Emerging Infections of International Public Health Importance

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Module 3:  Public Health Response  
LECTURE 4 Readings


 
WHO ResponseóSARS and Emerging Infections

David Heymann, MD

Dr. David Heymann is the World Health Organizationís Representative of the Director-General for Polio Eradication. Dr Heymann was appointed as the Executive Director, Communicable Diseases in July 1998. In this post, he has been responsible for the elimination of leprosy; the control of tropical diseases; emerging and other communicable diseases surveillance and control; tuberculosis; the prevention of blindness and deafness; and research and training in tropical diseases. He is well known for his recent success in the control of the 2003 SARS outbreak.  

 

Objectives:
  1. The reasons that emerging infectious diseases are important internationally
     
  2. The ways in which international public health legislation can help in stopping the international spread of infectious diseases
     
  3. The importance of international collaboration on emerging public health issues

 

Emerging/re-emerging infectious diseases 1996-2004

The most important message about this map is not the names but that on every populated continent there has been an emerging or re-emerging infectious disease.

[Figure:   Emerging/re-emerging infectious diseases 1996-2004]

This map shows just some of the infections which occurred between 1996 and 2004. They cause a great deal of human suffering and economic impact.

In the 14th century there was a quarantine for the plague in Venice. The quarantine was designed to keep ships at bay for 40 days before they could be allowed to dock, thereby keeping plague out of Venice at the time. Since then, and especially since the 19th century, travel has become easier and more important as a means of spreading infectious agents. This slide shows the various international health regulations that have been in place since the 14th century.

[Figure:   From Quarantine to International Health Regulations]

 

International health regulations

The international health regulations (IHR) are actually a set of three guidelines. The first are the regulations themselves. The second is a guide to ship sanitation and the third is a guide for hygiene and sanitation in aviation. These guides set out norms and standards for seaports and airports. They were designed to ensure maximum security against the international spread of disease with minimal interference in world traffic. Now the International Health Regulations are outdated; they require reporting of only three infectious diseases: smallpox, plague and cholera.

This chart for the IHR in 1969 shows how the system is designed to work; it is a passive reporting system.

[Figure:   Application of International Health Regulations]

When a country reports one of the three diseases this then gets published in the WHO weekly epidemiology record and from there either predetermined measures are instituted or there is a national containment activity. These regulations leave it up to the country that has reported the disease to stop the disease but they can ask for assistance from WHO.

This map shows the different sources of information to and from WHO for disease surveillance, both formal and informal.

[Figure:   Partnerships for global alert and response to infectious diseases: network of networks]

Today there are many more diseases of concern beside the three historic diseases and we have a much wider network capability than previously. Information now comes from many different sources and not just from a government source. The current network is a partnership for global alert and response to infectious diseases.

This graph shows the WHO information sources in 2003.

[Figure:   Information sources, public health risks reported to WHO, 2003]

As you can see from this slide only 23% of infectious disease information to WHO comes from the countries that are reporting this information. Most of the information is coming from non-official sites, such as Global Public Health Intelligence Network (GPHIN). Over 70% of information comes from these other sources. Because of this we have a resolution in the World Health Assembly that asked the WHO to revise the IHR.

New revisions to the International Health Regulations have been proposed.

[Figure:   Application of International Health Regulations, Proposed revision]

The new system would take all incoming information and process it through a decision analysis tree to determine the urgency of the situation. There will be a decision made with the country or with the site that reports it whether or not they should notify this event under the International Health Regulations. It will be events that are reported, not specific diseases. Whenever there is an event that is unexpected or that could spread internationally as a risk to international trade or other sanctions, these will figure high in this framework and there will be a decision that this should be reported to the International Health Regulations.

Once the decision tree in the middle is done, then thereís either a yes or a no as to its international importance. If it is not of international importance, then just the affected country would be responsible to contain the disease. If it is of international importance, then there will be a proactive response. With respect to differences of opinion between WHO and a member State on what constitutes a public health emergency, the IHR permits the Director General to establish an expert committee composed of experts from the IHR Expert Roster and representation of the member State to review the situation. This provides for a formal process of discussion of possible differences of opinion on what constitutes a public health emergency. There are also collaborative risk-based public health measures identified and recommended by WHO.

This chart represents the decision tree analysis for the new revised International Health regulations.

[Figure:   Decision tree analysis]

This shows the process by which to determine international importance of an event.

 

SARS as an example of WHO operationalization

Here we have again the global outbreak alert and response network.

[Figure:   Global outbreak alert and response network: surveillance network partners in Asia]

The 3 most important networks in the SARS outbreak were GPHIN, FluNet and the WHO country offices. Global Pacific Health Intelligence Network (GPHIN) is a computer application which crawls the web looking at all media, discussion and open sites it can enter in several different languages looking for reports of infectious diseases. This is based on keyword finding. This is then re-examined by WHO and Ministries of Health to determine its global importance.

The SARS example started on November 16, 2002 when GPHIN reported to WHO and outbreak of a respiratory illness in Guangdong province of China. The government was recommending isolation of anyone with symptoms. On the 7 December, WHO went to the Chinese government and they reported back that there was normal influenza activity. On February 11, 2003, the GPHIN again picked up information about an outbreak of atypical pneumonia among health workers. At that time there were 305 cases and 5 deaths. Influenza was not isolated from any of them. This was concerning as that part of the world has been known as the origin of new influenza pandemics.

[Figure:   Influenza A (H2N2), Global Pandemic 1957, emergence southern China]

Because of this concern Flu Net was called into action. This is a network of 110 laboratories in 84 countries around the world that look for influenza on a regular and constant basis.

[Figure:   Surveillance network laboratory partners: FluNet]

The red shows the industrialized countries and the yellow show developing country laboratories. These are all linked into the WHO. WHO is responsible for making sure the labs all have the necessary reagents and that the testing is standardized.

After FluNet was alerted they reported on an Influenza A H5N1 case in Fujian province. We did find out there was H5N1 circulating in this region. Then on February 20, 2003 the WHO went to all country offices in Asia and requested enhanced surveillance for respiratory diseases of unknown origin. By February 26, the Hanoi office reported a businessman with high fever, atypical pneumonia and respiratory failure. He had previous recent travel to China and Hong Kong when he was already quite ill. WHO sent a epidemiology team and sent out a global alert via the alert and response network. By early March 2003 both Hanoi and Hong Kong were having cases of this new disease. In Hong Kong, 77 medical staff had the same type of illness which was unresponsive to antibiotics. By March 15, Vietnam, Hong Kong, Singapore and Canada had all reported similar cases in their hospitals. By this date the following information was known:

  • Atypical pneumonia with rapid progression to respiratory failure, none had recovered yet
     
  • Health workers appeared to be at greatest risk
     
  • Unidentified cause, presumed to be an infectious agent
     
  • Antibiotics and antivirals did not appear to be effective
     
  • No vaccine available
     
  • Disease was spreading internationally through air travel from Asia to Europe and North America
  • Most emerging infections have source in animals (often zoonotic; in the past 20 years, we have had 32 new infections that have originated form animal species.)
     
  • Once barrier between animal and human is breached, severity and transmission of illness is not known
     
  • Health workers at risk and if infected can amplify transmission and serve as point of entry into community
     
  • Occasionally an emerging infection can become endemic (i.e. influenza, HIV)
     

On March 15, 2003, the WHO initiated a global outbreak containment strategy which consisted of the following:

  • Case definition provided including clinical description , Xray findings and geographical link
     
  • Disease was named severe acute respiratory syndrome (SARS)
     
  • International travelers were informed to notify health workers if they returned from one of the affected areas with disease manifestations compatible with the case definition

 

There were several strategies that provided an important and strong response.

This map shows what these strategies were and included the global outbreak alert and response network.

[Figure:   Strategies that increased power of epidemic control: global partnerships]

From there 115 experts in 17 countries were able to assist. These experts fielded teams in five countries but also fielded people to WHO to help with the response. Telephone and videoconferencing was also set up which allowed real time communication between clinicians, epidemiologists and virologists. The sharing of information was essential to allow containment for the good of the public. In addition real time electronic communication was available using regular email systems.

[Figure:   Strategies that increased power of epidemic control: real time electronic communications]

WHO could make daily updates and provide the world with information and travel recommendations.

Here is the WHO website on SARS with the updates posted and measures taken for control.

[Figure:   WHO website on SARS]

The information accumulated between March 15 and 26, 2003 was the following:

  • Person with SARS continued to travel internationally by air, infecting some fellow passengers
     
  • Asian businessmen were returning home in good health from travel to affected areas, only to get SARS later
     
  • There were 40 international flights which carried 37 symptomatic persons with SARS; on 5 of these flights, SARS was spread to at least one other person. 9 businessmen who had contact with SARS while traveling became ill on the return home.
     

On March 27, additional travel recommendations were initiated which called for active screening of departing passengers using two questions: history of contact with a person with SARS, presence of fever, cough or other signs compatible with SARS. The countries operationalized this themselves.

The photos here show the Hong Kong airport with their screening process.

[Figure:   Exit screening, international passengers and crew, Hong Kong International Airport]

[Figure:   Exit screening, international passengers and crew, Hong Kong International Airport]

There was some concern as not all the cases in Hong Kong could be traced to another case. An environmental factor through the sewage system was thought to be the source of an outbreak of SARS at a Hong Kong apartment complex.

As with many outbreaks, the perceived risk by the public is greater than the actual risk and can cause panic and use of unnecessary precautions.

[Figure:   Perceived risk of infection by public was much greater than the real risk: panic]

Travel recommendations at this time were also expanded and it was recommended to avoid non-essential travel to areas with outbreaks that met the following criteria:

  • >60 active cases and >5 new cases reported each day
     
  • Pattern of local transmission suggesting environmental factor or that containment measures were not completely effective
     
  • Specific information such as exportation of cases or contacts

 

SARS Corona Virus

The causative agent of SARS was identified rapidly using the laboratory network. It was identified as a new corona virus. In addition to the causative agent, we have information on the case fatality rates, the transmissibility and agents that are effective in killing the virus in the environment.

The SARS corona virus has the following characteristics:

  • Fully sequenced, very distantly related to other known corona viruses
     
  • Stable at room temperature in feces and urine for 1-2 days
     
  • More stable in patients with diarrhea (higher PH)
     
  • Loses infectivity after most known disinfectants
     
  • Killed quickly at 56 degrees celsius
     
  • Very high concentration in sputum (droplet spread)
     
  • Viral RNA present in feces (fecal spread, environmental spread)
     

SARS clinical characteristics:

  • Mean incubation period of 4-7 days
     
  • Initial illness-flu-like symptoms with malaise, fever-99%, myalgia-49%, HA and rigors, diarrhea
     
  • Week 2-cough-69%, shortness of breath-42%, rapid progression into respiratory distress (20% needed intensive care), leucopenia-70%, thrombocytopenia-45%
     
  • Transmission occurs primarily in week 2 usually by day 10
     
  • Mean time to hospitalization 3-5 days
     
  • Case fatality rate: overall 14%, in age <60-13%, in age >60- 43%
     

This slide shows CXR findings in SARS patients.

[Figure:   SARS: X-ray findings]

This is an epidemiology curve of the SARS outbreak from March 1-June 27, 2003.

[Figure:   Probable cases of SARS by date of onset worldwide, 1 March - 27 June 2003]

It shows the typical epidemiology of an infectious outbreak with primary and then secondary cases. As you can see the outbreak really started in December or January but was missed, possibly because of confusion with influenza outbreaks at the same time. The second and third spike show the number of cases from the original spread and did not really become contained until July 2003.

This slide shows the suspected source for 80% of the cases of SARS.

[Figure:   SARS: international amplification and transmission by guests at Hotel M, Hong Kong, 21 Feb -26 Mar 2003]

These were traced back to a hotel in Hong Kong. The source was a professor who came from Guangdong; he stayed on the 9th floor and infected people on that hotel floor. Sampling from his room found viral RNA in the carpet. After the exposure, people then traveled back to their respective countries, taking the infection with them.

This map shows the cumulative SARS cases as of June 2003 totaling 8460 cases and 808 deaths and where these occurred.

[Figure:   SARS cumulative number of probable cases worldwide as of 25 June 2003]

Results of the airport screening measures at the Hong Kong Airport showed that:

  • More than 1930 travelers reported sick on their declarations
     
  • 79 (4.1%) of them required hospital referral
     
  • 23 were admitted to the hospital
     
  • 2 were confirmed with SARS and prevented from international travel
     
  • Confidence was restored in business and other international travelers
     

The graph here shows passenger movement from Hong Kong international airport before and after the travel advisory.

[Figure:   Passenger Movement, Hong Kong International Airport, Mar-Jul 2003]

The rebound to pre-advisory levels was fairly rapid likely as a result of the confidence in the system that was put in place.

The strategies that helped contain the SARS outbreak were as follows:

  • Case identification (active surveillance)
     
  • Case isolation/hospital infection control measures
     
  • Contact tracing and quarantine if necessary
     
  • Surveillance and quarantine
     
  • International travel recommendations based on epidemiological evidence
     
  • Element of good fortune: did not spread to countries with weakest health systems
     

This slide shows a strategy that existed between public health and police system in Hong Kong

[Figure:   Strategies that contained SARS outbreaks: collaboration between public health and police system, Hong Kong]

The police has a database to track crime and could show clustering. The public health system set up an office in the police department, and entered the information they had on cases and did pick up several clusters. The slide shows one of these clusters from a restaurant where one case went and infected others. This was a very useful tool to rapidly identify clustered cases.

SARS was a costly disease but due to good cooperation and containment the cost output was short lived.

[Figure:   The cost of SARS: initial estimates for six month outbreaks, Asian Development Bank, 2003]

The Asian Development Bank estimated that SARS decreased Asiaís combined GDP by $18 billion and it cost the economies nearly $60 billion in lost demand and revenues. The good news is that there was rapid recovery once the outbreak was under control.

The following are ongoing international programs, prevention and control measures for SARS:

  • Continued case identification through surveillance--this is necessary to determine if the disease is now endemic, is seasonal or whether it has disappeared from the human population
     
  • Continued collaboration studies in Guangdong province to identify the animal reservoir and risk factors for transmission to humans--this is necessary to manage the risk of transmission to humans and prevent future outbreaks
     
  • Continued research and development--for diagnostic tests, vaccine development, antiviral medication
     
  • Continued global surveillance for influenza ad other emerging infectious diseases--need to identify the next major emergence of new influenza strain or other infection of international importance

 

Global Influenza: the ongoing emerging infection

We will now look briefly at influenza as an emerging infection. The great influenza pandemic of 1918-1919 is thought to have been caused by Influenza A (H1N1) and infected half of the world population at the time. It is estimated that 40 million people died worldwide; 500,000 deaths were in the US, >5 million deaths in India. The highest mortality was among young adults (20-30 years old). There was no vaccine available in those days or any antibiotics to treat secondary bacterial infections.

The table here shows the influenza outbreaks of last century with the number of deaths noted on the far right of the chart.

[Figure:   Influenza pandemics and recent outbreaks, 1918 - 2004]

This slide shows the hypothesis with how the 1957 Asian flu epidemic may have occurred with fowl and human genomes reassorting in an intermediate host (the swine); the H2N2 virus was able to pick up other genes and became a highly transmissible and highly pathogenic virus to humans.

[Figure:   Influenza pandemics and recent outbreaks: 1957 Asian Flu]

In the United States, in a non-epidemic year it is estimated that 30 million people are infected. The majority have a 7-10 day illness with high fever, cough, HA, muscle pain, and sore throat. An estimated 150,000 are hospitalized and there are 20,000-40,000 deaths per year. The estimated cost for influenza is $10 billion annually.

This global map shows the FluNet surveillance system in place.

[Figure:   Global surveillance of human influenza: Participating networks and laboratories, 2002]

This network continues to work year round for influenza, including new strains. It was also helpful in the SARS outbreak as well. The 110 laboratories transfer the information to one of 4 collaborating laboratories in Atlanta, London, Tokyo or Melbourne. The viruses are then analyzed in these 4 labs, looking at the genetic sequencing in order to provide this information to vaccine manufacturers of the influenza vaccine

This graph shows the antigenic shift and drift of influenza and the various components for vaccine from 1968-2002.

[Figure:   Antigenic shift and drift of influenza virus: vaccine composition, 1968-2002]

Each year in January/February there is a meeting of the vaccine manufacturers to make a decision as to what strains will go into the next seasonís vaccines. It takes 6 months to produce the influenza vaccine

 

Influenza A: 1997 Hong Kong outbreak

In 1997, there was an unknown influenza virus isolated in Hong Kong which turned out to be H5N1. This was the first time this strain was seen outside of birds. The humans who were infected were placed on reverse isolation and kept away from poultry as well as other people. The outbreak was controlled by this method as well as by the culling of millions of chickens.

[Figure:   1997 Avian Influenza Hong Kong ; destruction of chickens]

This slide shows the first attempt at global surveillance and pandemic planning.

[Figure:   Influenza A(H5N1), Hong Kong 1997: a first attempt at global surveillance and pandemic planning]

This graph shows the Hong Kong Investigation into the possible vectors and infected animals for the H5N1.

[Figure:   H5N1 investigation, Hong Kong, 1997]

 

Influenza outbreak in Madagascar 2002

Influenza outbreaks occur in developed and developing countries, and there was an outbreak in Madagascar in 2002. There were over 27,000 cases of influenza reported from mid-July to September. Of these there were 838 deaths primarily in children. The predominant strain was Influenza A, which in this outbreak had a <1% case fatality rate.

 

Prevention and Control of Influenza

As you have discussed in your previous lecture on influenza, one of the most effective strategies for prevention and control of influenza is vaccination of the at risk population.

This map shows the estimated influenza vaccine coverage in 2000.

[Figure:   Estimated influenza vaccine coverage, 2000]

(Note that there is a lack of vaccine coverage among developing nations who cannot afford this vaccine on an annual basis.)

There are some difficulties with the vaccine as the main prevention strategy:

  • Annual vaccine production is time intensive--takes 6-8 months to produce
     
  • Vaccine efficacy and content is constantly changing--so needs to be done annually
     
  • Antiviral drug production has a limited market and has high cost
     
  • Usually only 250 million doses of vaccine are produced annually
     
  • Uncertainty of epidemiology of influenza in developing countries

 

Where do we go from here?

Avian influenza may be the new pandemic, right around the corner.

[Figure:   Avian Influenza, poultry, 2004: the start of the next pandemic?]

With continued global cooperation and collaboration we will be much better able to identify, contain, control and prevent emerging infections as they continue to be present in our societies.

 


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