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INVESTIGATION OF AN EPIDEMIC
Dr. Amna Rehana Siddiqui
Department of Family and Community Medicine
February 28, 2011
OBJECTIVES
■ List and explain the steps of investigation of
an epidemic
■ Draw & interpret the epidemic curve
■ Compare food specific attack rates to identify
possible vehicles
■ List reasons for investigating an epidemic
WHAT IS AN EPIDEMIC ?
The occurrence of more cases in a
place (or population) and time
than expected (can be 1 case if endemicity was 0)
The terms outbreak and epidemic are
used interchangeably
It is due to breaks in a system that
needs to be identified & corrected
Types of Epidemics/Outbreaks
■ Propagated
Indicative of person to person
transmission e.g. Measles
■ Point-source
Indicative of a common exposure
to a contaminated vehicle or
reservoir e.g. food poisoning
ENDEMIC SITUATION
One that is usually present in a given
geographical area of a population
group in comparison with other areas
or populations
FROM ENDEMIC TO EPIDEMIC ?
■ Observation
■ Increase in disease events
■ Increase in risk factors
■ Surveillance (ongoing) reports
■ Predefined Threshold value
WHY INVESTIGATE?
■ Identify source of infection/s
urgently
■ Detect weakness in existing system
■ To prevent mortality and morbidity
■ To highlight public health needs
■ Could result in policy changes
■ To improve public health
■ To be well informed about agent,
host, and environment.
During an outbreak u need to devise a best strategy utilizing all steps e.g. u will
also be controlling an outbreak (e.g. advice to take precautionary measures) while
you r still defining cases; collecting data and at the same time communicating each
day to those who need to know ; e.g. newspapers; medical director, ministry of
health etc.
HOW TO INVESTIGATE ?
Example 1:
An undiagnosed case of
Crimean Congo hemorrhagic fever
(CCHF) infects a hospital worker
who gets moderately sick
Example 2:
You are requested to investigate food
poisoning cases after a gathering at a
local community hall
■ Identify potential investigation team
■ Research the disease
■ Make administrative arrangements
■ Clarify your and team members’ role
■ Identify & arrange for resources
■ Develop communication strategies
for team, hospital employees, and
public
STEP 1.
Prepare for fieldwork
STEP 2: Establish the existence
of epidemic
Does the observed number of cases
exceed the existing number ?
■ Literature search
■ Consult the experts / Government
■ Surveillance records
■ Previous reports
■ Is there a confirmed case ?
■ Are there additional cases?
■ Speak directly with the persons who
are affected
■ Clinical criteria
■ Laboratory methods available ?
■ Arrange to send samples to relevant
laboratories
■ Initial reports correct ?
■ Possible modes of spread
STEP 3
Verify the diagnosis
PS: STEPS ARE NOT IN ANY
Step 3 Continued
Possible Exposures
■ Possible Cause of illness
■ Try best to know your agent/disease
■ Clinical picture
■ Pathogenesis
■ Mode of transmission
■ Natural Reservoir
■ Common Vehicle or Vector
Step 3 Continued
Consider Chain of Infection
STEP 4
Define and identify cases
■ Develop a case definition, identify and
count cases
■ Develop a line listing for all
■ Create a working case definition for
CCHF
■ For hospital workers/Contacts
Any one with fever &/ sore throat
■ For Cases
Anyone with undiagnosed fever, or has
any type of bleeding
PS: STEPS ARE NOT IN ANY ORDER during outbreak
Step 4a:
Establishing a Case Definition
□ A case definition is a standard set of
criteria for deciding whether an
individual should be classified as
having the health condition of interest.
□ A case definition includes clinical
criteria and--particularly in the
setting of an outbreak
investigation--restrictions by time,
place and person.
□ Apply them consistently and without
bias to all persons under investigation.
□ To be classified as confirmed, a
case usually must have
laboratory verification. A case
classified as probable usually has
typical clinical features of the
disease without laboratory
confirmation. A case classified as
possible usually has fewer of the
typical clinical features.
CASE DEFINITION
□ Early in an investigation, investigators
often use a WORKING case definition
which includes confirmed, probable,
and even possible cases.
□ Later on, when hypotheses have come
into sharper focus, the investigator
may “tighten” the case definition
ACCORDINGLY /by dropping the
possible category.
DEFINING CASES
Step 4 continued
Case finding and Line listing
/Spread Sheet
Each row represents data for a subject
and columns represent following
■ Identification
■ Symptom onset date and time
■ Symptoms present
■ Suspected exposure date if known
■ Residence
■ Age
■ Gender
■ Laboratory tests
■ Confirmed case
Line Listing: example
ID Date
Surg
Sym
onset
age sex C/S Case
defn
OT # Surg
Type
Surg
001 Jan 1 Fev 33 M Await poss/
prob
1 clean Hern
002 Jan 1 Pain 25 M Staph CON
FIRM
2 clean Hern
003 Jan 1 Fev 28 F E coli ?2nd
await
1 clean Biop
004 Jan 1 Red 24 M Staph CON
FIRM
2 clean Hern
Each row represents data for a
subject
Change order by any column and
STEP 5
Descriptive epidemiology
■ Find cases systematically
■ Epidemic / Outbreak curve
■ Map
■ Identify demographic and other
characteristics of persons at risk
■ Tabulate and orient the data in terms of
■ Person
■ Place
■ Time
PS: STEPS ARE NOT IN ANY
ORDER
STEP 5 Continued
Epidemic Curve
■ Graph showing number of cases
on ‘Y’ axis and time line on ‘X’ axis
■ Indicates the magnitude of
epidemic over time
■ Can distinguish epidemic from an
endemic situation
■ Indicates pattern of spread
■ Outliers
EPIDEMIC CURVE for CCHF 2000
Propagated Outbreak
EPIDEMIC CURVE
Point Source
outbreak
STEP 5 Continued
Person: who is getting sick ?
■ Age
■ Sex
■ Race/Ethnicity
■ Socio-Economic Status
■ Behavior related
STEP 5 Continued
Place: where are the cases
coming from ?
■ Geographic
Distribution
■ Homes
■ Work
■ School
■ Orphanages
■ Hospitals/Clinics
STEP 5 Continued
Time: when are they getting
sick?
■ Onset of symptoms
■ Incubation Period
■ Infectious Period
■ Seasonality
■ Baseline vs. epidemic
Following things help
■ Open ended and wide ranging
interviews/history of travel/foods eaten
■ Descriptive epidemiology
■ Occupation/residence/raw meat use
■ Line listing of all subjects
■ Epidemic curve
■ Existing knowledge of disease
STEP 6
DEVELOP HYPOTHESES
Step 6:
Developing Hypotheses
□ All aspects of the investigation should be
addressed:
- source of the agent,
- mode of transmission, (vehicle/vector),
- exposures that caused the disease,
- any additional time, person, & place factors
e.g. CCHF transmitted by blood and body fluids what other means as there were
patients from occupations who were not exposed to blood and body fluids?
First, consider what you know about
the disease itself:
□ What is the agent’s usual reservoir?
□ How is it usually transmitted?
□ What vehicles are commonly
implicated?
□ What are the known risk factors?
DO EXTENSIVE Literature Search;
Be familiar with the disease
STEP 7
EVALUATE HYPOTHESES
■ Further analyze existing data
■ Compare ill populations with not ill
populations
■ Compare attack rates
■ Conduct statistical tests
■ Recommend Control Measures
Step 8
Execute additional Studies
□ Refine hypothesis
□ Calculate & compare attack rates (AR)*
□ Compare AR in Occupational exposure to
blood/body fluids with occupations not
exposed to blood/body fluids; e.g. HCW vs
Non HCW; butchers vs non butchers
□ 2. Which food item caused poisoning?
Compare attack rates (e.g. RR) in those who
ate meat and in those who did not eat meat
AR (a) in meat eaters=# who got sick / Total # who ate meat
AR (b) in not meat eaters=# who got sick / Total # who did not eat meat
Step 8
Execute additional Studies
□ Environmental & Laboratory tests (e.
g. home visit; left over food samples)
□ Do additional epidemiologic studies;
■ Case control;
■ Retrospective cohort studies;
■ Follow up to evaluate control measures;
Basic measure of infectivity
Attack rate =
# of new cases of specific disease in a time
population at risk during the same
period
Define Population
Retrospective cohort
Food
Items at
dinner
Ate food item
(exposed)
Did not eat
(unexposed)
RR=
a/b
Ill well AR
% (a)
Ill well AR
% (b)
RR
meat 29 17 63 17 12 59
spinach 26 17 60 20 12 62
potato 23 14 62 23 14 62
salad 13 11 54 28 19 60
Ice cream 43 11 80 3 18 14
Retrospective cohort
Food
Items at
dinner
Ate food item
(exposed)
Did not eat
(unexposed)
RR=
a/b
Ill well AR
% (a)
Ill well AR
% (b)
RR
meat 29 17 63 17 12 59 1.07
spinach 26 17 60 20 12 62 0.97
potato 23 14 62 23 14 62 1.00
salad 13 11 54 28 19 60 0.90
Ice cream 43 11 80 3 18 14 5.71
Case control
Exposure Case Control Total
Ate at A
restaurant
Yes 30 36 66
No 10 70 80
Total 40 106 146
Calculate the OR
Case control
Exposure Case Control Total
Ate at A
restaurant
Yes 30 36 66
No 10 70 80
Total 40 106 146
OR= (30 x 70) / (36 x 10) = 5.83
Example of Surgical Wound
Infections
□ Investigating Post operative Surgical Wound
Infections
□ Confirm; case definition, Determine outbreak
period, Epidemic curve, Line listing for risk
factors
□ Risk factors; OT, Doctors, Staff, Anesthetists,
type of surgery, ASA status, Duration of
surgery, aseptic conditions, etc.
□ Calculate attack rate for all
□ Evaluate hypothesis
RR of illness for the Theatre
Disease→
Exposure↓
SWI
Yes
SWI
No
Attack
Rate
OT 1 9 7
(9/16)
56%
OT 2 7 11
(7/18)
38%
Relative Risk= 56/38=1.4 (95% CI 0.70 – 2.98); (Chi sq) p=0.50
Risk Ratio: Attack rate in OT1 = 56/38 = 1.4
Attack rate in OT2
RR of illness for Surgery Duration
Disease→
Exposure↓
SWI
Yes
SWI
No
Attack
Rate
Duration
> 2 hrs 14 6
(14/20)
70%
Duration
<=2 hrs 5 12
(5/12)
29%
Relative Risk= 70/29 = 2.4, 95% CI 1.08-5.25; p value 0.03
Risk Ratio: Attack rate Duration > 2 hrs = 70/29 = 2.4
Attack rate Duration <= 2 hrs
STEP 9: Take Immediate
Control Measures
■ Surveillance for hospital employees
■ Surveillance for cases
■ Health education
■ Reduce panic
■ How to avoid exposures/Contacts
■ How and where to report
■ Appropriate quarantine and isolation
measures
■ Cohorting
PS: STEPS ARE NOT IN ANY
An outbreak might be controlled by :
- destroying contaminated foods,
- sterilizing contaminated water, or
- destroying mosquito breeding sites
- vaccinating animals/tick
prevention -An infectious food
handler could be removed from the
job and treated.
-Cancelling restaurant permit and
reviewing inspecting rules
Control Measures
reducing host susceptibility ,
- Immunization ,
- chemoprophylaxis for travelers
STEP 10
COMMUNICATE FINDINGS
■ Summarize investigation for
requesting authority
■ Prepare written report
■ Prevention of future similar outbreaks
The report should include:
□ Introducing the identification of epidemic
□ Methods; data collection, analyses, and
interpretations for environmental, laboratory,
and epidemiological methods
□ Results; descriptive as well as analytic
□ Implemented preventive and control
measures
□ Effectiveness of control measures.
□ Impacts relevant to prevention and control.
□ Make recommendations regarding future
surveillance and control.
□ Distribute report to others in disease control
programs as well as publish by doing studies.
The report:
□ A record of performance and a
document for potential legal issues.
□ Reference if the health department
encounters a similar situation in the
future.
□ Broader purpose for contributing to the
knowledge base of epidemiology and
public health.
STEP 10
FOLLOW UP
■ May execute further additional
studies
■ Maintain surveillance for a pre-
defined period of time
■ Evaluate interventions and control
measures
■ Formulate recommendations
Figure . Meningococcal disease during the 2000 Hajj: Jeddah, Mecca,
and Medina, January 24–June 5, 2000.
The number of cases of sero group specific meningococcal disease is shown by
date. The duration of the 2000 Hajj is indicated.
Cholera epidemic: evolution of Epidemiology
John Snow and the Broad Street Pump, 1854
Snows dot map of London
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02. EPIDEMIC Investigation-feb28Final.pdf

  • 1. INVESTIGATION OF AN EPIDEMIC Dr. Amna Rehana Siddiqui Department of Family and Community Medicine February 28, 2011
  • 2. OBJECTIVES ■ List and explain the steps of investigation of an epidemic ■ Draw & interpret the epidemic curve ■ Compare food specific attack rates to identify possible vehicles ■ List reasons for investigating an epidemic
  • 3. WHAT IS AN EPIDEMIC ? The occurrence of more cases in a place (or population) and time than expected (can be 1 case if endemicity was 0) The terms outbreak and epidemic are used interchangeably It is due to breaks in a system that needs to be identified & corrected
  • 4. Types of Epidemics/Outbreaks ■ Propagated Indicative of person to person transmission e.g. Measles ■ Point-source Indicative of a common exposure to a contaminated vehicle or reservoir e.g. food poisoning
  • 5. ENDEMIC SITUATION One that is usually present in a given geographical area of a population group in comparison with other areas or populations
  • 6. FROM ENDEMIC TO EPIDEMIC ? ■ Observation ■ Increase in disease events ■ Increase in risk factors ■ Surveillance (ongoing) reports ■ Predefined Threshold value
  • 7. WHY INVESTIGATE? ■ Identify source of infection/s urgently ■ Detect weakness in existing system ■ To prevent mortality and morbidity ■ To highlight public health needs ■ Could result in policy changes ■ To improve public health ■ To be well informed about agent, host, and environment.
  • 8. During an outbreak u need to devise a best strategy utilizing all steps e.g. u will also be controlling an outbreak (e.g. advice to take precautionary measures) while you r still defining cases; collecting data and at the same time communicating each day to those who need to know ; e.g. newspapers; medical director, ministry of health etc.
  • 9. HOW TO INVESTIGATE ? Example 1: An undiagnosed case of Crimean Congo hemorrhagic fever (CCHF) infects a hospital worker who gets moderately sick Example 2: You are requested to investigate food poisoning cases after a gathering at a local community hall
  • 10. ■ Identify potential investigation team ■ Research the disease ■ Make administrative arrangements ■ Clarify your and team members’ role ■ Identify & arrange for resources ■ Develop communication strategies for team, hospital employees, and public STEP 1. Prepare for fieldwork
  • 11. STEP 2: Establish the existence of epidemic Does the observed number of cases exceed the existing number ? ■ Literature search ■ Consult the experts / Government ■ Surveillance records ■ Previous reports ■ Is there a confirmed case ? ■ Are there additional cases?
  • 12. ■ Speak directly with the persons who are affected ■ Clinical criteria ■ Laboratory methods available ? ■ Arrange to send samples to relevant laboratories ■ Initial reports correct ? ■ Possible modes of spread STEP 3 Verify the diagnosis PS: STEPS ARE NOT IN ANY
  • 13. Step 3 Continued Possible Exposures ■ Possible Cause of illness ■ Try best to know your agent/disease ■ Clinical picture ■ Pathogenesis ■ Mode of transmission ■ Natural Reservoir ■ Common Vehicle or Vector
  • 14. Step 3 Continued Consider Chain of Infection
  • 15. STEP 4 Define and identify cases ■ Develop a case definition, identify and count cases ■ Develop a line listing for all ■ Create a working case definition for CCHF ■ For hospital workers/Contacts Any one with fever &/ sore throat ■ For Cases Anyone with undiagnosed fever, or has any type of bleeding PS: STEPS ARE NOT IN ANY ORDER during outbreak
  • 16. Step 4a: Establishing a Case Definition □ A case definition is a standard set of criteria for deciding whether an individual should be classified as having the health condition of interest. □ A case definition includes clinical criteria and--particularly in the setting of an outbreak investigation--restrictions by time, place and person. □ Apply them consistently and without bias to all persons under investigation.
  • 17. □ To be classified as confirmed, a case usually must have laboratory verification. A case classified as probable usually has typical clinical features of the disease without laboratory confirmation. A case classified as possible usually has fewer of the typical clinical features. CASE DEFINITION
  • 18. □ Early in an investigation, investigators often use a WORKING case definition which includes confirmed, probable, and even possible cases. □ Later on, when hypotheses have come into sharper focus, the investigator may “tighten” the case definition ACCORDINGLY /by dropping the possible category. DEFINING CASES
  • 19. Step 4 continued Case finding and Line listing /Spread Sheet Each row represents data for a subject and columns represent following ■ Identification ■ Symptom onset date and time ■ Symptoms present ■ Suspected exposure date if known ■ Residence ■ Age ■ Gender ■ Laboratory tests ■ Confirmed case
  • 20. Line Listing: example ID Date Surg Sym onset age sex C/S Case defn OT # Surg Type Surg 001 Jan 1 Fev 33 M Await poss/ prob 1 clean Hern 002 Jan 1 Pain 25 M Staph CON FIRM 2 clean Hern 003 Jan 1 Fev 28 F E coli ?2nd await 1 clean Biop 004 Jan 1 Red 24 M Staph CON FIRM 2 clean Hern Each row represents data for a subject Change order by any column and
  • 21.
  • 22. STEP 5 Descriptive epidemiology ■ Find cases systematically ■ Epidemic / Outbreak curve ■ Map ■ Identify demographic and other characteristics of persons at risk ■ Tabulate and orient the data in terms of ■ Person ■ Place ■ Time PS: STEPS ARE NOT IN ANY ORDER
  • 23. STEP 5 Continued Epidemic Curve ■ Graph showing number of cases on ‘Y’ axis and time line on ‘X’ axis ■ Indicates the magnitude of epidemic over time ■ Can distinguish epidemic from an endemic situation ■ Indicates pattern of spread ■ Outliers
  • 24. EPIDEMIC CURVE for CCHF 2000 Propagated Outbreak
  • 26. STEP 5 Continued Person: who is getting sick ? ■ Age ■ Sex ■ Race/Ethnicity ■ Socio-Economic Status ■ Behavior related
  • 27. STEP 5 Continued Place: where are the cases coming from ? ■ Geographic Distribution ■ Homes ■ Work ■ School ■ Orphanages ■ Hospitals/Clinics
  • 28. STEP 5 Continued Time: when are they getting sick? ■ Onset of symptoms ■ Incubation Period ■ Infectious Period ■ Seasonality ■ Baseline vs. epidemic
  • 29. Following things help ■ Open ended and wide ranging interviews/history of travel/foods eaten ■ Descriptive epidemiology ■ Occupation/residence/raw meat use ■ Line listing of all subjects ■ Epidemic curve ■ Existing knowledge of disease STEP 6 DEVELOP HYPOTHESES
  • 30. Step 6: Developing Hypotheses □ All aspects of the investigation should be addressed: - source of the agent, - mode of transmission, (vehicle/vector), - exposures that caused the disease, - any additional time, person, & place factors e.g. CCHF transmitted by blood and body fluids what other means as there were patients from occupations who were not exposed to blood and body fluids?
  • 31. First, consider what you know about the disease itself: □ What is the agent’s usual reservoir? □ How is it usually transmitted? □ What vehicles are commonly implicated? □ What are the known risk factors? DO EXTENSIVE Literature Search; Be familiar with the disease
  • 32. STEP 7 EVALUATE HYPOTHESES ■ Further analyze existing data ■ Compare ill populations with not ill populations ■ Compare attack rates ■ Conduct statistical tests ■ Recommend Control Measures
  • 33. Step 8 Execute additional Studies □ Refine hypothesis □ Calculate & compare attack rates (AR)* □ Compare AR in Occupational exposure to blood/body fluids with occupations not exposed to blood/body fluids; e.g. HCW vs Non HCW; butchers vs non butchers □ 2. Which food item caused poisoning? Compare attack rates (e.g. RR) in those who ate meat and in those who did not eat meat AR (a) in meat eaters=# who got sick / Total # who ate meat AR (b) in not meat eaters=# who got sick / Total # who did not eat meat
  • 34. Step 8 Execute additional Studies □ Environmental & Laboratory tests (e. g. home visit; left over food samples) □ Do additional epidemiologic studies; ■ Case control; ■ Retrospective cohort studies; ■ Follow up to evaluate control measures;
  • 35. Basic measure of infectivity Attack rate = # of new cases of specific disease in a time population at risk during the same period Define Population
  • 36. Retrospective cohort Food Items at dinner Ate food item (exposed) Did not eat (unexposed) RR= a/b Ill well AR % (a) Ill well AR % (b) RR meat 29 17 63 17 12 59 spinach 26 17 60 20 12 62 potato 23 14 62 23 14 62 salad 13 11 54 28 19 60 Ice cream 43 11 80 3 18 14
  • 37. Retrospective cohort Food Items at dinner Ate food item (exposed) Did not eat (unexposed) RR= a/b Ill well AR % (a) Ill well AR % (b) RR meat 29 17 63 17 12 59 1.07 spinach 26 17 60 20 12 62 0.97 potato 23 14 62 23 14 62 1.00 salad 13 11 54 28 19 60 0.90 Ice cream 43 11 80 3 18 14 5.71
  • 38. Case control Exposure Case Control Total Ate at A restaurant Yes 30 36 66 No 10 70 80 Total 40 106 146 Calculate the OR
  • 39. Case control Exposure Case Control Total Ate at A restaurant Yes 30 36 66 No 10 70 80 Total 40 106 146 OR= (30 x 70) / (36 x 10) = 5.83
  • 40. Example of Surgical Wound Infections □ Investigating Post operative Surgical Wound Infections □ Confirm; case definition, Determine outbreak period, Epidemic curve, Line listing for risk factors □ Risk factors; OT, Doctors, Staff, Anesthetists, type of surgery, ASA status, Duration of surgery, aseptic conditions, etc. □ Calculate attack rate for all □ Evaluate hypothesis
  • 41. RR of illness for the Theatre Disease→ Exposure↓ SWI Yes SWI No Attack Rate OT 1 9 7 (9/16) 56% OT 2 7 11 (7/18) 38% Relative Risk= 56/38=1.4 (95% CI 0.70 – 2.98); (Chi sq) p=0.50 Risk Ratio: Attack rate in OT1 = 56/38 = 1.4 Attack rate in OT2
  • 42. RR of illness for Surgery Duration Disease→ Exposure↓ SWI Yes SWI No Attack Rate Duration > 2 hrs 14 6 (14/20) 70% Duration <=2 hrs 5 12 (5/12) 29% Relative Risk= 70/29 = 2.4, 95% CI 1.08-5.25; p value 0.03 Risk Ratio: Attack rate Duration > 2 hrs = 70/29 = 2.4 Attack rate Duration <= 2 hrs
  • 43. STEP 9: Take Immediate Control Measures ■ Surveillance for hospital employees ■ Surveillance for cases ■ Health education ■ Reduce panic ■ How to avoid exposures/Contacts ■ How and where to report ■ Appropriate quarantine and isolation measures ■ Cohorting PS: STEPS ARE NOT IN ANY
  • 44. An outbreak might be controlled by : - destroying contaminated foods, - sterilizing contaminated water, or - destroying mosquito breeding sites - vaccinating animals/tick prevention -An infectious food handler could be removed from the job and treated. -Cancelling restaurant permit and reviewing inspecting rules
  • 45. Control Measures reducing host susceptibility , - Immunization , - chemoprophylaxis for travelers
  • 46. STEP 10 COMMUNICATE FINDINGS ■ Summarize investigation for requesting authority ■ Prepare written report ■ Prevention of future similar outbreaks
  • 47. The report should include: □ Introducing the identification of epidemic □ Methods; data collection, analyses, and interpretations for environmental, laboratory, and epidemiological methods □ Results; descriptive as well as analytic □ Implemented preventive and control measures □ Effectiveness of control measures. □ Impacts relevant to prevention and control. □ Make recommendations regarding future surveillance and control. □ Distribute report to others in disease control programs as well as publish by doing studies.
  • 48. The report: □ A record of performance and a document for potential legal issues. □ Reference if the health department encounters a similar situation in the future. □ Broader purpose for contributing to the knowledge base of epidemiology and public health.
  • 49. STEP 10 FOLLOW UP ■ May execute further additional studies ■ Maintain surveillance for a pre- defined period of time ■ Evaluate interventions and control measures ■ Formulate recommendations
  • 50. Figure . Meningococcal disease during the 2000 Hajj: Jeddah, Mecca, and Medina, January 24–June 5, 2000. The number of cases of sero group specific meningococcal disease is shown by date. The duration of the 2000 Hajj is indicated.
  • 51. Cholera epidemic: evolution of Epidemiology John Snow and the Broad Street Pump, 1854
  • 52. Snows dot map of London