There has been much recent speculation that global warming could affect the transmission of a range of vector-borne diseases in Europe. Particular focus has been placed on the increase of Lyme Disease, Tick-borne Encephalitis, West Nile virus and leishmaniasis, the re-emergence of malaria as well as the establishment of dengue transmission. Climate models predict a 2-5ºC increase in temperature and significant increases in precipitation in Europe during the next century. Results from biological and statistical models suggests that these changes could indeed increase the risk, particularly of malaria, TBE and Lyme disease. However, most predictions are based on model simulations which contain only a subset of the links between climate and vector-borne diseases and generally do not consider the effects of non-environmental variables such as socio-economy and agriculture. Analyses have shown that the historical distribution of European malaria – and its later disappearance - were more strongly related to vector competence, land cover and socio-economic factors than to climate. Although climate changes may improve conditions for transmission, the current state of these other determinants mean re-emergence of endemic transmission is extremely unlikely. It is therefore unlikely that climate changes alone can lead to the re-emergence of this disease. Similar analyses of the past or present distribution of other vector-borne diseases of interest for Europe can allow us to quantify the exact role of climate and make more valid predictions of the effect of future climatic changes.
In the 4th century BC Hippocrates said “ Whoever would study medicine aright must learn of the following subjects. First, he must consider the effect of the seasons of the year and the differences between them. Second, he must study the warm and cold winds, both those which are common to every country and those peculiar to a particular locality”.
We now know that the risk of all vector-borne diseases is a function of the spatial and temporal patterns of disease transmission (vector breeding habitats, host distribution, human activities etc.) all of which are related to environmental factors in complex ways. Temperature and humidity have the most important direct and indirect effects on vector biology and ecology through influences on insect development and survival, blood feeding and geographical distribution (1). Additionally, the development and transmission of the pathogen is also highly sensitive to temperature (2). Because of the large public health burden of vector-borne diseases (3) and the increasing concern about man-made climate changes, there has been growing interest in the mapping and predictive modelling of their geographical limits and transmission dynamics using environmental variables as driving factors (4). Some of this work, and much media attention, have been focused on the likelihood of tropical vector-borne diseases becoming key public health concerns in areas – such as Europe - where they are currently not transmitted or only of minor medical importance.
Vector-borne diseases in Europe
In past and current literature, five arthropod-borne diseases have been considered of importance to Europe. These are either currently transmitted (leishmaniasis, Lyme disease, tick-borne encephalitis, West Nile virus), previously endemic (malaria) or have been highlighted as potential emerging diseases with respect to global warming (dengue fever ).
From around the 13th century, malaria transmission was endemic in nearly all European countries, causing severe morbidity and mortality in the Mediterranean (5) and parts of western Europe (e.g. England and Holland, 6). In the early nineteenth century, the disease started disappearing from northern Europe due to various changes which reduced human-mosquito contact and cleared parasites from the human reservoir (7). However, the disease remained important in the Mediterranean and eastern Europe and prevalences were only reduced after the initiation of DDT spraying in the 1940s. This was followed by a string of country-wide eradications ranging from Spain in 1964 to the last focus in the Greek republic of Macedonia in 1975. The resurgence of malaria transmission in the former Soviet Union and European Turkey soon after caused concern that the disease could yet again spread to the rest of Europe. Since then, there have been numerous speculations about whether the import of cases from endemic areas in combination with anthropogenic climate changes can lead to the re-emergence of European malaria (8-10).
Lyme borreliosis (Lyme disease) is currently the most commonly reported zoonotic tick-borne infection in Europe. It is widely distributed in Europe with focal patches of high intensity transmission in areas of Bulgaria, The Czech Republic, Slovenia and Sweden (11). This focality is thought to be caused by a combination of the specific vegetation and climate requirements of the tick vector Ixodes ricinus (12) and the availability of mammalian hosts (13). It has been debated whether recently observed increases in the incidence of Lyme disease are due to climatic changes (14) or a combination of changed human behaviour and improved surveillance and diagnosis (15).
Tick-borne encephalitis (TBE) is a zoonotic viral infection distributed in coastal areas of Sweden, Poland, The Czech Republic, Central Europe and the former Soviet Republics. Disease is transmitted to humans by ticks (I. ricinus) through the involvement of wild mammal reservoirs such as deer, mice or voles. The distribution of TBE is obviously limited by its vector but also determined by both climatic factors, tick diversity and human behaviour (15,16). Like Lyme disease, the incidence of TBE in Europe has increased significantly during the past 20 years . Some studies report a strong correlation between this increase and observed temperature rises (17,14) but later evidence has since suggested that the relationship may have been clouded by analytical errors as well as increased awareness of the disease (18, 19).
Visceral (VL) and cutaneous (CL) leishmaniasis is transmitted by phlebotomine sandflies and distributed along the Mediterranean where it is of both veterinary and human health importance. Dogs and wild foxes are the main reservoirs but the prevalence of human VL cases has increased significantly since the 1990s due to a strong association with HIV-infection (20, 21). It has been speculated that a combination of increased importation of canine leishmaniasis into currently non-endemic areas (22) and climate changes may cause the disease to be introduced at higher latitudes, resulting in endemic transmission. The distribution of particularly sandfly vectors is probably linked to high average temperatures (23) but studies on tropical species also suggest a significant, if more important, relationship with land cover and soil types (24, 25).
The dengue virus is transmitted by culicine mosquitoes (Aedes aegypti and Aedes albopictus) and currently a major public health concern in parts of South America and Asia. Serologically confirmed dengue epidemics (transmitted by Aedes aegypti) were observed in Greece during the 1920s (26) but the disease and vectors were eradicated in the 1940s as a result of the anti malaria DDT campaigns. In the past twenty years Ae. albopictus, the second most important vector, has been found in Albania and Italy (27-29), possibly imported in used car tyres from Asia (30). There has been growing concern that climate changes could cause further spread of this mosquito in Europe as well as the return of Ae. aegypti (10).
West Nile virus (WNV) is transmitted by culicine mosquitoes (Culex pipiens, Culex molestus) through the involvement of bird reservoirs and was first isolated from a European population in 1958 (31). The current incidence of human infections is largely unknown although it is believed to be very small (32). Recent human epidemics in the USA generated much media attention and speculation that similar episodes could occur in large cities of Europe, particularly in the more favourable climatic conditions caused by climate changes.
Modelling climate-disease relationships
Reports about links between climate and all of the diseases listed above have been numerous. However, most are based on only considering climatic effects and, in order to be realistic, these need to be interpreted in the context of other determinants of disease. If we are to make sound predictions of the future, it is first necessary to quantify the relationship between climatic and non-climatic factors and various aspects of disease transmission. For some diseases, this has now been achieved to a certain degree by two main approaches: the statistical and the biological models.
The statistical (empirical) approach determines how different factors affect the temporal and spatial distribution of vectors and disease by the use of statistical models such as regression or discriminant analysis. Such models have been used to describe the link between environmental factors and a range of vector-borne diseases including malaria (e.g. 33-35), African Trypanosomiasis (e.g. 36, 37), leishmaniasis (38, 39) dengue (40) and Rift Valley fever (41), as a direct statistical relationship. Although only feasible when there are extensive records on vector/parasite distribution through time and/or space, statistical models have been the most frequently used to analyse and predict disease transmission and they can be just as accurate in terms of making predictions, as the more complex biological models (36).
In the biological method, information on the relationship between individual climatic variables and different aspects of vector and pathogen population dynamics are incorporated into a mathematical model, usually centred around the basic case reproduction R0. R0 is defined as the number of secondary cases arising from a primary one in a fully susceptible host population and endemic transmission can only take place if this exceeds 1. Biological models require detailed understanding of vector and parasite population dynamics and have so far only been developed for diseases with well-studied life cycle parameters such as malaria (e.g. 42-44), dengue (e.g. 45, 46) and tick-borne diseases (e.g. 47, 48). Such models are complex but more flexible than statistical ones and are able to provide specific insight into the dynamics of parasites and vectors in relation to temperature or humidity.
During the past 15 years, there has been a significant increase in the number of attempts to produce vector-borne disease “risk maps” based on the various environmental factors identified from statistical or biological modelling. This has been aided by advances in the availability of sophisticated mapping devices – Geographical Information Systems (GIS) – and up-to-date satellite images of climate surfaces (e.g. temperature and rainfall, 49). It is believed that both GIS and remotely sensed climate and vegetation images may in future become important components in the early warning of epidemics of vector-borne diseases world-wide (50-52).
Predicting the effects of climate changes on vector-borne diseases in Europe
Since the early 1990s, much emphasis has been placed on the potential threat effect of climate changes on human health. Convincing evidence suggests that our climate has indeed changed and that most of the global warming observed is likely to be due to human activities (9). During the 20th century alone, average temperatures in Europe increased by 0.8ºC and models predict further average increases of 2-5ºC by the end of this century (53). Additionally, it has been predicted that average precipitation at high latitudes will increase significantly (9). As already outlined, there are good biological reasons to why these climate changes should affect vector-borne diseases but the very complicated life cycles and a great range of confounding variables (e.g. drug resistance and man-made environmental modifications) makes it difficult to assess both whether climate change has already affected disease distributions, or to what extent continuing it will do so in the future. In spite of this, there have been a number of assertions that global warming may have already affected some vector-borne diseases in Europe; TBE and ticks in Sweden (14, 17), Aedes albopictus in the Mediterranean (29, 54) and malaria in Italy and Germany (55-57).
Progress in making reliable predictions for the future of vector-borne diseases in Europe can be made most easily on the basis of sound statistical modelling, including knowledge about the current or past relationship between climatic factors and disease/vector distribution. This has been attempted for some of the major diseases of interest (Tab.1), but often the results are conflicting due to model limitations such as in the need to make assumptions about missing parameter values in biological models (58), not accounting for geographical variations in vector characteristics (42), predicting presence or absence of transmission rather than on a continuous scale (59) and not acknowledging that areas described as ‘climatically suitable’ for malaria may be unsuitable due to other environmental and social conditions (60).
Common to the majority of these approaches is that there has been no attempt to use large historical or current datasets to quantify the relationship between climate and the various aspects of disease risk. For malaria, one of the most important determinant of disease risk is the presence of competent vectors. Recently Kuhn et al (35) used a historical database of the presence and absence of five important malaria vectors in Europe to create climate-driven risk maps for the current distribution of these vectors throughout the continent. The Hadley Centre (HADCM3) climate change model for the A2 SRES scenarios have since been applied to these predictions to determine the change in Anopheles distribution with projected climate changes (Fig 1). To take one example, Anopheles messeae was considered one of the most important malaria vectors in northern Scandinavia (61, 62). Our models currently predict it to be present in Scandinavia and north-west Europe, including the Baltic states and Russia. These predictions are difficult to assess, as there is only patchy and outdated information about its resent distribution. Climate change simulations indicate that the distributional limits of An. messeae may not change much but that the probability of presence could have increased significantly by the 2080s. Risk maps like these can potentially serve as important entomological baselines for the prediction of future disease risk, though we must be aware that there are many other factors which also play an essential role in determining the intensity of disease transmission.
Lessons for the future
A report recently published by the Chief Medical Officer in Britain claimed that “by 2050 the climate of the U[nited] K[ingdom] may be such that indigenous malaria could become re-established” (63). These statements are difficult to support without robust modelling and proper understanding of the quantitative relationships between climate and disease/vector distributions, along with the contributions of other determinants.
In general, the message is that we cannot predict the future unless we understand the past or the present. A good example of this is the case of British malaria. Recent analyses have shown that the disappearance of the disease from England was due to increasing cattle populations and decreasing acreages of marsh wetlands (7). Modelling scenarios suggested that projected (HADCM3) climate changes were likely to cause an increase in the risk of local malaria cases but that this was several orders of magnitude too small to lead to endemic transmission, given current socioeconomic conditions, surveillance and treatment programmes. This will probably also be the case in the rest of Western Europe where socio-economic and agricultural factors were the main determinants of transmission intensity (5, 10, 64). Even for those areas with current transmission (former Soviet Union and European Turkey), attribution of past changes to climate should be cautious as human migration, health system decays and cessation of control measures are considered to have made a greater contribution to the re-emergence of malaria (65-67).
For the other diseases discussed in this paper, the effect of climate on future transmission patterns is also likely to be outweighed by non-environmental factors. TBE and Lyme in humans is dependent on recreational habits (i.e. contact with tick-infested areas), host animal abundance and vegetation type, 15). Leishmaniasis is geographically limited by the distribution of the sandfly vector which is very habitat- and climate-specific, but stronger factors impacting on its prevalence is the existence of canine reservoirs and the prevalence of HIV-positive humans. However, the persistence of this disease in the Mediterranean in spite of the intensive historical DDT spraying here could suggest that climate may be more important in maintaining transmission than was the case for malaria (23). With respect to West Nile virus, there is little evidence that its emergence in Europe was linked to climatic factors and the number of human cases is relatively small in comparison to other public concerns. This was not the case with the recent epidemics in the USA where climate changes were widely cited in connection with the increase in human cases (e.g. 68). Here, the epidemics were most likely caused by changed bird migratory patterns and increased monitoring for human cases (69). The future of dengue virus transmission in Europe is also not certain. Findings of Ae. albopictus in the Mediterranean could suggest that the climate there has become more suitable for this mosquito, but a more likely scenario is that the climate has always been suitable for dengue vectors (as demonstrated by the historical epidemics in Greece) and the recent invasion is entirely due to a steady increase in imported mosquitoes because of intensified international trade. As for malaria, socioeconomic factors, particularly housing, are known to be important determinants of dengue transmission (70). These factors may make it difficult for the reproduction rate (Ro) to exceed 1 in Europe, despite increased temperatures and precipitation. However, this requires further investigation as ongoing transmission in Singapore and continuing outbreaks in Queensland show that it is possible for dengue to be maintained even in developed countries, given suitable climatic conditions and sufficient imported cases.
In conclusion, although modelling studies suggest that climate changes may increase the risk of transmission of vector-borne diseases in Europe, historical analyses suggest that, for malaria at least, socioeconomic conditions coupled with efficient surveillance and treatment will probably prevent this being translated into a real public health problem. Similar quantitative modelling of climatic effects, in the context of other influences, should improve our ability to make predictions for other vector-borne diseases.
1. Sellers RF. Weather, host and vector; their interplay in the spread of insect-borne animal virus diseases. J Hyg. 1980;85: 65-102.
2. Bradley DJ. Human tropical diseases in a changing environment. In Environmental change and human health. Wiley, Chichester (Ciba foundation symposium), 1993.
3. Curtis CF, Davies CR. Present use of pesticides for vector and allergen control and future requirements. Med Vet Entomol 2001; 15: 231-235.
4. Hay SI, Omumbo JA, Craig MH et al. Earth observation, geographic information systems and Plasmodium falciparum malaria in Sub-Saharan Africa. Adv Parasitol. 2000; 47: 174-216.
5. Bruce-Chwatt LJ, de Zulueta J. The rise and fall of malaria in Europe; a historico-epidemiological study. Oxford University Press, Oxford, 1980.
6. Dobson MJ. Contours of death and disease in early modern England. Cambridge University Press, Cambridge 1997.
7. Kuhn KG, Campbell-Lendrum DH, Armstrong B et al. Malaria in Britain: past, present and future. PNAS. 2003; 100: 9997-10001.
8. Kovats RS, Haines A, Stanwell-Smith et al. Climate change and human health in Europe. BMJ. 1999; 318: 1057-1068.
9. IPCC. Climate change 2001: impacts, adaptation and vulnerability. McCarthy JJ, Canziani OF, Leary NA, Dokken DJ, White KS (Eds). Cambridge University Press, Cambridge. 2001 .
10. Reiter P. Climate change and mosquito borne disease. Environ Health Perspect. 2001; 109: S141-S161.
11. WHO. WHO workshop on Lyme borreliosis diagnosis and surveillance. WHO/CDS/VPH/95.141, Warsaw, Poland, 1995.
12. Daniel M, Kolár J, Zeman P et al . Tick-borne encephalitis and Lyme borreliosis: comparison of habitat risk assessments using satellite data (an experience from the Central Bohemian region of the Czech Republic). Central European Journal of Public Health 1999;7:35-39.
13. Rizzoli A, Merler S, Furlanello C et al. Geographical information systems and bootstrap aggregation (bagging) of tree-based classifiers for Lyme disease risk prediction in Trentino, Italian Alps. J Med Entomol. 2002; 39; 485-492
14. Lindgren E, Tälleklint L, Polfeldt T. Impact of climatic change on the northern latitude limit and population density of disease-transmitting European tick Ixodes ricinus. Env Health Perspect. 2000; 108: 119-123
15. Randolph SE. The shifting landscape of tick-borne zoonoses: tick-borne encephalitis and Lyme borreliosis in Europe. Phil Trans R Soc Lond B. 2001; 356: 1045-1056.
16. Perret JL, Guigoz E, Rais O et al. Influence of saturation deficit and temperature on Ixodes ricinus tick questing activity in a Lyme borreliosis-endemic area (Switzerland). Parasitol Res. 2000;86:554-7.
17. Tälleklint L, Jaenson TGT. Increasing geographical distribution and density of Ixodes ricinus (Acari: Ixodidae) in central and southern Sweden. J Med Ent. 1998; 35: 521-526.
18. Hay SI. The world of smoke, mirrors and climate change. Trends Parasitol. 2001; 17: 466
19. Kovats RS, Campbell-Lendrum DH, McMichael AJ et al. Early effects of climate change: do they include changes in vector-borne diseases. Phil Trans R Soc Lond B. 2001; 356: 1057-1068.
20. Gradoni L, Scalone A, Gramiccia M et al. Epidemiological surveillance of leishmaniasis in HIV-1-infected individuals in Italy. AIDS. 1996; 10:785-91
21. Choi CM, Lerner EA. Leishmaniasis as an emerging infection.
J Investig Dermatol Symp Proc. 2001; 6:175-82.
22. Gothe R, Nolte I, Kraft W. Leishmaniose des Hundes in Deutschland: epidemiologische Fallanalyse und Alternative zur bisheringen kausalen Therapie. Tierärztl Prax 1997; 25: 68-73
23. Kuhn KG. Global warming and leishmaniasis in Italy. Bull Trop Med Int Health. 1999; 2: 1-2
24. Elnaeim DA, Connor SJ, Thomson MC et al. Environmental determinants of the distribution of Phlebotomus orientalis in Sudan. Ann Trop Med Parasit, 1998; 92: 869-876.
25. Thomson MC, Elnaeim DA, Ashford RW et al. Towards a kala azar risk map for Sudan: mapping the potential distribution of Phlebotomus orientalis using digital data of environmental variables. Trop Med Int Health. 1999; 4: 105-113.
26. Halstead SB and Papaevaneglou G. Transmission of dengue 1 and 2 viruses in Greece in 1928. Am J Trop Med Hyg. 1980; 29: 637
27. Romi R. History and updating on the spread of Aedes albopictus in Italy. Parassitologia. 1995; 37: 99-103
28. Romi R, Sabatinelli G, Savelli LG et al. Identification of a North American mosquito species, Aedes atropalpus (Diptera: Culicidae) in Italy. J Am Mosq Control Assoc. 1997; 13: 245-246.
29. Adhami J, Reiter P (1998). Introduction and establishment of Aedes (Stegoymyia) albopictus skuse (Diptera: Culicidae) in Albania. J Am Mosq Control Assoc 1998; 14: 340-343.
30. Knudsen AB, Romi R, Majori G. Occurrence and spread in Italy of Aedes albopictus with implications for its introduction into other parts of Europe. J Am Mosq Control Assoc. 1996; 12: 177-183
31. Bárdoš V, Adamcová J, Dedei S et al. Neutralizing antibodies against some neurotropic viruses determined in human sera in Albania. J. Hyg. Epidem. (Prague) 1959; 3: 277-282.
32. Hubálek Z., Halouzka J West Nile fever - a re-emerging mosquito-borne viral
1. disease in Europe. Emerg Infect Dis.1999; 5: 643-650.
33. Bouma MJ, Dye C, Van der Kaay HJ. Falciparum malaria and climate change in the North West Frontier Province of Pakistan. Am J Trop Med Hyg 1996; 55: 131-137
34. Omumbo J, Ouma J, Rapouda B et al. Mapping malaria transmission intensity using geographical information systems (GIS), an example from Kenya. Ann Trop Med Parasit. 1998; 92: 7-21
35. Kuhn KG, Campbell-Lendrum DH, Davies CR. A continental risk map for malaria mosquito (Diptera: Culicidae) vectors in Europe. J Med Ent. 2002; 39: 621-630.
36. Rogers DJ, Randolph SE . Distribution of tsetse and ticks in Africa: past, present and future. Parasitol Today. 1993; 9: 266-271
37. Hendrickx G, Napala A, Dao B et al . A systematic approach to area-wide tsetse distribution and abundance maps. Bull Ent Res. 1999; 89: 231-234
38. Cross ER, Newcomb WW, Tucker CJ. Use of weather data and remote sensing to predict the geographic and seasonal distribution of Phlebotomus papatasi in southwest Asia. AM J Trop Med Hyg 1996; 54: 530-536
39. Franke CR, Ziller M, Staubach C et al. Impact of the El Nino/Southern Oscillation on visceral leishmaniasis, Brazil. Emerg Infect Dis. 2002 Sep;8: 914-917.
40. Hay SI, Myers MF, Burke DS et al. Etiology of interepidemic periods of mosquito-borne disease. Proc Natl Acad Sci USA. 2000; 97:9335-9.
41. Linthicum KJ, Bailey CL, Tucker CJ et al. Application of polar-orbiting meteorological satellite data to detect flooding of Rift Valley Fever virus vector mosquito habitats in Kenya. Med Vet Entomol. 1990; 4: 433-8
42. Martens P, Niessen LW, Rotmans J et al. Potential impact of global climate change on malaria risk. Env Health Perspect. 1995; 103: 458-464
43. Massad E, Forattini OP. Modelling the temperature sensitivity of some physiological parameters of epidemiologic significance. Ecosystem Health.1998; 4: 119-129
44. Lindsay SW, Thomas CJ. Global warming and risk of vivax malaria in Great Britain. Global Change & Human Health. 2001; 2. 80-84.
45. Focks DA, Haile DG, Daniels E et al. Dynamic life table model for Aedes aegypti (Diptera: Culicidae): Simulation results and validation. J Med Ent 1993; 30: 1018-1028
46. Jetten TH, Focks DA. Potential changes in the distribution of dengue transmission under climate warming. Am J Trop Med Hyg. 1997; 57: 285-297
47. Perry BD, Lessard P, Norval RA et al. Climate, vegetation and the distribution of Rhipicephalus appendiculatus in Africa. Parasitol Today. 2000; 6: 100-104
48. Randolph SE. Abiotic and biotic determinants of the seasonal dynamics of the tick Rhipicephalus appendiculatus in South Africa. Med Vet Ent.1997; 11: 25-37
49. Hay SI, Tucker CJ, Rogers DJ et al. Remotely sensed surrogates of meteorological data for the study of the distribution and abundance of arthropod vectors of disease. Ann Trop Med Parasitol. 1996; 90: 1-19
50. Beck LR, Bradley M, Lobitz B et al . Remote sensing and human health: new sensors and new opportunities. Emerg Inf Dis 2001; 6: 217-226
51. Thomson MC, Connor SJ. Environmental information systems for the control of arthropod vectors of disease. Med Vet Ent. 2000;14: 227-244
52. Rogers DJ, Randolph SE, Snow RW et al. Satellite imagery in the study and forecast of malaria. Nature. 2002; 415: 710-715
53. Hulme M, Jenkins GJ. Climate Change scenarios for the United Kingdom: Summary Report. UKCIP Technical Report. Climatic Research Unit, University of East Anglia, Norwich. 1998.
54. Romi R, Di Luca M, Majori G. Current status of Aedes albopictus and Aedes atropalpus in Italy. J Am Mosq Control Assoc. 1999; 15: 425-427
55. Baldari MA, Tamburro A, Sabatinelli G et al. Malaria in Maremma, Italy. Lancet 1998; 351: 1246-1247.
56. Kruger A, Rech A, Su XZ et al. Two cases of autochthonous Plasmodium falciparum malaria in Germany with evidence for local transmission by indigenous Anopheles plumbeus. Trop Med Int Health. 2001; 6: 983-985.
57. Kampen H, Maltezos E, Pagonaki M et al. Individual cases of autochthonous malaria in Evors Province, northern Greece: serological aspects. Parasitol Res. 2002; 88: 261-266.
58. Martin PH, Lefebvre MG. Malaria and climate: sensitivity of malaria potential transmission to climate. Ambio. 1995; 24: 200-207.
59. Rogers DJ, Randolph SE . The global spread of malaria in a future, warmer world. Science. 2000; 289: 1763-1766.
60. Martens P, Kovats RS, Nijhof S et al. Climate change and future populations at risk of malaria. Global Env Change. 1999; 9:S89-S107.
61. Ekblom T. Studien über die Malaria und Anopheles in Schweden und Finland. Acta Pathologica et Microbiologica Scandinavica 1945; 59: S1-S89
62. Jetten TH, Takken W. Anophelism without malaria in Europe: A review of the ecology and distribution of the genus Anopheles in Europe. Wageningen Agricultural University, Wageningen, The Netherlands. 1994.
63. Department of Health. Getting Ahead of the Curve: a Strategy for Combating Infectious Diseases (including other aspects of health protection). A report by the Chief Medical Officer, Department of Health, London, United Kingdom 2002.
64. Riera Palmero J. Work, rice and malaria in Valencia in the XVIIIth century. Physis Riv Int Stor Sci. 1994; 31: 771-785
65. Ramsdale CD, Haas E. Some aspects of the epidemiology of resurgent malaria in Turkey. Trans R Soc Trop Med Hyg. 1978; 72: 570-580.
66. Sergiev VP, Baranova AM, Orlov VS et al . Importation of malaria into the USSR from Afghanistan, 1981-89. Bull World Health Organ. 1993;71:385-8.
67. Pitt S, Pearcy BE, Stevens RH et al. War in Tajikistan and re-emergence of Plasmodium falciparum. Lancet. 1998;352:1279.
68. Epstein PR. West Nile Virus and the climate. J Urban Health. 2001 Jun;78:367-371.
69. Peterson AT, Vieglais DA, Andreasen JK. Migratory birds modelled as critical transport agents for West Nile Virus in North America. Vector Borne Zoonotic Dis. 2003;3:27-37.
70. Reiter P, Lathrop S, Bunning M et al. Texas lifestyle limits transmission of dengue virus. Emerg Infect Dis. 2003;9:86-9.