Faculty Development Case of the Month: February 2024

Monthly Case from the Department of Medicine
Fever in a returning traveler: A case for cautious hydration

 

Submitted by:
Christina Mallarino-Haeger, MD
PGY-7 Infectious Diseases Fellow
Division of Infectious Diseases

Edited by:
Yoo Mee Shin, MD
Assistant professor,
Division of Hospital Medicine

Shaheen Fatima, MD
Assistant professor,
Division of Hospital Medicine

STORY AND CASE:
A 29-year-old man presented to the emergency department from Hartsfield Jackson International Airport with 9 days of generalized malaise, fevers, and severe diffuse myalgias and arthralgias that started after he spent a month in Guyana. He had no significant past medical, surgical, or family history. He spent his childhood in Guyana and migrated to Atlanta in his late teens and did not recall having any significant febrile illnesses during his childhood or during prior trips to Guyana. On his recent trip to Guyana, he spent his time in a house near the ocean, denied swimming in fresh or seawater, and had no significant animal or food exposures. He was up to date with all routine immunizations, had been vaccinated against yellow fever in his childhood, and did not take malaria prophylaxis during his travel. On presentation, he was afebrile, and his physical exam was unremarkable, including a negative tourniquet test. Labs were notable for a creatinine level of 1.2 mg/dL, white blood cells 8,300/mm3 with 61% lymphocytes, platelet count of 45,000/mm3, hematocrit of 52%, AST level of 135 IU/L, ALT level of 161 IU/L with normal alkaline phosphatase and bilirubin levels. Initial BinaxNOW™ Malaria test (Abbott, Chicago, IL) and blood smear were negative for malaria. Nasopharyngeal influenza A/B, SARS-CoV-2, and respiratory syncytial virus nucleic acid amplification tests (NAAT) were negative. Chest x-ray was normal. 

 Two additional blood smears obtained 12 hours apart were negative for malaria. He remained afebrile; he was managed with oral hydration and close monitoring of hematocrit, platelet counts, and fluid balance. 48 hours after admission, his AST and ALT downtrended to 73 IU/L and 92 IU/L, respectively. Platelets improved to 80,000/mm3 and hematocrit normalized, and blood cultures remained negative. Given clinical improvement and ruling out of malaria, he was discharged with close outpatient follow up. 

What’s the Diagnosis?
Dengue

ANSWER AND EXPLANATION
In this case, the differential diagnosis was broad, including malaria, dengue, typhoid, Zika, chikungunya and rickettsial diseases, but suspicion of dengue was high due to disease epidemiology, timeline, thrombocytopenia coupled with elevated hematocrit, and hepatocellular liver injury occurring at the time of defervescence. Given the high morbidity and mortality of malaria, it is paramount to perform three blood smears every 12 to 24h to rule it out in any traveler with fevers returning from an endemic region; in this case, malaria was ruled out. After the patient had been monitored for 48h, all labs were trending in the right direction, and he was feeling better, we discharged him, as we felt he was now out of the woods for progression to severe disease.   

PCR results came back about 3 days after he was discharged and serologies came back several days after PCR. This blood testing revealed positive dengue IgM, IgG, and serum dengue virus 2/4 RT-PCR. Chikungunya and Zika RT-PCR tests returned negative.  

One important clue supporting the diagnosis of dengue in this case was the presence of thrombocytopenia with an elevated hematocrit (as opposed to anemia seen in malaria). About half of patients with dengue will have detectable IgM between days 3 and 5 of symptom onset and this percentage increases to 80% and 99% by days 5 and 10, respectively [1]. Low levels of IgG titers can be detectable as early as 1 week after onset of symptoms [1]. A positive NAAT test confirms the diagnosis [2]. It is important to keep in mind that the mosquito species Aedes aegypti also transmits Zika virus. In this case, in addition to aiding with diagnostics, it was important to test for Zika as the patient was in a relationship with a woman of reproductive age. The Centers for Disease Control and Prevention (CDC) recommends using barrier protection or abstaining from sex for at least 3 months after the male partner returns from an endemic region [3].  

DISCUSSION
Dengue is a flavivirus transmitted by Aedes aegypti and is endemic in more than 100 countries, most notably the regions of Southeast Asia, South Pacific, Central and South America, and the Caribbean [4,5]. Illness begins after an incubation period of 5–7 days and usually follows three phases: febrile (lasts 2–7 days), critical (lasts 1–2 days), and convalescent or recovery (lasts 3-5 days). It is essential to recognize that the critical phase of illness usually ensues at the time of defervescence, which was around the time our patient presented [2]. This means that, in contrast with other febrile illnesses, the resolution of fever often precedes the critical window where there can be progression to severe disease. Warning signs include severe abdominal pain, hepatomegaly, mucosal bleeding, clinical fluid accumulation, lethargy, and increase in hematocrit with concomitant rapid decrease in platelet count [2]. Because dengue can result in increased vascular permeability and plasma leakage, judicious fluid management is paramount. Oral hydration should be encouraged with close monitoring of urinary output [6]. Prophylactic platelet transfusion is not recommended as it does not decrease risk of bleeding and can increase risk of fluid overload [2]. Conversely, peripheral red blood cell transfusion is essential for clinically significant bleeding or if hematocrit is dropping with unstable vital signs [6]. If there is need for intravenous fluids due to inability to have adequate PO intake, a stepwise approach to IV fluid hydration is recommended that varies depending on the state of disease severity. For patients who have warning signs and are hemodynamically stable, CDC recommends starting with 5–7 mL/kg/hour of an isotonic crystalloid for 1–2 hours, followed by 3–5 mL/kg/hour for 2–4 hours, at which time clinical status and hematocrit should be reassessed [6]. CDC’s complete guide and series of algorithms outlining the most appropriate next steps depending on disease severity can be found at https://www.cdc.gov/dengue/resources/DengueCheatSheet_ENG-P.pdf 

 CITATIONS

1. World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control: new edition. Geneva: World Health Organization; 2009. https://www.ncbi.nlm.nih.gov/books/NBK143157  
2. US Centers for Disease Control and Prevention. Dengue: for healthcare providers. https://www.cdc.gov/dengue/healthcare-providers/index.html 
3. US Centers for Disease Control and Prevention. Clinical guidance for healthcare providers for prevention of sexual transmission of Zika virus. https://www.cdc.gov/zika/hc-providers/clinical-guidance/sexualtransmission.html  
4. GL Mandell, JE Bennett, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9th ed. Amsterdam: Elsevier; 2020.  
5. Carrington CV, Foster JE, Pybus OG, Bennett SN, Holmes EC. Invasion and maintenance of dengue virus type 2 and type 4 in the Americas. J Virol. 2005;79(23):14680-7. 
6. US Centers for Disease Control and Prevention. Dengue quick guide/cheat sheet. https://www.cdc.gov/dengue/resources/DengueCheatSheet_ENG-P.pdf 

Interested in submitting a case of the month? Click HERE to learn more, read previous cases, and provide your Case of the Month.