The structure of this article is based on a lecture I attended at the Royal College of Physicians of Ireland a number of years ago. The talk, delivered by Infectious Diseases Specialist, Dr David Gallagher (Galway University Hospital), was memorable and his approach to this topic has helped me greatly in practice.

Disclaimer: This is a ‘pop’ article. The article is not endorsed by any clinical body. The author does not have a passport and, perhaps wisely, never journeys ‘beyond the Pale’ (Dublin and North East Wicklow).

Increasingly, we are required to deal with people returning from the tropics with fever. Such cases cause generalists considerable anxiety as we worry about our limited knowledge of the differential. In fact, the differential in the acute setting is itself quite limited. In this situation, three common infections should be foremost in our minds, Malaria, Dengue and the wonderfully named Chickungunya.

Malaria

The possibility of malaria must be considered in any febrile individual returning from a malaria endemic area. It is the tropical infection most likely to kill if not picked up early and treated appropriately. The classical manifestations described in textbooks (cyclical chills and fevers) are not generally relevant to the returning traveller. A ‘flu like illness’ often with gastrointestinal upset is typical in this group. As the presentation is non-specific, the key to avoiding missing the diagnosis is a high index of suspicion and knowledge of the limitations of available laboratory tests.

Alexander the Great with his physician, Philip of Acarnania. It has been postulated that at the age of 32 years, having conquered the known world and survived at least one previous tropical disease, Alexander died of malaria in Babylon in 323 BC.

Malaria: a few things the generalist should keep in mind

• It is possible for an individual with a previous history of treated malaria to develop new-onset infection. Acquired immunity against malaria wanes over time.
• The risk of developing malaria in tourists who take appropriate chemoprophylaxis for the appropriate time period is very small. However, data derived from US military experience suggests that even an individual taking appropriate prophylaxis may develop malaria if in an area of repeated high level exposure.
• A single negative pair of thick and thin films does not exclude malaria. Infection but not parasitemia may have been present at the time they are taken. Multiple thick and thin films are required. Six pairs collected over 48 hours has been suggested as adequate.
• In the presence of malaria infection, even in the hands of the most experienced laboratory technicians, thick films have a false negative rate of 10 to 15%. The false positive rate may be a s high as 25%.
• Rapid diagnostic tests (RDT) based on detection of malarial antigens in peripheral blood are available. Results are available to the clinician in minutes. A Cochrane review concluded that they perform well in practice:

“The sensitivity and specificity of all RDTs is such that they can replace or extend the access of diagnostic services for uncomplicated P. falciparum malaria…..If the point estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of 1000 patients where 30% of those presenting with symptoms have P. falciparum, Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and nine with Type 4 tests.” Abba et al, Cochrane review 2011.

• Treatment of malaria is imperfect. P. vivax or P. ovale parasitemia can recur many years after successful initial treatment.
• It is not uncommon for malaria to co-exist with other infections in the same individual at the same time.
• Malaria parasites may be detectable in the blood of people resident in endemic areas in the absence of disease.
• If you are required to treat a case of malaria, seek expert advice.

Source: Hahn WO and Pottinger PS. Med Clin North Am 2016 100(2): 289

Malaria parasites detected on a thick blood film

Dengue fever

This flavivirus infection produces a spectrum of illness severity ranging from asymptomatic infection to the potentially lethal clinical syndromes, Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). Presentation is nonspecific and again a high index of suspicion in subjects returning from endemic areas is required in order to avoid missing this diagnosis.

Dengue fever. The characteristic macular arch develops in over 50% of infected individuals.

Laboratory tests, RTPCR, viral isolation and serology can establish the diagnosis of dengue virus in the body. The interpretation of these tests is complicated and beyond the scope of this article.  There is no specific treatment for dengue and the key to appropriate management is that we look for ‘warning signs’ pointing towards the potential development of DHF and DSS. A patient manifesting these ‘warning signs’ should be admitted with close observation and supportive measures instigated as necessary. 

“Warning signs” in Dengue infection suggestive of progression to potentially lethal complications

• Abdominal pain or tenderness
• Persistent vomiting
• Effusions (chest or abdominal)
• Mucosal bleeding
• Lethargy or restlessness
• Hepatomegaly
• Increase in hematocrit concurrent with rapid decrease in platelet count

The global risk of dengue infection

Chickungunya

‘The illness of the bended walker”

This infection, originally described on the border of Tanzania and Mozambique derives its name from the local Makonde language. The name (“that which bends up”) refers to the contorted nature of those afflicted by the infection due to the associated joint problems. The disease is prevalent throughout the developing world.

‘Behind you’! An intrepid traveller takes a break from searching for gorillas (arrow) on a recent trip to Africa

The presentation is nonspecific but as the name implies may include joint problems. Diagnosis is confirmed by serologic methods, virus isolation (if available), and reverse transcription–PCR (RT-PCR). There is no specific treatment.

Incubation periods

The time between exposure to the infectious agents discussed here and the onset of  symptoms  (the incubation period) is important in deciding on a likely diagnosis or in excluding an unlikely diagnosis.

Dengue* 3 days (2 -10)

Chickungunye* 4 days (3 -10)

P. falciparum^ 7 to 14 days

^Incubation period may be prolonged by partially effective prophylaxis. P. ovale and P. vivax may manifest an incubation period of up to several years.

*Sources: Rudolph et al. Am J Trop Med Hyg 90(5): 882-891 2014, Bartoloni and Zammarchi. Mediterr J Hematol Infect Dis 2012 4(1) e2012026

A few other infections to keep in mind in the returning traveller

Typhoid: incubation period of one to two weeks. Presents with fever, headaches and abdominal pain. Diarrhoea may be a feature. Diagnosis ideally confirmed on culture of Salmonella typhi from body fluids supported by tests for relevant pathogen antigen or DNA in blood samples.

Hepatitis: check the LFTs and serology

Sexually Transmitted Disease (STD)

Taking a full sexual history is an essential part of the workup of an individual returning from abroad with a fever.

…and don’t neglect ‘home-town’ infections

A person may return from the tropics and pick up a ‘local’ infection. For example, it would be a disaster to miss a case of bacterial meningitis presenting with headache and fever when focused on the possibility of  P. falciparum infection in a returned traveller! As always, if you have time to think, keep an open mind.

Not just the tropics

It is worth being aware that tropical diseases themselves may be on the move. We might not think of Chickungunya or Dengue as being relevant to travel in Europe or the United States but they are and may become an increasingly prevalent problem in the near future.  The CDC website carries useful up to date information on the distribution of tropical diseases around the world and is well worth consulting when in doubt. 

Source: The Lancet Infectious Diseases. Editorial. Volume 14(10) 899 2014

It is remarkable that we got through this article without a photograph of or indeed mention of a mosquito. Doh!