Review
Imported malaria in children: a review of clinical studies

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Summary

Imported malaria is a preventable disease, yet it is responsible for several thousand cases and a substantial number of deaths every year. There has been a pronounced rise in the incidence of imported malaria in most developed countries over the past three decades and, more concerning, Plasmodium falciparum, which is responsible for almost all cases of severe malaria, is now the most prevalent species. Children account for around 15–20% of all imported malaria cases and must be considered separately from adults because they have different risk factors for developing malaria and a higher risk of developing severe disease since they are more likely to be non-immune to malaria. We did a thorough review of the literature since 1980 to identify and critically assess clinical case series on children with imported malaria with respect to travel destination, reason for travel, the use of antimalarial prophylaxis, clinical presentation, delay in diagnosis, laboratory features, complications, management, and outcome. Children living in non-endemic countries and travelling during school holidays to visit family and relatives in their parents' country of origin currently account for the largest proportion of cases in many European countries. This group of travellers deserves special attention because they often do not take antimalarial prophylaxis or other preventive measures. There is a need for standardised recommendations on management and prevention of imported malaria in children, which should be supported by large multicentre clinical trials. A prospective national surveillance study on imported malaria in children was launched in the UK and Ireland through the British Paediatric Surveillance Unit in 2006, which may provide answers to some of the questions raised in this Review.

Introduction

An estimated 10% of the world's population will have a clinical attack of malaria.1 More people are dying from malaria now than 30 years ago and malaria is returning to areas where it had previously been eradicated. It is estimated that there are between 300 million and 500 million cases of malaria every year and between 1 million and 3 million deaths attributable to malaria, mainly in young African children.2 These deaths are almost all caused by infection with Plasmodium falciparum.

Imported malaria is defined as an infection acquired in a malaria-endemic area but diagnosed in a non-endemic country after development of clinical symptoms. In most developed countries where malaria is not endemic, there has been a pronounced rise in the incidence of imported malaria in the past three decades.3, 4 In particular, the proportion of imported malaria cases caused by P falciparum has increased substantially since the 1980s.3, 4 The Malaria Programme in the WHO European Region, which collects annual data on laboratory-confirmed malaria cases from 51 countries in the region, reported an eight-fold increase in the number of imported malaria cases between 1972 and 1988 (from 1500 to 12 000 cases), followed by a more gradual rise to 15 500 cases in 2000.3 Most cases were imported into western Europe, with France, the UK, Germany, and Italy accounting for more than 70% of all cases in Europe in 1998. In 2002, the last year for which complete data is available, these four countries accounted for 78·5% of 13 227 cases. However, the true incidence of imported malaria is difficult to obtain because of substantial under-reporting—estimated at 20–60%—even in countries with enhanced surveillance.4, 5

Children account for around 15–20% of all imported malaria cases (figure).6 This group must be considered separately from adults because children have different risk factors for developing malaria and a higher risk of developing severe disease since they are more likely to be non-immune to malaria.7 The aim of this paper is to identify and critically review clinical case series on children with imported malaria with respect to travel destination, reason for travel, the use of antimalarial prophylaxis, clinical presentation, delay in diagnosis, laboratory features, complications, management, and outcome.

Section snippets

Clinical studies identified

An extensive literature search identified seven European (table 1) and six North American (table 2) clinical studies on imported childhood malaria between 1980 and 2005 that fulfilled the search criteria. Individually, the clinical studies provided limited information because most reported a small number (fewer than 100) of cases diagnosed over many years and involved children who developed malaria in different parts of the world and through different Plasmodium species. Only two studies, one

Diagnosis and investigations

Malaria remains a rare cause of fever in non-endemic areas and requires a high index of suspicion.9, 15 Frequently, not enough attention is given to obtaining a history of foreign travel or of immigration from a malaria endemic area.9 This problem is exacerbated by families who delay seeking medical advice because of unfamiliarity with health-care systems.7, 47, 48 In children, delays in diagnosis occur in 2–90% of cases in the reported series (Table 1, Table 2), resulting in treatment delays

Management

The management of malaria varies according to the plasmodium species responsible, national guidelines, antimalarial availability, and individual patient factors.20 Therapy usually does not differ between non-immune travellers and immigrants. There are no randomised controlled clinical trials on the optimum treatment of children with imported malaria and most of the recommendations are extrapolated from studies and experience with paediatric malaria in endemic countries.

Outcome

Data on outcome currently relies on national notification systems, which may grossly underestimate case fatality rates. Notifications to WHO have reported case fatality rates of around 1% in most European countries, which have remained constant since the 1970s. However, the number of malaria-related deaths has increased from fewer than ten in 1971 to more than 60 in 1999.3 A Review of deaths attributed to malaria in the USA identified specific risk factors for fatal malaria, including failure

Conclusions

Imported malaria is a preventable disease, yet it is responsible for several thousand cases and many deaths every year. The past three decades have seen a pronounced shift in the epidemiology of imported malaria as a result of increasing speed and ease of travel. The incidence of imported malaria in children has increased substantially and, more concerning, P falciparum, which is responsible for almost all severe malaria, is now the most prevalent species. Poor control of malaria in many

Search strategy and selection criteria

Information was obtained from Medline and PubMed searches for years between 1980 and 2005. Using the search term “imported malaria”, original articles in any European language relating to clinical case series on children with imported malaria were retrieved and their references searched for relevant clinical studies. Articles that focused only on epidemiology or those that combined children with adults were excluded. Online public-health sites for different countries were also scanned for

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