Nearly 18 years have passed since a radioactive plume escaped from Reactor 2 on Three Mile Island in Harrisburg, Pennsylvania, and dissipated into the atmosphere, but the debate over the potential health effects from the United States' worst commercial nuclear accident continues. In this issue of EHP, epidemiologists from the University of North Carolina at Chapel Hill (UNC) reevaluate the data from a 1990 study that concluded that no association between the accident and cancer was apparent in the surrounding population. According to that report, published in the September 1990 issue of the American Journal of Epidemiology, "The prior expectation based on estimated releases and conventional radiobiology--that no excess cancer [associated with the accident] would be found--was confirmed in most if not all respects."
But according to Steve Wing, one of the authors of the new study, it was precisely because these researchers expected to find no excess cancer that none was found. "The basic problem with that study was [its] circular reasoning . . . The people doing the research didn't really believe there was anything to find," he said.
According to Wing, he began to question the results of the 1990 study when someone involved with a class-action suit against the company that runs the TMI utility contacted him. "I was approached by someone who lived in the area of Three Mile Island who had known people with unusual symptoms [and who had seen] problems with pets and the environment" he said. Wing felt there were people in the community who had made noteworthy observations that weren't getting any attention.
This prompted Wing to review the 1990 study, which had been conducted by a group from Columbia University in compliance with a court order issued by Judge Sylvia Rambo of the U.S. District Court for the Middle District of Pennsylvania. According to Wing, the study contained several flaws, which he and his co-authors, David Richardson, Donna Armstrong, and Douglas Crawford-Brown, tried to resolve in their reevaluation. "We only used data collected by the group at Columbia," Wing said. "But we analyzed the cancer groups slightly differently," concentrating on all cancers rather than rare, but especially radiosensitive, varieties like lymphoma. "We also excluded some baseline [cancer] data that the original study included, because for one year, 1975, it was incomplete."
Wing also says that the use of relative, rather than absolute, measures of dose in the reevalutation was an improvement over the original study, which used official exposure estimates (confirmed by a model of the accident and thermoluminescent dosimiter readings) to compare with cancer incidence. "If the premise [in the original study] that maximum doses were no higher than average annual background levels is not open to question," the UNC researchers write, "then no positive association could be interpreted as evidence in support of the hypothesis that radiation from the accident led to increased cancer rates." Indeed, the original study did find a positive association between exposure and increases in two types of cancer--lung cancer and non-Hodgkin's lymphoma--but the Columbia group concluded that overall, the evidence did not show that these effects were the result of the 1979 accident. This conclusion, says Wing, was the result of author bias.
However, Maureen Hatch, a principal author of the 1990 study, says Wing's allegation that the researchers were biased is unfounded. "We did, in fact, hold open the possibility that there could have been substantial releases during the accident," Hatch said. According to her, the preponderance of evidence, especially the lack of an association between exposure and particularly radiosensitive cancers, pointed to the conclusion that the accident produced no measurable excess cancer in the surrounding population. Hatch counters that the UNC researchers' association with the plaintiffs in a suit against the company that runs Three Mile Island might have biased how they interpreted the data. Hatch's commentary on the reevaluation of the original study, which she conducted with Jan Beyea, Jeri Nieves, and Mervyn Susser, can also be found in this issue of EHP.
To Wing, the way in which the effects of the Three Mile Island accident were originally assessed is indicative of problems with the way the United States deals with its nuclear industries. "I think the whole story [of the accident's effects] is just beginning to come out because of a reluctance to release information that was viewed as bad publicity for the nuclear industry and the government," Wing said. "In the case of the Three Mile Island accident, it was very difficult for the researchers to question what the authorities were telling them." In particular, Wing finds fault with Judge Rambo's specifications of how the Columbia researchers should conduct their study and the way dose estimates were obtained under that court order. Wing maintains that, under such conditions, objective research was nearly impossible. He said that he hopes the reevaluation will open up the possibility of more studies on the long-term effects of the accident.
Though Hatch says that many of Wing's claims of impropriety in the 1990 assessment are "egregious," she agrees that further study is warranted. However, the small population around the plant and the long latency of many of the health effects of radiation make epidemiological studies difficult.
An Alternative to Methyl Bromide
Methyl bromide, with an estimated "ozone depleting potential" (ODP) of 0.65, falls into the EPA's Class 1 category of ozone depleters which consists of chemicals with an ODP of 0.2 or higher. Therefore, all production, importation, and use of the substance must cease by the year 2001 under the Clean Air Act.
Researchers now say that methyl iodide may be an effective replacement for methyl bromide, currently the most widely used universal fumigant in the world.
Better than bromide.
Plant pathologists Howard Ohr (left) and Jim Sims (right) use hot methyl iodide instead of methyl bromide to fumigate gladiolas.
Photo Credit: University of California - Riverside
In the United States, 80% of the methyl bromide used in 1990 was for agricultural purposes. The chemical was used mostly for soil fumigation, including the control of insects, nematodes, weeds, and plant pathogens, as well as for post-harvest, commodity, and quarantine treatments. The phaseout of methyl bromide is expected to have a major impact on U.S. agriculture, especially in California and Florida, where almost half of the nation's methyl bromide is used.
Finding a substitute for methyl bromide has been difficult because the chemcial is used for a variety of purposes. Therefore, it is expected that several chemicals or combinations of chemicals will be used as replacements for methyl bromide in most applications.
Researchers at the University of California at Riverside have conducted several studies on methyl iodide for use as a soil fumigant, and have found it to be as effective as methyl bromide and safer for the ozone layer. "The most important fact about methyl iodide is that it's not an ozone depleter because it will not reach the stratosphere," says Howard Ohr, an extension plant pathologist who is leading the research on methyl iodide at the University of California at Riverside. Ohr says methyl iodide is broken down by ultraviolet light before it can reach the stratosphere. It is estimated that methyl iodide remains in the atmosphere for four to eight days after use, while methyl bromide may remain for two years.
Another important factor is methyl iodide's effectiveness as a pesticide. "Methyl iodide has the same spectrum of kill that methyl bromide does," says Ohr. "In all our tests, methyl iodide is equal to or better than methyl bromide at killing organisms." In addition, Ohr says that at normal use temperature, methyl iodide is a liquid, making it safer for workers to apply than methyl bromide, a gas that can be toxic through inhalation.
However, there are some health concerns about methyl iodide. According to Ohr, methyl iodide has the same carcinogenicity as methyl bromide. Methyl bromide has been found to affect the respiratory system and nervous system, as well as cause genetic damage, such as birth defects. "With any harsh chemical there are drawbacks," Ohr says. "[Methyl iodide] has to be used with care and caution."
Some environmental groups are critical of the use of any chemicals as alternatives, encouraging, rather, the use of environmentally sustainable methods. "In the search for alternatives to methyl bromide, the consistent focus has been on finding a chemical silver bullet solution," says Kert Davies, an analyst for the Environmental Working Group, "but there isn't one." Davies says that not enough funds are being allocated to the search for sustainable methods. "What we need is creative, diligent research on nonchemical biological and cultural controls--long-term solutions," he said.
Ohr agrees that such alternatives would be ideal, but points out that they will not be developed and ready for implementation in the near future. "[Those sustainable alternatives] are not going to feed the world in the meantime," Ohr says. Methyl iodide is an effective soil fumigant that can be used in the interim until other alternatives are discovered, he says. Ohr says that many companies are interested in methyl iodide, and the next step will be for a company to buy the licensing rights from the University of California at Riverside and register the chemical with the EPA. Ohr expects that the licensing will occur in the next six months, and the registration could take up to seven years.
The EPA is currently reviewing the literature and research on methyl iodide, says Bill Thomas, director of the EPA's methyl bromide program. "[Methyl iodide] looks efficacious--it looks like it does a good job of controlling pests," Thomas said, "but the jury is still out on the toxic information and the environmental fate."
Fran Squeezes the Life Out of NC Waters
After Hurricane Fran ushered in more than 8 inches of rain and wind gusts up to 100 miles per hour at some inland locations, investigators looked below the surface of the disaster to gauge the impact on eastern rivers and estuaries. What they found overwhelmingly were lifeless waters devoid of oxygen.
North Carolina was the state hit hardest by the September 5-6 storm, which toppled beachfront houses and leveled miles of protective dunes. Inland, some rivers rose 15 feet above flood stage at velocities expected to occur only once in 500 years, the U.S. Geological Survey reported.
After Fran, runoff to coastal rivers, tidal creeks, and estuaries created conditions of oxygen-starved water, the distribution and duration of which some researchers say they've never before witnessed. The deluge carried a dangerous mix of components: raw human sewage (diverted from wastewater treatment plants shut down by power outages), animal wastes, and runoff from farm fields and urban areas all requiring a quick fix of oxygen to decompose and break down. As a result, major river stretches experienced prolonged periods of anoxia--up to 3 weeks--which contributed to at least 40 reported fish kills, according to Jim Overton, acting assistant chief of the North Carolina Division of Water Quality's Water Quality Section.
Overton wasn't able to estimate the number of dead fish, but said kills included largemouth bass and sunfish, as well as catfish--bottom-dwellers that are fairly tolerant of poor water quality. Evidence of Fran's casualties was quickly swept away by high-velocity currents.
North Carolina shellfishermen along the central and southeast coast came up virtually empty for September, a prime month for hand-harvest of clams. Due to runoff containing high counts of fecal coliform (harmless bacteria that piggyback with insidious pathogens), some shellfishing areas remained closed up to a month, says George Gilbert, assistant branch head for the North Carolina Division of Environmental Health's Shellfish Sanitation Branch. The branch closes shellfishing beds to protect consumers from eating seafood that may cause illness. Preliminary statistics showed clammers harvested only 6,778 pounds of clam meat in September 1996, compared to 62,357 pounds reported in September 1995, according to the North Carolina Division of Marine Fisheries (DMF). Lingering post-storm conditions had a less immediate impact on the oyster season, which opened later in the fall.
Fishermen trawling for brown shrimp in the New River were hauling in more stray crab pots, sticks, and other wooden debris than seafood in November, says Fritz Rohde, a biologist supervisor for DMF's southern district. "We've also not had a good show of striped mullet," he says, speculating that freshwater inundation sent these migratory fish prematurely offshore.
On the northeast Cape Fear River in the southeastern part of the state, Fran lowered dissolved oxygen concentrations already compromised when Hurricane Bertha flushed poorly oxygenated swampwater into the system in July, says Mike Mallin, a research associate with the University of North Carolina at Wilmington's Center for Marine Science Research. "At least four hog lagoons breached or were inundated in the northeast Cape Fear basin," said Mallin, who has been sampling water in the lower Cape Fear system since June 1995. "When Fran hit and we started receiving waste from hog lagoons, DO [dissolved oxygen] dropped to zero. In our records that's never happened before."
The minimum DO level suitable for sustaining aquatic life is 4 mg/l for swampwater and 5 mg/l for coastal waters. Extremely low dissolved oxygen was also measured for extended periods in the Neuse River, Contentnea Creek, and the Tar River, according to data reported for September 1996 in USGS Open-File Report 96-499, Aftermath of Hurricane Fran in North Carolina: Preliminary Data on Flooding and Water Quality.
After the storm.
Dissolved oxygen (DO) concentrations and biochemical oxygen demand (BOD) in the Neuse River are plotted for sites below Falls Dam in North Carolina during periods after Hurricane Fran. The minimum acceptable DO to protect aquatic life and wildlife, and for agriculture and recreation is 4 mg/l. BOD is a measure of the amount of oxygen required to biochemically degrade organic material and to oxidize reduced forms of nitrogen.
Source: Bales JD, Oblinger Childress CJ. Aftermath of Hurricane Fran in North Carolina: preliminary data on flooding and water quality. Open File Report 96-499. Raleigh, NC: United States Geological Survey, September 1996.
On the lower Neuse River on September 17, a North Carolina State University research scientist found no dissolved oxygen "from surface to bottom," and "water not safe for human contact." JoAnn Burkholder, an associate professor of aquatic ecology at NCSU, and her staff and students measured fecal coliform densities--from human sewage, swine wastes, and other sources--that exceeded the state's standard for human health protection throughout a 45-mile stretch of the Neuse River from Kinston to New Bern. Enterococci, another type of fecal bacteria, were 10 times higher than EPA recommendations for human health protection, Burkholder says.
Natural sources also contributed to low dissolved oxygen levels, including a major scouring of rich organic material from swamps and forested wetlands, according to James Pinckney, an assistant research professor within the Institute of Marine Sciences at the University of North Carolina at Chapel Hill. "[The hurricane] filled up a lot of wetlands along the margin [of the river] and actually flushed carbon that had been building up for years," says Pinckney, who also monitors water quality on the Neuse River. "All this carbon coming in and being decomposed creates high biochemical oxygen demand."
Burkholder agrees that swamp-flushing created an oxygen sag, but pins that development mostly on Hurricane Fran. Fran was more revealing of human development foibles such as construction of large animal waste lagoons in floodplains. "The fecal coliform levels and Enterococci in the Neuse River after Hurricane Fran were clearly suggestive of anthropogenic pollution sources," says Burkholder.
As for other oxygen-demanding substances, basinwide concentrations of such culprits as nitrogen and phosphorus were relatively small. But because of the volume of runoff, the total daily loadings of these nutrients were profound, says Pinckney, sometimes 1-2% of the annual amount of nitrogen for the entire system. The USGS also reported single-day inputs of phosphorus that ranged between 1 and 3% of the mean annual load. High concentrations of ammonia in localized areas and microbial pathogens from raw sewage may share the blame with low dissolved oxygen in some fish kills.
"One of the things that will be interesting over the next year is to see if that nitrogen gets translated into phytoplankton growth," says Pinckney, who studies the relationship of nitrogen inputs to phytoplankton production and nuisance algae blooms. Because estuaries by nature are nutrient traps, a lot of organic material drops out where river meets ocean. Under optimal conditions, a balance is struck between the supply of nutrients and uptake by organisms further up the food chain.
"Low oxygen events occur under pristine conditions because of the nature of the estuarine filter," says Dirk Frankenberg, a University of North Carolina at Chapel Hill professor of marine science and a panelist on a hurricane study group appointed by the North Carolina governor. "When we develop land with sufficient disregard for the capacity of receiving waters nearby, we aggravate a situation that is marginal under natural conditions. Add a hurricane on top of that, and we end up with a disaster. Normal conditions hint at where the problems will lie when hurricanes hit."
A lifelong fisherman on the Pamlico River in Aurora agrees that storms have the power to redistribute or reveal, not create, pollution. "I think if everybody would really be honest with it, it's a water quality problem, period," says Etles Henries, Jr., of Carolina Seafood, who describes his geographic location figuratively as the "end of the septic pipe."
"Short-term, [the floodwater] may have actually helped us--[it] took a lot of stuff that had settled on the bottom, came up high enough, and left fast enough so it may give us some help," he says. "But then in a few years, it'll fill back in. A hurricane can't hurt you; long-term, [hurricanes] have been around forever. Hopefully, it took more stuff off the bottom than it put on the bottom. Next June or July will tell.
NAS Says EMFs No Hazard
A new report by a committee of the National Academy of Sciences paints a rosy picture of household electromagnetic fields (EMFs), concluding that "no conclusive and consistent evidence" suggests a human-health hazard, and that, in fact, strong, low-frequency pulsed magnetic fields may actually help heal broken bones.
But the 31 October 1996 report also calls for additional research to answer lingering questions about EMFs, such as why intense magnetic fields seem to speed the development of breast cancer in laboratory animals subjected to chemical carcinogens.
Epidemiological studies since 1979 have shown a "weak but statistically significant" (1.5-fold) increase in leukemia among children living in homes exposed to high-level EMFs, the NAS report notes. Most of these studies can be called into question, however, because they rely on rough estimates of interior exposure levels based on outdoor wiring configurations or wire codes, said NAS committee chair Charles F. Stevens, a professor and investigator with the Howard Hughes Medical Institute at Salk Institute in La Jolla, California. Epidemiology studies have also failed to rule out other potential risk factors for childhood leukemia, such as the proximity of children's homes to high-traffic areas, Stevens added.
"There is not one shred of evidence that it's the [EM] fields that are causing this association with childhood leukemia," Stevens said. "In all the animal studies, there's not one case where we know that the effects that have been seen are detrimental versus beneficial. There's no evidence that any effects take place in humans."
At the Midwest Research Institute in Kansas City, Missouri, Senior Advisor Charles Graham said people exposed to magnetic fields at levels as low as 12 milligauss (a range common inside homes) experience heart-rate changes. "We do have reproducible effects," Graham said of his research, but he added that such effects are "not [health] risks, necessarily. . . . We don't know if they're risks or not."
In fact, the NAS report says, EMF studies show detrimental health effects only when exposure levels are 1,000-100,000 times stronger than those found in a typical residential setting. Overall, the report says, no evidence points to household EMFs as a cause for cancer, adverse neurobehavioral effects (such as schizophrenia or learning disabilities), or reproductive and development disorders. Though preliminary studies suggested that EMFs might increase cancer risks by inhibiting the production of the hormone melatonin, Stevens said, subsequent research failed to support this theory. Moreover, Graham said, EMFs seem to suppress melatonin production only in animals, not in humans.
A number of recent studies, including work by NAS committee member Maria A. Stuchly, have shown "a slightly earlier development of tumors" among rodents exposed to chemical carcinogens as well as EMFs, the report says. But such co-promotional effects "have not been replicated," said Stuchly, a professor at the University of Victoria in British Columbia. Nevertheless, the report says, researchers should reevaluate copromotional studies--especially the work of German researchers (W. Löscher and colleagues), who reported a 50% increase in the growth rate of mammary tumors among rats exposed to 50-Hz magnetic fields after receiving oral doses of the carcinogen DMBA.
Studies of possible copromotional effects are already underway at the NIEHS, as part of the EMF RAPID (Electric and Magnetic Fields Research and Public Information Dissemination) Program. In fact, Program Director Gary Boorman reports, NIEHS researchers recently attempted to replicate the German study of breast cancer development in rodents. Boorman expects to see completed data from that study within 8 months. A second, two-year study involving 100 animals subjected to slightly lower chemical doses in conjunction with longer-term exposure to EMFs should also be completed soon, he says. "The NAS report was a good report," he says. "But it did not include many of the RAPID studies, because they didn't look at much data after 1994. We hope to prepare a report for Congress in 1998 that will allow us to examine the wealth of data produced since 1994."
The congressionally mandated NAS report--prepared by a 16-member committee including David A. Savitz, a professor at the University of North Carolina at Chapel Hill whose carefully controlled epidemiological studies have consistently suggested an association between EMFs and cancer--may deal another blow to a draft report of the National Council on Radiation Protection and Measurements (NCRP), which calls for a 2-milligauss limit on EMFs near day-care centers, schools, playgrounds, and newly built homes within the next 10 years. Portions of the draft appeared in the July/August 1995 issue of Microwave News, though it still has not cleared the NCRP's exhaustive peer-review process. "It seems to have entered an NCRP black hole," observed MN Editor Louis Slesin, who faults the NAS report for emphasizing the need for "conclusive" evidence of an EMF-related health hazard. "That's a very harsh burden," he said, adding that researchers have not conclusively ruled out EMFs as the cause of reported increases in childhood leukemia.
Until such questions are resolved, says Jack Sahl, a senior research scientist and manager of the Health Research and Evaluation Division at Edison International in Rosemead, California, utilities and policymakers would be wise to adopt "precaution-based" strategies for minimizing any possible health risks. [See EHP 104:908-911 (1996).]
For example, Sahl said in an interview, Edison International has prepared a manual offering common-sense guidelines for minimizing EMF exposure risks when designing new buildings. Similarly, since 1989, the California Department of Education has avoided building new schools in close proximity to high-voltage power lines.
No federal legislation is pending to limit EMF exposure, Sahl says, and policymakers who once championed exposure limits, including Representative George Miller (D-California.), now seem to be backing away from the issue. The $600,000 NAS report was requested by Representative Joseph M. McDade (R-Pennsylvania) in response to constituent concerns in Scranton, Pennsylvania, where a utility company wanted to install high-voltage power lines near homes. (McDade's press secretary, Jake O'Donnell, says the power company subsequently decided to relocate its power lines.) Though he hasn't identified a specific EMF research agenda, O'Donnell says, McDade will probably heed recommendations set forth by the NAS committee, which recommended more stringent epidemiological studies incorporating accurate measurements of magnetic fields inside homes and strategies for answering questions about childhood leukemia. The NAS report also recommended a host of biological studies. For example, the committee said, researchers should identify the mechanism by which EMFs seem to promote bone-healing in animals.
New Protein Kinase Inhibitors
Swiss researchers are exploring a vast new sea of compounds that attack cancer cells at the genetic level. "Phenylamino-pyrimidines are a new class of potent and selective protein kinase inhibitors," said Jeurg Zimmermann, a project leader with the pharmaceutical division of CIBA-Geigy in Basel. The key to use of the phenylamino-pyrimidines (PAPs), Zimmermann said, is their selectivity. "A lot of compounds can attack protein kinases," he said, but if the compound doesn't select for specific enzymes, the subject cannot survive. PAPs tend to select certain protein kinases, such as protein kinase C (PKC), a calcium-dependent enzyme that is overexpressed in tumor cells. Throttling PKC with PAPs may result in the tumor being unable to grow or reproduce, and can possibly make it regress.
Zimmermann said another kinase that is commonly overexpressed in cases of gliomablastoma, a usually fatal brain cancer, is platelet-derived growth factor receptor (PDGF-R). In some laboratory mice that have been implanted with gliomablastoma tumors, the introduction of certain PAPs has brought the growth of the tumor to a standstill, has prevented other cells from developing the tumor, or has actually caused the tumor to regress, said Zimmermann.
Zimmermann and his colleagues chose to study the means of attacking the protein kinases, of which there are more than 200, because of the molecules' roles in signal transduction and cell proliferation, both of which are responsible for a cascade of events leading to cancer growth and metastasis in the body.
In a presentation at the American Chemical Society meeting in Orlando, Florida, Zimmermann demonstrated how rational drug design procedures, using pyrimidines--one of the main building blocks of DNA and RNA--have resulted in the synthesis of more than 500 compounds. Using pyrimidines as a base, scientists add various analogs to the pyrimidine until they discover a compound that looks as if it will attack a specific area of a cancer cell. Typically, scientists will develop numerous chemical varieties. Although "only about 10% of the compounds have shown any anticancer activity," Zimmermann said, several of the compounds that did limit tumor growth are now being studied further before they are tested in humans. "We have to test toxicity and pharmacokinetics to see if the drug gets into the bloodstream and can be of use therapeutically," he said.
"Rational drug design," said Theodore Friedmann, director of the gene therapy program at the University of California at San Diego, "is a common device utilized to manufacture chemicals that are likely to have an effect on treatment of some disease. Most drugs are developed using this procedure in laboratories, although other drugs are still commonly found by investigating organic compounds such as tropical earths."
By and large, Friedmann said, the use of rational drug design will result in an incremental increase in fighting a disease such as cancer. "We have hundreds of compounds that show some ability to fight cancer cells," he said, "which really testifies to the fact that we have very few drugs that really work well in destroying cancer cells. We use one for a while and when that stops working we go to another." But, he said, "occasionally something comes along that breaks the curve."
Zimmermann said he is encouraged that some of the PAPs being scrutinized by his team have shown a wide range of success on various tumors, including brain, breast, and bladder cell lines. More exciting, he said, is that some of the compounds are so selective they will inhibit PDGF-R, necessary for the growth of brain cancer cells, but will have no effect on other tumor lines, indicating an ability to be carefully fine-tuned into specific tumor killers.
Fungi Fighting Back
Just as many bacteria and viruses have become resistant to pharmaceuticals, fungi have been developing drug resistance over the past five years. At the same time, new fungal pathogens are emerging and previously identified rare fungal pathogens are re-emerging, resulting in rising morbidity, mortality, and costs, according to a report by Dennis Dixon, chief of the bacteriology and mycology branch of the National Institute of Allergy and Infectious Diseases, and colleagues published in the May/June 1996 issue of Public Health Reports. This is a major concern as immunosuppressed populations, which are more susceptible to infections, continue to grow, due in part to the AIDS epidemic.
Source: Dixon DM, McNeill MM, Cohen ML, Gellin BG, LaMontagne JR. Fungal infections: a growing threat. Public Health Reports 111: 226-235 (May/June 1996).
Dixon's report cites many reasons for the increase in fungal infections. Changing demographics and technology have increased population levels, and thereby increased the number of susceptible hosts for fungal infections. Land use and travel in areas endemic for certain fungal infections by people not previously exposed to the infections can cause them to be more susceptible. Also, because physicians in non-endemic areas may be unfamiliar with the new infections, diagnosis and treatment may be delayed. The authors also cite a breakdown in public health measures that has resulted in a failing laboratory infrastructure. They point out that there are currently few reference laboratories that identify unusual fungal pathogens, and they call for a strengthening of the system.
The authors also cite microbial adaptation and the growth of drug-resistant fungi as contributing to the increase in fungal infections. Because the number of fungal infections is increasing, effective antifungal pharmaceuticals are being more widely used, both in hospitals and by the public, as a result of over-the-counter sales. The researchers say that widespread use of pharmaceuticals was a factor in the increased drug resistance of bacteria and viruses and could be a stimulant for resistance among fungi.
Fungal pathogens may innately possess a tendency toward resistance or develop resistance to the drugs. "There are two patterns of resistance--intrinsic and acquired," says Thomas Walsh of the National Cancer Institute. "We are seeing both patterns increasing." In patients infected with HIV, the acquired resistance is increasing, he said.
Roy Hopfer, an associate professor of microbiology at the University of North Carolina at Chapel Hill, says the widespread use of antifungals is the major cause of increased resistance by certain fungal strains. "There is a natural selection for resistant organisms," he said. As more antifungals are used, the fungal pathogens that survive are those that are inherently resistant or that develop resistance to the medications, he said.
Hopfer says that one of the major antifungals to which fungi are becoming resistant is fluconazole. Because this pharmaceutical is nontoxic, it is prescribed more often than others, such as amphotericin B, which has been found to be toxic, Hopfer said. He says there is a trend among doctors to prescribe antifungals readily, especially among patients with HIV who are experiencing increased numbers of fungal infections. "It is easy to prescribe fluconazole, even on a suspicion of a fungal infection," Hopfer said, because of its success in the past.
In order to combat the growing resistance toward antifungals, many pharmaceutical companies are working to develop new drugs. However, Hopfer says that cutting back on the usage of the current drugs will help the problem. "Reducing the usage of any drug will tend to reduce the amount of resistance," he said.
The NCI is currently taking several steps to address the problem of growing antifungal resistance, says Walsh. Researchers are using molecular epidemiology tools to characterize resistance in patients, to characterize the mechanisms of artificial drug resistance, to identify the appropriate animal models that reflect the patterns of drug resistance, to identify new biochemical targets for new antifungals, and to develop new strategies to augment host defenses against pathogens and bring these strategies to clinical trials.
EHP
net
Taking Inventory of Toxics
By providing direct access to information that otherwise would be difficult
to obtain, the Internet has enabled many people to take an active role
in investigating and solving their problems. With the creation of the
Toxic Release Inventory
System (TRIS), the EPA has expanded this ability by making it much easier
for Americans to track and eliminate pollution. The TRIS page on the
World Wide
Web, located at
http://www.epa.gov/enviro/html/qmr.html#toxic
, provides information to anyone with Internet access on the more than
300 toxic substances that the EPA tracks. Industries that release any
of these chemicals must submit a Toxic Release Inventory to the EPA each
year. The data
from these forms are compiled into a searchable database that can be
accessed by selecting the TRIS Queries link on the TRIS home page.
The TRIS search form allows users a great deal of flexibility in deciding how their search will be conducted. With the top half of the form, users can specify what criteria they want matches to fulfill--whether they want the TRIS to display facilities carrying a certain name or identification, facilities within a certain geographical region, facilities of a certain industrial classification, or facilities that emit a certain chemical. With the bottom half of the form, users can dictate how the results will look and what information TRIS will display. For example, if a user wanted to know if industries were releasing mercury into waters near a city, they could simply specify the city, county, or zip code in the geography and specify "mercury" in the Chemical Search Option field. After picking option eight to display the search results by "Amounts and Names of Chemicals Released to Surface Waters," users will receive a nicely formatted report of all the industries releasing mercury into the waters in that area. The same search could be done using "sulfur dioxide" in the Chemical Search Option field and displaying results by Amounts and Names of Chemicals Released to Air for information on acid rain. For other searches, users may want to display results with the Facility Business and Contact Information option. For further information on how to use the TRIS, a User's Guide link is provided on the query page. Information on the timeliness and accuracy of TRIS data can be obtained through links on the home page.
When searching TRIS, it is sometimes hard to specify chemicals since many have more than one name. A helpful way to avoid this problem is to search for a chemical using the number assigned to it by the Chemical Abstracts Service (CAS). To do this, users must select the appropriate option from the pull-down menu over the Chemical Search Option field. CAS numbers can be obtained from a helpful list compiled by Genium Publishing at
http://www.genfo.com/cgi-bin/ cll-search.cgi?md=y.
The Environmental Systems Research Institute provides a more user-friendly way to search for Toxic Release Inventory information at
http://maps.esri.com/ESRI/mapobjects/toxic.htm.
This search form does not allow for as much flexibility as the EPA form, and the data here are not as current, but the program returns the results as points on a street map of the area in question. The ability of average citizens to see how close polluters are to where they live, work, and play is a novel phenomena and perhaps the first step to solving some of the problems of toxic pollution.
Last Update: March 19, 1997