Emerging Diseases

A Viewpoint on the Coming Impact of Emerging Diseases

Infectious disease is now the third leading cause of death in the United States, and the first leading cause in the Third World. These diseases are the most important public health crisis facing the health care community. As part of that community, dentists must be armed with the knowledge necessary to take their part in the war against these infectious agents.

During the past two decades, the world of public health has undergone radical changes in the thought processes regarding infectious diseases. It was once assumed that antibiotics and chemotherapeutic agents, along with vaccines, would reduce the spread of infectious diseases and bring them under control with a massive reduction in incidence.¹ The emergence of AIDS and the re-emergence of tuberculosis in the 1980s brought the assumptions of worldwide control of disease to a disappointing halt. The appearance and rapid spread of human immunodeficiency virus throughout the Western world forewarned of the AIDS pandemic, which unfortunately has come to fruition. Tuberculosis, which was virtually unheard of in the United States in 1985, crawled out of ancient history and back into the forefront of public health concern.² The appearance of multiple-drug-resistant strains of TB and a rapid spread of the disease in cities that had not seen the disease in 40 years have cast a pall on predictions of secure health. Infectious disease has become the third leading cause of death in the United States -- following heart disease and cancer -- and the No. 1 cause of death in the Third World.³

Under the leadership of the World Health Organization in Geneva and the Centers for Disease Control and Prevention in Atlanta, major steps are being taken to combat the emergence of new disease and re-emergence of older diseases. The entire world is taking up the challenge to combat the new plagues. Never before have communication and networking been brought into play for prevention and treatment at the level this globe is now seeing.⁴ The new enemy threatening us all is no longer worldwide destruction by nuclear weapons or even global starvation. It is infectious disease. We can no longer ignore these threats or fail to act to develop new controls that will slow the worldwide advance of pathogenic microbes.

In the process, we must learn new biotechniques, educate the public, and develop new clinical treatments. Preventive public health measures are critical. Public health agencies and public health infrastructure functioning at high levels are essential to the security of our citizens and stand as the first line of defense.⁵ Education of health care professionals with regard to all these issues must be a key element in this endeavor. For once, we have a chance to prevent a public health crisis. The dental profession is in a primary position to be interactive with public health care agencies and other members of the health care community in recognizing and combating emerging diseases. Oral examination often reveals key findings relating to extensive disease in the whole body. Oral lesions often signal childhood diseases, AIDS, venereal disease, and other conditions. As part of the health care community, dentists must be aware of the integrated attack on emerging disease and play their role in the allied effort to recognize and control infectious diseases. The dental profession by its very nature of exposure to blood, other body fluids, and the generation of aerosols by dental instrumentation with its resultant respiratory transfer potential must be in a ready state of awareness. Whether health care professionals have the time, commitment, resources, or communication to take proper action remains to be seen.

Why the Spread of Emerging Diseases?

With the Cold War over, the world no longer competes militarily and instead entered into an era of global trade, modernization, and economic development. International trade and travel increased. Human entry into remote areas of the world increased in the search for raw materials and led to contact with insect vectors and animals with zoophytic diseases not previously encountered. Further complicating the problem is the fact that modern modes of transportation can move disease from one end of the earth to another in as little as 24 hours.⁶ As employment opportunities increase in the industrial world, Third World citizens migrate for jobs on a legal or illegal basis. The dental profession cares for both sick and well people of every race and ethnicity. Dentists are exposed to everyone and everything because care and well-being are their credos. Dentists, therefore, must be aware of the rapid changes in public health policy and information transfer.

Insect or arthropod vectors are also being moved across the globe, further complicating disease transmission. One concern is that imported mosquitoes would be capable of feeding on native animal species harboring exotic microbes such as Hantaan virus or Lyme disease. If such a new invader is also capable of feeding on human blood, it would be a vector of transmission of rodent diseases to humans.

Global warming and emerging weather patterns are also being monitored as geobiologic mechanisms for the spread of disease.⁷ If, because of climate changes, mosquitoes migrate to areas once too dry or too cold, then they may transmit new diseases to these areas, which were formerly out of their ecological range. Another concern is whether they will then transmit the new disease directly to humans. Will mutations arise that allow different modes of disease transmission? The Hantavirus, or Four Corners Disease, became a newly discovered agent only because of climatic changes with excess rain leading to a huge increase in grasses subsidizing the rodent population.⁸ The Hantavirus, however, was not a new agent introduced to the United States, but one found throughout the country in traceable migration patterns over a period of tens of thousands of years.

Emerging Diseases: Population and Geography

The world's population rate is actually subsiding, but the population increase will still represent several billion more people in the next century. Environmental and economic conditions will intensify, and the results will affect the world's health as well. The gap between the richest and poorest will expand. Urbanization is increasing, and more people are being jammed together in closer quarters. Migration of peoples from crowded lands with limited opportunities and major problems is a continuing event. Illegal migration will help to spread disease from one land to another. World travel from sheer population growth in an expanding international economy will shrink the earth and its peoples. The United States will maintain its indigenous population with a low birth rate. The United States will, however, still increase its total population by 120 million in the next 50 years because of immigration.⁹

The disruption of health care services and, most vitally, public health services usually leads to the dissemination of disease. In many instances, large cities in wealthy nations may provide better health services, sanitation, and medical facilities. These services are dictated in many ways by the availability of monetary funds. Large increases in population in Third World nations can only lead to greater stresses on their already weakened infrastructure. The issue of infectious diseases will be a major factor for humanity in the next century. Dentistry, as a member of the health care society, must maintain its place of awareness in that interactive community.

Drug Resistance and Re-emergence of Disease

Microbial drug resistance has resulted in a decline of efficacy of antimicrobial agents, be they antibiotic or chemotherapeutic in nature. Microbes have the uncanny ability to slip out of drug control by mutation, which removes one of the clinician's most powerful weapons. Previously susceptible microbes, controlled by antibiotics for 50 years, have in the past decade jumped to drug resistance at a remarkable level.¹⁰ Vancomycin-resistant enterococci, methicillin-resistant staphylococci, penicillin-resistant pneumococci, and multiple-drug-resistant tuberculosis are just a few of the drug-resistant strains that have appeared with a wrath at the door of the embattled clinician.¹¹ The race is between the development of new drugs and the evolution of mutations, and that is a race the microbes are winning.

How Do We Combat the Selection of Resistant Microbes?

* Reduce the overprescribing of antimicrobials to reduce the selection of resistant microbes. This is an area where dentistry must do its part.

* Reduce excessive use of antimicrobials in commercial animal food.

* Interrupt the global spread of disease, if possible.

* Closely monitor the development and appearance of drug-resistant strains throughout the world.

* Continue to develop new drugs.

Current Status for Immunization of Health Care Workers

Recommendations have been made recently for the immunization of health care workers.¹² These suggestions include vaccines for hepatitis B, influenza, measles, mumps, rubella, and varicella. Immunization of all adults is recommended for tetanus, diphtheria, and pneumonia.

Vaccines for tuberculosis, such as the BCG vaccine, are not currently recommended in the United States. The TB vaccine is not sufficiently efficacious to be used, and the vaccine would interrupt TB skin testing because antibodies raised by vaccination would yield false positives.¹³ Intensive work is under way to develop a fully workable TB vaccine. Vaccines, however, take time and testing; and no set date can yet be assigned to a successful TB vaccine program.

To monitor the well-being of health professionals, immunization records should be kept for each health care worker. The record should reflect vaccination histories and documented disease. Records are expected to be updated and maintained.¹⁴ Vaccines remain a main line of defense against the invasion of infectious disease. The question remains whether vaccines can be developed rapidly enough and with sufficient ability to neutralize invading microbes. Vaccines are not easy to produce at a feasible cost for worldwide use. The human race has also been stymied in an attempt to develop vaccines against venereal disease, AIDS, influenza, hepatitis type C, and tuberculosis, to name a few. Still, vaccines are the best means of prophylaxis available. Yet the question remains, will vaccines be successful with newly emerging diseases. Rapid mutation of viruses and bacteria from antibiotic-susceptible types to multiple-drug-resistant forms will greatly challenge scientists working in drug therapy.

The importance in updating health care workers and the public on vaccines has prompted the CDC and the public health training network to sponsor a live satellite broadcast in September 1998. This communication outreach was designed to update and inform health care professionals on both vaccination and patient counseling. Topics included information on new vaccines, such as those for rotavirus, Lyme disease, and attenuated influenza. Recommendations on measles and the vaccination of health care workers were important topics. Participants were able to interact with instructors via toll-free telephone and fax lines, in addition to obtaining continuing education credits. It is expected that this style of communication will continue to be used and expanded. Additional information and registration will be available from county and state health agencies via their immunization programs. A list of state immunization coordinators is available on the World Wide Web at http://www.cdc.gov/phtn.¹⁵

The effectiveness of childhood vaccination programs continues to be impressive.¹⁶ The current measles, rubella, mumps, and chicken pox vaccine program has led to a reduction in childhood disease approaching elimination in the United States. The critical issue is to be able to continue vaccine production against new diseases. DNA-type viruses are basically more resistant to mutational changes than are RNA viruses. RNA viruses act through the enzyme reverse transcriptase to make DNA from RNA, and they have a tendency to make errors in replication. This loss of fidelity leads to higher mutational rates, thereby adding to the difficulty of vaccine production.¹⁷

Governmental Concerns
The fiscal year 1999 budget reflect the U.S. government's concern regarding health care matters. The CDC is receiving $2.6 billion, an increase of $95 million over fiscal year 1998. The emerging infectious disease program is expected to receive $79 million, some $20 million more than fiscal year 1998. All other elements of research -- both basic and applied -- are receiving substantial increases, which indicates the federal government's increasing interest in infectious diseases.¹⁸ The long-range governmental approach views containment, early diagnosis, and international cooperation as areas of primary importance. Information exchanged with the World Health Organization, international health agencies, and U.S. health agencies will be further enhanced to reinforce efforts toward awareness and combating emerging diseases.

Emerging vs. Re-emerging Diseases

There are numerous diseases, such as TB, that disappear, then re-emerge years later to attack society again. In other instances, diseases re-emerge on a continuous basis, as is the case of influenza, which returns on a yearly basis in a genetically modified form. In still other instances, a disease may lie dormant or be found at low levels and suddenly and inexplicably break out in huge numbers.

An example of this phenomenon is the respiratory syncytial virus (RSV). The disease appears in a few short months and soon after explodes into widespread dissemination.¹⁹ The epidemiology is constantly studied while also being monitored in other countries around the world. At present, no clear-cut mechanism of transmission and rapid dissemination is known.²⁰

Hemorrhagic Fevers

Emerging diseases appear from unknown quarters and enter society from unknown backgrounds. The hemorrhagic fevers are a group of emerging diseases that have received public recognition through movie and media exposure. Ebola virus has been widely publicized yet is only one of a number of hemorrhagic diseases. In fact, there are Old World and New World hemorrhagic fever viruses found in the Arena Virus Group. A listing of current New World infectious agents is shown in Table 1.

Hemorrhagic fever viruses have mortality rates ranging from 15 percent to 30 percent with exceptions such as Ebola and Marburg viruses, which range up to 80 percent mortality.²¹ Ebola has received the greatest amount of publicity, yet its animal reservoir in nature has never been found, though hundreds of animal species in Africa have been examined for presence of the virus. There is no treatment for Ebola, and the virus is lethal. Outbreaks have been contained in Africa, although monkey-targeted strains have appeared in an animal colony in the United States. The virus is on the skin of patients, and it is presumed transmittable via topical skin. Needle transfer occurs readily, but other modes of transmission, vector or otherwise, are entirely feasible. Will Ebola strains targeted for humans ever appear in the United States? The more appropriate question seems to be not whether, but rather, when, where, and how severe.


Old World Emergers and Relevant Outbreaks

Old World emergers and relevant outbreaks are shown in Table 2. Ebola and Marburg agents make up the filovirus group. Ebola virus has four very distinct types, almost four different groups. The animal reservoir is unknown, and it is quite possible that there are more than four types. There are no therapies, and no vector is known. We are in a vulnerable position if the agent appears in the United States.²²

The spread of European diseases such as measles and smallpox into the New World after its discovery, exploration, and colonization gives us a historical perspective of what could lie in the future in the third millennium.²³

Dengue Fever

Dengue and yellow fevers are members of the Flavivirus group. Yellow fever has an effective vaccine and is under general control. The Dengue virus can be partly controlled by vector control and has some supportive therapy. Yet Dengue has spread throughout South America, Central America, the Caribbean, and even into the U.S. Gulf Coast in the past two decades. Generally not life threatening, it has a severe morbidity and lasts from three to seven days. A sudden onset of fever, frontal headache, nausea, vomiting, and liver enzyme elevation are followed by several other signs and symptoms. Convalescence may be prolonged for weeks. Dengue and the mosquito Aedes aegyptai are linked. The spread of the mosquito makes a trail for the Dengue virus. Urbanization and economic expansion in Third World countries mark the increase of Dengue transmission. Epidemics become larger as geographic expansion of the virus continues. Unprecedented population growth is also a major factor in Dengue spread. There are no vaccines. Mosquito control is a must along with improvement in the public health system infrastructure. Research for a workable vaccine and into epidemiology and pathogenesis is an absolute necessity.

Tuberculosis

With TB, one never knows where or how severe an outbreak may be. Source or index people are capable of widespread disease transmission be they in small rural communities or large cities. Increased virulence within strains capable of rapid dissemination and transmission has been reported with only minimal exposure.²⁴

Tuberculosis has been on the list for disease elimination, but the disease has resisted all efforts to be subdued. Vaccines are under test, but these are long-term ventures. Environmental control methods such as ventilation, HEPA air filtration, and ultraviolet light radiation have reduced TB transmission in some health care settings.²⁵

The CDC has actually recommended chemotherapy as a preventive measure for the control of TB in people who are at high risk for the disease but do not actually have it. Without a quality vaccine, however, TB control is an illusion. Easily spread by aerosol transmission, Mycobacterium tuberculosis will remain a problem in the health care industry. The slow-growing nature of the microbe, coupled with the emergence of multiple-drug-resistant strains, has added to the current problem.²⁶ The recognition of a continuous, productive cough is perhaps the best sign for the presence of disease. Skin testing for exposure to TB will continue to be expanded in the attempt to monitor the disease spread in health care workers.

The Global Picture of HIV

In 1996, a decline in the deaths from AIDS finally occurred in the United States. This downward trend was apparently due to the introduction of multidrug therapy or "cocktails" containing protease inhibitors and other chemotherapies. Unfortunately, HIV mutations soon appeared, bypassing the efficacy of these therapy regimens.²⁷ Furthermore, ceasing therapy will allow the re-appearance of the AIDS virus in serum and some virus is found in semen even when serum levels are undetectable. While the drugs are at least temporarily effective at costs of $10,000 to $30,000 per year in First World nations, that expense option is not easily accommodated in the Third World, so the worldwide pandemic is increasing in intensity.²⁸ Developing nations with large populations, low income levels, and inadequate public health infrastructures truly have severe problems with AIDS. It is estimated that the number of people with HIV is currently 900,000 in North America and 600,000 in Western Europe. Yet, since the advent of AIDS in the early 1980s, more than 40 million people throughout the world have contracted the virus, with almost 12 million dead. Some 16,000 people in the world contract HIV on a daily basis. Sub-Saharan countries and nations in Southeast Asia have extremely high rates of HIV Infection. The sub-Saharan area contains two-thirds of the world's AIDS population and 90 percent of all the childhood AIDS.²⁹ Unprotected sex and untested blood supplies are the main causes behind Southeast Asia's recent explosion of AIDS, and India soon will lead the world in HIV-positive people, with up to 5 million infected. Burma, Vietnam, and parts of China are also entering levels in the danger zone.

What are the causes behind disease expansion? Social levels are extremely important. The disease may first appear among the wealthier, well-traveled classes, but rapidly spread to the poor and the disenfranchised. Sexual exploitation and lack of access to social and public health services are factors in the dissemination of AIDS. Education is always a major control mechanism in the spread of disease, at any level of society. Areas where AIDS has not previously been detected, or has been at low levels, are now starting to explode with large numbers of infected people. Southern Africa and Cambodia are starting to experience this new onslaught. The spread of this disease into populations not yet touched is virtually certain to happen.³⁰ Chemotherapy is very expensive and limited in long-term use based on the mutational abilities of the virus. The same problem exists for vaccines. Can we develop a vaccine that works for multiple strains? It must be noted that the serological test for AIDS is not for the presence of the virus, but for the presence of the antibody. If we already mount an antibody immune attack on the AIDS virus by being infected, how much better can a vaccine induced by artificial immune response be? Protected sex and monogamous relationships are of paramount importance. There are no easy solutions to HIV, but society must take the difficult ones. We really have no choice.

Centers for Disease Control and Prevention Strategies for the 21st Century

To prevent emerging diseases in the next century, the CDC has recently updated its strategy.³¹ The CDC has been compelled to assume new standards of strategy because of increased global poverty, rapid growth of the world's population, migration, international travel, food distribution, and increased travel. The CDC's strategy is to deal with today's diseases with treatment and tomorrow's with prevention. The four main goals of the CDC's strategic approach are:

* Surveillance and response;

* Applied research;

* Infrastructure and training; and

* Prevention and control.

Ultimately, a stronger and more flexible public health system will be expected to evolve, one that is capable of rapid response to existing disease and simultaneously capable of controlling anything from an emerging disease outbreak to a bioterrorist attack. To implement such a strategy will require an enormous effort of all parties: the health care industry, health departments, universities, and virtually every segment of society. Dentistry, as part of the health care community, must be aware of the international problems and remain prepared in infection control measures and the recognition of disease in patients.

Author/John W. Beierle, PhD, is an associate professor of basic sciences at the University of Southern California School of Dentistry.

References

1. Sudre P, et al, A tuberculosis overview of the situation today. Bull World Health Organization 70:149-59, 1992.
2. Dolin PJ, et al, A global tuberculosis incidence and mortality during 1990-2000. Bull World Health Organization 72:213-20, 1994.
3. Swartz MN, Use of anti-microbial agents and drug resistance. N Eng J Med 385(5):101-2, 1998.
4. Centers for Disease Control and Prevention, Preventing emerging infectious disease: A strategy for the 21st Century. MMWR 47(RR-15):1-14, 1998.
5. Institute of Medicine, Emerging infections: microbial threats to health in the United States. National Academy Press, Washington, DC, 1992.
6. Ewald PN, Evolution of infectious disease. Oxford University Press, New York, 298, 1994.
7. Pan American Health Organization, Guidelines for the prevention and control of Dengue and Dengue Hemorrhagic fever in the Americas. Pan American Health Organization, Washington, DC,1994.
8. Peters CJ, Ksiazek TG, Hantavirus pulmonary syndrome: the first 100 U.S. cases. J Infect Dis 173:1297-1303, 1996.
9. MMWR, Recommendations for prevention and control of tuberculosis among foreign-born persons. MMWR 47(RR-16):1-29, 1998.
10. Pablo-Mendez A, et al, Global surveillance for anti-tuberculosis/drug resistance, 1994-1997. N Eng J Med 338:1641-9, 1998.
11. Centers for Disease Control and Prevention, Staphylococcus aureus with reduced susceptibility to vancomycin -- United States 1997. MMWR 46:1204-7, 1997.
12. Centers for Disease Control and Prevention, General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices. MMWR 43(RR-1):1-38, 1994.
13. Centers for Disease Control and Prevention, Development of new vaccines for tuberculosis. MMWR 47(RR-13):1-6, 1998.
14. Centers for Disease Control and Prevention, Guidelines for preventing the transmission of Mycobacterium tuberculosis in health care facilities, 1994. MMWR 43(RR-13):1-132, 1994.
15. Centers for Disease Control and Prevention, Satellite broadcast on immunization update. MMWR 47(RR-34):717, 1998.
16. Centers for Disease Control and Prevention, Measles, mumps, rubella vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps. MMWR 47(RR-8):1-57, 1998.
17. Hill AV, Genetics of infectious disease resistance. Curr Opin Genet Dev 6:348-53, 1996.
18. Overview of the President's FY 1999 proposed federal R&D budget. ASM 64(4):196, 1998.
19. Centers for Disease Control and Prevention, Update: Respiratory syncytial virus activity -- United States, 1997-98 season. MMWR 47(RR-48):1043-5, 1998.
20. Peters CJ, Hemorrhagic fevers: how they wax and wane in emerging infections. Scheld W, Armstrong D, Hughes, eds. Am Sor Micro, Washington, DC, 1998.
21. Peters CJ, Emerging infectious Ebola and other filoviruses. Western J Med 164:36-8, 1996.
22. Cartwright FF, Disease and History. Doreset Press, New York, 1972, p 243.
23. Centers for Disease Control and Prevention, Dengue outbreak associated with multiple serotypes -- Puerto Rico. MMWR 47(44):952-6, 1998.
24. Valway SE, et al, An outbreak involving extensive transmission of a virulent strain of Mycobacterium tuberculosis. N Eng J Med 338(10):633-89, 1998.
25. Centers for Disease Control and Prevention, Guidelines for preventing the transmission of Mycobacterium tuberculosis in health care facilities, 1994. MMWR 43(RR-13):1-132, 1994.
26. Moore M, et al, Trends in drug resistant tuberculosis in the United States, 1993-1996. JAMA 278:833-7, 1998.
27. Centers for Disease Control and Prevention, Public health service guidelines for the management of health care workers. Exposures to HIV and recommendations for post-exposure prophylaxis. MMWR 47(RR-7):1-33, 1998.
28. Centers for Disease Control and Prevention, Report of the NIH panel to define principle of therapy of HIV infection. MMWR 47(RR-5):1-82, 1998.
29. Mann JM, Tarantola DJM, HIV 1998: The global picture. Scientific American 82-3, July, 1998.
30. Baily ML, Brunhawn RC, The impart of HIV and other STDs on human populations. Are predictions possible? Infect Dis Clin N Am 7:771-92, 1993.
31. Centers for Disease Control and Prevention, Preventing emerging infectious diseases. A strategy for the 21st Century. Overview of the updated CDC plan. MMWR 47(RR-15):1-14, 1998.

To request a printed copy of this article, please contact/John W. Beierle, PhD, USC School of Dentistry, Los Angeles, CA 90089-0641.