TUBERCULOSIS

WHO defines Tuberculosis as potentially serious contagious infectious bacterial disease caused by
Mycobacterium tuberculosis Although tuberculosis primarily affects the lungs, other organs may also
be affected. TB is treatable with a six months course of antibiotics. WHO declared 24th March as In-
ternational World TB day.
Tuberculosis is a Neo-latin word consisting of:
Tubercle means Round nodule or swelling
Osis means condition
PREVELANCE:
In 2009, 9.4 million incident cases of TB and a prevalence of 137 cases of TB per 100 000 population
were reported globally. The five countries with largest number of cases were India, China,
Afghanistan,Indonesia and Pakistan. Pakistan stands 5thamong 22 countries with high burden of
Tuberculosis. Estimated prevalence of TB in Pakistan is 350 cases per 100 000 population
AETIOLOGY:
TB is caused by Tubercle bacilli which belong to genus Mycobacterium.
Mycobacterium species include:
M. Tuberculosis complex: M. tuberculosis, M. bovis, M. africanum.

PATHOPHYSIOLOGY:
Inhalation of Air borne droplets containing M. tb

Travel through the respiratory tract to the alveoli/distal airways

Engulfment by activated alveolar macrophages, dendritic cells and alveolar epithelial cells

Replication of [Link]

Bursting of cells, release of bacilli-entrance into other cells

Local proinflammatory response, recruitment of mononuclear and DCs

Infected macrophages, DCs spread to lymph nodes (LNs)

T-cell activation in LNs- T-cell activation in lymph nodes-initiation of cell mediated immunity (CMI)

Migration of activated T cells

Formation of granulomas

Liquefaction of granulomas
Containment of [Link]
Neutrophil influx (Dormant bacilli)
Primary T.B Latent T.B

MDR, XDR & TDR

TRANSMISSION:
Tuberculosis is transmitted to other persons by infected droplet generated by coughing or sneezing of
patient having pulmonary Tuberculosis. These tiny droplets dry rapidly, attach themselves to fine dust
particles and the smallest of them may remain suspended in the air for several hours. Only those parti-
cles that are less than 10 micron in diameter reach (>10 micron particles reside) of the pulmonary al-
veoli the healthy individual through inhalation resulting in infection.

RISK FACTORS / CAUSATION OF TUBERCULOSIS (HOST, AGENT & ENVIRONMENT):

Tuberculosis is caused by interplay of environmental and genetic factors which can be explained in the
form of an epidemiological triad:
Agent: Agent for the casing TB is Mycobacterium tuberculosis, which is an acid-fast, gram-positive,
aerobic, non-motile, rod-shaped organism. Two of its forms cause disease in humans: Human variety
and the Bovine variety.
Host: Man is the host for TB. Host factors that make him susceptible for the disease are as follows:
1- Age: Infants and children are not only more susceptible to develop TB than of their immunologic
immaturity, though no age is immune from TB. In Pakistan, more than 75% of active TB cases belong
to the productive age group (15-59 yrs).
2- Gender: The incidence of TB is high in males as compared to females in all age groups except
childhood, when incidence is higher in females.
3- Heredity: Some people resist TB more effectively than others. This maybe explained in part by the
genetic factors related to TB. HLA – DR 2 has been associated with the susceptibility to TB in Asian
population.

4- Nutrition: Malnutrition increases morbidity due to TB as well as its mortality, especially in re-
source poor settings. Poor nutrition affects the immune system and thus predisposes a person to tuber-
culosis.
5- Education: Lesser the education, higher is the TB prevalence. In one study it was found that in ur-
ban areas that people with no schooling suffer from TB four times than those who have tertiary level
education.
6- Occupation: Working in overcrowded and ill-ventilated places increases its chances of spreading.
Some occupational diseases like silicosis and anthracosis increases the susceptibility to TB
Environment: Certain environmental factors prone a person to TB. These include:

1- Overcrowding: Overcrowding leads to poor hygienic conditions, poor ventilation and contact of
infectious case with more people increasing the chances of transmission of TB.

2- Economic status: The association between TB and poverty is well established. Poverty can in-
crease person’s vulnerability to TB. Crowding, malnutrition, poor air ventilation and poor sanitation
all are related to poverty and have been associated with increased probability of being infected with
TB as well as activation of the infection.
Some features contrasting latent infection with active tuberculous disease
Latent infection Active disease
Bacilli present in Ghon focus Bacilli present in tissues or secretions
Sputum smear- and culture-negative Sputum commonly smear- and culture-positive in
pulmonary disease
MTb can usually be cultured from infected tissue
Tuberculin skin test usually positive Tuberculin skin test usually positive (and can ul-
cerate)
Chest X-ray normal (small calcified Ghon focus Chest X-ray shows signs of consolidation/ cavita-
frequently visible) tion/effusion in pulmonary disease
Asymptomatic Symptomatic-night sweats, fevers, weight loss
 and cough common
Not infectious to others Infectious to others if bacilli detectable in sputum

DIAGNOSTIC TEST:

 PULMONARY TB
Chest X-ray to look for changes to the appearance of tongs that are suggestive of TB Samples of
phlegm will also often be taken and checked for the presence of TB bacteria
 EXTRAPULMONARY TB
CT scan, MRI scan or ultrasound scan of the affected part of the body Endoscopy - the endoscope can
be inserted through a natural opening, such as your mouth, or through a small cut made in your skin
(laparoscopy) if there's a need to check other parts of the body.
 URINE AND BLOOD TESTS
Biopsy-a small sample of tissue or fluid is taken from the affected area and tested for TB bacteria.
Lumbar puncture, where a small sample of cerebrospinal fluid (CSF) is taken from the base of spine.
 TESTING FOR LATENT TB
In some circumstances, there is a need to have a test to check for latent TB For example, you may
need to have a test if you've been in close contact with someone known to have active TB disease in-
volving the lungs, or if you've recently spent time in a country where TB levels are high.
 MANTOUX TEST
The Mantoux test is a widely used test for latent TB. It involves injecting a small amount of a sub-
stance called PPD tuberculin into the son of forearm. It's also called the tubercular skin test (TST)
If having latent TB infection, the skin will be sensitive to PPD tuberculin and a small, hard red bump
will develop at the site of the injection, usually within 48 to 72 hours of having the test. If having a
very strong skin reaction, patient may need a chest X-ray to confirm whether the patient is having ac-
tive TB disease.
 INTERFERON GAMMA RELEASE ASSAY (IGRA)
The interferon gamma release assay (IGRA) is a blood test for TB that's becoming more widely avail-
able. The IGRA may be used to help diagnose latent TB, if patient is having a positive Mantoux test if
previously had the BCG vaccination- the Mantoux test may not be reliable in these cases as art of TB
screening
TREATMENT OF TUBERCULOSIS
First-Line Agents
Drug Dosing Side Effects Dose Ad- Needs to consider
(Adult) justment in
Renal Im-
pairment
Isoniazid 900mg Increased aminotrans- No Peripheral neuropathy prevent-
ferases (asymptomat- able with pyridoxine 10–
ic),clinical hepatitis, 25mg; ↑serum level of pheny-
peripheral neuropathy, toin. Hepatitis more common
CNS effects, lupus like in older patients and alcohol-
syndrome, hypersensi- ics.
tivity reactions
Rifampin 600 mg Pruritus, rash, hepato- No Orange-red discoloration of
toxicity, GI (nausea, body secretions (sweat, saliva,
anorexia, abdominal tears, urine) .Drug interactions
pain),flu like syndrome, due to induction of hepatic mi-
thrombocytopenia, re- crosomal enzymes (warfarin,
nal failure antiretroviral agents, cortico-
steroids, diazepam, lorazepam,
triazolam, quinidine, oral con-
traceptives, methadone, sul-
fonylureas).
Rifabutin 300 mg Neutropenia, uveitis, No Orange-red discoloration of
GI symptoms , poly body secretions (sweat, saliva,
arthralgias, hepatotoxi- tears, urine). Weaker inducer
city, rash of hepatic microsomal en-
zymes than rifampin.
Rifapentine 600 mg Pruritus, rash, hepato- Unknown Drug interactions due to induc-
toxicity, GI (nausea, tion of hepatic microsomal en-
anorexia, abdominal zymes (see rifampin).
pain),flu like syndrome,
thrombocytopenia, re-
nal failure
Pyrazinamide 1g Hepatotoxicity, nausea, Yes Monitor aminotransferases
anorexia, polyarthralgi- monthly.
as, rash, hyperuricemia,
dermatitis
Ethambutol 800 mg Optic neuritis, skin Yes Routine vision test recom-
rash, drug fever mended, 50% excreted un-
changed in urine.

Second line Agents

Drug Dosing Side Effects Dose Ad- Needs to consider

(Adult) justment in
Renal Im-
pairment
Cycloserine 1g CNS toxicity (psychosis, Yes May exacerbate seizure dis-
seizures), headache, tremor, orders or mental illness.
fever, skin rashes Some toxicity preventable
by pyridoxine (100–
200mg/d). Monitor serum
concentrations (peak20–
35mcg/mL desirable).
Ethionamide 1g GI effects (metallic taste, Yes Must be given with meal and
nausea, vomiting, anorexia, antacids. Monitor ami-
abdominal notransferases and thyroid-
pain),hepatotoxicity, neuro- stimulating hormone month-
toxicity, endocrine effects ly.
(alopecia, gynecomastia,
impotence, hypothyroid-
ism), difficulty in diabetes
management
Streptomycin 1g Vestibular or auditory dys- Yes Audio metric and neurologic
function of eighth cranial- examinations recommended;
nerve, renal dysfunction, 60%–80% excreted un-
skin rashes, neuromuscular changed in urine. Monitor
blockade renal function.
Amikacin 1g Ototoxicity, nephrotoxicity Yes Less vestibular toxicity than
streptomycin. Monitoring
similar to streptomycin
Capreomycin 1g Ototoxicity, nephrotoxicity Yes Monitoring similar to strep-
tomycin.
p- 8– GI intolerance, hepatotoxi- Yes Liver enzyme and thyroid
Aminosalicylic 12g/d city, malabsorption syn- function Should be moni-
acid (PAS) in two drome, hypothyroidism tored.
 to three
doses
Levofloxacin 500 to Nausea, diarrhea, abdominal Yes Do not give with divalent or
1,000 pain, anorexia, headache, trivalent cations (aluminum,
mg/d dizziness, QT prolongation, magnesium, iron, etc.).
tendon pain or rupture
Moxifloxacin 400 Nausea, diarrhea, abdominal No See levofloxacin
mg/d pain, anorexia, headache,
dizziness, QT prolongation,
tendon pain or rupture

DRUG-DRUG INTERACTIONS:

Anti-TB drugs have interactions with NNRTIs (NNRTIs are one of 6 classes of antiretroviral drugs
(ARVs) used to treat HIV as part of antiretroviral therapy (ART).), protease inhibitors, beta-blockers,
theophylline, digoxin, anticoagulants, antidepressents, contraceptives, corticosteroids, antifungals,
tetracyclines, Ca+ channel blockers ,chloramphenicol etc.
DRUG-FOOD INTERACTIONS:
• Isoniazid: Take 1hour before or 2 hours after meals. Avoid alcohol and smoking. Should not
be taken with antacids and metals and iron containing products
• Rifampin: Take 1 hour before or 2 hours after meals. Take 1 hour before antacids. Avoid al-
cohol.
• Ethambutol: May be taken with food.
• Pyrazinamide: May be taken with food.

TYPES OF TREATMENTS:
 Supervised treatment
 Unsupervised treatment

SUPERVISED TREATMENT (Directly Observed Therapy)

DOT means that a trained health care worker or other designated individual (excluding a family
member) provides the prescribed TB drugs and watches the patient swallow every dose.
 Studies show that 86-90% of patients receiving DOT complete their therapy, compared to 61% for
those on self-administered [Link] helps patients finish TB therapy as quickly as possible,
without unnecessary [Link] helps prevent TB from spreading to others, decreases the risk of drug-
resistance resulting from erratic or incomplete treatment, decreases the chances of treatment failure
and relapse.
DOT includesdelivering the prescribed medication,checking for side effects, watching the patient
swallow the medication, documenting the visit, answering questions
 Do not allow the patient to try self-administering medications and missing doses before providing
DOT.
UNSUPERVISED TREATMENT
 Take your pills at the same time every day for example; you can take them before eating breakfast,
during a regular coffee break, or after brushing your teeth. Ask a family member or a friend to
remind you to take your [Link] off each day on a calendar as you take your [Link] your
pills in a weekly pill dispenser. Keep it by your bed or in your purse or pocket.

TREATMENT IN CO MORBIDITES:

CO MORBIDITES DRUGS EFFECTS ADVERSE EFFECTS MONITORING

 PREGNANCY Most anti-tuberculosis Ototoxic To The Fetus streptomycin should
drugs are safe for use in not be used during
pregnancy except strep- pregnancy
tomycin

BREASTFEEDING All anti- tuberculosis Hepatitis BCG vaccination

drugs are compatible
with breastfeeding.
Baby should be given
prophylactic Isoniazid
for at least 6 months

ORAL CONTRA- Rifampicin interacts Risk of decreased pro- Higher dose of estrogen
CEPTIVE THERAPY with oral contraceptive tective efficacy against (50 ug) may be taken
medications pregnancy

HIV PATIENTS ON Anti-retroviral and anti- Increases the risk of Adjust the HIV or TB
ART TB drugs interact re- drug toxicity regimens
ducing each other’s ef-
ficacy

DIABETES Rifampicin levels may Diabetics are at in- Require higher level of
be lower in diabetics, it creased risk of drug monitoring and dose
raises blood glucose side effects adjustment.
levels in diabetics and
non-diabetics

NATIONAL TB CONTROL PROGRAMME

Our Mission
A TB FREE PAKISTAN

Vision
Universal Access To TB Care achieving Zero TB Death.

Goal
To reduce by 50% the prevalence of TB in the general population by 2025 in comparison with 2012.

Objectives
 To increase the number of notified TB cases from 298,981 in 2013 to at least 420,000 by 2020 while
maintaining the treatment success rate at 91%.

 To reduce by at least 5% per year by 2020 the prevalence of MDR-TB among TB patients who have
never received any TB treatment.

 Strengthen programmatic and operational management capacity of the TB Control Program while
enhancing public sector support for TB control by 2020.

ROLE OF PHARMACIST:
Pharmacists play a pivotal role in the management of patients with TB by providing their expertise
within an interdisciplinary team approach to patient care.
  They can assess the appropriateness, efficacy, and safety of antituberculous therapy by
monitoring patients and ensuring medication adherence.
 They can educate patients and clinicians about the expected therapy outcomes and the side
effects as well as drug interactions associated with antituberculous agents.
 Minor adverse events such as gastrointestinal disturbances are common in the first few weeks
of therapy and usually do not necessitate discontinuation of first-line agents.
 Patients may choose to take their medications with food, although absorption may be delayed.
Other adverse events such as drug-induced hepatitis, pyrazinamide-induced hyperuricemia, and
ethambutol-induced optical neuritis are more serious, require further evaluation, and may
necessitate discontinuation of therapy.
 Pharmacists may recommend pyridoxine to decrease the risk of isoniazid-induced neuropathy.
They should screen patients with comorbid conditions such as HIV infection for potential drug
interactions, particularly those patients receiving rifamycins and protease inhibitors.
 Pharmacists can also educate patients and clinicians about the importance of adherence and
DOT to ensure efficacy and minimize resistance.
LIFESTYLE MANAGEMENT:
 People with active TB disease should
stay home from work and school until
the doctor says it's safe to return.
 Wear a mask to cover your nose and
mouth. Cover your mouth with a tissue
when coughing and sneezing, then seal
the tissue in a bag to throw it away.
 Take all of your medications on time
and for the full period. Ask friend or
family member to remind you about
medicine; mark days off on a calendar
as you take the pills; or use a pillbox
that has a section for each day to help
you remember to take your medicine on
schedule.
 TB patients are encouraged to be
physically active. Moderate intensity
physical activity provides a boost to
your immune system and helps prevent
the development of active tuberculosis
infection.
 Consume fresh fruits (juices),
vegetable, healthy diet with less salt, fat-free or low-fat milk or equivalent milk products.

Drug-resistant TB:
MDR-TB (Multidrug-resistant TB)
It is caused by bacteria that are resistant to at least isoniazid and rifampicin, the most effective anti-TB
drugs. MDR-TB results from either primary infection with resistant bacteria or may develop in the
course of a patient's treatment. Fluor quinolones (levofloxacin or moxifloxacin), bedaquiline and line-
zolid are strongly recommended for a longer MDR-TB regimen.
XDR-TB (Extensively drug resistant TB)
It is a form of TB caused by bacteria that are resistant to isoniazid and rifampicin, that is, MDR-TB, as
well as any fluoroquinolone and any of the second-line anti-TB injectable drugs including amikacin,
kanamycin or capreomycin. Risk factors for XDR-TB include previous treatment for TB, HIV
infection, homelessness, and alcohol use. Treatment outcomes were significantly improved when later
generation fluoroquinolones were added to the treatment regimen for XDR-TB
TDR-TB (Totally drug resistant TB)
It is defined as resistance to all first-line and second-line agents. All of these TDR-TB cases were
HIV-negative. Centre for disease control and prevention termed the disease “untreatable”.

Tuberculosis Case study

HS is a 52 years old Hispanic female who present to emergency department with complaints of cough,
productive of small amount of yellow sputum within last [Link] has experience increasing fatigue,
occasional shortness of breath on exertion, and mild chest discomfort. She has had periodic night
sweats, last night her temperature was 38.9C. Two nights ago, she noticed streaks of bright-red blood
in her sputum without any particular order or taste. The only medication she has taken is an over the
outer cough preparation. Three months ago the patient presented to a free clinic and diagnosis revealed
a diagnosis of type 2 diabetes. A purified protein derivative (PPD) test, required for work clearance,
was placed. She noticed to have a positive PPD test, but because her chest x-ray showed no active dis-
ease, she was cleared to work.
Physical Examination:
Vital signs: BP 144/92 mmHg, Pulse 82, RR 18, T 37.90C
Neck and Lymph nodes: Few small 2-3 mm, non-tender, freely movable lymph nodes in left anterior
cervical and axial area
Chest: Configuration and expansion symmetrical. Percussion symmetrical bilaterally. Breath sounds
and vocal fremitus are normal. Afew rales are noted at the left apex posteriorly.
Other areas of examination was normal.
Laboratory:
Skin test results: PPD (tuberculin) 16 mm at 48 hours.
Chest x-ray: Bilateral upper lobe infiltrates with well-defined cavitating legion of the left apex
Questions
Q. No. 01: What groups are at highest raise for developing TB?

Q. No. 02: In patients with laboratory confirmed drug susceptible active pulmonary mycobacterium
tuberculosis, what are the standard medications and duration of treatment?

Q. No. 03: The patient’s liver function test are slightly elevated. Why is this important and does it
change the management of her TB infection?

Q. No. 04: How is the therapeutic efficacy assessed in the treatment of TB?
Q. No. 05: How does this information change your recommended drug combination and duration of
therapy?

Q. No. 06: Make a prescription analysis form of patient having smear positive pulmonary TB?

Rx Dosage Brand Generic Strength Class Frequency Duration Instructions

form