How to Approach Traveler’s Fever

Is that even a term? I think I just made it up. Oh well, you’ll get the idea if you keep reading.

Does your patient have a fever after traveling? How soon (or late) after traveling do you worry that the fever may be related to an exposure abroad? Of course, the answer is very complicated with literally thousands of diseases worldwide to worry about. Thankfully, most patients from the US and other developed countries have been vaccinated in childhood to protect against measles, tetanus, and the like. Also, many people will visit a travel clinic to receive more vaccines and sometimes prophylactic medicines so it is very important to ask about all childhood and recent vaccines as well as any other medications they were given as prophylaxis.

Generally speaking, in regards to incubation periods, usually we should consider possible exposures abroad as the culprit for any fever that begins within 1-4 weeks of travel. Of course, my first go-to is the CDC Traveler’s Health website where there is a wealth of information including disease endemic to the area where the patient traveled as well as the incubation times for these disease. There, when you can select information for clinicians on a wide range of topics including recommendations and warnings about particular countries. Your first step should always be, check the CDC. If the country is listed in the triage note, I often look at the CDC page even before entering the room to get my differential diagnosis going.

Mostly we are going to talk about the mosquito-vector diseases here.

Fever in a recent traveler is a very difficult diagnosis to make, in my opinion, and I find it frustrating that patients often expect the US based ED to know all the disease presentations from world-wide travel. For me, I have to write this stuff down as reminders (welcome to my peripheral brain.)

MOSQUITO-BORNE ILLNESSES 

Of course, the best treatment is prevention. To safeguard against these you should always have good mosquito protection when traveling to tropical areas. Common sense says to wear pants and long sleeves, use netting if needed, and avoid the dusk and dawn feeding times, but as far as bug spray is concerned the DEET options are still the best. The distribution of the following diseases is generally around the equator illustrated in the map above (which also includes Lyme and other tick-borne illnesses discussed further below and aren’t commonly considered in traveler’s fever cases).

The list of illnesses with a mosquito vector includes the following:

• Chikungunya Virus (CDC Chikungunya Virus, WHO Chikungunya Virus)

• Dengue Virus (CDC Dengue, WHO Dengue)

• Eastern Equine Encephalitis Virus (CDC Eastern Equine Encephalitis)

• Japanese Encephalitis Virus (CDC Japanese Encephalitis Virus, WHO Japanese Encephalitis Virus)

• La Crosse Encephalitis (CDC La Crosse Encephalitis)

• Malaria (CDC Malaria, WHO Malaria)

• St. Louis Encephalitis (CDC St. Louis Encephalitis)

• West Nile Virus (CDC – NIOSH – West Nile Virus)

• Yellow Fever (CDC Yellow Fever, WHO Yellow Fever)

• Zika Virus (CDC – NIOSH – Zika Virus)

Five different human malaria Plasmodium species and their life stages in thin blood film (Source: K. Silamut and CDC).

Thankfully, a lot of these are rare, and a major clue to the presentation lies in the names that have the word “encephalitis.” This means that a major feature is just that - encephalitis - a sick patient with AMS or other neuro symptoms. In general, these are not going to be the patients that walk into your ED waiting room with a fever, wondering if it is a disease picked up on their last trip to the Caribbean. For now, being rare and fairly dramatic in presentation, we will skip these.

In terms of the common mosquito-borne illnesses, malaria ranks at the very top because it is generally more severe, and because it is treatable (besides supportive care). Most healthy travelers will recover from all of these disease and usually can be treated outpatient. Malaria is also, generally easier to test for by looking at a thin smear. Most labs can handle this in an hour or two. I’ve even had an excited lab tech call me about the blood smear, and I even went to the lab to check it out myself!

Therefore, think malaria first when considering a fever in a traveler to a tropical or endemic area because this can and should be treated. There are tests for the other diseases listed but it may be unnecessary to send tests for chickungunya and zika due to milder symptoms and low complication rate. There may be a lower threshold to send tests dengue but actually most people are asymptomatic with the disease.

Now, on to the most common mosquito vector diseases

1. Malaria has a distribution all around equator just like dengue, more in sub-Saharan Africa.

   • Prophylaxis: Good if taking as recommended, but not perfect. Therefore, you must consider in patients who may have missed some doses or even taking it correctly as it is not 100% protective.

   • Tests: Send a thin smear to look for malaria, high sensitivity to rule out the disease but not perfect either. Start with this test. Then add thick smear, blood cultures, and any other tests for disease that enter your differential (like Dengue). If thin smear negative, usually you can discharge a well-appearing patient. Malaria usually more severe than the following diseases so being well enough to go home with malaria has a good prognosis. 

   • Treatment: Here I would say just look it up and/or ask your friendly ID doc who would likely love a consult for this disease. For tests, just remember ACT (artemisinin combination therapy, commonly lumefantrine/artemether). This is usually oral, but there is an IV version if sick (vomiting, hypotensive). Usually patient can be discharged on 3 days of oral treatment, 6 if high resistance in the area of travel. Quinine and doxy is older option.

   • Disposition: Most people do not become ill enough to need hospitalization. Obviously, there will be exceptions based on age, baseline health, etc. Thankfully, the most common of the species (falciparum) does not go onto cause recurrent disease, although people can be reinfected, whereas some other species (vivax & ovale) do reside in the liver and can be recurrent. Return precautions and ID follow-up is a must.

2. Dengue has the same distribution as malaria, but more in Southeast Asia. The key is to think of both malaria and dengue because they have so much overlap

   • Prophylaxis: None, use mosquito protection

   • Best test is IgM/IgG, but often a send out lab that can take a week or so.

   • Symptoms: Muscle aches and headache common. Hemorrhagic shock is rare and more common in repeat infections. 

   • Treatment: Supportive

   • Disposition: Usually, home. The shocky patients will obviate the need for admission.

3. Chickungunya has a smaller but similar area of tropical distribution. For more, scroll down.

   • Prophylaxis: None, use mosquito protection

   • Tests: This is self-limited and diagnosed primarily on symptoms and exposure alone. Testing often not needed.

   • Symptoms: Flu-like symptoms as with the other but joint pain (which is usually generalized and can be severe) is distinguishing feature.

   • Treatment: primarily NSAIDS for arthralgias and supportive care.

4. Zika has the same as above in terms of geographical spread. May test in pregnancy. 

   • Prophylaxis: None (but I bet you could make billions if you invented one)

   • Tests: Also usually not done but because zika has gotten a lot of press lately there may be some concerned pregnant patients in whom you might consider testing. Otherwise test is not needed

   • Symptoms: Flu-like illness

   • Treatment: Supportive care

5. Yellow Fever is also a tropical disease. Thankfully, the CDC says, “Yellow fever is a very rare cause of illness in U.S. travelers” which means we can probably stop there, but for completeness sake.

   • Prophylaxis: None

   • Tests: Essentially none as it is diagnosed based on other lab findings, symptoms, and travel to Africa or South America.

   • Symptoms: Per the CDC “Illness ranges from a fever with aches and pains to severe liver disease with bleeding and yellowing skin (jaundice).

   • Treatment: None, nothing to treat or cure the infection. Supportive care and managing complications is the task. The “yellow” refers to jaundice so assessing and treating potential liver failure is needed.

6. Don’t forget “normal” common fever causes. Patients could return with influenza or other common viral illnesses. Of course, always look for clues of more dangerous illnesses like encephalitis or meningitis and treat any patient in hemorrhagic or septic shock (rare but possible with dengue and malaria) aggressively with early ID intervention.

Bottom line: Test travelers to endemic areas with fever for Malaria first. A thin smear is fairly sensitive and rapid. If this is negative and the patient looks well, discharge home is a reasonable option. Dengue is usually a send-out test, most infections are mild, and you will know when to admit because rarely the patient will be in hemorrhagic shock. Dengue, chickungunya, and zika all are usually flu-like illnesses that just need supportive care. Also, remember the “normal” cause of fever we see and work-up all the time in the US. Fever after traveling does not mean a rare disease only.

Of course, other bacterial and parasitic causes of fever in travelers include leptospirosis, typhoid fever, trypanosomiasis and schistosomiasis all of which need a separate discussion (to come).

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Chikungunya!

It's spelled how it sounds, yet I still have trouble spelling it. The name, chikungunya, is from an African dialect meaning "stooped walk" or "that which bends up" referring to its primary manifestation of joint pain. I hadn’t even heard of the disease until several years out of PA school, but after working in an ED that saw plenty of immigrants from the Caribbean Islands, I quickly learned that this is generally not a dangerous disease and mostly treated symptomatically. That being said, is is good to have some idea of some basic pathophysiology and possible complications. Here's a reminder of the highlights of the disease...

• Endemic in some parts of West Africa, chikungunya has now been found on every other continent including the Americas. Even though experience was in patients who returned from tropical areas (the first cases in the Caribbean islands was confirmed in 2013 and in Florida in 2014), it is technically not defined as a tropical disease because it has spread to places like Italy in 2007.

• Chikungunya is primarily transmitted by mosquito vectors, extremely rarely by blood products or maternal-fetal transmission.

• The incubation period is usually 3-7 days (range of 1-14 days) before abrupt onset of fever and malaise.

• Symptoms: Acute illness is about 7-10 days

  • Fever may be over 39 C for 3-5 days

  • Polyarthralgias (usually symmetric and distal more than proximal) 2-5 days after fever. Pain can be quite intense and disabling. Joint effusions can be present.

  • Maculopapular rash in 1/2 to 3/4 of patients usually on trunk and limb, sometimes puritic (25-50%)

  • Conjunctivitis sometimes occurs

  • Lymphadenopathy can occur

• Severe complications can occur in the elderly and chronically ill. These can include organ failure (respiratory failure, renal failure, hepatitis, cardiovascular collapse), but watch especially for neurologic findings - meningoencphalitis most common, also flaccid paralysis, Guillain-Barre, cranial nerve palsies as well.

• Diagnosis

  • Most diagnosed by fever/arthragias with travel to endemic area and mosquito exposure

  • Tests are available if needed - RT-PCR of chikungunya virus RNA if patient presents 1-7 days after symptom onset and if >7 days, chikungunya virus serology by ELISA or IFA (although I’ve never sent off any of these tests)

  • If patient could have chikungunya based on mosquito exposure in endemic areas also consider dengue and Zika virus.

  • There are many other mimics, with the most common being viral illnesses like parvovirus B19

• Treatment:

  • There is no antivirals for chikungunya!

  • Supportive care - rest, acetominophen, NSAIDs, etc

  • Caution with using aspirin and NSAIDs in patients with dengue

• Prevention is the key! That means avoiding mosquito bites.

• If you really want to take a deep dive into chikungunya, check on its geographic distribution, as well as get information for providers and patients, of course, check out the CDC.