We're having a heat wave, a tropical heat wave. (Book Excerpt).

"Great to see you again"; "nice to meet you after all these years"; "what do you think this meeting is really all about?" -- these are the usual pre-session exchanges. These casual, customary exchanges took place in May 2000 at the elegant Lausanne Palace and Spa where there was a bottle of Pol Roger champagne to accompany the muesli at the breakfast buffet. The fifteen participants in a workshop called "Contextual Determinants of Malaria" had been gathered together by the organizers, Elizabeth Casman and Hadi Dowlatabadi of Carnegie Mellon University's Department of Engineering and Public Policy (a curious but intriguing academic amalgam). Our assignment was to ponder upon the determinant of global warming on the epidemiology of malaria--that is, its global distribution, intensity and anopheline vectors. The fifteen ponderers were a mixed bag of malaria experts from India, South America, Europe, Southeast Asia, the United States and, by proxy, Africa. There were orthodox, field-oriented, general purpose mala riologists; orthodox, field-oriented medical entomologists; administrator-malariologists from the World Health Organization's central casting in Geneva and from regional satellite offices; laboratory research-type, mathematical epidemiology modellers, who may never have seen a malaria parasite under the microscope or a malarious patient, but had the data and knew the numbers; and climate change experts. There were also three representatives from the workshop's major angel, ExxonMobil. Later disclosed in the acknowledgments of sponsorship were the American Petroleum Institute, the Electric Power Institute, along with the National Science Foundation and the National Oceanographic and Atmospheric Administration. That evening at the informal reception, the ExxonMobilites were asked why they were paying for the meeting, They explained that malaria was a health problem for the workers in their tropical operations. And then they said candidly and cryptically: "There is, of course, the problem of emissions". Was the workshop a kind of preemptive legal strike, asking the right question and hoping to get the right answer?

Here we were in Switzerland, modern-day malaria prophets attempting, like the ancient oracles, to divine an impending disaster. When the bones were cast, the tarot cards read and the accepted notions reviewed, the portents were that mosquitoes would flourish in the new warm humid environments, breeding faster, drinking blood more frequently and living longer. Malaria, the epitome of a tropical disease, would surely follow. More infections would be due to the dangerous malaria parasite, Plasmodium falciparum, which requires a minimum of 18[degrees]C (65[degrees]F) to complete its life cycle, whereas the nonlethal Plasmodium vivax can make do with a cooler 16[degrees]C (61[degrees]F). Ergo, as the temperate zones turn tropical, they will become malarious--a killing malaria. The oracle has spoken. Leave your offering at the temple altar.

Then the iconoclast oracles, led by Paul Reiter, the entomologist-historian of the Centers for Disease Control and Prevention's dengue unit in Puerto Rico, presented a different view that was closer to reality (see his comprehensive review: Climate change and mosquito-borne disease in Environmental Health Perspectives, March 2001,109:141-61). It is true that of the approximately 3,500 species of mosquitoes, including the malaria-transmitting anophelines, most are tropic and subtropic. Mosquitoes are almost everywhere, adapting to virtually every habitat that is not permanently frozen. And the most massive numbers are not in the Congo but in the sub-Arctic after the spring thaw. Clearly, malaria is not a tropical disease. One hundred years ago, it was endemic in Sweden to the 15[degrees]C (59[degrees]F) isotherm. Until 1955, Poland was wracked by severe seasonal outbreaks. Turn-of-the-twentieth-century America was malarious in almost all States east of the Mississippi. DDT, better housing, health care and wat er management have eliminated endemic malaria in the United States and Europe.

That is, the parasite has been eliminated. The anopheline vectors remain in place, waiting, waiting. These potential vectors don't need global warming to pioneer their way to the north, although it is possible that their tropical cousins will join them in the warmed-up America and Europe. Any mini-outbreak in an industrialized country would be swiftly contained. The Camegie Mellon meeting concluded with the right answer. ExxonMobil need not worry; no one is going to sue them because they got malaria in Detroit, made tropical by the emissions from a Detroit-built SUV.

While global warming has not made Finland or Maine malarious, it has, in fact, brought the disease to areas formerly malaria-free. Malaria now occurs in newly warmed highland areas and semi-desert areas in Africa and New Guinea, where anopheline mosquitoes were always present but the ambient temperature had been too low for the malaria parasite's development. Take the case of Wajir--a town in the semi-desert of northern Kenya, with an environment that restricts the mosquitoes breeding. In November and December 1997, the weather changed, propelled by El Nino, which is considered by some experts to be influenced by global warming. Wijir was inundated by torrential rains. Anopheline mosquitoes proliferated and malaria was soon to follow. Of the 60,000 inhabitants, 40 per cent came down with malaria. They had not developed the protective immunity acquired by people exposed constantly to malaria--1,500 died, 108 of whom were children under five years of age. Similar examples of "new" malaria can be given for the h ighland areas of Burundi, Zimbabwe, Madagascar, New Guinea and Kenya. The consensus had been that global warming would have only a "marginal" effect on malaria endemicity. Small niches, such as mountain and environments, could be affected. A cascading effect was considered but deemed unpredictable from the presently known facts. The creation of new semi-deserts in tropical zones could actually reduce malaria; but this would cause population movements and create new man-made habitats for the malaria mosquitoes.

If malaria is a false canary that doesn't drop dead in the global warming mine, what about other arthropod-borne diseases, those transmitted by ticks or fleas? In these infections we may have firmer evidence from temperate areas of climate change's impact on the public's health.

On a warm March day in 1998, Ivan Doervitch of Togliatti, Russia, went to visit his brother, who had a wheat and sheep farm twenty miles away. Doervitch was hot; he had spent his boyhood on a cooperative farm, but city life had made him soft, and he was sweating after a short walk through the sheep pasture, But it was not all a physical softness, he thought. The seasons had been crazy these last years--warm winters without snow. His brother told him that he may have to give up wheat farming for another crop that would tolerate the higher temperatures. He had read in the newspaper that even Murmansk was warmer, that ships could make the northern passage to America. America again!

The newspaper said it was warmer because America was putting all those hot gases into the air. And the Americans complained about a little thing like Chernobyl. He looked down and saw ticks crawling up his pants leg. Damned bugs were everywhere that year, and he brushed them away.

Doervitch returned home to the city, relaxed in a hot bath, and when he dried himself found two ticks, their heads embedded in the flesh near his groin. He applied a burning cigarette to those vermin, then for antiseptic he splashed some vodka over the bites, and for good measure drank a glass of the antiseptic.

Five days later, he came down with a severe case of the "flu". He had a fever, chills, a piercing headache and his muscles ached. He was nauseous, vomited and had diarrhoea. When he looked in the mirror, he saw a face flushed borscht red. The next day, he was worse, much worse. His trunk was covered with a rash. There was profuse bleeding from his nose and gums. This was no flu; he was frightened and with the help of his neighbour, Doervitch managed to get to the Togliatti Central Hospital. He was admitted to the infectious disease ward, examined and a blood sample taken. The chief doctor, Olga Balaban, knew the diagnosis even before the serum sample had been analyzed by the Sanitary and Epidemiological laboratory for specific antibody; it was the Crimean-Congo fever. There were 37 patients like Doervitch in her ward. She lost about a quarter of her patients to the disease. Three days later the laboratory report confirmed her clinical impression. Luckily, Doervitch was alive and recovering. He went home from the hospital later in the week and in his last conversation with Dr. Balaban, she explained to him that he had had an untreatable viral disease that was transmitted by ticks. Normally, the virus "lived" harmlessly in domestic animals, as well as in some wild animals. Probably some birds were also infected; she had read about an outbreak of Crimean-Congo hemorrhagic fever in workers in a South African ostrich abattoir. It was present in many parts of Africa, the Middle East and central Europe, although it had been a relatively rare infection in humans. However, the warm winters had explosively increased the tick population; a walk in the surrounding woods or fields was sure to bring tick bites.

A year later, Doervitch was still convalescing and unable to work He was tired all the time and had become bald and didn't hear very well. Damn those Americans and their hot gases.

Sweden has also been experiencing an outbreak of a climate-influenced, tick-transmitted viral infection-- the tick-borne encephalitis (TBE). TBE also begins with a walk in tick-infested woods or meadows. It incubates for about a week after the tick bite and then begins with flu-like symptoms--fever, chills, headache and muscle ache. In the ensuing acute phase, the two tick-transmitted viruses depart in their clinical ways. Whereas the Crimean-Congo virus is hemorrhagic, manifested as rashes and bleeding gums and nose, the TBE virus goes for the brain and its covering tissue--it is a meningoencephalitis. A neurological disease--an inflammation of the brain--the signs and symptoms of TBE are tremors, intense headache and personality changes. Most cases of TBE recover naturally with few after-effects, but a few progress to more severe motor derangements that may end fatally. In its epidemiological natural history, the TBE virus is transmitted mainly by the brown, eight-legged "castor bean" tick, Ixodes ricinus. Similar to the Crimean-Congo disease, TBE is a zoonosis with natural reservoir hosts in wild and domestic animals-- deer, small brush-inhabiting mammals, cattle and sheep.

In 2001, Drs. Elisabet Lindren of Stockholm University and Rolf Gustafson of Stockholm's Huddinge University Hospital reported that in the previous 20 years there had been a rising incidence of TBE in Sweden. In attempting to explain why this once relatively rare infection in humans had become so relatively prevalent, Lindren and Gustafson turned to what has become the usual epidemiological suspect--global warming. The weather data from 1960 to 1998 revealed that Sweden, along with Europe's northern tier, had markedly and progressively warmed since 1980. They wrote: "There has been a global warming trend during the last two decades of the 20th century, with the years 1990, 1995 and 1997 having the highest mean temperatures ever registered in the northern hemisphere"; and "the spring vegetation season has advanced by 12 days on average between 1960 and the mid-1990s." In these climatic changes, they saw the link to TBE: "The findings indicate that the increase in TBE incidence since the mid-1980s is related to the period's change toward milder winters and early arrival of spring."

Earlier, warmer springs and prolonged autumns leading to shorter, warmer winters had led to a burgeoning tick population feeding more frequently. Moreover, the warming of the northlands had allowed the ticks to advance into higher latitudes. The ticks flourished because there was abundant food for them. Warmer weather leads to more vegetation and more food for the ruminants, especially deer. Well fed, their population expanded. Then everything in the TBE food chain prospered--more ticks that fed on more deer, and the TBE virus enjoying the augmented populations of both their arthropod and mammalian hosts. Meanwhile, the abnormally wet and warm weather was bringing yet another virus to humans--American humans.

In an area called the Four Corners, where the boundaries of Utah, Colorado, New Mexico and Nevada meet, that same change in the weather was making the desert bloom. One desert's denizen--the deer mouse (Peromyscus maniculatus)--thrived on the new, abundant food source and with a full belly, it bred like, well, deer mice. During 1993, it is estimated that their population increased an astounding twentyfold. It was in the Four Corners in that year that local residents, mainly Navajo Indians, sickened with the "flu", then became short of breath, then breathless and then, for 40 per cent of the afflicted, dead. The disease came to be known as the Hantavirus Pulmonary Syndrome.

The hantavirus family came to American attention during the Korean War when, from 1951 to 1953, over 2,000 American United Nations troops developed a severe haemorrhagic fever. Transmission experiments, in which urine and blood from patients were inoculated into some brave and/or ignorant volunteers, proved that the cause was a pathogenic virus. Virologists named it the Hantaan virus for the river in Korea, an epidemic focus. It took another 25 years to explain the Hantaan virus' facts of life. It is a virus of rodents--later study on the enzyme-amplified genome indicated that the virus had paired with rats and mice approximately 20 million years ago. It is transmitted to humans via contaminated rodent droppings or urine. It is an RNA virus that the taxonomic (name calling) virologists included in the Bunyaviridae family. Serological research showed there were more than twenty species! varieties of Hantaan virus widely distributed throughout Asia and Africa where they caused haemorrhagic disease, complicated by kidney damage. But until 1993, Americans thought themselves safe from the Hantaan gang of viruses.

In 1993, in the Four Corners, that comfortable notion came to an end. Fifty-four local residents, mostly Navajo Indians, came down with what at first seemed to be the flu--that catch-all conglomerate of symptoms that is both true flu and too often the prodromal opening round of so many other infectious diseases. All had been healthy before their illness, even those who died. Their average age was 34 years. But X-rays showed a picture of lung infiltrates, a waterlogged, drowning lung. The number of platelets (thrombocytes)--the small blood cells involved in clotting-- was markedly reduced. The heart and lungs failed in the 40 per cent of the patients who died.

A Hantaan-type virus was isolated from the Four Corners patients, but its RNA sequence did not match that of any of the thirty or so known Euro-Asian species. This new American virus was named the Four Corners virus. However, according to the Scripps Research Institute's Dr. Michael B. A. Oldstone, this name was not good for business. The Four Corners economy largely depended on tourism. Having a virus and the deadly disease it caused named after it was obviously not going to be a tourist attraction.

According to Dr. Oldstone, after some political arm-twisting the virus was renamed the Sin Nombre virus, which is Spanish for "no-named" virus. And who says scientists have no sense of humour?

Unlike the Euro-Asian hemorrhagic Hantaan infections, the Sin Nombre virus mainly targets the lungs, although subsequent clinical observations have found that haemorrhage and renal disease may accompany the pulmonary disease, the Hantavirus Pulmonary Syndrome. But as in all the Hantaan-group viruses, the main zoonotic reservoirs are rodents. Surveys of deer mice from Four Corners showed that about 10 per cent carried the virus. The following winter was particularly harsh, and many deer mice took refuge in human habitations, garages and storage sheds. The virus was transmitted when the human householders came in contact with the infected mouse droppings.

Now that the Hantavirus Pulmonary Syndrome has been delineated as a clinical entity, it has been reported in some 300 cases in 31 States. However, the American Southwest remains the main focus of the disease, with 73 per cent of the infections coming from that region.

We have gone through most of the catalogue of infectious disease categories that are, or could be, affected by global warming--vector-borne infections, mosquitoes (malaria and West Nile), ticks (TBE) and zoonotic infections (Hantavirus, rodent reservoirs). There remains a last category, the waterborne infections, dominated by cholera--perhaps the most potentially dangerous and devastating of the climate-influenced diseases. Over centuries, its epidemics, the death by diarrhea, have been feared throughout the world.

The father of bacteriology, Germany's Robert Koch, put cause and effect together with his 1883 discovery of the comma-shaped bacterium he named Vibrio comma, since renamed Vibrio cholerae. Infection begins by ingesting the microbe in fecally contaminated food or water. After a short incubation period--less than a week--the fever and diarrhea begin and untreated get worse and worse with a massive discharge of the "rice water" stool. Modern research has shown that the bacterium adheres to the intestinal lining by means of specific molecules. This is followed by the Vibrio's production of a very powerful toxin affecting the permeability of the intestine's cells. There is a massive excretion of water into the gut and the body, losing so much fluid, goes into shock. About 50 per cent of those infected and untreated with the most virulent strains die. These most virulent strains' genes transcribe the most potent toxin and other factors of intense pathogenicity. There are, however, other strains, such as the El Tor strain (named for the El Tor quarantine station in Saudi Arabia) that, while responsible for fever and diarrhea, are seldom lethal.

Now no one need die, or even be ill with cholera for long. Antibiotics such as ciprofloxicin and ampicillin can cure.

One of the simplest ways to rescue the desperately diarrhoeic is by oral rehydration with a sugar-salt solution that restores both fluid and essential electrolytes.

Even so, the poorest of the poor, especially the Bangladeshis, remain at great risk to lethal cholera each monsoon season when the Brahmaputra River at its Bay of Bengal delta inundates the coastal villages. The few sewers back up and latrines overflow into the drinkingwater wells. Cholera is the constantly recurring seasonal curse. Yet the Brahmaputra's largesse is so great that when the rains cease, villagers eagerly return to farm the renewed soils, even those on the river's islands. A prolonged monsoon means a prolonged cholera season, and this happened in 1991 and 1992 when El Nino extended and intensified the rains.

Climate and cholera seemed to have a relatively simple relationship--human feces in the rain-inundated sewer/well system. Dr. Rita Colwell, Director of the National Science Foundation, and her group made the complicating, disturbing discovery--cholera is, in a sense, a climate influenced vector-borne disease, the vectors being the creatures of plankton-copepods, algae, the larvae of myriad invertebrate species. Vibrio cholerae have adherent surface molecules which "glue" them to the plankton creatures and there they survive over long periods of time. When the oceanic waters warm by aberrant climate changes, the coastal waters become a soup of plankton and their Vibrio cholerae bacteria. Current work by the National Aeronautics and Space Administration indicates that these plankton blooms can be detected by satellites and serve as predictors of where cholera outbreaks are most likely to occur.

Temporary climate changes undoubtedly affect the epidemiology of cholera and other waterborne infections. What is more uncertain are the effects of global warming. One prediction holds that, as the polar ice caps thaw, the sea level will rise. Sewers will back up in the inundated coastal regions. Drinking water will become contaminated, leading almost certainly to the spread of water-borne diarrhoeal diseases such as cholera. However, another group of experts assert that this is an alarmist prediction, that the earth will warm but slowly. Minnesotans will not wake up one fine morning to find themselves in the tropics. There will be plenty of time to apply our wealth and technology and create the infrastructure to meet the new challenges. What will happen to the peasant poor in the tropics, such as the Bangladeshis, is unpredictable. The organization Physicians for Social Responsibility claims that there will be "death by degree". Others believe that social and scientific responsibility will meet the medical c hallenges of global warming--that you really can't boil the lobster one degree at a time without its knowing it and, given the opportunity, climbing out of the pot.

Robert S. Desowitz, a leading epidemiologist, is Professor Emeritus of tropical medicine and medical microbiology at the University of Hawaii. These excerpts are reprinted from his book, Federal Bodysnatchers and the New Guinea Virus/Tales of Parasites, People, and Politics, with permission of the publisher W W Norton & Company, Inc. [C]2002 by Robert S. Desowitz.