objectives case study€¦ · · 2017-10-26objectives identify cases of dengue fever. recognize...

O b j e c t i v e s ■ Identify cases of dengue fever.

■ Recognize the difference between dengue fever, dengue hemorrhagic fever, and dengue shock syndrome.

■ Identify what to avoid in the treatment of the various dengue syndromes

C a s e S t u d yA 32-year-old man with no medical history presents with a fever of 3 days’ duration associated with myalgia, diffuse abdominal pain, vomiting, and lower extremity petechial rash. He is lethargic. His blood pressure is 110/94 mm Hg, and heart rate is 110 beats/min. Saturation by pulse oximeter (Spo

2) is 97% on room air, and

temperature is 37.2°C (98.96°F). He lives in Puerto Rico. One week before his symptoms appeared, he attended an outdoor picnic, where he was bitten by mosquitoes multiple times.

– What is the differential diagnosis?

– What immediate interventions are needed?

– What additional evaluations are indicated?

C h a p t e r 2

Dengue FeVer

F C C S : Tr o p i c a l D i s e a s e s

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I . I N T R O D U C T I O NIn the past decades, the transmission of dengue and the frequency of epidemics have increased significantly, especially in tropical regions in the American continent. Dengue is a mosquito-borne infection; its vector is the mosquito Aedes aegypti. The four distinct dengue viruses (DENV-1, -2, -3, and -4) all cause a similar clinical syndrome, which ranges from no symptoms to dengue shock syndrome (DSS). The severity of disease results from a secondary infection with a second strain of the virus, especially in hyperendemic areas. This is thought to be due to an erratic immune response to the virus that includes non-protective antiviral antibodies and the surface of the virion and, through interaction with the Fc receptor, focuses secondary dengue viruses on the target cell, the result being enhanced infection. The induction of vascular permeability and shock depends on multiple factors, including the presence of enhancing and non-neutralizing antibodies, age (susceptibility to dengue hemorrhagic fever [DHF]/DSS drops considerably after age 12 years), sex (females are more affected than males), race (whites are more affected than blacks), nutritional status (malnutrition is a protective factor), the sequence of viral infection (DENV-1 followed by DENV-2 is more dangerous than DENV-4 followed by DENV-2), and the infecting serotype (DENV-2 is apparently more dangerous than other serotypes). It is important to recognize the early stages of dengue fever, DHF, and DSS, because of the low mortality rate with early recognition.

I I . D I A G N O S I SDengue fever is characterized by the acute onset of high fever 3 to14 days after being bitten by a mosquito. Additional signs and symptoms are frontal headache, retro-orbital pain, myalgia, arthralgia, hemorrhagic manifestations, rash, low white blood cell count, anorexia, and nausea. Usually these symptoms last about 1 week, except for anorexia and weakness, which may persist for several weeks. Most of these dengue infections can produce minimal or no symptoms in those infected. Some of the main complications are febrile seizures and dehydration.

D e n g u e F e v e r 2

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The diagnosis is made by immunoglobulin M enzyme-linked immunosorbent assay (ELISA) or paired serology during recovery, or by antigen detection ELISA or reverse transcriptase-polymerase chain reaction during the acute phase. The virus is readily isolated from blood in the acute phase if a mosquito inoculation or mosquito cell culture is used.

In some cases, patients may develop DHF, a severe and sometimes fatal form of dengue. This usually appears around the time the fever subsides (3-7 days after the symptom onset). The patient may develop warning signs of severe disease:

■ Severe abdominal pain

■ Persistent vomiting

■ Marked change in temperature (from fever to hypothermia)

■ Hemorrhagic manifestations

■ Changes in mental status

The World Health Organization has determined that four criteria must be present to diagnose DHF, five criteria for DSS (Table 1). The main difference between dengue fever and DHF is plasma leakage due to increased vascular permeability.


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DSS is the most severe form of dengue infection. It is diagnosed using the four criteria for DHF, plus evidence of circulatory failure (Table 1). Mortality rates may be as high as 10%, but with early recognition and experienced centers, this drops to as low as 1%.

I I I . T H E R A P YFor DF, therapy consists mainly of relieving pain, controlling fever (avoiding aspirin or nonsteroidal anti-inflammatory agents to avoid hemorrhagic complications and Reye syndrome in pediatric patients), and reminding the patient to drink lots of water, especially in the setting of high fever. The World Health Organization has developed guidelines for different groups according to the severity of disease. Group A consists mainly of outpatient management, group B consists of patients with warning signs, and group C encompasses patients with compensated shock and hypotensive shock.

W o r l d H e a l t h O r g a n i z a t i o n D i a g n o s t i c C r i t e r i a f o r D e n g u e

Dengue Hemorrhagic Fever1. Fever or recent history of fever lasting 2 to 7 days2. Hemorrhagic manifestation (positive results on tourniquet test, petechiae or hematomas,

epistaxis, gingival bleeding, microscopic hematuria)3. Thrombocytopenia (<100,000 platelets/mm3)4. Increased vascular permeability (increased hematocrit [>20% above the population mean

for age and sex], hematocrit decreased by 20% after intravenous fluids, pleural effusions, ascites, hypoproteinemia, and hypoalbuminemia)

Dengue Shock Syndrome1. Fever or recent history of fever lasting 2 to 7 days2. Hemorrhagic manifestation (positive results on tourniquet test, petechiae or hematomas,

epistaxis, gingival bleeding, microscopic hematuria)3. Thrombocytopenia (<100,000 platelets/mm3)4. Increased vascular permeability (increased hematocrit [>20% above the population mean

for age and sex], hematocrit decreased by 20% after intravenous fluids, pleural effusions, ascites, hypoproteinemia, and hypoalbuminemia)

5. Circulatory failure (rapid, weak pulse and narrow pulse pressure [<20 mm Hg] or hypotension for age, restlessness, or cold, clammy skin)

T a b l e 1


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Regardless of group classification, it is crucial to recognize the critical period, which begins with defervescence and lasts 24 to 48 hours. It is also important to monitor fluid intake and output, vital signs, and hematocrit levels. Early shock must be recognized and treated accordingly. In patients with refractory shock, colloids such as albumin may be administered if two to three boluses of isotonic solution have already been given. Finally, if a patient has significant bleeding, consider transfusing packed red blood cells or whole blood.

Some actions should be avoided in the management of dengue, such as the use of corticosteroids, since they may increase the risk of gastrointestinal bleeding, hyperglycemia, and immunosuppression. Platelet transfusions should be avoided in patients with low platelet counts, since they have not been shown to decrease the risk of severe bleeding and may result in fluid overload and prolonged hospitalization. Isotonic solution should be used for fluid replacement, and half normal (0.45%) saline should be avoided even as maintenance fluid because it leaks into third spaces and may lead to development or worsening of ascites and pleural effusions. Finally, it should never be assumed that intravenous (IV) fluids are necessary; always check for tolerance of oral administration, and decrease the IV fluid rate as hemodynamic status and urine output improve. Disseminated intravascular coagulation should be treated only if clear laboratory evidence of its existence is found and if laboratory monitoring of therapy is feasible; there is no proven benefit of such therapy.

Proper patient management is based on group classification and hemodynamic status as specified by the World Health Organization.

A . G r o u p A : O u t p a t i e n t M a n a g e m e n t o f F e v e r a n d M o n i t o r i n g

Patients classified as group A receive outpatient management for treatment. During the febrile phase and subsequent critical phase, follow the complete blood count and watch for dehydration signs. Warning signs that disease is progressing include decreased platelet count and increased hematocrit. Defervescence indicates the beginning of the critical phase. Fever should be controlled


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with acetaminophen, avoiding aspirin and nonsteroidal anti-inflammatory agents. Patients should be admitted to the clinic or emergency department if they exhibit a decrease in urination, dry mouth, listlessness, agitation, confusion, tachycardia, cold or clammy extremities, sunken eyes or, in an infant, depressed fontanelle.

B . G r o u p B : I n p a t i e n t M a n a g e m e n t f o r P a t i e n t s w i t h W a r n i n g S i g n s

After admitting the patient to the hospital, at least one baseline complete blood count is required. Vital signs should be evaluated every 4 hours or more frequently, and intake and output should be monitored, with fluid intake encouraged. If oral fluid intake is adequate, the patient should be observed for early signs of shock and severe dengue. If fluid intake is inadequate, check the hematocrit and give isotonic crystalloid solution, normal saline, or Ringer lactate in a stepwise manner, as illustrated in Figure 1. The patient’s hematocrit and clinical status should be reassessed. If the patient is stable and does not show a change in hematocrit, IV fluids can be decreased. However, if vital signs worsen or the hematocrit rapidly increases, the crystalloids should be increased, and the hematocrit should be rechecked. If shock develops, the patient is reclassified into group C and treated accordingly.


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Figure 1. Group B: Inpatient Management for Patients with Warning Signs

Reproduced with permission from: Centers for Disease Control and Prevention. Dengue Clinician Guidelines. 2009. http://www.cdc.gov/dengue/resources/DENGUE-clinician-guide_508.pdf. Accessed September 18, 2014.


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C . G r o u p C : I n p a t i e n t M a n a g e m e n t f o r P a t i e n t s w i t h C o m p e n s a t e d S h o c k

Patients with shock should be treated in the intensive care unit. Baseline hematocrit and organ function tests should be obtained, fluid intake and output should be closely monitored, and the hemodynamic status and vital signs should be verified every 1 to 2 hours. If the hemodynamic status improves, the steps in group B treatment should be followed (Figure 1). If there is no improvement, the hematocrit should be reassessed; if it is decreasing, packed red blood cells should be transfused (Figure 2). If the hematocrit increases, administer a crystalloid bolus infusion at a rate of 10- 20 mL/kg over 1 hour. The isotonic solution rate should be decreased if the clinical status improves, and with continued improvement, the steps in Figure 1 should be followed. If the clinical status does not improve, the hematocrit should be verified and reassessed for an increasing or decreasing trend. If hypotensive shock develops, the steps in Figure 3 should be followed.


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Figure 2. Group C: Inpatient Management for Patients with Compensated Shock



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D . G r o u p C : I n p a t i e n t M a n a g e m e n t f o r P a t i e n t s w i t h H y p o t e n s i v e S h o c k

Initially follow the steps taken in patients with compensated shock (Figure 2). Obtain baseline hematocrit and organ function test results, closely monitor fluid intake and output, but assess hemodynamic status and vital signs hourly. An isotonic crystalloid or colloid bolus of 20 mL/kg should be administered within 15 minutes. If the patient’s hemodynamic status improves, administer an isotonic crystalloid or colloid infusion at 10 mL/kg over 1 hour. With continued improvement, IV fluids should be decreased (Figure 3, Box B). If the hemodynamic status does not improve, the hematocrit should be reassessed; packed red blood cells should be given if it is decreasing. The patient’s clinical status should be reassessed, and if it is improving, the colloid solution can be decreased (7-10 mL/kg/h) for 1 to 2 hours. With continued improvement, reduce IV fluids in a stepwise manner (Figure 3, Box B). If no clinical improvement is evident, the hematocrit should be verified and reassessed for an increasing or decreasing trend, and the previous steps followed.

E . C r i t e r i a f o r D i s c h a r g i n g P a t i e n t s

Discharge criteria include the absence of fever for at least 24 hours without the use of antifever therapy (physical or medical), return of appetite, visible clinical improvement, appropriate urine output, stable hematocrit, 2-day recovery from shock, no respiratory distress from pleural effusion or ascites, and a platelet count >50,000/mm3.

K E Y P O I N T S ■ Dengue fever is characterized by the acute onset of high

fever 3 to 14 days after being bitten by a mosquito. Additional signs and symptoms are frontal headache, retro-orbital pain, myalgia, arthralgia, hemorrhagic manifestations, rash, low white blood cell count, anorexia, and nausea.


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Figure 3. Group C: Inpatient Management for Patients with Hypotensive Shock



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■ Dengue hemorrhagic fever develops around the time the fever subsides (3-7 days after symptom onset), and patients may develop warning signs of severe disease, such as severe abdominal pain, persistent vomiting, marked change in temperature (from fever to hypothermia), hemorrhagic manifestations, or changes in mental status.

■ Dengue hemorrhagic fever is defined by fever or a recent history of fever lasting 2 to 7 days, any hemorrhagic manifestation, thrombocytopenia (<100,000 platelets/mm3), and evidence of increased vascular permeability.

■ The main difference between dengue fever and dengue hemorrhagic fever is plasma leakage caused by increased vascular permeability.

■ The most severe form of dengue infection is dengue shock syndrome, diagnosed by the presence of the four criteria for dengue hemorrhagic fever, plus evidence of circulatory failure.

■ Early shock must be recognized and treated accordingly. The critical period begins with defervescence and lasts 24 to 48 hours. Close monitoring of fluid intake and output, vital signs, and hematocrit levels is required.

■ Colloids may be given in refractory shock.

■ Use of packed red blood cells or whole blood transfusions is indicated for clinically significant bleeding, but platelet transfusions should be avoided.

■ Avoid the use of corticosteroids.

■ Do not use half normal (0.45%) saline, and do not assume that intravenous fluids are necessary.


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S u g g e s t e d R e a d i n g s1. Barrera R. Simplified pupal surveys of Aedes aegypti (L.)

for entomologic surveillance and dengue control. Am J Trop Med Hyg. 2009;81(1):100-107. http://www.ajtmh.org/content/81/1/100.full.pdf. Accessed September 17, 2014.

2. Centers for Disease Control and Prevention. Dengue clinician guidelines. 2009. http://www.cdc.gov/dengue/resources/DENGUE-clinician-guide_508.pdf. Accessed September 18, 2014.

3. Centers for Disease Control and Prevention. Interim guideline for managing patients with suspected viral hemorrhagic fever in U.S. hospitals. May 19, 2005. https://stacks.cdc.gov/view/cdc/22139. Accessed May 30, 2016.

4. Gregory C, Santiago L, Arguello, D, Hunsperger E, Tomashek K. Clinical and laboratory features that differentiate dengue from other febrile illnesses in an endemic area—Puerto Rico, 2007-2008. Am J Trop Med Hyg. 2010;82(5):922-929.

5. Horstick O, Jaenisch T. Comparing the usefulness of the 1997 and 2009 WHO dengue case classification: a systematic literature review. Am J Trop Med Hyg. 2014;91(3):621-634. http://www.ajtmh.org/content/91/3/621. Accessed May 30, 2016.

6. Hunsperger E, Yoksan S, Buchy P, et al. Evaluation of commercially available dengue virus immunoglobulin M tests. Emerg Infect Dis. 2009;15(3):436-440.

7. Kasper D. Infections caused by arthropod- and rodent-borne viruses. In: Harrison’s Infectious Diseases. 17th ed. New York, NY: McGraw-Hill Medical; 2010:971-984.

8. Puerto Rico Department of Health. http://www.salud.gov.pr.


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9. Simmons CP, Farrar JJ, Chau NVV, Wills B. Dengue. N Engl J Med. 2012;366(15):1423-1432. http://www.nejm.org/doi/full/10. 1056/NEJMra1110265. Accessed May 30, 2016.

10. Smith J, Amador M, Barrera R. Seasonal and habitat effects on dengue and West Nile virus vectors in San Juan, Puerto Rico. J Am Mosq Control Assoc. 2009;25(1):38-46. http://www.bioone.org/doi/pdf/10.2987/08-5782.1. Accessed August 24, 2014.

11. World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf. Accessed September 24, 2014.

objectives case study€¦ · · 2017-10-26objectives identify cases of dengue fever. recognize...

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