essential skills for the tb nurse case manager ... · test (tst) vs. interferon gamma release assay...
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Epidemiology of TB
Leonard Mukasa, MBChB, PhDMay 3, 2017
Essential Skills for the TB Nurse Case Manager Little Rock, ARMay 3‐4, 2017
Leonard Mukasa, MBChB,PhD has thefollowing disclosures to make:
No conflict of interests
No relevant financial relationships with any commercial companies pertaining to this educational activity
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EXCELLENCE EXPERTISE INNOVATION
EpidemiologyofTB
LeonardMukasa,MBChB,PhDChiefEpidemiologyOfficer
TBControlProgram
May3,2017
• No conflict of interests
• No relevant financial relationships with any commercial companies pertaining to this educational activity
LeonardMukasa,MBChB,PhDhasthefollowingdisclosurestomake:
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Outline Tuberculosis Elimination
Transmission vs. Reactivation
Recent TB outbreaks in Arkansas Why do they occur ? Where have they been reported in AR? When were outbreaks reported in AR? Who are involved in outbreaks ? How to Responding to an Outbreak
TB Genotyping TB Genotyping Information Management System (TB GIMS) Whole Genome Sequencing of M.tuberculosis (WGS)
TB 101
Mycobacterium tuberculosisRobert Koch, March 24, 1882
PathogenesisLatent Tuberculosis Infection (LTBI) Active Disease
1843‐1910
Infection Disease
Dynamic process on a continuum
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Time Place
Person
Epidemiology 101
Questions:• Who?• Where?• When ?
What can we doabout it?
Informed Action
Disease does not randomly occur in populations
1989: Strategic Plan for Elimination of Tuberculosis in US
Goal: TB incidence 1 case per 1,000,000 population by 2010
How have we done to date? 2016 TB Surveillance Report
Arkansas : 30 cases per million United States: 29 cases per million
MMWR April 21, 1989 / 38(S‐3);1‐25; Ending Neglect, IOM, May 2000;
2 of 10 members: Dr. William Stead, Little Rock, AR Dr. George Comstock, Chair, Baltimore, AR
Step 3 in 1989 Plan (Screen for LTBI):All U.S. residents should have the results of at least one tuberculin skin test in their medical records, and those whose test result is positive should be evaluated and counseled regarding their risk of developing tuberculosis
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Normal Infection
Disease
Primary PreventionAdministrativeEngineeringVaccine
Death
Secondary PreventionTreat the Infection
Tuberculosis Missed Opportunities:The Context
Rapid diagnosisTreat TB
Time
Hea
lth
100
84
16
Problem Two……………………………………….Epidemiological Basis for TB Elimination (US)
Latent TB Infection (LTBI)
No Active TB over life time
Active TB
6.4 9.6
40% 60%Salpeter et al. 1998
2 years > 2 years
Who is in this group?
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Latent TB Infection Cases Detected, by Screening Method: Tuberculin SkinTest (TST) vs. Interferon Gamma Release Assay (T.SPOT.TB);
International Students, University of Arkansas, Fayetteville, 2008‐2013
Academic Year Screening Method
Students Screened
LTBI (%)Reported
Prevalence Ratio
2008‐2010 TST 1266 529 (41.8) 7.9
2010‐2013 T‐SPOT.TB 1938 102 (5.3) 1.0
When IGRA Preferred to TST
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Year Number Cases
Rate
2016 9,287 2.9
2015 9,563 3.0
2014 9,421 2.9
2013 9 582 3 0
Increase TB cases forfirst time in 23 years
CDC 2016
Tuberculosis Incidence, United States, 2002‐2016
CDC 2016
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CDC 2016
CDC 2016
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Arkansas and United States TB Cases Rates, 1971‐2016
0
5
10
15
20
25
30
Arkansas TB Cases Rate National TB Cases Rate
3
Paul Reagan, MD
Joe Bates, MD
William Stead, MD; State TB Control Officer, 1973‐1998
Rosalind Abernathy, MD
Trends in TB Cases — Arkansas, 1995–2016Two Factors: (1) Birth outside United States, (2) Prior 1951 birth‐cohort
0
10
20
30
40
50
60
0
50
100
150
200
250
300
95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16
Percentage Foreign ‐born
Cases
TB Cases Percentage Foreign‐born
U‐shaped curve concern
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Year Total TB Cases
Non‐US Born Cases
US‐Birth‐Cohort Cases
After 1950 Prior 1951
2009 82 23 31 28
2010 78 24 35 19
2011 85 24 37 24
2012 70 23 25 22
2013 72 24 23 25
2014 93 35 34 24
2015 90 31 40 19
2016 91 45 30 16
TOTAL 661 229 (34.6%) 255 177 (26.8%)
Targeted Testing(61.4% Total Cases)
Implication of Systematic TB Screening of Two Groups: Non‐US Birth and US Birth‐CohortPrior to 1951, on TB Incidence in Arkansas, 2009‐2016
Impact Screening of Population at
Risk
Environment(Airspace)
Host (Person)
Epidemiology 102
Questions:• Who?• Where?• When ?• What? • Why?
What is possible remedy ?
Informed Action
Biology Medicine Mathematics Technology Economics Policy
Agent (M.tb)
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What is a TB Genotype Cluster ?
• Two or more cases with a matching genotype
• Usually suggests recent transmission (< 5 years)
1996‐2003
RFLP MIRU‐VNTRSpoligotyping(1% of genome)
PCR ‐‐‐‐Digital data
2004‐2016
WGS(99% of genome)
2018‐2020
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Tuberculosis Genotyping Information Management System(TB GIMS)
CDC*Linkage *Timeliness
CDC 2016
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55.844.2
Unique
Clustered27.4 72.6
Overall US‐birth cohort prior 1951
TB Genotyping Clusters Overall and by Birth Cohort; Evidence of Remote TB TransmissionArkansas, 2009‐2014 (N= 347)
Genotyping Methods: Spoligotyping, Multiple Insertion Repeat Units (MIRU) 24‐locii
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Clusters Start as Unique Strains: Timing the Questions
Time 1 Time 2Time 0
?Old hypothesisProposal
And /or vs. Either /or
infection
disease“The enduring power of bad ideas”
Paul Krugman
Weak versus Strong Ties
Infectious Period
All TB Cases are a Result of Transmission
Clustered Non‐clustered
Hotspots Analysis:Getis‐Ord Gi* (clustered vs. non‐clustered)
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Population:Hempstead 22,084Howard 13,300
TB Cases in Southwest Arkansas, 2000‐2015
ARKANSAS TB CASES BY COUNTY 2016
COUNTY TB_CASESBaxter 1Boone 1Clark 1Faulkner 1Garland 1Greene 1Hot Spring 1Johnson 1Lafayette 1Lawrence 1Lee 1Lincoln 1Ouachita 1Phillips 1Pike 1Saint Francis 1Scott 1Union 1Yell 1Crawford 2Dallas 2Grant 2Jefferson 2Little River 2Madison 2Saline 2White 2Desha 3Benton 4Sebastian 4Craighead 6Pulaski 18Washington 21
TOTAL 91
ARKANSAS TB CASES BY COUNTY 2015
COUNTY TB_CASES
Baxter County 1
Boone County 1
Calhoun County 1
Chicot County 1
Clark County 1
Columbia County 1
Faulkner County 1
Fulton County 1
Grant County 1
Lafayette County 1
Polk County 1
Pope County 1
Sebastian County 1
Benton County 2
Bradley County 2
Clay County 2
Garland County 2
Miller County 2
Saline County 2
Crittenden County 3
Craighead County 4
Mississippi County 4
Hempstead County 5
Howard County 5
Pulaski County 17
Washington County 27
TOTAL 90
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Tuberculosis Outbreak among Marshallese in Arkansas
2014–2015
Laura K. Lester, DVM, DACVPM
Major, US Army Veterinary Corps
CDC Epidemic Intelligence Service Officer
Arkansas Department of Health
2015 CSTE Annual Conference
June 15, 2015
Center for Surveillance, Epidemiology, and Laboratory Services
Division of Scientific Education and Professional Development
Claims1788:John Marshall, English explorer1874: Spain1885: Germany1917: Japan, World War 11944: United StatesIndependenceRepublic of the Marshall Islands, 1979Compact of Free Association with USA, 1986
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CDC 2016
TB Among Marshallese in Arkansas, 1997–2016(N = 161)
0
5
10
15
20
25
97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16
Cases
YearRMI US‐Born
Zero Cases
Dr. Joseph Bates Outreach Clinic
ADH Plan for Mass ScreeningMarshallese Outreach Team
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Epidemiology of TB Among Marshallese in ArkansasA Conceptual Framework: Reactivation and Transmission
Arrival in US
Infected~30%
Not Infected~70%
TB
Converters
Progression
Transmission
US‐BornChildren
• Identify and screen arrivals quickly
• Population‐basedscreening
• Traditional CI
TB Outbreak Among Marshallese in Arkansas;2014–2015* (N = 34)
*January‐March 2015
0
1
2
3
4
5
6
7
Cases
Month
RMI US‐Born
No. Screened Positive TB/LTBI Proportion (%)
412 165 40.0
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January June December
2015
TB Death
Index Case
GOOO17 Pediatric GOO858 Pediatric UniquePending
2008
2009
2010
2011
2012
2013
2014
Spatial Distribution of TB Cases in 2014‐2015* Outbreak (N = 34)(Only Case‐Genotype G00017 Displayed for 2008–2013)
*January–March 2015
Clinical Pediatric
TB Death
Time to TB Diagnosis Among Marshallese in ArkansasAfter Arrival in US , 1997‐2017* ( N= 127)
Kaplan-Meier Curves
Years
Quartile Estimates Time to TB Diagnosis (Yrs.)
755025
5.4 (3.7–6.5)2.0 (1.1 – 2.9) 0.6 (0.3 –0.8)
* January
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Characteristic Place of Birth P‐value
Marshall Islands (n=23) United States (n=11)
Gender, males (%) 12 (52.2) 4 (36.4) 0.39
Age, years0‐45‐1516‐6465+
3 (13.0)5 (21.7)14 (61.0)1 ( 4.3)
8 (72.7)3 ( 27.3)
00 0.001
Diagnosis Positive M. tuberculosis CultureClinical
12 (52.2)11 (47.8)
2 (18.2)9 (81.8) 0.06
Genotypes, GENTypeG00017G00858G27282G28815
6111
2000
Major Site Disease, Pulmonary (%) 17 (73.9) 10 (90.9) 0.22
Diabetes Mellitus, age > 16 yrs. 5 (33.3%) 0
HIV Status, Positive (%) 0 0
Residing in Washington County 22 (95.6) 11 (100.0)
Demographic and Clinical Characteristics of TB Cases;Marshallese Outbreak —Arkansas, 2014–2015 (N = 34)
Index CaseAge 6 months
11/18/13 3/31/14 5/28/14‐‐‐6/5/14 6/10/14
Born to teenage parents, Arkansas
Outpatient visit in Arkansas,
Hx cough 3 weeks
Admitted Hawaii hospitalTST 20mm
CXR LLL infiltrateGastric aspirate –M.tb +ve (Xpert)
Trip with Grandparents
Back to ArkansasGrandparents/Parents Asymptomatic
TST –veWho is source case ??
3/20/13 6/2013 7/2013 11/18/13 6/19/14
Uncle, age 28 yrs. AFB smear 4+CXR cavitary
Source CaseAge 28 years
Arrived in US Start Work at
Poultry PlantCOUGH
Index case born
Missed Opportunity to Screen for TB
Index case dx
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Death from TB MeningitisA Fatal Missed Opportunity
Born in Arkansas
5/5/13 6/2014 8/1/14 1/15/15 1/15/15 1/19/15
Source Case
Grandmother TB caseCough 4 weeksAFB smears rareCXR cavitaryDiabetes Mellitus
TB meningitisMiliary TB cxr TB Drugs Steroids
ExpiredAdmitted PICU
Children Hospital
Dx. Seizures
• A 20‐month old child not identified as contact to grandma August 2014• But, 2 older siblings were screened and initiated LTBI treatment June 2014• Child admitted community hospital Jan 10‐13, 2015 treated for pneumonia• Re‐admitted for febrile seizures Jan 14, 2015; evacuated to Little Rock• Child died of TB meningitis on Jan 19, 2015; culture confirmed positive with
same genotype as cluster
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Origin of Tuberculosis (TB) Cases among Marshallese in Arkansas; 2014–2015 (N = 23)
• The Republic of the Marshall Islands (RMI) consists of 29 atolls each made up of many islets and 5 islands in the central Pacific
• Total land area is about 70 square miles• Mean height of land is about 7 feet above sea level• Majuro Atoll (capital) consists of 25,000 people and only
3.5 square miles of land
http://www.rmiembassyus.org/Geography.htm
Lobat; LomarJenrok
Rita
Long Islands
Ebey
http://upload.wikimedia.org/wikipedia/commons/9/9f/Kwajalein_Atoll%3Bp12(map).gif
http://www.pacifictravelweb.com/islands/marshall_islands/majuro_map.gif
Each star represents one case from that village
6.0
2.0
K1
J5J13J9J4*J15K2
Other G00017
5.0
4.0
J2
1.0
1.0
5.0
3.0
MRCA 7.0
Other G00017
Other G00017
Other G00017
Whole Genome SequencingDifferentiates the 8 cases
8 Cases in Cluster
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Discussion (1)
• Incidence of TB in this community was significantly higher than the rest of the state with case rate of 230 per 100,000 Marshallese compared to only 3.1 per 100,000 Arkansans and 3 per 100,000 US in 2014.
• Evidence indicates that some Marshallese rapidly reactivate with TB soon after arrival; others arrive with active disease.
• Marshallese Consulate has no reliable mechanism for determining the population of current Marshallese and new arrivals; intent should be to promote Arkansas Department of Health (ADH) initiatives to screen them for TB in a timely fashion.
• Arkansas has limited resources to screen 6,000 people, and then to manage the follow‐up on approximately 1,800 latent TB infections (LTBI), based on an estimated 30% positivity rate in this community; will include additional active cases.
• Current outreach team has a nurse and 3 outreach workers. An additional 4 nurses, 4 outreach workers, and 4 administrative assistants are needed to screen and treat TB in this population.
Discussion (2)
• Marshallese in Arkansas comprise 14% of the estimated 70,000 Marshallese worldwide; Arkansas should be grandfathered in the Compact of Free Association for access to resources.
• Major industries in the area should consider partnering with ADH to facilitate pre‐employment screening and follow‐up treatment of cases and LTBI.
• Springdale school district is ready and willing to participate in screening and case management initiatives.
• Opportunities for screening have been missed in the immunization programs; emphasis should be placed on identifying at‐risk children.
• Health literacy strategies need to be developed considering the health belief models of this population.
• Marshallese live in crowded conditions in Arkansas, similar to their situation in the RMI, promoting intense transmission.
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Dr. Joe Bates Outreach ClinicTeam; Hope in Action
Caleb Klipowicz in Marshall Islands 2012‐2013; an Emerging Anthropologist
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Second Generation Surveillance for TuberculosisAnswer to the Marshallese Question: Policy and Health Equity
TB Case Rate
Cases LTBICompletedTreatment
2014 2024
Years
0
230
0
3000
Using Smartphones in the Fight Against TB
Video Directly Observed Therapy (VDOT)
Adherence to Treatment Treatment Completion Drug Resistance
High patient load Driving distance Ease on patients
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The Threat of Tuberculosis Transmission Among the US‐born: Lessons from Two Outbreaks, Arkansas
Marco A, Patil N, Voyles J, Egbe Y, Mukasa LNArkansas Department of Health, Little Rock, USA
February 15 1913
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• Forty-four percent of TB cases in Arkansas are in genotype clusters, based on spoligotyping and MIRU-24 loci.
• In recent years, TB transmission is occurring in hard to reach homeless population, and lately a TB outbreak associated with a night club was identified.
• In this report, we describe characteristics of the two clusters and lessons learned.
Background
• Homeless persons at increased risk for TB
• Crowding in homeless shelters
• Tracking homeless persons difficult
• Regulations pertaining to TB screening in shelters are lax
TB Transmission Associated with Homeless Shelters: Factors
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TB Cases in Homeless, Arkansas, 1998-2013
0
2
4
6
8
10
12
Nu
mb
er o
f C
ases
2007‐42Miller
2009‐73Pulaski
2007‐96Pope
2008‐71Pulaski
2010‐11Boone
2010‐71Pulaski
2008‐61Washington
2010‐72Pulaski
2010‐67Pulaski
2010‐53Pulaski
2011‐13Sevier
2011‐43Pulaski
2011‐42
Washington2011‐01Pulaski
2011‐44Pulaski
2011‐30Pulaski
2011‐
2010‐
2009‐
2008‐
2007‐
Year Diagnosis
TB Cluster, Genotype AR‐0049, Arkansas, 2007‐2013( n = 18)
2013‐ 2013‐01Pulaski
2013‐18Pulaski
Pulaski CountyWashington CountyOther Counties
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Characteristics of Clustered TB CasesLinked to Homeless Shelter,( N = 18)
Characteristic Number Proportion (%)
Substance AbuseYesNo 10 55.6
8 44.4
RaceBlackWhite 12 66.7
6 33.3
GenderMaleFemale 16 88.9
2 11.1
Age in yrs, mean(Range) 47.5 (28-86)
HIV Status, positive 2 11.1
Homeless Based Cluster, Central Arkansas
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Cluster Snapshot for G00010, 2009‐2016
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Contact Identified235
Negative199 (87.3%)
Positive29 (12.7%)
Screened: TST228
Contact Identified309
Screened: T-SPOT.TB
302
Positive38 (12.6%)
Negative264 (87.4%)
Tuberculosis Contact Investigation, Homeless Cluster, 2007-2014 (N = 18)
Mass Screening Homeless SheltersLittle Rock, March – May 2014
Patient-contact Data, 2007-2013
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TB Transmission Associated with Night Clubs: Factors
• Hot, crowded environment
• Clubbers may not know each other outside night club
• Social networks in other cities, travel history important
• Night club to family, and community transmission
• Alcohol and drug use
2011-54
2013-152013-07
2010-31
2013-
2012-
2011-
2010-
Year Diagnosis
TB Cluster, Genotype G02192, Desha County, 2010-2013, (n = 10)
2012-492012-01
2011-47
dob 7/2011
Arrows indicate epidemiologic links
Night club
Nebraska
2011-75
2013-29
2010-31
dob 6/2002: clinical case
2016-29
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Potential for Intense TB Transmission at the Nightclub
• Low ceiling• Improvised ventilation system• No windows : Dark Inside
• 50-80 patrons a night• Maximum occupancy 150• Operates Friday --Sunday
Drive-through Surveillance
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Characteristics of Clustered TB Persons, Dumas (N=8)
Characteristic Number Proportion (%)
RaceBlack, non-HispanicOther
8 100.0
0 0.0
GenderMaleFemale
3 37.5
5 62.5
Age, mean (Range) 30 (0.6-37)
HIV status, positive 0 0.0
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Discussion
• Intense TB transmission among the US-born population is still reported in Arkansas
Homeless shelters Night club
• Control of TB outbreaks requires a dedicated outreach effort, including incentives and enablers.
• Treatment of TB Infection is by 12-dose isoniazid-rifapentine regimen, DOT
Recommendation
• Develop TB screening protocols for all homeless shelters in Arkansas
• TB Program should engage homeless population coalition on a routine, long term basis
• Review ventilation systems for night clubs
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RVCTNOThe UniqueIdentifier
Both TST and IGRA
SputumAFBSmear
Sputum Culture
Positive, n(%) Negative, n(%)
Total
Positive 90 (64.3) 2 (0.9) 92 (54.4)
Negative 50 (35.7) 27 (93.1) 77 (45.6)
Total 140 (100.0) 29 (100.0) 169 (100.0)
Tuberculosis Cases, by Sputum Examination Status, Arkansas, January 2009‐March 2012(n = 169)
Target for GeneXpert
The Diagnostic Gap of 10‐42 days
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Treatment Latent TB Infection (LTBI)
Game‐Changing Tools at ADH, 2012
9 Months Isoniazid
3 Months (12 doses)Isoniazid / Rifapentine