For the U.S. Government to help in controlling an incipient - or raging - epidemic in another country, three things must occur. First,reliable information must reach the United States. Second, U.S.scientists and public health officials must evaluate theinformation and decide what measures should be taken. Third, U.S.officials must help the affected country implement thosemeasures. However, U.S. participation in an epidemiologicinvestigation within another nation is dependent upon a formalrequest for assistance from the foreign government. This was thepattern of events during the Ebola virus investigation (see "Lessons Learned From the Ebola Virus Outbreak in Zaire").If no request is received, our Government may still takeaction to minimize the risk of disease importation into theUnited States (see "Plague in India").

The informal global surveillance network

When a cluster of cases of an emerging infectious disease occursin a remote part of Africa, Asia, Eastern Europe, or theAmericas, the international community may or may not learn aboutit. In some cases, an American company or Government agencyoverseas (the Army, Peace Corps, USAID, a U.S. embassy) or an WHOofficial may report an unusual illness to the CDC and seekassistance in testing specimens for diagnosis. Occasionally, acolleague from another industrialized country who is working in adeveloping area will provide the first notification of anemerging disease. Through international conferences andscientific collaborations, U.S. infectious disease experts havemade contacts with colleagues all over the world. As aconsequence, these experts receive informal calls from foreigncolleagues requesting advice and assistance when an unusualoutbreak occurs.

In some cases -- if the notification arrives quickly enough -- thisinformal surveillance system works. When international resourcesare successfully mobilized, assistance in diagnosis, diseasecontrol and prevention can be made available to local healthauthorities. Clinical specimens can be sent to a diagnosticreference laboratory to rule out known disease agents (see "The Informal Global Network"). Epidemiologists can be sentinto the field to investigate the source of the new infection anddetermine how it is transmitted. Public health officials can usethis information to implement appropriate control measures. Oncethe infectious agent has been identified, which is often adifficult task, experimental scientists can start to developdiagnostic tools and treatments if the agent is a newlyrecognized one.

However, a new infectious disease can be easily overlooked,especially when the disease originates in a part of the worldthat lacks effective domestic disease surveillance and moderncommunications. Left unchecked, the disease may spread far andwide before it is recognized and reported.

Evaluation of disease surveillance information

When reports of a potential epidemic and requests for assistancereach the United States, scientists evaluate the information andprovide advice on further investigations, the availability ofdiagnostic tests, and treatment. Within the United States, CDCtakes the lead in evaluating surveillance information. In manyinstances CDC and USAID will offer to send diagnostics, drugs, orvaccines to the affected area.

Response to international disease outbreaks

When the U.S. Government learns of an epidemic in anothercountry, agencies consult with each other on what the UnitedStates response should be. Among the Government agencies withrelevant expertise in this area are CDC, FDA, NIH, DoD, andUSAID.

Lack of an executive function for response to epidemics. The U.S.Government response to international epidemics occurs on an adhoc basis. As described below (and in the inventory thataccompanies this report), many Government agencies anddepartments have resources that can facilitate an effectiveresponse to epidemics of infectious diseases.

The authority of CDC, for instance, does not cover internationaldisease control and prevention, and USAID has limited technicaland financial resources in this area. In practice, individualGovernment workers who become aware of outbreaks do what they canto coordinate agency efforts and provide aid to affectedcountries. But there is no formal structure or designatedresources for this activity.

Resources for emergency responses. At present, the U.S. Government has no funds set aside for responses to internationaldisease outbreaks. Government disaster assistance groups such asthe Federal Emergency Management Administration and USAID'sOffice of Foreign Disaster Assistance (OFDA) do not takeresponsibility for infectious disease emergencies. At CDCalthough approximately65% of the budget is dedicated to the prevention andcontrol of infectious diseases, about 95% of these funds areearmarkedfor AIDS, TB, and sexually transmitteddiseases and vaccine preventable diseases. Moreover, USAIDhas limited resources available for international outbreakinvestigations. Thus, when a new or re-emerging disease issuspected in another country, there is very little flexibility inany U.S. Government agency's budget to provide for aninvestigation.

Importation of infectious diseases into the United States. Eachtime an infected person (or a contaminated food or sick animal)enters the United States, an opportunity arises for a contagiousmicrobe to spread to the American people. CDC strives to preventthis in two ways. One protective measure is to issue advisoriesthat caution against travel to or from the site of an epidemic.CDC also provides information on travelers' health, includinginformation on recommended vaccinations and on regimens for drugprophylaxis. A more comprehensive line of defense relies on localsurveillance systems, at the state, county, and city levels.Unfortunately, our local public health surveillance systems areno longer adequate because of our past complacency aboutinfectious diseases, poor planning, and lack of resources.

Screening of travelers at U.S. ports of entry. Under the PublicHealth Service Act and the Foreign Quarantine Regulations, allaircraft and ships captains are required to radio the nearest CDCquarantine station at their port of arrival when they have an illperson or when a passenger has died. CDC has the authority todetain, isolate, or conditionally release any person believed tobe infected or exposed to a communicable disease. CDC staffsquarantine stations at seven ports of entry at major airports inNew York, Miami, Chicago, Seattle, San Francisco, Los Angeles,and Honolulu. Each station provides backup for other ports intheir geographic area of responsibility. At ports of entry whereCDC does not have staff, the gap is filled by airline workers, byphysicians on contract with CDC, and by officials of theImmigration and Naturalization Service (INS). U.S. civilians,foreign nationals (including tourists, business travelers,long-term visitors), and immigrants can enter at any of theseairports, as well as seaports and land border areas. There areapproximately 50 international airports in the United States andmore than 150 other legal entry points.

The identification of persons carrying pathogens capable ofcausing serious disease outbreaks is made difficult by the verylarge number of people entering the United States fromincreasingly remote locations. Most American cities can bereached within 36 hours from anywhere in the world, either bydirect or by connecting flights. The incubation periods of mostinfectious diseases (the time between infection and theappearance of symptoms) is considerably longer than 36 hours.Because only obviously ill patients are identified by screeningat ports of entry, routine state and local surveillance effortsare relied on to identify infected travelers who become ill sometime after entry into the United States.

Screening of soldiers. Military personnel who return to theUnited States are not routinely quarantined. Military personnelwho become ill overseas are evacuated to DoD medical facilitiesin the United States. Military personnel who are not sick returnto their unit bases. Deployed reservists are more apt to re-entercivilian health-care channels than active duty personnel. Themedical tracking of all deployed military personnel after theyreturn home is being improved by DoD to facilitate therecognition and diagnosis of latent infections.

Food-borne and animal-borne diseases. CDC's quarantine programalso coordinates with the U.S. Department of Agriculture (USDA),U.S. Fish and Wildlife Services, Department of Interior, and FDAto ensure that other possible carriers of human disease (food andanimals) are managed appropriately.

USDA's Food Safety and Inspection Service (FSIS) plays animportant role in disease control and eradication. FSIS samplesfood products for a number of pathogens and protects the foodsupply by retaining or recalling products. FSIS inspects forconditions and collects samples to test for many diseases such asrabies, tuberculosis, brucellosis, and pseudorabies which can betransmitted to humans. This inspection is crucial for thesurveillance and monitoring system of the USDA-APHIS.

The Animal and Plant Health Inspection Service (APHIS) of theUSDA is responsible for protecting American livestock and poultryfrom foreign and domestic diseases. Many diseases of humans arecarried by and transmitted from animals or animal products(Ebola, anthrax, cryptosporidium, hantavirus, Rift Valley fever, Lyme disease, E. coli, tuberculosis, brucellosis, rabies,pseudorabies, to name to few). APHIS carries out thisresponsibility through several activities:

1) exclusion of foreign animal diseases,

2) disease exclusion through import testing,

3) domestic animal disease control and eradication, and

4) national animal health monitoring.

The USDA's animal health infrastructure and mission is, in part, built on the important task of excluding and rapidly responding to the introduction of these pests and diseases. APHIS inspectsanimals entering the United States from foreign countries at theborder or port of entry. APHIS establishes quarantine and testingrequirements for imported animals to reduce the risk of diseasesand operates several USDA quarantine facilities.

In addition to exclusion activities, APHIS operates programs tocontrol and eliminate diseases in domestic livestock, includingthose that also affect humans. Interstate movement and transport of infected and exposed animals are regulated in an effort to stop further spread of the diseases. Monitoring of animaldiseases is maintained through APHIS' National Animal HealthMonitoring System.

Conclusion

Three steps are involved in responding to a disease outbreak --surveillance, evaluation, and implementation of control measures.Surveillance begins with accurate diagnosis and requires openlines of communication among doctors, scientists, and governmentofficials. Evaluation requires epidemiologic and laboratory basedinvestigations. Disease control requires that public healthinfrastructures are in place and that resources are available toprocure and distribute medical supplies, such as drugs andvaccines. Significant improvements can be made in surveillanceand response to international epidemics, if U.S. agencies aregranted mandates and authority to make the most effective use ofU.S. expertise in public health.

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The Informal Global Network

Sometimes the informal global surveillance and response systemfor infectious diseases works very well, however, sometimes itdoes not - as the following examples illustrate.

Successful Surveillance to Prevent Disease Transmission:Venezuelan Equine Encephalitis in Peru
During 1994 and early 1995, the U. S. Naval Medical ResearchInstitute Detachment (NAMRID) in Lima, Peru, detected severalcases of dengue fever, oropouche, and Venezuelan equineencephalitis (VEE) in northern Peru. These diseases are caused byarboviruses, which are carried by insect vectors, and vaccinesagainst several arboviral illnesses are available. CDC followedup on the NAMRID reports and determined that VEE had occurredamong Peruvian soldiers stationed in the area of the borderdispute with Ecuador. The health authorities in Peru and Ecuadorwere notified and control measures were implemented.

After these occurrences, it came to the attention of CDC that theU.S. Army was planning to deploy troops in this area to mediatethe border dispute. CDC notified the U.S. Army at Fort Detrick,Maryland, and the Southern Command in Panama, and advised thatall troops be immunized against VEE before deployment.

An Epidemic Spreads from Continent to Continent: Dengue Fever inAsia
In recent years several Caribbean countries have experiencedepidemics of dengue fever but have failed to report them, fearingthat the news would have a negative impact on their touristindustries. The outbreaks became known only after touristsreturning to their home countries became ill.

Although CDC and WHO received rumors of outbreaks of dengue anddengue hemorrhagic fever (DHF) in Asia during the late 1980s, CDCdid not receive official information about them, and nodiagnostic samples were sent for confirmation. (DHF and denguefever are different clinical manifestations of the same viralinfection.) Eventually, CDC's WHO Collaborating Centre forReference and Research on Dengue and DHF received blood samplesfrom a pediatrician in the area of Asia, and the presence of aspecific strain of dengue virus was confirmed. In 1994, whendengue fever broke out in Central America, scientists isolatedthe same strain of virus from the Central American blood samples,indicating that the virus that caused DHF in Asia had spread tothe Americas.

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Plague in India

In August 1994, CDC received informal reports of bubonic plaguein Maharashtra state, India. Bubonic plague is carried by fleasthat live on rodents. That summer, many flea-infected rats haddied because of a drought, and some of the fleas had apparentlymoved to human hosts. In September, reports were also received ofpneumonic plague (a different clinical manifestation of the sameinfection) in Gujarat state, India. Pneumonic plague spreads morequickly than bubonic plague, because it is transmitted from oneperson to another by coughing. CDC sent diagnostic reagents to India and offered technical assistance, but the Indian Governmentdid not request on-site assistance.

The U.S. Government took several steps to ensure that plague would not be imported into the United States. The StateDepartment invited two American epidemiologists to New Delhi toassist the U.S. embassy and to be available if Indian doctors or political authorities requested help. In addition, CDC issued advisories to international travelers, notified state healthauthorities, and increased surveillance at U.S. airports. FDA worked with pharmaceutical manufacturers to accelerate efforts toincrease supplies of plague vaccine. In October, CDC participatedin a WHO-led investigation, and by October 27 determined that noinfectious disease emergency existed. Effective surveillance, followed by prompt diagnosis and treatment, could have reducedthe magnitude of the crisis and saved India much of the estimated$2 billion in revenues lost from tourism, exports, and shipping. The U.S. agencies which participated in the Government response to the plague in India included the Departments of State, Justice(Immigration and Naturalization Service), Agriculture, and Transportation; the Public Health Service (including CDC and FDA)of the Department of Health and Human Services; USAID; and stateand local health departments. Despite the cooperation of these agencies, the U.S. Government had domestic obstacles to overcomein responding to this international health emergency. At present,CDC has the only laboratory in the world that serves as areference laboratory for plague. Unfortunately, support for that laboratory has decreased to the point where there is only one full-time employee with experience and training in plagueepidemiology and treatment. To respond effectively, CDC had to pull staff and resources from other programs.

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Public Health Terms

Reference Laboratory: A specialized laboratory to which clinicalspecimens (such as sputum, stool, spinal fluid, or blood samples,or organisms isolated from them) can be sent (from a primary carelaboratory) for diagnosis, identification, or confirmation. ManyWHO Collaborating Centres function as reference laboratories.

Sentinel Surveillance System: A network of individuals,facilities, or laboratories that monitors changes in theincidence of disease in a systematic way. Such networks usuallyinclude many strategically located outposts and are designed toserve as early warning systems for disease outbreaks.

Epidemic or Outbreak: The occurrence of cases of a disease abovethe expected number or baseline level, usually over a givenperiod of time, in a geographic area, or in a specific populationgroup.

Emerging Infection: A new or newly identified pathogen orsyndrome which has been recognized over the last two decades, orwhich has resulted in new manifestations of disease.

Re-emerging Infection: A known or previously identified pathogenor syndrome which is increasing in incidence, expanding into newgeographic areas, affecting new population groups, or whichthreatens to increase in the near future.

Zoonosis: A disease that can be transmitted from animals tohumans.

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