Objectives of outbreak investigation [3,4,9,11,14]:

1. The primary motivation of any outbreak investigation is to control the spread of the disease within the initial population at risk or to prevent the spread to additional population
2. To determine the causes of the disease, its source, its mode of transmission
3. To determine who is at the risk of developing the disease
4. To determine what exposures predispose to the disease
5. To know the magnitude of the problem
6. The multifactorial etiology of the disease is brought to the surface
7. To identify new infective agent
8. To determine the effectiveness of the control measures
9. To identify methods for the present & future prevention & control
10. Research opportunities
11. Training opportunities
12. Program considerations
13. Public, political or legal concerns

Explanation of the terms

1.        Epidemic: Increase in the number of cases of a disease clearly in excess of what is expected.

2.        Outbreak: When an epidemic occurs suddenly & in a relatively limited geographic area, it is described as a disease outbreak [5]. While an outbreak is usually limited to a small focal area, an epidemic covers larger geographical areas & has more than 1 focal point. The number of cases of diseases, which are needed for it to be called an outbreak, depends on past historical patterns of the disease, case fatality & complication rates, and potential of spread to other areas. For some diseases even a single case constitutes an outbreak, for example, polio, guinea worm, etc. States & districts should establish criteria on the number of cases that constitute an epidemic based on their local situations [2].

3.        Cluster: An aggregation of cases in a given area over a particular period, regardless of whether the number of cases is more than expected, is a cluster [14].

4.        Outbreak Epidemiology: Study of a disease cluster or epidemic in order to control or prevent further spread of the disease in the population [3].

5.        Field Epidemiology: Although no medical or epidemiological dictionary has yet to include this term, a definition has been proposed by Goodman. The essential elements of field epidemiology are [4]:

(a)     The problem is unexpected

(b)     An immediate response may be necessary

(c)     Public health epidemiologists must travel to & work on location in the field

(d)     The extent of investigation is likely to be limited because of the imperative for timely intervention

6.        Threatened or Potential Epidemic: It is said to exist when the circumstances are such that the epidemic occurrence of a specific disease ma reasonably be anticipated [1].

7.        Emergency: It can be defined only within the context of the social, political and epidemiological circumstances in which it occurs. The characteristic features of an emergency caused by an epidemic or threatened epidemic therefore include the following, although not all need be present & judgment must be exercised in assessing their importance [1]:

(1)     There is a risk of introduction & spread of the disease in the population

(2)     A large number of cases may reasonably be expected to occur

(3)     The disease involved is of such severity as to lead to serious disability or death

(4)     There is a risk of social &/or economic disruption resulting from the presence of the disease

(5)     The national authorities are unable to cope adequately with situation because a lack or insufficiency of:

                                 i.Technical or professional personnel

                                ii.Organizational experience

                              iii.Necessary supplies or equipments

(6)     There is a danger of international transmission

The types of situation that may come within the category of emergencies will differ from country to country, depending on 2 local factors:

(1)      The preexisting state of endemicity

(2)      The presence or absence of a means of transmission

Factors which promote the occurrence of outbreaks [3]:

1.  Changes in the environment

2.  Changes in the industrial practices

3.  Changes in the agricultural patterns and food processing

4.  Changes in the international transportation of the people, foods and goods

5.  Changes in the human behavior

6.  Increase in the number of people at risk

7.  Increase in the density of population

8.  Immunosuppression

Opportunities offered by the investigation of an outbreak :

1.  Allows epidemiologists to identify risk factors of a disease[3]

2.  Allows epidemiologists to determine the preventive measures that will limit and control the spread of the disease [3]

3.  They meet the public service [6]

4.  They meet the scientific need. Field investigations have led to the discovery of such diseases as Lyme disease & Legionnaires disease [6]

5.  Field investigations also identified the causal association between vinyl chloride & angiosarcoma of the liver and oral contraceptive use & hepatocellular adenoma [6] 

6.  Provide important supplementary information, not often gained from other surveillance methods. This includes age-specific attack rates, CFR, rate of serious disability & estimates of vaccine efficacy [11].                   

Unique aspects of field epidemiology [4,15]:

The methods of epidemic field investigations suffer from limitations that result from the need to act rapidly. These are:

1.  If the outbreak is ongoing at the time of the investigation, there is great urgency to find the source and prevent additional cases. Because of legal liability and the financial interests of persons and institutions involved, there is pressure to conclude the investigation quickly, which may lead to hasty decisions regarding the source of the outbreak.

2.  Field investigations usually rely on a variety of data sources that often are incomplete, less than accurate, or are collected for other purposes.

3.  Epidemiologists on the field are often faced with analyzing small numbers, significantly decreasing the statistical power of their studies.

4.  Because one often arrives late in the epidemic or, indeed, after the fact, there may be no specimens to collect for analysis or acute blood samples to test

5.  There may be a modest amount of publicity surrounding the investigation. As a result, members of community may have preconceived ideas of what happened & who was responsible, making collection of unbiased data difficult

6.  Because vested interests are commonly involved, there will often be some reluctance to participate

7.  There commonly will be conflicting pressures forced by the community or others to intervene & recommend the prevention & control measures before all the evidence is in or before the completion of a scientifically acceptable investigation.

8.  Many a times, statistical association between the disease & the exposure may not be found. Two other explanations for failing to find a "statistically significant" link between one or more exposures and risk for illness also need to be consideredthe number of persons available for study and the accuracy of the available information concerning the exposures. Thus, if the outbreak involves only a small number of cases (and non-ill persons), the statistical power of the analytic study to find a true difference in exposure between the ill and the non-ill (or a difference in the rate of disease among the exposed and the unexposed) is very limited. If the persons involved in the outbreak do not provide accurate information about their exposure to suspected sources or vehicles of infection because of lack of knowledge, poor memory, language difficulty, mental impairment, or other reasons, the resulting misclassification of exposure status also can prevent the epidemiologic study from implicating the source of infection. 

Therefore, in every field investigation, the pressures of time & necessary action will always be balanced against the need for good science.

Trigger events (warning signals) for outbreak investigations [2]:

1.        Clustering of cases or deaths in time and/or space

2. Unusual increase in cases and/or deaths
3. Acute hemorrhagic fever
4. Severe dehydration following diarrhea (usually with vomiting) in patients >5 years of age
5. Acute fever with altered sensorium
6. Acute fever with renal involvement
7. Even a single case of measles or any other epidemic prone disease from a tribal or poorly accessible area
8. Unusual isolate
9. Shifting in age distribution of cases
10. High vector density
11. Natural disasters

If the personnel at the local levels are alert about these warning signals & respond rapidly, it may be possible to arrest the outbreak at an early stage when control measures are most effective & can usually be undertaken within local resources. An important purpose of a surveillance system is to prevent outbreaks or detect them in the early stage.

DISEASE REQUIRING INVESTIGATIONS [2]

The diseases that require investigations can broadly be classified into 4 groups:

1.  Endemic diseases with the potential of causing focal or large outbreaks for example, malaria, cholera, measles, viral hepatitis, meningococcal meningitis, etc.

2.  Diseases for which eradication or elimination goals have been set. A single case of such diseases should be treated as an outbreak for example, poliomyelitis, guinea worm & yaws.

3.  Rare but internationally important diseases with high case fatality rates with the potential of importation due to conducive epidemiological conditions for example, yellow fever.

4.  Outbreaks of unknown etiology

General lines of action during epidemics [1]

When an epidemic occurs, the resulting panic among the population & the pressures of various kinds leave no time for reflecting on the soundness of the actions necessary to control the situation. Success in dealing with an epidemic therefore depends largely on the state of preparedness achieved in advance of any action. The basic initial step is to institutionalize an emergency health service (EHS) headed by a coordinator responsible for preparing contingency plans in which all available & necessary resources in different situations are identified. Another important step is the establishment of an early warning system to detect any unusual incidence of a communicable disease that could cause an emergency situation. It would be an error to consider as an epidemic a hitherto unrecognized endemic situation or a mere seasonal increase in the incidence of a disease. It would also be an error to neglect the significance of a single case of a new disease in a country, which might well be the prelude to a further dramatic spread.

TABLE I GENERAL LINES OF ACTION [1,3]

Although the approach to the understanding of an outbreak should be a systematic one, the experience shows that each epidemic is different from all the others; this is what, at the same time, causes it to spread among the population & makes it both difficult & interesting for the epidemiologist. This is where the epidemiological sixth sense, which can be acquired only by personal experience, is so valuable. Above all, an open mind, free from any preconceived ideas & a refusal to jump to hasty conclusions are the best safeguards in reaching the correct conclusion.

STAGE I PREPAREDNESS [2]

It is important that preparatory action is taken so that the district is able to meet the eventualities if an outbreak occurs. The recommended preparatory actions include:

1.  Identify a Nodal Officer at the state & district level: It is important for receiving information about unusual events & for ensuring that necessary follow-up action is taken in a timely & effective manner.

2. Strengthen the routine surveillance system: An effective surveillance system must be established/strengthened in each district. Adequate facilities must be established at the district level for rapid & efficient analysis of the surveillance data. The nodal officer & other key personnel should receive training in the use of computers particularly in softwares such as EpiInfo etc.

3.  Constitute inter-disciplinary teams (Rapid response teams) at state/district levels: It comprises of epidemiologist or public health specialist, microbiologist, clinician(s), entomologist & concerned program officer. Necessary administrative orders, if issued by the nodal officer, authorize the team to move quickly to the site of the outbreak. This is particularly important in the event of an unusual outbreak for which the services of the expert team may be required at short notice.

4.  Train medical & other health personnel: They should be trained in the principles of outbreak investigations including recognition of early warning signals, epidemiological & entomological parameters, differential diagnoses, laboratory support & specific control measures.

5. List the laboratories at regional/state/district level: A list of laboratories with full address, telephone & fax numbers and e-mails along with the type of tests conducted should be maintained. The nodal officer should identify gaps in laboratory services at each level that can be filled within the given resources.

6. List the high risk pockets in the rural/urban areas: Spot maps of these areas may be prepared so that special attention could be given to the surveillance reports from these areas.

7.  Establish a rapid communication network: In the event of an outbreak, the state nodal officer is required to be notified immediately. The district officers may also need technical & other support in the event of an unusual outbreak or if the diagnosis is not confirmed. Since NICD is the nodal office at the national level, it is expected notification of the outbreak would be made immediately to NICD, also indicating if any technical support is required. Under the national disease surveillance program, it is expected that the district & state levels will be linked to NICD through e-mails & fax. Telephone facilities are expected at the PHC level.

8.  Undertake IEC activities for community participation: Community level IEC activities should be supported so that the key messages regarding the control of the diseases & prevention of the outbreaks are known. Health education materials, which have been prepared in advance and field-tested in advance & field tested will be useful if there is an outbreak in the area because such material may be required at short notice. The medical & health personnel should establish contact with the local community leaders.

9.  Ensure that essential supplies are available: The nodal officer must ensure that essential supplies are in place in the peripheral health facilities & that adequate buffer stocks are maintained at the district level. Inventories should be checked. Life saving medicines such as ORS packets may also be kept at the village level especially in the high risk pockets.

10.     Set up an inter-departmental committee, including the NGOs: During outbreaks, the cooperation of other government departments, NGOs and the community often becomes necessary.

STAGE II INVESTIGATION

Outbreaks should be seen as excellent opportunities to analyse why they occur, identify high risk groups and areas, and evaluate control measures. Efforts therefore, should be made to investigate all the outbreaks as well as the threatened outbreaks

The outbreak epidemiologist is the Sherlock Holmes or the disease detective of public health. Outbreak investigation is a systemic process of evaluating data to form hypotheses, then collecting additional data to test the hypotheses. An understanding of the basic steps of outbreak epidemiology can guide the type of data to collect & how to collect them; however, each outbreak is unique, & it is equally important to be aware of how the current outbreak differs from the previous outbreaks [3]. There are a series of steps that can be used to guide any epidemiologic field investigation and these are outlined in Table I.

In broad sense, the outbreak epidemiologists really do 2 things. First, they collect information that describes the setting of the outbreak, namely, over what time period people became sick, where they acquired the disease, and what the characteristics of the ill people were. These are the descriptive aspects of the investigation. Often, simply by knowing these facts and the diagnosis, the epidemiologist can determine the source & the mode of spread of the agent & can identify those primary at risk of developing the disease. Common sense will often give these answers, and relatively little, if any, further analysis is required. However, on occasion, a second operation, analytical epidemiology, must be used, hopefully to provide answers [4].

A hallmark of outbreak epidemiology is that these steps do not necessarily proceed in a specified sequence. In actuality, several steps in the investigation usually occur simultaneously. These steps are tailored to the situation & depend on factors such as the urgency to implement control measures, the availability of the staff, resources & time, and the difficulty in obtaining the data. Actions and reactions proceed, based on new & cumulative information. Most obviously, measures to control the spread of disease must be implemented early in the investigation & may be altered as data are collected & analyzed.

[A] RECOGNITION & RESPONSE TO A REQUEST FOR ASSISTANCE [4]:

The report. The regional health officer may learn of an epidemic from a variety of sources such as the local health department, a private physician, a hospital administrator, a concerned citizen, or perhaps even the news media. Generally, the most direct & reliable source of information is a local health official. Reports of a possible or real epidemic from others such as private physicians, hospital etc may reveal only a segment of the overall picture of the epidemic or may, indeed, not reflect the existence of an epidemic at all. Therefore, when reports such as these are received at the regional level, the regional official should contact the local health officials & inform them of the reports. Local health officials will usually try to verify such reports and, if verified, they will often investigate the epidemic themselves.

The request. However, if the local health officials request assistance, the regional epidemiologist, before making any decision, should try to acquire as much information as possible regarding the diagnosis, the normal occurrence of the disease & the population primarily affected. The local health departments will be able to provide a considerable amount of valuable information, which can be used in planning for the investigation. It is important to find out exactly why the request for assistance is coming. Regardless of the motivation behind a call for assistance, there must be an established official basis for such a request & official local permission for an epidemiological investigation. Many a field study has been aborted simply because either those requesting assistance had no authority to do so or state, regional, or national teams were investigating without local permission.

[B] CHECKING OF INITIAL INFORMATION ON AN EPIDEMIC:

As soon as the initial information on an outbreak reaches the central level, the EHS coordinator must determine whether the information is correct [1].

[C] FORMULATION OF PLAN OF ACTION:

The EHS advisory committee should meet to formulate a plan of action based on the analysis of the situation and taking technical, economic and political factors into account.

[D] PREPARE FOR THE FIELD WORK:

Preparing for the outbreak investigation & planning the investigation are critical to a successful outcome. It is imperative to identify the investigation team members, to assign responsibilities, to begin the investigation as soon as possible & to conduct progress meetings at regular intervals [3]. Field teams have to carry out 2 functions simultaneously investigation and control. In organizing field teams, attention must be paid to the following factors [1]:

1. Selection of personnel for the team: The ideal composition of a typical field team is given below. However, it can be modified according to the situation [1].

TABLE II COMPOSITION OF A TYPICAL FIELD TEAM

2.       Definition & allocation of sectors: Each team is allocated a sector depending upon the size of the field.

3.       Instructions to the team: Once the field team has been formed, certain key instructions should be emphasized [4]:

(a)     Identify the team leader & the person to whom he/she should report regularly at the regional level.

(b)     Specify when & how communications should be established with the regional home base for information & guidance.

(c)     Emphasize the need for the team to meet with appropriate local health officials immediately upon arriving in the field

(d)     In general, the regional team should try to avoid direct contact with the news media & should always defer to local health officials.

(e)     Before leaving to conduct an investigation, the team leader or his immediate supervisor should write a memorandum. It should summarize how & when the region was contacted, what information was provided by the local health department, what the proposed response by the region is, what the agreed upon commitments of both the local & regional health authorities are, who is on the field team, and when the latter is expected to arrive in the field.

4.       Collaboration & consultation: Now is the time to obtain assurance of cooperation & commitment among the team members (specially the microbiologists) rather than during the field visits or near the end when specimens have already been collected & await testing. Not only must the microbiologists schedule the processing of the specimens, but also they should be asked to recommend what kinds of specimens to collect & how they should be collected & processed. Advice on statistical methods may also be sought at this time.

5.       Equipments and logistic support: The equipments and information needed by the field teams may be as under [1,6]:

(1)     Travel documents, maps

(2)     Money (cash)

(3)     Copies of sample questionnaire

(4)     Paper for line listing or coding of the data

(5)     A hand-held calulator

(6)     A camera

(7)     Pocket references on microbial, physical or chemical agents

(8)     Bedding, mosquito-nets, insect repellants

(9)     Canned food, drinks, water filters & tablets for water purification

(10)  Prophylactic drugs for team members

(11)  Rehydration fluids

(12)  Medicines for the population

(13)  Special protective equipments

(14)  Special equipments for collecting lab specimens

(15)  Special equipments for control measures insecticides, sprayers, chlorinators, syringes, etc

6.       Safety precautions: The mode of transmission of the disease is the key to the precautions that the EHS coordinator should recommend.

7.       Medical evacuation of the team members falling ill

[E] CONFIRM THE EXISTENCE OF AN OUTBREAK:

While confirming the existence of an outbreak, the important questions to ask are are there cases in excess of the baseline rate for that disease & setting? Is the reported case actually a case of the disease or a misdiagnosis? Do all (or most) of the suspect cases have the same infection or similar manifestations? Those investigating the epidemic must be aware of the background level of disease in the population under surveillance [3]. One must also be acutely aware of the artefactual causes of increase (pseudo-epidemics) or decrease in numbers of reported cases, such as changes in local reporting practices, increased interest in certain diseases because of local or national awareness, or changes in the method of diagnosis. Even the presence of a new physician or clinic in the community may lead to a substantial increase in reported number of cases [4]. A review of existing state, local, or facility baseline rates of disease can be compared with the current case number. It is important to take into account the population in which the cases are occurring. The excess frequency should be considered with the help of epidemic threshold curve. The periodic frequency for the preceding period, say 3 years is plotted on a graph. The method of moving averages should be used, for plotting average frequency in a selected period. Another graph at mean plus 2 SD level is superimposed on it. Any fluctuations within these 2 graphs should be treated as endemic fluctuations in frequency & anything beyond it, as epidemic fluctuations [9].

Sometimes it is extremely difficult to establish satisfactorily the existence of an epidemic. Yet because of local pressures, epidemiologists may be obliged to continue the investigation even if they believe that no significant health problem exists [4].

[F] VERIFY THE DIAGNOSIS:

It is the first step of an epidemic investigation. Since it may happen sometimes that the report may be spurious & arise from misinterpretation of the clinical features by the lay public, it is necessary to verify the diagnosis as soon as possible [12]. This involves a review of available clinical & lab findings that support the diagnosis & often involves obtaining more clinical or lab information that is initially provided. One should not attempt to apply newly introduced, experimental or otherwise not broadly recognized confirmatory tests atleast not at this stage. Not every case has to be confirmed. If most patients have the expected or similar clinical features, and, perhaps, 15 to 20% of the cases are lab confirmed, one does not need more confirmation at this time.