Veteran With Febrile Illness Following Trip to Vietnam

June 1, 2006

This patient has a febrile illness that began shortly after he returned from foreign travel. The differential diagnosis is intriguing--malaria, yellow fever, typhoid fever, and dengue.

A 59-year-old man presents with a severe febrile syndrome of several days' duration. The syndrome includes retro-orbital pain, 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.

What is the most likely diagnosis in this patient?A. Malaria.
B. Yellow fever.
C. Typhoid fever.
D. Dengue.

(Answer and discussion on next page.)

CORRECT ANSWER: D

This patient has a febrile illness that began shortly after he returned from foreign travel. The differential diagnosis is intriguing; 3 of the 4 entities listed are real possibilities. However, several clinical clues point to dengue (choice D) as the most likely choice. The acute onset of fever and associated retro-orbital pain, 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 manifestation elicited by the blood drawing tourniquet (a positive result on an inadvertently performed "tourniquet test") is another strong clinical marker for dengue--and especially for its more severe variant, dengue hemorrhagic fever.1

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 dengue hemorrhagic fever is the leading cause of hospitalization and death among children in Asia.1,2

Dengue is clearly a risk for travelers to tropical areas, where it is endemic; in fact, the incidence figures for dengue (2% to 16% of febrile travelers) are second only to those for malaria.3 There is no vaccine or prophylactic regimen for dengue.

Malaria (choice A) remains the most common cause of fever in a returned traveler,3 and the time frame for its development is similar to that of dengue. If the patient was compliant with malaria prophylaxis as he states, this diagnosis is less likely--but not impossible. The statistics alone require that a blood smear for malaria be obtained and analyzed.

Yellow fever (choice B), another illness caused by a flavivirus, is unlikely for 2 reasons. First, the patient seems to have received appropriate vaccinations. Second, he was not in an area where yellow fever is endemic (sub-Saharan Africa or South America).

The presence of neutropenia makes typhoid fever (choice C) a possibility. The incubation period for typhoid (10 to 20 days) overlaps those of dengue and malaria, and it, too, causes high fevers and headache. Usually, however, there is a GI component to typhoid fever--typically constipation (initially), abdominal pain, and diarrhea (usually in the second or third week). These symptoms were absent in this patient, and his severe myalgias and arthralgias are not typical of typhoid. In addition, his pre-travel vaccinations probably included one for typhoid. Nonetheless, blood cultures should be performed to exclude this diagnosis in any traveler in whom a significant febrile syndrome develops within the appropriate time frame.

Outcome of this case. Appropriate smears were obtained and examined for malaria parasites; several sets of blood cultures were also performed. The results were negative for both malaria and typhoid. The patient's leukopenia and thrombocytopenia, together with the clinical findings, led to further testing for dengue (an IgM enzyme-linked immunosorbent assay [ELISA]), which provided additional evidence of this diagnosis.

Although the results of his "tourniquet test" were positive, he never manifested plasma leakage or more severe thrombocytopenia. Thus, he met only 1 of the 3 diagnostic criteria for the far more serious dengue hemorrhagic fever (hemorrhagic manifestations, platelet count of less than 100,000/µL, plasma leakage documented by clinical signs or laboratory findings).1 This was fortunate; dengue hemorrhagic fever is associated with mortality as high as 20%, and expert fluid replacement measures are required to prevent death.4,5

The patient's illness was managed on an outpatient basis using acetaminophen, bed rest, and oral fluids, with frequent status checks. His platelet count slowly recovered to normal levels. He defervesced on the seventh day, and his recovery was complete by day 14.

References:

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.

Wills B, Nguyen MD, Ha TL, et al. Comparison of three fluid solutions for resuscitation in dengue shock syndrome.

N Engl J Med

. 2005;353:877-889.

5.

Molyneux EM, Maitland K. Intravenous fluids-getting the balance right.

N Engl J Med

. 2005;353:941-944.