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  • RECENT ADVANCES OF TUBERCULOSIS MANAGEMENT

    Qais Abdulmajeed Haddad

    Consultant ID & IC

    Security Forces Hospital Program

    Riyadh - Saudi Arabia

  • RECENT ADVANCES OF TUBERCULOSIS MANAGEMENT

     History

     Epidemiology

     Latent Tuberculosis

     Diagnosis

     Therapy

     Vaccine

     Infection Control

     Future Trends

  • 1.5 m/year = 4110/day

  • Pulmoary Tuberculosis

     TB Pleural effusion

     Tuberculous meningitis

     CNS Tuberculoma

     Milliary tuberculosis

     Renal & urogenital tuberculosis

     Bone & joint tuberculosis

     GIT tuberculosis

     TB Peritonitis

     Ileocecal TB

     Colonic TB

     Hepatic TB

     TB retinitis

    Extrapulmoary Tuberculosis

  • Tuberculosis History

    Neolithic skeleton (stone age)

    Spinal TB Pre-Columbian skeleton

    Early Egyptian remains

    After 1850 Laennec Pulmonary & Extrapulmonary

    tuberculosis is one disease

    1865 F. Villemin Tuberculosis transmitted to guinea pig by injecting diseased tissue

    1882 Koch AFB & its pathogenicity

  • 1840 1920 1860 1900 1940 1960 1980 2000 1880

    1993: TB cases decline due to

    increased funding and enhanced TB

    control efforts

    Mid-1970s: Most TB

    sanatoriums in U.S.

    closed

    1884:

    First TB

    sanatorium

    established

    in U.S.

    1865:

    Jean-Antoine

    Villemin

    proved TB is

    contagious

    1943:

    Streptomycin

    (SM) a drug used

    to treat TB is

    discovered

    1882:

    Robert Koch discovers

    M. tuberculosis

    Mid-1980s:

    Unexpected rise in

    TB cases

    1943-1952:

    Two more drugs are

    discovered to treat

    TB: INH and PAS

    TB History Timeline

    Rifampicin introduced 1967

  • M. tuberculosis causes most TB cases in the world

    Mycobacteria that cause TB:

    M. tuberculosis

    M. bovis

    M. africanum

    M. microti

    M. canetti

    Mycobacteria that do not cause TB (NTM)

     e.g., M. avium complex, M. chelonae

    Types of Mycobacteria

  • TB TRANSMISSION

    Dots in air represent droplet nuclei containing

    M. tuberculosis

  • Probability that TB will be transmitted depends on:

    Infectiousness of person with TB disease

    Environment in which exposure occurred

    Length of exposure

    Virulence (strength) of the tubercle bacilli

    The best way to stop transmission is to:

    Isolate infectious persons

    Provide effective treatment to infectious persons as

    soon as possible

    TB Transmission

  • WHO Global TB Report 2014

     Incidence: 9 million (2013)

     95% occurs in low- and middle-income countries

     Alarming increase in the number of patients with MDR-TB and XDR-TB has been noted (East Europe & Africa)

     Globally, 45% drop in mortality between 1990 & 2012

     Mortality: 1.5 million / year

     0.5 million are children

     HIV co-infection with TB:

     360,000 deaths / year

     13% of total active TB infections

  • RR-TB (Rifampicin Resistant)

    MDR-TB (INH+Rifampicin Resistant)

  • Latent Tuberculosis

  • LTBI VS. TB DISEASE

    Latent TB Infection (LTBI) TB Disease (in the lungs)

    Inactive, contained tubercle

    bacilli in the body

    Active, multiplying tubercle

    bacilli in the body

    TST or blood test usually

    positive

    TST or blood test usually

    positive

    Chest x-ray usually normal Chest x-ray usually

    abnormal

    Sputum smears and cultures

    negative

    Sputum smears and cultures

    may be positive

    No symptoms Symptoms such as cough,

    fever, weight loss

    Not infectious Often infectious before Rx

    Not a case of TB A case of TB

  • PPD VS IGRA

    Latent TB infection (LTBI) diagnosis remained to

    be dependent on PPD (Mantoux test) which

    was first described by Robert Koch in 1890

    PPD needs two patient visits and liable for

    observer error in reading

     Interferon-Gamma Release Assays (IGRAs) are

    whole-blood tests that can aid in diagnosing LTBI

    with one patient visit

  • QFT-TB Gold T-Spot Initial Process Process whole blood

    within 16 hours

    Process peripheral

    blood mononuclear

    cells (PBMCs) within 8

    hours, or if T-Cell

    Xtend® is used, within

    30 hours

    M. Tuberculosis Antigen

    Single mixture of

    synthetic peptides

    representing ESAT-6,

    CFP-10 & TB7.7.

    Separate mixtures of

    synthetic peptides

    representing ESAT-6 &

    CFP-10

    Measurement IFN-g concentration Number of IFN-g producing cells (spots)

    Possible Results Positive, negative, indeterminate

    Positive, negative,

    indeterminate,

    borderline

  • Isoniazid

    only

    Isoniazid + Rifapentine P Value

    Rates of Treatment

    completion

    69% 82%

  • 1148 patients had a median age of 30 years

    and a median CD4 cell count of 484/ml

     This was an open-label, randomized trial of LTBI in HIV

    patients (PPD 5mm or more)

    Divided in 4 blocks 2:2:2:1

     rifapentine (900 mg) plus isoniazid (900 mg) once

    weekly for 12 weeks

    Rifampin (600 mg) plus isoniazid (900 mg) twice weekly

    for 12 weeks

     Isoniazid (300 mg) daily for duration of the study (≤6 yrs)

    Control regimen of isoniazid (300 mg) daily for 6 months

  • Conclusions

    The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment completion rate

    Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid

  • A Trial of Mass Isoniazid Preventive Therapy

    for Tuberculosis Control

     In the intervention clusters, 27,126 miners (66.2%) underwent screening. Of these miners, 23,659 (87.2%) started taking isoniazid for 9 months

     If active tuberculosis was diagnosed, they were referred for treatment

    Conclusions: Mass screening and treatment for latent tuberculosis had no significant effect on tuberculosis control in South African gold miners, despite the successful use of isoniazid in preventing tuberculosis during treatment

  • Laboratory Diagnosis of Tuberculosis

    AFB smear by ZN stain and culture remain the

    gold standard in diagnosis

  • Detecting AFB by fluorochrome stain using

    fluorescence microscopy

    The smear may be stained by auramine-O dye. In this method

    the TB bacilli are stained yellow against dark background &

    easily visualized using florescent microscope

    Advantages:

    - More sensitive

    - Rapid

    Disadvantages:

    - Hazards of dye toxicity

    - more expensive

    - must be confirmed by Z-N stain

  • Cultures on L J media

    Lowenstein –Jensen medium is an egg based media with

    addition of salts, 5 % glycerol, Malachite green & penicillin

    Advantages: - Specificity about 99 %

    - More sensitive (need lower no. of bacilli 10-100 / ml)

    - Can differentiate between TB complex & NTM using biochemical reactions

    - Sensitivity tests for antituberculous drugs

    ( St, INH, Rif., E)

    Disadvantages: Slowly growing ( up to 8 weeks )

  • Rapid Radiometric Culture System

    BACTEC

     specimens are cultured in a liquid medium (Middle

    brook7H9 broth base ) containing C14 – labelled palmitic

    acid & PANTA antibiotic mixture

    Growing mycobacteria utilize the acid, releasing

    radioactive CO2 which is measured as growth index (GI)

    in the BACTEC instrument

     The daily increase in GI output is directly proportional to

    the rate & amount of growth in the medium

  • Microscopic-Observation Drug-Susceptibility

    Assay for the Diagnosis of TB

    A single MODS culture of a sputum sample offers

    more rapid and sensitive detection of

    tuberculosis and multidrug-resistant tuberculosis

    than the existing gold-standard methods used

    Moore DA et al, N Engl J Med 2006;355:1539-50.

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