Global Health: Framework for Infectious Disease Surveillance
(Correspondence, 07/20/2000, GAO/NSIAD-00-205R).

Pursuant to a congressional request, GAO examined the global infectious
disease surveillance framework, (with particular emphasis on its
operations in developing countries), focusing on: (1) functions involved
in infectious disease surveillance and response framework.

GAO noted that: (1) primary functions in infectious disease surveillance
include detecting and reporting cases of disease in target populations,
analyzing and confirming this information to identify outbreaks and
clarify longer-term trends, responding to outbreaks when they occur, and
supporting longer-term management of disease control programs; (2)
global surveillance and response efforts are carried out through a loose
framework of formal, informal, and ad hoc arrangements linking numerous
entities, including elements of national health care systems, as well as
the media and internet discussion groups, laboratories and other
institutions participating in disease and region specific networks, and
nongovernmental organizations; (3) national public health authorities
bear basic responsibility for surveillance functions; (4) on the global
level, the World Health Organization, an agency for the United Nations,
plays a central role; (5) the organization works to strengthen national
and international surveillance capacity and coordinates international
efforts to monitor disease trends and detect and respond to outbreaks;
(6) the Centers for Disease Control and Prevention and the Department of
Defense make significant contributions to these global efforts--for
example, through assisting in outbreak response; (7) foreign assistance
agencies, including the multilateral development banks, such as the
World Bank, and the Agency for International Development, as well as
private foundations, are important sources of support for strengthening
surveillance capacity around the world; and (8) this support is
generally provided within programs aimed at other objectives, such as
control of specific diseases.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  NSIAD-00-205R
     TITLE:  Global Health: Framework for Infectious Disease
	     Surveillance
      DATE:  07/20/2000
   SUBJECT:  Infectious diseases
	     International cooperation
	     Public health research
	     Developing countries
	     Disease detection or diagnosis
	     International organizations
IDENTIFIER:  DOD Global Emerging Infections Surveillance and Response
	     System

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GAO/NSIAD-00-205R

B-285759

July 20, 2000

The Honorable Mitch McConnell

Chairman

The Honorable Patrick Leahy

Ranking Member

Subcommittee on Foreign Operations

Committee on Appropriations

United States Senate

The Honorable Bill Frist

Chairman

The Honorable Russell Feingold

Ranking Member

Subcommittee on African Affairs

Committee on Foreign Relations

United States Senate

Subject: Global Health: Framework for Infectious Disease Surveillance

In its simplest terms, public health experts define disease surveillance as
the generation of "information for action." Infectious disease surveillance
provides national and international public health authorities with
information that they need to plan and manage efforts to control the
diseases.

In recent years, public health officials have expressed concern about the
adequacy of the global framework for infectious disease surveillance. In
1995 both the World Health Assembly (the governing body of the World Health
Organization) and the U.S. National Science and Technology Council
determined that, in light of the global public health threat posed by
infectious diseases, existing surveillance arrangements could not be
considered adequate. Both organizations, for example, found serious
deficiencies in the ability of health systems to diagnose infectious
diseases and investigate their sources and modes of transmission. Since
then, concern about the framework's capacity has increased as public
dialogue has intensified on HIV/AIDS, West Nile fever, and other infectious
disease threats to U.S. and global public health.

In view of this ongoing concern, you asked us to examine the global
infectious disease surveillance framework, with particular emphasis on its
operations in developing countries, since infectious diseases are an
especially grave problem in these countries. This letter constitutes the
first portion of our response to your request. As agreed with your offices,
it describes (1) functions involved in infectious disease surveillance and
(2) key entities and their roles in the global surveillance and response
framework. In the spring of 2001 we intend to provide you with a second
report analyzing the framework's strengths and weaknesses and proposals for
improving its performance.

RESULTS IN BRIEF

Primary functions in infectious disease surveillance include detecting and
reporting cases of disease in target populations, analyzing and confirming
this information to identify outbreaks and clarify longer-term trends,
responding to outbreaks when they occur, and supporting longer-term
management of disease control programs.

Global surveillance and response efforts are carried out through a loose
framework of formal, informal, and ad hoc arrangements linking numerous
entities, including elements of national health care systems, as well as the
media and internet discussion groups, laboratories and other institutions
participating in disease- and region-specific networks, and nongovernmental
organizations. National public health authorities bear basic responsibility
for surveillance functions. On the global level, the World Health
Organization, an agency of the United Nations, plays a central role. The
organization works to strengthen national and international surveillance
capacity and coordinates international efforts to monitor disease trends and
detect and respond to outbreaks. The U.S. Centers for Disease Control and
Prevention and the U.S. Department of Defense make significant contributions
to these global efforts - for example, through assisting in outbreak
response. Foreign assistance agencies, including the multilateral
development banks, such as the World Bank, and the U.S. Agency for
International Development, as well as private foundations, are important
sources of support for strengthening surveillance capacity around the world.
This support is generally provided within programs aimed at other
objectives, such as control of specific diseases.

BACKGROUND

National security and public health experts agree that infectious diseases
pose a substantial direct and indirect threat to U.S. interests. In the most
direct sense, experts point out that these diseases pose an increasing
danger to the health of the U.S. population. For example, travelers from
disease-endemic areas enter the United States every day before sufficient
time has passed for them to display symptoms of diseases that they may have
contracted while abroad. Infectious diseases also pose a substantial
obstacle to U.S. efforts to encourage economic growth and betterment in the
lives of the poor in the developing world. According to the World Health
Organization (WHO), infectious diseases like malaria and tuberculosis
account for about half of all premature deaths in the world, and nearly
two-thirds of deaths among children under 5 years of age. Infectious
diseases are a particular problem in developing countries. Malaria alone,
for example, kills more than 1 million people each year, most of them in
Africa, and imposes an immense burden in terms of days of productive labor
lost to illness. Furthermore, as the National Intelligence Council has
observed, there is an indirect but real relationship between high rates of
infectious disease and political instability.

Public health experts at institutions such as WHO and the U.S. Centers for
Disease Control and Prevention (CDC) point out that effective action to
monitor and control infectious diseases has become more difficult in recent
years because of the emergence of new diseases and the reemergence of
diseases that were formerly considered to be under control. In the past 3
decades, more than 30 previously unknown diseases have been identified,
including Ebola and a number of other deadly hemorrhagic fevers. Yellow
fever and tuberculosis, among others, have resumed their former status as
major threats to public health. Excessive, uncontrolled use of antimicrobial
drugs has complicated the picture further by encouraging the evolution of
disease strains that are highly resistant to known forms of treatment.
Figure 1, which shows some of the hundreds of disease outbreaks of
international public health importance identified by WHO since 1994,
provides a sense of the challenge now facing international public health
authorities.

Figure 1: Selected Outbreaks of Emerging and Reemerging Infectious Diseases,

1994-99

Note: Enclosure I provides information on these diseases and others
mentioned in

this letter.

Source: WHO.

INFECTIOUS DISEASE SURVEILLANCE FUNCTIONS

Infectious disease surveillance is an essential task for public health
authorities in every country. This task involves four primary functions. The
first of these is detecting cases of disease in the population and reporting
this information so that it can be used in public health decision-making.
The second is analyzing and confirming reported information to detect
outbreaks and identify longer-term disease trends. The third function is
providing timely and appropriate responses to disease outbreaks. Finally,
surveillance involves providing information to assist in longer-term
management of health care policies and programs. Each of these functions is
an integral part of disease surveillance.

Detecting and Reporting Disease

The most basic surveillance functions are detecting disease in the
population being surveyed and reporting relevant data so that the data may
inform public health decision-making. A variety of approaches to performing
these functions are available, including passive and active surveillance,
and "sentinel" and "syndromic" reporting. These approaches are not mutually
exclusive - they can be, and often are, combined to provide a fuller
understanding of the incidence of infectious disease in a target population.

"Passive" surveillance is the most broadly employed approach. In this
approach, national or district-level authorities prepare a list of
"notifiable" diseases, guidelines for diagnosing these diseases, and
specifications for information to be gathered when these diseases are
detected (for example, the patient's age and the date of onset of disease.)
National or district level authorities then rely upon local health care
providers to detect cases of disease and report information on these cases
as specified. When instituting passive reporting requirements, national or
district authorities must make arrangements for collecting this information
from localities throughout the country or region. Public health experts at
WHO commented that responsible authorities should also create feedback
mechanisms to let health care providers know that the information they are
providing is being put to use. Feedback, in the form of regular bulletins on
epidemiological trends, progress toward disease control targets, or efforts
to control outbreaks, can help motivate health care providers to continue
investing the effort required to meet reporting requirements.

Deciding which diseases should be "notifiable" is a key element in this
process. WHO's International Health Regulations require member countries to
monitor only

three diseases: cholera, plague, and yellow fever. Beyond this, each country
must decide upon a list of diseases that will be subject to regular
reporting. In the United States, more than 50 diseases are considered
"notifiable" at the national level. Developing country lists are usually
less extensive. For example, the Ethiopian Ministry of Health had 17
diseases under surveillance as of 1999. Developing countries commonly
emphasize diseases that the donor community has targeted for control or
outright eradication, including polio and other vaccine-preventable
diseases.

"Active" surveillance is often employed to help compensate for the reporting
shortfalls commonly encountered in passive reporting arrangements. In this
approach, health workers from the district or national levels "make the
rounds" to seek out possible cases. Such efforts are commonly made to ensure
complete reporting in situations where an epidemic is occurring or is deemed
likely to occur or during campaigns to eradicate individual diseases. For
example, active surveillance has been a prominent feature of the
international campaign to eradicate polio. These efforts may be organized
into regular surveys.

"Sentinel" reporting is also employed to supplement the information obtained
through broadly focused passive reporting. Sentinel reporting relies on
comparatively small numbers of specially equipped practitioners to provide
information on diseases of particular concern. One common example is the
enlistment of sexually transmitted disease clinics to monitor HIV incidence
through blood testing. Sentinel reporting is particularly useful for
generating "early warnings" of changes in disease patterns, including the
emergence of new diseases.

"Syndromic" reporting is another tool that can be employed to increase a
system's effective reach - at a cost of reduced specificity in the
information reported. In this approach, health care providers are asked to
report syndromes - that is, collections of symptoms - rather than attempting
to make exact diagnoses that are beyond their capacity. This can be
particularly useful in developing country settings where health care
providers may have very limited ability to make firm diagnoses themselves or
to refer questionable cases to laboratories for rapid clarification.

Analyzing and Confirming Disease Information

Public health officials at the district, national, and (in some cases)
international levels are responsible for aggregating and analyzing
information reported from lower levels. These activities often extend to
providing laboratory analysis and other investigative assistance to confirm
or clarify initial diagnoses made by individual health care providers -
especially in developing countries where local diagnostic capacity is often
quite limited. Higher-level data aggregation is particularly important where
cases are too dispersed in time or location to be recognized at the local
level.

In carrying out these analyses and investigations, responsible officials
examine disease information along three basic dimensions: person, time, and
location. In other words, they seek to clarify who is getting sick, when
they are getting sick, and where. Epidemiologists use this information to
calculate rates of sickness and death in specific populations and at
specific times, and to compare these rates over time and location. In
combination with identifying the pathogens causing particular illnesses, the
answers to these questions provide a basis for taking action. For example,
by analyzing who was getting sick and when, public health officials in the
former Soviet Union were able to determine that a 1990-95 resurgence of
diphtheria had been caused by gaps in the diphtheria immunization program.

Public health officials responsible for analyzing and interpreting disease
data must proceed with caution. Among other things, these officials must
take into account the proportion of disease cases health care providers are
likely to detect and report. This is affected by such factors as the
likelihood that persons with certain health conditions will seek medical
care. People with sexually transmitted diseases, for example, may be
reluctant to seek treatment. To complicate matters, these proportions are
subject to change. For example, increased public concern about a particular
disease may increase the likelihood that people who believe they have this
disease seek treatment -- and that health care providers report seeing these
patients. One of the first steps that an official faced with an apparent
increase in reporting of a particular disease must take is to determine
whether this increase might be due to such changes.

Responsible officials must also take into account the likelihood of health
care providers being able to make accurate diagnoses. Even in advanced
countries like the United States, attaining a high degree of certainty in
patient diagnoses can be a challenge. Health care providers may be
unfamiliar with some diseases, or they may lack the ability to distinguish
among diseases with similar symptoms. Health care providers rarely have
immediate access to comprehensive laboratory facilities, and, in developing
countries in particular, may lack training in making diagnoses and access to
even the simplest diagnostic tests.

WHO guidelines for clinical (that is, symptom-based) diagnosis of dengue
fever provide a sense of the difficulty of making confident diagnoses. WHO
defines a clinical case of dengue fever as an acute illness of 2-7 days'
duration characterized by fever and two or more of a number of other
symptoms. Several of these, like headache, rash, and muscle or joint pain,
may be caused by a number of other disease agents, in addition to the dengue
virus. WHO officials noted that national or district public health officials
can increase the reliability of diagnostic reports from the field by
ensuring that health care providers throughout the country or region employ
clear, consistent case definitions.

Responding to Epidemics

In addition to detecting unusual patterns of disease and investigating their
causes, responsible public health officials must determine the likely
seriousness of an epidemic in medical and socioeconomic terms and, in
cooperation with others, devise and carry out appropriate response measures.

The likely course of events in any given epidemic will vary depending upon
the pathogen involved and local circumstances - including weather,
prevailing living conditions, and the effective reach of existing public
health facilities. Public health officials who have an understanding of the
likely course of events in a given situation will be in a better position to
develop an appropriate response. Ebola hemorrhagic fever and meningococcal
meningitis - two diseases of particular concern in Africa - provide an
instructive comparison.

According to WHO officials, most Ebola transmission takes place through
direct physical contact with the skin or mucous membranes of persons
currently sick with this disease. Consequently, Ebola outbreaks actually
endanger relatively small numbers of people and can be halted relatively
easily through application of containment measures in the affected locality.
Meningococcal meningitis, in contrast, is most often acquired through
inhaling respiratory droplets from infected but asymptomatic carriers of the
disease. The disease presents a high risk of widespread transmission,
especially in dry weather when people's mucous membranes become irritated.
Africa's meningitis belt countries experience periodic epidemics that cross
national boundaries to infect large numbers of people. Proper responses to
these epidemics include mass vaccination of threatened populations and the
delivery of appropriate medicine to large numbers of sick people.

Epidemic response measures include interventions designed to ensure that
persons already sick with a disease receive proper care and to reduce or
eliminate further transmission. One element in such a response may be
procurement and distribution of diagnostic materials (and associated
training) that will permit health care providers to identify disease
pathogens faster and with more certainty. Both health care providers and
members of the public (who may need to care for sick family members) may
require instruction on appropriate case management techniques - that is, how
to care for persons infected with the disease in question. In major
epidemics, it may become necessary for public health officials to simplify
normal approaches to case management in order to permit the health system to
cope with unusually large numbers of patients. Health systems may need to
rapidly expand available treatment facilities and provide them with supplies
of antimicrobial drugs, vaccines (if appropriate), and other materials that
may be needed to combat the epidemic. Logistics - that is, managing the
procurement, delivery, and distribution of these supplies - can be a major
challenge.

Effective communication with concerned members of the public is an important
element in epidemic response. An epidemic's direct consequences (that is,
sickness and death among those who contract a disease) may be substantially
amplified by adverse public reaction. Unconfirmed, misinformed, or
incomplete announcements can confuse health care providers and members of
the public alike and prompt them to take inappropriate actions. In
cooperation with the media and with the support of national leaders, public
health officials must work from the earliest moment to provide the public
with accurate information on the disease's transmissibility and means of
treatment.

Effective epidemic response can require the participation of many elements
of society, including (in addition to health care providers) political
leaders at varying levels of authority, nongovernmental organizations, and -
in some situations -- representatives from the agricultural, veterinary,
environmental, public works, law enforcement, and transportation sectors.
WHO officials therefore strongly recommend creation of epidemic response
committees to coordinate action by all parties. This is particularly
important in developing countries where, because of local institutional
weaknesses and lack of resources, outside agencies such as WHO and CDC are
likely to play a vital role in epidemic response.

Reassessing Longer-term Policies and Programs

Surveillance systems are important sources of information for longer-term
management of health programs at all levels. Over the long term,
surveillance system can provide public health authorities with insight into
changing disease patterns. For example, surveillance systems are providing
international public health authorities with information on the worldwide
spread of HIV/AIDS and strains of tuberculosis that are resistant to
antimicrobial drugs. Information on such trends can be used to inform
decision-making on health care priorities and associated resource allocation
decisions.

Surveillance systems are also important tools in monitoring, assessing, and
refining disease control interventions. At the international level, the most
well-known example is the use of surveillance to manage the ongoing effort
to eradicate polio. Surveillance data are also important inputs to
decision-making at the national and local levels. For example, continued
surveillance was important in assessing the impact of revised vaccination
practices adopted in the wake of the diphtheria epidemic in the former
Soviet Union which was mentioned earlier in this letter. Officials at the
U.S. Agency for International Development (USAID) and WHO observed, however,
that developing countries' surveillance efforts often do not produce
information that can be relied upon to document changes in the health impact
of major diseases or the impact of disease control programs.

GLOBAL SURVEILLANCE: A NETWORK OF NETWORKS

As acknowledged in the previous discussion of surveillance functions, basic
responsibility for monitoring and responding to disease trends lies with
national governments around the world. On the global level, however, disease
monitoring and response functions are carried out through a framework of
formal, informal, and ad hoc arrangements that WHO officials characterize as
a "network of networks." In addition to public health officials in
ministries of health and national disease control centers in individual
countries, key entities in this framework include (1) WHO, (2) the media and
internet discussion groups, (3) disease and region-specific networks (which
include infectious disease laboratories), (4) nongovernmental organizations,
and (5) foreign assistance agencies and private foundations. However, since
support for surveillance activities is generally provided within programs
aimed at other objectives (like control of specific diseases), these
organizations could not readily estimate their overall expenditures for
surveillance activities. Figure 2 presents one illustration of this global
framework. A brief overview of the key entities follows.

Figure 2: Global Surveillance of Communicable Diseases: A Network of
Networks

Source: WHO.

The World Health Organization

WHO plays a central role in the global disease surveillance and response
framework. However, WHO officials are quick to point out that the
organization cannot perform these functions alone - they place great
emphasis on their role in marshaling and coordinating relevant efforts by
multiple parties, including technical and donor agencies around the world.

WHO itself can be regarded as a network of organizations, as it is organized
along both geographic and functional lines. WHO maintains six regional
offices. Each of these maintains a network of country representative offices
and formulates policies and undertakes initiatives within its own area of
the world in line with WHO's global priorities. With regard to surveillance,
for example, WHO's Western Pacific Regional Office is working to strengthen
influenza surveillance and epidemic response planning in its region, while
WHO's regional office for the Americas is encouraging integration of disease
surveillance activities among countries that share the Amazon River basin,
as well as in other regions of Latin America.

Within WHO's Geneva headquarters, the Division of Communicable Diseases
plays a central role. The Division's mission is to "strengthen national and
international capacity in the surveillance, prevention and control of
infectious diseases." However, other headquarters units also make
contributions. For example, the Department for Vaccines and Biologicals
coordinates worldwide efforts to control vaccine-preventable diseases.
Strengthening national and global surveillance for these diseases is an
important element in this office's work. Similarly, WHO maintains a separate
department for HIV/AIDS and other sexually transmitted infections, and
surveillance is a key element in this office's mission as well.

To strengthen surveillance and control at the national level, WHO generates
and disseminates standards and guidelines for creating, operating, and
assessing national disease surveillance systems and supports and
disseminates the results of research into surveillance and control issues.
WHO works with national governments to assess and redesign national
surveillance strategies and to improve surveillance capacity through, for
example, training in epidemiologic and laboratory techniques and emphasizing
improved communications. At the regional and global levels, WHO collaborates
with numerous other organizations to create, maintain, and improve networks
of laboratories and other institutions and administers the International
Health Regulations.

In 1997, WHO created an "outbreak verification" mechanism in order to
generate timely, accurate information on disease outbreaks around the world
and to provide the organization with a basis for encouraging a rapid and
coordinated response. The system draws from multiple sources -- including
the Global Public Health Intelligence Network, a worldwide web search engine
developed and maintained by Health Canada. When suspected outbreaks of
international importance are identified, WHO staff seek confirmation from
health authorities in the countries involved and others who may have
knowledge of the events in question. Outside laboratories like those
maintained by CDC are often asked to perform analyses to identify the
pathogens that are causing the outbreak. Having clarified the situation, WHO
disseminates accurate information on the outbreak and works to organize a
response. Response efforts can involve numerous partners. For example, the
response to one epidemic of unexplained origin in Kenya and Somalia, later
determined to be Rift Valley fever, involved representatives from 31
different governmental and nongovernmental agencies, including elements of
CDC and the Department of Defense. Enclosure II provides more detail on this
outbreak.

The Media and Internet Discussion Groups

Nongovernment sources - including the media and Internet discussion groups -
are playing an increasingly important role in infectious disease
surveillance and response. For example, WHO has found that 71 percent of the
outbreaks confirmed through its outbreak verification procedure in a recent
2-year period were initially reported through informal or unofficial
sources, including the media and Internet discussion groups, as well as
nongovernmental organizations.

As agents of a government-sponsored body, WHO officials must normally obtain
country consent before disseminating information on outbreaks. WHO officials
note that their efforts to verify - and notify - infectious disease
outbreaks in a timely manner have sometimes been delayed by national
governments concerned about the potential adverse consequences of
acknowledging that outbreaks are taking place in their countries. However,
the expansion of media coverage and, especially, electronic communication
via the Internet, is decreasing the likelihood that national officials can
successfully keep outbreaks hidden for any length of time.

As in so many other areas, Internet discussion groups have become an
important means of sharing timely information on infectious disease events
and trends around the world. A number of disease-specific and regionally
focused surveillance networks (described at greater length later) maintain
such discussion groups. For example, organizations and individuals
interested in eradication of dracunculiasis (guinea worm disease) share
information through a WHO-maintained Internet discussion group known as
"Dracerad." Others groups are more generally focused. One of these - ProMED
- is particularly important. A program of the International Society for
Infectious Diseases, ProMED was created in 1994 to establish a direct
relationship among scientists and doctors around the world by making it
possible for all to share information and discuss emerging disease concerns
on a timely basis. More than 18,000 people subscribe to the ProMED
listserve, which provides information on human, animal, and plant diseases.
The system generates approximately seven postings per day, 7 days a week.
While ProMED accepts information from any source, expert moderators screen
this information before it is posted.

While making a contribution to timely outbreak identification, the media can
also contribute to effective outbreak response. According to WHO, for
example, the local affiliate of the British Broadcasting Corporation made a
valuable contribution to the international response to the previously
mentioned Rift Valley fever outbreak in East Africa. The affiliate's
broadcasts both drew attention to the problem among national and
international authorities and helped provided the public with accurate
information about the epidemic. According to USAID, the Voice of America has
increased its reporting on health issues of interest in developing
countries, including infectious diseases of particular concern, like
HIV/AIDS, and outbreaks in these countries.

Disease-specific Networks

To encourage the advancement and efficient application of expertise on
specific diseases (or categories of disease), WHO has fostered the creation
of international networks focusing on specific types of disease. Infectious
disease laboratories form the core of these networks. As already indicated,
laboratory support is a critical element in infectious disease surveillance,
but capacity to provide this support is unevenly distributed around the
world and is particularly lacking in developing countries. Networking helps
make these laboratory facilities accessible to the global community.

Examples of formal global networks include those focusing on influenza,
polio, and antimicrobial resistance. These networks perform a variety of
functions. For example, laboratories in 83 countries participate in WHO's
global Influenza Program, which monitors the evolution and global
distribution of influenza virus and applies this information to make annual
recommendations concerning the composition of influenza vaccines. One
hundred and forty-eight laboratories around the world participate in the
Global Network for Polio Eradication. Participating laboratories cooperate
to confirm suspected cases of polio and to distinguish among strains of the
disease. These analyses provide the basis for appropriately targeted
response measures when polio cases are confirmed and help participating
scientists to advance global understanding of the evolution of the polio
virus - laying the groundwork for more effective response measures in coming
years. In collaboration with the French National Institute for Health and
Medical Research and the United Kingdom's Department for International
Development, WHO recently inaugurated an "Anti-Microbial Resistance
Information Bank" - an internet service that is intended to encourage
greater collaboration among antimicrobial resistance monitoring efforts
throughout the world.

Public health professionals with whom we spoke noted that, in practice,
informal networking among laboratories is often the key to addressing
pressing problems. For example, in the fall of 1998, Malaysia experienced a
sharp increase in cases of illness and death from a disease that was
initially identified as Japanese encephalitis. However, in March 1999,
scientists at the University of Malaysia determined that a different viral
agent was likely causing the outbreak. Finding themselves unable to
precisely identify this agent, the Malaysian scientists contacted CDC for
assistance. Malaysian personnel subsequently traveled to CDC's Division of
Vector-Borne Infectious Diseases in Fort Collins, Colorado with samples for
analysis. Laboratory work at the Colorado facility advanced the
investigation, which concluded when staff from the CDC's National Center for
Infectious Diseases in Atlanta, Georgia, identified the previously unknown
pathogen, named the "Nipah" virus, that had caused the outbreak.

Many of the institutions that participate in these networks have been
designated as official WHO "collaborating centers." WHO collaborating
centers provide training, research, consulting, and other forms of service
to assist the organization in pursuing its objectives. Approximately 1,300
institutions carry this designation, though WHO officials observed that
these institutions vary considerably in their ability to contribute to
international operations. WHO's Department of Communicable Disease
Surveillance and Response maintains active relationships with approximately
270 of the centers. Figure 3 displays one set of WHO collaborating centers.

Figure 3: WHO Collaborating Centers for Arboviruses and Hemorrhagic Fevers

Note: An arbovirus is one that is transmitted by mosquitoes or other
arthropods. These include the pathogens that cause yellow fever and dengue.
Enclosure III contains a list of the collaborating centers shown on this
map.

Source: WHO.

Contributions From the Centers for Disease Control and Prevention

With 30 WHO-designated collaborating centers focused on particular
infectious diseases and with five research centers abroad, CDC constitutes
the single largest pool of expertise and resources available to the
international system. As of the spring of 2000, nearly 90 staff members were
working abroad on infectious-disease related matters. CDC devoted
approximately $100 million in fiscal year 1999 to international activities
related to infectious disease surveillance, control, and prevention,
including laboratory analysis to identify pathogens involved in outbreaks of
international significance. CDC could not provide a separate accounting for
surveillance activities alone. CDC has been an active participant in WHO
efforts to provide epidemiology training to developing countries. For
example, it has helped to establish national field epidemiology training
programs in over 20 countries.

Military Networks

Particularly in developing countries, military health care systems may have
capacities that match or exceed those available in the civilian sector.
Countries with substantial worldwide commitments have an especially strong
incentive to develop the capacity of their military health care systems in
order to protect their own personnel around the world. WHO is working to
encourage cooperation in surveillance activities among laboratories
worldwide that are operated by national military establishments.

Contributions From the U.S. Department of Defense

The U.S. Department of Defense plays a noteworthy role in global
surveillance and response through its Global Emerging Infections
Surveillance and Response System. This system links the Department's
overseas laboratories and its service-specific preventative medicine
programs in a coordinated program focused on contributing to timely
recognition and control of emerging and reemerging infections. The
Department maintains medical research laboratories in five foreign countries
(Egypt, Kenya, Indonesia, Peru, and Thailand). According to Defense
officials, these laboratories assist in conducting surveillance for
influenza, drug-resistant malaria, intestinal organisms, and hemorrhagic
fevers and help to build local capacity around the world. The Department's
research facilities in Indonesia and Egypt and three facilities in the
United States have been designated as WHO Collaborating Centers for
infectious disease. The Department budgeted approximately $7 million to
support Global Emerging Infections Surveillance and Response System
activities during fiscal year 2000.

Region-specific Networks

With WHO's encouragement, public health authorities in a number of regions
have fostered the creation of regional surveillance networks. In 1996, for
example, the secretariat of the Pacific Community launched the Pacific
Public Health Surveillance Network to improve surveillance and response in
the Community's 22 member states and territories. One prominent feature of
this network is the sharing of surveillance data through the Internet. This
is also a prominent feature of some other subregional networks, such as the
European Union's Eurosurveillance project and the Mekong Basin Disease
Surveillance System. Twenty-one Caribbean countries benefit from the
activities of the Caribbean Epidemiology Center. This center - a
decentralized unit of WHO's regional office for the Americas -- provides a
range of epidemiological and laboratory analysis services to participating
countries.

While Internet capacity is extremely limited in Africa, this continent is
nonetheless the location of some of the more ambitious efforts to encourage
subregional cooperation for more effective surveillance and response. In the
wake of the major meningitis epidemics in 1995 and 1996, WHO fostered the
creation of an International Coordinating Group on Vaccine Provision for
Epidemic Meningitis Control in the African meningitis belt countries. This
group, which includes concerned national governments, nongovernmental
organizations, and makers of vaccines and other medical supplies, works to
improve meningitis surveillance and foster greater preparedness for epidemic
response in this region. WHO's Africa region is also encouraging greater
collaboration for surveillance within five subregional "epidemiological
blocks" that face similar sets of disease challenges. According to WHO
officials, this effort involves creation and implementation of national
plans to strengthen surveillance as well as the establishment of subregional
laboratory networks, and the promotion of improved communications among
public health officials within these "blocks." This effort emphasizes the
integration of existing, disease-specific surveillance operations.

Nongovernmental Organizations

Nongovernmental organizations play a vital role in disease surveillance and
control in many developing countries. Even when "normal" conditions prevail,
many people in the world's poorest countries do not receive health services
from government-supported clinics or private practitioners but from
organizations such as Doctors Without Borders and Catholic Relief Services.
Because they constitute the professional presence in the field, these
organizations conduct surveillance and participate in outbreak response
efforts when necessary.

These organizations play a particularly vital role in the increasing portion
of the world that is plagued by complex humanitarian emergencies --
humanitarian crises in countries or regions where there has been total or
considerable breakdown of authority resulting from internal or external
conflict and where a situation has developed that requires action going
beyond the mandate or capacity of any single agency. These emergencies may
last for many years. According to WHO, about half of all disease outbreaks
of international importance are now occurring in such situations. With some
noteworthy exceptions (Kosovo, Afghanistan, and East Timor) most of the more
than 100 million people currently affected by such emergencies live in
Africa. According to WHO, populations in 11 African countries are affected
by complex emergencies. Figure 4 illustrates the living conditions generated
by such an emergency in the eastern portion of the Democratic Republic of
Congo in 1997.

Figure 4: Complex Emergency Conditions: Refugees in Eastern Democratic
Republic

of Congo

Source: S. Collins, through WHO.

Responsibility for arranging a humanitarian response to complex emergencies
falls to the U.N.'s Office for the Coordination of Humanitarian Affairs,
and, according to WHO, this organization usually relies upon either WHO or
the United Nations Children's Fund to coordinate the health sector portion
of these responses. However, responsibility for actually delivering health
services - and hence front-line responsibility for disease surveillance -
most often falls to health-oriented nongovernmental organizations. In
southern Sudan, for example, where government services ceased functioning
years ago, nongovernmental organizations, including Doctors Without Borders
and Oxfam, provide such health care services as are available.

Given the difficulty of detecting and addressing disease in these
populations, such outbreaks may generate high levels of death and disease
before they are addressed. For example, a cholera outbreak in eastern
Democratic Republic of Congo in 1994 killed 12,000 people in 3 weeks. In the
same region several years later, a measles outbreak spread to over 1,000
children before being detected.

Foreign Assistance Agencies and Private Foundations

Foreign assistance agencies like the USAID and the multilateral development
banks, as well as private foundations, are important sources of support for
strengthening surveillance activities - both within individual developing
countries and at regional and global levels. However, because these
organizations most often support surveillance activities as elements within
(a) programs aimed at controlling or eradicating specific diseases or (b)
broadly focused health sector improvement or infectious disease control
programs, it is difficult to estimate the amount of funds that they provide
for surveillance as such with any precision.

For example, over the last 30 years many organizations, including the World
Bank, the African Development Bank, USAID, and private companies and
foundations, have supported an intensive effort to eradicate river blindness
- a disease that was once endemic in much of Africa. A portion of the more
than $500 million devoted to this cause to date has gone toward
surveillance, but an estimate of the portion devoted to this purpose is not
available. Surveillance activities have also received substantial support
through donor assistance to international initiatives aimed at (among other
things) eradicating guinea worm disease, addressing the global HIV/AIDS and
tuberculosis pandemics, and controlling vaccine-preventable diseases. The
international campaign to eradicate polio, in particular, has focused donor
resources on establishing functional polio case detection and response
mechanisms in every country, no matter how limited these countries' general
surveillance capacity.

We identified a few major foreign assistance agency efforts to improve
national infectious disease control programs, with substantial emphasis on
upgrading surveillance. For example, the World Bank is providing a total of
approximately $150 million to strengthen the national infectious disease
surveillance and control systems in Argentina and Brazil. The Asian
Development Bank is providing $87 million to support a similar effort in
Indonesia. Many other agency-supported projects contain surveillance
components. For example, the African Development Bank identified
surveillance components in 15 current projects aimed at a variety of
purposes, including creating national health management systems and
strengthening disease-specific control or eradication programs. USAID
identified about $11 million in support for surveillance-specific operations
within a variety of country-specific and regional health sector programs
during fiscal year 1999. However, agency officials noted that this figure
does not present a complete picture of USAID investments in surveillance. It
does not include surveillance support provided through other programs,
including those focused on child survival and on specific diseases such as
polio, tuberculosis, and HIV/AIDS, where meaningful separation of
surveillance funding from funds devoted to other purposes is quite
difficult.

From 1998 through 1999, "extrabudgetary" funds - that is, contributions from
foreign assistance agencies and private foundations - provided more than 70
percent of the $28.2 million budget of WHO's Department of Communicable
Disease Surveillance and Response. Donor contributions and temporary
assignment of personnel from technical agencies such as CDC have enabled
this office to more than double its staffing level. Financial support from
foreign assistance agencies and private foundations has also made possible
initiatives like that currently being undertaken to strengthen surveillance
and response capacity within subregional epidemiological blocks in Africa.
The WHO Africa regional office's project to introduce integrated disease
surveillance in the West African epidemiological block, for example, is
being supported by (among others) USAID, the European Union, the United
Kingdom's Department for International Development, and the Rockefeller and
United Nations Foundations.

AGENCY COMMENTS

We received oral comments on a draft of this report from the Departments of
State, Defense, and Health and Human Services (including CDC); USAID; the
offices of the U.S. Executive Directors of the World Bank, the Asian
Development Bank, and the African Development Bank; and the World Health
Organization. These institutions stated that the report provided an accurate
overview of surveillance functions and correctly identified and described
the roles played by major participants in global infectious disease
surveillance. Some of them provided technical corrections and proposed
language changes, which we incorporated as appropriate. CDC and USAID
suggested that we expand upon the discussion of the roles that they play in
the global framework. USAID also recommended that we provide more
information on difficulties commonly encountered in trying to carry out
effective surveillance operations in developing countries. We inserted some
additional information on relevant activities of CDC and USAID, as well as
the problems often encountered in conducting infectious disease surveillance
in developing countries.

SCOPE AND METHODOLOGY

To assemble the information required to produce this letter, we consulted
with senior officials from WHO's Geneva and regional offices, CDC, the
Departments of State and Defense, USAID, the multilateral development banks
(the World Bank, the Inter-American Development Bank, the Asian Development
Bank, and the African Development Bank), public health institutions in the
state of Maryland, private foundations, and nongovernmental organizations.
We examined documents generated by all of these institutions, including case
histories of specific disease outbreaks. We obtained funding information
from the U.S. agencies just cited, WHO, and the multilateral development
banks.

We conducted our work from January through June 2000 in accordance with
generally accepted government auditing standards.

- - - - -

As agreed with your offices, unless you publicly announce the contents
earlier, we plan no further distribution of this report until 2 days after
its issue date. At that time, we will send copies of this report to
interested congressional Committees; the Honorable Madeleine K. Albright,
Secretary of State; the Honorable Donna Shalala, Secretary of Health and
Human Services; the Honorable Lawrence H. Summers, the Secretary of the
Treasury; the Honorable J. Brady Anderson, Administrator of USAID; the
Honorable William Cohen, the Secretary of Defense; Dr. Gro Harlem
Brundtland, Director General of the World Health Organization; and other
interested parties. We will also make copies available to others on request.

Please contact me on (202) 512-4128 if you or your staff have any questions
concerning this report. Key contributors to preparing this report were Lynne
Holloway, Michael McAtee, Ann Baker, Kay Halpern, and Ashley Bander.

Jess T. Ford, Associate Director

International Relations and Trade Issues

DISEASE INFORMATION

This enclosure provides descriptive information on the diseases mentioned in
the body of the letter. This information is derived primarily from WHO
documents and was reviewed for accuracy by officials from CDC.

African trypanosomiasis, also known as sleeping sickness, is transmitted
through the bite of the tsetse fly and can last for a few weeks to a several
years. Early signs include fever, general weakness, headaches, and an aching
sensation. Later symptoms include sleep disturbance, confusion, or
convulsions, leading to permanent lethargy, coma, and death if left
untreated. It is estimated that 300,000 people in 36 sub-Saharan African
countries suffer from this disease. Available treatments are costly and
dangerous, and some are losing their effectiveness. In addition, some drugs
are no longer available.

Anthrax, a bacterial disease of animals, can be transmitted to humans in
three ways, with varying results. Entry through the skin causes localized
infection, and, if untreated, leads to death in 20 percent of cases.
Inhalation generally leads to shock and death 1 to 2 days after the onset of
acute symptoms. Anthrax occurs after the consumption of contaminated meat
and causes inflammation of the intestinal tract, nausea, vomiting of blood,
and severe diarrhea, with death occurring in 25-60 percent of cases. Anthrax
can be treated with antibiotics and can be prevented through vaccination.
The disease is present in agricultural regions worldwide.

Brucellosis, a disease of animals, is transmitted to humans through contact
with infected animals or contaminated milk. Infection produces a wide range
of symptoms, including fever, generalized aches and pains, and fatigue,
which may last from a few weeks to several months. Brucellosis responds to
the same antibiotics used to treat tuberculosis and is beginning to exhibit
a similar drug resistance. The disease occurs worldwide.

Cholera is caused by a water- and food-borne bacterium. Infection results in
acute watery diarrhea, leading to extreme dehydration and death if left
unaddressed. Known vaccines and antibiotics have only limited impact on the
disease - treatment focuses on rehydration. According to CDC, recent cholera
outbreaks have killed about 1 percent of those becoming ill. A major
international public health problem, cholera is prevalent in over 80
countries and causes over 100,000 deaths each year.

New-variant Creutzfeldt-Jakob disease was first described in March of 1996.
The disease is believed to be transferred through consuming products from
cows infected with bovine spongiform encephalopathy (mad cow disease). As of
December 1999, there have been 50 reported cases, primarily in Great
Britain. The disease starts out with depression or, less often, a
schizophrenia-like psychosis. As the disease progresses, unsteadiness and
involuntary movement occur, and shortly before death an infected person is
rendered immobile and mute.

Crimean-Congo hemorrhagic fever is transmitted through tick bites or contact
with bodily fluids of infected animals or people. It was first identified in
1944 in the Crimea and has been found in Africa, Asia, the Middle East, and
Eastern Europe. Symptoms are many and varied but can include hemorrhage,
fever, dizziness, stiffness and muscle pain, nausea, mood swings, and sore
eyes. This disease has a fatality rate of 30 percent. Blood transfusions and
the drug ribavirin have been beneficial in treating the disease. A vaccine
has been developed and used on a small scale but is not considered safe and
effective for wider use.

Cryptosporidiosis is caused by a microscopic parasite. It can be spread
through contaminated water, uncooked contaminated foods including fruits and
vegetables, and any surface that has been in contact with the parasite. The
parasite can survive outside the body for long periods of time and resists
chlorine disinfection. Symptoms include diarrhea, stomach cramps or upset
stomach, and a slight fever. People with weak immune systems may have more
serious reactions. There is no effective treatment.

Dengue fever, a mosquito-borne infection caused by four distinct but closely
related viruses, is a severe, flu-like illness with specific symptoms that
vary based on the age of the victim. Dengue hemorrhagic fever is a
potentially lethal complication that may include convulsions. There is no
treatment for dengue fever beyond supportive therapy. With treatment,
fatality rates can be less than 1 percent; without it, they can exceed 20
percent. There is no vaccine. Dengue is endemic in more than 100 countries
and generates an estimated 50 million cases every year.

Diphtheria is a respiratory disease occurring worldwide that is spread
through human-to-human contact. Symptoms range from mild to severe and can
be complicated by damage to the heart muscle or peripheral nerves. The
disease is fatal 5-10 percent of the time, even with treatment by
administration of antibiotics and diphtheria antitoxin. Untreated, the
fatality rate can be much higher. There is an effective vaccine for
diphtheria, which is typically provided through national childhood
vaccination programs.

Escherichia coli O157:H7 is a harmful strain of a bacteria commonly found in
the gut of warm-blooded animals. It appears mainly in cattle and can be
spread to humans through improperly prepared beef or milk products, as well
as through other foods or the water supply. Symptoms can include abdominal
cramps and watery or bloody diarrhea, usually without fever. Treatment with
antibiotics is not recommended and may lead to more serious complications.
According to CDC, about 3 to 5 percent of patients develop serious
complications that can lead to kidney failure.

Ebola hemorrhagic fever, a viral disease, is transmitted by human-to-human
contact, causing acute fever, diarrhea that can be bloody, vomiting, and a
variety of other symptoms. There is no known cure, though some measures,
including rehydration, can improve the odds of survival. Ebola kills more
than half of those it infects. The Ebola virus was identified for the first
time in 1976 and is still considered rare but has caused a number of
outbreaks in central Africa.

Echinococcosis, also called Alveolar Hydatid disease, is caused by a
parasitic tapeworm found worldwide but mostly in the Northern Hemisphere.
Humans become infected by swallowing the tapeworm eggs, either on
contaminated food, or after contact with an animal carrier. Symptoms are
slow to appear and usually involve the liver. They mimic liver cancer or
cirrhosis and can include abdominal pain, weakness, and weight loss. Surgery
is the most common form of treatment, although follow-up medication is often
needed.

Encephalitis -- inflammation of the brain -- can be caused by a variety of
infectious organisms.

Enterovirus 71 is one of several causes of hand-foot-mouth disease. This is
a moderately contagious disease that is transmitted through human-to-human
contact. Symptoms include fever, poor appetite, sores in the mouth, and a
rash with blisters. It can lead to encephalitis. It occurs mainly in young
children, but adults may also be at risk. The disease occurs worldwide, and
there is no specific treatment for it beyond relief of specific symptoms.

Guinea worm disease, formally known as dracunculiasis, is transmitted in
water contaminated with parasite larvae. The mature parasite conducts a
painful journey through the body, usually emerging through the foot with
intensely painful swelling and blistering. Perforation of the skin is
accompanied by fever, nausea, and vomiting, and an infected person can stay
ill for several months. Fatalities are rare, but secondary infection and
permanent deformity can occur. According to CDC, the disease is present in
13 African countries.

HIV/AIDS: Human Immunodeficiency Virus is a disease of the immune system
that leads to AIDS -- Acquired Immunodeficiency Syndrome. Weakened immune
systems mean a greater susceptibility to opportunistic diseases like
pneumonia and tuberculosis. The disease is transmitted through contact with
bodily fluids of infected persons. Drugs are available that can prevent
transmission from pregnant mothers to their unborn children. These same
drugs can help slow the disease. As of December 1999, 33.6 million people
worldwide were living with HIV/AIDS.

Hendra virus causes disease in both humans and many species of animals. In
humans, it causes a respiratory disease that is often fatal. It was
discovered in 1994, and is not found outside of Australia.

Human monkeypox is caused by a virus related to smallpox and is susceptible
to the smallpox vaccine. Since the smallpox vaccine is no longer used,
monkeypox is becoming an increasing concern in Central and Western Africa.
It is transmitted to humans through contact with infected animals and
appears to be increasingly transmittable through human-to-human contact.
Fatality rates have ranged between 2 and 10 percent.

Influenza, or flu, is a respiratory infection caused by three types of
virus, of which two (Influenza types A and B) lend themselves to epidemics
and are found worldwide. There is an influenza vaccine, but the viruses
change so quickly that the vaccine must be updated every year. Several drugs
exist to treat influenza.

Japanese encephalitis is a mosquito-borne viral disease. Infection can be
mild, with only fever and headache, to severe, with neck stiffness, stupor,
tremors, spastic paralysis, and coma. There are 30,000 to 50,000 cases
annually, with a 30-percent fatality rate. The disease occurs primarily in
Asia and is not treatable beyond supportive therapy. There is a vaccine
available, but it is expensive and occasionally causes adverse reactions.

Lassa fever is caused by a virus transmitted through contact with infected
rats. It occurs in Africa and was first described in the 1950s. Symptoms
include deafness, fever, nausea, vomiting, diarrhea, and, in more severe
cases, seizures and hemorrhage. This disease has a fatality rate of 15
percent and is difficult to distinguish from several other diseases. No
vaccine is currently available, although ribavirin has been used as a
preventative measure as well as to treat the disease.

Leishmaniasis, a parasitic disease transmitted by sandflies, is endemic in
88 countries, affecting an estimated 12 million people. There are four
types. Visceral leishmaniasis is the most severe form, causing irregular
bouts of fever, weight loss, swelling of the spleen and liver, and anemia.
If untreated, it has a fatality rate of almost 100 percent. Mucucutaneous
leishmaniasis produces disfiguring lesions on the mucous membranes.
Cutaneous leishmaniasis produces ulcers on exposed parts of the body and can
lead to permanent scarring or disfigurement. Diffuse cutaneous leishmaniasis
never heals on its own and often relapses. Leishmania/HIV co-infections
occur frequently.

Leptospirosis is a bacterial disease transmitted via the urine of infected
animals contaminating water, food, or soil. It occurs worldwide but is most
common in temperate or tropical climates. According to CDC, this disease is
particularly difficult to diagnose. Symptoms can include fever, chills,
muscle aches, vomiting, diarrhea, hemorrhage, and respiratory failure. Some
cases progress to a second phase, which can include kidney or liver failure
or meningitis. In rare cases, death occurs. Leptospirosis is treatable with
antibiotics, especially when given early in the course of the disease.

Lyme borellosis, or Lyme disease, is a bacterial illness transmitted by
ticks. The area around the tick bite develops a "bull's eye" rash, typically
accompanied by fever, headache, and musculoskelatal aches and pains. If
untreated by antibiotics, arthritis, neurologic abnormalities, and, rarely,
cardiac problems follow. It is rarely, if ever, fatal. There is an effective
vaccine for adults at high risk.

Malaria is a tropical parasitic disease, transmitted by mosquitoes and
endemic in 101 countries and territories. About 40 percent of the world
population is considered at risk for malaria. Ninety percent of the cases
are in sub-Saharan Africa, but malaria is now reemerging in countries where
it was once under control. Symptoms include fever, shivering, pain in the
joints, headache, repeated vomiting, convulsions, coma, and in severe cases,
death. Malaria is becoming increasingly resistant to known primary drug
treatments.

Measles is a highly contagious viral disease that often strikes children,
causing fever, conjunctivitis, congestion, and cough, followed by a rash
that lasts 2 to 4 days. This disease is transmitted through human-to-human
contact, and secondary infections often cause further complications.
Sustained efforts to immunize children have reduced the prevalence of this
disease, but it still occurs worldwide, with an estimated 31 million cases
leading to 1 million deaths every year.

Meningitis, a condition that may be caused by several disease agents, is an
infection and severe inflammation of the fluid membranes that surround the
brain and spinal cord. Meningococcal meningitis, caused by a particular type
of bacteria, is characterized by sudden onset of fever, headache, neck
stiffness, and altered consciousness and is transmitted by person-to-person
contact. Untreated epidemics can incur fatality rates of over 50 percent.
However, epidemic fatality rates in the last 30 years have generally been in
the 8-12 percent range. There is a vaccine for this disease, but it loses
its effectiveness over time and must be repeated.

Nipah virus is a newly emerging disease causing encephalitis. It is believed
to be transmitted through contact with infected pigs. Symptoms include
headache, fever, muscle spasms, coma, and brain damage. There is no
treatment beyond alleviation of symptoms.

Omsk hemorrhagic fever is caused by a virus in the same family as the
viruses causing yellow fever, Japanese encephalitis, West Nile fever, and
dengue. It is found only in central Russia.

O'nyong-nyong fever is a viral illness spread by mosquitoes. It causes
symptoms such as joint pain, rash, high fever, and eye pain. Fatalities are
rare. Epidemics of this virus have occurred twice since its appearance in
1962 in Africa.

Pertussis, or whooping cough, is a highly contagious bacterial disease found
worldwide, mostly in developing countries. There are 20 million to 40
million cases with 200,000 to 300,000 deaths every year. It is spread
through human-to-human contact, in the air. Symptoms include runny nose and
sneezing, a mild fever, and a cough that gradually becomes more severe,
turning into paroxysms of coughing that cause vomiting and exhaustion.
Pertussis is treatable with antibiotics. Pertussis vaccine is commonly
administered as part of routine childhood immunization programs.

Plague is a severe bacterial infection that is usually transmitted to
persons by infected rodent fleas (bubonic plague) and uncommonly by
person-to-person respiratory exposure (pneumonic plague). Symptoms of
bubonic plague include swollen, painful lymph glands ("buboes"), fever,
chills, headache, and exhaustion. Persons with pneumonic plague develop
cough, bloody sputum, and breathing difficulty. Plague is treatable with
antibiotics. However, unless diagnosed and treated early, it is highly
fatal. There are an estimated 1,000 to 3,000 cases of plague worldwide each
year.

Poliomyelitis, or polio, is a virus transmitted through human-to-human
contact. In most cases, there are no symptoms, or only mild, flu-like
symptoms. Five to 10 percent of the cases can lead to aseptic meningitis,
while only 1 percent of infections lead to the acute flaccid paralysis
typically associated with polio. There is an effective vaccine, commonly
included as part of routine childhood vaccination. However, the disease is
still considered endemic in 61 countries.

Rabies is a viral disease transmitted through contact with the saliva of
infected animals. It is estimated that 40,000 to 70,000 people die from it
every year. Symptoms progress from respiratory, gastrointestinal, or central
nervous system affliction to hyperactivity to complete paralysis, coma, and
death. Once symptoms start to appear, the disease is not treatable.
Multiple-dose courses of vaccine and immunoglobulin can be used to prevent
onset of the disease if administered immediately after contact with a
suspected carrier.

Reston virus is a variety of the Ebola virus found in Asia. It is found
mostly in monkeys. Humans can become infected with Reston virus and produce
antibodies but do not suffer from the effects of a hemorrhagic fever.

Rift Valley fever is caused by a virus transmitted by mosquitoes or contact
with body fluids of infected animals or people. The disease was first
detected at the turn of the century and occurs in many parts of Africa. Rift
Valley fever usually causes a flu-like illness lasting 4 to 7 days, but
about 1 percent of the cases develop into a more severe hemorrhagic fever,
with an approximately 50 percent fatality rate. No treatment for Rift Valley
fever has been found, beyond supportive measures. Vaccines are being
developed, but they are not yet widely available for human use.

River blindness, or onchocerciasis, is a parasitic disease endemic in 37
countries, nearly all in Africa. Blackflies transmit the larva to humans,
where it grows into a parasitic worm with a lifespan of 12 to 15 years. This
worm spawns millions of microscopic parasites, which travel throughout the
body, causing unbearable itching, skin disfigurement, and vision impairment
or blindness. Treatment with the drug ivermectin kills the infant parasites
but has very limited effect on the adult worms, if any.

Ross River virus is a mosquito-borne disease found in Australia that cannot
be treated beyond relief of symptoms. Symptoms include swollen joints, sore
muscles, rash, fever, sore throat, and fatigue.

Tetanus, or lockjaw, is caused by a toxin produced by a bacterium found in
the intestines of many animals and in the soil. It is transmitted to humans
through open wounds, and is a particular problem in newborn infants because
of unsanitary birthing practices. Symptoms include generalized rigidity and
convulsive spasms of skeletal muscles. It is fatal about 30 percent of the
time. It can be treated with an antitoxin, and there is an effective
vaccine, commonly included in childhood vaccination programs. Tetanus occurs
worldwide.

Tuberculosis is an airborne contagious disease that is estimated to kill 2
million people each year. Over one-third of the world's population is
thought to be infected. A person with a healthy immune system can become
infected, but not fall ill. Symptoms of tuberculosis can include a bad
cough, coughing up blood, pain in the chest, fatigue, weight loss, fever and
chills. There are several drugs that can be used to treat tuberculosis, but
the disease is becoming increasingly drug resistant. The available vaccine,
commonly administered to children, has only a limited effect.

Typhoid fever is a bacterial illness that occurs worldwide, mostly in
developing countries. It is spread through contaminated food and water and
causes a high fever, stomach pains, and sometimes a rash. It is treatable by
antibiotics, and there is a vaccine, although it is not 100 percent
effective. If untreated, the disease causes death in 20 percent of cases.

Venezuelan equine encephalitis is a mosquito-borne viral disease that can be
transmitted to humans from equine hosts. Symptoms in humans include flu-like
symptoms of fever and headache. Severe illness and death can occur in the
young and the elderly and those with weakened immune systems.

West Nile fever is a mosquito-borne viral encephalitis. Symptoms include
fever, head and body aches, rash, and, in more serious cases, stupor, coma,
convulsions, and paralysis. Death occurs in 3-15 percent of cases. There is
no vaccine for the West Nile virus, and it is not treatable beyond
supportive therapies. It occurs in Africa, Eastern Europe, West Asia, the
Middle East, and, most recently, in the United States.

Yellow fever is a mosquito-borne virus, endemic in over 40 countries of
Africa and Central and South America and constituting an estimated 200,000
cases and 30,000 deaths every year. Symptoms include fever, muscle pain,
headache, loss of appetite, and nausea. Fifteen percent of patients progress
to a toxic phase, which can include jaundice, abdominal pain, and bleeding
from the mouth, nose, eyes, or stomach. The kidneys deteriorate and may
fail. Half of the patients who enter this phase die. There is no treatment
for yellow fever beyond supportive therapies. A safe and highly effective
vaccine for yellow fever is available but is often not included in national
vaccination programs.

OUTBREAK RESPONSE - RIFT VALLEY FEVER 1998

Beginning in October 1997, unusually heavy rains swept across Kenya and
adjacent parts of Somalia. As the rains continued, flooding began to occur.
By December 1997, local officials in Kenya began to receive reports of
unusually high levels of fatal hemorrhagic illness among domestic animals.
These reports were soon followed by reports of acute fever in humans,
accompanied by severe headache, muscle pain, hemorrhage, vomiting, and
diarrhea. In late December, the Kenyan Ministry of Health and the World
Health Organization (WHO) office in Nairobi were informed that nearly 500
people had died from this unexplained illness - some of them within 24 hours
of becoming ill. Concerned institutions, including the Ministry, the WHO
missions in Kenya and Somalia (where cases had also been detected), Doctors
Without Borders, the African Medical and Research Foundation, and the Kenyan
Medical Research Institute, established a task force to look into this
outbreak.

Shortly thereafter, officials from WHO, the International Federation of the
Red Cross, the African Medical and Research Foundation, the Kenyan Ministry
of Health, Doctors Without Borders, and Mï¿½decins du Monde participated in a
field investigation. By December 30, analysis of tissue samples by South
Africa's National Institute for Virology and CDC showed that a substantial
portion of the deaths being reported were caused by Rift Valley fever, while
others were caused by other hemorrhagic fever pathogens.

When the disease diagnosis had been confirmed, the task force devised and
launched a public education campaign on how to deal with the outbreak. (For
example, people in affected areas were advised not to slaughter sick
animals.) Health care workers were informed about appropriate case
management techniques. Large-scale active surveillance and response efforts
were organized, with helicopter transport provided by the Kenyan government,
WHO, and international relief organizations.

The task force established four research groups to investigate the oubreak's
human epidemiology, to conduct laboratory investigations, and to study
veterinary and entomological aspects of the event. Two teams from CDC
assisted in defining the prevalence of Rift Valley Fever infection and the
geographic distribution of the outbreak in Kenya and neighboring countries.
Four U.S. Department of Defense laboratories, including the U.S. Army
Medical Research Unit in Kenya, also made contributions to these
epidemiological investigations. The U.S. Naval Medical Research Unit in
Egypt established a capability to perform Rift Valley fever diagnostic
assays, and the U.S. Army Research Institute of Infectious Diseases in
Maryland supplied human Rift Valley Fever vaccine (not yet approved for
general use) to immunize at-risk laboratory workers.

International efforts to investigate and provide an effective response to
this outbreak were complicated by transportation difficulties (flooding,
poor roads), lack of security in regions along the Kenya-Somalia border, and
the fact that nurses and lab personnel in Kenya were on strike during the
outbreak. Ultimately, though precise estimates are impossible, health
officials estimate that at least 89,000 persons became ill during the
outbreak - though in many the illness was limited to its milder (nonfatal)
form. At the same time, livestock owners reported losing substantial
portions of their herds.

WHO COLLABORATING CENTERS FOR ARBOVIRUSES AND

HEMORRHAGIC FEVERS

Instituto Nacional de Enfermedades Virales, Pergamino, Argentina

Queensland University of Technology, Brisbane, Australia

University of Western Australia, Nedlands, Australia

Instituto Adolfo Lutz, Sao Paulo, Brazil

Instituto Evandro Chagas, Belem, Brazil

Laboratory Centre for Disease Control, Ottawa, Canada

Institut Pasteur de Bangui, Central African Republic

Instituto de Medicina Tropical Pedro Kouri, Havana, Cuba

University of Helsinki, Finland

Institut Pasteur, Paris, France

Aristotelian University of Thessaloniki, Greece

National Institute of Virology, Pune, India

U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia

Instituto Superiore di Sanitï¿½, Rome, Italy

Nagasaki University, Japan

Kenya Medical Research Institute, Nairobi, Kenya

Asan Institute for Life Sciences, Seoul, Republic of Korea

University of Malaya, Kuala Lumpur, Malaysia

Erasmus University Hospital, Rotterdam, Netherlands

University of Ibadan, Nigeria

Ivanovsky Institute of Virology, Moscow, Russia

Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow, Russia

Institut Pasteur de Dakar, Senegal

Slovak Academy of Sciences, Bratislava, Slovak Republic

Institute of Microbiology and Immunology, Ljubljana, Slovenia

National Institute for Virology, Sandringham, South Africa

Swedish Institute for Infectious Disease Control, Stockholm, Sweden

Uganda Virus Research Institute, Entebbe, Uganda

Public Health Laboratory Service, London, United Kingdom

Centers for Disease Control and Prevention, Atlanta, Georgia

Centers for Disease Control and Prevention, Fort Collins, Colorado

Centers for Disease Control and Prevention, San Juan, Puerto Rico

University of Texas Medical Branch, Galveston, Texas

U.S. Army Medical Institute of Infectious Diseases, Fort Detrick, Maryland

(711478)

  
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