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How to advise travellers of the risks of malaria

Carolyn Driver
RGN RM RHV
FPCert
MSc(TravelMed)
Independent Travel Health and Immunisation Specialist Nurse
Cheshire

Malaria is a complex disease that threatens 40% of the world's population.(1) It also represents a significant risk to tourists travelling to exotic countries. In the UK an average of 2,000 cases of malaria are imported annually with approximately nine deaths, although this figure has been tending to rise in recent years.(2) Last year 27 cases of falciparum malaria were found in British tourists returning from The Gambia over a three-month period. Tragically three of them died.(3) Many of these individuals were taking no chemoprophylaxis, and the remainder were taking incorrect medications. It is vital therefore that travellers departing from the UK for malarious areas of the world are given appropriate advice and prescribed effective prophylactic medication.

What is malaria?
Malaria is a parasitic disease that is transmitted to humans by the female anopheline mosquito. The causative organism is a microscopic protozoa called plasmodium. There are many species of plasmodium, but only four that affect humans:

  • Plasmodium falciparum.
  • Plasmodium ovale.
  • Plasmodium vivax.
  • Plasmodium malariae.

The plasmodium lifecycle cannot be complete without the human and mosquito being part of the cycle.
When an infected mosquito bites an individual, the parasites enter the blood and, after a period of 7-15 days multiplying in the liver, emerge and systematically invade and destroy the host's red blood cells. This is known as the erythrocytic (or blood) stage. At this point, the host experiences fever and other nonspecific symptoms. However, the parasites continue to multiply, and as the destruction of red blood cells increases multiple organ damage occurs and delirium, seizures and coma can occur, leading to death from multiple organ failure and secondary infection.
During the blood stage, some of the parasitic cells undergo sexual reproduction, forming gametocytes. If these are taken up by another mosquito during feeding, they will infect her and she will then pass the infection to another individual at her next feed.

Signs, symptoms and diagnosis
An individual will be asymptomatic until the disease has reached the blood stage. As the symptoms are similar to many viral infections, diagnosis is often missed or delayed. (The blood phase is not usually reached until six to seven days after infection, and therefore malaria can usually be eliminated if an individual becomes ill less than one week after entering an endemic area.)
P falciparum can cause a rapid illness resulting in multiple organ failure and death, sometimes within as little as 24 hours. Early diagnosis and treatment is vital to prevent such fatalities. P ovale and P vivax can have greatly increased "incubation" periods as they form hypnozoites, or dormant cells, during the liver phase, which can become active many months and sometimes years after infection.
Differential diagnosis can only be made by examining thick and thin blood films on which the parasites can be seen. Delay in diagnosis is frequently a feature in fatal cases in the UK so travellers to malarious countries should be encouraged to mention their travel history if they experience a severe febrile illness up to two years after their journey. It is equally important that any healthcare professional treating an individual for a febrile illness enquires about a possible travel history.
Suspected falciparum malaria should be treated as a medical emergency, and the patient should be sent straight to an appropriate unit rather than bloods being sent off and the patient waiting at home for the result. If the correct treatment is commenced early there is a good chance of complete recovery. An individual will never develop complete immunity to malaria, and those who are born and raised in endemic areas will lose any partial immunity quickly after leaving the infected zone. Thus a very important group to target for pretravel advice are those returning to visit family and friends in countries of origin (VFRs).(4) They will often not seek travel advice and need to be targeted opportunistically.

Prevention
Malaria is an entirely preventable disease provided that the correct preventive measures are employed. This relies on the traveller obtaining accurate and complete information about the risk at their destination. The adviser must ensure that the traveller understands the mode of transmission for malaria and the importance of bite avoidance measures as well as chemoprophylaxis. This is most simply described as the ABCD of malaria prevention:(2)

  • Awareness of the risk.
  • Bite avoidance.
  • Compliance with chemoprophylaxis.
  • Diagnose breakthrough malaria swiftly and obtain prompt medical treatment.

Advising the traveller
Once a travel history has been taken, the level of risk to the individual needs to be established (see Box 1). For some countries this will be simple as the whole country is at high risk for malaria transmission; for others, however, it is more complex as transmission may only occur in certain parts. The traveller's itinerary in conjunction with a resource, such as TRAVAX (see Resources), can help as the country information pages contain maps that outline the malaria risk areas. It is not good practice to simply prescribe malaria chemoprophylaxis if the adviser is not sure of the risk.
It is important that the individual understands the personal protection measures as these will help to prevent the many other insect-borne infections that are likely to exist at their destination, in addition to backing up the chemoprophylaxis that may be required (see Box 2).

Chemoprophylaxis
All the currently available medications may cause side-effects, and the aim is to prescribe them when the risk of malaria outweighs the risk of possible adverse reactions. If an individual is unsure, then they should always check with an additional source rather than prescribe "just in case".

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Once a risk has been established, the next issue for consideration is which type of malaria is the predominant strain for the area in question, and most importantly whether or not there is resistance to chloroquine.
Where there is no resistance to chloroquine this remains the drug of choice. In areas with slight-to-moderate resistance to chloroquine the combination of chloroquine and proguanil should be used. There are very few areas left where these drugs are appropriate, but as they are available without prescription it is most important that those travellers who will be using them receive adequate bite avoidance advice and are not simply dispatched to the pharmacy to purchase their medication.
The majority of travellers going to areas with a high risk of P falciparum malaria will need to take one of the alternative drugs, and in most cases they will have a degree of choice. Apart from the borders of Myanmar and Cambodia with Thailand (where there is some resistance to mefloquine), there is currently little resistance to any of the three licensed regimens of:

  • Mefloquine (Lariam).
  • Doxycycline (Vibramycin).
  • Atovaquone and proguanil (Malarone).

These three regimens are equally effective against P falciparum, and thus it is important to choose the regimen that the traveller is most likely to comply with. Contraindications that will rule out one or more for an individual may exist, but if this is not the case then the best way to proceed is to explain the regimens and most common side-effects and cost for each one, and facilitate the individual to choose the one they are happiest with. It can be helpful to use information sheets on each medication, which can be compiled "in-house" using information from datasheets and resources such as the Malaria Advisory Committee Guidelines and TRAVAX (see Resources). Patient information leaflets produced by the drug manufacturers can be accessed online via the electronic medicines compendium (http://emc.medicines.org.uk).

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When describing the different options to travellers it is important to describe the regimens so that the individual understands how long before and after travel the medications must be taken. All antimalarials should be taken with food as this both reduces gastrointestinal side-effects and improves bioavailability of the drug.  It is especially important that doxycycline is taken with a good drink so that it clears the oesophagus, and the individual should not lie down for at least half an hour after taking the medication.
There are occasions when a traveller may spend time in a chloroquine-sensitive area and then move to an area of chloroquine resistance, such as travelling from the Indian Subcontinent to Cambodia, Laos or Vietnam. In this case it is less complicated to advise the individual to take one medication throughout the period of risk, so they should choose a drug that will work in all areas - here it would be either doxycycline or Malarone.
All of the recommended medications require a private prescription from the GP, and the traveller then purchases them from a pharmacist at retail price. Travellers who have been correctly advised will understand why it is vital that they buy the correct medication for themselves or their family and not allow cost to obstruct the decision-making process. Equally, there is a responsibility for the travel health adviser to ensure that they are giving the appropriate advice and using good information sources to ensure that they are not advising drugs when there is no risk or where alternatives would be appropriate.

Conclusion
Malaria prevention involves a good understanding of how the disease is transmitted and a combination of methods that need to be adopted to avoid infection.  Travellers must also be aware that a small risk of infection will always exist and that they therefore should be vigilant about reporting their travel history should they succumb to a severe febrile illness for up to two years after their return from an endemic area.

References

  1. Stürchler D. Global epidemiology of Malaria. In: Schlagenhauf P, editor. Travellers' malaria. Hamilton, Ontario: BC Decker; 2001.
  2. Bradley D,  Bannister B.  Guidelines for malaria prevention in travellers from the United Kingdom for 2003. Commun Dis Public Health 2003;6:180-99.
  3. Health Protection Agency. Further cases of falciparum malaria in travellers returning from The Gambia - update. Commun Dis Rep CDR Wkly 2006;16(2):1-2.
  4. Health Protection Agency. Malaria imported into the United Kingdom in 2005: implications for those advising travellers. Commun Dis Rep CDR Wkly 2006;16:23.

Resources
Malaria Advisory Committee's Guidelines for Malaria Prevention in Travellers from the UK
W:www.hpa.org.uk
Malaria Reference Laboratory
W:www.malaria-reference.co.uk
Travax:
A to Z of Healthy Travel
W:www.travax.nhs.uk
British National Formulary
W:www.bnf.org/bnf
National Travel Health Network and Centre
W:www.nathnac.org

Telephone helplines for healthcare professionals
NaTHNaC
T:0845 602 6712
Malaria Reference Laboratory
T:020 7636 3924