Tuberculosis (TB) outbreaks

1. Tuberculosis OutbreaksTuberculosis Outbreaks
© Dr. Tong Ka Io
2013.09

2. TB outbreaks in literatureTB outbreaks in literature

3. © Tong Ka Io 2013

4. 1950s: An Outbreak of Respiratory Tuberculosis in a School
(1951 UK)

6. 1960s: Epidemiology of an Outbreak of Tuberculosis Among School
Children (1962 USA)

8. 1970s: Tuberculosis Outbreak in a Circus: Report of a Cooperative
Investigation (1973 USA)

9. 1980s: Tuberculosis in a primary school: the Uppingham outbreak
(1985 UK)

10. Why a sharp increase of TB outbreakWhy 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

11. 1990s: Multidrug-Resistant Tuberculosis Outbreak on an HIV Ward
— Madrid, Spain, 1991–1995

12. 1990s: An Outbreak of Multidrug-Resistant Tuberculosis among
Hospitalized Patients with the Acquired Immunodeficiency
Syndrome (1992 USA)

13. 1990s: An outbreak of multidrug-resistant tuberculosis involving
HIV-infected patients of two hospitals in Milan, Italy (1998)

14. 1990s: A Comparison of Outbreak- and Nonoutbreak-Related
Multidrug-Resistant Tuberculosis Among Human Immunodeficiency
Virus–Infected Patients in a South African Hospital (1999)

15. 1990s: A school- and community-based outbreak of Mycobacterium
tuberculosis in Northern Italy, 1992-3

16. 1990s: Outbreak of Tuberculosis
Among Regular Patrons of a
Neighborhood Bar
(1995 USA)

17. Recognizing TB outbreaksRecognizing TB outbreaks

18. 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

19. Health events in a TB outbreakHealth events in a TB outbreak
 Latent TB Infection (LTBI)
 Active TB Disease (TB)
 Serious forms of TB
 Death

20. 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

22. Diagnosis of active TB diseaseDiagnosis of active TB disease
 History
 Exposure
 Symptoms
 Physical examination
 Complementary
evaluation
 TST and IGRA
 Radiograph
 Bacteriology

23. 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)

26. Epidemiological linkEpidemiological link
 Traditional
 Social Network Analysis (SNA)
 Molecular

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

29. Outbreak of isoniazid resistant tuberculosis in north London (2004)

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

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

33. Characterization of recentCharacterization of recent
TB outbreaksTB outbreaks

35.  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

37.  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)

38.  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

40.  Major clusters = 7
 Cases per cluster = 62.6 (18~228)
HIV Infection and Geographically Bound Transmission of Drug-
Resistant Tuberculosis, Argentina (2012)

41.  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)

42. Characterization of recent TBCharacterization of recent TB
outbreaksoutbreaks
 Spatial distribution and setting
 Magnitude and impact
 Agent – drug resistance
 Source of infection
 Host
 Environment

43. 186 TB outbreaks reported since 2000186 TB outbreaks reported since 2000
© Tong Ka Io 2013

44. Outbreak settingsOutbreak settings
© Tong Ka Io 2013

45. 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
 ……

46. 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

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

48. 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
 ……

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

50. 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 factors
School; substance
misuse; ethnic group;
super-spreader
Whole-genome sequencing to delineate Mycobacterium tuberculosis
outbreaks: a retrospective observational study (2012 UK)

51. 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
 ……

52. Tuberculosis Outbreak
in a Community Hospital
—
District of Columbia
(2002 USA)

53.  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)

55. 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
 ……

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

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

58. Ongoing outbreak of
tuberculosis in a low-
incidence
community: a molecular-
epidemiological
evaluation
(2004 Germany)

59. 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
 ……

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

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

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

63. Multidrug-Resistant
Tuberculosis Outbreak
among US-bound Hmong
Refugees, Thailand, 2005

64. Other settingsOther settings
 Church / mosque
 Military / navy ship
 Supermarket
 ……

65.  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)

66. Characterization of recent TBCharacterization of recent TB
outbreaksoutbreaks
 Spatial distribution and setting
 Magnitude and impact
 Agent – drug resistance
 Source of infection
 Host
 Environment

67. 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
 ……

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

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

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

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

72. An outbreak of pulmonary tuberculosis in young Australians
(2007)

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

74. 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%
 ……

75. 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
 ……

76. Characterization of recent TBCharacterization of recent TB
outbreaksoutbreaks
 Spatial distribution and setting
 Magnitude and impact
 Agent – drug resistance
 Source of infection
 Host
 Environment

77. 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
 ……

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

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

80. Characterization of recent TBCharacterization of recent TB
outbreaksoutbreaks
 Spatial distribution and setting
 Magnitude and impact
 Agent – drug resistance
 Source of infection
 Host
 Environment

81. 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……

82. Characterization of recent TBCharacterization of recent TB
outbreaksoutbreaks
 Spatial distribution and setting
 Magnitude and impact
 Agent – drug resistance
 Source of infection
 Host
 Environment

83. High risk groupsHigh risk groups
 HIV
 Homeless
 Incarceration
 Migrants
 Mental illness
 Substance use
 Alcohol
 Marijuana
 Crack cocaine
 Transvestite /
transsexual

84. 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
 ……

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

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

87. Tuberculosis Outbreak in Marijuana Users, Seattle, Washington,
2004

88. Characterization of recent TBCharacterization of recent TB
outbreaksoutbreaks
 Spatial distribution and setting
 Magnitude and impact
 Agent – drug resistance
 Source of infection
 Host
 Environment

89. Environmental factorsEnvironmental factors
 Crowding
 Ventilation
 Medical device (ex. Bronchoscope)

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

91. Responding to TB outbreaksResponding to TB outbreaks

92. What to do in face of a TBWhat to do in face of a TB
outbreak?outbreak?
1. Terminate the ongoing transmission
 Identify and manage active TB cases
 Identify and manage LTBI
1. Prevent similar outbreak in the future
 Identify and manage contributing factors

93. Every TB case began as a TB contact

94. Contributing factorsContributing factors
1. Undiagnosed source case
2. High risk group
3. Social behavior
4. Environment

96. Factors
contributing
to the cause
of a
community
outbreak of
tuberculosis
(2004 UK)

97. Areas visited by TB patients

100. Hierarchy of ICHierarchy of IC

101. Actions at two levelsActions at two levels
© Tong Ka Io 2013