Fever in returning travellers

Fever is the presenting complaint in many returning travellers who are unwell, and the practice nurse needs to be alert to the possibility of serious illness acquired abroad

The returning traveller who is unwell presents significant challenges in primary care. People travel more widely and adventurously than ever before, often well off the beaten track and without much thought to the health risks.

While diarrhoea is the most common health problem in travellers,¹ fever occurs in 2-12%, and can be a sign of serious illness. It is particularly important to be alert for malaria, but this is not the only cause.

The practice nurse may be the first point of contact for patients with undifferentiated symptoms and possible exotically acquired disease. It is essential be alert to the possibility of disease acquired abroad, since it is essential that the opportunity for diagnosis is not missed.

ASKING THE RIGHT QUESTIONS

First you must to recognise that the patient in front of you IS a returning traveller. They may not say so, and indeed they may not think they are if it is some time since they returned.

Most travel related infections present within six months of return, with most serious febrile illnesses presenting within a month. However although a few infections such as plasmodium vivax malaria can take up to a year and, a few, such as schistosomiasis can present even later.

Remember, therefore, in any febrile patient to include history of recent travel in your screening questions.

Where to start

As always you need to begin both with a systematic approach to history taking and information gathering, whilst at the same time assessing your level of concern. You are trying to answer two questions simultaneously:

1. Is this patient mildly, moderately or severely unwell? And

2. What are the possible causes of the patient's symptoms?

You will make an initial judgment on the first question fairly swiftly. If you think the patient is severely unwell seek help and admission before proceeding with further detective work. Basic observation will tell you if you need to start taking vital measurements before attempting a detailed verbal history.

As long as the patient is not severely unwell you should proceed to look for possible causes of fever, particularly looking for falciparum malaria. A patient in whom this is possible must be considered severely ill even if they seem apparently well.

Once falciparum malaria has been excluded, patients require hospital admission only if severely ill (e.g. toxic, respiratory distress, jaundice, altered consciousness, bleeding).

Never feel inadequate in assessing a patient who may have a disease you have never seen and may not even have recently read about.

Your skills in stratifying risk can be used in any patient, and they will help you with the initially judgment of whether they are seriously unwell.

However, as you gather information on travel, exposure and symptoms (see box 1), remember that you may be looking at an illness outside your common practice.

THE DIAGNOSTIC SIEVE

Good history-taking rules out some options and allows you to test the possibility of those that remain. The diagnostic sieve is a process of going through conditions you need to consider. It is aimed at excluding (or identifying) infections that are serious, treatable, or transmissible.

While most illnesses in returned travellers are caused by common infections (such as bacterial pneumonia), the list of possible causes of fever is long, and it's important to remember that some of the diseases you are less familiar with may be serious.⁶

Table 1 gives a list of some symptoms and incubation periods of infections relevant to returning travellers.⁴ This may allow you to exclude some infections from the differential diagnosis.

Remember that, although most febrile illnesses in returned travellers will be due to infection, don't forget the possibility that pulmonary emboli (sometimes with superadded pneumonia) can also be associated with fever.

PUBLIC HEALTH ISSUES

There is a risk to the public if diseases are imported into the UK. This is not always substantial. Many diseases — such as malaria — cannot be spread without the right insect vector, so they cannot be spread in the UK. However, others such as lassa fever and ebola virus are capable of transmission, as is the case with travellers' diarrhoea, pandemic flu and avian flu.

Many practice nurses will have worked through the flu pandemic and concerns around avian flu, when we became particularly conscious of imported disease and its importance to our communities.

Dangerous viral haemorrhagic fevers such as Lassa fever are fortunately very rare in returning travellers (although if suspected, because of known travel to an affected area, public health advice is essential).

Remember to give the traveller advice on how to avoid spreading their illness. This is particularly true if they have associated diarrhoea or vomiting and are involved in preparing food for others.

Remember also potential risks of contact with the immunosuppressed and pregnant women who may be particularly susceptible.

Finally remember the statutory need to notify — the list of notifiable diseases (box 2) includes bacterial dysentery, cholera, malaria and dengue.

KNOWING YOUR STUFF

"¦and worrying about what you don't know

One of the difficulties we all face in patients returning from abroad is the feeling that they may have conditions we don't know much about. This is true, but a systematic approach will still pay dividends in ruling out some things in order to answer the questions:

• What infections are possible given where and when the patient travelled and what they did there?
• How ill is the patient and how ill might they become?
• What help do we need with diagnosis?
• What treatment is required?

Tables 2 and 3 mention some of the conditions that we may see in returning travellers, and the areas where these infections are found. Table 4 sets out the commonly used investigations. More specific detail regarding a few important infections is given below together with recommendations for further study.

We have access to huge and well laid out resources on the Internet that tell us about geographic-specific risks and diseases. It's important to use these, to have familiar travel sites that you know how to navigate in order to get information readily.

If you are not sure if the patient in front of you needs investigation you can always involve a colleague or speak to your local infectious diseases consultant.

Seek advice about treatment too. In some areas of the world common bacteria are highly antibiotic resistant. Some bacteria produce an enzyme called NDM-1,3 which gives them resistance to virtually all available antibiotics. Enteric fever, the term used to describe either typhoid or paratyphoid fever, has also become increasingly resistant.

SPECIFIC CAUSES OF FEVER

This article provides only the briefest of overviews of a few of the most important conditions. The interested reader can easily discover a great deal more detail with a simple Internet search.

Malaria

A minimum incubation period of 6 days means that short term travellers will develop their symptoms after returning home.⁴

Malaria is transmitted by the anopheline mosquito, usually biting between dusk and dawn. There are four types, of which plasmodium falciparum is by far the most dangerous.

There are no specific symptoms: most patients have a history of fever, chills, headache, myalgia, arthralgia and malaise. GI or respiratory symptoms are sometimes seen. About half of affected patients are afebrile at presentation as the fever fluctuates, often with no specific pattern. Complications can include cerebral malaria with neurological symptoms including fits and altered consciousness, pulmonary oedema and blackwater fever (failure of coagulation with gross haematuria).

A significant number of travellers to malaria endemic countries do not take malaria prophylaxis, or take it inadequately. Malaria prophylaxis may delay onset of symptoms and obscure microscopic diagnosis. Chemoprophylaxis should be stopped while a patient is being investigated for malaria.

Patients with a high Plasmodium malariae parasite count who have returned from Asia should have P. knowlesi excluded. This is a potentially lethal form of primate malaria that can be passed to humans.

Dengue and chikunyunga

These infections are both mosquito borne viruses with short incubation periods: 4—8 days for dengue and 2—3 for chikunyunga. Both occur widely through the tropics and are transmitted by day-biting Aedes mosquitoes.

Dengue normally causes a mild febrile illness, but dengue haemorrhagic fever can occur, with headache, myalgia, red rash that becomes petechial, and back pain. Dengue shock syndrome is rare in returning travellers but causes collapse and circulatory shock.

Chikunyunga is similar to dengue although arthralgia and athropathy predominate. Both are diagnosed on serology.

Enteric fever (typhoid and paratyphoid)

Once malaria is excluded, enteric fever is the most important tropical disease needing treatment in travellers from Asia (it is uncommon in Africa). Incubation is 7—18 days and fever is the most common symptom. Other symptoms can include headache, constipation or diarrhoea, dry cough and occasionally neurological symptoms. GI bleeding, bowel perforation and encephalopathy are serous complications. Typhoid vaccine provides incomplete protection against typhoid and none against paratyphoid. Diagnosis is by serology.

Acute schistosomiasis

This mainly occurs in Africa, usually following swimming in freshwater. Lake Malawi is particularly notorious. It is caused by a fluke released from snails, which penetrates intact skin. Incubation is long — 2—9 weeks — and symptoms include fever, lethargy, myalgia, arthralgia, cough, wheeze, headache, rash, diarrhoea and hepatosplenomegaly. Eosinophilia is common, but finding the schistosomes in stool or terminal urine sample is difficult. Serology may not be positive for 6 months so schistosomiasis is treated empirically in patients with fever, urticaria, and history of freshwater swimming in the tropics (especially Africa) within the previous 8 weeks.

Fever with diarrhoea

Despite the advice of 'boil it, cook it, peel it or leave it', the most common returning traveller presentation from tropical travellers is diarrhoea,¹ presenting in over a third of patients.

Traveller's diarrhoea usually refers to diarrhoeal illness experienced by traveller in the first week or two of a stay abroad. It is rarely life threatening and it mostly occurs during travel. About a third of patients with TD have fever.⁴ E coli, particularly invasive/aggressive forms, campylobacter, salmonella and shigella are particularly likely to cause fever, norovirus and rotavirus less so.

Patients with diarrhoea and a fever are constitutionally unwell and are in the subgroup who may need treatment. Diarrhoea with fever raises the possibility of a number of infections that may be of particular concern.

The diarrhoea may be caused by any of numerous pathogens (bacteria, parasites and viruses) picked up from contaminated food and water in the new, foreign environment. Patients will not always have a temperature, but the presence of a temperature and other constitutional symptoms helps you assess how unwell they are and whether they need treatment. Remember patients who have non-infective causes for their diarrhoea are much less likely to be pyrexial.

Traveller's diarrhoea (TD) has been defined as 'three or more loose stools in 24 hours with or without at least one symptom of cramps, nausea, fever or vomiting.' It particularly affects those who travel from industrialised countries to developing countries, notably in Latin America, Africa and Southern Asia.²

Between 20% and 60% of travellers are affected by TD around the world.³ TD increases with the exotic nature of the destination, the climate and poor local infrastructure. The traveller's own level of precautions around drinking water, hand sanitisers and so on also play an important role.

The most common causes are bacterial (60—85% of cases), mostly enterotoxin-forming Escherichia coli. E.coli will usually cause mild self-limiting diarrhoea for less than 72 hours. Parasites account for about 10% and viruses for 5%.

Other important causes of travellers diarrhoea are cholera, typhoid and paratyphoid, salmonella, clostridia, Yersinia, shigella, bacillus cereus, amoebae and giardia.

Some of these will require medical treatment, sometimes with antibiotics, although most travellers' diarrhoea tends to be self-limiting and passes within a week. Determining who to treat depends partly on how unwell they are and partly on the causative organism.

Diarrhoea lasting for longer than 14 days suggests more unusual organisms, and stool testing for giardia, entamoeba, cyclospora and cryptosporidium is needed.

Bloody diarrhoea (dysentery) occurs more commonly with some pathogens (salmonella, shigella and campylobacter species). The latter commonly causes fever. Amoebic colitis, which usually has a slower onset, also causes bloody diarrhoea with fever.

In children aged under 5 years rotavirus is a common pathogen.

Most TD is managed at home with oral rehydration. However, it is important to identify patients who have more severe symptoms and those at risk of dehydration.

Oral rehydration is appropriate for low-risk patients. The very young, the elderly and other higher-risk may need more careful monitoring. Racecadotril is designed to be used with rehydration treatment.^2,5 It reduces the amount of water released into the gut during an episode of diarrhoea. It can be used for all patients over 3 months of age.

In patients with other risk factors (the young, the elderly or other comorbid conditions), admission should be considered. It should also be considered in those with frequent bloody diarrhoea, high fever or poor general condition.

Fever with TD: points to remember

Other systemic infections causing fever (e.g. severe sepsis including meningococcal septicaemia and toxic shock syndrome, malaria, typhoid, atypical pneumonia, influenza, measles, viral haemorrhagic fever) may have diarrhoea at presentation.

Remember also that fever and diarrhoea are both common in travellers, and may have separate aetiologies.

SUMMARY

The returning traveller presents an enormous challenge as they may have any one of a wide range of diseases that are unusual to us, some of which may be serious.

We need to keep our heads, be systematic and exclude the important things including malaria. Seeking advice when unsure, careful safety-netting and reading up on diseases with which you may be unfamiliar will help the practice nurse negotiate this interesting area safely and well.

REFERENCES

1. Looke D F M and Robson J M B Infections in the returning traveller. Med J Aust 2002: 177(4): 212-219

2. Hill DR, Ryan ET. Management of travellers' diarrhoea. BMJ. 2008 Oct 6;337:a1746. doi: 10.1136/bmj.a1746.

3. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010 Sep;10(9):597—602.

4. ESNM12: Acute diarrhoea in children: racecadotril as an adjunct to oral rehydration, NICE (Mar 2013)

5. Johnston V, Stockley J.M, Dockrell D, et al. Fever in returned travellers presenting in the United Kingdom: Recommendations for investigation and initial management Journal of Infection (2009) 59: 1-18

6. CDC (US Centers for Disease Control) Travellers health: wwwnc.cdc.gov/travel/yellowbook/2014/chapter-5-post-travel-evaluation/fever-in-returned-travelers