Investigating an Outbreak of Disease

Threat of outbreaks
Knowledge of medicine and diseases has increased enormously during the last few
decades. With the advance of knowledge, public health services in many countries can
implement effective prevention programmes and are able to protect people from many
unnecessary illnesses and death. However, people around the world still suffer and die
from various known and unknown outbreaks. Some outbreaks are small and involve
only a few persons but some affect more than 10 000 individuals (Fig. 1). During 1997,
most countries had at least one infectious disease outbreak and several had as many
as eight (WHO 1999). Outbreaks can happen anywhere, from a very remote area where
no health facility exists to nosocomial outbreaks in a very sophisticated hospital where
hundreds of health personnel are employed. It is a challenge for the government and
public health professionals of all countries to detect and control these outbreaks as early
as possible. Outbreak investigations also provide the opportunity to discover new
aetiological agents, to understand factors that promote the spread of the diseases, and
at the same time to identify the weaknesses of existing prevention and health
programmes. For these reasons, all public health professionals should have the ability
to conduct and support outbreak investigations.

What is an outbreak?
The terms outbreak and epidemic can be used interchangeably. But outbreak is more
understandable for most people and conveys a greater sense of urgency. Some
epidemiologists prefer to use the term epidemic only in a situation that covers a very
wide geographical area and involves large populations. For example, it is possible to
use the term ‘outbreak of HIV’ to describe a sharply increasing HIV prevalence rate
among commercial sex workers in a city where the normal rate was low in the previous
year. But the term ‘HIV epidemic’ can be used when an abnormally high HIV prevalence
is found among sex workers in many cities of the country.
In general, the term outbreak is used for a situation when diseases or health events
occur at a greater frequency than normally expected in a specified period and place
There is often a misunderstanding that only communicable diseases can cause
outbreaks. Non-communicable outbreaks such as mass sociogenic illness are
sometimes reported as acute outbreaks of unexplained illness, especially in school
settings (CDC 1990, 1996).
Because the criteria for judging an outbreak can be very subjective, it is useful to define
the term in a more measurable fashion. The criteria for judging that an outbreak has
happened can be one of the following.
1. The occurrence of a greater number of cases or events than normally occur in the
same place when compared to the same duration in past years. For example, the
epidemic of Kaposi’s sarcoma, a manifestation of AIDS, was confirmed in New
York when almost 30 cases were reported in 1981, whereas only two or three
cases had been reported in previous years (Biggar et al. 1988).
2. A cluster of cases of the same disease occurs which can be linked to the same
exposure. The term ‘cluster’ is an aggregation of two or more cases which is not
necessarily more than expected. For example, three athletes were admitted to
hospital with an acute febrile illness and all of them had participated in a triathlon
in Springfield, Illinois (CDC 1998a). After receiving this report, the responsible unit
started to suspect that an outbreak of febrile illness might be occurring among
athletes who participated in the triathlon. The investigation revealed that
Leptospira was the cause of the illness.
3. A single case of disease that has never occurred before or might have a significant implication for public health policy and practice can be judged an outbreak which deserves to be investigated. The first documented case of avian flu (H5N1) in the Hong Kong Special Administration Region in a 3-year-old boy in May 1997 alerted the local authorities and scientists around the world to start a full-scale investigation (Lee et al. 1999).
How can an outbreak be detected?
Public health professionals need to maintain monitoring or surveillance of the disease
situation in their local area or country, and also at the international level. It is possible to
identify an outbreak by monitoring many sources of information, which will help to detect the abnormal occurrence of disease. Some useful sources are listed below.
Health personnel
Doctors and nurses in a hospital have a good opportunity to observe an abnormal
increase in the number of patients with a particular disease or syndrome. An outbreak of
suspected mushroom food poisoning in a northern province of Thailand was reported to
an epidemiologist during a business telephone conversation with his colleague. The
epidemiologist started an investigation and identified the first confirmed outbreak of
Clostridium botulism food poisoning associated with home-canned bamboo shoots in
the country (CDC 1999a). Without this personal contact, this outbreak would not have
been investigated. Thus, public health authorities should maintain a cordial relationship
with doctors and hospital staff both in the governmental and private sectors. Conversely,
doctors should report all suspected outbreaks to the local public health authorities.
Laboratory
Every laboratory or network can serve as an excellent source of outbreak notification.
The avian flu outbreak in the Hong Kong Special Administrative Region was first
discovered by the Influenza Surveillance Network, which reported an abnormal
influenza, type A (H5N1) (Lee et al. 1999). Without the necessary laboratory capacity,
the avian flu might have been overlooked and not triggered a field investigation. A public
health professional should communicate regularly with laboratory technicians and vice
versa. The laboratory scientists can prevent further spread if they report abnormal
findings to the public health authorities regularly and without delay.
Official disease notification systems
Most countries have official systems for notification of cases and deaths from specific
diseases from hospitals. The system was designed to detect an outbreak by comparing
cases occurring in the current week or month with the average number of cases in the
same area during the same period in past years.
For some diseases, like HIV/AIDS, a sentinel surveillance system was designed to
monitor and detect abnormal trends in particular sentinel populations and sentinel sites.
The first HIV sentinel serosurveillance in Thailand, which started in June 1989, detected
that the HIV prevalence among commercial sex workers in a popular northern tourist
province was 44 per cent. The finding was very alarming and prompted a field
investigation to confirm the high prevalence and to look for risk factors of HIV infection
among sex workers (Siraprapasiri et al. 1991). The investigation confirmed the outbreak
and revealed the low level of condom use, which led to a recommendation for condom
promotion in this high-risk population.
One of the most important functions of epidemiologists and public health professionals
is to perform regular analyses of reported disease data. Unfortunately, this task has
been neglected and the usefulness of disease reporting systems has been downgraded
and often serves only as a vital statistics report. If this neglect of the reporting system
can be overcome, the public health system will regain this powerful tool to detect and
control outbreaks.
Newspapers or media
In fact, public health professionals learn of outbreaks from the media more often than
from the official surveillance system. Newspapers receive outbreak news directly from
their journalists or people in the community and are able to report them immediately.
The Program for Monitoring Emerging Diseases (ProMED), the prototype for a
communications system that monitors emerging infectious diseases globally and an
initiative of the Federation of American Scientists and co-sponsored by the World Health
Organization (WHO), obtains much of its outbreak news from local or international
media. While timeliness is the strength of the media, the validity of the information is
often poor and therefore it requires verification.
Village health volunteers
In rural areas where there are no health facilities and communication is limited, village
leaders or village health volunteers can often help to recognize an abnormal increase in
the numbers of some clinical diseases such as diarrhoea, dysentery, measles, fever,
death of unknown aetiology, and so on. For example, the head man in a village of
Kachin State in the Union of Myanmar informed the health authorities that seven
villagers had died from febrile illness. This information triggered a field investigation,
which revealed that malaria was the cause of the outbreak (Dr Myint Win, personal
communication, 1999).
Purposes of outbreak investigation
An outbreak investigation can have many purposes as follows.
Controlling the current outbreak
This should be the primary or ultimate goal. If the investigation can start early the
findings can guide implementation of appropriate control measures to stop further
spread. The avian flu (H5N1) outbreak investigation found a link between infection and
illness in chickens and in humans. The same virus was found in both chickens and
patients. There were a total of 18 cases and six deaths before the Hong Kong Special
Administrative Region decided to kill all 1.5 million chickens in the islands within 3 days
to end the outbreak. There have been no cases since (Lee et al. 1999). The key to
achieving this goal is to eliminate the delay in detecting the outbreak, to start the
investigation as soon as possible, and to implement the appropriate preventive steps
indicated by the investigation immediately.
Prevention of future outbreaks
Not all investigations start at the beginning or before the peak of the outbreak. The
findings or lessons learned from the investigation may be too late to help fully control
the current outbreak but they can still contribute to the prevention of future outbreaks.
With good investigation, the weaknesses of the prevention programme can be identified.
If recommendations are taken seriously, the chance of recurrence of the same outbreak
or other diseases that share common risk factors can be reduced.
Research to provide knowledge of the disease
Information about new diseases and their natural history, clinical spectrum, incubation
period, and so on, can often be best learned during an outbreak investigation. The most
recent outbreak of encephalitis in Malaysia, which continued until the end of April 1999,
and resulted in 257 cases and 100 deaths, prompted an international outbreak
investigation which resulted in the discovery of a new nipah virus (CDC 1999b, c). The
mode of spread from infected pigs to humans was revealed but there is still much more
to be learned.
Evaluation of the effectiveness of prevention programmes
Investigation of an outbreak of disease, which is the target of a public health
programme, may reveal weaknesses in that programme. Investigation of an outbreak of
vaccine-preventable diseases often identifies populations that have not received the
vaccine. For example, the investigation of a measles outbreak that occurred in 1993 in
Espindola, a rural community in the Peruvian Andes, revealed that more than a quarter
of the 553 residents were affected and that more than 3 per cent of those with measles
had died. One year before the outbreak, a national measles campaign targeting children
under 15 years of age had been conducted. Although national coverage reported the
coverage to be 78 per cent, the investigation found that only 4 per cent of the children in
Espindola had actually been vaccinated (Sniadack et al. 1999).

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Evaluation of the effectiveness of the existing surveillance system

Some aspects of the surveillance system can be evaluated during an outbreak, such as the timeliness, validity, sensitivity, appropriateness of case definitions, and utilization of the surveillance information.
Training health professionals
The Epidemic Intelligence Service of the United States Centers for Diseases Control and Prevention (CDC) and 20 Field Epidemiology Training Programs around the world use real outbreaks as an opportunity for training as well as to provide service to investigate the causes and determinants of outbreaks.
Responding to public, political, or legal concern In many situations, the investigation has to be conducted because the media has publicized the complaints of people to politicians, or even rumours. The main objective for this kind of investigation is to verify the outbreak and diagnosis. If it is groundless,
the investigator can supply the media with new information that can end the rumours. Conversely, if it is a true outbreak then the investigator needs to decide what steps need to be taken.
In general, for a real outbreak, many objectives can be achieved fully or at least partially. However, the ultimate goal is to control the current outbreak and to prevent future ones. It is unethical for investigators to compromise this ultimate goal with other goals such as training or non-essential research that does not directly contribute to the control activities.

Components of an investigation team
The term ‘investigators’ represent the people who are directly involved in planning and conducting the outbreak investigation from start to finish. In principle, local health professionals at the district or provincial level should take the role of investigators and start the work as soon as possible. For complicated or difficult field investigations, investigators from additional disciplines or even international experts can provide assistance. It is best to form an investigator team with a single principal investigator in charge of the operation. A good investigative team should include the following people.

1. A field epidemiologist who is technically competent to conduct field investigations systematically. The field epidemiologist usually serves as one of the primary investigators and should be involved in all the investigative steps.
2. Disease control people who are experienced in implementing basic disease control measures such as food and environmental sanitation, vector control, vaccination, and so on. If available, an educator who can provide essential knowledge to villagers in clear terms will also be very useful for disease control
implementation.
3. Laboratory technicians who are able to provide basic and advanced laboratory support to the investigative team. Laboratory technicians might not need to travel to the field and collect the specimens by themselves except when a special collection procedure is required.
4. Specialists in particular areas; for example, a veterinarian would be very helpful for an outbreak investigation of zoonotic diseases. An entomologist is a key member for an outbreak investigation of vector-borne diseases. A social scientist with expertise in qualitative methods will help identify risk behaviours among affected populations and assess the acceptability of the recommended interventions.
5. Public health administrators, who are good at providing logistic support, mobilizing resources, and providing administrative expertise for the team.
6. Public relations person. In certain conditions when the outbreak has caused panic or has gained the intense attention of the public, the investigative team should recruit or appoint a person to be in charge of public relations and press releases.
This person should appropriately reassure and not unduly alarm the public. In practice, all of these team members are not always available at the subdistrict or district level due to limited human resources. Public health professionals and field epidemiologists need to have basic knowledge of all these relevant disciplines and be able to assume tasks if needed.
Owing to the sudden nature of the field investigation, it is better to establish in advance a list of people who will be on call and ready to join the investigative team once an outbreak has occurred.

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Prior to the implementation of an investigation

The principal investigator should consider all of the following issues before initiating a
field investigation.

Assessing the existence of the outbreak
No matter how the outbreak news was obtained, the investigator should confirm the
validity of the information. The best way is to have direct communication with the

responsible local health authority or field staff. It is not unusual for the information to be
groundless. Sometimes the outbreak did happen but the media incorrectly quoted the

name of the place. The investigator should carefully check with all other possible local
health authorities in order not to miss the outbreak.

Gathering the available basic information
If the local health authority or field staff confirms the existence of the outbreak, the
investigator should ask for additional information related to the situation and control
measures being implemented.

Information related to the disease situation
1. What are the main symptoms and signs of the patients?
2. By whom and how was the diagnosis made, for example using only clinical or also
laboratory evidence?
3. How many patients were seen and how many have died?
4. What was the average age of the patients and were there any differences in sex
distribution?
5. Where did the patients come from? Are they clustered or scattered?
6. When was the increased number first observed and what is the trend at the
moment?

Information related to control and response activities
1. What has already been done in terms of the field investigation and implementation
of control activities?
2. Are there any serious constraints to compromise the field investigation and in
implementing control measures?
3. Who are the key people responsible for the investigation and control activities?
It is not necessary to gather all of this information before leaving for the field but having
it will help the investigator to plan an effective investigation.

Ensuring that clinical specimens and suspected materials were collected
It is absolutely vital to contact the doctors who saw the cases and made the diagnosis to
obtain relevant clinical specimens such as serum, blood, and so on, for future laboratory
tests. The items to which the cases were exposed, such as food and water, should be
collected immediately before anything is destroyed unintentionally. The investigator
should contact the local and reference laboratories so that the necessary supplies and
equipment can be obtained immediately.

Obtaining permission and adequate support from the local and national
authorities
The investigative team should ask the permission of the local health authority, and in
some situations a national authority. This will create a sense of shared responsibility
and partnership. Most of the time, local authorities are pleased to receive assistance. In
a few situations, the local authority might be unhappy having outside people for the field
investigation because of the sensitive nature of the problem. The investigator needs to
convince local authorities that a thorough and good investigation will benefit their
organization more than harm it. The investigator should also request field support from
the key authorities such as field staff who will facilitate the fieldwork, providing
transportation, medication, and so on.

Field operation plan
The investigator needs to have a short meeting among team members to summarize
the situation, set up the objectives of the investigation, divide responsibility among team
members, and check the readiness of laboratory and logistical support.
It is also important to plan the duration of the field investigation. The investigative team
should stay in the field until all investigation processes such as data collection, analysis,
interpretation, and the executive summary have been completed. Leaving the field
without accomplishing all these objectives will cause delay in the implementation of
control measures. Most outbreak investigations should plan to obtain preliminary results
and recommendations within 1 or 2 weeks and no later than a month after the
investigation begins. This is to make sure that the findings will be in time to assure
control of the current outbreak. Additional studies and subsequent investigations can be
done later.
This initial plan usually needs to be revised once the team arrives in the field. A normal
practice in the field is that the team members should have a meeting at the end of each
day to review and plan specific activities for the next day.

Reviewing current knowledge of the outbreak
The investigator or one of the team members should be assigned to review current
knowledge of the outbreak. The Control of communicable diseases manual (Chin 2000)
is very useful for a quick review of most infectious diseases. Searching the literature
from the Internet, using as key words the ‘outbreak and name of the disease’, is useful
to learn about previous studies done in different countries and settings.
The investigation team should not spend too much time preparing a perfect plan
because of the urgency of the outbreak, but rather should obtain what is most
necessary and start the investigation as soon as possible.

Steps of outbreak investigation
An outbreak investigation is an observational study in nature because the events have
already happened. Every outbreak investigation needs to start with a good descriptive
study followed by analytical studies whenever possible and necessary. Conclusions
about the causes, mechanisms, and determinants of the outbreak need to be based on
sound epidemiological, clinical, laboratory, and environmental evidence.
A descriptive study can help to identify the risk population and risk area so that
immediate interventions can be directed to the most needy people and area. A good
descriptive study can also generate hypotheses about how the outbreak has spread and
what factors contributed to the abnormal occurrence of the disease. In theory,
hypotheses derived from a descriptive study should be confirmed by further analytical
study. In reality, this is not always possible because of many constraints.
It is preferable to translate the methodology for outbreak investigation into steps of
action. Gregg (1996) has divided the outbreak investigation process into 10 steps. With
a slight modification, this chapter will also divide the investigation process into 10 steps
(Box 1). Steps 1 to 4 use descriptive epidemiology to generate basic facts and
hypotheses, steps 5 to 7 are processes to test hypotheses and make conclusions, and
steps 8 to 10 emphasize the important of communication of the results and follow-up of
the recommendations.

Ten steps to take in an outbreak investigation

1. Confirm the existence of the outbreak

2. Verify the diagnosis and determine the aetiology of the disease

3. Develop a case definition, start case-finding, and collect information on cases

4. Describe person, place, and time and generate hypotheses

5. Test hypotheses using an analytic study

6. Do necessary environmental or other studies to supplement the epidemiological
study

7. Draw conclusions to explain the causes or the determinants of the outbreak
based on clinical, laboratory, epidemiological, and environmental evidence

8. Report and recommend appropriate control measures to concerned authorities
at the local, national, and, if appropriate, international levels

9. Communicate the findings to educate other public health professionals and the
general public

10. Follow-up of the recommendations to assure implementation of control
measures

This outline of steps for outbreak investigation does not imply a strict sequence of
action. In real outbreak investigation, many steps can happen at the same time
depending on the situation.