May 2004

The Global Threat of Infectious Diseases

Battling AIDS on the Front Lines

Investigating the Mechanisms of Tumorigenesis

Effecting Change in the Health Care System

Understanding the Psychology of Terrorism

Shifting Sands

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Bryn Mawr College
A newsletter on research, teaching, management, policy making and leadership in Science and Technology

The Global Threat of Infectious Diseases
By Dorothy Wright

Within the past 15 months, the world has received a crash course in the threat to public health of new and re-emerging infectious diseases. Severe acute respiratory syndrome (SARS) was initially reported in Asia in February 2003 and quickly became a global outbreak. Within a few months, SARS spread to more than two dozen countries in Asia, North America, South America and Europe. Before the outbreak was contained, there were 8,098 human cases of probable SARS worldwide, of which 774 resulted in death, according to the World Health Organization (WHO).

In mid-December 2003, a highly pathogenic strain of avian influenza A (H5N1) was first identified in fowl in South Korea and spread through nine Asian countries. By March, Vietnam and Thailand reported 34 confirmed human cases of bird flu, of which 22 later died, according to WHO, and millions of birds had been killed to contain the epidemic.

Of course, infectious diseases are nothing new. Illnesses caused by micro-organisms and transmitted from one creature to another have no doubt plagued the planet ever since life began. However, a variety of factors today make infectious disease a serious global threat to public health.

In its 1998 publication, Preventing Emerging Infectious Diseases: A Strategy for the 21st Century (http://www.cdc.gov/ncidod/emergplan/1toc.htm), the Centers for Disease Control and Prevention (CDC), Atlanta, identified a number of societal, technological and environmental causes that contribute to the global spread of new and re-emerging infectious diseases, including: unprecedented population growth; growing poverty and urbanization; rapid and increasing international travel and transport of animal and food products; human encroachment on wilderness habitats; and the development of resistance to antibiotics and other antimicrobial drugs.

Globalization

Michelle BarryMichele Barry ’74, an expert in clinical tropical diseases, has pointed out the public health threats posed by increased globalization. She explains that globalization has widened the health disparities between the rich and poor, and has brought both new and re-emerging diseases from underdeveloped nations to the West.

“Simply put, the world’s health problems become our health problems when borders are crossed with impunity. Diseases immigrate along with people,” says Barry, professor of medicine and global health at Yale University School of Medicine, New Haven, Conn., and past president of the American Society of Tropical Medicine and Hygiene.

As an example, Barry notes that the proportion of tuberculosis (TB) cases in the United States occurring in foreign-born individuals increased from 30 percent in 1992 to 46 percent in 2000. While the total number of multidrug-resistant TB cases in the country decreased from 3 percent in 1992 to 1 percent in 2000, the share of multidrug-resistant cases occurring in the foreign-born U.S. population increased from 31 percent to 72 percent. These data show that tuberculosis in the United States has become a reflection of tuberculosis elsewhere in the world.

To address the public health threats of globalization, Barry advocates for global sharing of lifesaving medical technologies, building public health infrastructures, and redirecting research priorities to help narrow the “egregious globalization gaps” that accelerate the spread of new and re-emerging infectious diseases.

One of the largest disparities, Barry says, is the “Research 10/90 Gap”. “This term,” she explains, “refers to the fact that only 10 percent of biomedical research funding is targeted to the diseases that account for 90 percent of the global disease burden.” Redirecting the research priorities of the wealthiest nations to ameliorate the problems of the poorest is only part of the solution. Another problem is the “brain drain” of qualified researchers from the developing world to the West. “In the case of 20 African countries, it is estimated that more than 35 percent of nationals with a university degree are living abroad, mostly in the United States, Canada or Europe,” Barry says. Without a solid base of resident researchers, she explains, it is difficult for developing nations to set appropriate priorities and conduct relevant research.

The pharmaceutical R&D gap is another important disparity. Virtually all new drug development is conducted by a handful of multinational pharmaceutical giants, and their R&D is directed at serving the health interests of patients in North America, Europe and Japan, which account for 80 percent of the world pharmaceutical market.

“The development of lifesaving drugs is left to the whimsies of a market economy,” Barry says. “What is really stunning is that of almost 1,400 drugs approved between 1975 and 1999, only 16 were for TB or tropical diseases. And two-thirds of those 1,400 new drugs were ‘me, too’ drugs” that treat the same disease.”

As president of ASTMH, Barry marshaled the support of the society’s membership for the Drugs for Neglected Diseases Initiative of Médecins Sans Frontièrs. The initiative seeks to create a needs-driven drug development network to narrow the pharmaceutical R&D gap for neglected diseases. ASTMH also lobbied successfully to reinstitute production of praziquantel, the preferred treatment of schistosomiasis, which a pharmaceutical company discontinued for lack of a profitable market.

Reservoirs and Vectors

Nine of the last 10 emerging human pathogens, including the viruses that cause SARS and avian influenza, have come from the animal “reservoir” — that is, a source or carrier that harbors the pathogen. Infection can occur by direct contact between humans and the animal reservoir (for example, by handling or working with infected animals) or transmission could occur by consuming meat or eggs from infected animals. Infection can also be transmitted by a vector that transfers the pathogen from reservoir to host — for example, a mosquito that feeds on an infected animal and then bites a human.

Marguerite Neill“Not every one of these newly emerging pathogens has represented a full-blown species jump, but that is what worries us greatly about animal pathogens that move to infect humans,” says Marguerite Neill ’73, associate professor of medicine at Brown Medical School, Providence, R.I., and a member of the Division of Infectious Disease at Memorial Hospital of Rhode Island. She explains that some pathogens from animals can occasionally infect humans but go no further because they are not efficiently transmitted from one person to another, such as rabies. But if an animal pathogen easily and frequently infects humans and ample opportunities exist for that, then a significant disease burden may result, such as has happened with West Nile virus and mad cow disease.

The worst case scenario for a species jump could occur when an animal pathogen adapts to easily infect humans and evolves the pathogenic mechanisms to continue to be transmitted from one person to another, Neill explains; HIV is one such example.

The medical and public health community is watching the current situation with avian influenza with great concern — if avian influenza evolved to a type that readily infects humans with subsequent facile transmission among the general population, a worldwide pandemic with many deaths would be the result. “This leads one to ask, how good is our surveillance of diseases or emerging pathogens in animal populations?” Neill says. “There has clearly been a wake-up call that animal surveillance is spotty at best, and is not integrated extensively with surveillance in human populations.”

Neill cites the example of West Nile virus, which was first documented in the United States in August 1999 in New York City. West Nile virus is carried by birds and transmitted to humans through mosquito bites. “People in the eastern United States developed encephalitis, and the lab investigators said, ‘Hey, it’s a known agent that causes humans to be sick; it’s just not an agent that’s supposed to be in this hemisphere,’” she recalls. “There is not a well-developed set of pipelines for communication between the various players that would be involved with looking at the bird population, such as wildlife experts, and the human population, such as public health specialists.”

Environmental Changes

Climatic and ecological changes have brought together people and pathogens that have not previously met. For example, Barry notes that the mosquito vector of dengue fever, which is endemic in Southeast Asia, is on the move. “We are seeing small epidemics in the Caribbean, and we are starting to see it now on the Texas-Mexico border as global warming allows the mosquito to move northward,” she says.

Monica Schoch-SpanaHuman encroachment on wilderness habitats also facilitates contact with new pathogenic reservoirs and vectors. “For example, housing developments in formerly forested areas of the northeastern United States brought people into contact with vectors of Lyme disease,” notes Monica Schoch-Spana ’86, a senior fellow at the Center for Biosecurity at University of Pittsburgh Medical Center. “There is speculation that Ebola and HIV were transmitted to humans as major ecological changes brought people together with these pathogens.”

Drug-Resistant Bacteria

Not all new and re-emerging infectious diseases grab global headlines and worldwide public attention. For example, infectious disease specialists are increasingly worried about recent changes in Staphylococcus aureus, a common cause of skin and surgical wound infections and sometimes pneumonia and endocarditis. Staph aureus in the community has acquired resistance to methicillin, and methicillin-resistant Staph aureus (MRSA) is now causing many community infections that may be harder to treat effectively with the usual antibiotics.

“We used to see MRSA only in hospitals, where people had been on a lot of antibiotics. But now we are seeing it all over the community, for no apparent reason,” says Patricia Murray ’75, an infectious disease physician in private practice in Santa Monica, Calif. “The incidence and severity of community-acquired MRSA have escalated dramatically over the past year. This new community-acquired strain can cause serious infection in minor wounds.”

Patricia MurrayThere are theories about the evolution of MRSA from a hospital- to a community-acquired infection, but no definitive answer. “Over the last 10 to 15 years we have seen increasing drug resistance and other changes in gram-positive bacteria in general,” Murray explains. “Fifteen years ago, we saw that the invasive group A streptococcus infections, what the news media call the ‘flesh-eating strep,’ were making a toxin that we now know is the same toxin we saw 20 years earlier in scarlet fever. Gram-positive bacteria can spread drug-resistant genes from one to another, so we anticipate there will be more drug resistance in the gram positives. Evolutionary changes in bacteria are of major importance in infectious disease.”

At the same time, Murray says, “Antibiotic overuse in areas such as animal feed can cause people to be sensitized to antibiotics they have never received. This can result both in allergic reactions and decreased effectiveness because people receive sub-therapeutic doses of antibiotics through the food they eat.”

Infectious disease specialists are using whatever works to fight drug-resistant diseases, including older antibiotics to which current bacteria have not been exposed. “Research and development into new antibiotics has dried up because pharmaceutical companies don’t see a strong enough market incentive to invest the money,” Murray says. “So the number of new antibiotics in the pipeline is way down from what it was 20 years ago.”

Tunnel Vision

Schoch-Spana says Americans’ faith in quick cures has led to tunnel vision in public health policy. “I hate to generalize, but in the United States we think we will be able to pull a magic cure out of the medicine chest when something infectious comes along,” she observes. “We are so enamored of our science and technology that we think we’ll find a pill or a vaccine. That focus on curative intervention has taken away consideration from how to create a robust public health system that can follow disease trends in our population and develop better preventive models.”

One critical shortcoming is the lack of epidemiological expertise in state and local health departments. “Because of the historic advantages of clean water, good sewage treatment systems, and good health care — at least for many of us — we haven’t lived with the outbreaks of infectious disease that envelop entire populations in other areas of the world,” Schoch-Spana says. “As a result, we have not invested enough in the infrastructure it takes to deal with outbreaks of infectious disease.”

Schoch-Spana says federal investment in public health has been inadequate to build a robust infrastructure. “Over the last two years there was a federal appropriation of about $2 billion for state and local health departments,” she says. “Of course, $2 billion divided by 280 million Americans is not a lot of money.”

Moreover, the economic downturn has led to cutbacks in state and local public health budgets. “There has been no net gain in the money going into public health because what the feds ‘giveth’ the governors and mayors ‘taketh away’ in lean economic times,” Schoch-Spana says.

Hospital Preparedness

Sharon Brodie Wright ’88, director of the Infection Control Unit and a member of the Division of Infectious Diseases at Beth Israel Deaconess Medical Center, Boston, says many hospitals are inadequately prepared for an infectious disease epidemic. “We may not be on the alert for the next emerging infection,” she says. “Regular hospital precautions for a patient presenting with fever and respiratory symptoms or rash would protect other patients and health care workers from infection. But if hospitals do not apply them stringently in our day-to-day work, we run the risk of experiencing what happened in Toronto with SARS.”

In addition, resources are scarce. “Last year here there were eight suspected cases of SARS in Massachusetts, and we had three of them in our hospital,” Wright says. “We were trying to prepare in case there were more. But when finances are tight and space is very limited, it’s very hard to ramp up staffing and identify an area that can be made into an infectious disease ward. Most hospitals can’t do that.”

Global Health Security

Infectious disease and public health specialists agree that dealing with new and re-emerging infectious diseases requires a multipronged approach. The objectives of CDC’s strategy for prevention of new and emerging infectious diseases are organized under four goals: surveillance and response, applied research, infrastructure and training, and prevention and control. Similarly, the strategy of WHO’s Department of Communicable Disease Surveillance and Response for achieving “global health security” focuses on containment of known risks, response to unexpected outbreaks and improved global preparedness.

Neill says the world’s recent experience with SARS and avian influenza shows that international communication and cooperation work. “For example, during SARS, CDC was talking with Health Canada, and they were in cooperation with WHO, which was communicating with public health officials in Singapore and Thailand. WHO provided electronic linkages and conference calls between SARS researchers and clinicians.”

Neill says the “stovepipe systems” for surveillance data in human and animal infectious diseases also must be linked. “Salmonella is the only pathogen that comes quickly to my mind as one for which there is even an attempt to integrate the two data systems and ask questions of each,” she says. “Human cases are reported and tallied by CDC, and a separate surveillance system looks at salmonella isolates from animals and maintains a database at the U.S. Department of Agriculture. The eyes of people who are used to looking at human health also need to be looking at animal pathogen surveillance data. We need cross-talk between the relevant agencies, such as CDC and USDA.”

Schoch-Spana says, “The United States must make a sustained investment in rebuilding our public health infrastructure.” The process will take decades, as did the process of building our national highway system. Meanwhile, she says, “Much of our state and local public health work force has no formal training in epidemiology, so even a small incremental change — putting two trained epidemiologists in each state health department — would be an immense improvement.”

Wright says proper hospital respiratory precautions must be part of business as usual, and not limited to emergency situations. “Anyone who presents with symptoms of respiratory viral illness should be given a paper surgical mask to wear, and we should be encouraging everyone to use good hand hygiene,” she says.

Both Schoch-Spana and Barry remind us that our definitions of new and re-emerging infectious diseases depend on where we live — one country’s new pathogen may well be another’s ongoing scourge. Barry urged her colleagues in ASTMH to take the lead in closing the gaps that prevent eradication of tropical diseases that cause so much misery in underdeveloped parts of the world and, in some cases, threaten to expand their reach. In particular, she says, there must be more R&D devoted to the “neglected diseases,” such as malaria and TB, and “very neglected” diseases” — African sleeping sickness, schistosomiasis, oncocerciasis, lymphatic filariasis, Chagas disease, and visceral leishmaniasis.

Barry also proposes creation of a U.S. Global Health Service Corps to train the next generation of American physicians in global health issues and international collaboration. Modeled after the National Health Service Corps, which places physicians in underserved urban and rural communities in the United States, a global corps would recruit physicians, nurses, dentists and public health specialists for one to two years of service in underdeveloped countries. Barry says a U.S. Global Health Service Corps would not only improve the lives of people in underdeveloped countries, it could also enhance U.S. medical capabilities to cope with new and re-emerging infectious diseases. She believes, “The best way to learn about emerging diseases is to have people on the ground in underdeveloped countries working in partnership with their colleagues.”

 

About Our Sources

Michele Barry '74 is a professor of medicine and global health and director of the Office of International Health at Yale School of Medicine. She is co-founder of Yale’s International Health Program. A past president of the American Society of Tropical Medicine and Hygiene, Barry is an expert on tropical diseases and the impact of globalization on public health. She is the health consultant for the Ford Foundation overseas programs and is an elected member of the Institute of Medicine of the National Academy of Science. Barry earned her M.D. from Albert Einstein College of Medicine and did her tropical medicine training at Walter Reed Hospital and overseas sites.

Patricia M. Murray '75 is an infectious disease physician in private practice in Santa Monica, Calif. Murray is affiliated with six hospitals in the greater Los Angeles area, including Saint John’s Hospital and Health Center and Santa Monica-UCLA Medical Center in Santa Monica. She is a fellow of the Infectious Diseases Society of America (IDSA), chair of the board of the State and Regional Society of IDSA, and a founder and past president of the Infectious Diseases Association of California. Murray, who lectures on AIDS prevention and infectious disease precautions, earned her M.D. from Chicago Medical School.

Marguerite A. Neill '73 is an associate professor of medicine at Brown Medical School and a member of the Division of Infectious Disease at Memorial Hospital of Rhode Island. She is a nationally recognized expert on food-borne pathogens. Neill chairs the Bioterrorism Work Group of the Infectious Diseases Society of America, and has led the Society’s effort to develop their Web site on bioterrorism. She has served on the U.S. Department of Agriculture’s National Advisory Committee on Microbial Criteria for Food Safety, and has published extensively on national biodefense preparedness as well as on infectious disease. Neill earned her M.D. at George Washington University School of Medicine.

Monica Schoch-Spana '86 is a senior fellow at the Center for Biosecurity at University of Pittsburgh Medical Center. She is chair of the center’s Working Group on Governance Dilemmas in Bioterrorism Response, which seeks to enhance government leaders’ ability to effectively manage the conflicts of interest, priority and purpose that emerge during public health crises. A medical anthropologist, Schoch-Spana has served as a technical adviser to the Ad Council’s national campaign on emergency preparedness in conjunction with the Department of Homeland Security and the Sloan Foundation. She earned her M.A. and Ph.D. at Johns Hopkins University.

Sharon Brodie Wright '88 is director of the Infection Control Unit and a member of the Division of Infectious Diseases at Beth Israel Deaconess Medical Center, a staff scientist in the Division of Infectious Diseases at Children’s Hospital in Boston, and an instructor of medicine at Harvard Medical School. Wright has worked with government and the medical community on bioterrorism response and has lectured on bioterrorism at MIT and Boston area hospitals. She earned her M.D. at Columbia University College of Physicians and Surgeons and her M.P.H. at Harvard School of Public Health.

 

Dorothy Wright contributes news and feature articles on science, technology, engineering and general interest topics to a variety of publications, including Civil Engineering and Engineering News Record.

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