Background
Over the last 30 years there has been a rapid increase in emerging and re-emerging infectious diseases in the human population [
1‐
3], with over 175 species of pathogens now classified as emerging or re-emerging [
4]. Emergence of these diseases are frequently associated with ecological changes [
1] and many are transmitted by insect or tick vectors [
1,
4,
5]. Because of the sensitivity of malaria to a range of environmental factors there is concern that the disease may spread to new regions of the world [
6,
7], previously disease free, like the UK.
Malaria was once common in marshland communities in central and southern England between 1500 and 1800, before finally disappearing in the early 1900s [
8]. Those areas most badly affected included the Fens, Thames estuary, the Kent coast, the Somerset levels, the Severn Estuary and the Holderness of Yorkshire; all substantial areas of marshland. The disease declined progressively from the 1850s onwards, as living conditions in the marshes improved and quinine, an effective anti-malarial, became more affordable and was used more frequently. The last significant epidemic of malaria in England and Wales occurred in 1917 and 1918, with the main focus on the Isle of Sheppey, near the mouth of the Thames Estuary [
9,
10]. During this epidemic, there were 330 cases of locally-transmitted vivax malaria when infected servicemen returning from Macedonia were billeted near salt marshes. Indeed, all reported cases of locally transmitted malaria in the 1900s were vivax malaria, except for an unusual case of falciparum malaria in Liverpool [
11]. Whilst vivax malaria is a serious and debilitating infection, it is rarely a killer like falciparum malaria [
12]. Thus although historically mortality rates in the marshlands of southern England were several orders higher than inland areas, it is unlikely that the elevated mortality in the marshes was due to vivax malaria.
There are six species of Anophelines in Britain capable of transmitting both temperate and tropical strains of vivax malaria:
Anopheles atroparvus, Anopheles algeriensis,
Anopheles claviger,
Anopheles daciae,
Anopheles messeae and
Anopheles plumbeus[
13,
14].
Anopheles atroparvus is considered the most important vector of vivax malaria in the UK, since its distribution coincides best with the historical distribution of the disease [
15]. It also rests inside homes and will feed on people [
16].
Modelling the threat from malaria is a necessary first step in estimating the populations at risk and where they live [
17‐
19], helping to inform disease surveillance programmes across the world. To date there have been two broad approaches to modelling the distribution of malaria: process-based models and statistical ones. Process-based models of malaria spread are considered favourable since they are based on an understanding of the biology of malaria. They are largely driven by the manner in which temperature influences mosquito survival, frequency of blood-feeding and the development of parasites within mosquitoes [
20,
21]. The major concern with this approach is that the models are solely temperature driven and no allowance is made for two potentially important environmental parameters known to affect vector populations; rainfall and relative humidity. Rainwater, groundwater and diluted seawater provide mosquito breeding habitats, along with a moderately humid environment which is conducive to vector survival [
22]. Statistical models capture the climate envelope of where the disease is present and produce relatively robust models of the disease's current distribution [
18,
19]. However, they lack the clarity and understanding provided by process-driven models. Rarely are the two different modelling approaches used together. A simple process-driven model of malaria was compared with a statistical model to examine the risk of malaria transmission in the UK today and in the future under projected climate change.
Discussion
The simple temperature-driven processed-based model demonstrated that present temperatures in the south of England are able to support transmission of vivax malaria for a few months each year. For most areas, this is just for two months, although the heat island effect of London means this city could support transmission for three months. If the climate becomes warmer, conditions for transmission become more favourable and last for longer. Under the UKCIP02 medium-high scenario used here, the risk of transmission is predicted to increase in the south of England, spreading northwards towards the Scottish border. The areas at greatest risk include the Thames Estuary, the Suffolk coast, the Fens, Romney marshes, the Southampton coastline, the Severn Estuary and parts of the South-West coastline. Interestingly, by 2030, the areas where the climate is predicted to be suitable for malaria for three to four months are those that once supported malaria in the past: coastal and inland marshes of southern England. It is important to appreciate that this analysis reflects average monthly values, and that in reality there will be large variations in climate from year to year, making some years considerably more suitable for malaria transmission than others.
It is likely that our predictions are robust for two reasons. Firstly, 93 of the 96 sites where malaria was recorded in the early-nineteenth century occurred within the climate suitability map for malaria in 1961-90, as reported previously [
37]. Although the cases and climate surfaces were from different periods, the summer temperatures, when conditions are best for transmission, were similar. Secondly the climate suitability map generated using a statistical model, fitted to an independent data set, was very similar to that generated using the process-based model.
An analysis of the statistical models demonstrated that the most important parameter to include was the mean temperature of the warmest month, providing support for using the temperature-driven process-based model in the analysis. Risk of malaria also increased with higher human population densities and drier conditions. Whilst it is logical to appreciate that the risk of an infective mosquito feeding on a person will be greater when there are more people, it is perhaps surprising that malaria was predicted to be more likely in drier conditions. This unexpected result was largely due to five cases of malaria occurring around the Suffolk coast that could not be accounted for by warm temperatures or high population density. However, since this region is close to saltmarsh, the favoured habitat of the historical malaria vector, An. atroparvus, it may simply reflect that the cases lived close to suitable vector habitats. This raises a general problem with our mapping approach. And that is, although climate governs the distribution of vectors and the pathogens they transmit at a broad scale, the actual risk depends on local conditions (e.g. habitat type) and the complex interactions between pathogen, vector and people.
Within the temperature-suitability zone we are uncertain where the vectors occur. The actual distribution of potential vectors in the UK is poorly defined and is based on data collected over 100 years ago or by entomologists in an unsystematic fashion [
31,
38‐
40]. The concern is that these distributions may not reflect the true distribution of vector species. As a proxy measure to identify sites likely to have
An. atroparvus, a landcover map of saltmarsh areas was used as a filter over the temperature-suitability map, since this mosquito is a coastal species, tolerant of brackish water [
41].
At first sight these maps may give the impression that there is a significant risk of malaria returning to the UK. However, the field studies cast doubt on this conclusion and demonstrate the importance of carrying out fieldwork to validate the model predictions. In 2003, a survey of adult mosquitoes was carried out on the saltmarsh on the Isle of Sheppey [
42], the last place in England to experience an epidemic of malaria [
9]. Using two carbon dioxide baited CDC light traps and two Mosquito Magnet
® traps mosquitoes were sampled continuously from June to September, the period when most mosquitoes are searching for a host. At 1240 ha this is the largest area of saltmarsh in the UK/England, yet only 40
An. maculipennis (probably
An. atroparvus) were collected. Of 83 blood-fed
An. maculipennis collected from a horse stable, a derelict school and a derelict concrete pill box on the Isle of Sheppey (RH unpublished data), and analysed using a precipitin test [
43], just two had fed on people indicating that around 2% of the population fed on people. The risk of being bitten by a potential malaria mosquito is, therefore, extremely low, even though there is a general problem with nuisance biting by other mosquito species on the Island [
42].
How likely is it that vivax malaria could be transmitted in the UK? Malaria transmission requires that a potential vector should feed on someone carrying gametocytes, the stage of the parasite that is capable of maturing and becoming infective within a mosquito. Between 9-24 days after taking an infectious blood meal of gametocytes, depending on temperature [
26] a vector mosquito will be potentially able to transmit the infection to anyone that it bites. In 2003 there were 206 cases of imported vivax malaria and approximately 66% of these were contracted by visitors to the Indian subcontinent [
44]. It is likely that this will under-represent the true number of people with circulating gametocytes since even in areas of low transmission many infectious semi-immune patients will not appear sick [
45]. Nonetheless, overall there are likely to be relatively few people carrying vivax gametocytes in the country, and since most of these are amongst people of Asian decent who tend to live in major urban areas, away from coastal marshes, the possibility of
An. atroparvus, biting an infectious patient are remote. There remains the possibility that there are other vectors of vivax malaria in the UK since not all indigenous cases of malaria recorded in the 1917/18 outbreak lived near saltmarsh. In such cases,
An. plumbeus or
An. claviger might have transmitted the infection.
Overall, it is seems extremely unlikely that vivax malaria will be locally transmitted within the UK. Therefore, not more than a few very rare cases of autochthonous malaria in the UK would be expected over the next 50 years. Indeed, one is much more likely to be struck by lightning [
46] than to get malaria from an English mosquito.
The threat posed by malaria in Europe has been assessed previously [
47‐
49]. Processed-based [
50] models and statistical ones [
19] have both been used to explore the global risk of malaria, whilst at the local and countrywide scales processed-based models, of differing levels of complexity, have been used for assessing future risk in Europe (France [
51,
52], Germany [
53] and Portugal [
54]). The present study differs from these since it uses both processed-based and statistical models to explore the risk of malaria, and validates both models with independent data sets of historical cases of malaria.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
SWL conceived the study and developed the process-based model. SAR and SGW did the statistical analysis and SGW and DGH carried out the spatial analysis. RAH carried out the fieldwork. SWL and SGW wrote the manuscript, and all authors contributed to the drafts and read and approved the final manuscript.