Tuberculosis (TB) outbreaks

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Tuberculosis (TB) outbreaks

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Tuberculosis OutbreaksTuberculosis Outbreaks

© Dr. Tong Ka Io

2013.09

TB outbreaks in literatureTB outbreaks in literature

© Tong Ka Io 2013

1950s: An Outbreak of Respiratory Tuberculosis in a School(1951 UK)

1960s: Epidemiology of an Outbreak of Tuberculosis Among School Children (1962 USA)

1970s: Tuberculosis Outbreak in a Circus: Report of a Cooperative Investigation (1973 USA)

1980s: Tuberculosis in a primary school: the Uppingham outbreak(1985 UK)

Why a sharp increase of TB outbreak Why a sharp increase of TB outbreak reports since 1990s?reports since 1990s?

1. Decrease of TB burden

2. HIV/AIDS

3. MDR-TB

4. DNA fingerprinting techniques

1990s: Multidrug-Resistant Tuberculosis Outbreak on an HIV Ward — Madrid, Spain, 1991–1995

1990s: An Outbreak of Multidrug-Resistant Tuberculosis among Hospitalized Patients with the Acquired Immunodeficiency Syndrome (1992 USA)

1990s: An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients of two hospitals in Milan, Italy (1998)

1990s: A Comparison of Outbreak- and Nonoutbreak-Related Multidrug-Resistant Tuberculosis Among Human Immunodeficiency Virus–Infected Patients in a South African Hospital (1999)

1990s: A school- and community-based outbreak of Mycobacteriumtuberculosis in Northern Italy, 1992-3

1990s: Outbreak of Tuberculosis Among Regular Patrons of a Neighborhood Bar(1995 USA)

Recognizing TB outbreaksRecognizing TB outbreaks

What is a TB outbreak?What is a TB outbreak?USCDC:

1. Increase of TB cases above expected

2. During a contact investigation: 2 contacts ≧having TB disease

3. Outside of a CI: 2 cases ≧within 1 year found linked

4. Genotyping: transmission link missed during a CI within the prior 2 years

Health events in a TB outbreakHealth events in a TB outbreak Latent TB Infection (LTBI)

Active TB Disease (TB)

Serious forms of TB

Death

Diagnosis of LTBIDiagnosis of LTBI Tuberculin Skin Test (TST)

Mantoux Test

Interferon-gamma release assay (IGRA)

QuantiFERON®-TB Gold test (QFT-G)

T-Spot®.TB test

Diagnosis of active TB diseaseDiagnosis of active TB disease History

Exposure

Symptoms

Physical examination

Complementary evaluation

TST and IGRA

Radiograph

Bacteriology

Bacteriological diagnosticsBacteriological diagnostics Sputum smear

Culture

Drug sensitivity test (DST)

Molecular

Nucleic Acid Amplification (NAA, ex. PCR)

Genotyping (ex. RFLP, VNTR, RAPET…)

Whole Genome Sequencing (WGS)

Epidemiological linkEpidemiological link Traditional

Social Network Analysis (SNA)

Molecular

A Preventable Outbreak of Tuberculosis Investigated through an Intricate Social Network (2001 USA)

Outbreak of isoniazid resistant tuberculosis in north London (2004)

Whole-Genome Sequencing and Social-Network Analysis of a Tuberculosis Outbreak(2011 USA)

Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study (2013 UK)

Characterization of recent Characterization of recent TB outbreaksTB outbreaks

Total = 124

Average per year = 28.5 (increasing from 1996 to 2001)

Cases per outbreak = 4.8 (2~25)

Place of contact

Hospital 20.0% Community and/or prison 18.5% Family and/or friends 13.8% School 7.7% Work 7.7% Public house 6.2% Shared house or flat 6.2% Nursing home 4.6%

Evaluation and Utilization as a Public Health Tool of a National Molecular Epidemiological Tuberculosis Outbreak Database within the United Kingdom from 1997 to 2001

Total = 27

Cases per outbreak = 3.9 (3~8)

Site of transmission

Family 70.4% Community 22.2% School 3.7% Workplace 3.7%

Mean diagnostic delay = 72.6 days

Study of Tuberculosis Outbreaks Reported in Catalonia, 1998-2002(Spain)

Total = 27

Cases per outbreak = 8.5 (4~16)

Risk factors for patients

Substance abuse 58% Incarceration history 32% Homelessness 20% HIV co-infection 12%

Hotspots

Drug house 63% Homeless shelter 19% Correctional facility 15% Household 15% Workplace 15% Church 11%

Tuberculosis Outbreak Investigations in the United States, 2002–2008

Major clusters = 7

Cases per cluster = 62.6 (18~228)

HIV Infection and Geographically Bound Transmission of Drug-Resistant Tuberculosis, Argentina (2012)

Total (2008~2009) = 9

Cases per outbreak = 14.7 (3~35)

Duration = 16.4 (3~43) months

Using statistical methods and genotyping to detect tuberculosis outbreaks (2013 USA)

Characterization of recent TB Characterization of recent TB outbreaksoutbreaks Spatial distribution and setting

Magnitude and impact

Agent – drug resistance

Source of infection

Host

Environment

186 TB outbreaks reported since 2000186 TB outbreaks reported since 2000

© Tong Ka Io 2013

Outbreak settingsOutbreak settings

© Tong Ka Io 2013

School outbreaksSchool outbreaks 2001, UK, school, 1 student caused 77 cases and 254 LTBI, rates of

transmission 20%~90%

2007 report, Japan, cram school, 1 teacher caused 46 cases (students 24.6%, teachers 42.9%, guardians 8.3%), LTBI among students 70%

2011, China, senior high school, 45 student cases

2001 report, Japan, junior high school, 1 student caused 31 cases

1.9% of those received chemoprophylaxis developed TB and 25% of those not

2009, China, high school, 1 student caused 23 student cases

Of students with LTBI in February 2009 who refused prophylaxis, 50% (11/22) had probable/confirmed TB in April 2010

……

Assessing the effect of foreign travel and protection by BCG vaccination on the spread of tuberculosis in a low incidence country, United Kingdom, October 2008 to December 2009

Outbreak of Pulmonary Tuberculosis in a Chinese High School,2009–2010

Family outbreaksFamily outbreaks 2001 report, Italy, family, MDR, 3 TB meningitis, 2 deaths

1996, Spain, household and hospital, HIV-MDR, 4 cases, 4 deaths

1999, UK, family and church, 20 cases

……

Two Tuberculosis Genotyping Clusters, One Preventable Outbreak (2009 USA)

Household outbreaks

Community outbreaks

Total (1994~2011) 25 11

Cases/outbreak 2.5 15.3

Duration 20 (0~125) months 81 (9~144) months

Risk factorsSchool; substance misuse; ethnic group; super-spreader

Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study (2012 UK)

Hospital & clinic outbreaksHospital & clinic outbreaks 1995~1996, Portugal, hospital for people with HIV, MDR, IC and treatment of suspect

cases reduced the incidence from 42% to 11%

1992~1993, Italy, hospital for people with HIV, MDR, 33 cases, IC decreased attack rates from 28.9% to 0

2003 report, Japan, ENT clinic, 1 doctor infected 18 patients, including 15 cases of TB otitis media

2008~2009, USA, hospital and living facility, 18 mentally ill patients, 2 deaths, LTBI 88%

2010 report, Taiwan, hospital, 1 patient infected 15(42.9%) HCWs, onset within 11m after exposure

2003 report, Japan, hospital, 1 pregnant woman caused 13 cases, including 2 miliary with meningitis

1994~1996, USA, methadone clinic, MDR, 13 patients with HIV

……

Tuberculosis Outbreakin a Community Hospital —District of Columbia (2002 USA)

Total (1998~2001) = 156

Largest-scale nosocomial outbreaks:

23 cases in mental hospital 19 cases in ENT clinic 17 cases in general hospital 14 cases in maternity hospital ……

Increase of risk for HCWs

Gap of infected HCWs / infected elderly patients Delay in diagnosis TB patients in severe conditions Medical procedures inducing coughing

Nosocomial Infection of Tuberculosis (2003 Japan)

Homeless shelter outbreaksHomeless shelter outbreaks 2002~2003, USA, homeless facilities, 48 cases, LTBI 30%

1998~2001, USA, homeless shelter for people with HIV, 25 cases

2007~2011, USA, homeless shelter, 28 cases, 1 death

……

Outbreak of Tuberculosis Among Homeless Persons Coinfected with Human Immunodeficiency Virus (2003 USA)

Outbreak of Tuberculosis Among Homeless Persons Coinfected with Human Immunodeficiency Virus (2003 USA)

Ongoing outbreak of tuberculosis in a low-incidencecommunity: a molecular-epidemiological evaluation(2004 Germany)

Child care center outbreaksChild care center outbreaks 2005, Spain, nursery, 1 assistant caused 27 children cases, LTBI

63%

2005 report, Sweden, 1 assistant caused 21 cases, LTBI 25%

2009, Ireland, child care centre, 18 children with active TB

1999~2001, England, nursery, 1 teacher caused 12 children cases and 55 LTBI

2003 report, UK, nursery, 1 cook infected 2 children, 1 died of TB meningitis

……

A Tuberculosis Outbreak in a Private-Home Family Child Care Center in San Francisco, 2002 to 2004

Drug-Susceptible Tuberculosis Outbreak in a State Correctional Facility Housing HIV-Infected Inmates — South Carolina, 1999–2000

Multistate Outbreak of MDR TB Identified by Genotype Cluster Investigation (2012 USA)

Multidrug-Resistant Tuberculosis Outbreak among US-bound HmongRefugees, Thailand, 2005

Other settingsOther settings Church / mosque

Military / navy ship

Supermarket

……

Total (1961~2008) = 8

Cases per outbreak = 9.6 (2~53)

LTBI% = 6.3%~54.5%

Types of transport

Single trip: Train, bus

Repeated trips: School bus, commuter bus

Risk factors

Length of exposure

Proximity to index case

Type of ventilation

Evidence for airborne infectious disease transmission in public ground transport – a literature review (2012 Germany)

Characterization of recent TB Characterization of recent TB outbreaksoutbreaks Spatial distribution and setting

Magnitude and impact

Agent – drug resistance

Source of infection

Host

Environment

Large / ongoing outbreaksLarge / ongoing outbreaks 1995~2006, London, Isoniazid-monoresistant TB, 293 cases

1996~2010, Sweden, Isoniazid resistant TB, 115 cases

1997~2010, Germany, “Hamburg Clone”, 86 cases

1983~1997, USA, ongoing transmission of a HS-resistant strain in homeless population

……

Large outbreak of isoniazid-monoresistant tuberculosis in London, 1995 to 2006: case–control study and recommendations

High rate of transmission among contacts in large London outbreak of isoniazid mono-resistant tuberculosis (2009)

Genomic Stability over 9 Years of an Isoniazid Resistant Mycobacterium tuberculosis Outbreak Strain in Sweden

Tuberculosis Outbreak in a Low-Incidence State — Indiana, 2001–2004

An outbreak of pulmonary tuberculosis in young Australians (2007)

Use of DNA Fingerprinting To Investigate a Multiyear, Multistate Tuberculosis Outbreak (2002 USA)

Extensive outbreaksExtensive outbreaks 2011 report, Spain, primary school, 1 staff caused 7 children

cases, LTBI 94% among highly exposed children

2003 report, Japan, junior high school, 1 student caused 34 cases, LTBI 90% among homeroom classmates

2008, USA, hospital and living facility for mentally ill patients, 18 cases, LTBI 88%

……

Fatal outbreaksFatal outbreaks 1995~2001, USA, multiyear and multistate outbreak, 39 cases,

6 deaths

2012, Puerto Rico, long term care for mentally ill patients, 8 cases, 4 deaths, LTBI 81%

2007~2009, Micronesia, MDR, 13 cases, 4 deaths

1996, Spain, household and hospital, HIV-MDR, 4 cases, 4 deaths

2003 report, UK, nursery, 1 cook infected 2 children, 1 died of TB meningitis

……

Characterization of recent TB Characterization of recent TB outbreaksoutbreaks Spatial distribution and setting

Magnitude and impact

Agent – drug resistance

Source of infection

Host

Environment

XDR/MDR-TB outbreaksXDR/MDR-TB outbreaks 2007, Japan, Hemodialysis facitily, 1 relapsed XDR patient

infected 5 HCWs and 1 patient

2005, South Africa, MDR, 58 cases

2005, Thailand, refugee camp, MDR, 20 cases

2003 report, Norway, MDR, immigrants, 20 cases

2008, Micronesia, Island, first MDR outbreaks, 17 cases

……

Islands of Hope: Building Local Capacity to Manage an Outbreak of Multidrug-Resistant Tuberculosis in the Pacific (2011 Micronesia)

Two Simultaneous Outbreaks of Multidrug-Resistant Tuberculosis — Federated States of Micronesia, 2007–2009

Characterization of recent TB Characterization of recent TB outbreaksoutbreaks Spatial distribution and setting

Magnitude and impact

Agent – drug resistance

Source of infection

Host

Environment

Source of infectionSource of infection School: teacher, student

Family: adult, adolescent

Medical facilities: patient, dead patient, doctor

Homeless shelter: user

Child care: staff

Prison: inmate

Bar: patron

Miscellaneous: singer, soldier……

Characterization of recent TB Characterization of recent TB outbreaksoutbreaks Spatial distribution and setting

Magnitude and impact

Agent – drug resistance

Source of infection

Host

Environment

High risk groupsHigh risk groups HIV

Homeless

Incarceration

Migrants

Mental illness

Substance use Alcohol

Marijuana

Crack cocaine

Transvestite / transsexual

HIV-TB outbreaksHIV-TB outbreaks 1992, Cuba, long term care for people with HIV, 60 cases

1995~1996, Portugal, hospital for people with HIV, MDR, IC and treatment of suspect cases reduced the incidence from 42% to 11%

1992~1993, Italy, hospital for people with HIV, MDR, 33 cases, IC decreased attack rates from 28.9% to 0

1999, USA, prison for inmates with HIV, 31 cases, LTBI 71%

1998, USA, homeless shelter for people with HIV, 25 cases

1994, USA, methadone clinic, MDR, 13 patients with HIV

……

HIV Infection and Multidrug-Resistant Tuberculosis—The Perfect Storm (2007 USA)

An Outbreak of Tuberculosis Among Adults With Mental Illness(2012 USA)

Tuberculosis Outbreak in Marijuana Users, Seattle, Washington, 2004

Characterization of recent TB Characterization of recent TB outbreaksoutbreaks Spatial distribution and setting

Magnitude and impact

Agent – drug resistance

Source of infection

Host

Environment

Environmental factorsEnvironmental factors Crowding

Ventilation

Medical device (ex. Bronchoscope)

An Outbreak of Bronchoscopy-Related Mycobacterium tuberculosis Infections Due to Lack of Bronchoscope Leak Testing (2002 USA)

Responding to TB outbreaksResponding to TB outbreaks

What to do in face of a TB What to do in face of a TB outbreak?outbreak?

1. Terminate the ongoing transmission

Identify and manage active TB cases

Identify and manage LTBI

2. Prevent similar outbreak in the future

Identify and manage contributing factors

Every TB case began as a TB contact

Contributing factorsContributing factors1. Undiagnosed source case

2. High risk group

3. Social behavior

4. Environment

Factors contributing to the cause of acommunity outbreak of tuberculosis (2004 UK)

Areas visited by TB patients

Hierarchy of ICHierarchy of IC

Actions at two levelsActions at two levels

© Tong Ka Io 2013

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