1. 1. The Potential Impact of Global Climate Change on the Facilitated Emergence of Malaria and Leishmaniasis in Non-Endemic Areas and the Possible Shortcomings of Climate Change Research Modeling Dave Porter, 2011 ABSTRACT In recent decades, the impacts of global warming has seen increased discussion, and opposite sides are currently locking horns about whether it is anthropologically accelerated or a further progression of a natural cyclical process. However, there are some solid conclusions that can be made, given the levels of current data. It has been observed that eleven of the last twelve years were among the warmest since the beginning of systematized temperature recording, in terms of average global temperature (Holy et al, 2010). Rising sea levels, increased degradation of our atmospheric ozone, and the increase in average temperature in both terrestrial and aquatic environments, the latter being incredibly sensitive to change, may create irreversible changes to our world and way of life. There is another potential effect of global warming that is backed up by strong observational evidence there is a link to the increased emergence of parasitic infections and the increase in global temperatures. Traditionally, the historical patterns of vector range ecology and disease transmission rates have been used as a basis for the design of control and prevention strategies to protect the health of the public as well as the agriculture that sustained them. That had been possible only because the global climate and most regional environmental conditions seemed to remain relatively constant year in and year out (Suntherst, 2004). This is no longer the case, and scientists and researchers must adapt to these changing conditions. As the distribution range of parasitic infections increases beyond the usual tropical and sub-tropical limitation seen, populations of humans and animals will be put at risk for infections not normally observed in the region. This report will detail the emergence of leishmaniasis and malaria and trematode infections in non-endemic areas, facilitated by the onset of global warming as well as potential shortcomings of the computer models usedto predictthese events. THE POTENTIAL INCREASES IN MALARIA EMERGENCE RISK FACILITATED BY CLIMATECHANGE Malaria is a parasitic disease caused by members of the Plasmodium genus, which are transmitted to human hosts by mosquitoes of the genus Anopheles. Four major species of Plasmodium cause disease in humans P. falciparum (having the most significant fatality risk), P. vivax, P. ovale, and P. malariae. Malaria is endemic to Africa (especially sub-Saharan Africa, where its economic and social effects are devastating), Southeast Asia (where drug- resistant strains are emerging at alarming rates) and parts of Central and South America. The Anopheles vectors require ample rainfall and humid climates with consistently high temperatures for breeding and this coincides with the incidence of malarial transmission as well (Paaijmans et al, 2009). The sporogonic phase of the parasite, occurring in the mosquito, is most critically impacted by temperature. Paaijmans et al reference the basic reproductive number (R0), which defines the number of cases of a disease that arise from the index case introduced into a population of susceptible hosts. R0 can be linked exponentially with the success of the sporogonic phase of the Plasmodium life cycle, because it influences the number of infected vectors that survive long enough no transmit the parasites to humans during blood
2. 2. meals (Paaijmans et al, 2009). The possible interaction with global warming rates is obvious as the latitudinal and altitudinal range of vectors increases, coupled with a productive sporogonic phase, the population of infected mosquito vectors is increased in these areas (Holy et al, 2010). Interestingly, there is a strong statistical correlation between the diurnal temperature range and the sporogonic development of Plasmodium (Alonso et al, 2011, Paaijmans et al, 2009). Diurnal temperature fluctuations straddling a mean temperature of more than 21o C (70o F) decrease the rate of parasite development (thereby decreasing R0) compared to constant diurnal temperatures at respective level (Paaijmans et al, 2009). Conversely, fluctuations around mean diurnal temperatures less than 21o C increase parasite development (increasing R0) compared to constant equivalent temperatures. It should be noted that adult mosquitoes themselves are not adversely affected by temperature until it surpasses 35- 36o C (95-97o F), when the mosquitos mortality rate begins a significant increase (Paaijmans et al,2009). There is a meteorological principle that states that large bodies of water tend to reduce daily temperature ranges relative to those of waterless areas, and this may in turn allow global warming facilitated malaria emergence to become more prominent in coastal regions and maritime harbors. The humidity in air near bodies of water is higher than that of dry, inland air, and because of waters high specific heat value, the air temperature of this moist air will be less (assuming equal sunlight). The observation that P. falciparum sporogonic rates are increased when mean diurnal temperature fluctuate slightly around 21o C (Paaijmans et al, 2009) lends credence to this hypothesis. Areas near a significant water source tend to have larger human populations than dry landlocked regions as well, because of ease of commerce and transport. In addition, it should be noted that these bodies of water might promote breeding of mosquitoes, if the salinity levels of the water doesnotimpede larval growth. Some opponents to these theories argue that increases in epidemic malaria in East African highlands are not due to climate change, but due to other factors (Alonso et al, 2010). Findings found that although temperatures tended to fluctuate around a mean high temperature of 19- 21o C, malaria outbreaks in 1994 and 1997 were not strongly correlated with temperature, at least to the extent that Paaijmans et al describe. A consolidated figure from the 2010 work of Alonso et al is featured below. From this figure, which shows the number of clinically diagnosed malaria cases recorded from 1966-2002 at an inpatient hospital in highlands of the Kericho district of western Kenya, along with the respective temperature readings for each respective year, it can be seen at first glance that spikes in temperature fluctuating near 21o C do not always coincide with increased malaria diagnoses in this region (Alonso et al, 2010). There are several other factors that may contribute to this finding; not limited to an increase in clinical knowledge and malarial diagnostic prowess from 1970 to 2002, the emergence of HIV/AIDS in the population, an increase in travel to endemic lowland areas by the observed population. Land use was not likely to be significantly affected, because Alonso et al
3. 3. stated that this data was taken on a permanent tea farm with a relatively constant population of workers and their dependents. A constant increase in temperature,leading to a net increase of 1o C in 30 years, was observed and documented (Alonso et al, 2010). This observation was further investigated through climatological modeling, which led to interesting results. A condensed figure depicting the results of Alonso et al is shownbelow. This figure shows the observed cases of malaria taken from the aforementioned Kenyan hospital records (a red line in both graphs) with the median number of expected cases of malaria (the dark grey line in both graphs; calculated from simulated models) and the expected cases in the 5th -95th percentile of expected cases (the shaded light grey areas; also calculated from simulated models) to serve as a margin of error (Alonso et al, 2010). The top graphs dark and light grey components represent the estimated number of malaria diagnoses modeled with the trend of increasing temperature and standard environmental variables. The dark and light grey components of the bottom graph depict the estimated number of cases without temperature increases of 1o C per 30 years being considered in the model. The significant discrepancyin malarial epidemics in the late 1990s in the bottom graph is indicative that temperature may play a factor in determining malarial epidemics. Comparing the two graphs in this figure can allow for the visualization of this principle in the top graph, the median number of expected malaria cases appears to be on a steady increase, which may coincide with the average temperature increase in the region. The analogous line on the bottom graph does not increase at all, further illustrating the possibility that temperature is a factor in malarial epidemics. Although a correlation may be made, more analytical research and experimentation is needed to demonstrate the strengthof thiscorrelation. In another modeling experiment, Holy et al describe a potential emergence of malaria in Germany, where the disease was once endemic. Historically, through various anthropological interventions such as wetland drainage, DDT application and improved medical care and diagnosis, P. vivax was eradicated from Germany, although it should be noted that the indigenous Anopheles vectors have persisted up to the present day (Holy et al, 2010). Because the vector is still present and breeding successfully, a return of Plasmodium to the region through global warming facilitated migration of infected mosquitoes could have grave consequences. In August 1997, two autochthonous cases of malaria were reported from a hospital in Germany which could be traced back to infections by Anopheles plumbeus, which had bitten an immigrant from Angola, a country in south-central Africa, with a chronic case of P. falciparum malaria (Holy et al, 2010). Two maps of Germany, quantifying the potential malarial transmission months during two differing timeframes are shown. These maps were created by modeling the basic reproductive rate (R0) of the Anopheles vector native to Germany Anopheles atroparvus infected with Plasmodium vivax, the malarial agent most likely to returnto Germany(Holyetal, 2010).
4. 4. From these figures, which colorfully depict the seasonal malaria transmission months from 1961-1990 and 1991-2007 in Germany, it can be deduced that the length of the malaria transmission season has increased in a majority of Germany (Holy et al, 2010). This information can be extrapolated and used to predict the risk of malaria infection if the causative organism presents itself in Germany once more. Of significant interest are the regions in southwest Germany, where the transmission season lasts for five months out of the year (the regions of dark red). These areas, near the Frankfurt/Rhine-Main Metropolitan Region (population 5.6 million), are of elevated risk of potential malarial epidemics, should Plasmodium return to the region for multiple reasons, not limited to the length of the malarial transmission season and the relatively dense populations. It is of epidemiological significance that this metropolis borders the Rhine and Main Rivers, which could facilitate the spread of malaria to other major cities in Germany through the transport of Plasmodium along established commercial shipping routes. The Rhine and Main could serve as breeding grounds for the local Anopheles as well, perpetuating the effects of a potential Plasmodium resurgence. Additional modeling should be done to predict the effects of these possible events. THE POTENTIAL INCREASES IN LEISHMANIASIS EMERGENCE RISK FACILITATED BY CLIMATECHANGE Another parasitic disease that may potentially become more prevalent worldwide through global warming facilitated ecological range expansion is leishmaniasis. Leishmaniasis is caused by three different complexes of Leishmania parasites, and is distributed worldwide. In North America, the female sand flies of the genus Lutzomyia are responsible for transmitting the New World form of the disease through their blood meals while in parts of Europe, Africa, Asia and the Middle East, the responsible vectors are sand flies of the genus Phlebotomus. Phlebotomus are the major vectors involved in the transmission of Old World cutaneous leishmaniasis, which is caused by the Leishmania tropica complex. In Central and South America, New World cutaneous leishmaniasis is caused by the L. mexicana complex. The L. donovani complex the causative agents of visceral leishmaniasis (the most deadly form of leishmaniasis) are distributed in Central America (L. chagasi), India (L. donovani) and the Middle East (L. infantum)
5. 5. and are of significant public health importance in these respective regions. Mucocutaneous leishmaniasis is caused by the L. braziliensis complex, and is endemic to the countries of the Amazon River Basin, most notably Brazil. Although the increase in leishmaniasis in recent decades is due to economic development, human migration and civil wars, rapid global urbanization and the subsequent invasion of the sand fly habitat by humans, the spread of leishmaniasis may also be affected by climate change and the currenttrendof global warming. New World cutaneous leishmaniasis, caused by the L. mexicana complex, is endemic along the border between the United States and Mexico, where it is transmitted mainly by Lutzomyia diabolica and Lutzomyia anthophora with a highest incidence in the autumn months (Gonzlez et al, 2010). Several reservoir hosts are suspected, including the wood rats of the genus Neotoma, which occupy niches along the USA- Mexico border, as well as in the eastern United States. Gonzlez et al constructed a computer model that would predict the climate change induced ecological range expansions of Leishmania, Lutzomyia as well as Neotoma in an effort to predict the spread of cutaneous leishmaniasis in the United States and northern Mexico. Current warming rates, regional economics, environmental use trends, and the population density of vectors, reservoir hosts and potential human hosts were taken into account while programming the model (Gonzlez et al, 2010). A consolidated figure from the work of Gonzlez et al is shown showing the estimates of the ecological range of Lutzomyia diabolica and Neotoma floridana isshowntothe right. The top graph depicts the modeled predictions of the range of the Leishmania vector, Lutzomyia diabolica, in 2080 while the bottom graph depicts the modeled range of the common Leishmania reservoir host, Neotoma floridana in 2080. Experts do not currently classify leishmaniasis as an endemic disease to the eastern United States, although isolated cases have been documented (Gonzlez et al, 2010). However, given the nature of the modeled predictions in the aforementioned figure, current climate change trends may increase the range of Lutzomyia and Neotoma, posing public health risks to the populations of these regions. Though the predicted ecological range expansion of Lutzomyia diabolica is less extensive than that of fellow vector Lutzomyia anthophora, the northward shift is more pronounce, as indicated in figures not shown in this report. Because of this result, its a strong possibility that the potential spread of New World cutaneous leishmaniasis in eastern North America will be limited by the ecological expansion of the sand fly Lutzomyia diabolica (Gonzlezetal,2010). Also worth elaborating upon is the potential that the current southern boundary range of Neotoma floridana may potentially become unsuitable for the reservoir host to flourish, and would likely migrate northward (Gonzlez et al, 2010). Judging by additional modeling figures of other species of Neotoma as well as that of the aforementioned N. floridana in the work of Gonzlez et al, which are not shown in this report, this is a very possible outcome.
6. 6. However, it is to be noted that there are multiple reservoir hosts for New World cutaneous leishmaniasis not in the Neotoma genus, including other rodents native to northern Mexico(Wynsberghe etal,2000). REVIEW OF SEVERAL CONFOUNDING VARIABLES THATMAY EFFECT CURRENTCLIMATECHANGEMODELS In addition, it is very important to remember that global warming facilitated parasitic disease emergence in non-endemic regions should not be considered an event solely caused by holistic climate change, itself. Climate change is a complex,multifactorial event. The multiple anthropological and natural environmental alterations that contribute to climate change may have profound effects on parasites, their vectors, and their reservoir hosts as shown in the chart below (Suntherst, 2004), which proposes multiple ways that certain contributors to accelerated climate change can also affect parasitic disease emergence. All these factors contribute in different ways to parasitic disease emergence. It is important to consider each both individually and holistically when proposing climate change models as well as subsequent parasitic emergence prevention and control measures. For example, if global warming (an increase in temperature) is being caused by the destruction of large forested regions (a decrease in habitat); it would be inappropriate to only program the climate change computer
7. 7. model to take only temperature into account. Deforestation removes heat sequestering and shade-providing vegetation, which leads to an increase in sunlight and UV rays reflecting off the now-barren ground, which increases temperature. In addition, deforestation lowers humidity levels (less evapotranspiration from the forest), increases the speed of winds (due to less resistance from foliage) and prevents the sequestration of atmospheric toxins, such as ground level ozone. It is also important to take these factors into account when proposing intervention strategies and prevention plans, because they may allow for more pronounced outcomes(Bushetal,2011). There exists an opposition to the methods used to predict global warming, saying that cannot possibly accurately predict the effects of global warming on a grand scale, because of the multifactorial causes. For example, some experts argue that it is not plausible to use models to predict the future distribution of parasitic vectors because it is not possible to know how land-use will change (Alonso et al, 2010). Alonso et al also criticize models that do not take the effect of temperature and humidity into account, which may confound the results and invalidate the conclusions made from said results. Another informative figure from the elegant work of Robert Suntherst can further illustrate this principle,andcanbe seenabove. The differences between these maps of Australia can be easily seen. Map A shows the risk of P. falciparum malaria in a generalized way, taking into account only the temperature needed for sporogonic development within the mosquito. Map A does not include the important variables of ideal developmental humidity and the geographical range of A. farauti; the only Anopheles vector indigenous to Australia, which only inhabits the northern peninsulas of the Australian continent (Suntherst, 2004). These maps can serve as forewarnings for the scientific community and those involved in climate change research and its effects on multiple factors, not just parasitic disease emergence. More accurate modeling methods are needed before the risks and potential consequences of climate change can be concretelydetermined. CONCLUSIONS Whether or not it is due to actions of humankind or a natural cycle, the Earth is warming at a rate that may have potential consequences. Although the future effects of this relatively slow process (slow by our own reckoning, not that of geologic time) may not be realized in our lifetimes, our descendants may experience detrimental effects to the biosphere not limited to coral reef destruction due to increasing ocean temperatures, ozone depletion due to increased greenhouse gas production, and parasitic disease emergence through expansion of natural vector and parasite biotic ranges.
8. 8. Some climatologists have predicted that if current rates of global warming continue unchecked, average global temperatures will rise by 6.4o C by 2099 (Holy et al, 2010). The effects of range expansion of malaria and leishmaniasis may have far-reaching consequences as the diseases emerge in latitudinal and altitudinal areas where they are not currently found due to climate restrictions. It is important to remember that climate science is a relatively new discipline and modeling methods need additional improvements before solid predictions may be made about the future effects of climate change. However, it would be unreasonable to dismiss the very real possibilities of future vector and parasitic ecological range expansions due to the effects of climate change. More research must be done on this topic to discover possible preventativeactions. REFERENCES 1.) AlonsoD, et al.(2010). Epidemicmalariaandwarmer temperaturesinrecentdecadesin anEast Africanhighland. Proceedingsof theRoyalSociety; 278: 1661-1669. 2.) Bush K,et al.(2011). Impactsof Climate Change onPublicHealthinIndia: Future Research Directions. EnvironmentalHealth Perspectives;[E-Pub]. 3.) GonzlezC,et al.(2010). Climate Change andRiskof LeishmaniasisinNorthAmerica:Predictions fromEcological Niche Modelsof VectorandReservoirSpecies. PublicLibrary of Science: Neglected Tropical Diseases; 4(1): e585. 4.) HolyM, etal. (2011). Potential malariaoutbreakinGermanydue toclimate warming:riskmodeling basedon temperature measurementsandregionalclimatemodels. EnvironmentalScienceand Pollution Research;18: 428435. 5.) Paaijmans K,etal. (2009). Understandingthe linkbetweenmalariariskandclimate. Proceedingsof the NationalAcademy of Sciences;106(33): 13844-13849. 6.) Suntherst,R.(2004). Global Change andHuman VulnerabilitytoVector-BorneDiseases. Clinical Microbiology Reviews;17(1): 136173. 7.) Wynsberghe N,etal.2000. Retentionof Leishmania(Leishmania)mexicanainNaturally Infected Rodentsfromthe State of Campeche,Mexico. Memriasdo Instituto Oswaldo Cruz;95(5):595- 600.