure is 80/50 mm Hg ( 5th percentile), and Glasgow Coma Scale score is 12. He has a weak pulse, cold extremities, and a capillary rell time of 6 to 8 seconds. His abdomen is diffusely tender, with the liver enlarged 4 cm below the right costal margin. A petechial rash is present over his chest and trunk. Meningeal signs are absent. All other physical ndings are unremarkable. Initial laboratory results reveal a white blood cell count of 2.5 103/mcL (2.5 10 9/L) with 58% neutrophils, 8% bands, 10% lymphocytes, 18% atypical lymphocytes, and 4% monocytes; hemoglobin of 14 g/dL (140 g/L); hematocrit of 42% (0.42); and platelet count of 27 103/mcL (27 10 9/L). Electrolyte values are normal, and urinalysis shows trace blood. Coagulation prole reveals a prothrombin time of 17.8 seconds, activated partial thromboplastin time of 44 seconds, D-dimers of 4.4 mcg/mL (normal, 0.50 mcg/mL), and brinogen value of 200 mg% (normal, 183 to 503 mg%). Liver function tests reveal a total protein of 5.6 g/dL (56 g/L), albumin of 3 g/dL (30 g/L), aspartate aminotransferase of 455 U/L, alanine aminotransferase of 324 U/L, alkaline phosphatase of 140 U/L, total bilirubin of 1.2 mg/dL (20.5 mcmol/L), and direct bilirubin of 0.1 mg/dL (1.7 mcmol/L). Smears for malarial parasites are negative. The parents share their concern about multiple relatives who had self-limiting fevers and body aches in the Caribbean, from where they had returned 4 days ago. The child has been to the Caribbean twice within the past 2 years. The clinical and laboratory picture suggest dengue shock syndrome. The boy is admitted to the intensive care unit and started on intravenous hydration. On the second hospital day, he has two episodes of vomiting containing blood and develops frank hematuria. Laboratory results show a platelet count of 14 103/mcL (14 10 9/L), prothrombin time of 19.5 seconds, INR of 1.2, and partial thromboplasPediatrics in Review Vol.31 No.4 April 2010 e29

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tin time of 52 seconds. His hematocrit is 33% (0.33), a 22% decrease from the initial value. He receives platelet and fresh frozen plasma transfusions. There is no recurrence of bleeding, and by the fourth hospital day, he is hemodynamically stable and has improvement in hematocrit and platelet counts (34% [0.34]and 90 103/mcL [90 10 9/L], respectively). On day 5, he continues to be afebrile, is feeling better, and is discharged. Viral studies sent on the third hospital day are strongly positive for dengue virus infection, with a dengue virus IgM ELISA titer of 5.4 (negative, 1.11) and dengue virus IgG ELISA titer of 12 (negative, 1.11).

ndings, and laboratory markers. There are four major clinical syndromes: 1) undifferentiated fever, 2) dengue fever, 3) dengue hemorrhagic fever (DHF), and 4) dengue shock syndrome (DSS). Most cases are mild. However, DHF case fatality rates can reach 20% if not treated appropriately or in a timely manner. It is highly likely that dengue cases are unreported in the United States because physicians often do not include it in the differential diagnosis of travelers returning from endemic areas. (6)(7)

Pathogenesis
Dengue virus is an arbovirus of the avivirus family that has four different serotypes (DEN-1, -2, -3, and -4). Its classication is based on biologic and immunologic characteristics. (8) Because there is no cross-protection between the different serotypes, lifetime immunity is obtained only after infection by each type. Therefore, persons living in endemic areas may be infected more than once with different serotypes. Genetic variation within each serotype confers distinct virulence capacity and epidemic potential that may result in epidemics by the same serotype in different years and locations. (5) After repeated infections, the chance of developing DHF and DSS increases. (9)

Introduction
According to the World Health Organization, about 50 million dengue infections and 25,000 deaths occur worldwide annually, making dengue one of the most important arthropod-borne viral diseases in humans. All continents are endemic for dengue except Europe. An estimated 2.5 billion of the worlds population live in areas at risk for epidemic dengue transmission, and it remains a leading cause of morbidity and mortality among children in some Asian countries. Most of the severe cases and deaths occur in children younger than 15 years of age. (1)(2) The rst reported epidemic occurred in the French West Indies in the 17th century, (3) but it was the Southeast Asia pandemic created by the ecological disruption that followed World War II that is credited for its worldwide spread. Over the past several decades, the gradually increasing incidence has been attributed to multiple factors, including global demographic changes with associated uncontrolled urbanization and population growth, overcrowding with inappropriate sanitation, infrastructural problems, lack of preventive programs for epidemic transmission, and poor mosquito control efforts. (4)(5) Most cases in the United States are imported from other countries. Currently, dengue fever is the most common cause of fever in travelers returning from certain high-risk areas that include the Caribbean, Central America, and South Central Asia. Areas bordering Mexico and southeastern states serve as niches for imported and locally acquired cases of dengue due to population migration. According to the Centers for Disease Control and Prevention, Aedes aegypti and Aedes albopictus are the established vectors in these areas and are a potential threat for dengue transmission throughout the United States. Dengue fever is caused by the dengue virus and is transmitted by the bite of an infective female Aedes mosquito. The diagnosis is based on history, physical
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Mosquito Cycle
A aegypti is the primary vector responsible for transmission; other vectors include A albopictus, A polynesiensis, and A niveus. A aegypti is primarily a daytime feeder. It breeds mainly in articial water collections created by poor sanitation or infrastructure such as jars, plates, owerpots, glass containers, drainpipes, and cupboards. Although transmission is year round, the rainy season creates ideal larval habitats and ecologically suitable niches for mosquito breeding and subsequent endemicity. (10) The life cycle begins when an uninfected female mosquito takes blood from an infected person during the viremic phase of illness. Within the mosquitos digestive system, the virus replicates for 8 to 12 days (extrinsic incubation period). When this infective mosquito bites again, it transmits the virus to another person by injecting its salivary uid. Once the virus is in the body, it replicates in target organs and is released into the blood (intrinsic incubation period). Symptoms appear 3 to 14 days after inoculation and may last up to 7 days or more. Dengue should not be considered in the differential diagnosis of a patient who develops fever more than 2 weeks after leaving a dengue endemic area. (2)

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Clinical Presentation of Dengue Infection

Infection with dengue viruses in children can have varied presentations, ranging from asymptomatic to severe shock and death. Table 1 lists denitions of probable and conrmed dengue syndromes. (2)(11)

Undifferentiated Fever
Patients are mildly symptomatic, with nonspecic ulike symptoms. This pattern usually occurs during a primary infection with dengue viruses and may be the most common manifestation.

Dengue Fever
Classic dengue fever is characterized by abrupt onset of high-grade fever (temperature of 38.9C to 40.6C) associated with headache (especially retroorbital pain that worsens with eye movement), severe myalgia, arthralgia, nausea/vomiting, altered taste sensation (often described as metallic), and sometimes a rash. (2)(12)(13) The constellation of symptoms of severe and incapacitating body ache, back pain, and arthralgia often is called break bone fever. Fever may last from 2 days to 1 week

and occasionally is described as having two peaks or being saddle-backed, that is, the initial 2 to 5 days of fever are followed by 1 to 2 days of defervescence, after which the temperature may rise again. (8)(14)(15) Dengue fever rash may be erythematous, macular, or maculopapular, and lymphadenopathy may be present. Infants and young children usually present with nonspecic symptoms such as fever, runny nose, rash, and diarrhea; older children and adults have the classic break bone fever, as described previously. Dengue fever can have hemorrhagic manifestations without including the entire constellation of DHF. The hemorrhagic manifestations associated with dengue fever include a positive tourniquet test (Figure), petechiae/purpura, mucosal bleeding, and gastrointestinal bleeding. (8)(14) The child in the rst case had petechiae and a positive tourniquet test. Most patients who have dengue fever recover uneventfully. Rarely, patients may present with uncommon manifestations such as seizures, paresis, meningitis, and mental status changes that can include lethargy, somnolence, and coma.

Table 1.

WHO and CDC Denitions of Dengue Clinical Syndromes

Clinical Case Denition

(2)(11)

Type Dengue Fever

Dengue Hemorrhagic Fever (DHF)

Dengue Shock Syndrome (DSS)

Probable dengue fever: Fever of 2 to 7 days duration, with two or more of the following: Headache, retroorbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leukopenia, and supportive serology or occurrence at the same location and time as other conrmed cases of dengue. Conrmed dengue fever: Conrmed by laboratory criteria (isolation of the dengue virus, demonstration of the dengue virus antigen, serology, or genomic sequence). All of the following criteria must be fullled: 1. Fever or history of acute fever, lasting 2 to 7 days, occasionally biphasic 2. Hemorrhagic manifestations in the form of at least one of the following: - A positive tourniquet test - Petechiae, ecchymosis, or purpura - Bleeding from the mucosa or injection sites - Hematemesis, melena, hematochezia, hematuria, increased menstrual ow 3. Thrombocytopenia (<100 103/mcL [100 109/L]) 4. Objective evidence of plasma leakage caused by increased vascular permeability, as evidenced by one or more of the following: - A rise in the hematocrit (dened as >20% over baseline) - A drop in hematocrit following volume replacement treatment <20% of baseline - Low albumin or - Pleural effusion, ascites, or other effusions DHF plus evidence of circulatory failure manifested by shock or all of the following: - Rapid and weak pulse - Narrow pulse pressure (<20 mm Hg) or hypotension for age (systolic pressure <80 mm Hg for children younger than 5 years of age or <90 mm Hg for children 5 years of age and older) - Cold, clammy skin and altered mental status

CDC Centers for Disease Control and Prevention, WHO World Health Organization Pediatrics in Review Vol.31 No.4 April 2010 e31

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Table 2.

Grades of Dengue Hemorrhagic Fever (11)

Grades Grade I Denitions Fever and nonspecic constitutional symptoms, with a positive tourniquet test being the only hemorrhagic manifestation Grade I manifestations plus spontaneous bleeding Circulatory failure manifested as rapid /weak pulse, with cold skin, restlessness, and narrow pulse pressure or hypotension Profound shock with nondetectable pulse or blood pressure

Grade II Grade III*

Grade IV*
Figure. Positive tourniquet test.

* Grades III and IV constitute dengue shock syndrome.

Dengue Hemorrhagic Fever

DHF is a potentially fatal illness marked by high fever, hemorrhagic manifestations, and evidence of plasma leakage (Table 1). DHF begins with the sudden onset of a high temperature that lasts 2 to 7 days, with accompanying chills, ulike constitutional symptoms, and a ushed face. As the fever subsides, patients may recover or progress to a state of plasma leakage. Features of plasma leakage include ascites, pleural effusion (right-sided in most cases), and rarely, pericardial effusion associated with a high mortality. (8)(16) If untreated, the condition may deteriorate rapidly to profound shock and death within hours. (12) The hemorrhagic manifestations of DHF include skin hemorrhages such as petechiae, purpura, and ecchymoses; bleeding from mucous membranes (epistaxis, gingival bleeding); and bleeding from the gastrointestinal, vaginal, and urinary tracts. These manifestations usually occur after the fever subsides, with the gastrointestinal tract being the most common site of bleeding. DHF is classied into four grades according to severity (Table 2). Laboratory abnormalities associated with DHF include thrombocytopenia ( 100 103/mcL [100 109/ L]), leukopenia, prolonged prothrombin time and activated partial thromboplastin time, elevated brin degradation products, low serum albumin, and elevated liver enzymes, as in the patient in case 2. Atypical lymphocytosis ( 15%) and electrolyte abnormalities also may be seen. Recovery from DHF usually is uneventful, marked by a return of appetite and often a recovery rash (erythematous petechial rash with islands of clearing). (2)(8) In a few patients, symptoms such as weakness and malaise may persist for several weeks after the acute illness has subsided. symptoms and has a high mortality rate of 10% to 47%. (2)(17) Warning signs of DSS include severe abdominal pain; persistent vomiting (with or without blood); abrupt change of temperature from fever to hypothermia; and altered mental status, including irritability, somnolence, or obtundation. In DSS, capillary leakage and loss of intravascular volume result in shock rather than in hemorrhage (Table 1). (11)

Complications of Dengue Infections

Severe dengue complications include liver dysfunction, encephalitis, cardiomyopathy (usually reversible), pancreatitis, acalculous cholecystitis, peripheral neuropathy, and acute renal failure. (8)(13)(18) Liver involvement is one of the most important gastrointestinal manifestations, especially with infection by DEN-3 and DEN-4 serotypes, (19) and it can present as acute hepatitis with elevated liver enzyme values (aspartate aminotransferase being more signicantly elevated than alanine aminotransferase), jaundice, altered mental status, seizures, and severe hypoglycemia. Transaminase values are highest on day 9 of illness and normalize within 3 weeks. (18) Central nervous system (CNS) disease is attributed to various factors, including direct viral invasion of the CNS, liver failure, electrolyte disturbances, and cerebral edema. Some case series have reported a high mortality rate (up to 20%) in children who develop encephalopathy. (20) (21)

Diagnosis
Dengue infection can be diagnosed via serologic methods, virus isolation, or molecular methods (Table 3). Table 4 shows the characteristics of similar infections that should be in the differential diagnosis of dengue fever.

Dengue Shock Syndrome

Most patients who have DHF do not develop DSS. DSS occurs during defervescence 3 to 6 days after the onset of
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Table 3.

Methods of Laboratory Diagnosis of Dengue Infection

Comments The IgM ELISA is the most common test for serologic diagnosis. Sensitivity is 83.9% to 98.4% and specicity is 100%. IgM antibodies remain detectable from day 5 to 4 to 5 weeks of illness. (2)(22) Virus isolation methods are employed to determine the serotype of the infecting virus. Because this procedure takes 2 weeks and is costly, it is used primarily for research purposes. Mosquito inoculation technique is more sensitive than cell cultures and is the preferred method of virus isolation. (23) RT-PCR is a rapid method of diagnosis (allowing detection within 24 hours). It is more sensitive than virus isolation and useful in the early phase of illness when antibodies are not circulating. However, this method is costly and needs expertise. (2)(24)

Diagnostic Method Serology: ELISA Hemagglutination inhibition test Complement xation tests Antigen capture enzyme immunosorbent assay Virus Isolation: Mosquito cell cultures Mosquito inoculation: Toxorhynchites amboinensis or Aedes albopictus are used commonly for inoculation Molecular Methods: RT-PCR for viral RNA

ELISA enzyme-linked immunosorbent assay, IgM immunoglobulin M, RT-PCR reverse transcription polymerase chain reaction

Table 4.

Differential Diagnosis of Dengue Fever

Classic Signs and Symptoms Fever, headache, myalgias, malaise, respiratory tract symptoms. (25) High fever, chills, rigor, sweats that may be paroxysmal. Vomiting, diarrhea, cough, arthralgias, abdominal and back pain, hepatosplenomegaly, anemia, and thrombocytopenia are common. (26) Fever, headache, malaise, anorexia, abdominal pain, hepatosplenomegaly, rose spots, altered mental status. (27) Initial phase: Fever, chills, headache, vomiting, transient rash, myalgias of calf and lumbar regions, and conjunctival discharge (nonpurulent). Second phase: meningitis, liver disease, and renal failure. (28) Differentiating Features of Dengue

Disease Inuenza

Malaria

Typhoid fever

Leptospirosis

Meningococcemia Fever, chills, malaise, prostration, rash (macular, maculopapular, petechial). Can progress to fulminant with disseminated intravascular coagulation, purpura, shock, and death. (29) Chikungunya Fever, rash (petechial or maculopapular) of trunk or limbs, arthralgias, arthritis. Other: Headache, conjunctivitis, and photophobia. Travel history is usually positive for Africa or Asia. (30) Rash, posterior auricular or suboccipital lymphadenopathy, headache, conjunctivitis, polyarthritis. (31)

Rubella

Similar to undifferentiated fever form Dengue should be included in differential diagnosis when there is a history of travel to endemic area Fever can have a biphasic pattern but is not cyclic Thrombocytopenia may be present in both; diagnostic studies are needed Typical break bone features are absent Severe disease may be difcult to differentiate from DSS, and diagnostic studies may be needed Biphasic presentation in leptospirosis and eye ndings Usually exposure to animals/farms Travel history to high-risk areas may be absent in leptospirosis DHF or shock due to dengue may be undistinguishable from meningococcemia; it is reasonable to manage as meningococcemia, and dengue fever should be considered as a possibility in returned travelers Febrile illness in dengue does not last as long and is not followed by arthralgic disease, which is prolonged in chikungunya Rash does not have the cephalocaudal distribution of rubella; similar to undifferentiated fever form

DHF dengue hemorrhagic fever, DSS dengue shock syndrome

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Treatment
Treatment is supportive. Fever is controlled with acetaminophen. Nonsteroidal anti-inammatory agents should be avoided due to their anticoagulant properties and risk of Reye syndrome in children. Most cases of dengue fever are mild and occur as undifferentiated fever or classic dengue fever. Early recognition and treatment decreases morbidity and mortality. Home therapy with adequate uid intake and bed rest should be reinforced. Patients do not have to be admitted to the hospital or receive intravenous uids unless they present with severe vomiting, dehydration, bleeding, altered mental status, clinical deterioration, or evidence of DHF or DSS. Patients who have DHF and can be managed as outpatients include those who have platelet counts of at least 50 103/mcL (50 109/L), no active bleeding (besides the petechiae), and a hematocrit that is not elevated. Patients who have DHF and those who are in shock should be treated in an intensive care setting. Hematologic, cardiovascular, and uid and electrolyte status should be observed and supported. The platelet transfusion threshold in DHF is controversial, and transfusion is required only in patients who have severe thrombocytopenia or hemorrhagic manifestations. (8) When dengue is considered in a differential diagnosis, acute-phase (0 to 5 days) and convalescent-phase samples (14 to 21 days) should be collected and sent for viral isolation and serology.

travel, global migration, and climate change continue to affect this global reemergence. (32) Dengue never should be overlooked in countries whose prevalence is low, such as the United States. Dengue fever continues to appear, and the possibility of epidemics exists even after several years of sporadic outbreak.

Summary
Today, dengue is considered among the most important arthropod-borne viral diseases in humans. It is transmitted by the bite of an infective female Aedes mosquito. (2)(6) According to the World Health Organization and Centers for Disease Control and Prevention, the incidence of dengue in the United States is increasing and may be underreported due to inadequate disease recognition and low index of suspicion. (1)(7) Children younger than 15 years of age are at highest risk for severe disease and death. (2)(25) The spectrum of dengue viral infections includes four categories: undifferentiated fever, dengue fever, DHF, and DSS. (1)(11) DHF and shock forms should be managed aggressively in an intensive care setting to prevent morbidity and mortality. (2)(12) Dengue should be considered in the differential diagnosis of any child who develops fever within 2 weeks of travel to endemic areas. (2)

Prevention/Infection Control
Pretravel counseling for all patients visiting endemic regions should emphasize measures to prevent humanvector contact. Using repellants containing N,Ndiethyl-3-methylbenzamide (DEET), wearing protective clothing (long-sleeved shirts and pants) during the mosquito-biting period (morning and afternoon), and using bed nets can minimize mosquito bites. Insect repellants can be used safely in children older than 2 months of age. Travelers also can reduce their risk by staying in screened or air-conditioned areas when possible and avoiding potential mosquito breeding sites. Eliminating mosquito breeding by covering water containers and eliminating standing water can prevent the transmission of dengue virus. Worldwide epidemic control involves aggressive initiatives targeting prevention of dengue transmission and includes educating the medical community and improving public health infrastructure that provides integrated A aegypti control and an active, laboratory-based surveillance system that has a rapid response contingency plan for epidemic prevention. However, factors such as air
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References
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Fever. Publication No. 117. Geneva, Switzerland: World Health Organization; 2008 2. Division of Vector Borne Infectious Disease. Dengue Fever. Atlanta, Ga: Centers for Disease Control and Prevention; 2008 3. Howe GM. World Geography of Human Diseases. New York, NY: Academic Press; 1977 4. Guzman MG, Kouri G. Dengue: an update. Lancet Infect Dis. 2002;2:33 42 5. World Health Organization. Initiative of vaccine research: vector-borne viral infections. The World Health Report. 2003 6. Centers for Disease Control and Prevention. Travel-associated dengueUnited States, 2005. MMWR Morb Mort Wkly Rep. 2006; 55:700 702 7. Centers for Disease Control and Prevention. Travel-associated dengue infections, 20012004. MMWR Morb Mort Wkly Rep. 2005;54:556 558 8. Malavige GN, Fernando S, Fernando DJ, Seneviratne SL. Dengue viral infections. Postgrad Med J. 2004;80:588 601 9. Halstead SB. Dengue haemorrhagic fevera public health problem and a eld for research. Bull WHO. 1980;58:121 10. Promprou S, Jaroensutasinee M, Jaroensutasinee K. Climatic factors affecting dengue hemorrhagic fever: incidence in southern Thailand. Dengue Bulletin. 2005;29 11. World Health Organization. Dengue in the Context of Inte-

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Pediatrics in Review Vol.31 No.4 April 2010 e35

Diagnosis and Management of Dengue Fever in Children Ashlesha Kaushik, Carol Pineda and Helen Kest Pediatr. Rev. 2010;31;e28-e35 DOI: 10.1542/pir.31-4-e28

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