"Concentric Circles: A Twenty-first Century Context for Climate and Health"
Dr. Rita R. Colwell
Director
National Science Foundation
Keynote Lecture
10th Asian Conference on Diarrhoeal Diseases and Nutrition (ASCODD)
Dhaka, Bangladesh
December 8, 2003
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Good afternoon, and a special greeting to so many good friends here in the audience. Coming here is like coming home. I would like to thank Dr. Sack and the Organizing Committee for their exceptional work in preparing for this festive occasion, commemorating the founding of the ICDDR,B. This opportunity to deliver the keynote lecture at ICDDR,B, which is so close to my heart, is a great honor.
It has been a fascinating and challenging journey to this podium. Thinking back over the decades, we have come a long way to the integrative point of view that Vibrio cholerae is a normal component of the ecosystem—an organism that can never be eradicated but only controlled. I can recall when the viable but non-culturable form of Vibrio cholerae—the dormant state that cholera can assume in the environment—was referred to by some as "Colwell's ghosts." In fact, that memory led me to come up with a tongue-in-cheek title for my lecture, which is: "The Environmental Dimensions of Cholera: From Pariah to Paradigm."
[Title slide]
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I have actually titled my talk "Concentric Circles: A Twenty-First Century Context for Climate and Health." Today's study of infectious disease must draw insights from a series of contexts, each nesting like a concentric circle within the next, from nanoscience to genomics, and from ecology, geography and social science to climatology and mathematics.
The connections between cholera--an ancient water-borne disease--and the environment provide a paradigm for this perspective. Fully dimensional understanding of an infectious disease, whether cholera, hantavirus, or malaria, now reaches from countries to continents and beyond, and connects medicine to many viewpoints across science and engineering, and even to daily life.
[Slide 2: earth from space with cloud veil]
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A global context indisputably frames all human health issues in the 21st century. This context is formed of several realities: the worldwide movement of people and goods, the new recognition that earth processes operate on a global scale, and a dynamic international scientific enterprise.
Science and engineering have always flourished across national borders, but the global scale of research in this century is unprecedented. As research grows increasingly interdisciplinary, more scientific questions surmount national borders.
Health issues are no longer just a matter between patient and physician—if they ever were—but now encompass an individual's complex relationship with the global environment. As Gro Harlem Brundtland—former director of the World Health Organization—has said, "In the modern world, bacteria and viruses travel almost as fast as money. With globalization, a single microbial sea washes all of humankind. There are no health sanctuaries."
[Slide 3: concentric circles transition graphic with the words: Infectious Disease and Environment: The Context]
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I plan to speak briefly about what I view as the concentric circles surrounding infectious disease—the international setting and the philosophical construct of biocomplexity. Next I will touch upon several cases of infectious diseases in their ecological and climatological contexts. All of this leads up to the core of my talk: the case of cholera in its environmental setting. I'll conclude by highlighting some of the concentric circles of other disciplines that parallel our own: insights from mathematics, ecology and social science.
[Slide 4: WHO pie chart-leading causes of death]
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Here is a quick snapshot from the World Health Organization that puts our work in perspective. Infectious diseases cause about one quarter of deaths worldwide (and those do not include cancer, cardiovascular and respiratory diseases, many of which have been shown to be caused by infections).
[Slide 5: WHO graph-6 leading infectious killers]
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Broken down into the six leading infectious killers, diarrheal diseases, not long ago number one, come in third overall—but still rank second for children under age five.
[Slide 6: WHO pie chart: main causes of death among children]
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Zeroing in on causes of death for children four years old and under, infectious diseases cause almost two-thirds, or 63%, of these deaths.
[Slide 7: WHO graph-reported outbreaks of known infectious diseases, 1998-99]
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Another snapshot by WHO: this one shows some outbreaks of known infectious diseases. Outbreaks of cholera substantially exceeded those of any other disease.
[Slide 8: Composite of two WHO images: frequent flyer world map and graph of increased international travel]
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These figures show some of the largest "concentric circles'" that frame today's global context for environment and health. As the lower right graph shows, international travel has skyrocketed in the past half century, up to almost 500 million international arrivals per year or more.
We can see here where all these travelers are arriving. The routes circumscribing the world map are the most popular air routes between continents. Note the large vertical arrows at the bottom of the map, which give the percentage of increased arrivals over the mid-1990s in different locations. International arrivals increased in every region, but in Africa and the Middle East, they jumped by almost half.
[Slide 9: SARS]
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While travelers, goods and diseases circumnavigate the globe ever faster, so does knowledge. In the case of SARS, for example, although there was an initial delay in the news that the disease was spreading, the world's response to the virus was swift. Canadian and US researchers were able to map the virus' genome in a matter of weeks. Now, SARS researchers can find different coronavirus sequences posted on the Web by colleagues all over the world.
This unprecedented intensity and rapidity of international cooperation is reassuring in the rapid progress achieved. It shows that scientific endeavor is as global in scale as the problems and pathogens we target. As one example, Singapore and the United States are setting up a regional center in Singapore next year to combat health threats to the region, with SARS as its first focus.
[Slide 10: Biocomplexity spiral]
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The international arena that I've described is one context for our work; let me now sketch another, conceptual, context. This is the framework I call biocomplexity, which denotes the study of complex interactions in biological systems, including humans, and their physical environments. Ecosystems do not respond linearly to environmental change, nor do the pathogens that live in them. Here, I use the form of a spiral, so symbolic of life at every level, to underscore the point that understanding demands observing at multiple scales, from the nano to the global.
The spiral of complexity begins to unfurl at the most minute scale of the atom, and curves up through successive levels of life, through the cell, the organism, the community, the ecosystem. Complexity principles emerge at each level. With the perspective of biocomplexity, disciplinary worlds, formerly discrete, intersect to form fuller, more nuanced viewpoints. We're ready for this new perspective that integrates across disciplines and scales, a perspective that roots epidemiology firmly in ecology.
[Slide 11: concentric circle transition image with phrase: The ecology of infectious disease]
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Training the biocomplexity lens on health and environment, we learn how linear and simplistic is the notion that we can successfully eradicate a disease from the face of the planet. Infectious disease is a moving target—as climate shifts, any disease with an environmental stage or vector will be affected. As we recognize signals from climate models and incorporate them into health measures, new opportunities arise for proactive—rather than reactive—approaches to public health. I'll turn now to a brief survey of only a few cases of infectious diseases in their ecological contexts.
[Slide 12: pitcher plant cluster]
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Ecology has immediate lessons for epidemiology, and the National Science Foundation has supported studies that bring the two together. Take the mosquito that lays eggs in these beautiful North American carnivorous plants called pitcher plants. (Similar plants harbor mosquitoes in Southeast Asia.) Although this particular mosquito is not a disease vector, the adaptation of this formerly tropical insect to the climatic gradient of North America carries insights for the spread of disease.
[Slide 13: mosquito ovipositing in pitcher plant]
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This mosquito, like many organisms, uses day-length to regulate seasonal development, as explained by William Bradshaw and Christina Holzapfel of the University of Oregon, who study this phenomenon. Mosquito populations have now adapted to the climate of North America from Florida to Canada. Disease-carrying invaders, like the Asian tiger mosquito, must similarly adapt to cold and to different day-lengths. As spring comes earlier and growing season has lengthened over the latter half of the last century, the pitcher plant mosquito has adapted to shorter photoperiods, especially in the north.
[Slide 14: graph]
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In a rare example of a documented genetic shift due to warming, this graph shows, as latitude increases, the mosquito's genetic shift to shorter photoperiods (that is the left axis, in hours). Bradshaw has detected this genetic shift over as short as five years; as he says, "This is evolution at breakneck speed!"
[Slide 15: Not available]
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Among vector-borne diseases, malaria is one of the most sensitive to climate. Models of avian malaria in Hawaii may have lessons for the more complex global issues of human malaria.
Neither malaria nor mosquitoes are native to the Hawaiian Islands. Since the system involves introduced disease, it also serves as a model for emergent mosquito-born diseases such as West Nile Virus in North America. The Hawaii project team is led by David Duffy of the University of Hawaii—and includes 15 other principal investigators and 200 interns(!).
[Slide 16: Not available ]
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The Hawaiian situation is complex. Hawaii has lost about three-quarters of its bird species to extinction since humans arrived. Diseases--malaria and avian pox carried by introduced mosquitoes--are thought to be a major current threat to Hawaiian rainforest birds. Mauna Loa on the Big Island rises from coral reef, through forest, up to permafrost, furnishing a laboratory to study malaria in different habitats. Different strains of malaria afflict birds, and one bird can carry several strains at one time. Many mainland U.S. birds are immune to malaria. Now, some Hawaiian birds, especially those without a refuge from the disease, are evolving resistance as well. Climate likely drives malarial transmission in the birds.
[Slide 17: Not available ]
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Here is another story of a pathogen intertwined with climate. This one began in 1993 in the Four Corners area of the United States, when young and otherwise healthy people began dying from an unknown disease. At the time, in fact, some suspected bioterrorism.
The culprit turned out to be a Hantavirus unknown in the New World until the outbreak, and now familiar to all of you. The mortality rate of those infected with the virus was 70% in the first few weeks. Was the new virus a mutant, or had the environment been harboring it all the time? The carrier turned out to be a rodent, the deer mouse pictured here.
[Slide 18: Not available ]
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Biologists working at an NSF-supported Long-Term Ecological Research site, led by Terry Yates of the University of New Mexico and his team, were able to detect the deadly virus in mouse tissue that had been archived years before. (The map shows the study site locations.) As it happened, Native American legends corroborated a history of outbreaks.
In addition, the investigators showed a link between climate and the outbreak of disease. Mild and wet winters associated with a periodic climate pattern, El Nino-Southern Oscillation, had provided more food for the rodents, whose populations had increased dramatically in 1993.
[Slide 19: Not available ]
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Eventually, researchers found a time lag between the rodent population increase and the increase in human infections. It turns out that there is a time lag between the peaking rodent populations and the increase in disease incidence in the rodents. This graph shows that densities of hanta-infected mice are correlated with total deer mouse densities one year earlier.
[Slide 20: Not available ]
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In this graph, the black line shows rodent density. The red line shows density of rodents infected with the hantavirus. The green bars plot human cases. A take-home message is that the key predictor of disease cases is not the increase in numbers of rodents, but the increase in infected rodents (in red). The researchers are now pursuing a "trophic cascade hypothesis," developed to explain the changing levels of human risk for zoonotic diseases associated with climate variability. The cascade of disease through the trophic levels is apparently set off by El Nino.
[Slide 21: Not available ]
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Here we see a map of New World hantaviruses. All but one have been discovered since 1993. They were here all the time but we just didn't know it.
[Slide 22: Canyon del Muerto]
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In New Mexico, the researchers have now developed a predictive model indicating areas of highest risk for hantavirus. Canyon del Muerto, pictured here peppered with red dots, seems to be a likely place for hantavirus to exist for years beyond human awareness.
[Slide 23: Not available ]
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I turn now to another infectious disease—campylobacter—which emerged as a leading cause of gastroenteritis in some countries about a quarter century ago. Public health interventions, focused on food-borne transmission, have not decreased disease incidence. In fact, we see--in the graphs at right—an annual rise over the ten-year period. Also, the disease has displayed a striking and consistent seasonal pattern. My student Valerie Louis observed a significant correlation between increased temperature and the seasonal peak of campylobacter infections in England and Wales.
These figures show campylobacter incidence by district during the 1990s. At left are annual cases per 100,000 people. At right are the annual rates in different districts.
[Slide 24: Not available]
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Of particular interest to this conference is the dramatic seasonal effect of campylobacter noted in infants and children under five years old who were infected during the seasonal peak at more than twice the rate of older people. The red line shows the weekly incidence rate for children aged 1-4; note the sharpness of the peak for that age class compared to all the other age classes. The seasonal effect, or sharpness of the spikes, becomes less pronounced in the older age groups. Such seasonality related to age has not been discerned for this disease before. Certainly, children under five are a prime target for public health measures.
The bottom graph shows that males—the blue line—have a higher rate of infections than females, no matter what the age group.
More broadly, campylobacter infects humans through a wide array of ecological pathways, forming a rich canvas for applying the biocomplexity approach to public health policy.
[Slide 25: 4 USA maps showing CWD spread]
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Moving to another example, here is a complex disease in a wild animal population, but with implications for human health, potentially, worldwide. These USA maps show the spread of chronic wasting disease in mule deer from around 1996 to 1999. Colorado and Wyoming are the only places in the world where a prion disease has been found in a wild population. Proteins are prions devoid of genetic material that can nonetheless spread through a population.
[Slide 26: mule deer brain: before and after]
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Prions are also implicated in bovine spongiform encephalopathy in cattle and Creutzfeld-Jacob disease in humans. The images show the brain of a mule deer, before and after chronic wasting disease has struck.
[Slide 27: summer and winter home range, and movement patterns from winter to summer]
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Here we see plots of summer and winter movements of mule deer in different game management units. Such movements could help spread the disease. In some areas up to 15% of mule deer are infected, according to N. Thompson Hobbs and Elizabeth Williams of Colorado State University, who are leading the study. Their goal is to understand and predict how chronic wasting disease spreads over space and time. While the pathology and clinical features of the disease are well known, understanding of transmission is primitive, say the researchers. The disease dynamics unfold in an environment undergoing dramatic change, including one of the fastest growing human populations in the country.
[Slide 28: concentric circles transition slide with words: the case of cholera]
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From malaria to hantavirus, from prion diseases to cholera, we are beginning to trace the concentric circles -minute to massive—that surround the mysteries of infectious disease. I will turn now to my own research on the case of cholera.
[Slide 29: life at undersea vent]
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Where did cholera come from? The requirement of Vibrio cholerae for salt to grow led us to suggest that its ancestral home is the sea, perhaps a deep-sea vent such as this one. Genomics has helped to substantiate this theory.
[Slide 30: East Pacific Rise: map]
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In 1999, during dives by the submersibles Alvin and Nautile, sulfide chimneys were collected from undersea hydrothermal vents on the East Pacific Rise. Vibrio species isolated from the chimneys were identified that bore significant similarity to Vibrio cholerae, suggesting that it is autochthonous, or native, to the deep sea.
[Slide 31: small chromosome]
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In 2000, the genomes of the two chromosomes possessed by V. cholerae were sequenced. The discovery of two chromosomes was interesting, because bacteria were presumed to have a single chromosome. Both chromosomes are necessary for metabolism and replication.
[Slide 32: large chromosome]
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The toxin genes, of which there are fifty, reside on the large chromosome. The sequencing data confirm that V. cholerae is a versatile organism, able to live in several habitat types, as well as to infect the human gastrointestinal tract. Recent research by Andrew Camilli and colleagues, reported in the journal Nature in 2002, even suggests that when V. cholerae passes through the human gut, certain genes appear to greatly accelerate their activity—becoming up to 700 times more infectious than control bacteria. Lateral transfer of genetic material is clearly occurring in this organism. Virulence genes are distributed in environmental strains of V. cholerae from various serogroups—apparently an environmental reservoir of such genes. We know that 0139, the new serogroup, acquired novel DNA from other cholera bacteria in its environment. This underscores the versatility of cholera, and gives even greater credence to the significance of the environment in understanding cholera's complexity. We also know, however, that it is difficult to isolate V. cholerae 01 from the environment, where it is competing with some 250 other serotypes.
In fact, bacterial viruses have been found to play an important role in the microbial ecology of aquatic ecosystems. Lysogeny, integration of the phage into the host bacterium, occurs more frequently in 01 El Tor and 0139 strains than in 01 classical strains, and is believed to impart antibiotic resistance to the host bacterium. Phage infection may give rise to new toxigenic variants, and polylysogeny can occur, as Erin Lipp, a postdoctoral fellow in my lab has shown.
In that recent study, Erin, Eric Espeland, and I observed classical and El Tor strains of cholera infected with a temperate phage. At least three prophages (inserted DNA) were found to exist in one strain of El Tor. Should such a mechanism operate in the wild, genetic material such as toxin genes could be transmitted in the environment via multiple temperate phages.
[Slide 33: List of VBNC organisms]
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A major insight from the past few decades is the discovery that pathogens such as cholera can exist in a viable state even though they cannot be cultured. This list gives a quick glimpse of some of the pathogens in which the "viable but non-culturable" phenomenon has been studied, from E. coli to Helicobacter pylori to Legionella and Salmonella.
[Slide 34: Not available ]
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Cholera's interactions with its environment are another major line of inquiry. The ecological relationship of cholera and planktonic copepods was first established in 1983 when Anwar Huq and myself showed that V. cholerae attach to live copepods in the Chesapeake Bay and around Bangladesh. This strongly suggests that cholera is probably not an eradicable disease, because its causative organism lives naturally in riverine, brackish and estuarine ecosystems.
Currently, my student, Tonya Rawlings at the University of Maryland, is investigating whether the seasonality of cholera in endemic areas is associated purely with temperature and salinity, or whether V. cholerae's interactions with given species of hosts—namely these copepods—also affect its seasonal abundance. At present, she is investigating whether two epidemic variants of cholera, O1 and 0139, may have preference for attaching to specific genera of copepods. Here we see three copepod genera: Oithona, Eurytemora, and Acartia. Not all bacteria compete well for space on surfaces. The pathogenic species of V. cholerae attach best. Here is another example of cholera's environmental capabilities, and further evidence of its autochthonous aquatic nature.
We are finding that Eurytemora is more prevalent in the upper Chesapeake Bay, with more Acartia in the lower Bay. We have also noted seasonal fluctuations in the prevalence of these species. We need to do intensive work in various environments to see if copepod species selectivity—for example, the ability of 01 to attach better to a particular copepod species—might be linked to a more severe cholera epidemic when that particular copepod is more abundant.
Adhesive ability is an important attribute of V. cholerae, whether in the environment or in the human gut. The "environmental" capabilities of V. cholerae include its ability to secrete a powerful chitinase, which assists its growth on chitin surfaces. Besides colonizing copepods, V. cholerae is also present in shellfish. Our hypothesis is that cholera originally evolved commensally with marine animals such as copepods, which provided them a surface to grow, nutrition and perhaps other mutual benefits. In the ocean ecosystem generally, the breakdown of chitin is an important ecological function. Another interesting capability is V. cholerae's production of a mucinase, which enables it to penetrate the mucus barrier that covers the gastrointestinal epithelium.
Carla Pruzzo of the Universita Politecnica delle Marche has reported preliminary data that serum from Mytilus hemolymph, a mussel, increases attachment in the intestinal epithelial cells. The upshot is that when Vibrio is ingested with seafood, cholera acquires "bridging molecules" which make cholera very adhesive in the intestine. As Pruzzo explains, "Both virulence and infectivity depend on both bacterial properties and environmental factors."
[Slide 35: 3 graphs]
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One more point about copepods: Here we see the results of a three-year study of ponds in Matlab to see if plankton numbers or other measures of water quality could predict the presence of Vibrio cholerae as detected by fluorescent antibody. The top graph shows copepod nauplii (a young lifestage); the center shows copepod adults; and the bottom is V. cholerae. Copepod nauplii and adults, whether used singly or with other variables, were the best predictors of V. cholerae.
[Slide 36: biofilm "cartoon"]
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Here we see an artist's rendition of another environmental function: the formation of a bacterial biofilm. At this meeting, John Mekalanos is speaking about how biofilms enhance colonization in V. cholerae; I will just make the observation that this protective clustering behavior is yet another mechanism for cholera's life cycle in the aquatic environment, which also serves to protect it from stomach acid when ingested by humans.
Biofilm formation is an intriguing part of the complexity of cholera's lifestyle. It is one of the many bacterial processes—along with production of virulence factors and bioluminescence—that are regulated by the special bacterial communication called quorum sensing.
[Slide 37 V. Louis table 8: conditions that favor occurrence of V.ch]
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Other environmental attributes of V. cholerae are its salinity and temperature tolerances. This table, from Valerie Louis' work, gives a broad overview of temperature and salinity ranges in various experimental settings from the laboratory to the Chesapeake Bay, and from California to Louisiana, Florida, England and Japan. The salinity most favorable for V. cholerae was between 2 and 14 ppt.
[Slide 38: C. Bay sampling sites]
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Here we see sampling sites in the Chesapeake Bay, which were used to investigate how salinity affects cholera concentrations. V. cholerae is more common in the northern part of the bay where salinity is low and when the weather is warmer. In fact, temperature and salinity—both of which display seasonal patterns—combined to predict the presence of V. cholerae with an accuracy between 75.5 and 88.5%.
[Fig 3, V. Louis salinity paper]
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Here we see results from sampling sites along the north-south transect in the bay just shown. The top graph shows the percentage of samples testing positive for V. cholerae. The bottom graph plots temperature and salinity from north to south (left to right).
Changes in salinity from year to year, due to the influx of freshwater from the Susquehanna River at the head of the bay, may cause V. cholerae populations to fluctuate greatly. We find that salinity variation is a useful indicator of cholera variability in the Chesapeake Bay.
With climate change, shifting rainfall patterns in the mid-Atlantic region could modulate V. cholerae populations in the Bay. With carbon dioxide increasing in the atmosphere, global warming and more rainfall, river flow could increase, lowering salinity and driving up V. cholerae populations. This is a parallel here with the Bay of Bengal, monsoons and cholera.
[Peruvian coast]
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In the Southern Hemisphere, the coast of Peru, shown on this map, has added new insights to the cholera story. Here, cholera surfaced in 1991 after a century of absence in Latin America. Cholera has recurred in Peru since then, following a seasonal pattern, with the greatest number of cases in summer (June-March) in Lima and other major cities along the coast.
[Table 4-Lipp et al]
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Erin Lipp and others studied the seasonal distribution in coastal Peru of total V. cholerae, V. cholerae 01, and ctxA. The percentages for each are shown in this table. V. cholerae detection followed ambient temperature increases and coincided with or preceded annual outbreaks of cholera in summer.
[Ana Gil graph: SST and cholera rate per 100,000]
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Again off the Peruvian coast, we have reported a significant correlation between cholera incidence and elevated sea surface temperature. This study by Ana Gil and others covered October 1997-June 2000 and included the 1997-98 El Nino event. The lines show sea surface temperature at different study sites, while the bars give rates of cholera at the same four sites.
[El Nino-SST slide]
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The climate-cholera link seen in the 1997-98 El Nino year suggests that an early warning system for cholera risk can be established for Peru and neighboring countries.
Interestingly, though not related directly, both El Nino events and cholera outbreaks have increased since the 1970s. This pattern surfaces in both Peruvian waters and the Bay of Bengal. We suggest that sea surface temperature and height, as well as plankton blooms, can be remotely sensed and used to forecast outbreaks.
[Bangladesh photomontage]
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Human beings and the "concentric circle" called social science, which we use to study ourselves, are very much a part of cholera's complex story. In addition to laboratory results and satellite studies, we have used social science to find a practical tool for removing cholera from drinking water in Bangladesh. This tool--available even in the poorest household--is the sari cloth.
Folded eight to ten times, the cloth becomes a 20-micron mesh filter, as we determined by electron microscopy. Straining water through several layers of sari cloth may be enough to prevent ingestion of infectious levels of cholera bacteria.
[micrographs of old and new sari cloth]
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The pictures show why old sari cloth, not new, is preferred—because its holes are smaller and better able to trap the plankton. Laboratory studies show that old sari cloth folded at least eight times filtered out more than 99% of the V. cholerae attached to plankton.
[Filtration fig]
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We have published in PNAS the results of a three-year study carried out in 65 villages in Matlab, Bangladesh, comprising a total study population of about 133,000 people. You can see the result here for filters made of sari cloth and nylon net versus the control group. The incidence of cholera was roughly half among those who used sari filters, compared to the control. The severity of disease also appears to have been reduced in villages that filtered, but this will need confirmation by continued work.
[transition: concentric circle slide: other disciplines' contributions to infectious disease study]
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Many concentric circles formed by the perspectives of other disciplines frame our study of infectious disease, whether cholera or others. Such multidisciplinary circles surround us with new and deeper ways to understand. In this final portion of my talk, I'll draw on three examples from disparate disciplines that have direct implications for epidemiology, illuminating the intricate and subtle paths that pathogens can take.
[three networks]
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Theorists of mathematical networks have come up with some intriguing results in the past few years. Older models classified networks as organized or random, until Steven Strogatz and Duncan Watts proposed a third type of network as more realistic. They examined three diverse real-world systems: the nervous system of C. elegans, the hundreds of thousands of actors in the Internet Movie Database, and the power grid of the western United States. They found that a third model, the small world network--which included "short cuts" to increase connectedness-- best depicted the three systems.
[Idahlia Stanley painting]
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Small world networks among human beings—pictured here in a painting by Idahlia Stanley—have short connections and many clusters. Shortcuts can be beneficial; on the Internet, for example, they can bypass information traffic jams. However, similar shortcuts in a social network can be devastating, enabling infectious diseases to spread more easily. Such shortcuts have been created, in fact, by air travel, forming routes for disease to spread across the world in a matter of hours.
[montage of honeybee pictures]
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Research on networks in insect colonies has just begun. The honeybee pictures here show a queen honeybee surrounded by a retinue of workers; two specialized workers—a forager and a storer—exchanging food; and densely packed bees in the background.
[hemacytometer slide with polystyrene microspheres]
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In a study using a honeybee colony to model the influence of social organization on epidemiology, Brian Smith and Dhruba Naug of Ohio State University are using these microspheres (the dots) as stand-ins for actual pathogens. Bees are fed the microspheres and, in turn, pass them on when they exchange food. Sample bees are ultimately dissected to trace transmission routes in the hive through the ingested spheres. Here the microspheres from bee guts are ready for counting.
[graph: influence of group size on epidemiology]
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Here, bee colony size clearly affects the level of infection. The red bars, denoting a large colony, show that many individuals will have small amounts of infective material. By contrast, in a small colony, denoted by the blue bars, a few individuals have a large amount of infective material. This simply shows how a particle that does not replicate diffuses through a group via social exchange.
[graphs: higher temperatures enhance survival of infected bees]
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A honeybee colony has extraordinary capabilities to thermoregulate—such as to fight off infection. Bees infected with a protozoan die faster at a lower temperature (the graph at left) but survive at a higher temperature just as long as uninfected bees.
[Matlab maps: GIS and cholera vaccine project]
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My final example, a brief one, is close to home, from a new study of the efficacy of cholera vaccine trials in Bangladesh using a geographic information system. The maps here show the Matlab region from three different scales in the GIS database. The study, led by Michael Emch of Portland State University, aims to show the importance of bringing a spatial perspective to bear—because existing vaccination methodologies have spatial biases. It will show how geographic methods can be used to improve vaccine trials.
[concentric circles graphic: reprise]
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Today, in a world where people, pathogens and invading pests travel around the world both purposefully and in unintended ways, through both natural and man-made means, we can no longer circumscribe the dynamics of an infectious disease with a neat and orderly framework and expect to contain and understand its complexity.
In a world of ever-more-rapid change, the patterns of disease expand across the scales and explanations must draw upon biological, physical and social science. For the first time we can begin to integrate the complexity of these patterns, if we allow ourselves to step out into these many dimensions.
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