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19 January 2011

Reviewing the evidence for malaria advice and maps for TRAVAX® and Fitfortravel® - update

Introduction

Malaria remains a major public health threat in over 100 countries in which it is endemic, as well as in those countries which have in recent years made efforts to remove the vector.1 The World Health Organization (WHO) estimates a decrease in cases between 2000 and 2009, from 233 million cases in 2000 (and 244 million in 2005) to 225 million in 2009 and in deaths from 985 000 deaths in 2000 to 781 000 in 2009. On the other hand resistance to malarial therapies, including artemisinin-based therapies remains a cause for concern,1 as does the evidence that surveillance may still be substantially under-estimating the true burden of disease in many countries.2

It is still not well understood how the burden of disease in endemic countries and the risk it presents to non-immune travellers relates to the risk it presents to indigenous populations (who may have some immunity to the parasite through regular exposure).3 Studies by Behren’s and co-workers suggest that incidence may not be a useful indicator of risk to travellers.4-6 Any conclusions are, however, impaired by bias due to lack of discrimination between travellers types, lack of knowledge concerning antimalarials use, assumptions about accuracy of surveillance,2 and the role that outbreaks play in mortality among travellers to previously low risk malaria areas.7-8

Provision of malaria advice is an important part of the pre-travel consultation. HPS provides malaria advice to health care professionals via TRAVAX and to the general public through FitforTravel. The recommendations are intended to support informed choices concerning prophylactic measures based on a risk assessment of the individual travellers involving knowledge of their current health, and the demographics and itinerary of intended travel. The recommendations take the form of:

  1. a description of malaria risk areas in each country with comment on which prophylaxis should be used according to reported resistance patterns and
  2. malaria maps outlining risk areas covered by the text and including geographic landmarks.

From September 2010 to January 2011, we undertook a systematic review of the malaria text recommendations and malaria maps on TRAVAX and FitforTravel to identify where risks had changed. As of January 2011, recommendations for all countries with a malaria risk have been updated with the exception of seven malaria risk countries where further research is required.

The overall aims of this exercise were:

  • to produce text and maps describing malaria distribution and risk within each country based on documented data sources and process
  • to make recommendations for prevention, including use of chemoprophylaxis, based on documented data sources and process
  • to make this information appropriate, easily understood and accessible for travel health practitioners using TRAVAX and the general public accessing FitForTravel.

Methods

Text recommendations

In order to produce the text recommendations for all the countries included, the following steps were taken:

A. Guidance Group:

An expert group was convened employing HPS staff experienced in guidance production in travel medicine.

B. Data for Risk recommendations:

  1. Guidance on areas of risk from the WHO, the US Centres for Disease Control and Prevention (CDC), and the HPA Advisory Committee on Malaria Prevention in UK Travellers (ACMP) were reviewed and compared.
  2. When there were discrepancies between data from the above authorities or if advisory guidance lacked clarity, additional data was sought from other sources. These sources included national datasets from national public health sites, data from WHO regional sites, WHO reports and publications such as the Malaria Atlas Project (http://www.map.ox.ac.uk/).
  3. Recent outbreak notification alerts, such as from ProMED and WHO, were reviewed and in some cases local experts were also consulted to identify any further areas of risk.
  4. HPA Malaria Reference Laboratory data was reviewed to identify which countries constituted the greater risks to UK travellers.

C. Data for Chemoprophylaxis recommendations:

Guidance on prophylaxis from WHO, CDC, and ACMP were reviewed and compared. Where discrepancies were observed between the sources, further data (from WHO and national Ministry of Health sources) were sought to aid interpretation.

D. Analysis:

Countries were analysed on a regional basis, using Geographic Information Systems, in order to ensure that border discrepancies (e.g. low risk areas in one country adjoining high risk areas in another) were accounted for where possible.

E. Final Text Recommendations:

After the most up-to-date data from the sources were collated and any discrepancies considered and resolved, one overall recommendation for each country addressing risk and prophylaxis was produced by the HPS expert group. Where time allowed, the recommendations were sent to other UK experts for consultation.

Malaria Maps

When producing the malaria maps, it was essential that the map recommendations corresponded with the accompanying text recommendations. Text recommendations are interpreted for transference into the maps based on the WHO definition of risk areas9 and maps shaded as follows:

High risk:         antimalarials usually advised = dark pink
Variable risk:    antimalarials usually advised = mid pink
Low to no risk:  antimalarials not usually advised = light pink

Results

The recommendations for 101 countries were reviewed, resulting in the maps of 54 countries being changed, while prophylactic changes were made for 18 countries.

Of the changes in prophylaxis recommendations, eight were due to downgrading of risk to recommending that antimalarials will not be usually advised, while eight were due to the appearance of chloroquine resistance resulting in atovaquone, doxycycline or mefloquine being the recommended prophylaxis in high risk areas.

The analysis on data on seven countries (India, Sri Lanka, Bangladesh, Nepal, Indonesia, Malaysia and Vietnam) proved problematic and analysis of this is still ongoing and will be published later this year.

Examples of maps which were changed due to WHO data were Egypt and Morocco. In the case of Egypt distribution declined from being very limited in the El Faiyum governorate area to ‘not normally present unless imported’, while distribution for Morocco changed from a very small risk of benign malaria in eastern parts to being malaria free.

Examples where other data aided in decision making were Saudi Arabia and Botswana. In the case of Saudi Arabia, data from the Kingdom of Saudi Arabia Ministry of Health and from the Malaria Atlas Project were used to identify risk areas. In the case of Botswana, data from the Malaria Atlas Project were used along with data from Craig and co-workers to define the risk area10 where CDC and WHO were found to conflict.

In producing the maps the aim was to clarify the key so that (Figures 1a and 1b) green was replaced by pale pink to indicate low to no risk rather than malaria free. In addition, cross-hatching was removed and the maps were designed to be as accurate as possible with respect to malaria risk occurrence.

Discussion

Production of malaria recommendations for TRAVAX and FitforTravel is carried out following a systematic review of the evidence for both risk and for prophylaxis. The review process seeks to ensure that, while HPS is consistent with WHO, it can explain to stakeholders the rationale for both WHO recommendations and any differences that may exist between HPS recommendations and those of other authorities such as CDC. While the reviewing process is resource intensive, taking up to 12 hours per country, the benefits are an increased understanding of malaria epidemiology among the guidance developers which can be communicated to stakeholders.

Nonetheless, the recommendations did not seek to discriminate along lines of malaria endemicity as other epidemiological studies do.11-13 Rather the aim was to utilise available data and provide information that is useful to the end-user in making risk assessments associated with travel. The recommendations and maps contribute to the advice the clinician may give a traveller to a country with malaria risk.

The recommendations are based on advice from recognised authorities such as WHO, CDC, ACMP and epidemiological data. Inconsistencies did arise between authorities, such as for Botswana, where epidemiological studies provided additional data for interpretation. Inconsistencies can even occur within an authority such as in the case of Haiti where WHO recommended both chloroquine AND atovaquone/doxycycline/mefloquine as first choices. A review of the available data on chloroquine-resistance resulted in our recommending chloroquine as first choice. The use of national data and other sources is not clear cut however. National datasets may be out-of-date, may be presented at low resolution so as not to allow discernment of high risk areas, or may be based on poor quality surveillance methods, while other sources, such as the Malaria Atlas Project, may not deal comprehensively with the issue of vivax malaria. In dealing with the data the guidance group from HPS sought to use a precautionary approach in making recommendations and in resolving issues of prophylaxis and geographical risk.

User surveys consistently confirm that the malaria advice and maps are popular, user-friendly, visual aids during the pre-travel consultation, and assist in the provision of malaria prevention advice. It is essential that TRAVAX and FitforTravel recommendations are used appropriately, in conjunction with a comprehensive pre-travel risk assessment and in the wider context of general travel health advice.

The pre-travel risk assessment, conducted over a minimum of 20 minutes, face-to-face, entails taking a detailed history regarding the traveller and the nature of the trip to be undertaken.14 Demographic, medical and travel data including details of underlying conditions, current medications, personal interests, and accommodation are all useful in identifying the traveller’s risks and what preventative measures are advisable.1

Where travellers are going to countries with malaria, the recommendations and maps can be used for more detailed planning of prophylaxis with appropriate information about the available choices, efficacy, side-effects and costs. It may be that certain travellers, for example: infants, children and pregnant women travelling to areas with a high incidence of malaria and where there is chloroquine resistance to P. falciparum malaria, should be advised against travelling.

References

  1. WHO. World Malaria Report 2010: WHO, Geneva, 2010.
  2. Mudur G. Malaria deaths in India have been underestimated, new study indicates. BMJ 2010;341:c5981.
  3. Doolan DL, Donbano C, Baird JK. Acquired immunity to malaria. Clin Microbiol Rev 2009;22(1):13-36.
  4. Behrens RH, Carroll B, Beran J, Bouchaud O, Hellgren U, Hatz C, et al. The low and declining risk of malaria in travellers to Latin America:is there still an indication for chemoprophylaxis? Malaria Journal 2007;6(114).
  5. Behrens RH, Carroll B, Hellgren U, Visser LG, Siikamäki H, Vestergaard LS, et al. The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator? Malaria Journal 2010;9:266.
  6. Behrens RH, Carroll B, Smith V, Alexander N. Declining incidence of malaria imported into the UK from West Africa. Malaria Journal 2008;7(235).
  7. Anon. Cluster of malaria cases from northern Goa. HPS Weekly Report 2007;41(1).
  8. Jelinek T, Behrens RH, Bisoffi Z, Bjorkman A, Gascon J, Hellgren U, et al. Recent cases of falciparum malaria imported to Europe from Goa, India, December 2006-January 2007. Eurosurveillance 2007;12(2).
  9. WHO. International Health and Travel. Geneva: World Health Organization, 2010.
  10. Craig MH, Sharp BL, Mabaso MLH, Kleinschmidt I. Developing a spatial-statistical model and map of historical malaria prevalence in Botswana using a staged variable selection procedure. Int J Health Geogr. 2007;6:44.
  11. Lysenko AY, Semashko IN. Geography of Malaria (A medical-geographical study of an ancient disease). Medical Geography. Moscow, 1968:25-146 (in Russian: available in English here http://www.rollbackmalaria.org/docs/lysenko/lysenko.pdf).
  12. Guerra CA, Snow RW, Hay SI. Mapping the global extent of malaria in 2005. Trends in Parasitology 2006;22(8):353-8.
  13. Snow R, Guerra C, Noor A, Myint H, Hay S. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 2005;434:214-217.
  14. Chiodini J, Boyne L, Grieve S, Jordan A. RCN Competencies: an integrated career and competency framework for nurses in travel health medicine. http://www.rcn.org.
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Author(s): L Boyne, F Genasi, C Redman, H Sutton, C Smith, M White Vol: 45 No: 03 Year: 2011 Page:

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