HISTORY of

Tuberculosis

Tuberculosis Is an
Ancient Disease
Spinal Tuberculosis
in Egyptian
Mummies
History dates to
1550 – 1080 BC
Identified by
PCR
TB HISTORY TIMELINE

1993: TB cases decline

1865:
due to increased funding
Jean- 1884: 1943:
and enhanced TB control
Antoine First TB Streptomycin
efforts
Villemin sanatorium (SM) a drug used
proved TB is established to treat TB is
contagious in U.S. discovered

1840 1860 1880 1900 1920 1940 1960 1980 2000

1943-1952:
1882: Two more drugs are Mid-1980s:
Robert Koch discovers discovered to treat Unexpected rise in
M. tuberculosis TB: INH and PAS TB cases
Tuberculosis
TB is a specific disease caused by infection with a bacteria
called Mycobacterium tuberculosis. It can also affect
intestine, meningitis, bones and joints, lymph glands, skin
and other tissues of the body.
Bovine TB is carried by cattle, by eating food that has
been contaminated by the bacteria or from drinking un-
pasteurized milk from cows that are infected with the
virus.
 Problem statement
TB is one of most important public health problems
worldwide. It has got high priority within the health
sectors. It stands 7th in the ten leading causes of global
disability adjusted life years (DALYS) lost and expected
to maintain its position even in 2020 AD. India accounts
for nearly 1/3 rd of the global tuberculosis burden.
Unfortunately the prevalence and incidence rates remain
same as in 1954-58 and with the increase in the country’s
population, the absolute number of TB cases must have
increased many fold but total cases detected in 1994 were
more or less same as in 1987 which indicates poor case
detection and case management.
 Cont:
The World Tuberculosis Day is being observed on 24th March every
year. The theme chosen for World TB Day-2004 (WTBD) is “
Every Breath Counts- Stop TB Now”. The Prime Minister on
March 25, 2004 said by 2005, the entire country would be covered
by DOTS (directly observed treatment, short course, a
comprehensive and cost-effective strategy for TB control. He said
more than a decade ago, the WHO declared TB a global emergency
and in India determined steps were taken to control this epidemic
by launching the revised national TB control program in 1997. The
DOTS strategy adopted under this programme is one of the notable
successes in public health in India, he said, adding that its coverage
has increased from 130million five years ago to 800 million of the
population in the current year. He said the TB control programme
in India has so far prevented 2.6 million infections. It has also
saved 5,00,000 lives. 31st December 2003, the total number of
patients who had been treated under the RNTCP was 26,39,194.
TB TRANSMISSION
 TB is spread person to person
through the air via droplet
nuclei

 M. tuberculosis may be expelled

when an infectious person:
Coughs
Sneezes
Speaks
Sings

 Transmission occurs when

another person inhales droplet
nuclei
TB TRANSMISSION

Transmission is defined as the spread of an

organism, such as M. tuberculosis, from one
person to another.
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
INCUBATION PERIOD
The time from receipt of infection to the
development of a +ve tuberculin test ranges
from 3-6 weeks
Incubation period may be week, month or
year
EPIDEMIOLOGICAL INDICES
Indices or parameters are needed to measure the
tuberculosis problem in a community

For planning and evaluation of control measures

Indices are also required for international

comparison
 Following epidemiological indices are
generally used in TB :

a) Prevalence of infection:-
 It is the percentage of individual who show a
positive reaction to the standard tuberculin
test.
b) Incidence of infection (Annual infection rate):-
 It is the percentage of population under study
who will be newly infected by M. tuberculosis.
 It reflects the annual risk of being infected in a
given community.
c) Prevalence of disease (Case rate) :-
 It is the percentage of individuals who’s sputum
is positive for tubercle bacilli on microscopic
examination.
 It is the best available practical index to estimate
the number of infectious cases or case load in a
community.
d) Indices of new cases :-
 It is the percentage of new tuberculosis cases per
1000 population occurring during one year.
e) Prevalence of suspect cases :-
 It is based on X- Ray examination of chest.
 Drawback of this index is that radiography
cannot reveal with any certainty.
 That’s why it has no epidemiological
significance.

f) Case detection rate :-

no. of new and relapse cases in a year
estimated incidence of such cases in same year
g) Prevalence of new drug resistance cases :-
 The patients resistance to anti- tuberculosis
drugs.

 Mortality rate :-
 The no. of deaths from TB per lakh population
was used as the index of the TB problem in a
community.
 At present time it has no significance.
SOME DEFINATIONS OF TB CASES
NEW CASES – A patient with sputum +ve PTB
who has never treated for TB or has taken anti-
tuberculosis drug for less than 4 week.
RELAPSE – A patient who return smear +ve
having previously been treated for TB and cured.
Return after default- A patient who return
sputum smear +ve after having left treatment for
at least 2 months.
TRANSFER IN- A patient recorded in another
administrative area register and transferred
into another area to continue treatment.
TRANSFER OUT- A patient who has been
transfer to another area registered and
treatment result are not known.
CURED– Initially smear +ve positive patient
who completed treatment and had –ve smear
result on at least two occasions.
COHORT- A group of patients in whom TB
has been diagnosed and who were registered
for treatment during a specified time period.
NATURAL HISTORY OF TB
 GLOBAL BURDEN OF TB
2 billion infected, i.e. 1 in 3 of global population
9.4 million (139/lakh) new cases in 2008, 80% in
22 high-burden countries
About 5.7 million cases were notified through
DOTS programme during 2010
Global incidence of TB has peaked in 2004 and is
declining
1.77 million deaths in 2007, 98% in low-income
countries
1.4 million deaths in 2010
MDR-TB -prevalence in new cases around 3.6%
 GLOBAL SITUATION
Since 1995, over 21 million patients have been
diagnosed and treated in DOTS programmes.
In 2007, 5.5 million new and relapse TB cases were
initiated on treatment under DOTS strategy.
 2.5 million new smear positive patients registered
in 2006, 85% were successfully treated under DOTS.
TUBERCULOSIS IN INDIA
 Estimated incidence
 1.96 million new cases annually
 0.8 million new smear positive cases annually
 75 new smear positive PTB cases/lakh population per
year
 Estimated prevalence of TB disease
 3.8 million bacillary cases in 2000
 1.7 million new smear positive cases in 2000
 Estimated mortality
 330,000 deaths due to TB each year
 Over 1000 deaths a day
 2 deaths every 3 minutes
Prevalence of TB infection
 40% (~400 million) infected with M. tuberculosis
(with a 10% lifetime risk of TB disease in the absence
of HIV)
Estimated Multi-drug resistant TB
 < 3% in new cases
 12% in re-treatment cases
TB-HIV
 ~2.31 million people living with HIV (PLWHA)
 10-15% annual risk (60% lifetime risk) of developing
active TB disease in PLWHA
 About 80% of TB patients are between 15-54 year of
age, while two- third of the cases are male.
PAKISTAN MOVED UP TWO SPOTS TO 6TH IN THE
LIST OF COUNTRIES .

“In 2010, after the registration of 0.413

million patients of which 0.3 million are
suffering from TB in their lungs.
Pakistan moved up two spots to 6th in the
list of countries with the highest number of
TB patients in the world, according to a
(WHO) report. TB kills around 48,000
Pakistanis every year.”
 “Pakistan alone accounts for
44% of total TB burden in the
Eastern Mediterranean Region
of the WHO comprising 23
countries.”
 -The incidence of sputum positive TB cases in
Pakistan is 80/100,000 per year and for all
types it is 177/100,000.
-TB is responsible for 5.1 percent of the total national
disease burden in Pakistan. The impact of TB on socio-
economic status is substantial.

 Source: National Tuberculosis control program

DOTS ENDORCEMENT IN
PAKISTAN.
Directly Observed Treatment Strategy (DOTS) is the
internationally recommended strategy for TB control.

NTP Pakistan adopted DOTS (Directly Observed
Treatment, Short course) strategy in 1995.
More than one million people have TB in Pakistan.

ONE PERSON IS INFECTED

EVERY TWO MINUTES AND ONE
DIES EVERY EIGHT MINUTES.
The marginalization and poverty of sick people has
fuelled another trend.
-W.H.O.
 Infection Control
1. Involve patients & 6. Rapid TB diagnosis and
community in advocacy treatment
campaigns 7. Improve room air ventilation
2. Infection control plan 8. Protect health care workers
3. Safe sputum collection (Screen)
9. Capacity building
4. Cough etiquette and cough
hygiene 10. Monitor infection control
practices.
5. Triage TB suspects to fast
tract or separation
Progression to TB Disease
TB and HIV
In an HIV-infected person,
TB can develop in one of
two ways:
 Person with LTBI becomes
infected with HIV and then
develops TB disease as the
immune system is weakened

 Person with HIV infection

becomes infected with M. Image credit: Mississippi State Department of Health
tuberculosis and then rapidly
develops TB disease
HIV Counseling
All persons with suspected and confirmed TB
disease should be offered HIV counseling and
blood testing, in addition to treatment.
This is because TB is more likely to occur among
HIV positive individuals.
HIV Counseling
 Treatment recommendations may differ for HIV
infected persons.
 It is best to offer HIV counseling and testing in the
health care facility.
 Follow up testing and counseling is essential.
Laboratory and Physical
examination of TB
Laboratory and Physical Examination
Following methods are used for laboratory and
physical examination of TB
Chest radiography
Sputum examination
Tuberculin testing
PCR test to detect TB
TB antibody testing
Bronchoscopy
 Radiology
Chest radiography is the most important method to detect
TB
 TB’s characteristics of a chest radiograph favor the
diagnosis of tuberculosis as following
shadows mainly in the upper zone
patchy or nodular shadows
the presence of a cavity or cavities, although these, of
course, can also occur in lung abscess, carcinoma, etc
the presence of calcification, although a carcinoma or
pneumonia may occur in an areas of the lung where
there is calcification due to tuberculosis
bilateral shadows, especially if these are in the
upper zones
the persistence of the abnormal shadows without
alteration in an x-ray repeated after several weeks
this helps to exclude a diagnosis of pneumonia or
other acute infection
Sputum examination
There are direct smear
and culture methods.
Direct smear
examination is only
positive when a large no
of bacilli begin to
excrete
Bacteriologic Examination
TB bacteriologic examination is done in a
laboratory that specifically deals with M.
tuberculosis and other mycobacteria

Clinical specimens (e.g., sputum and urine) are

examined and cultured in laboratory
Bacteriologic Examination (2)
Bacteriologic examination has 5 parts

Specimen collection

Examination of acid-fast bacilli (AFB) smears

Direct identification of specimen (nucleic acid

amplification)
Specimen culturing and identification

Drug susceptibility testing

 Bacteriologic Examination (3)
Specimen Collection
For pulmonary TB,
specimens can be collected
by:
Sputum sample

Induced sputum sample

Bronchoscopy

Gastric washing TB patient coughing up sputum in a sputum collection booth

Bacteriologic Examination (4)
Sputum Sample Specimen Collection
Easiest and least expensive method is to have patient
cough into sterile container

HCWs should coach and instruct patient

Should have at least 3 sputum specimens examined

Collected in 8-24 hour intervals

At least one early morning specimen

Bacteriologic Examination (5)
Induced Sputum Collection
Induced sputum collection should be used if
patient cannot cough up sputum on their own

Patient inhales saline mist, causing deep coughing

Specimen often clear and watery, should be

labeled “induced specimen”
 Bacteriologic Examination (6)
Bronchoscope
 Bronchoscopy may be used:

If patient cannot cough up enough

sputum

If an induced sputum cannot be

obtained

 Procedure: instrument is passed

through nose or mouth into lung to Bronchoscopy being performed on a patient

obtain pulmonary secretions or lung

tissue
 Bacteriologic Examination (7)
Gastric Washing
 Usually only used if sample cannot be obtained
from other procedures

 Often used with children

 Tube is inserted through nose and into stomach to

obtain gastric secretions that may contain sputum
 Bacteriologic Examination (8)
Extra pulmonary TB
Specimens other than sputum may be obtained

Depends on part of body affected

For example:

Urine samples for TB disease of kidneys

Fluid samples from area around spine for TB meningitis

Bacteriologic Examination (9)
Examination of AFB Smears

Specimens are smeared

onto glass slide and
stained

AFB are mycobacteria

that remain stained after
being washed in acid
solution
AFB smear
Bacteriologic Examination (10)
Examination of AFB Smears
Number of AFB on smear are counted

According to number of AFB seen, smears are

classified as 4+, 3+, 2+, or 1+

For example, 4+ smear has 10 times as many AFB than

3+ smear

If very few AFB are seen, the smear is classified

by the actual number of AFB seen
5. Bacteriologic Examination (11)
Examination of AFB Smears
Classification Infectiousness of
Smear Result
of Smear Patient
Probably very
4+ Strongly positive
infectious
Probably very
3+ Strongly positive
infectious
2+ Moderately positive Probably infectious

1+ Moderately positive Probably infectious

Actual number
of AFB seen (no Weakly positive Probably infectious
plus sign)
May not be
No AFB seen Negative
infectious
 Tuberculin testing
 A tuberculin skin test is done to see if you have ever
had tuberculosis (TB). The test is done by putting a small amount of
TB protein (antigens) under the top layer of skin on your inner
forearm. If you have ever been exposed to the TB bacteria
(Mycobacterium tuberculosis), your skin will react to the antigens
by developing a firm red bump at the site within 2 days.
 The TB antigens used in a tuberculin skin test are called purified
protein derivative (PPD). A measured amount of PPD in a shot is
put under the top layer of skin on your forearm. This is a good test
for finding a TB infection. It is often used when symptoms,
screening, or testing, such as a chest X-ray, show that a person may
have TB.
 A tuberculin skin test cannot tell how long you have been infected
with TB. It also cannot tell if the infection is latent (inactive) or is
active and can be passed to others.
 Tuberculin testing
A reaction of less then 05nm
is considered as negative.
5-9mm is considered positive
(+)
10-19mm is considered
positive (++)
More then 20mm is
considered positive (+++)
A positive tuberculin test
indicates TB infection with or
without disease.
Observation and Inference
48-72 hours later  diameter of indurations is
measured transversely to the long axis of the forearm.
Indurations > 10mm is suggestive of natural infection.
5-10 mm  borderline; considered positive in
immunocompromised host
<5mm  Negative mantoux test does not rule out TB
False Negatives
Test done in incubation period of TB
For several weeks following measles
During Corticosteroid therapy
Overwhelming TB infection (milliary, meningits)
Severe Malnutrition
If given Sub Cutaneous instead of Intra dermal
Inactive Tuberculin
False positive
Atypical mycobacteria
BCG vaccine
Infection at site of test
 Classification of the Tuberculin Skin Test Reaction
An indurations of 5 or more An indurations of 10 or An indurations
millimeters is considered more millimeters is
positive in
of 15 or more
considered positive in
-HIV-infected persons -Recent immigrants (< 5
millimeters is
years) from high-prevalence considered
countries positive in any
-A recent contact of a person -Injection drug users person, including
with TB disease
-Persons with fibrotic changes on -Residents and employees of
persons with no
chest radiograph consistent with high-risk congregate settings known risk
prior TB factors for TB.
-Patients with organ transplants -Mycobacteriology laboratory However,
personnel
targeted skin
-Persons who are Persons with clinical
immunosuppressed for other conditions that place them at testing programs
reasons (e.g., taking the high risk should only be
equivalent of >15 mg/day of conducted
prednisone for 1 month or -Children < 4 years of age
among high-risk
longer, taking TNF-
 antagonists) - Infants, children, and groups.
adolescents exposed to
adults in high-risk categories
PCR to detect Tuberculosis
White blood cells and ESR
The white blood count is usually normal.
In practice the white blood count is only useful in a
minority of cases, When the patient is less ill and
the radiological shadowing less extensive the count
is often normal or high normal
ESR is often elevate
 Treatment

• TB is treatable and curable, even

in people living with HIV
• First line TB drugs
Rifampicin (R)
Isoniazid (H)
Ethambutol (E)
Pyrazinamide (Z)
 Treatment
Divided into two phases:

Intensive phase (all 4 drugs)

for 2-3 months depending on
if the patient has been
treated before.
Continuation phase
(rifampicin and isoniazid) for
4-6 months, depending on
whether you have been
treated before.
 Treatment
The Aims of anti-TB Treatment

a. To cure the patient of TB

b. To prevent death from active TB
or its late effects
c. To prevent TB relapse or
recurrent disease
d. To prevent the development of
drug resistance
e. To decrease TB transmission to
others.
 Treatment Support

Essential for:

• Monitoring side effects

• Encouraging the patient to

keep taking treatment

• Provision of extra care needed

(psycho-social)
 Treatment and care of HIV related TB

Provide HIV testing and counselling

Introduce HIV prevention methods
Introduce co-trimoxazole preventive therapy (CPT)
Ensure HIV care and support
Introduce antiretroviral therapy (ART)
 CPT and ART: the earlier the better
• Early ART and CPT are linked to better outcomes in TB treatment

• ART during TB treatment rather than after reduces mortality by

over 50% (SAPIT trial South Africa)
• ART after 2 weeks v 8 weeks reduces mortality from 27% to 5%
(among drug users in Tehran)
• Death was strongly associated with absence of ART

• Cotrimoxazole reduces mortality by 50%

What is DOTS?

DOTS is a comprehensive
strategy recommended by
WHO for the detection and
cure of tuberculosis.
A trained health care worker or
a designated individual
provides the prescribed anti-
tuberculous drugs and watches
the patient swallow every dose.
 procedure:
Patients with infectious tuberculosis are:
 Identified using microscopy services.
 Health workers then observe and record patients
swallowing the full course of the correct dosage of
anti-TB medicines for 6 to 8months.
 Sputum smear testing is repeated after two months,
to check progress, and at the end of treatment.
 A recording and reporting system documents
patients' progress throughout, and the final outcome
of treatment.
The five components of DOTS:
1. Effective political and administrative commitment.
2. Case finding primarily by microscopic examination of
sputum of patients presenting to health facilities.
3. Short-course chemotherapy given under direct
observation.
4. An effective drug supply and management system.
5. Systematic monitoring and evaluation system.
 DOTS IN PAKISTAN:
Pakistan ranks 8th amongst the top 22 TB burden countries in
the world. According to estimates about 300,000 new cases are
added each year with Punjab having a quarter of the total disease
burden.
DOTS program was started in Pakistan in 1995, under the
National TB Control Program however the non-availability of
funds from regular health budget brought it to a halt.
In 2000, it was revived and funds were allocated to it seeking
to provide 100% TB care to its population by 2005.
By 2005, DOTS had been set up all over Pakistan.
TARGET:
 Increase cure rates to 85% and above.
 Increase case detection to 70%.
 100% DOTS coverage by 2005.
 Reduce mortality and morbidity from TB by 50% by
the year 2010.
 To achieve Millennium Development Goals by
2015.
ACHIEVEMENTS:
 DOTS coverage in Pakistan achieved in May 2005
 Achievement of TB related MDG Targets by 2008
 DOTS expansion to 36 districts of Punjab.
 Capacity building of districts; Training of doctors and
paramedics, at all levels healthcare.
 Expansion of laboratories network.
 Advocacy, communication and social mobilization:
media, news letter, billboards.
 Engaging all care providers: Private as well as public.
CHALLENGES:
 Financial constraints.
 Emergence of MDR-TB and HIV.
 Capacity building constraints.
 Inadequate laboratory services.
 Inadequate information systems.
 Unaccounted migration from high prevalence areas
with inadequate DOTS coverage.
The Stop TB Strategy:

WHO developed a new six point Stop TB Strategy in

2000 which builds on the success of DOTS while also
explicitly addressing the key challenges facing TB.
Vision: A world free of TB.
Goal: To reduce dramatically the global burden of TB
by 2015 in line with the MDGs and the Stop TB
targets, to achieve major progress in the research and
development for tuberculosis cure.
To eliminate tb by 2050.
Objectives:
To achieve universal access to high
quality diagnosis and treatment for
people with TB.
 To reduce the suffering and socio-
economic burden associated with TB.
To protect poor and vulnerable populations from TB,
TB/HIV and MDR-TB.
 To support the development of new tools
and enable their timely and effective use.
COMPONENTS:
1. Pursue high-quality DOTS expansion and
enhancement.
2. Address TB/HIV, MDR-TB and other challenges.
3. Contribute to health system strengthening.
4. Engage all care providers.
5. Empower people against tuberculosis.
6. Enable and promote research.
Tuberculosis in Children
Tuberculosis in Children
Usually reported between 10% to 20% all tuberculosis
cases.
 the source of infection is usually an adult, often a family
member with sputum smear positive TB.
Progressive primary tuberculosis:
Progression of TB depends on the age of the child,
number of tubercle bacilli, and host resistance.
Apparently healed focus or nodes may contain viable
organisms for many years.
During 1st 4-8 weeks, organisms are disseminated in the
blood stream.
Progressive pulmonary disease
Progressive primary infection: Progression
of recently acquired pulmonary primary
infection
Endogenous exacerbation: reactivity of
organisms and breakdown of primary
lesions acquired > 5 years previously
Exogenous exacerbation: Re-infection by
newly acquired bacilli in persons with
healed primary lesions
Symptoms of childhood tuberculosis

1. Failure to thrive } &

2. Intermittent fever } are the commonest symptoms
3. Pleural effusion
4. Ascites
5. Abdominal mass (Painless)
6. Limp / Arthritis
7. Painless lymphadenopathy
8. Persistent skin ulcer
9. Sterile pyuria
10. Meningitis
Pulmonary lesions in tuberculosis
- the primary complex
 Complications of the primary focus
1.Rupture of focus into pleural space
causing serous effusion
2. Rupture of focus into bronchus
causing cavitation.
3. Enlarged focus, sometimes
laminated or “coin” shadow
 Complications of regional nodes
1. Incomplete (ball-valve) bronchial obstruction,
emphysema of middle & lower lobes
2. Complete bronchial obstruction, collapse of
right lower lobe
3. Erosion of node into bronchus & segmental
consolidation
4. Rupture of node into pericardium:
tuberculosis pericardial effusion
Sequelae of bronchial complications
1. Stricture of bronchus at site of erosion
2. Cylindrical bronchiectasis in area of old collapse
3. Wedge shadow: contracture & fibrosis of
segmental lesion
4. Linear scar of fibrosis following segmental lesion
Symptoms
Primary complex – mild fever, anorexia, weight loss,
decreased activity, cough

Progressive primary complex – high grade fever,

cough. Expectoration and hemoptysis – usually
associated with cavity and ulceration of bronchus.
Abnormal chest signs – decreased air entry, dullness,
creps
Endobronchial tb – wheeze!!
Fever, troublesome cough, dyspnea, wheezing and
cyanosis

Pleural effusion – follows a rupture of a subpleural

focus. Also by hematogenous spread from primary
focus. Occurs coz of hypersensitivity to
tuberculoproteins.
Fever, cough, dyspnea, pleuritic chest pain.
Treatment policies in children with
tuberculosis (IAP)
Preventive Therapy In Mantoux Positive : 6 HR
Primary complex }
Isolated LNE } 2 HRZ + 4 HR
Pleural Effusion }

Progressive Pulmonary Tuberculosis }

Multiple LNE } 2 HRZE + 4 HR

Miliary, Bone, Renal, Pericardial } 2 HRZE + 7HR

TB Meningitis } 2 HRZE + 10 HRE +
Prednisolone / Dexamethasone
Drug-Resistant TB
Drug Resistance
Natural or Primary
Acquired
Initial
Multidrug resistance (MDR)
Drug-Resistant TB
Caused by M. tuberculosis
organisms resistant to at
least one TB treatment drug
Isoniazid (INH)
Rifampin (RIF)
Pyrazinamide (PZA)
Ethambutol (EMB)

Resistant means drugs can

no longer kill the bacteria
Drug-Resistant TB
Primary Resistance Caused by person-to-person
transmission of drug-resistant organisms

Secondary Resistance Develops during TB treatment:

• Patient was not

given appropriate
treatment regimen
OR
• Patient did not
follow treatment regimen as
prescribed
Drug-Resistant TB
Mono-resistant Resistant to any one TB treatment drug

Poly-resistant Resistant to at least any 2 TB drugs (but not

both isoniazid and rifampin)
Multidrug resistant Resistant to at least isoniazid and rifampin, the
(MDR TB) 2 best first-line TB treatment drugs

Extensively drug Resistant to isoniazid and rifampin, PLUS

resistant resistant to any fluoroquinolone AND at least 1
(XDR TB) of the 3 injectable second-line drugs (e.g.,
amikacin, kanamycin, or capreomycin)
 Treatment of resistant tuberculosis
INH-resistant TB: 18 RZE
Rifampicin-resistant TB: 18 – 24 HZE
Multidrug-resistant TB:
Treat for 24 month. after culture
conversion with regimen containing 3
second-line drugs, including IM
aminoglycoside/ SM, one fluoroquinolone
and one oral 2nd line drug.
2nd Line drugs
Drug resistant cases or when first line drugs cant
be used
Eg. Cycloserine, ethionamaide,kanamycin

Other drugs
Strictly for drug resistant cases
Eg. Quinolones, rifamycin, amikacin, imipenem,
ampicillin
 Phases of Treatment
Intensive Phase
 Eliminate bacterial load
 Prevent emergence of drug resistant strains
 Atleast 3 Bactericidal Drugs used

Continuation Phase
 Continue and complete therapy
 Atleast 2 Bactericidal drugs used

Steroids
 Anti inflammatory effect – millary, peritonitis, pericarditis
 TB meningitis
Revised National TB Control Program
(RNTCP) Treatment
 Bacille Calmette Guérin Vaccine
Vaccine finally first used in July 1921, providing mainly
children with protection
Derivative of virulent Mycobacterium bovis
1/10000 of 1 mg of M. bovis killed a 400g
guinea pig
With a protective waxy coating and resistant to many
physical and chemical agents, the slow-growing deadly strain
was tamed by Calmette and Guérin in Lille, France
Used transplantation every 3 weeks in potato-
beef bile medium
Initial Reaction
Eagerly received worldwide except for hesitation
by scientific authorities in the US
“Everybody knows how well the new formula for
protection against tuberculosis was received in
France and abroad. It flourished, and the
dispensary is still the basis of the prophylaxis of
tuberculosis.” - Camille Guérin
Lübeck disaster
Death of 75 infants by M. tuberculosis contaminant
Fears heightened of vaccine, but disproved
BCG: complications
Local ulcers and regional
lymphadenitis in normal
hosts: 4 to 30 per 1000
vaccinated infants
Osteomyelitis (0.1 to 30 per
100,000 doses)
Disseminated BCG
infection (0.1 per 100,000
doses
Death: 0.02 per million
It is recommended that where the risk of childhood TB
is high, BCG should be given to infants as early as
possible, even if mothers are known to have HIV
infection
A recent review has concluded the benefits of
immunization outweigh the risk of complications.
A consensus view currently exists, however, that BCG
should not be given to infants with active HIV disease
and that the vaccine is contraindicated in older
asymptomatic children who are found to be HIV
positive.
 Immunization of children at risk of
infection with HIV
The available data is not adequate to permit definitive
conclusions about the effectiveness of BCG vaccine to
protect HIV-infected children or adults against
tuberculosis.
 Adverse events associated with BCG
vaccination in children infected with HIV

Dissemination 0-31%

Lymphadenitis 0-24%
 Adverse events associated with BCG
vaccination in children infected with HIV
More than 28 cases of disseminated BCG infection have
been reported in HIV-infected children and adults
Progressive immune suppression can lead to the
reactivation of latent BCG organisms, causing regional or
disseminated disease
 TB vaccines: the future
Current Tuberculosis Vaccine Development
Advances in mycobacterial molecular genetics and the
establishment of the genome sequence of Mycobacterium
tuberculosis, make it possible to generate a vast new
repertoire of potential TB vaccine candidates.
An improved vaccine that would provide greater
protection against M. tuberculosis, although technically
feasible, is still far from being an achievable goal.
First US TB vaccine trial in 60
years begins
A new vaccine, made with several proteins from
MTB will enter the first phase of human safety
testing
This is the first recombinant TB vaccine to reach
human trials in the US
It combines two TB proteins known to stimulate
strong immune responses in humans
Optimal time for giving BCG to
infants
There is some evidence to suggest that later
immunization during infancy may confer a higher
degree of immunity.
BCG immunization at 3 months of age was found in
one study to provide a higher rate of tuberculin
protein skin responses with fewer complications than
when given during the first three days of life.
 Timing of BCG vaccination in
Canadian Cree infants
Lymphocyte response to PPD were measured at birth and
at intervals
The stimulation index in infants who received vaccination
at birth rose from 3.1 to 35.3
The SI in infants who were immunized between 9 months
and 2 years rose from 2.2 to 52.9 (p<0.05)
We cannot expect this of BCG
The vaccine, given to infants and children, may protect
the immunized individuals (somewhat unreliably) but
will do little else to check the spread of the disease and
thus can do little ultimately to control TB.
Children with TB pose a negligible infectious risk to
others. They acquire TB not from each other but, for the
most part, from adults with TB not preventable by BCG
Vaccination at birth has no effect on transmission of TB
in adults, who represent the bulk of highly infectious
cases
Vaccination at school-leaving age, practiced in
Britain and in Norway, was developed to address
this deficiency, but so far there has been no
unequivocal demonstration of the effectiveness of
this strategy in reducing transmission of M.
tuberculosis.
4. BCG should not be given to infants with active HIV
disease; it is contraindicated in older asymptomatic
children who are found to be HIV positive
5. It may protect the immunized individuals; it will not
affect the spread of the disease and thus can do little
ultimately to control TB
Prevention &
Control
 Elements of a Tuberculosis Control Program
X-ray
Targeted testing/
LTBI treatment
Pharmacy
Inpatient care
Medical evaluation
Clinical
and follow-up Services Laboratory
Non-TB medical Social
services Interpreter/ HIV testing and
services counseling
translator Occupational health,
services Patient school, jail, shelter,
education Data collection LTCF screening
Coordination of Documentation
medical care Epidemiology
Home Contact
evaluation Case DOT investigation and Surveillance
Outbreak Data analysis
Housing Management Investigation Program
Isolation, Follow-up/treatment evaluation &
QA, QI for case
detention of contacts planning
management
Consultation on Data for local, state, national
difficult cases surveillance reports Training
Federal TB State TB Control Program
Guidelines
Control Program Funding
State statutes, Information
National surveillance Training regulations, for public
policies, guidelines
Technical assistance Funding VDH/DDP/TB
Jan 2007
Global Policy: MDR-TB and XDR-TB

1. Strengthen basic TB control, to prevent

M/XDR-TB
2. Scale-up programmatic management and
care of MDR-TB and XDR-TB
3. Strengthen laboratory services for adequate and timely
diagnosis of MDR-TB and XDR-TB
4. Ensure availability of quality drugs and their rational use
5. Expand MDR-TB and XDR-TB surveillance
6. Introduce infection control, especially in high HIV
prevalence settings
7. Mobilize urgently resources domestically and
internationally
8. Promote research and development into new
diagnostics, drugs and vaccines
THANKS