recent advances of tuberculosis day/session 3/recent advances of tآ recent advances of...
Post on 27-Jul-2020
1 views
Embed Size (px)
TRANSCRIPT
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.