DEFINITION OF EMERGING INFECTIONS
GLOBAL BURDEN

COSTS

DEATHS
THE FACTORS OF EMERGENCE:


HUMAN DEMOGRAPHICS AND BEHAVIOR
TECHNOLOGY AND INDUSTRY
ECONOMIC DEVELOPMENT AND LAND USE


Ebola
INTERNATIONAL TRAVEL AND COMMERCE


Dengue


HIV
MICROBIAL ADAPTATION AND CHANGE


Tuberculosis
DECLINE OF PUBLIC HEALTH


Food Safety


COMMUNICATION NETWORKS

Readings

Institute of Medicine definition of emerging infections

New, reemerging or drug resistant infections whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future

Institute of Medicine Report, 1992

This is the Institute of Medicine definition. Most infectious diseases could be fit in here. So the definition isn’t really very helpful because it doesn’t rule anything out.

New infections are emerging over the entire expanse of the globe. Wherever you find people, you will find the emergence of infections. The risk of emergence is not confined to poor countries:as shown by the E. coli epidemic in Japan, one of the most affluent economies in the world. There are global pandemics of HIV and cholera, and we in the US of course have annual influenza. We compiled all of the Asia-Pacific Promed reports (a very good email-based service for the early warning of infections) over the last two years to demonstrate that our neighborhood is also heavily impacted by the emergence of new infectious diseases.

Click here for Promed information

Surveillance and diagnostics are not uniform, thus the information we’re working on is imperfect.

  COSTS

Costs of common infectious diseases can be broken into treatment, or direct costs and indirect costs which are lost time from work or lost work due to death or disability.

The US has estimated the cost in lost productive activity.in this country alone:

Disease	Estimated Cost
Intestinal infections	$23 billion in direct medical costs, lost productivity
Food Borne diseases	$5-6 billion in medical and productivity costs
Sexually Transmitted Diseases (excluding AIDS)	$5 billion in treatment costs
Influenza	$.5 billion in direct costs and $12 billion in lost productivity
Antibiotic Resistant bacterial infections	$ 4 billion in treatment costs (and increasing)
Hepatitis B infection	$720+million in combined direct and indirect costs

These are costly infections and therefore worthy of political notice. In the last congressional session, the USAID received an additional $50 million appropriation, which is a lot for that agency, simply to address emerging infections.

  DEATHS

1 in 5 deaths worldwide are due to infections, according to the Centers for Disease Control. This recent study by Murray looked at all the worldwide death in 1990. they found that 14.4 million were related to infectious diseases or perinatal disorders. However, the problem with international mortality classification, is that only 30% of deaths worldwide are clinically diagnosed. The other 70% are ‘well, we think it was this,’ or estimated from what happened when the hospital deaths were projected over to the whole country, so that here the information is particularly imperfect." One thing to keep in mind is that infectious diseases have been the major cause of death in many parts of the world forever. I gave a talk on emerging infections in the Central African Republic two years ago, and they said, ‘well, this is very interesting, but emerging infections for whom?

The factors of emergence: what are they, and how do they work? The factors of emergence refers to the outline, but this is a theoretical construct, and there has been very little empiric testing.

How would you test this hypothesis, which is that changes in human demographics and behavior, increased numbers of people, and urbanization have an impact on the emergence of disease. Empirically, you say ‘of course, that’s common sense.’ When you move to the cities, there is more people concentrating. It simply must have an impact on the emergence of disease. How do you actually prove that? We haven’t seen any interdisciplinary project funded to look at these aspects, but there are bits of information that suggest that this is the case.

Other factors include economic development and land use, technology and industry, international travel and commerce, microbial adaptation and change and the breakdown of public health measures..

Even though technology and industry, are supposed to be good things, our ability to lyophilize blood products and transport them over borders had a lot to do with infecting hemophiliacs with HIV when we had a tainted blood supply and were the major exporter of factor VIII. So technology can be a two-edged sword. If you didn’t have the ability to do very sophisticated Duramater transplants in neurosurgery, you wouldn’t have any cases of BSE in Thailand or Japan due to this transplant issue. So medical technology and our ability to transport biological and human material probably also has a role in the dissemination, transportation and emergence of new diseases.

Technology and industry also alter land use patterns in ways that contribute to emergence. Deforestation is an example of land use patterns that have contributed to emergence. Logging in the equatorial rain forest has forced people into areas they didn’t visit previously and they are being exposed to things in terms of simian viruses that they haven’t been exposed to before.

  Ebola
Land use changes that prompt exposure to new vectors and diseases are thought to be one of the factors related to Ebola, although the reservoir for Ebola still has not been identified.

The experience with Ebola, involves a number of emergence factors. First, the Kikwit outbreak had been going on for 3 or 4 months before anybody took notice of the fact that hundreds of people were dying in this relatively small town. Health care workers were absolutely key to the spread of Ebola in Kikwit, due to the lack of fresh tap water in the hospital. People had to bring water in. This makes isolation nursing much more difficult.

The question of international transmission of Ebola is interesting . In subsequent outbreaks the Kikwit region has been quarantined to prevent people from leaving. However in the Sierra Leone outbreak, a grandmother got on the train because she was afraid she was sick, went to the capital to see her daughter, her daughter realized that she had Ebola, put her back on the train. She went on these very crowded trains to the area of the outbreak and died of Ebola. In the course of her travels she had exposed about 150 people per train ride over a large part of the country. Yet there was very little transmission. Ebola seems to be hard to catch.

This shows you on the left the epidemic curve of Ebola patients and shows you the healthcare workers in green and the major role that they played because of their very intimate contact with body fluids. On the right, there is a more schematic discussion of how that transmission occurred. This shows that you really had to have very direct contact. As soon as they instituted barrier nursing, they had a drop-off in transmission.

We know that TB transmission is able to occur on long flights. We know that 400 million people per year travel now internationally, so we’re having an increasing incidence of risk being able to transmit not only Tuberculosis but Influenza, which has been documented to be transmitted on airplanes. These are new things that are coming into disease transmission—means of transportation.

  Dengue

Dengue fever in Africa, just as Dengue fever all over the world, has changed. We’re seeing major Dengue epidemics throughout the world's tropical regions. Compare Africa prior to 1990 when Dengue and epidemic transmission was confined to Nigeria. During the epidemic transmission of 1991-1994 Dengue has become much more widespread on the continent. Although most of the talk that we will hear on Dengue will focus on Asia and the Americas and the problems of our region, it’s not confined to the new world.

Dengue has been rapidly increasing throughout the Americas. (compare reports up to 1981 to those for 1991-1995) Historically we have had outbreaks of Dengue back to the 1700’s as far north as Philadelphia, so although it’s not a new disease or a new virus or new pattern for our country, it is one that is new in this particular century. This is a classic example of vector control failure (map of the vector Aedes aegypti, Aedes albopictus in the United States) compounded by the factors of emergence. The movement of people and the movement of goods both have impacted the spread of Dengue in our region and in Asia.

The vectors have been travelling by barge. Old rubber tires are being shipped from market to market by barge. They are in demand in less developed markets as usable tires. The tires containing little pockets of water create a perfect microenvironment for the breeding of Aedes aegypti. As they were shipped from place to place in the Caribbean. This was an absolutely perfect way to move those mosquitoes around. There are now public health regulations that call for the pest removal in rubber tire cargoes before they are shipped internationally. However, like most of our public health regulations, it was closing the barn door when the cow was already out.

There are four Dengue serotypes viruses. We used to have one for each geographic zone, and now we’ve had enough mixing through air travel that we have all four in every tropical zone. This is what’s referred to as "hyperendemicitiy". The serotypes traveled by airplane in human hosts. Dengue really is a classic example of how we have enhanced the breadth and speed of epidemic transmission through our activities. The serotype moved within the human and the vector moved through human activity.

  HIV

Another classic emerging infection is HIV. Although HIV is transmitted only through sexual or blood contact in the period of a decade it went all the way around the global community and infected every inhabited continent.

We’re still not having 100% blood screening around the world for HIV. (moderate 70-99% -lower 50-79%) You can see that we have a long way to go in terms of screening the blood supply around the world.

Until recently trade in biologicals was very important to the transportation of HIV. The major source of infection in a country like Costa Rica was through hemophiliacs who were infected through tainted product from the United States.

In Asian-Pacific scenarios, we have already exceeded the 1993 worst case projections for 1997. This is going to impact emerging infections in ways that we don’t really understand.

The emergence of resistant organisms is an international problem. The problem involves all different kinds of microbes utilizing a number of different genetic mechanisms.. We trying to understand exactly what the Pacific Rim factors are in terms of exposure to antimicrobials. We believe there is pressure coming from the administration of antimicrobials, either directly or from residuals in our food. More than half the supply of antimicrobials is veterinary for growth enhancment. You can’t be a chicken and not be on tetracycline your entire life in this country.

We face the emergence of Superbugs—Streptococcus and penicillin, Gonococcus and quinolones, Staphylococcus and vancomycin, tuberculosis and isonizid, rifampin, malaria and chloroquine, mefloquine—different kinds of bugs, different kinds of mechanisms, but they’re all getting less treatable. This falls under the rubric of emergence because we believe it’s due to human activity changing the ecological pressures in the creation and administration of antimicrobials. Big hospitals are a great place to create increased resistance, especially the staph drug resistance.

This ties into the breakdown of public health. We have no monitoring program for the emergence of resistance. Certain sentinel groups in certain states are now monitoring certain bugs, however there is no systematic prospective surveillance for the emergence of resistance. Our data is largely confined to special studies. WHO found that of the 33 international collaborators that were to look at drug resistance in TB, 3 were in the Asia Pacific, and only one of those reported; the United States. There may not even be the capacity to create a test for Tuberculosis resistance in many of the economies around Asia Pacific. There is a shift in emergence of drug resistance from hospital acquired to community acquired since the 1950’s. Thus we definitely have a need for some kind of community-based systems that are prospective and relatively rapid turn-around.

  Tuberculosis

Tuberculosis is one of the oldest recognized infections in humankind. Its one that we’re extremely familiar with but seem to not be able to vanquish, nonetheless.

I believe that most of our TB drug resistance here in Seattle-King County is foreign born. Folks go back to their home country and sometimes become infected during family visits. Then they bring a new or partially treated infection back with them. The only certification that you need to have to come into the United States is that your Tuberculosis has been treated, but there’s no guarantee that it’s been completely treated. This is the most common scenario for all the west coast cities in the United States as well as for Auckland, New Zealand, Sydney, Australia. Most of this seems to be coming from the Philippines and Vietnam, where there’s a lot of empiric treatment of Tuberculosis by the people themselves. The diagnosis of Tuberculosis is a great stigma in the Philippines so when people begin to cough and lose weight and say that they have "bad lungs". The drugstores in the Philippines dispense an over-the-counter medication for "bad lungs" called "Rifaavite", which is rifampin and vitamins. This incomplete treatment is part of the reason why we’re seeing so much resistance coming from people emigrating from the Philippines. However they are not certainly the only place where resistance is manufactured. Recently New York City did a great job of manufacturing resistance by partially treating Tuberculosis. It’s not strictly a problem that happens elsewhere in the world.

WHO recently did a cross-sectional study of 33 international centers and documented what they call the "hot spots" of Tuberculosis. The emergence of tuberculosis resistance is not only caused by the lack of complete and adequate treatment. The HIV epidemic in Asia also confounds the treatment of Tuberculosis. As many of you know, the cellular arm of immunity, which is that which is attacked by the HIV virus, is also that primary host-response for Tuberculosis in other microbacterial infections.

International travel now moves 400 million people annually, the pace of travel is more rapid, commerce, as we have talked about, has also grown. This has occurred at the same time as the decline of international and national public health.

During the late 1970’s as the International Monetary Fund and World Bank moved internationally to shore up economies, especially in Latin America and Africa, they forced a reduction in public sector investment. This eliminated a lot of people from the ministries of health in Latin America and Africa during those years. There is a huge debate over whether this actually had a negative impact on public health. The bank has published figures showing that these countries were economically better off in two years time than they had been. The other side of this debate says, as a result of the loan conditions the public health sector didn’t have the capacity to respond to x, y and z, immunization levels dropped, nutrition dropped, etc. A similar reduction in public health funding was seen in this country at the same time.

There is a serious lack of diagnosis and treatment in many areas of the world. In Kikwit, the Ebloa outbreak went with very high mortality for quite a while before there was really a serious alarm. That’s because Meningitis outbreaks sweep through that part of the country regularly and kill hundreds to thousands of people along the Meningitis belt. Mortality is not unusual. Lack of access to treatment is not unusual. It has become something that is not as shocking as it really needs to be, because after a while, if there’s no capacity to address a continuing problem, people have to accommodate to it.

  Food Safety

With the emphasis on free trade, the opening of new markets, new providers for food and increased trade in foodstuffs, we begin to see food associated problems that we had not seen before. Although import and export is one factor, highly consolidated food processing has also contributed. Hence the emergence and distribution of E. coli 0157:H7 .

Atypical Jacob Creutzfeldt, Bovine Spongiform Encephalopathy, has emerged in the UK as a food safety problem along with E. coli, Salmonella and other more traditional pathogens. There have been only been 23 or 24 cases of this new variant of Jacob Creutzfeldt (a degenerative neurological disease which is basically untreatable - it was generally thought to be a disease of older people). It was thought to be related to some kind of a slow virus, but the etiology is unknown. In Great Britain they began to see clusters of cases occurring in young people who had a lot of beef exposure. The biology of the prion which is thought to be the causing agent for this problem is not at all clear. It seems to have a very long incubation period. For example, one case occurred in a woman who was a vegetarian after 1985. She died this year. This implies that if it’s really coming from beef, either she was getting beef from some other source like gelatin capsules or it has a long incubation period. If it has such a long incubation period, since the major epidemic of mad cow disease occurred in the mid-1980’s, we’re still not at the end of that human epidemic in the UK. That is the basis on which beef exports from Great Britain were halted. The United States doesn't accept beef or beef products from Great Britain or from any European country unless they have surveillance in place for this problem.

The safety assurance that we can provide through public health, even through FDA inspection, etc., has not kept pace with changes in the industry.

(globalization of the food supply).

We need to understand the risks so that we can communicate about emerging infections, and we also need to collaborate a lot more effectively in science across economies. That’s going to take a new infusion of resources and a new vision of how important this is. To get the political mandate to create that new system of international public health is going to take an additional vision from Capitol Hill. I think that the appropriation to the USAID and enhanced appropriations to NIH and CDC emerging infections could best be in both an international and domestic approach to this problem.

Our project at the University of Washington is to link through a telecommunications network to the 19 major Asia Pacific economic cooperative countries. We’re trying to get these countries, which are primarily interested in making money through free trade, interested in the idea that trade needs to be safe. If you’re going to enhance trade and travel in the region, you have to be sure that your public health infrastructure is adequate to address and enhance that activity. The European Union is way ahead of us. They are much closer geographically, more homogenous, the economies there are close historically, and they’ve been able to cooperate and collaborate a lot more expeditiously. Our "community" extends around the Pacific Rim, speaks many different languages, practices different religions, has different ways of doing things, and covers a much broader range of wealth as demonstrated by the GNPs.

The US Government has helped improve communications by launching an interagency process called CISET. The CISET process allows the USDA and the FDA to talk to the CDC and the NIH and the USAID and even the CIA and the military. Finally there is a new unit at the WHO. It’s unique in the history of the WHO as the first unit that promises to be in place at any outbreak of a new emerging infection that’s causing mortality within 48 hours.

Remember, don’t put anything in your mouth if you don’t know where it came from or where it’s been. This involves food safety. If you go to your supermarket produce department during the dead of winter, you know that the produce didn’t come from your own state and you know there’s no infrastructure for inspection in many of the exporting countries. Even though International law says that country is responsible for guaranteeing the quality of product. Keep your immunizations up, support public health in your community.

Readings:

Emerging Infections 1992 Report (Textbook), Institute of Medicine, pp.34-117.

New York Academy of Sciences. Disease and Evolution: Global Changes and Emergence of Infectious Diseases. M.E. Wilson ed. "Globalization, Development, and the Spread of Disease: The Harvard Working Group on New and Resurgent Diseases". Vol. 740, pp. 160-170.