Guide to differential diagnosis


After 2 years of pandemic where traveling was barely possible, tropical diseases are once again becoming important. At this year’s conference for internal medicine specialists, tropical medicine specialist Fritz Holst, MD, of the Center for Tropical and Travel Medicine in Marburg, Germany, explained what questions you should ask travelers with fever in your home. practice and how to proceed with a suspected case.

The following article is based on the lecture “Differential diagnosis of fever after a trip to the tropics”, which Holst gave at the 128th conference of the German Society for Internal Medicine in Wiesbaden.

A meta-analysis of studies on the topic, “travellers returning from the tropics with fever,” was published in 2020. According to the analysis, purely tropical infections account for a third (33%) of fever diagnoses in the world following an exotic journey. Malaria accounts for a fifth (22%), 5% is dengue and 2.2% is typhoid (enteric fever).

In 26% of returning travelers surveyed, non-tropical infections were the cause of fever. Acute gastroenteritis was responsible for 14% and respiratory infections for 13%. In 18% of cases, the cause of the fever remained uncertain.

In Germany, the number of malaria cases has increased, Holst said. In Hesse, for example, there was recently a death due to malaria. “What we should do has again been forgotten,” he warned. Greater attention should also be paid to prophylaxis.

The way to do it

Holst outlined the following steps for treating recently returned travelers who are ill:

  • Seriously ill or not: If there are signs of a serious illness, such as dyspnea, signs of bleeding, hypotension, or central nervous system symptoms, the patient should be referred to a clinic. A diagnosis should be made within one day and treatment should be initiated.

  • Communicable or dangerous disease: This issue should be quickly clarified to protect healthcare workers, especially those caring for patients. By using a complete medical history (discussed below), a range of illnesses can be clarified.

  • Disease outbreak in country of destination: Ask about possible epidemics in the country the traveler visited.

  • Malaria? Immediate diagnosis: Malaria should always be ruled out in patients in the office on the same day using a thick blood smear, even in the absence of fever. If this is not possible due to time constraints, the affected person should be transferred directly to the clinic.

  • Fever independent of travel? Exclude other causes of fever (eg, endocarditis).

  • Involve tropical medicine specialists in a timely manner.

Nine mandatory questions

Holst also listed nine questions clinicians should ask this patient population.

Where were you exactly?

Depending on the regional prevalence of tropical diseases, certain pathogens can be quickly excluded. About 35% of travelers returning from Africa suffer from malaria, while typhoid is much rarer. In contrast, typhoid fever and dengue fever are much more prevalent in Southeast Asia. In Latin America, this is the case for both dengue fever and leptospirosis.

When did you travel?

Using the incubation time of the pathogen in question, as well as the return time, you can determine which diseases are possible and which are not. In one patient who came to the office 4 weeks after his return, dengue fever or typhoid were excluded.

Where did you spend the night?

Whether in an unsanitary bed or under the stars, the question of how and where travelers spent the night provides important evidence for the following nocturnal vectors:

  • Sandflies: leishmaniasis

  • Kissing insects: Chagas disease

  • Fleas: spotted fever, bubonic plague

  • Mosquitoes: Malaria, dengue fever, filariasis

What did you eat?

Many infections can be attributed to careless eating. For example, when eating fish, crabs, crayfish, or frogs, especially if raw, liver fluke, lung fluke, or ciguatera should be considered. Mussels toxins have been found on the coasts of Kenya and even in the south of France. In North African countries, you should be careful when consuming unpasteurized dairy products (eg camel milk). They can transmit the pathogens of brucellosis and tuberculosis. In beef or pork that has not been thoroughly cooked, there is a risk of trichinosis or tapeworm. Even vegetarians should be careful. Common liver fluke infections are possible after eating watercress.

What did you do?

You can only get certain diseases through certain activities, Holst said. If long-haul travelers tell you about the following excursions, listen up:

Was there contact with animals?

Due to the risk of rabies following contact with biting cats or monkeys, Holst advises long-distance travelers to get vaccinated.

Were there new sexual partners?

In case of new sexual contacts, tests for hepatitis A, B, C and HIV should be carried out.

Are you undergoing medical treatment?

The patient may already be under medical supervision due to illness.

What prophylactic measures did you take before travelling?

To advance in the differential diagnosis, we must also ask questions about prophylactic measures. Vaccination against hepatitis A provides very effective protection against infections, while vaccines against typhoid provide a much lower level of protection.

Diagnostic tests

As long as there are no abnormalities, such as meningismus or heart murmurs, other diagnoses include routine infectious disease laboratory tests (C-reactive protein, blood count, etc.), blood culture (aerobic , anaerobic), a urine dipstick and rapid tests. for malaria and dengue fever.

To rule out malaria, a thick blood smear should always be done on the same day, Holst said. “The rapid test is sometimes negative. But often, tertiary malaria is only detected in the thick blood smear. And you have to repeat the diagnosis the next day.” For this, it is important to know that a single test result does not immediately exclude malaria. In contrast, the detection of malaria antibodies is obsolete. Depending on the result, other tests include serologies, antigen tests, and polymerase chain reaction.

Treat early

A complete set of results is not always readily available. Here is the advice of the experts: “If you already have a hunch, then start therapy, even without a definitive diagnosis.” This applies in particular to the suspected diagnoses in the following table.

Sickness Treatment
Malaria Atovaquone/proguanil, artemisinin
Typhoid Quinolone, cephalosporin, azithromycin
Meningitis Cephalosporin plus ampicillin
Rickettsia Doxycycline
Leptospirosis Doxycycline, macrolide, cephalosporin
Tuberculosis Tuberculostatic agents
Shigellosis Ceftriaxone, quinolone
Dengue fever No treatment available, monitor for potential complications

This article was translated from Coliquio.


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