Emerging Infections of International Public Health Importance

Objectives:

Understand the risk factors for emerging/reemerging infections internationally and their impact
Understand international conventions designed to maximize international public health security
Understand the importance of partnerships in controlling infectious diseases worldwide
Understand the other infectious disease problems facing the world in general
Understand why strong public health is the best way to detect and respond to both the naturally occurring and deliberately caused infectious diseases

This talk uses specific examples to illustrate the different factors that contribute to infectious disease outbreaks. I will also talk about some of the global surveillance networks that exist and the role they play. Finally, I will talk about some of the changes in international public health regulations as they relate to emerging infections.

This map shows some of the outbreaks involving emerging and reemerging infections in the past 6 years. What this readily demonstrates is that outbreaks are taking place everywhere in the world. Every country is vulnerable. Some of these outbreaks represent the reintroduction of diseases previously eliminated from certain areas. Others are new infections not previously seen in an area before. Still others arise from the misuse of antibiotics and the resulting selective pressure for the development of antimicrobial resistance. At WHO headquarters in Geneva, we have systems in place for the daily tracking of suspicious disease events and the verification of outbreaks of international concern. It is still difficult, however, to track all the outbreaks happening in the world, especially as many occur in remote areas beyond the reach of health services and surveillance systems.

In 2000, an outbreak of leptospirosis occurred in athletes participating in the Eco-Challenge multisports event in Malaysia. Most of the participants had already returned to their native countries before the outbreak was detected and the source of exposure identified.

This map emphasizes that travel is an important factor in disseminating diseases. This shows the dispersion of the leptospira cases, having traveled home during the silent incubation phase of the disease. Of the 309 athletes from 26 countries who participated, 109 fell ill and 25 became severely ill, requiring prolonged hospitalization. Travel history is an important factor when looking at exposure and possible diagnoses. In this example, the infection traveled around the world in humans and could have spread to others.

Malaria is a disease that is transmitted by a vector, the anopheles mosquito. This map shows the number of countries and cases of confirmed or probable cases of airport malaria. Airport malaria is malaria transmitted in a non-endemic country by mosquitoes that have "hitchhiked" on the airplane and bite persons living in the vicinity of international airports, who then acquire malaria without leaving the country. Deaths can occur because malaria is not suspected and not diagnosed in time.

This slide shows the potential exposure to the causative agent of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) from international trade. The trade was through goods exported from the United Kingdom prior to the 1990’s. BSE, or "mad cow disease", was identified in 1986 as a new disease in cattle. From 1986 until 1990 there was ongoing trade in a range of products, as illustrated here, including ruminant-derived meat and bone meal animal feed, that may have been contaminated with the BSE agent before risks to humans were identified. vCJD, the related human disease, was first identified in 1996 when restrictions on beef trade from the United Kingdom were imposed. That meant a full decade in which the causative agent was allowed to spread around the world.

This slide shows the migration of Rift Valley fever identified in Yemen and Saudi Arabia in 2000. This was the first time Rift Valley fever was identified outside the Rift valley region of East Africa. This virus has its reservoir in livestock and the disease is transmitted by mosquitoes. In 1999, the El Nino phenomenon brought increased rain and flooding. Animals and humans were crowded more closely together on islands of dryness and the mosquito population was high due to the presence of abundant stagnant water. Mosquitoes feeding on unimmunized cattle infected with the Rift Valley fever virus transmitted it to people. When these livestock were imported by Yemen and Saudi Arabia, the disease traveled with them.

In 1998 a cholera outbreak occurred in Tanzania. The European Union imports fresh-water and marine fish from Tanzania but does not have the safeguards in place to distinguish infected from uninfected fish. When news of cholera in this region became known, the EU placed a ban on imports from Tanzania. Tanzania had only one avenue to appeal the ban which was via the International Health Regulations, which are administered by WHO. The WHO Director General can conduct a risk assessment for the countries imposing a ban. This was done in the case of cholera and found there was never any risk of cholera transmission. Based on this evidence, the ban was lifted but not before huge financial costs occurred. Tanzania lost US $36 million from the unnecessary ban.

This slide shows the timeline of the Tanzania situation. It was over 6 months before the ban was lifted causing serious economic hardship for Tanzania.

This slide shows some of the infectious disease outbreaks from 1990-2000 and their economic cost to the countries involved. As you can see the BSE outbreak in the UK cost that country over US $9 billion. The Nipah virus outbreak in Malaysia cost over US $540 million. We can see from this slide that these outbreaks impose a significant financial burden on affected countries.

An additional difficulty for the economic burden of emerging and reemerging infections is that they are competing for limited dollars that also must be used to fight the ongoing infectious diseases that cause high mortality and thus have a higher profile.

This slide lists the 6 top causes of mortality in developing countries.Only one of these (HIV/AIDS) would be considered an emerging infection. The others are some of the more common infections worldwide that contribute to much of the mortality (45%) in the developing world. The newer (emerging) diseases must compete with these dollars which is a difficult task.

The emerging infections also have to compete for funding with the top infectious causes of disability, listed in this slide. Some of these diseases are currently being targeted by the international community, led by WHO, for eradication or elimination: polio, guinea worm, leprosy, lymphatic filariasis, and onchocerciasis. This, however, requires ongoing funding to support these programs to realize those goals, and such initiatives, which are time-limited, are attractive to donors.

Emerging and reemerging diseases resulting from breakdown in public health infrastructure

The following slides show the trends of some old infectious diseases that have reemerged as a result of the breakdown of public health infrastructure.

This first slide illustrates that cholera cases were under good control from 1983-1991 when there was a large epidemic in South America with the return of cholera to that country. While the rates of cholera cases have declined since then they have never returned to the previous low levels. Cholera outbreaks continue to be reported in many countries worldwide.

This slide shows the current reported cases of cholera globally. The darker the color the higher the number of cases. This slide illustrates the global nature of this disease that, until a decade ago, had been virtually non-existent in South America for almost a century.

The opening up of the borders of the former Soviet Union just after 1990 caused significant civil disturbance. This civil unrest led to the disruption of the immunization programs in the former Soviet Union contributing to an outbreak of diphtheria cases in this region. This outbreak appears under control now due to reinstitution of the immunization programs.

Yellow fever has a very good, effective vaccine available for use. However, lapses in the immunization program for yellow fever in Africa in the late 1980s resulted in a large increase in cases, with particularly large outbreaks in Burkina Faso and Ghana. With reinstitution of vaccination programs in Africa, the rates of the disease again fell to pre-epidemic proportions. WHO now coordinates a mechanism that maintains a stockpile of the vaccine, prepositioned in high-risk countries, for use in the emergency containment of outbreaks.

These 2 slides show the increase in reported dengue fever cases world wide. The resurgence of this disease is linked to decreased public health support and funding for vector control programs. Over the past five decades, incidence has increased 30-fold. A pandemic in 1998 was unprecedented in number of cases and geographical areas affected, and this trend continues. In addition to decreased public health interventions, increased urbanization and population growth also contribute some to the resurgence of dengue and its much more deadly form, dengue hemorrhagic fever.

These 2 slides contrast the countries that had meningococcal meningitis serogroup C epidemics between the early and late 1990’s. These slides show that meningitis cases increased and expanded in the so-called meningitis belt in sub-Saharan Africa. One hypothesis for this increase is the greater frequency of droughts in this part of Africa. This dryer climate is ideal for spread of meningitis in an area.

The Ebola outbreak of 1995 is another example of a breakdown in public health interventions. This graph shows the outbreak broken down by those who were health care workers and those who were not. The index case likely infected the health care workers who then became infected because of lack of basic infection control precautions. These health care workers then probably carried the disease back to their families and community. We now know that spread of Ebola can be prevented through use of isolation, strict barrier nursing, and avoidance of contact with infected body fluids.

A change in the manufacturing of meat and bone meal products in the late 1970’s likely led to the introduction of the BSE agent into the cattle industry and subsequently into the food chain for human consumption. It was thought that temperatures reached during rendering of cattle carcasses inactivated the infectious agent for BSE. However with a decline in the tallow market and change in the manufacturing process these infectious particles in contaminated meat were allowed to enter the cattle feed.

This slide shows the number of confirmed cases of human variant Creutzfeldt-Jacob disease worldwide as of August 2001. Not all of these cases are from beef consumption. Some followed infected dura mater transplants and a few were caused by contaminated hospital instruments. These figures have continued to increase since 2001 and it is unclear how the magnitude of the disease burden will evolve. The minimum incubation period is around 13 years so it may take many more years to see the peak of this epidemic.

Today there are strong concerns and fears about the intentional use of biological agents to cause disease in humans and animals. The recent anthrax cases in the United States point to this very real possibility. Many agents can be considered as biological warfare agents.

This slide shows the potential agents that are regarded by WHO as candidates for intentional use. The possibility of this happening makes it even more important to have a public health infrastructure that can recognize these outbreaks in a timely fashion and have treatment and control measures in place immediately.

The common defense of global health security requires a global partnership. This security is founded on several pillars depicted in the slide below.

Surveillance is a key component to containing a known infectious agent as well as detecting an unknown or unexpected outbreak. Several surveillance systems are in place for a variety of diseases. I will highlight a few of them here.

First the global surveillance network for human influenza virus. This is a network of 110 laboratories in 83 countries constantly monitor circulating strains of the influenza virus and serving as an early warning alert to the emergence of influenza virus variants and novel strains. They then send this information to 4 main centers that collect these data and enter them into a FluNet program. This "net" allows influenza outbreaks and epidemics to be monitored and tracked. It is also used to gather information that guides the yearly composition of influenza vaccine development. This system for influenza surveillance, which was set up by WHO in 1947, provides the model for keeping close watch over other worrisome diseases, including dengue, drug-resistant salmonellosis, and rabies.

This slide shows the various subtypes of influenza virus that are identified through surveillance and are then used for vaccine development. The trend over time shows how the viruses propagate and then disappear or mutate over time. The virus is highly unstable and undergoes a continuous antigenic drift. These viruses are recognized early in the year and then experts make their best determination of which viruses are most likely to circulate during the winter months, when influenza rates are highest. The vaccine takes 6 months to produce and distribute and this process is repeated annually in preparation for each influenza season.

Global surveillance of infectious disease is important but needs to be organized differently than surveillance for single diseases, such as influenza and dengue. This surveillance needs to be done through formal networks which are already established.

This slide shows the global surveillance networks that exist worldwide, both the formal networks as well as the informal networks. Many non-governmental organizations (NGO) and individuals reporting via electronic sites (ProMed) are an essential part of this network as well.

This slide shows the surveillance networks that exist for Asia alone and how they overlap geographically as well.

One of the most powerful networks we have is the Global Public Health Intelligence Network (GPHIN) which is based out of Canada. This is a customized search engine that continuously scans world Internet communications, including over 950 news feeds and discussion groups, for rumors and reports of suspicious disease events. Human review and computerized text mining are used to filter, organize, and classify the more than 18,000 items it picks up every day, of which around 200 merit further analysis by WHO.

This shows the outbreak of infectious diseases related to food animals over a 10 day period. GPHIN was able to pick up 9 outbreaks in this time period from a variety of countries. This shows how powerful and sensitive this tool can be. Most of these outbreaks could have been overlooked with regular surveillance.

This is one example of the utility of this network. GPHIN picked up a story of an outbreak of highly fatal respiratory illness in Afghanistan. The information was relayed to the WHO, who then did a preliminary investigation, made the diagnosis and could advise on control.

The investigation in this instance was delayed because of rebel fighting in the area. The outbreak was identified as influenza and the mortality rate was high because of secondary pneumonias.

This slide shows some of the WHO-facilitated response missions from 1998-2002. These occur worldwide but there is a propensity for many of these to be in Africa and Asia. Information is entered on a daily summary sheet which is then distributed within WHO headquarters, to regional and country offices. It gives information on the disease syndrome, where the outbreak is, and what the WHO focal points are. Once a week this list is sent out to all the partners in the global alert response and an email list of over 770 participants.

One of the key pillars is to strengthen country public health infrastructure and training so they can do the diagnosis, prevention and controls themselves.

This is an example of a public health laboratory field training program. It is a 2 year epidemiology training program for laboratory technicians selected from a variety of countries. They do an intense 6 week training course and are sent to their own country for a 2 year program.

Field epidemiology is also an important component to train field epidemiologists or non-laboratory public health personnel. This program is called the TEPHINET. It is an international network of 25 training programs in public health intervention and epidemiology. New programs in India, Japan and Jordan have recently been added. This program is jointly supported by WHO, Health Canada, and the CDC. Guidelines are developed which are then distributed worldwide which can be used by a country to help model and develop their own national guidelines.

The International Health Regulations (IHR), which are administered by WHO, provide the only legally binding framework for the surveillance and reporting of epidemic-prone diseases and the application of measures to prevent their international spread. Historically, one of the first efforts to prevent international spread occurred in 1374 with the quarantine of ships carrying plague-infected rats off the Venice harbor for 40 days until any infected humans died of plague. The current International Health Regulations have been in force since 1969 and are woefully inadequate to address the current infectious disease situation.

The 1969 IHR objective was to have maximal security against international spread of infectious diseases with minimal interruption of trade and travel and to do so by undertaking prevention measures at all ports, for travelers and transportation of goods. These regulations are applied to all countries. Reporting is officially required for only 3 infectious diseases, plague, cholera and yellow fever.

These 1969 regulations, which have undergone only slight revision, ignore more than 90% of the infectious diseases of international importance. Also, the regulations have not prevented the interruption of trade and travel as we have seen with the outbreak of plague in India.

The other drawback was the absence of an enforcement mechanism to ensure that countries reported these diseases in a timely fashion. There was little incentive. Countries that did report promptly were likely to face trade sanctions and other economic losses as a result.

The current challenges we face with revision of the International Health Regulations are:

This flow diagram shows the proposed application of the revised IHR regulations. A country or an informal network (GPHIN) provides notification of a disease of potential international importance. If able, a country should attempt to control the disease outbreak by itself. They can also ask for assistance in control from WHO when needed. These outbreaks will be reported in the Weekly Epidemiological Record. Pre-set public health measures will be recommended by WHO to the affected country.

One of the challenges to these regulations is to make sure that what is reported is of urgent international importance and thus avoid overreactions to strictly local events. We need to be able to recognize the known infectious agents and diseases as well as the unknown or unusual presentations of disease. We need to ensure enough sensitivity to identify a new or reemerging public health risk.

These 2 slides show how the revised IHR might work given a suspected infectious disease outbreak of Rift Valley fever. There are 4 basic steps: notification, coordinated outbreak investigation, risk assessment through IHR decisional tree, and recommendations for action. On the positive side, the climate for strengthened IHR is now good. Aided by GPHIN, WHO is likely to learn about a suspicious disease event promptly, regardless of whether it is officially reported. GOARN extends the promise of rapid, authoritative, and politically neutral assistance, and this is a powerful incentive to report. Prompt assistance and containment help reduce the social and economic disruption caused by outbreaks.

In summary, emerging and reemerging infectious diseases cause human death and suffering. They occur frequently or sporadically on every continent. They can travel throughout the world in humans, vectors, food and animals in less time than the usual incubation period. They are associated with high economic cost, arouse media interest and compete with funding for other infectious and non-infectious diseases.

The opportunities for partnership exist to increase and improve international public health security. They can decrease negative impact on health and economic development. There is a common opportunity to strengthen capacity to contain known infectious disease risks, detect and respond to unexpected risks and to ensure sound public health practices. Part of a strong national defense is a strong public health network and infrastructure.

Study Questions:

What have been the major factors that led to the importance of emerging infections?
What are the International Health regulations? Identify their limitations.
Define syndromic surveillance and how it can be used for prevention and control of emerging infections.