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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.