Malaria after international travel: a GeoSentinel analysis, 2003–2016

An estimated 214 million infections and 438,000 deaths attributed to malaria occurred globally in 2015 [1]. Although there have been improvements in global malaria control since 2000, malaria remains a threat to international travellers. Malaria is endemic throughout the tropics and sub-tropics, regions visited by an estimated 25–30 million international travellers annually [2], resulting in an estimated 30,000 travel-related malaria infections [3]. Imported malaria may occur more often along certain travel routes in these areas, and may result in secondary transmission [4] if the infection is brought back to a non-endemic country. Most of the reported 17,471 imported malaria infections among US travellers from 2004 to 2014 were acquired while travelling in Africa; Plasmodium falciparum or Plasmodium vivax comprised the majority of infections [5]. Most P. falciparum exposures cluster in Africa and the Caribbean (Hispaniola) and P. vivax exposures occur most frequently in Central America, South America, Asia, and Oceania [4].

Despite the risk of malaria when travelling to an endemic country, and the ability to prevent malaria with proper chemoprophylaxis and mosquito-bite precautions, most international travellers do not have a pre-travel clinical visit with a healthcare provider [6]. However, even among travellers who do receive pre-travel care, some may be non-adherent to chemoprophylaxis due to forgetfulness or medication side-effects, or they may decline to take chemoprophylaxis due to cost, peer advice or low perceived risk [7]. Furthermore, travellers may be prescribed a medication ineffective for the intended travel area [5]. The increasing connectivity of malaria-endemic countries with non-endemic countries via air travel [4, 8], the lack of adequate pre-travel preparation, and personal behaviour that may increase Anopheles mosquito exposure [9] may keep malaria as a continued threat to travellers’ health.

The purpose of this analysis is to describe the demographic characteristics, trip details, clinical visit information, and disease attributes of travellers diagnosed with malaria at GeoSentinel Global Surveillance Network sites following travel to malaria-endemic areas.

GeoSentinel, a specialized surveillance network, captured surveillance data from travel medicine facilities around the world and facilitated the description of malaria cases among returned travellers. The WHO’s World Malaria Report 2015 indicated that malaria infections, mostly involving persons living in endemic areas, declined by an estimated 18% from 2000 to 2015 [1]. Efforts to eliminate malaria contributed to this decline, and the WHO’s Global Technical Strategy for Malaria 2016–2030 aspires to continue reducing malaria incidence and mortality by 90% in high-burden countries [1, 13]. Despite improvements in malaria control, imported malaria to the USA has increased since 1973 [5] and stabilized in the UK [14]. These data, together with GeoSentinel data, indicate that malaria continues to pose a health risk to travellers and surveillance of global travel-related malaria infection is essential to travellers’ health, as well as elimination efforts.

Specific traveller groups may more frequently acquire malaria while abroad than others [6]. Males were more frequently diagnosed with malaria than females; males are thought to be at higher risk of malaria [15], possibly from higher travel frequency or increased exposure to mosquito bites from various activities [16]. However, women, children or migrants from high-burden countries may share a similar malaria infection frequency as men, but did not receive care at GeoSentinel surveillance sites. Travellers with malaria more frequently acquired infection in sub-Saharan Africa than other regions. Sub-Saharan Africa remains the most heavily concentrated region for malaria transmission and, likely, traveller exposure [1]. The majority of the malaria burden and malaria deaths worldwide are from 15 African countries [1]; Nigeria and the Democratic Republic of the Congo accounted for approximately 40% of malaria mortality per WHO in recent years [13]. Although the 12 deaths were not exposed to malaria in these two countries, 11 (92%) were exposed in other countries in West or Central Africa. Malaria was also more frequent among VFRs than tourists, business travellers, or other traveller groups, consistent with other published reports [5]. This may be due to a lack of risk awareness among VFRs due to previous residence in a malaria-endemic area, financial barriers that prevent VFRs from obtaining a pre-travel visit or filling prescriptions for prophylactic medications, cultural or language barriers in accessing pre-travel care, adoption of local health-related behaviour during their trip, or travel to areas with high transmission intensity, sometimes for an extended time or with little advance notice [11, 17–19]. A Global TravEpiNet analysis of pre-travel healthcare visits that found VFRs were more likely than non-VFRs to visit malaria-endemic countries [20]. In this analysis, VFRs were most frequently infected with P. falciparum; this finding is consistent with surveillance findings from Europe, including the UK, where more than 80% of imported P. falciparum malaria was among VFRs [21, 22]; this finding is likely due to a high frequency of travel to West Africa. Preventing malaria (particularly severe malaria caused by P. falciparum) among VFRs is best if done proactively; this includes increasing malaria awareness, promoting pre-travel visits and inquiring about future travel plans [23]. Diminishing the burden of imported malaria among travellers to sub-Saharan Africa and VFRs must be a continued focus of malaria prevention efforts. Diminishing this burden will also prevent re-introduction of malaria to locations that have achieved malaria elimination.

This is the largest analysis to date describing characteristics of child travellers with malaria from North America and Europe [24]. One in 10 children treated at GeoSentinel clinics had severe malaria and children <5 years of age accounted for almost half of all severe paediatric cases. Previous studies demonstrated that children account for 15–20% of all imported malaria cases, and approximately 5–10% of children have illness classified as severe, according to WHO criteria [24]; up to one-third of children surviving severe or cerebral malaria will have persistent neurocognitive impairment [25]. Approximately 80% of children diagnosed with malaria were VFRs, and exposure was most common in sub-Saharan Africa. Appropriate preventive care and chemoprophylaxis targeting child VFRs is crucial to help limit travel-related morbidity in this group [24, 26], particularly when travelling to regions where P. falciparum predominates. Prevention efforts must include encouraging pre-travel visits for both adults and their children and providing training and education to paediatricians who may be the only healthcare provider a child sees before travelling. Improved identification of potential child travellers and better adherence to preventive measures is imperative to prevent malaria morbidity and mortality in this population.

The majority of severe malaria infections was caused by P. falciparum in both adults and children in this analysis, consistent with both WHO reports [12] and US traveller surveillance findings from 2014 demonstrating that 83% of severe cases imported to the USA were P. falciparum [5]. Almost all severe malaria infections were acquired in Sub-Saharan Africa, and most frequently among VFRs. A recent multicentre European study describes a similar pattern of geographic exposure and reason for travel among travelers with severe malaria to this current study, but in comparison, report a smaller percentage of travelers ≤18 years with severe malaria (5% vs 7% respectively) [27]. The reason for this difference is unknown, but may be a result of small numbers in each study’s cohort.

Most military travellers with P. vivax in this analysis were French, and 58% were exposed to malaria in French Guiana. A possible explanation for this finding is the increasing proportion of vivax malaria found in French Guiana and an increase in French military missions to the country from 1998 to 2008 [28]. However, there is reporting bias, since the Marseille GeoSentinel site contributed the greatest number of records in this analysis, resulting in a large proportion of travellers returning from French-speaking countries.

One in 10 travellers with malaria traveled for 1 week or less, and 40% of short-term travellers with a species diagnosis had P. vivax. Short-duration travel is often viewed as low risk and, in some cases, prophylaxis may be declined or not recommended. However, malaria remains a risk even for short stays in an endemic area, and therefore a risk–benefit evaluation of malaria chemoprophylaxis should be considered. A limitation regarding acquiring clinical data from short-term travellers with P. vivax or P. ovale, is their infection cannot be definitively linked to the most recent travel.

The highest proportion of completed pre-travel visits was among travellers diagnosed with P. ovale. Although the reason for this finding is unclear, it may be from greater pre-travel preparation for longer-duration trips, given that travellers with P. ovale had the longest median trip duration (55 days). It may also be due to a larger proportion of travellers seeking pre-travel health advice before travelling to Africa, where P. ovale is concentrated. It is also possible that compliance with chemoprophylaxis may prevent symptomatic primary infections with P. ovale, but not relapses weeks to months later. This latter hypothesis is further supported by the finding that travellers with P. ovale had an almost 2-month delay between returning from travel and visiting a GeoSentinel site. However, although both P. ovale and P. vivax have longer median duration between return and presenting to a GeoSentinel site and both may have a delayed presentation due to hypnozoite reactivation, these findings did not hold for P. vivax, suggesting the presence of confounders for this hypothesis.

This analysis of GeoSentinel surveillance data has several limitations. Given the specialized nature of the sites that comprise the surveillance system, these data may not be representative of all travellers with malaria. GeoSentinel is not population-based, so malaria rates and risks cannot be determined. GeoSentinel does not routinely collect information regarding malaria chemoprophylaxis, including the medication taken and compliance; as such, chemoprophylaxis appropriateness or traveller adherence or identify the specific reasons why these travellers became infected cannot be assessed. Nevertheless, given the low proportion of receipt of pre-travel counseling among travellers diagnosed with malaria in this analysis, preparation for travel to malaria-endemic regions was likely inadequate. Severe malaria may not be adequately captured in GeoSentinel, as not all sites have in-patient treatment capabilities and diagnosis relies on clinical identification and provider discretion. Similarly, death is not well-recorded through GeoSentinel surveillance, reflected in the absence of deaths reported among patients with cerebral malaria and the absence of species determination. Data are collected from a single time point, and may not capture a later death, therefore a case fatality rate cannot be calculated. More than 400 travellers did not have Plasmodium species information available in GeoSentinel; the entry of a specific Plasmodium species was not required prior to 2017, resulting in confirmed malaria without a Plasmodium species diagnosis. Also, the lack of diagnostic methodology information collected in GeoSentinel does not allow for independent validation of species diagnoses or mixed-species identifications; although microscopy is the gold standard for malaria diagnosis in most centres [1], mixed-species infections may be overlooked or incorrectly characterized [29, 30]. Despite these limitations, GeoSentinel is the largest surveillance system providing clinical data on travellers, and contributes valuable data on the epidemiology of infectious diseases acquired during international travel and migration.

Despite general improvements in control programmes, malaria continues to cause serious illness in international travellers, particularly VFRs. By identifying the characteristics of travellers with malaria, prevention efforts may be enhanced, such as proactively asking patients about upcoming travel during routine healthcare contacts, ensuring access to appropriate chemoprophylaxis, increasing risk awareness, and reinforcing the need for prevention measures among higher-risk travellers, including children.