Communicable disease surveillance

Robert Allard MDCM MSc FRCPC

October 2003

Infectious diseasesurveillance designs

Traditional disease notification Outbreak investigation Cluster investigation Enhanced surveillance Sentinel surveillance Emerging infectious diseases

diagnosis-based surveillance syndromic surveillance

Molecular biology and surveillance

Definition“Surveillance, when applied to a disease, means the continued watchfulness over the distribution and trends

of incidence through the systematic collection, consolidation and

evaluation of morbidity and mortality reports and other relevant data.

Intrinsic in the concept is the regular dissemination of the basic data and interpretation to all who have contributed and to all others who need to know.

The concept, however, does not encompass direct responsibility for control activities.”

A.D. Langmuir, 1963

COMMUNICABLE DISEASESURVEILLANCE or RESEARCH? Ongoing Generates hypothesis Incomplete data on

population Simpler analysis Rapid dissemination of

results Results not necessarily

generalizable Triggers intervention

Time-limited Tests hypothesis Complete data on sample

More complex analysis Slower dissemination of

results Aims at generalizability

Looser link to intervention

Traditional disease notification Legal framework List of reportable (or notifiable) conditions Verification and analysis Investigation Public health intervention Dissemination of results Evaluation and updating

DISEASE SELECTION CRITERIA Incidence Morbidity Mortality / severity / lethality Communicability / potential for outbreaks Preventability Changing pattern in previous 5 years Socioeconomic burden Public health response necessary Public perception of risk International and other sector consideration

Rank (Priority for Canadian government, first 12 of 43) 1988 19981 Measles HIV 2 Tuberculosis AIDS 3 AIDS Laboratory confirmed influenza 4 Hepatitis B Tuberculosis 5 Pertussis Measles 6 Salmonellosis Rabies 7 Rubella Pertussis 8 H. influenzae Invasive meningococcal disease invasive disease9 Diphtheria Hepatitis C 10 Chickenpox Botulism 11 Meningococcal Poliomyelitis infection 12 Gonococcal Creutzfeld-Jacob Disease infection

Legal framework Required for

transmission of confidential information investigation intervention

Varies between jurisdictions Québec specifics:

no more anonymously reportable conditions HIV-AIDS is “provincially reportable” duty to “signal” non-reportable conditions distinction between “surveillance” and “vigie” surveillance ethics committee

VALIDITY OF REPORTS(False positives) Nosologic definitions

May be different from clinical definitions Laboratory confirmation The problem of nearly eliminated diseases

Most positives are false positives• Poor clinical diagnostic accuracy• Importance of eliminating alternate Dx

Only confirmed cases enter statistics

COMPLETENESS OF REPORTING(False negatives) Varies by

Type of reporting (active, passive) Source of reports Disease

Need not be high, provided it is stable More important if intervention is possible

Stages in the reporting of shigellosis (CDC, ca. 1970)

0102030405060708090

100

Inf Symp Cons Cult Pos Report Inv Neg

ROUTINE INVESTIGATIONOF REPORTED CASES MD, patient and/or relative are interviewed Not all cases can be investigated

Intervention possible Transmissibility is high Case is unusual Outbreak is suspected

ANALYSIS OF SURVEILLANCE DATA

“Monitoring trends is the cornerstone objective of most surveillance systems.”

Buehler, Modern Epidemiology (1998), p. 438

Standard outputs Periodic reports

Mail and internet Monthly Commented

Newsletter Special alerts

fax and e-mail Annual report

MAIN MONTHLY SURVEILLANCEOUTPUT, MONTREAL    2003 au 12 juil. 2002 au 13 juil. 2001 au 14 juil.

    Courant Cumulatif Courant Cumulatif Courant Cumulatif

Maladie   N Taux N Taux N Taux N Taux N Taux N Taux  

Amibiase   11 7.8 76 7.7 9 6.4 63 6.4 8 5.7 77 7.9  

Botulisme   0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0  

Brucellose   0 0.0 1 0.1 0 0.0 0 0.0 0 0.0 1 0.1  

Campylobactériose   27 19.2 181 18.3 52 37.0 224 22.8 37 26.5 184 18.8  

Chancre mou   0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 1 0.1  

Infection à Chlamydia trachomatis   182 129.1 1706 172.9 201 143.2 1697 172.7 195 139.5 1598 163.3  

Choléra   0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0  

Coqueluche   3 2.1 17 1.7 6 4.3 65 6.6 7 5.0 74 7.6  

Diarrhée épidémique   0 0.0 27 2.7 1 0.7 4 0.4 0 0.0 5 0.5  

Encéphalite transmise par arthropodes   0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0  

Entérite à E. coli O157:H7   0 0.0 4 0.4 2 1.4 19 1.9 9 6.4 27 2.8  

Entérite à Yersinia enterocolitica   2 1.4 16 1.6 5 3.6 13 1.3 2 1.4 20 2.0  

Fièvre paratyphoïde   0 0.0 3 0.3 1 0.7 2 0.2 0 0.0 4 0.4  

Fièvre typhoïde   1 0.7 5 0.5 0 0.0 8 0.8 1 0.7 4 0.4  

Fièvre Q   0 0.0 0 0.0 0 0.0 1 0.1 0 0.0 0 0.0  

Giardiase   16 11.4 153 15.5 19 13.5 117 11.9 18 12.9 135 13.8  

Detail of preceding table:

“Figure 1” analysis

ANNUAL FORECASTS

Importance of explainingthe main surveillance resultsNote explicative concernant les statistiques des maladies infectieuses à déclaration

obligatoire (MADO) et autres maladies infectieuses sous surveillancePériode 08 de l’année 2003 (semaines 29 à 32 13-07-2003 au 09-08-2003])

Shigellose

L’excès significatif de cas de shigellose s’explique par une éclosion parmi le personnel d’un établissement de soins de Montréal. Quinze cas ont été identifiés, dont treize confirmés par culture (S. sonnei) et deux reliés épidémiologiquement à un cas confirmé. Les symptômes ont commencé entre le 14 et le 18 juillet. De plus, quelques cas ont été déclarés dans la communauté, dus au même agent, et apparemment reliés à un ou des restaurants. Les organismes impliqués dans l’enquête (DSP, CUVM, MAPAQ) ont exploré divers liens possibles entre tous ces cas. L’éclosion est maintenant considérée comme terminée et des aliments achetés à la cafétéria semblent être la source commune de l’infection pour les cas dans l’établissement.Remerciements à Mme Hélène Rodrigue pour l’information.

Outbreak investigation Time, place, person

or Who, what, where, when, why?

or rather Who, what, where, when, how? How = by what mode of transmission? Two basic modes:

Person-to-person Common source

DESIGNS FOROUTBREAK INVESTIGATIONS Descriptive

Common exposure • Suitable when exposure is very specific

Person to person contacts Case-control

Controls are:• Other attendees at event who remained healthy• Population sample (often drawn by RDD)

Case-case Controls are:

• Cases of other reportable diseases• Cases of the same disease, caused

by a different strain than caused the outbreak

CLUSTERING:temporal and spatial

Cluster:

“A geographically bounded group of occurrences of sufficient size and concentration to be unlikely to have occurred by chance.”

(Knox, 1989)

WHY THE INTERESTIN CLUSTERING? Cases are effects. If effects are clustered, their causes could

also be. Causes with the same effects may be one

and the same. A common cause may be easier to

identify (how ?) remove or control.

TEMPORAL CLUSTERING Based on time-series (of numbers of notified cases) Time unit:

Week Month (period)

Favourite statistical methods: ARIMA or Box-Jenkins modelling “Figure 1” method

Box-Jenkins modelling:the time series and the forecasts

SPATIAL CLUSTERING Less useful for surveillance in urban

compared to rural environments Very many methods exist Most require more or less unrealistic

assumptions

WNV-INFECTED CORVIDS (red)

SMOOTHED MAP OF INFECTED CORVIDS(Thanks to Christian Back)

HUMAN WNV CASES(a few days later, Sept. 19, 2003)

GROWING IMPORTANCEOF ZOONOSES vCJD, SARS, WNV, monkeypox, rabies etc. Disease trends in other species have to be

followed and related to trends in humans Interdisciplinary collaboration essential Worrisome development,

but very stimulating work

ENHANCED SURVEILLANCE Priority problem identified Concept is elastic: traditional surveillance plus any

combination of Extra resources allocated Increased collaboration between government levels Standardized data collection Increased data quality control Access to better laboratory tests Increased analytic possibilities Other surveillance methods

Greater potential to guide policy making?

SENTINEL SURVEILLANCE Does not seek completeness Uses purposely selected sources of information Prefers sources likely to observe earliest occurrence

of phenomenon under surveillance May be active or passive Relies heavily on real-time communication Positive findings often trigger other forms of

surveillance

CHOICE OF SENTINELS Physicians Pharmacies Laboratories Hospitals Public health Units, etc. Combination of sources

(see http://www.cdc.gov/foodnet/surveys.htm)

SUCCESS FACTORS (?) Linked to professional organizations Passive Provide feedback and other benefits Surveillance objectives are

Relevant Flexible Suggested by participants

IMPORTED FALCIPARUM MALARIA IN EUROPE European Network on Surveillance of

Imported Infectious Diseases About 45 hospital departments of infectious

diseases 1659 patients seen in 1999-2000 About 10% of all patients with malaria seen in

Europe

Results: European travellers 48%

Immigrants 52% Country of infection: West Africa for 63% Chemoprophylaxis had been taken by

• 40% of travellers• 28% of immigrants

Lethality: 5 patients (all travellers) Useful results, but is it surveillance?

Continuous collection, analysis, reporting? No denominators or analysis of trends

EMERGINGINFECTIOUS DISEASES

Strategic/political aspects of the concept “Emerging infections are those diseases whose

incidence has increased within the past two decades or … threatens to increase in the near future.” (NY ACAD SCI)

An emerging infection can be due to an agent previously unknown previously unknown in humans previously unknown in a given area previously non pathogenic or less pathogenic previously non resistant to antibiotics previously controlled by preventive measures

SOME EMERGING AGENTS 1973 Rotavirus 1977 Ebola virus 1977 Legionellosis 1981 HIV 1982 E.coli O157:H7 1982 Lyme disease 1983 H. pylori

1986 BSE, CJD (prions) 1989 Hepatitis C 1992 Cholera O139 1995 HHV-8 1999 WNV 2001 Anthrax 2002 SARS CoV

FACTORS IN EMERGENCE Microbial adaptation and change

Drug resistance New virulence or toxin production

Environmental changes Global warming Deforestation

Societal events Impoverishment War Immigration

Human behaviour Sexual, drug use Travel Use of child care facilities

Food production Globalization

Health care Widespread use of antibiotics Immunosuppressive drugs

Public health infrastructure Curtailment of preventive programs

EID: diagnosis-based surveillance SARS: severe acute respiratory syndrome Originated in SE Asia in November 2002 Single agent suspected early (SARS CoV) Importation to Toronto (“superspreader”) Canada-wide alert in April 2003 Canadian case definition based on WHO’s This case definition was crucial to

Day-to-day surveillance and control activities Description of outbreak

Surveillance case definition: Suspect Case: A person presenting with:

Fever (over 38 degrees Celsius)AND Cough or breathing difficultyAND One or more of the following exposures during the 10 days prior to

the onset of symptoms:• Close contact with a person who is a suspect or probable case• Recent travel to an "Area with recent local transmission" of SARS

outside of Canada• Recent travel or visit to an identified setting in Canada where exposure

to SARS may have occurred (e.g., hospital [including any hospital with an occupied SARS unit], household, workplace, school, etc.). This includes inpatients, employees or visitors to an institution if the exposure setting is an institution.

Probable Case: A suspect case with radiographic evidence of infiltrates

consistent with pneumonia or respiratory distress syndrome (RDS) on chest x-ray (CXR).

OR A suspect case with autopsy findings consistent with the

pathology of RDS without an identifiable cause.

Exclusion Criteria A suspect or probable case should be excluded if an

alternate diagnosis can fully explain their illness.

SARS EPIDEMIC CURVE, CANADA, 2003

EID: syndromic surveillance Observes the occurrence not of diagnosed

disease but of a pre-defined syndrome Syndrome = “a pattern of symptoms

indicative of some disease”, usually unidentified

The syndrome may be associated with one or more disease entities

A diagnosis is sought (for surveillance) only when a cluster of the syndrome is detected

EXAMPLES OF SYNDROMES FOR SURVEILLANCE Fever + upper or lower respiratory signs or

symptoms (plague,anthrax, ricin, staph. toxin or …)

Fever + rash (smallpox or …)

Fever + hemorrhages (Ebola, Marburg or …)

Fever + GI symptoms (salmonellosis or …)

Cranial-nerve impairment (botulism or …)

Fever + unexplained death

OPERATIONALIZATION OF SYNDROMIC SURVEILLANCE Most promising general source of information:

emergency department (or other primary care source) presenting complaints (PC)

Information is computerized on site transmitted periodically to central server scanned to extract PCs and other information

PCs are syntesized onto syndromes if possible Clusters of syndromes are tested for Significant clusters flagged for further investigation

Simple temporal analysis of HMO data(Thanks to Richard Platt)

Simple spatial analysis of HMO data(Thanks to Richard Platt)

MOLECULAR BIOLOGYAND SURVEILLANCE

Based on ability to distinguish different strains of same agent, based on its nucleic acid (genotype)

Different methods, short of sequencing, can be used

Must be able to detect mutations that are Frequent enough to have produced many

different strains over the years Rare enough not to occur during an outbreak

DNA electrophoretic pattern

Uses of fingerprinting Prove that cases in an outbreak are related Prove that suspected vehicle is the true common

source Identify outbreaks missed by traditional methods

TB in chronic care hospitals for old people Help select cases and controls in a case-case study

Cases: cases caused by the outbreak strain Controls: cases caused by non outbreak strains Goal: identify mode(s) of transmission specific to this

outbreak

Example of case-case study Listeriosis outbreak (meningitis, sepsis, especially in

pregnant women) in France Positive L. monocytogenes culture from normally

sterile site between 99/11/12 and 00/02/28 Cases: 29 strain-associated cases

Excluded were:• 2 deaths• 1 case whose status (as case) was known before interview

Controls: 32 non strain-associated cases

Results: Adjusted ORs and 95% CI

• Jellied pork tongue: 75.5 (4.7 - 1216)• Pâté de campagne: 8.9 (1.7 - 46.1)• Cooked ham: 7.1 (0.7 - 71.8)

All cases had eaten at least one of the above Recommendation against eating the pork tongue

made on Feb. 22, 2000 Outbreak strain in foodstuffs

Identified in some (rillettes: OR = 1.1 [0.3 – 3.8]) Not identified in jellied pork tongue

• No recall, as specific brand could not be incriminated

CONCLUSIONLevel Main surveillance challenge Local: best use of scarce resources

Provincial: adequate response to non-local outbreaks

National: uniformization of standards while respecting provincial autonomy

International: uniformization of quality of data in the face of wide economic and cultural disparities

Selecting the most appropriate design is relevant at every level.