Tuberculosis
identify clinical features, diagnosis and screening of TB
examine global epidemiology and risk factors
pharmacotherapy
challenges for treatment and effect
methods for prevention
bacterial infection caused by mycobacterium tuberculosis complex
global problem and affects developing countries
multidrug resistant tb remains a risk to public health
Infection
mode:
airborne disease and source of infection is passed from individuals with the active form
people are infected by inhaling bacterium via droplets during coughing or sneezing
patients are considered infectious if they have sputum smear positive pulmonary disease
patients with negative smear disease on at least 3 samples are less infectious than those who are positive
risk:
being born in high prevalence areas
children, adult males
people with untreated infection
immunospressed
underserved groups with limited social opportunities
excessive alcohol or drug intake
aetiology:
m tuberculosis has 3 different species → m bovis and m africanum are commonly known
m tuberculosis is most notable
m bovis - from bovine from milk but rare now due to elimination process
m africanum is causative agent for tb in west africa
m.tuberculosis:
inhalation and deposition in lungs leads to;
immediate clearance
primary active disease
active disease with progressive lung disease or other organ disease
latent infection - no active tb symptoms and is dormant and contained as bacteria is dormant in body
clinical:
symptoms:
prolonged respiratory symptoms (more than 2 weeks)
chronic cough, weight loss, fevers, night sweats, productive purulent sputum and haemoptysis
extrapulmonary → other organs except lungs like lymph nodes, pleura, skeletal sites, cns and abdominal sites → usually same symptoms but have weight loss and sweats
diagnosis:
looking at clinical presentation of cough, pleural effusions
sputum microbiology and chest radiography
sputum microscopy and mycobacterial culture are considered gold standard
screening:
screening for latent m tuberculosis is indicated for groups in which prevalence for latent infection is high
found using tuberculin skin test and interferon y release assay
they tests persons immunological memory against TB → use of mantoux test
interferon y release assay test - blood test based on detecting response of WBC to tb antigens - rarely gives false positives
mantoux test - results are read 48-72hrs later → transverse diameter of area of induration is measured with ruler and result is recorded in millimeters
treatment and prevention
BCG vaccine:
has live attenuated strain of m bovine
70-80% effective against severe forms of TB in children rather than adults
protection lasts 15 years
treatment:
cure patient
prevent death from active forms
prevent relapse
prevent drug resistance
prevent transmission
multitherapy may be required to achieve these and may not require hospital admissions
treatment for fully sensitive Tb needs use of four first line anti Tb drugs → isoniazid, rifampicin, pyrazinamide and ethambutol
streptomycin used to be used by no longer recommended for uncomplicated use
isoniazid and rifampicin is most effective esp when it comes to reducing drug resistance
rifampicin and pyrazinamide have sterilising activity and kill semi dormant resistant bacteria
phases of treatment:
initial phase of 4 drugs and continuation of 2 drugs in extreme cases
most patients with full strain get 6 month course
isoniazid and rifampicin with pyrazinamide and ethambutol for 2 months.
rifampicin and isoniazid with pyridoxine hydrochloride (aka vit B6 prescribed to prevent peripheral neuropathy associated with isoniazid for the next 4 months
active tb in cns should be on 12 month course
regimens:
supervised and unsupervised
depends on individual as they all have different adherence
daily dosing schedule is offered in active pulmonary tb and 1st choice in active extrapulmonary tb
treatment success from completion of therapy with negative sputum smears
directly observed therapy:
direct obs of swallowing medication
offered to;
current risk or history of non-adherence
previous infection of tb
history of homelessness, drug or alcohol misuse
those in prison, young offender in last 5 years
major psychiatric or memory disorder
multidrug resistant tuberculosis
treatment for latent tb
isoniazid monotherapy for 6months in adult and children
rifampicin and isoniazid daily for 3 months or 6months isoniazid monotherapy for children under 15
extrapulmonary tuberculosis:
12 month treatment → initial 2 months and 10 month continuation
initial high dose of dexamethasone or prednisolone and then withdrawn slowly over 4-8weeks
pericardial tuberculosis - oral prednisolone and slowly withdrawn over 2-3 weeks
resistance
monoresistance = to 1 anti-tb drug
mdr tv = multidrug resistance to at least isoniazid and rifampicin
treatment of drug resistance is complex → 2nd line anti-tb drugs are less effective than 1st line
treatment of mdr tb: use moxiloxacine with amikacin or capreomycin with any of prothionamide, cycloserine, linezolid or clofazimine → need at least 5 of any
rifampicin resistance:
6 months oral or bedaquiline, pretomanid, linezolid and moxifloxacin
9 month - bedaquiline for 6 months and then 4-6monghs of pyrazinamide and clofazimine followed by levofloxacin
longer regimens have 18 month duration
monitoring
urea and electrolyte
lfts every 2-4 weeks for 2 months
uric acid
vit d
full blood count
HIV and Hep screening
visual/sight testing
nutrition
adjustments:
renal disease:
pyrazinamide and ethambutol have dose interval extended to 3 times weekly in stage 4 and 5 kidney disease
isoniazid and rifampicin can be continued
isoniazid used with caution due to ototoxicity and neuropathy
liver disease:
close monitoring of lfts
treatment to be suspended if there is rise of plasma ast or alt if greater than 5 times the upper limit.
treatment interruption:
all potential causes of hepatotoxicity should be investigated
once enzyme levels return then treatment may restarts
start with ethambutol hydrochloride and either isoniazid or rifampicin
pregnancy and breastfeeding:
risk to both mother and baby
1st line anti-tb drugs are compatible
weigh risks of harm and benefit if using 2nd line as they are not compatible
close contacts:
latent screening should be offered if in contact with active tb
share enclosed space for a while
priority to children below 5, known/suspected immunocompromise, suspected contact with mdr-tb or anyone with symptoms suggestive of TB
Questions
Single Best Answer (SBA) Questions
Question 1.
A patient presents with a chronic cough lasting 3 weeks, fever, night sweats, and has recently coughed up blood-stained sputum. What is the most appropriate initial investigation to confirm active pulmonary TB?
a) Chest Radiography (Chest X-ray)
b) Tuberculin Skin Test (Mantoux test)
c) Sputum microscopy and culture
d) Interferon-Gamma Release Assay (IGRA)
Answer:
c) Sputum microscopy and culture
Your notes correctly identify sputum microbiology as the key diagnostic tool, stating "sputum microscopy and myobacterial culture are considered gold standard" for active TB. While a chest X-ray (a) is important, it is not confirmatory. The Mantoux test (b) and IGRA (d) are for screening for latent infection, not diagnosing active disease.
Question 2.
What is the primary public health goal of treating a patient with active, sputum smear-positive pulmonary tuberculosis?
a) To prevent the development of liver toxicity from the medication.
b) To provide pain relief and manage the patient's cough.
c) To prevent the transmission of TB to others.
d) To ensure the patient completes their course of vitamins.
Answer:
c) To prevent the transmission of TB to others.
A core objective of TB treatment is to render the patient non-infectious. Your notes list "prevent transmission" as a key goal. Sputum smear-positive patients are the main source of infection, and effective treatment rapidly reduces infectiousness.
Question 3.
For a patient with fully sensitive, active pulmonary TB, what is the standard initial phase (first 2 months) of treatment?
a) Isoniazid and Rifampicin
b) Isoniazid, Rifampicin, and Pyrazinamide
c) Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol
d) Rifampicin, Ethambutol, and a fluoroquinolone
Answer:
c) Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol
Your notes explicitly state that treatment for "fully sensitive Tb needs use of four first line anti Tb drugs → isoniazid, rifampicin, pyrazinamide and ethambutol" for the initial 2-month phase. This four-drug regimen is crucial to prevent the emergence of drug resistance.
Question 4.
A patient on standard TB therapy reports blurred vision and difficulty distinguishing colours. Which anti-TB drug is the most likely cause?
a) Isoniazid
b) Rifampicin
c) Pyrazinamide
d) Ethambutol
Answer:
d) Ethambutol
This is a classic, dose-related adverse effect of Ethambutol. Your notes appropriately list "visual/sight testing" under monitoring parameters, primarily for this reason.
Extended Matching Questions (EMQ)
Questions 5-7:
For each patient scenario, select the MOST appropriate management option.
Options:
A. Standard 6-month regimen (2HRZE/4HR)
B. 12-month regimen for extrapulmonary TB
C. Directly Observed Therapy (DOT)
D. Treatment for Latent TB (e.g., 6H)
E. Refer for MDR-TB treatment regimen
Question 5.
A 45-year-old man is diagnosed with fully sensitive pulmonary TB. He is homeless and has a history of alcohol dependence.
Answer:
C. Directly Observed Therapy (DOT)
Your notes list "history of homelessness, drug or alcohol misuse" as key indications for DOT to ensure adherence and prevent treatment failure or resistance.
Question 6.
A 28-year-old woman is diagnosed with tuberculous meningitis.
Answer:
B. 12-month regimen for extrapulmonary TB
Your notes specify that "active tb in cns should be on 10 month course" and for "extrapulmonary tuberculosis: 12 month treatment". CNS TB requires a longer duration of therapy.
Question 7.
A healthcare worker who is asymptomatic has a positive IGRA test after screening. They have no evidence of active disease.
Answer:
D. Treatment for Latent TB (e.g., 6H)
This is a classic case for Latent TB Infection (LTBI) treatment. The goal is to prevent progression to active disease. Your notes state "isoniazid monotherapy for 6months" is an option for latent TB.
Clinical Scenarios (OSCE/Patient Style)
Scenario 1: Counselling on TB Treatment
Patient: "I've been told I have TB and need to take four different tablets for two months, and then two for another four months. That seems like a lot. Why do I need so many, and what happens if I miss some?"
How do you, as the pharmacist, counsel this patient?
* Explain the Rationale: "It's completely understandable to be concerned. We use these four different medicines together for the first two months because it's the most effective way to attack the TB bacteria from different angles. Using just one or two could allow the bacteria to become resistant, making the infection much harder to treat."
* Emphasise Adherence: "Taking every single dose is the most important part of your recovery. If doses are missed, the bacteria can regrow and become resistant to the medicines. This can lead to a relapse or a form of TB (MDR-TB) that requires treatment for much longer with more toxic drugs."
* Manage Side Effects: "We will monitor you closely with blood tests. It's also important to know about potential side effects. For example, the tablet called Pyridoxine is given to prevent nerve damage from Isoniazid. Also, your urine and other bodily fluids might turn a harmless orange-red colour from Rifampicin. Most importantly, report any nausea, yellowing of the skin, blurred vision, or persistent tingling in your hands or feet immediately."
Scenario 2: Managing a Treatment Interruption
A patient on the initial phase of TB treatment presents to the pharmacy. Their routine blood test shows their ALT (a liver enzyme) is 8 times the upper limit of normal. They feel nauseous but are not jaundiced.
What is the appropriate course of action?
* Immediate Action: "Based on these results, you should stop taking all your TB medications immediately and contact your TB clinic or doctor today. Do not restart until they advise you to."
* Investigation: "The high liver enzymes suggest potential drug-induced hepatotoxicity, which is a known risk with these medicines. The doctor will investigate other potential causes."
* Re-challenge Strategy: "Once your liver tests return to normal, the doctor will likely re-start your treatment in a controlled way. They will often begin with a 're-challenge' using the less liver-toxic drugs first, such as Ethambutol with either Isoniazid or Rifampicin, and monitor you very closely before re-introducing all medications."
Prescription Review & Public Health
Question 8: Regimen and Monitoring
A standard prescription for the initial phase of TB is written as: Isoniazid, Rifampicin, Pyrazinamide, Ethambutol, and Pyridoxine. List the key monitoring parameters that should be in place for this patient over the first 2 months.
Answer:
* Clinical Symptoms: Inquire about nausea, vomiting, jaundice, visual disturbances, and skin rashes.
* Liver Function Tests (LFTs): Monitor ALT/AST every 2-4 weeks for 2 months (as per your notes: "lfts every 2-4 weeks for 2 months").
* Renal Function: Urea and Electrolytes (U&Es).
* Full Blood Count (FBC)
* Uric Acid (as Pyrazinamide can cause hyperuricaemia).
* Visual Acuity and Colour Vision (baseline and if symptoms develop, due to Ethambutol).
Question 9: Contact Tracing Prioritisation
A case of active, sputum smear-positive pulmonary TB is diagnosed in a factory worker. The public health team is identifying close contacts for screening. According to your notes, which contact should be prioritised as the highest risk?
a) A 60-year-old healthy co-worker who shares a break room.
b) A 40-year-old co-worker with well-controlled diabetes.
c) A 3-year-old child of the factory worker.
d) A 30-year-old co-worker who smokes.
Answer:
c) A 3-year-old child of the factory worker.
Your notes state that priority for latent TB screening should be given to "children below 5". Young children are at significantly higher risk of progressing from infection to severe, disseminated active TB disease. They share an enclosed space (the home) for prolonged periods.