Man With Febrile Illness Following Foreign Travel

A 64-year-old man presents with a severe febrile syndrome of several days’ duration. The syndrome includes fatigue and severe myalgias and arthralgias. There is no cough, sputum production, rhinorrhea, or severe GI symptoms (such as vomiting or diarrhea). He has taken acetaminophen with minimal relief.

HISTORY

The patient was previously healthy; his only medical condition is mild hypertension, which is successfully managed with a diuretic. He returned 1 week earlier from a summer trip to Vietnam, which he took with a group of fellow veterans to visit places where they had fought during the war. He says he received “vaccinations” before he left and is adamant that he was compliant with malaria prophylaxis. To his knowledge, none of his travel companions have fallen ill since their return to the United States.

PHYSICAL EXAMINATION

This ill-appearing man is in moderate distress. He has flushed facies but no discrete rash. Temperature is 39°C (102.2°F); heart rate is 108 beats per minute and regular. His conjunctivae are injected. Chest is clear, and abdomen is soft and nontender. He has no edema.

LABORATORY RESULTS

Hemoglobin level is normal. White blood cell count is 3900/µL, with a neutrophil count of 1900/µL; platelet count is 117,000/µL. Results of a chemistry panel are normal except for mildly elevated alanine aminotransferase and aspartate aminotransferase levels. When the patient returns to the examining room after the blood draw, “spots” are noted on his arm below the venipuncture site.

Which of the following statements about diagnostic and management considerations for this patient is not true?

A. Diagnosis may be effectively accomplished by direct demonstration of viral components in the blood.
B. The incidence of serious post-viral neurologic sequelae such as paralysis is expected to be about 20%.
C. The major acute morbidity and mortality risks are bleeding and vascular leak.
D. No effective vaccine is yet available.

(Answer and discussion on next page)

Correct Answer: The incidence of serious post-viral neurologic sequelae such as paralysis is expected to be about 20%.
This patient has a febrile illness that began shortly after he returned from foreign travel to a tropical area. The differential diagnosis in such instances is always intriguing and includes malaria, yellow fever, and West Nile virus infection. However, several clinical clues point to dengue as the most likely choice. The acute onset of fever and associated fatigue and severe myalgias and joint pain are all part of the classic presentation of dengue. (The severity of the myalgia and joint pain gave rise to the illness’s common name, “breakbone fever.”)

The patient’s travel history and the time frame of the illness make the diagnosis even more likely. Dengue is endemic in Southeast Asia and has an incubation period of 4 to 14 days; symptoms developed in this man 7 days after he returned from Vietnam. Finally, the hemorrhagic manifestations elicited by the blood drawing tourniquet (a positive result on an inadvertently performed “tourniquet test”) are another strong clinical marker for dengue.¹

EPIDEMIOLOGY

The virus that causes dengue belongs to the family Flaviviridae and is transmitted by a variety of common Aedes mosquitoes, including the ubiquitous Aedes aegypti. The latter is a daytime, multiple-bite, human blood feeder that is frequently found in urban, modern, ground-level settings, such as old tires, tin cans, and other objects likely to contain standing water.² Dengue is the most common arboviral disease in the world, and it is a leading cause of hospitalization and death among children in Asia.^1,2

Dengue is clearly a risk for travelers to endemic tropical areas. In fact, the incidence figures for dengue (2% to 16% of febrile travelers) are second only to those for malaria.³

MORBIDITY AND MORTALITY

Recently, the World Health Organization (WHO) revised the severity of dengue fever into two categories: dengue or severe dengue. The latter includes patients who display plasma leakage sufficient to cause shock or accumulation of serosal fluid sufficient to cause respiratory distress (or both) and/or severe bleeding.⁴ These are the major morbidities that can result in mortality (choice C). Dengue hemorrhagic fever complicates about 3% of cases and has a mortality of 10% to 20% if not recognized and appropriately managed. Dengue shock syndrome complicates about 1% of cases and has a mortality approaching 40% if not quickly recognized and managed.¹

DIAGNOSTIC STUDIES

A variety of accurate diagnostic studies are now available to confirm the diagnosis of dengue. Which to choose depends on the time line of the patient’s illness. During the acute febrile illness, which typically lasts 3 to 7 days, detection of viral nucleic acid in serum by polymerase chain reaction (PCR) is confirmatory, with sensitivities approaching 90%.⁴ Thus, choice A is a true statement and is not the correct answer. Another serologic test uses an enzyme-linked immunosorbent assay (ELISA) to detect seroconversion with IgM antibodies between paired samples. In fact, a single positive IgM specimen in a patient with the typical clinical syndrome is commonly used worldwide to establish the presumptive diagnosis.⁴

SEQUELAE

Once the acute febrile phase and the critical phase pass (in those patients unfortunate enough to develop leak syndrome, shock, or hemorrhagic manifestations), recovery ensues with improvement occurring quite rapidly. A major symptom that remains in some patients is profound fatigue that can last weeks. Permanent neurologic sequelae such as residual paresis, paralysis, or cognitive deficits that are part of polio or West Nile virus infection cases do not occur in dengue, which makes choice B a false statement and thus the correct answer.

TREATMENT

Unfortunately, there is currently no specific antiviral therapy available for dengue. Supportive care with judicious fluid management in leak/shock cases and blood and platelet transfusion in hemorrhagic cases can significantly lower mortality rates. Similarly, no safe and effective vaccine yet exists for the worldwide common disease, which makes choice D a true statement.

OUTCOME OF THIS CASE

An IgM ELISA serology demonstrated antibody to dengue virus antigens, and the presumptive diagnosis of dengue was made. Although the results of his “tourniquet test” were positive, he happily never developed clinical evidence of plasma leak, shock, or more severe hemorrhagic manifestations and his complete blood cell count normalized. He was afebrile by day 7 and asymptomatic by day 14.

REFERENCES:

1. Wilder-Smith A, Schwartz, E. Dengue in travelers. N Engl J Med. 2005;353: 924-932.

2. Guzman MG, Kouri G. Dengue: an update. Lancet Infect Dis. 2002;2:207-208.

3. Lesho EP, George S, Wortmann G. Fever in a returned traveler. Cleve Clin J Med. 2005;10:921-927.

4. Simmons CP, Farrar JJ, van Vinh Chan N, Wills B. Dengue. N Engl J Med. 2012;366:1423-1432.