2. Describe an epidemic in terms of person, place and time. Describe key factors to consider when developing a case definition.

Transcription

1 SARS Outbreak Study 1 Intrductin One f the mst imprtant tls f Infectius Disease Epidemilgy is utbreak investigatin. The fllwing exercise will shw yu hw epidemilgical methds were applied t an utbreak f SARS in the fictitius city f Epiville. Gd luck and have fun! Faculty Highlight: Dr. Ian Lipkin Dr. Ian Lipkin, head f the Center fr Infectin and Immunity, is a pre-eminent figure in the area f Emerging Infectius Diseases Epidemilgy. In the fall f 1999, Dr. Lipkin and his team first identified West Nile Virus in New Yrk State encephalitis victims. He is currently the head f the Jerme L. and Dawn Green Infectius Disease Labratry at the Mailman Schl f Public Health. Dr. Lipkin is amng the researchers frm arund the wrld wh cllabrated n the investigatin f the SARS utbreak in the spring f Thrugh a cllabratin with ther Clumbia researchers, he recently received a $3 millin NIH grant supprting the develpment f technlgy t bth detect and discriminate amng multiple infectius diseases- including the SARS-assciated crnavirus. Read mre abut Dr. Lipkin s wrk: 1. Severe acute respiratry syndrme crnavirus persistence in Ver cells 2. Real-Time Plymerase Chain Reactin fr Detecting SARS Crnavirus, Beijing, 2003 Step 1: Learning Objectives A. Describe the principles f an utbreak investigatin 1. Define an utbreak. 2. Describe an epidemic in terms f persn, place and time. Describe key factrs t cnsider when develping a case definitin. Describe hw the chice f case definitin can influence an utbreak investigatin. List different surveillance methds used t ascertain cases. 3. List the six steps in an utbreak investigatin. 4. Describe the rle f an epidemilgist during an utbreak investigatin. B. Describe the principles f utbreak management 1. Describe different methds f utbreak management as they pertain t the epidemilgical triad (i.e., hst, agent and envirnment). 1

2 C. Explain the imprtance f unrestricted flw f infrmatin amng different public health agencies during an utbreak investigatin and the timely cmmunicatin f this infrmatin t the public. Step 2: Student Rle - Yur Plan f Actin The Epiville Department f Health -- the site f yur internship -- has been abuzz with activity cncerning an utbreak f unusual cases f pneumnia deaths amng patients in the Epiville General Hspital. Yur supervisr, Dr. Zapp, gives yu an assignment: acquaint yurself with the Department's surveillance and reprting systems and cllect all available infrmatin abut this utbreak. Upn pring thrugh the heavy flis in the Department's library, yu learn a lt f infrmatin abut disease surveillance. In Epiville, all hspitals, physicians and labratries are required t reprt any suspicius symptms that culd pse a ptential health risk t the general public. These reprts prvide the valuable clinical and demgraphic data the Department needs fr mnitring disease trends and public health interventin. Yur new clleagues als clue yu in t WEPI1 TV, which is the best place t hear the latest infrmatin abut what's happening in Epiville. As it s happens, Stew O'Neil did a piece n the new utbreak in last night's news. Yu turn t the WEPI1 channel website t read the text file f his reprt. Transcript Reprter: Stew O'Neil Gd evening. I am Stew O'Neil and yu are listening t WEPI Channel 1 news. Frm ur Health and Medicine Desk - dctrs at the Epiville General Hspital reprt a suspected utbreak f Severe Acute Respiratry Syndrme. Since its first appearance in China's Guangdng prvince in Nvember 2002, SARS has spread s quickly as t alarm glbal health fficials. This spread has been facilitated by wrld air travel. We spke with hspital fficials wh reprt a steady rise in unusual pneumnia cases ver the past tw weeks. The hspital administratr, wh declined t be interviewed, has tld us that the majrity f patients came frm Area B f Epiville. As f nw, 12 persns have died frm what may turn ut t be SARS. If yu have experienced high fever, cugh, difficulty in breathing, and have visited friends r relatives in Area B within the last tw weeks, yu may want t see a dctr." Based n yur wn research and the newscast, yu decide t lk fr the fllwing backgrund infrmatin n the internet: Infrmatin abut SARS n the Epiville Department f Health Website Epiville Map frm the Epiville Chamber f Cmmerce Website SARS case definitin frm the Wrld Health Organizatin (WHO) Website Getting infrmatin frm bks and the net is fine, but Dr. Zapp tells yu that nthing beats the fieldwrk. She directs yu t visit the Epiville General Hspital t d the preliminary wrk fr the utbreak investigatin. Step 3: Data Cllectin 2

3 Infectius Ward f the Epiville General Hspital Yu begin yur detective wrk with the infectius disease ward f the Epiville General Hspital. Yu start by reviewing the charts f patients wh died frm the mysterius disease. The administratr at the Admissins Office tells yu that they suspect that this is severe acute respiratry syndrme (SARS), but the hspital has nt yet received the materials t cnduct diagnstic tests that culd cnfirm these suspicins. Yu decide t create a list with the names f the patients wh have died frm the mysterius disease, their symptms upn admissin t the hspital, symptm duratin and if any patient family members became sick as well. Yu end up reviewing 12 charts f the patients wh seem t have died frm the same disease. Six persns were 60 and lder, 4 persns were in the age range f 25 t 50, and 2 were children (3 and 11 years ld). As yu review the charts, yu suddenly realize that all f the patients wh died frm the disease als happened t have the same street address and lived in the Amy Apartment Cmplex. Yu decide t prceed by ging ver t their place f residence. Amy Apartment Cmplex Yu arrive at the Amy Apartment Cmplex and speak t Mr. Jnes, ne f the cmplex managers. Mr. Jnes tells yu that ne tragedy after anther has struck this set f buildings and peple f all ages, yung and ld, are cming dwn with a severe flu and are dying. Peple are panicking and hardly anybdy has left the building ver the last three days. He has received 100 phne calls frm tenants abut breaking rent cntracts. (The cmplex cntains 200 apartments and serves a ttal f 600 residents.) Aside frm thse persns wh have already passed away, there are 70 ther peple wh have cme dwn with similar respiratry flu-like symptms. Mst f these individuals were hspitalized at the nearby Epiville General Hspital. Yu take dwn the names f these peple wh reprted being affected with flu-like symptms and race back t the Department f Health. Step 4: Data Analysis Back at the DOH: Yu suspect that what yu have n yur hands is an utbreak f SARS. Befre ging any further with yur investigatin yu need t get guidance frm yur supervisr. Dr. Zapp cmpliments yu n the jb well dne and utlines the fllwing steps f the utbreak investigatin t aid yur wrk: 1. Define the epidemic a. Define the "numeratr" (cases) b. Define the "denminatr" (ppulatin at risk fr develping disease) c. Calculate attack rates 2. Examine the distributin f cases by persn, place, and time 3. Lk fr cmbinatins (interactins) f relevant variables 4. Develp hyptheses based n the fllwing: a. Existing knwledge (if any) f the disease b. Analgy t diseases f knwn etilgy 5. Test hyptheses 3

4 a. Further analyze existing data utilizing an apprpriate study design b. Cllect additinal data 6. Recmmend cntrl measures Yu return t yur mdest cubicle at the DOH and eagerly embark upn the first steps f an utbreak investigatin: descriptive analysis. The epidemic shuld be characterized using the criteria in the case definitin. NOTE: Despite yur hard wrk, n case definitins are perfect because f pssible case misclassificatin. Fr instance, a diagnstic test may shw that a persn has the disease when in fact they d nt (false psitives), r cnversely, that a persn is free f disease when in fact he r she is truly infected (false negatives). It is very imprtant t have reliable and valid diagnstic tls t decrease the number f false psitives and false negatives. The csts f misdiagnsing a case and delaying the apprpriate treatment, especially in the case f such a deadly infectin as SARS, can be significant. (Fr mre infrmatin n this tpic, please see Aschengrau pp ) 1. Based n what yu just have learned, hw wuld yu g abut preparing a case definitin fr this utbreak in Epivillle? a. Cmpile a table f symptms frm all suspected SARS cases and frm patients with ther diagnsed respiratry illnesses, then prvide infrmatin in terms f PPT. Crrect. This answer meets bth the clinical criteria f suspected SARS and PPT restrictin f the case definitin (i.e., this answer fulfills the first step f an utbreak investigatin, defining a case, as well as the secnd step f an utbreak investigatin, defining the epidemic in terms f PPT). b. Cmpile a table f symptms f all patients wh were admitted t the hspital during the same time that the first patients were admitted t the Epiville General Hspital. Incrrect. This answer des nt meet the clinical criteria f SARS. It des, hwever, meet the time requirement f PPT (i.e., this answer fulfills the first step f an utbreak investigatin, defining a case, but nt the secnd step f an utbreak investigatin, defining the epidemic in terms f PPT. c. Cmpile a table f symptms f all patients wh were admitted t the Epiville General Hspital ver the last year and wh lived in the Amy Apartment Cmplex. Incrrect. Here yu are ignring the clinical criteria f the case definitin in an attempt t capture the place element f PPT (i.e., everyne wh lived in the Amy Apartment Cmplex). Thus, this answer fulfills the secnd step f an utbreak investigatin, investigating PPT, but nt the first step f an utbreak investigatin, defining a case. With yur case definitin at hand, yu g back t the Epiville General Hspital t review the charts f the 70 persns wh reside at the Amy Apartment Cmplex. Based n yur review f the charts, yu cnfirm that 53 ut f the 70 suspected cases in the apartment cmplex are mst likely t be SARS cases. Out f the 17 patients wh did nt meet the case definitin, 5 had similar symptms as SARS cases but their chest X-rays were clear, thers (6) recvered within a week (this was an indicatin that they just had flu), and the rest (6) had pneumnia f knwn etilgy. All f these 53 individuals are alive and battling the disease. The case definitin yu came up with is remarkably similar t the case definitin f SARS develped by the Wrld Health Organizatin (WHO) in Yu remember frm yur reading at the beginning f the day that surveillance is an essential feature f epidemilgic practice and is ften divided int tw types : passive and active. Mst f the surveillance dne n a rutine basis is called passive surveillance. In passive surveillance, physicians, labratries, and hspitals are required t reprt 4

5 diseases frm the list f reprtable diseases (usually a list f diseases) and are given the apprpriate mailing frms and instructins, with the expectatin that they will reprt all f the cases f reprtable disease that cme t their attentin. Active surveillance requires peridic telephne calls r persnal visits t the reprting individuals/hspitals/labratries t btain required data. 2. Wuld yu categrize each f the fllwing activities as passive r active surveillance? a. Hspitals reprting SARS cases t the Department f Health Passive surveillance b. Yur visit t the Amy Apartment Cmplex Active surveillance c. Yur review f case recrds Active surveillance 3. What type f surveillance d yu think is mre difficult t carry ut and why? a. Passive surveillance Incrrect. Althugh it may seem that passive surveillance is mre difficult t carry ut because yu need t get physicians, hspitals, and labratries t cmply with reprting f disease n a rutine basis, it is relatively simple t set up a system where health care wrkers fill ut the necessary reprts and submit them t the DOH. b. Active surveillance Crrect. Active surveillance is mre difficult t carry ut. Active surveillance is mre labr-intensive and cstly because the DOH has t hire additinal staff wh will have t make telephne calls and/r visit the medical facilities. The next mrning, yu are eager t shw yur case definitin and reprt n yur visit t the Amy Apartment Cmplex t yur supervisr. Dr. Mrissa Zapp cmpliments yu n yur gd wrk and recmmends that yu cntact tw ther hspitals in the city t see if they have similar cases that were nt reprted thrugh passive surveillance. Yur advisr's suspicins are cnfirmed. There have been 3 suspicius deaths at the Star hspital. Yu set ut t d yur detective wrk immediately. The hspital administratr tells yu that they had a 70 year ld man admitted tw weeks ag with respiratry symptms, and that a dctr and nurse wh were taking care f him gt sick within a week f his admissin. When the administratin realized hw cntagius the disease was, the patient, dctr and nurse were put int islatin. Unfrtunately, by the time extrardinary precautin measures were instituted, 20 additinal staff members had becme infected, including 5 medical residents. All f them had visited the patient's rm while attending the weekly runds and may have had clse physical cntact with the patient. The hspital administratin ntified the DOH by a phne call abut the situatin, but failed t fllw up with prper dcuments. Emplying yur understanding f PPT, yu decide t review the chart f the elderly man wh was admitted t the hspital. His chart reveals that he lives in the Amy Apartment Cmplex. Several days befre he gt ill, n August 1, 2003, he had attended an annual luau party held in the garden f the Amy Apartment Cmplex. Apprximately 300 ther tenants als attended. Nw that yu have gathered infrmatin n all the suspected SARS cases, yu are ready t create a spt map (Fr mre infrmatin n mapping, please see Giesecke pg. 23). 5

6 4. Given the place f residence f each "SARS affected-case" map the distributin f cases [Open Map]. D yu see any clustering? a. Clustering arund the hspital Incrrect. Althugh the secnd utbreak ccurred in the Star Hspital, the affected persnnel live all arund the city (aside frm the five medical residents wh live in the husing near the hspital). If yu created a spt map by place f wrk, yu wuld have bserved clustering arund the hspital. b. Clustering arund the Amy Apartment Cmplex Crrect. Yu bserve clustering arund the Amy Apartment Cmplex because mst f the cases have the same place f residence. Yur map cnfirms a gegraphic clustering f cases arund the apartment cmplex. Yu add place f residence as a necessary cmpnent f yur case definitin. c. N clustering Incrrect. Yu d bserve a clustering f cases arund the Amy Apartment Cmplex. Nw that yu have mapped ut all the cases accrding t the place f residence, yu are ready t d sme data analysis. The best measure t use in describing an epidemic is cumulative incidence. Cumulative incidence is calculated as the number f new cases ver a defined study perid, divided by ppulatin at risk ver that perid. Cumulative incidence is usually expressed per 100, per 1,000, per 10,000, r per 100,000 (Fr mre infrmatin, please see Aschengrau pp ). Let's calculate the cumulative incidence fr 5 residential areas f Epiville. Area a Ppulatin Size SARS Cases Frm the Outbreak at the Amy Apartment Cmplex SARS Cases Frm the Outbreak at the Star Hspital c Ttal SARS Cases Reprted frm 08/03 t 08/24 A 14, B 53, b 4 70 C 13, D 12, E 8, a The Amy Apartment Cmplex is lcated in Area B, the Star Hspital is lcated in Area C, the staff f 110 persns wh wrks at the Star Hspital resides all ver Epiville and Epiville suburbs. b 65 cases were hspitalized at the Epiville General Hspital and 1 case was hspitalized at the Star Hspital. c 22 cases frm the Star hspital include nly staff members. Hspital staff reside in different areas f Epiville. 5. In the table abve, Epiville is divided int five residential areas: A, B, C, D, and E. Calculate the cumulative incidence f SARS (per 1,000) in each area. Cumulative incidence is calculated as fllws: [# f new cases f disease / # in candidate ppulatin] ver a specified perid f time (Please see Aschengrau pp ). a. What is the cumulative incidence f (3/14,000)*1,000=0.21 per 1,000 ver a three-week 6

7 SARS (per 1,000) in Area A? b. What is the cumulative incidence f SARS (per 1,000) in Area B? c. What is the cumulative incidence f SARS (per 1,000) in Area C? d. What is the cumulative incidence f SARS (per 1,000) in Area D? e. What is the cumulative incidence f SARS (per 1,000) in Area E? perid.+ [+Please nte that a specified perid f time is a critical element in calculating incidence.] (70/53,000)*1,000=1.32 per 1,000 ver a three-week perid. (5/13,000)*1,000=0.38 per 1,000 ver a threeweek perid. (8/12,000)*1,000=0.67 per 1,000 ver a threeweek perid. (2/8,000)*1,000=0.25 per 1,000 ver a threeweek perid. 6. In which area d yu bserve the highest cumulative incidence f SARS? Why? a. Area D because the largest number f Star hspital emplyees resides there Incrrect. While it is true that the greatest number f Star persnnel reside in Area D, Area D des nt have the greatest verall number f SARS cases. Prprtinally, Area D has a lwer cumulative incidence f SARS than ne ther area in Epiville. b. Area B because it has the largest ppulatin Incrrect. Area B has the largest ppulatin and therefre, the largest ppulatin at risk fr develping SARS. Cumulative incidence is, hwever, defined as the number f new cases divided by the number f persns at risk during a specified time perid. Therefre, knwing the number f persns at risk is nt enugh t cnclude that the cumulative incidence is highest in area B. c. Area B because this is where the Amy Apartment Cmplex is lcated and where the largest number f new cases live. Crrect. Cumulative incidence is a functin f bth the number f new cases and the number f peple at risk. Yu will get the greatest cumulative incidence when yur numeratr (number f new cases) is large and/r when the denminatr (number f peple at risk) is small. Since the greatest number f cases happens t have ccurred in the Amy Apartment cmplex that is lcated in Area B, the cumulative incidence is highest in this area as well (1.32 per 1,000 per three-week perid). Disease transmissin refers t any mechanism by which an infectius agent is spread frm a surce r reservir t anther persn. The mechanisms, r mdes f transmissin, are divided int tw categries: direct and indirect. Fr instance, a disease can be transmitted frm persn t persn by means f direct cntact (e.g., influenza). Indirect transmissin usually ccurs thrugh a cmmn vehicle (e.g., cntaminated air r a cntaminated water supply) r thrugh a vectr such as a msquit]. (Fr mre infrmatin, please see Giesecke pp and the Epiville glssary). 7. Based n the cases frm the Amy Apartment Cmplex, which mde f transmissin is mst 7

8 prbable? a. Indirect: fd r water. Incrrect. Symptms f the disease are nt indicative f fd r water pisning, r f intestinal disease. Additinally, if the disease were transmitted via fd r water, we wuld anticipate that the majrity f the Amy Apartment Cmplex residents wuld have fallen ill subsequent t the luau. b. Direct: Persn-t-Persn Crrect. All cases ccurred clse in time-- shrtly after each f the cases attended the luau where they were in clse cntact with ne anther fr several hurs. c. Indirect: vectr-brne (cckraches) Incrrect. Only 66 f the 600 residents at the Amy Apartment Cmplex fell ill with SARS. It is unlikely that these 66 persns all came in cntact with cckraches within such a shrt time perid unless the apartment cmplex was really infested, which was nt the case. 8. Based n the cases frm the Star Hspital, which mde f transmissin is mst prbable? a. Direct: Only thrugh bdily fluids Incrrect. While it is pssible that thse wh tk care f the index patient at the Star Hspital gt infected by tuching the patient, it fails t explain why 20 additinal medical persnnel gt sick. b. Indirect: Air-brne thrugh the hspital ventalatin system Incrrect. The index case was hspitalized in the regular inpatient ward. If the disease were airbrne, it wuld have quickly spread arund the hspital thrugh the building s cmmn airshafts. c. Direct: Persn-t-Persn Crrect. All cases ccurred clse in time shrtly after admissin f the index case.this suggests that the surce f infectin was the same fr all individuals at Star hspital. Further, the statements given by the Star Hspital cases suggests that they were in clse physical cntact with the initial case while visiting the index case. This suggests that the transmissin ccurred via direct cntact with cntaminated water drplets emanating frm the sick case s sneezing r cughing. Step 5: Outbreak Cntrl Just as yu are ging ver yur descriptive analysis, Dr. Zapp calls yu in yur ffice t let yu knw that SARS diagnsis has been cnfirmed fr all 12 dead cases frm the Amy Apartment Cmplex. Yur primary gal nw is t plan an effective utbreak management. During the utbreak management it may be necessary t take the fllwing measures: quarantine (islate a persn until he r she is n lnger infectius), islate cntacts, and cnduct additinal surveillance (passive and active). 9. What d yu think wuld be an apprpriate measure t cntrl the utbreaks given what we knw abut SARS? 8

9 a. Islatin and quarantine Crrect. We want t islate an infected persn until he r she is n lnger infectius. Further, we want t quarantine thse wh have been expsed and may be infected but are nt yet ill. Separating expsed peple and restricting their mvements is intended t stp the spread f the infectin. Quarantine is medically very effective in prtecting the public frm disease. b. Educate the public n hw t avid infectin Incrrect. While this is a necessary precautin fr thse individuals wh may ptentially cme int cntact with diseased individuals, public awareness alne wuld nt be sufficient t address the tw utbreaks in questin. Intellectually curius? Learn mre abut the labratry methds used in the utbreak investigatin. 9

10 Use f Labratry Methds fr SARS Diagnsis Vide: Dr. Ian Lipkin Recmmendatins n interpretatin f labratry results: Psitive SARS diagnstic test findings a. Cnfirmed psitive PCR fr SARS virus at least 2 different clinical specimens (eg. naspharyngeal and stl) OR the same clinical specimen cllected n 2 r mre days during the curse f the illness (eg. 2 r mre naspharyngeal aspirates) OR 2 different assays r repeat PCR using the riginal clinical sample n each ccasin f testing b. Sercnversin by ELISA r IFA negative antibdy test n acute serum fllwed by psitive antibdy test n cnvalescent serum OR fur-fld r greater rise in antibdy titre between acute and cnvalescent phase sera tested in parallel c. Virus islatin Islatin in cell culture f SARS-CV frm any specimen; plus PCR cnfirmatin using a validated methd. (Reference: Cnfirmatin f psitive PCR The PCR prcedure shuld include apprpriate negative and psitive cntrls in each run, which shuld yield the expected results: 1 negative cntrl fr the extractin prcedure and 1 water cntrl fr the PCR run 1 psitive cntrl fr extractin and PCR run the patient sample spiked with a weak psitive cntrl t detect PCR inhibitry substances (inhibitin cntrl) If a psitive PCR result has been btained, it shuld be cnfirmed by: repeating the PCR using the riginal sample OR having the same sample tested in a secnd labratry. Amplifying a secnd genme regin culd further increase test specificity Recmmendatins fr labratries testing fr SARS Reference labratries shuld be identified at natinal level. Antibdy testing ELISA and IFA tests are being develped by research labratries. Because SARS a new disease in humans, SARS- CV antibdies are nt fund in ppulatins that have nt been expsed t the virus. An antibdy rise between acute and cnvalescent phase sera tested in parallel is very specific. Step 6: Discussin Questins Carefully cnsider the fllwing questins related t yur wrk. Write dwn yur answers and be prepared t discuss them during the seminar sectin. 1. Based n what yu knw abut HIV and SARS, hw is SARS different frm HIV? (Hint: cnsider the fllwing bullet pints t cmpare these 2 epidemics) Strategies fr preventin Mdes f transmissin Time frm disease emergence t its identificatin 10

11 Resurces Invlvement f glbal cmmunity 2. What d yu think yu shuld d with yur findings at the end f the utbreak investigatin? In answering this questin, cnsider the fllwing: the imprtance f infrmatin flw between public health agencies pssible barriers t sharing data varius ways t cmmunicate yur findings t ther agencies and then t the public. Explre the NYC DOH Website t learn mre n the varius strategies emplyed by public health agencies t infrm the public f their wrk. 3. Recent estimates put the ecnmic cst f the 2003 SARS epidemic at mre than a billin dllars. Hw d yu think the SARS utbreak culd have affected the ecnmy f Epiville? What abut the nn-ecnmic csts f this epidemic? 4. Read an article abut stigmatizatin f SARS patients. Intellectually curius? Based n what yu knw abut SARS, what d yu think is mst prbable, eradicatin r eliminatin f SARS? 11