Global Microbial Threats in the 1990s

Global Microbial Threats in the 1990s

I. Introduction

By the mid-1950s, the threat of infectious diseases appeared to be receding in the United States. Deaths from infection, commonplace in our grandparents' time, were no longer a frequent occurrence. American physicians used fast-acting, effective drugs to combat often fatal bacterial diseases such as meningitis and pneumonia. The incidence of childhood diseases such as polio, whooping cough, and diphtheria, was declining due to the use of vaccines. Meanwhile, in other parts of the world, chemical pesticides like DDT were lowering the incidence of malaria, a major killer of children, by controlling populations of parasite-carrying mosquitoes.

As it turned out, our collective -- and quite understandable -- euphoria did not take into account the extraordinary resilience of microbes, which have a remarkable ability to evolve, adapt, and develop resistance to drugs in an unpredictable and dynamic fashion. Moreover, disease-carrying insects have developed resistance to pesticides in a very short time.

Today, most health professionals agree that new microbial threats are appearing in significant numbers, while well-known illnesses thought to be under control are re-emerging. Most Americans are aware of the epidemic of the acquired immunodeficiency syndrome (AIDS) and the related increase in tuberculosis (TB) cases in the United States. In fact, there has been a general resurgence of infectious diseases throughout the world, including significant outbreaks of cholera, malaria, yellow fever, dengue, and diphtheria, as well as illnesses caused by antibiotic-resistant bacteria. There has also been a resurgence of fungal infections for which there are very few treatments. Furthermore, the incidence of AIDS is increasing in many countries.

New diseases have also appeared within the United States, including Lyme disease, Legionnaires' disease, and most recently, hantavirus pulmonary syndrome (HPS). HPS was first recognized in the southwestern United States in 1993 and has since been detected in more than 20 states and in several other countries in the Americas. Other new or re-emerging threats in the United States include multi-drug resistant TB, antibiotic-resistant staphylococcal, enterococcal, and pneumococcal infections, and diarrheal diseases caused by the parasite Cryptosporidium parvum and by certain strains of Escherichia coli bacteria. In fact, only one antibiotic remains consistently effective against common hospital-acquired staphylococcal infections. Meanwhile, the number of new antibiotics introduced into the U.S. market has declined; not one new antibiotic was approved in 1994. In the race between drug-resistant bacteria and new drugs, the resilient bacteria are winning.

Savings Due to Vaccination

Smallpox. The economic benefits of the Smallpox Eradication Program have been substantial for all of the countries in the world, as preventive measures and treatment facilities for smallpox are no longer needed. The cost to the United States for the successful 13-year campaign to eradicate smallpox throughout the world was about $30 million. Since smallpox was eradicated in 1977, the total investment has been returned to the United States every 26 days.

Polio. Once a common cause of disabilities or death, polio has been eliminated from the Americas. The current drive towards global eradication is one of the great challenges of our generation. Once the global eradication program is completed (t arget date: 2000), the United States will save millions of dollars yearly on vaccination costs alone, since there will no longer be a need to immunize newborns. Based on the current rate of progress toward eradication, WHO predicts a global savings of $5 00 million by the year 2000, increasing to savings of $3 billion annually by the year 2015.

Other Infectious Diseases of Childhood. Health economists estimate that for every dollar spent on the measles/mumps/rubella vaccine, $21 are saved; for the diphtheria/tetanus/pertussis vaccine, $29 are saved; and for the polio vaccine $6 are saved.

Why are infectious diseases re-emerging as major threats to human health?

The reasons for the resurgence of infectious diseases are complex and not fully understood. Contributing factors include population shifts, increased urbanization and crowding, environmental changes, and worldwide commerce and travel. Some specific causes are

Infectious microbes do not recognize national borders

The modern world is a very small place, where any city in the world is only a plane ride away from any other. Infectious microbes can easily travel across borders with their human or animal hosts. In fact, diseases that arise in other parts of the world are repeatedly introduced into the United States, where they may threaten our national health and security. Since 1973, more than 30 new pathogenic microbes have been identified and numerous known diseases have re-emerged (see Table 2 Examples of pathogenic and infectious diseases recognized since 1973 & Table 3 Re-emerging infections during the last two decades and factors contributing to thei r re-emergence).

Without preventive public health measures in the United States and abroad, uncontrolled outbreaks can grow into major epidemics. However, our earlier successes in controlling infections have bred complacency, and the components of the U.S. public health system that protects the public from infectious microbes have been neglected, concentrating their resources on a few targeted diseases.

Nevertheless, the subject of emerging infectious diseases is beginning to receive sustained public attention. In 1992, the Institute of Medicine's report, "Emerging Infections: Microbial Threats to Health in the United States," clarified the issue of emerging diseases for policymakers in government and in academia. In response, the CDC issued the 1994 report "Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States." Other U.S. Government agencies, including NIH, USAID, and DoD have also examined the issue of U.S. vulnerability to epidemics and re-emerging health problems.

Quite recently, public discussion has been further focused on the global issue of emerging diseases by the publication of two best-selling, non-fiction books, The Hot Zone by Richard Preston, and The Coming Plague by Laurie Garrett, and by popular movies such as "Outbreak," starring Dustin Hoffman. Concerns about antibiotic-resistant bacteria and food-borne diseases, as well as the recent plague outbreak in India and the Ebola outbreak in Zaire, have been widely discussed in many news magazines, in print and on television. This media attention has informed the American public of the reasons why it is in our national interest to strengthen disease surveillance and control efforts internationally.

International health and U.S. foreign policy

A global system for infectious disease surveillance and response will help protect the health of American citizens and people throughout the world. In addition, the improvement of international health is a valuable component of the U.S. effort to promote worldwide political stability through sustainable economic development. Healthy people are more productive and better able to contribute to their countries' welfare. Also, a global disease surveillance and response network will enable the United States to respond quickly and effectively in the event of an attack involving biological or chemical warfare, as the experience gained in controlling naturally occurring microbes will enhance our ability to cope with a biological warfare agent, should the need arise. The release of nerve gas in the Tokyo subway system in March 1995 has underscored our need to be well prepared to counteract deliberate attempts to undermine human health.

Thus, the effort to build a global surveillance and response system is in accord with the national security and foreign policy goals of the United States. Moreover, leadership in global infectious disease surveillance and control is a natural role for the United States. American business leaders and scientists are in the forefront of the computer communications and biomedical research communities (both public and private sector) that provide the technical and scientific underpinning for disease surveillance. Furthermore, American scientists and public health professionals have been among the most important contributors to the international efforts to eradicate smallpox and polio.

The challenge ahead outstrips the means available to any one country or to international organizations. The U.S. Government must not only improve its capacity to meet the growing threat of emerging infectious diseases, but also work in concert with other nations and international bodies. Although international efforts must be coordinated to prevent global pandemics, disease surveillance must be the responsibility of each sovereign nation. However, individual governments may not easily share national disease surveillance information, fearing losses in trade, tourism, and national prestige. Nevertheless, because U.S. experts are often consulted on problems of infectious disease recognition and control, the U.S. Government is usually informed about major disease outbreaks in other countries, although not always in an official or timely fashion. To ensure that we continue to be notified when an unusual outbreak occurs, we must encourage and support other countries' efforts in national disease surveillance and respond when asked for assistance. We must strive to develop a sense of shared responsibility and mutual confidence in the international effort to combat infectious diseases.

There is much room for optimism. If the United States takes the lead, we can expect that other nations will contribute resources to a global surveillance system. Both Canada and the European Union have recently decided -- in spite of tight budgets -- to provide substantial funds ($7 and $10 million per year, respectively) to strengthen infectious disease surveillance and control. It is also absolutely critical that developing nations be engaged in an international effort that is in their own interests. In May 1995, WHO passed a resolution urging member states "to strengthen national and local programmes of surveillance for infectious diseases, ensuring that outbreaks of new, emerging, and re-emerging infectious diseases are identified." Soon after the resolution was drafted, WHO issued a report urging the strengthening of global disease surveillance and control, and encouraging greater use of WHO Collaborating Centers in this endeavor.

Are infectious disease surveillance and control cost-effective?

The direct and indirect costs of infectious disease are staggering (see Table 1). Clearly, public health measures that prevent infectious diseases can be extremely cost-effective. In 1994 and 1995 two major U.S. health-care expenses have been for the treatment of tuberculosis and AIDS. The Public Health Service budget for fiscal year 1996 includes $343 million to combat TB and nearly $3 billion to combat AIDS. TB is a very old, well-known disease that has re-emerged sometimes in a drug-resistant or multidrug-resistant form. AIDS, on the other hand, is a new disease, unrecognized before the 1980s. When the first cases of AIDS and drug-resistant TB were detected in the United States, control measures were delayed, partly because of a lack of surveillance information and incomplete understanding of the epidemiology of these diseases.

Table 1 Estimated costs of common infectious diseases in the United States

Disease 		     Financial Cost

Intestinal infections $23 billion in direct medical costs and lost productivity Food-borne diseases $ 5-6 billion in medical and productivity costs Sexually-transmitted $ 5 billion in treatment costs diseases(excluding AIDS) Influenza $ 5 billion (direct medical costs) and $12 billion (lost productivity costs) Antibiotic-resistant $ 4 billion in treatment costs and increasing bacterial infections Hepatitis B virus infection $720+ million in combined direct and indirect costs
These costs, combined with dollars spent on AIDS and TB, exceed $120 billion per year.


For many years, the United States had in place a surveillance system to monitor cases of TB. However, during the 1980s, federal and local spending on infectious disease control declined, and in 1986 the surveillance system for multidrug-resistant TB was discontinued. Consequently, there was no warning signal when drug-resistant TB emerged in the late 1980s. This lack of early warning undoubtedly contributed to the more than $700 million in direct costs for TB treatment incurred in 1991 alone. Surveillance of drug-resistant TB was not reinstated until 1993, by which time multidrug-resistant TB had became a public health crisis and millions of federal dollars had been appropriated.


As mentioned above, AIDS is a new disease that was unknown before the 1980s, and thus, was not on any surveillance lists. AIDS weakens the immune system, allowing other infections to take hold. Therefore, it can be difficult to diagnose since its clinical presentation may involve a variety of symptoms, and its incubation period (the time between infection and the appearance of symptoms) can be many years. Nevertheless, long before AIDS was diagnosed in the United States and Europe, a distinct syndrome called slim disease (now known to be a form of AIDS) that causes its victims to waste away was recognized by African doctors. In fact, an aggressive, slim-associated, generalized form of Kaposi sarcoma, distinct from the classical form, has been described in Uganda since at least 1962. Some health workers believe that if a global surveillance network had been in place in the 1970s, AIDS might have been identified earlier, perhaps before it became well established in the United States. Epidemiologists might have gained a head start in learning how AIDS is transmitted and prevented, and many lives might have been saved. However, other health experts believe that the lack of disease surveillance and specimen collection facilities in central Africa in the 1960s and 1970s make it nearly impossible to be sure, even in retrospect, if AIDS was present at that time.

Table 2 Examples of pathogenic microbes and infectious diseases recognized since 1973

Year   Microbe                 Type      Disease
1973 Rotavirus Virus Major cause of infantile diarrhea worldwide 1975 Parvovirus B19 Virus Aplastic crisis in chronic hemolytic anemia 1976 Cryptosporidium parvum Parasite Acute and chronic diarrhea 1977 Ebola virus Virus Ebola hemorrhagic fever 1977 Legionella pneumophila Bacteria Legionnaires' disease 1977 Hantaan virus Virus Hemorrhagic fever with renal syndrome (HRFS) 1977 Campylobacter jejuni Bacteria Enteric pathogens distributed globally 1980 Human T-lymphotropic Virus T-cell lymphoma-leukemia virus I (HTLV-1) 1981 Toxic producing strains of Staphylococcus aureus Bacteria Toxic shock syndrome (tampon use) 1982 Escherichia coli O157:H7 Bacteria Hemorrhagic colitis; hemolytic uremic syndrome 1982 HTLV-II Virus Hairy cell leukemia 1982 Borrelia burgdorferi Bacteria Lyme disease 1983 Human immunodeficiency Virus Acquired immunodeficiency virus (HIV) syndrome(AIDS) 1983 Helicobacter pylori Bacteria Peptic ulcer disease 1985 Enterocytozoon bieneusi Parasite Persistent diarrhea 1986 Cyclospora cayatanensis Parasite Persistent diarrhea 1988 Human herpesvirus-6 Virus Roseola subitum (HHV-6) 1988 Hepatitis E Virus Enterically transmitted non-A, non-B hepatitis 1989 Ehrlichia chafeensis Bacteria Human ehrlichiosis 1989 Hepatitis C Virus Parenterally transmitted non-A, non-B liver infection 1991 Guanarito virus Virus Venezuelan hemorrhagic fever 1991 Encephalitozoon hellem Parasite Conjunctivitis, disseminated disease 1991 New species of Babesia Parasite Atypical babesiosis 1992 Vibrio cholerae O139 Bacteria New strain associated with epidemic cholera 1992 Bartonella henselae Bacteria Cat-scratch disease; bacillary angiomatosis 1993 Sin nombre virus Virus Adult respiratory distress syndrome 1993 Encephalitozoon cuniculi Parasite Disseminated disease 1994 Sabia virus Virus Brazilian hemorrhagic fever 1995 HHV-8 Virus Associated with Kaposi sarcoma in AIDS patients

Table 3 Re-emerging infections during the last two decades and factors contributing to their re-emergence

      Disease or Agent              Factors in Re-emergence
Viral Rabies Breakdown in public health measures; changes in land use; travel Dengue/dengue hemorrhagic fever Transportation, travel and migration; urbanization Yellow fever Favorable conditions for mosquito vector Parasitic Malaria Drug and insecticide resistance; civil strife; lack of economic resources Schistosomiasis Dam construction, improved irrigation, and ecological changes favoring the snail host Neurocysticercosis Immigration Acanthamebiasis Introduction of soft contact lenses Visceral leishmaniasis War, population displacement, immigration, habitat changes favorable to the insect vector, an increase in immunocompromised human hosts Toxoplasmosis Increase in immunocompromised human hosts Giardiasis Increased use of child-care facilities Echinococcosis Ecological changes that affect the habitats of the intermediate (animal) hosts Bacterial Group A Streptococcus Uncertain Trench fever Breakdown of public health measures Plague Economic development; land use Diphtheria Interruption of immunization program due to political changes Tuberculosis Human demographics and behavior; industry and technology; international commerce and travel; breakdown of public health measures; microbial adaptation Pertussis Refusal to vaccinate in some parts of the world because of the belief that injections or vaccines are not safe Salmonella Industry and technology; human demographics and behavior; microbial adaptation; food changes Pneumococcus Human demographics; microbial adaptation; international travel and commerce; misuse and overuse of antibiotics Cholera Travel: a new strain (O139) apparently introduced to South America from Asia by ship, with spread facilitated by reduced water chlorination and also food

Common Types of Antimicrobial Drug Resistance

In recent years, antimicrobial drug resistance has become a serious problem in the United States and abroad. Antimicrobial resistance occurs when a disease-carrying microbe (bacteria, virus, parasite, or fungus) is no longer affected by a drug that previously was able to kill the microbe or prevent it from growing.

The types of antimicrobial drug resistance include

Antibiotic resistance. Resistance to drugs that kill bacteria or keep them from growing. Antibiotic resistance is a growing problem in American hospitals. It affects the treatment of bacterial pneumonia, TB, ear infections, and many other common bacterial illnesses.

Antiviral resistance. Resistance to drugs that prevent the replication of viruses. Antiviral resistance is a serious problem in the treatment of AIDS, which is caused by the HIV retrovirus. For instance, most strains of HIV become resistant over time to the drug AZT, which is a first-line drug against AIDS.

Antiparasite resistance. Resistance to drugs that kill parasites or keep them from growing. For example, common medicines and prophylactic treatments for malaria, including chloroquine, are no longer reliably effective because drug resistance is spreading among malarial parasites.

Antifungal resistance. Resistance to drugs that kill fungi or keep them from growing. Drug resistance has developed to the drugs for the treatment of candida infections which are common in AIDS patients worldwide.

Multidrug resistance. A bacterium, parasite, or fungus which has developed resistance to several previously potent drugs, sometimes through a non-specific mechanism that allows the microbe to eject or neutralize drugs of different chemical structures. In the United States, multidrug-resistant TB is on the rise.

Pesticide resistance. A microbe-carrying insect or animal (disease vector) becomes resistant to an agent that previously was used to kill it. The most common type of pesticide resistance is insecticide resistance. Insecticides are used in many parts of the world to kill mosquitoes that carry malaria parasites. Other insect vectors include tsetse flies (which carry parasites that cause African sleeping sickness) and reduviid bugs (which carry parasites that cause Chagas' disease, a serious disease prevalent in South America.)

Lessons Learned From the Ebola Virus Outbreak in Zaire

(Written on May 18, 1995, one week after the CDC team arrived in Kikwit, Zaire)

Researchers at CDC's biosafety level-four laboratory in Atlanta, Georgia, confirmed on May 10 that a mysterious disease outbreak in Kikwit, Zaire, was caused by the deadly Ebola virus. On the following day, the Government of Zaire informed its citizens of the danger and began to institute quarantine measures. At the government's invitation, WHO investigators arrived in the capital city, Kinshasa, on May 10, where a 3-person CDC team joined them on May 11.

A few days earlier, on May 6, the U.S. Embassy in Zaire had learned that Kikwit, an area about 350 miles from Kinshasa, was suffering an outbreak of an unusual hemorrhagic fever.

A medical professor at the University of Kinshasa reported that the symptoms of the fever patients were the same as those seen in an earlier Ebola outbreak (in 1976). The Ebola virus, which is transmitted through contact with infected bodily fluids, causes a fatal illness in 50-90 percent of its victims, and there is no known drug treatment or vaccine.

The Government of Zaire has quarantined the Kikwit area and closed the road leading from Kinshasa to Bandundu State, where Kikwit is located. The U.S. Embassy has declared the outbreak a disaster, and USAID's Office of Foreign Disaster Assistance (OFDA) has authorized the payment of $25,000 to non-governmental organizations (NGOs) in the area for the purchase and transport of disposable protective clothing, plasma, body bags, and essential medicines and supplies. OFDA has also requested a Department of Defense airlift to transport equipment and supplies, including plasma, plastic hospital gowns and sterile needles.

The Vice Prime Minister of Zaire, Kamanda Va Kamanda, accompanied the WHO and CDC doctors to Kikwit on May 12, where the international team set about its primary task of containing the outbreak of Ebola fever. As part of that effort the team is trying to trace the outbreak's first casualty to gain clues to the virus's animal or insect host (its "reservoir"). The international team has been joined by additional doctors from Zaire and elsewhere, including government and NGO medical workers from Belgium, South Africa, and Sweden.

The different national groups that make up the WHO-led international team bring different resources and types of expertise to the cooperative effort. For instance, Belgian doctors from the organization Medicins Sans Frontieres focus on providing clinical care and specialize in building and operating safe, sanitary, functional hospitals and clinics. Zairian doctors from the University of Kinshasa are familiar with most local health problems and take the lead in clinical diagnosis, case management, and clinical work-up. The CDC team provides expertise in filoviruses (the class of virus to which Ebola belongs), experience in disease surveillance and case investigation, and access to laboratory diagnosis via the facilities in Atlanta.

Lessons from Kikwit. It is useful to examine the international team's experiences in Zaire for ideas on how to improve U.S. preparedness for controlling infectious diseases outbreaks in countries with poorly developed health and communications infrastructures. One week into the investigation, the three CDC investigators report that the team's efforts are hampered by difficulties with transportation and communication, and by lack of money and personnel. Because the average incubation time (the time between infection and the appearance of symptoms) for Ebola is 7 days, each week's delay in instituting control measures means that a new generation of the virus has time to spread.

1) Transportation. To investigate suspected Ebola cases, doctors must be able to travel quickly from community to community in an area where there are few paved roads and no public transportation. The USAID mission to Zaire, which in past years could be relied on for assistance with logistics and organization, was closed in 1994. The U.S. Embassy and OFDA have provided some help, as the CDC team did not arrive in Zaire with authorization to purchase or rent cars or bicycles.

2) Money. The CDC team in Kikwit has no funds at their disposal to obtain radios, cars, bicycles, or additional medical supplies. An initial $20,000 was spent on essential equipment and medical supplies. A week into the investigation, the team has requested $781,000 to allow six doctors to work in Zaire for three months. In comparison, the team that responded to the hantavirus outbreak in New Mexico in 1994 involved 24 people working for 18 months at a cost of 4.5 million dollars. (Note: On May 23 OFDA allocated $750,000 for the CDC team and USAID's Bureau of Global Programs Field Support and Research supplied another $43,000.)

3) Personnel. The Zairian medical authorities have requested that the CDC send three additional epidemiologists and one operations/logistics manager to provide help with travel, communications, and procurement. In the United States, at CDC's biosafety level-four laboratory in Atlanta, additional technicians are needed to process the hundreds of potentially dangerous clinical samples sent from Zaire. The international team (not only the CDC doctors) are dependent upon the efforts of this unique laboratory. (Update: The funds provided by USAID/OFDA on May 23 will be used to support additional personnel in Zaire.)

4) Communication. To prevent the spread of Ebola fever, medical workers must report all suspicious fever cases to the national health authorities so that appropriate follow-up measures can be instituted. There are very few telephones and no radio station in Kikwit, although radio transmissions are received from Kinshasa. The lack of reliable communication has hampered the international team members' initial efforts to coordinate with each other and the national health authorities of Zaire.
Poor communication has been a problem from the beginning of the outbreak. Although the first case of Ebola probably occurred as early as December, 1994, the international community only learned about the outbreak in May, after the Ebola virus had nearly 20 weeks to spread. This delay reflects the weak health care systems and the poor state of infectious diseases surveillance in most of Africa. Over the last ten years, with the end of the post-colonial era, the end of the Cold War, and the decline of Western interest in tropical medicine, the public health infrastructures in many African countries have deteriorated. Infectious disease surveillance is nearly non-existent, and emerging and re-emerging diseases frequently go unreported.

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