Latent tb infection
This presentation is the property of its rightful owner.
Sponsored Links
1 / 44

Latent TB infection PowerPoint PPT Presentation


  • 114 Views
  • Uploaded on
  • Presentation posted in: General

Latent TB infection . Dr CC Leung TB & Chest Service Public Health Services Branch Centre for Health Protection Department of Health 香港特別行政區 衞 生署 衞 生防護中心胸肺科. 香港地理及人口. 中國大陸之南部 人口數目 = ~6,800,000 土地面積 = 1098 平方公里 人口密度 = 每平方公里 ~6500 人. 香港的醫療系統. 公營私營 基層醫療服務 30%70%

Download Presentation

Latent TB infection

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Latent tb infection

Latent TB infection

Dr CC Leung

TB & Chest ServicePublic Health Services BranchCentre for Health ProtectionDepartment of Health香港特別行政區衞生署

衞生防護中心胸肺科


Latent tb infection

香港地理及人口

  • 中國大陸之南部

  • 人口數目 = ~6,800,000

  • 土地面積 = 1098 平方公里

  • 人口密度 = 每平方公里~6500人


Latent tb infection

香港的醫療系統

公營私營

基層醫療服務30%70%

醫院服務90%10%


Latent tb infection

香港診治結核病之服務

結核病患者

衞生署

胸肺診所

19 間診所

每年約6,000 症

衞生署

普通科

門診部

醫管局

急症部

基層

私家醫生

醫管局胸肺醫院

主要有5 間醫院

約800 病床

7,000 住院人次

私家醫院

醫管局

專科門診

醫管局

一般醫院

第二層


Ltbi screen and treat

LTBI: Screen and Treat ?

  • Disease

    • Natural History / Impact

  • Diagnostic / Treatment Tools

    • Effectiveness / Limitations

  • Goal of Intervention

    • Personal protection / Public health control

  • Cost-effectiveness

    • Individual level / Community perspective


Latent tb infection1

Latent TB Infection

  • Infection by the tubercle bacillus is pre-requisite for development of disease

  • Latent Period

    • Long and Variable

    • Asymptomatic and Non-infectious

    • Provide an opportunity for intervention


From infection to disease

From Infection to Disease

  • Risk of developing disease

    • Multiple factors related to interaction between pathogen and human host

  • Lifetime Risk:

    • About one in ten (average)

  • The risk is greater initially

    • 5% within initial 2-5 years

    • 5% during the rest of lifetime


Predisposing conditions

Predisposing Conditions

  • HIV infection

  • Steriod / Immunosuppresant / anti-TNF

  • Silicosis

  • Chronic Renal Failure / hemodialysis

  • Diabetes Mellitus

  • Underweight

  • Gastrectomy / Jejunoileal Bypass

  • Malignancy / Debilitated State

  • Alcoholism / Smoking / Injection Drug Use


Active tb disease 2003

Active TB Disease - 2003

WHO Fact sheet N°104 (Revised April 2005)


Can we wait until disease

Can we wait until disease ?

  • Airborne spread

    • major challenge in control

  • Nonspecific symptoms

    • delay in diagnosis

  • Serious forms

    • grave consequences

  • High bacilli load

    • mutation and resistance


Diagnostic tools

Diagnostic tools

  • Traditional standard

    • Tuberculin test

  • Newer interferon-γrelease test

    • T Spot-TB®(Oxford Immunotec)

    • QuantiFERON®-TB Gold (Cellestis)


Tuberculin test

Tuberculin test

  • Intradermal injection preferred for better standardization

  • 2 units of PPD-RT23 (equivalent to 5 units of PPD-S)


Latent tb infection

Largest transverse diameter of induration read between 48-72 h


Specificity tst

Specificity (TST)

  • PPD contains a mixture of proteins

    • not entirely specific to the tubercle bacillus

    • potential cross-reactivity with other mycobacterial species

  • Positive reaction can occur with:

    • Active disease / Latent Infection

    • BCG vaccination / Booster

    • Other mycobacterial species


Bcg vaccination hk

BCG Vaccination(HK)

  • BCG vaccination

    • First introduced in April 1952

  • Neonatal vaccination

    • 99% coverage since 1970’s

  • Revaccination

    • Stopped only in 2000


Sensitivity tst

Sensitivity (TST)

  • Exact sensitivity for latent TB infection uncertain in absence of gold standard

  • Around 80%-90% sensitivity in active TB cases,

    • Varies with strength of tuberculin / cut-off point

    • Trade-off between sensitivity and specificity

  • False negative can also occur with a number of other conditions


Latent tb infection

False-negative (TST)


Predictive values tst

Predictive values (TST)


Interferon release test

Interferon-γRelease Test

  • Earlier version:

    • Measures the production of interferon- (IFN-) in T-lymphocytes upon stimulation with PPD.

  • Newer assays:

    • PPD is replaced by ESAT-6 and CFP10 (specific for MTB and not present in BCG and most MOTT)


Quantiferon tb gold

QuantiFERON® -TB Gold

  • Whole blood assay

    • Stimulate lymphocytes

      • in fresh whole blood

      • with ESAT-6 and CFP10

    • Measure IFN- level by

      • Enzyme-linked immunosorbent assay

  • Cell isolation not required

  • Variable background response:

    • Cut-off value may not be too sharp

  • Approved by FDA, USA in May 2005


T spot tb

T Spot-TB®

  • ELISPOT test

    • Isolation of lymphocytes from fresh blood

    • Incubation with ESAT-6 and CFP10

    • Enzyme-Linked ImmunoSPOT assay

      • For INF--producing T-lymphocytes

  • More tedious, but may be more sensitive

  • Approved for use in Europe


Sensitivity and specificity

Sensitivity and Specificity

  • Estimation is difficult

    • No gold standard for latent TB infection

  • Estimate of Sensitivity

    • positive rate in bacteriologically confirmed TB

      • 45/47 (Elispot, Lavani 2001)

  • Estimate of specificity

    • negative rate in BCG vaccinated subjects without risk factor for exposure

      • 26/26(Elispot, Lavani 2001)

Lavani et al, Lancet 2001;23:2017-21


Elispot vs tst school outbreak uk

ELISPOT vs TST(School Outbreak, UK)

  • Good Agreement

    • 89% concordance, kappa=0·72, p<0·0001

  • ELISPOT correlated better with

    • proximity (p=0·03)

    • duration of exposure (p=0·007)

  • TST more likely to be positive

    • in BCG-vaccinated vs unvaccinated (p=0·002)

  • ELISPOT results

    • Not associated with BCG vaccination (p=0·44).

Ewer K, et al. Lancet 2003; 361: 1168–73


Potential advantages

Potential advantages

  • Higher sensitivity

    • ?Help rule out infection / disease

  • More specific (specific antigens)

    • ?Help to rule in infection / disease

  • No booster effect on repeated testing

    • Good for serial surveillance

  • One clinic visit instead of two:

    • May facilitate uptake


Limitations

Limitations

  • Require prompt delivery of fresh blood

  • Technically much more demanding

  • Currently much more expensive

  • Test for infection rather than disease

  • Clinical experience is limited at this stage

    • Changes with time after exposure and treatment

    • Not fully evaluated in terms of the risk of disease development


Treatment of ltbi

Treatment of LTBI

  • Single drugs or simple combinations of two drugs

  • Isoniazid for 6 to 12 months

    • 5mg/kg daily (maximum 300mg)

    • 15mg twice weekly (maximum 900mg) (US)

  • Alternative regimens

    • Rifampicin for 4 months (US)

    • Isonoazid and Rifampicin for 3 months (Europe)


Hepatotoxicity

Hepatotoxicity

  • Notwithstanding the use of only one or two drugs, hepatotoxicity remains an important side effect

  • While untreated active TB often kills, only one out of ten latently infected subjects will actually develop disease.

  • Caution is therefore required in subjecting these asymptomatic individuals to treatment.


Possible approaches

Possible Approaches

  • Population Approach:

    • All infected individuals within the community

  • Targeted Approach:

    • High risk of Disease / Grave Consequence


Factors for consideration

Factors for Consideration

  • Goal of intervention

    • Personal Protection / Public Health Control

  • Cost-effectiveness

    • Prevalence of infection / Risk of Disease

    • Limitations of Diagnostic / Treatment Tools


Tb notification rate hong kong

TB Notification Rate (Hong Kong)


Latent tb infection

Reactivation vs Recent Transmission

TB

cases

Progressive primary *

Exogenous reinfection *

Endogenous reactivation #

1950

2000

Year

Ageing of the TB epidemic


Aging of the tb epidemic

Aging of the TB Epidemic

  • Population-based IS6110-based RFLP study

    • 24.5% (of 691 isolates) belonged to clusters

    • Recent transmission: 15 to 20%

    • Endogenous reactivation

  • Treat active disease by DOTS

    • Control recent transmission But

    • Little impact on endogenous reactivation

      Chan-Yeung M, et al. J Clin Microb 2003;41:2706-8


Population approach

Population Approach

  • Treatment of latent TB reduces endogenous reactivation

  • Can we treat every infected one to eliminate TB from our population?


Estimated infection rate hk

Estimated Infection Rate (HK)

*Estimation based on: Incidence (smear-positive cases) = ARI * Styblo ratio


Tst profile hk primary students 1999

TST Profile (HK Primary Students 1999)


Number to treat hk primary students

Number to Treat ( HK Primary Students)

Leung CC et al. Risk of TB among school children in Hong Kong. Arch Ped Adol Med, in press


Targetted approach hk

Targetted Approach (HK)

  • High-risk groups:

    • Recent Contacts

    • HIV

    • Silicosis

    • Immunosuppressive Treatment / Anti-TNF


Household contacts hk 2002 2003

Household Contacts ( HK 2002-2003)


Recent vs remote infection

Recent vs Remote Infection

  • Remote infection

    • Much lower risk of disease

    • Increases with age

  • Interferon-γrelease test

    • More specific BUT

    • May not differentiate between recent and remote Infection


Predictive value of positive test for recent infection reinfection

Predictive Value of Positive Testfor Recent Infection / Reinfection

Assume: 100% sensitivity & specificity; 20% recent transmission


Targetted approach impact

Targetted Approach: Impact

  • Personal protection

    • More cost-effective than population approach

  • Limited Impact on TB control

    • Prevent few cases, e.g. Close contacts

      • Initial screening:

        • Only 2% of all notifications locally

        • Not directly preventable as already disease

      • Later 5 years: only another 4% at best


Looking into future

Looking into Future

  • Researches and Development:

    • Better characterization of disease risk

    • Newer diagnostic tools

      • Simpler, and more affordable

      • Better ability to predict actual disease risk

    • Better treatment regimen

      • Shorter, safer and more effective

      • Affordable and Acceptable for wide application


Thank you

Thank You


  • Login