GHA 1654-9716 1654-9880 Global Health Action Vol. 2, November 2009, pp. 1–8 sici xxx PUBMED Abbreviation Birgitta Evengård

*Birgitta Evengård Department of Clinical Microbiology Division of Infectious Diseases Umeå University Umeå 90185 Sweden

Rainer Sauerborn Department of Clinical Microbiology, Division of Infectious Diseases Umeå University

Umeå Sweden

Department of Public Health and Clinical Medicine, Centre for Global Health Research Umeå University

Umeå Sweden

Department of Tropical Hygiene and Public Health, Institute of Public Health University of Heidelberg

Heidelberg Germany

Global Health Action CLIMATE CHANGE AND INFECTIOUS DISEASES Influence of climate in diseases The Arctic, looking down to the North Pole. The purpose of this article is ‘to join the dots’ and thus stimulate discussion. Inevitably, the different dots (issues) themselves cannot be elaborated on in detail here. For this, we refer the interested reader to a wide-ranging list of references. Of all regions in the world, the Arctic is particularly affected by global warming. The proportional increase in surface air temperature has been twice the average global increase. Importantly, warming since 1980 has been strongest in the wintertime at 1°C per decade. It comes as no surprise that the sea-ice cover has decreased by 10% during this period 1. Warming is projected to an increase of 2–9°C by the end of the century, a much higher increase than the projected global mean of 1.1–6.4°C 1. Thus, models project a substantial decrease in snow and sea-ice cover over most of the Arctic by the end of the 21st century 2. An already noticeable change was the opening of both the Northwest and the Northeast passages for traffic in 2008. The Barent Sea has been ice-free and open during summer for the past four years. The health effects of these changes in the far North, particularly in the distribution and incidence of infectious diseases, have received little attention so far both in the published literature 3 4 and in the media. Climate change will affect the distribution of infectious diseases directly as well as indirectly. Disruptions in the operation of water supply and sewage facilities increase the risks for intestinal infections through the spread of water and food-borne infections. Some recent examples include a 30-fold increase in hepatitis A in one Russian region after flooding. Also, reduced access to clean water may increase skin infections, many of which are caused by multi-resistant bacteria. As the boreal forest extends north, areas for certain animals such as foxes carrying rabies or echinococcosis and beavers carrying Giardia intestinalis will expand. Another effect of warmer average temperatures and changes in the relative length of seasons is the changing pattern in vector-borne diseases. Insects that exist today in the south of the region transmit different rickettsia species such as Mediterranean spotted fever and Q-fever, and viruses such as West Nile virus. These and the Chikungunya virus, recently established in Europe, could potentially move northwards, although this is less likely, as temperatures needed are higher than most models predict. However, the transmitting vector can change, as has occurred with the transmission of Dengue virus and Chikungunya virus from Aedes egyptii to Aedes albopictus, an insect that thrives in colder temperatures. Ticks transmit both Lyme disease 5 and tick-borne encephalitis (TBE) 6, see Box 1. While the incidence of TBE has halved since the late 1990s in Russia, the incidence rate tripled in Arkhangelsk Oblast, in the North, during the same period. In the 1980s, there were relatively few cases of TBE in the Russian Federation, including 300 cases per year in Arkhangelsk Oblast, but rising temperatures from 2001 increased incidence to 2,300 cases per year in 2007, a 10-fold increase within a decade. There have been several excellent recent reviews on this topic, to which we refer the reader 13 14 15 16 17 18 . Table 1 compares the major climate-sensitive infectious diseases in the tropics with those in the Arctic. The list is neither exhaustive nor exclusive. Furthermore, the listed diseases are not necessarily limited in their prevalence to the tropics or the Arctic. Infective agents Climate-sensitive diseases Tropics Arctic Parasite Malaria Giardiasis Leishmaniasis Cryptosporidiosis Schistosomiasis Echinococcosis multilocularis Trypanosomiasis Toxoplasmosis Bacteria Meningococcal meningitis Lyme borreliosis Relapsing fever Tularaemia Vibrio parahemolyticus infections Brucellosis Multi-resistant Staphylococcus aureus Haemophilus influenza, Streptococcus pneumoniae and Mycobacterium tuberculosis Rickettsia Rocky mountain spotted fever, South African tick typhus, Queensland tick typhus and more Mediterranean spotted fever Virus Dengue fever Nephropathia epidemica (Puumala virus) Yellow fever Tick-borne encephalitis Rift Valley fever Russian summer and spring encephalitis West Nile fever West Nile fever Hantavirus cardio-pulmonary syndrome Chikungunya Ross river virus fever Dengue fever Chikungunya Rabies Crimean-Congo haemorrhagic fever Hepatitis A A large proportion of the populations in both these extreme climate zones share the characteristic of living in close proximity to their ecosystems, in fact living on them 3 19. This makes these populations highly vulnerable to the health effects of climate change. We consider here five main common characteristics and requirements, respectively, regarding climate-sensitive infectious diseases: Exposure to new patterns of climate-sensitive infectious diseases. Disease surveillance and early warning systems. Health system preparedness. Enhanced global efforts towards developing drugs and vaccines. Common challenges for research. The pathways leading from the presence of pathogens, vectors and host animals to manifestations of infectious disease in humans are non-linear and complex. Apart from climate change, they are influenced by human immune response, human behaviour (particularly regarding land use 20 21), the quality of social and health systems, the development of drug resistance and many more. They all have a strong influence on whether or not diseases will manifest in populations and how they will spread. With some caveats, it is generally true that some pathogens such as salmonella respond directly to higher temperatures in terms of their proliferation. Vector-borne diseases react indirectly to changes in temperature and humidity, as insect vectors and their associated pathogens undergo possibly accelerated life cycles as ambient temperature increases (up to a certain point). They, in turn, frequently depend on host vertebrates, which have their own climate-dependent migration patterns. We would therefore expect some of these diseases to expand pole-wards and upwards in terms of altitude. Certain vectors have a particular potential to act in joining the dots between the south and the north. The species mentioned below exist today in southern Europe: Mosquitoes (Anopheles, Culex and Aedes) can give rise to malaria (different species), West Nile virus, Dengue virus and Chikungunya virus, respectively. Ticks (Ixodes ricinus, Dermacentor reticulates, Hyalomma marginatum and Rhipecephalus sanguineus) transmit Borrelia burgdoferi (leading to Lyme borreliosis), TBE virus (TBE-encephalitis), Tularaemia franciscella (tularaemia), Coxiella burnetii (Q-fever), Bunyaviridae viruses (Crimean-Congo haemorrhagic fever), Rickettsia conorii (Mediterranean-spotted fever). Sandflies (Phlebotominae) transmit Leishmania donovani and Leishmania infantum. Autochthonous (locally transmitted) cases of most of these infectious diseases have been reported in Europe. The last case of indigenous malaria in Sweden was reported during the 1930s. Even if other parameters, such as socio-economic situations and well-performing health systems, influence the epidemiology of these infections, higher temperatures could-in a longer-term perspective-move the northern limits of these infections as locally transmitted malaria cases occurring in Italy have shown. West Nile virus has expanded to Canada, and the northward movement of TBE is described in Box 1. A particularly instructive case, albeit from a veterinary infectious disease, is Blue Tongue, a frequently fatal disease of cattle, goats, sheep and deer. Between 1998 and 2005, this insect-borne disease (spread by the biting midge Culicoides imicola) spread northwards in Europe. In 2006, it reached central and northern Europe including Switzerland, the Netherlands, Belgium and Germany. The spread of the disease could be explained by the basic reproductive number R _0, which is temperature-dependent 22 23. In 2007, Blue Tongue disease appeared for the first time in Britain. Gubbins et al. 23 reported the greatest risk of spread in Britain (R ₀ between 2 and 4) in a temperature range from 15 to 25°C. The case of highland malaria in Africa has been hotly debated in the literature 24 25 26 27 . The emerging consensus 28 seems to reflect many factors influencing the upward move of malaria transmission in the Kenyan highlands (Fig. 2), but shows that climate change is among them 29.

The world, showing the tropics (blue zone) and countries containing INDEPTH health and demographic surveillance sites (yellow). Source: www.indepth-network.org

Changing seasonal patterns of infectious diseases have been reported for many climate-sensitive infectious diseases including malaria 30 31, tularaemia 32 and TBE 33. Not surprisingly, inter-annual variability of climate, too, has been shown to have an influence on infectious diseases: increases in the incidence of malaria, dengue fever, Rift Valley fever, hantavirus infections, cholera and other diseases have been associated with the El-Nino-Southern Oscillation (ENSO). For an overview, see Kovats et al. 34 and Anyamba et al. 35. The few studies on possible relationships between infectious diseases and the North Atlantic Oscillation (NAO) have been inconclusive so far. Palo 36 performed time-series analyses between the frequency of cases of nephropathia epidemica and the NAO index and did not find a significant association. Hubalek 37 found an association between the NAO index and some infectious diseases such as toxoplasmosis. Intriguingly, Lyme Borreliosis and TBE showed no relationship at all. More research is certainly needed in this arena. In conclusion, in spite of the extremely different ecosystems in the Arctic and the tropics, the nature of transmission frequently via vectors, generates similarities between climate-sensitive diseases in both areas. This is illustrated in Table 2 using the example of tularaemia and malaria. Common effects on diseases transmission Tularaemia Malaria Source: Rydén et al. 32. Incidence sensitive to inter-annual climate changes NAO ENSO (El Nino) Length of transmission period Increased Increased Expansion of geographical coverage Yes Yes, both latitudinal and altitudinal Human land-use important Yes Yes Given the dynamics and the complexity of climate-sensitive infectious diseases, particularly those transmitted by mosquitoes or rodents, both regions need to develop and sustain surveillance and early warning systems. While a global early warning system, such as the Global Alert and Response Network (GOARN), which was developed by the World Health Organization 38, is impressive, it cannot achieve the task of monitoring the imperceptible extension of infectious diseases into new areas. We discuss below some specific issues pertaining to the Arctic and the tropics. As populations are relatively small and scattered over a large area, it makes sense to develop a region-specific surveillance system to detect significant trends in infectious diseases. Linking existing national monitoring systems is the basis for appropriate and coordinated actions. Standardising laboratory methods and clinical surveillance definitions across borders facilitates comparing and analysing regional epidemiological data. An example of such a network is the ‘International Circumpolar Surveillance System for Emerging Infectious Diseases’ 39. This network links hospital and public health laboratories for the purposes of monitoring invasive bacterial diseases and tuberculosis in Arctic populations 39. It is planned to extend this surveillance network to climate-sensitive infections. There are three main weaknesses in most developing countries with regard to disease reporting: Firstly, health services ‘see’ only a fraction of those suffering from diseases, typically less than one fifth. Those who do visit health services are certainly not representative of the entire population. It is therefore quite possible to miss an increase in cases, if those occur in remote (geographically barred) or in poor (financially barred) populations. Secondly, incomplete reporting may generate fluctuations in case numbers, which are reporting artefacts, rather than actual changes in case frequencies. Thirdly, case verification is difficult and lengthy, given the dearth of reference laboratories. Population-based health surveillance on a national scale 40 would be ideally implemented using a random sample of sentinel sites. This is however quite expensive and out of reach for many low-income countries. Another possibility would be to use existing population-based surveillance systems, such as the INDEPTH network (www.indepth-network.org) as a tool for the surveillance of climate-sensitive infectious diseases in the tropics. This network currently covers about two million people in the tropics under demographic and health surveillance in some 30 sites, mainly in Africa and Asia (see Fig. 2). Ascertainment of cause of death is standardised across sites and as valid as possible in the absence of facility-based biomedical exams. Many of these research centres include high quality laboratories, which could be included in systematic surveillance and early warning systems. Although certainly not strictly representative of their countries’ general population, these sites provide population-based data which is unbiased by the different barriers associated with health care utilisation. In addition, they are certainly faster and more valid in their case ascertainment than the average local health service. Particularly in low-income countries in the tropics, under-performing health services must be strengthened to meet the additional challenge of climate-sensitive infectious diseases. In the language of climate policy, this would be called a ‘no regrets’ strategy, something ‘…whose benefits equal or exceed their costs to society, excluding the benefits of avoided climate change’ 41. Hence, strengthening health systems is a sensible policy even in the absence of climate change. Priority action should be considered in the following areas: Protection of the infrastructure, particularly communications networks, against extreme weather events such as floods, storms and heat waves. Training health staff about diseases which might be expected to occur or increase and the local measures that should be taken. This applies, for example, as much to Lyme disease in northern Sweden as to malaria in the latitudinal and altitudinal fringes of its current distribution. Establishing decentralised stocks of drugs, vaccines and equipment for preventing or treating climate-sensitive diseases. Establishing fast routine reporting systems for climate-sensitive infectious diseases. Part of preparedness pertains to the active cooperation of health sector staff with colleagues from other relevant sectors, such as forestry, agriculture and meteorology. The need for such inter-sectoral cooperation is obvious, as the control of climate-sensitive infectious diseases, particularly those borne by vectors, strongly depends on information and action from these sectors. Table 3 illustrates the common characteristics of adaptation measures, using the example of two otherwise unrelated diseases, tularaemia in the Arctic and malaria in the tropics. Common adaptation Tularaemia Malaria Source: Rydén et al. 32. Early warning systems based on meteorology In place (e.g. in Sweden) At a research stage Early warning systems based on case detection Active and passive Passive Surveillance possible Yes Yes Preparedness of health services Moderate Low Involvement of other sectors (forestry, agriculture and infrastructure) Yes Beginning The development of vaccines against dengue fever and malaria is an important global research priority per se. The importance is accentuated by the projected increase in the burden of these diseases burden due to climate change. In principle, the need for vaccine development arises also in the case of Lyme disease 42. The debate should be re-opened in view of its anticipated spread northwards into the Arctic. Drug treatment of malaria currently hinges primarily on one single type of drug, the artemisinin derivates. Given that we have evidence of in-vitro markers of resistance, particularly in south-east Asia 43, clinical resistance is imminent 44. The need for research and development of anti-malarial drugs is highlighted in view of potential effects of climate change on malaria transmission. The same holds for drugs against other tropical climate-sensitive diseases, such as leishmaniasis and trypanosomiasis against which we urgently need new, less toxic and more effective drugs. Surprisingly, research output on the links between climate and infectious diseases is limited for both regions, particularly as far as intervention-oriented research is concerned. In both regions, researchers essentially face a similar agenda: The attribution of changes in infectious diseases to climate change. This almost invariably involves modelling techniques, linking regional climate models or at least time-series of meteorological data to models of infectious diseases. For example, the Arctic is a region characterised by complex and incompletely understood climate processes, making climate modelling for this region challenging. Local climate data need to be coupled to large-scale data flows. There is a rapid development in the field, but, so far, regional models have not been used for the Arctic Climate Impact Assessment (ACIA). The validation of early warning and surveillance systems for climate-sensitive infectious diseases. The development and evaluation of evidence-based adaptation strategies, their protective effectiveness and costs. The identification of most vulnerable population sub-groups and subsequent targeting of adaptation interventions to them. For example, there are 40 different ethnic groups in northern Russia. These minorities speak different languages as well as the language of the nation they live in and they have their own customs and cultures. Adapting the research methodology used according to these differences is important and needs special consideration. Research training. Few health researchers are comfortable with modelling infectious diseases, let alone with using climate models and linking them to disease data 45. Many of the required techniques, such as time series analysis and analysis of remote sensing data are new, particularly to public health researchers and epidemiologists. Techniques for working with multi-sectoral data sets, e.g. from meteorology and agriculture, need to be learnt. While we need to raise interest for this issue within the global research community, a special effort in training and capacity building is needed in low income countries, where climate effects will be first and most strongly felt 46. The task of understanding the nexus between climate change and infectious diseases is not made easier by the complex simultaneous ecological, social and health service influences, as the debate on highland malaria illustrates 28 Fig. 3.

Time trend for malaria in the Kenyan highlands. Source: Ref. 29.

The transition from knowledge to knowledge-based actions is another challenge. The key issue is: What degree of confidence or certainty do we need in order to act? The United Nations Framework Convention on Climate Change has clearly stated that action is needed in the presence of uncertainty if the potential adverse effects are severe and irreversible (‘Precautionary Principle’ 47). In spite of obvious contrasts in geography and the respective biospheres, these challenges are common to researchers and policy makers both in the Arctic and in the tropics. Many lessons can be shared. Joining the dots essentially means connecting the people who work around these dots across different parts of the globe. The authors have not received any funding or benefits from industry to conduct this study. Box 1. Tick-borne encephalitis (TBE) in Sweden. TBE was first discovered in Sweden in the 1950s and the reported annual numbers of cases have increased ever since. Up to 1979 approximately 25 cases were reported each year. During the 1980s around 40 cases were reported annually and during the 1990s the number rose to 60–80 7. In the last 10 years the incidence increased further to about 140 cases annually. About 224 cases were reported in 2008 8. All cases of encephalitis admitted in Stockholm County have been serologically tested for TBE since the late 1950s 9. Viral meningo-encephalitis has been a notifiable disease in Sweden since 2004. TBE causes more than half of the cases of viral meningo-encephalitis reported to the Swedish Institute for Infectious Disease Control (SMI), with most of the patients contracting TBE in Sweden. Only a few patients were infected in other European countries 8. Most cases occur in the central-eastern parts of the country, particularly in the archipelagos surrounding Stockholm 10. In the eastern parts of the country the risk areas have remained unchanged 7. In the 1990s new TBE-endemic areas became established around lake Vänern and lake Vättern, mainly close to the water where the climate is milder 7. Other areas where the disease seems to be emerging is in the south (Skåne and Blekinge) and in the west, the Bohuslän and Dalsland areas 10. During the last few years, additional foci have appeared. The virus has spread north along the east coast and cases have been reported from Dalarna in central Sweden, and Bohuslän on the west coast 10. Climatic factors such as mild winters and early arrival of spring are thought to have contributed to the spread of the tick Ixodes ricinus further north and to an increase in tick density 10 11. Other factors contributing to the increase in TBE may include increasing host animal populations such as roe deer, and more people spending time in endemic areas due to an increase in summer cottages 12. 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