Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis. It spreads through the air when people with active TB cough, sneeze or talk. Recent developments in TB management include using a combination of antibiotics like INH, RIF, pyrazinamide, and ethambutol for 2 months followed by INH and RIF for 4 months to treat active TB. Managing TB in high-risk groups like those with HIV, diabetes, smoking history requires extra precautions. Experts should be consulted for treating TB in pregnant women or those with HIV to minimize drug interactions and risks.
2. INDEX
2
S.NO. TITLE PAGE
NUMBER
1 INTRODUCTION 3
2 PATHOPHYSIOLOGY 13
3 EPIDEMOLOGY 18
4 ETIOLOGY&RISK FACTORS 19
5 MANAGEMENT
Pharmacological and non pharmacological
25
6 RECENT ADVANCEMENT IN MANAGEMENT 39
7 REFERENCE 45
3. INTRODUCTION TO
TUBERCULOSIS3
TB is an airborne disease caused by the
bacterium Mycobacterium tuberculosis (M.
tuberculosis)
M. tuberculosis and seven very closely related
mycobacterial species (M. bovis, M.
africanum, M. microti, M. caprae, M. pinnipedii,
M. canetti and M. mungi) together comprise
what is known as the M. tuberculosis complex.
4. 4
TB is not easily caught – you have to be in
fairly prolonged close contact with someone
with TB (for example, living in the same
household) – but everybody should be aware
of the symptoms of the disease so they can
seek treatment as soon as possible.
TB is curable with a course of
special antibiotics.
5. 5
Not everyone with TB of the lungs is
infectious, and as long as they are
taking the proper treatment most
people that were infectious become non-
infectious quickly – generally after about two weeks –
as long as they are taking the proper treatment.
While anyone can catch TB, some groups of people
are more at risk than others. These include people
who: • have lived in the same household –
or been in prolonged close contact –
with someone with infectious TB
• are living in unhealthy or overcrowded conditions, inc
luding those who are homeless or sleeping rough
6. 6
• have lived, worked or stayed for a
long time in an area with a high rate of TB, e.g. south-
east Asia, subSaharan Africa and some countries
in eastern Europe
• may have been exposed to TB in
their youth when the disease was
more common in this country
• are the children of parents whose
country of origin has a high rate of TB
• have been in prison
• are unable to fight off infection
(immunosuppressed) due to illness
(e.g. HIV infection) or treatment
• are dependent on drugs or misuse alcohol
• do not eat enough to stay healthy.
7. TRANSMISSION AND
PATHOPHYSIOLOGY
7
M. tuberculosis, by far the commonest, is
transmitted between humans through the airborne
route.
M. bovis may penetrate the gastrointestinal
mucosa or invade the lymphatic tissue of the
oropharynx when ingested in milk from diseased
cows.
Human infection with M. bovis has decreased
significantly in developed countries as a result of
the pasteurisation of milk and effective
tuberculosis control amongst cattle. Infection with
the other organisms is relatively rare.
TRANSMISSION:
8. 8
Tuberculosis is usually spread from person-to-
person through the air by droplet nuclei (<5
microns) that are produced when a person with
pulmonary or laryngeal tuberculosis coughs,
sneezes, talks or sings.
Droplet nuclei, which are small particles 1 to 5 µm
in diameter containing 1-5 bacilli, are highly
infectious. They are so small that air currents
normally present in any indoor space can keep
them airborne for up to 4 hours. These droplets
are small enough to reach the alveolar spaces
within the lungs, where the organisms replicate.
9. 9
Three factors determine the likelihood of
transmission of M. tuberculosis:
• The number of organisms expelled into the air
• The concentration of organisms in the air,
determined by the volume of the space and its
ventilation
• The length of time an exposed person breathes
the contaminated air
One cough can produce 3,000 droplet nuclei and
a sneeze up to a million droplet nuclei; the
infectious dose of tuberculosis is 1 to 10 bacilli
10. 10
The most infectious cases are those with
smear positive pulmonary TB,
Smear negative pulmonary TB cases are
much less infectious.
Extra-pulmonary cases are almost never
infectious, unless they have pulmonary
tuberculosis as well.
Individuals with latent tuberculosis infection
are not infectious, as they do not have
replicating bacteria and cannot transmit the
organism.
11. 11
50-60% of HIV positive people infected with
TB will go on to develop active disease.
Immunosuppressive conditions such as
silicosis, diabetes mellitus, and prolonged use
of corticosteroids and other
immunosuppressive drugs are used; also
increase the risk of progression to active TB.
12. 12
BCG(bacille calmetee guerin) immunisation
gives variable protection against the
progression of TB from infection to disease.
The main benefit of BCG is the protection
against the development of the serious forms
of TB in children, such as TB meningitis and
disseminated TB.
13. PATHOGENESIS
13
After inhalation, the droplet nuclei are carried
down the trachea-bronchial tree and deposited
in a respiratory bronchiole or alveolus where
they are ingested by alveolar macrophages
that produce a nonspecific response to the
bacillus. Infection depends both on the
bacterial virulence and the inherent
microbicidal ability of the alveolar macrophage
that ingests it. If the bacillus is able to survive
initial defences, it can multiply within the
alveolar macrophage.
14. 14
The tubercle bacillus grows slowly, dividing
approximately every 25 to 32 hours within the
macrophage. The mycobacterium has no
known endotoxins or exotoxins, so there is no
immediate host response to the infection. The
organisms grow for 2 - 12 weeks and reach
103 to 104 in number, which is sufficient to
elicit a cellular immune response that can be
detected by a reaction to the tuberculin skin
test. The destruction of macrophages and
release of tubercle bacilli products and
chemokines stimulates an immune response.
15. 15
Before the development of cellular immunity,
tubercle bacilli spread via the lymphatics to the
hilar lymph nodes and from there through the
bloodstream to more distant sites. Certain organs
and tissues are notably resistant to multiplication
of these bacilli. The bone marrow, liver and spleen
are almost always seeded with mycobacteria, but
uncontrolled multiplication of the bacteria in these
sites is unusual. Organisms deposited in the
upper lung zones, kidneys, bones and brain find
environments that favour their growth. Numerous
bacterial divisions may occur before specific
cellular immunity develops, limiting multiplication.
16. 16
Primary infection
Primary infection occurs on first exposure to
tubercle bacilli. This usually occurs in childhood
so primary TB is often thought of as childhood TB.
However, it can occur at any age in a previously
unexposed individual
Primary infection is usually asymptomatic and a
positive tuberculin skin test 4-6 weeks after
infection is the only evidence of infection.
17. 17
Post-primary TB / Secondary TB
Post-primary TB is the pattern of disease that
occurs in a previously sensitised host. It occurs
after a latent period of months or years after
primary infection. It may occur either by
reactivation of latent bacilli or by re-infection.
18. EPIDEMOLOGY
18
TB has been around for at least 4000 years Egyptian mummies
show signs of the disease.
Around 2 billion people (about one third of the world’s population)
are infected with TB and are therefore at risk of developing
active TB (TB disease) at some time in their life.
The World Health Organization (WHO) estimates that across the
world, more than 9 million people develop TB disease every year.
TB also causes just under 2 million deaths every year. Alongside malaria
and HIV it is one of the greatest infectious disease challenges in the world
today.
In subSaharan Africa, the HIV epidemic is making people much
more susceptible to developing TB disease.
In London, the number of TB cases has doubled since the 1980s,
accounting for almost 3500 cases each year.
In the UK, because of good access to effective services, death from TB is
rare.
19. ETIOLOGY AND RISK
FACTORS19
ETIOLOGY:
TB and HIV
Infection with HIV increases the risk of progression of
recent M. tuberculosis infection and of reactivation of
latent M. tuberculosis infection by 5–15% annually. It
also increases the rate of relapse and re-infection.
HIV is responsible for a large increase in the
proportion of patients with smear-negative pulmonary
and extrapulmonary TB. These patients have inferior
treatment outcomes, including excessive early
mortality, compared with HIV-positive, smear-positive
pulmonary TB patients due to late presentation,
diagnosis and initiation of treatment
20. 20
TB and Diabetes
The prevalence of TB disease is higher in patients with
diabetes compared to those without diabetes mellitus and
DM prevalence is high amongst people with TB disease .
The relative risk of death among TB patients with Diabetes
mellitus is high compared to non diabetic TB patients .
TB and smoking
Passive and active exposure to tobacco smoke is
significantly associated with TB exposure and disease.
Smoking is a risk factor for TB, independent of alcohol use
and other socioeconomic factors. The risk is higher in
children exposed to passive smoking. Active smoking is
associated with recurrent TB disease and death due to TB
disease
21. 21
TB and alcohol
High alcohol consumption (on average >40g alcohol
per day) with or without an alcohol use disorder is
associated with three fold risk of developing TB. Low
to medium alcohol consumption is not associated with
an increased risk of TB disease
TB and silicosis
Silicosis is an occupational lung disease caused by
inhalation of silicon dioxide in crystalline forms such
as quartz, cristobalite or tridymite. Workers at greatest
risk are those that blast rock and sand such as
miners, quarry workers and stone cutters.
22. 22
RISK FACTORS:
Diabetes
Head or neck cancer
Illnesses thatsuppress the immune system,such as
HIV or AIDS
Kidney disease
Long term stroid use
Malnutrition
Mediction that suppress the immune system,such as
anticancer medications.
Pregnancy
Radiotheraphy
23. CLINICAL PRESENTATION
OF TB23
Pulmonary TB
Symptoms
The main symptoms of pulmonary
tuberculosis are:
• Persistent coughof 2 weeks or more or
any duration if HIV positive
• Fever for more than 2 weeks •
Drenching night sweats
• Unexplained weight loss (more than 1.5
kg in a month)
24. 24
2 Extra-pulmonary TB
Extra-pulmonary TB can present with non-specific
symptoms such as unintentional weight loss (more than
1.5 kg in a month), night sweats and fever for more than 2
weeks. Other symptoms depend on the site or organ
affected. The most common types of extra-pulmonary
tuberculosis are:
• TB lymphadenitis
• Tuberculous pleural effusion (usually single-sided)
• TB of the bones and joints
• Tuberculous pericardial effusion
• TB meningitis
• Disseminated / miliary tuberculosis
• Tuberculous empyema • TB peritoneal effusion
26. 26
TREATING ACTIVE TB
The standard TB treatment regimen INH, RIF,
pyrazinamide, and ethambutol for 2 months followed by INH and
RIF for
4 months.
• Appropriate samples should be sent for culture and
susceptibility testing
prior to initiating therapy for all patients with active TB. This data
should
guide the initial drug selection for the new patient. If susceptibility
data are
not available, the drug resistance pattern in the area where the
patient
likely acquired TB should be used.
• If the patient is being evaluated for the retreatment of TB, it is
imperative
to know what drugs were used previously and for how long
27. 27
Patients must complete 6 months or more of treatment. HIV-
positive
patients should be treated for an additional 3 months and at least
6 months
from the time that they convert to smear and culture negativity.
When
INH and RIF cannot be used, treatment duration becomes 2
years or more,
regardless of immune status.
• Patients who are slow to respond, those who remain culture
positive at 2
months of treatment, those with cavitary lesions on chest
radiograph, and
HIV-positive patients should be treated for 9 months and for at
least 6
months from the time they convert to smear and culture
negativity.
28. Pregnant Women
28
Untreated TB disease represents a greater hazard to a pregnant woman and her
fetus than does its
treatment. Because of the risk of TB to the fetus, treatment of TB in pregnant women
should be
initiated whenever the probability of maternal disease is moderate to high. Th initial
treatment
regimen should consist of INH, RIF, and EMB. Although all of these drugs cross the
placenta, they
do not appear to have teratogenic effcts. Streptomycin is the only anti-TB drug
documented to
have harmful effcts on the human fetus (congenital deafness) and should not be
used. Although
detailed teratogenicity data are not available, PZA can probably be used safely
during pregnancy and
is recommended by the World Health Organization (WHO) and the International
Union Against
Tuberculosis and Lung Disease (IUATLD). If PZA is not included in the initial
treatment regimen,
the minimum duration of therapy is 9 months.
29. Breast-feeding
29
Breast-feeding should not be discouraged for
women being treated with fist-line anti-TB drugs,
because the small concentrations of these drugs
in breast milk do not produce toxicity in the
nursing
newborn. Pyridoxine (vitamin B6) supplementation
(25 mg/
day) is recommended for all women taking INH
who are either pregnant or breast-feeding. The
amount of pyridoxine in multivitamins is variable,
but generally less than the needed amount.
30. Infants and Children
30
Infants and children with TB disease should be
treated with the regimens recommended for
adults, with the exception that EMB is not
used routinely in children. For children whose
clarity
or sharpness of vision cannot be monitored,
EMB is usually not recommended except
when the
risk of drug resistance is high
31. HIV-Infected Persons
31
Management of HIV and TB coinfection is complex, and the clinical and
public health
consequences associated with the failure of treatment and other negative
outcomes are serious. HIV
infected patients are on numerous medications, some of which interact with
anti-TB drugs. It is
therefore strongly recommended that experts in the treatment of HIV-
related TB be consulted..
Every effort should be made to use a rifamycin-based regimen for the entire
course of therapy in
coinfected patients. Th key role of the rifamycins in the success of TB
disease treatment mandates
that the drug-drug interactions between the rifamycins and antiretroviral
drugs be managed
appropriately, rather than using TB treatment regimens that do not include
a rifamycin or by
withholding antiretroviral therapy until completion of anti-TB therapy.
32. 32
Of particular concern is the interaction of rifamycins with
antiretroviral agents and other anti
infective drugs. Rifampin can be used for the treatment of TB with
certain combinations of
antiretroviral agents. Rifabutin, which has fewer drug-drug
interactions due to its decreased induction of the cytochrome P450
system, may also be used in place of rifampin and appears
to be equally effctive, although the doses of the rifabutin and
antiretroviral agents may require
adjustments and should be administered with expert consultation.
Threfore, patients with HIV-related TB disease should be treated
with a regimen including a
rifamycin for the full course of TB disease treatment, unless the
isolate is resistant to the rifamycins
or the patient has a severe side effct that is clearly due to the
rifamycins.
33. Renal Insuffiency and End-stage
Renal Disease33
Renal insuffiency complicates the management of
TB disease because some anti-TB drugs are
cleared by the kidneys. Alteration in dosing of anti-
TB drugs is commonly necessary in patients with
renal insuffiency and end-stage renal disease
(ESRD) requiring hemodialysis. Th dosage of
antiTB drugs should not be decreased because
the peak serum concentrations may be low and
smaller
doses may decrease drug efficy. Instead, the
dosing interval of anti-TB drugs should be
increased.
34. Extrapulmonary TB Disease
34
As a general rule, the principles used for the treatment of pulmonary
TB disease also apply to
extrapulmonary forms of the disease. A 6-month treatment regimen
is recommended for patients
with extrapulmonary TB disease, unless the organisms are known
or strongly suspected to be
resistant to the fist-line drugs. If PZA cannot be used in the initial
phase, the continuation phase
must be increased to 7 months. Th exception to these
recommendations is central nervous system
TB, for which the optimal length of therapy has not been
established but some experts recommend
9 to 12 months. Most experts do recommend corticosteroids to be
used as additional therapy for
patients with TB meningitis and pericarditis.
35. Management of patients with drug-
resistant35
Management of patients with drug-resistant TB disease is based on
the following guidelines:
• A single new drug should never be added to a failing regimen;
• In patients with MDR organisms resistant to fist-line drugs in
addition to INH and RIF,
regimens employing four to six drugs that are new to the patient and
to which the isolate
shows in vitro susceptibility appear to be associated with better
results;
• Patients with multidrug-resistant organisms should receive the
highest priority for DOT, which
should be administered either in the hospital, home, or other facility;
• Th use of drugs to which there is demonstrated in vitro resistance
is not encouraged because
there is little or no efficy of these drugs and alternative medications
may be available;
36. 36
• Resistance to RIF is associated in nearly all instances with cross-
resistance to rifabutin and
rifapentine (RPT);
• Thre is no cross-resistance between SM and the other injectable
agents, amikacin, kanamycin,
and capreomycin (although resistance to all may occur as
independent events); cross-resistance
between amikacin and kanamycin is not universal but frequently
seen;
• Resistance to PZA is uncommon in the absence of resistance to
other fist-line drugs; if
monoresistance to PZA is observed, consideration must be given to
the possibility that the
disease is caused by M. bovis, not M. tuberculosis; and
• Intermittent therapy should not be used in treating TB disease
caused by drug-resistant
organisms, except perhaps for injectable agents after the initiation
phase (usually 2 to 3
months) of daily therapy
37. NON-PHARMACOLOGICAL
METHOD37
Isolate patients with possible Tb infection in a
private room with negative pressure(air exhausted
to outside or through a high-efficiency particulate
air filter)
Wear high efficiency disposable masks sufficient
to filter the tubercle baacillus.
continue isoltion until sputum smears are negative
for 3 consecutive determinations(usually after
approximtely 2-4wk of treatment)
Surgical resection of an infected lung may be
considered to reduce the bacillry burden in
patients with MDR-TB.
38. 38
Surgery is recommended for patients with
MDR-TB whoes prognosis with treatment is
poor.
Procedures include segmentectomy,lobectomy
and pneumonectomy.
39. RECENT DEVELOPMENT IN
MANAGEMENT39
WHO has recently launched its innovative “End TB Strategy” ,
supporting the TB elimination strategy
and the vision of a TB-free world with zero death, disease
and suffering due to TB .
The new strategy clearly supports universal access to high-
quality MDR-TB diagnosis and treatment.
However, since the market launch of rifampicin in the early
1960s, no new anti-TB drug has been specifically developed
until recently, while significant progress has been achieved in
the area of diagnostics (e.g. Xpert MTB/RIFtest)
The treatment regimens, approved TB drugs and the dosage
of anti-TB drugs recommended by the
evidence-based WHO guidelines ( presently under revision)
40. 40
“ New” and “ retreatment” cases are clearly separated, 30 days of previous
anti-TB treatment being the cut-off
New TB cases (irrespective of HIV status) should be treated for the first 2
months (intensive phase) with isoniazid, rifampicin, pyrazinamide and
ethambutol, followed by isoniazid and rifampicin for the remaining 4 months
(continuation phase) [17]. The daily dosage is recommended (although the
three times weekly dosing can be used during the continuation phase under
directly observed therapy) as well as
the fixed-dose combinations [18].
Drug susceptibility testing (DST) (rapid and/or conventional ) is strongly
recommended by WHO in all cases and particularly for those previously
treated [1].
While awaiting DST results, in settings with a medium or low probability of
MDR-TB, retreatment cases could initially be treated with an empiric
regimen including isoniazid, rifampicin, pyrazinamide, ethambutol and
streptomycin for 2 months, followed by isoniazid, rifampicin, pyrazinamide
and ethambutol for 1 month, and isoniazid, rifampicin, and ethambutol for 5
months.
