TUBERCULOSIS

DR MOSES KAZEVU

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WARM UP: THEORY

A 72-year-old homeless man has been feeling unwell for the past 5 weeks with fever and a productive
cough. His fellow homeless men have brought him to the emergency medical unit and they say he has lost
more than 10% of weight over the past 2 months.

Examination reveals he is confused and tachypneic with a respiratory rate of 36/minute. His BP is
80/50mmHg. You order a CXR and you find that he has infiltrates on upper and middle lobes on the right
side. HIV test is negative.
A. What is your diagnosis? (2 marks)
B. What are the markers of severity in this patient? Mention 5 (5 marks)
C. Mention 5 complications of this condition? (5 marks)
Sputum is sent for Gen-Xpert and report shows: MTB detected (medium): Rif resistance NOT DETECTED
D. You decide to start him on first line TB medication. List the name of the drugs you will prescribe and 2
common side effects of each drug. (8 marks: 2 marks per drug and side effects)

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TUBERCULOSIS
• This is a chronic necrotizing disease caused by Mycobacterium tuberculosis
complex usually affecting the lungs and sometimes some other organs.
• Tuberculosis is caused by a range of mycobacterium including the species M.
tuberculosis (most common), M. bovis (reservoir cattle), M. africanum (reservoir
human) and M. microti.
• M. tuberculosis is an encapsulated obligate aerobe, facultative intracellular
pathogen rod-shaped, non-spore forming, thin bacterium.
• The mycolic acid in the cell wall and the capsule impede phagocytosis.
• They are slow growing with a generation time of 12-18 hours.
• Due to high lipid content in the cell wall, they are relatively impermeable and stain
only weakly with Gram-stain.
• The bacterium is demonstrated by acid fast staining technique.
• When stained with a dye combined with phenol and washed with acidic organic
solvents, they resist decolorization and therefore are termed ‘acid-fast bacilli’-
AFB.

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TB CLASSIFICATION
• Pulmonary tuberculosis (PTB): 80% of
cases
• 75-80% of all PTB cases are smear-positive
PTB.
• 20-25% of all PTB cases are smear-
negative PTB.
• Extra-pulmonary TB (EPTB)- 20% of cases.

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TRANSMISSION
• Adults with smear positive TB such as cavitory TB and laryngeal TB are
the sources of infection.
• Patients who are culture-negative pulmonary TB and extra pulmonary
disease are not infectious.
• M. tuberculosis is commonly transmitted from a patient with infectious
tuberculosis to a healthy individual through:
• Inhalation of droplets excreted via coughing, sneezing or speaking.
• Only a small number of bacteria need to be inhaled to develop
infection but not all those who are infected develop active disease.
• The outcome is dependent on a number of factors including the
host’s immune response.
• Drinking non-sterilized infected cow milk could also transmit M. bovis
but the incidence seems to be decreasing because of health education
on boiling or pasteurizing milk.

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FACTORS FACILITATING
TRANSMISSION
• Presence of a contact
• Infectivity of the contact (patients with heavy
bacterial load)
• Duration of contact (prolonged exposure)
• Intimacy (how close the source and the
subject are)
• Environment: overcrowding, poor ventilation
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NOTE
• Patients who acquire the infection may not
develop the disease.
• The rate of clinical disease is highest during
late adolescence and early adulthood but the
reasons are not clear.
• Infections are more common in young women
than men.

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FACTORS THAT INCREASE RISK OF

DEVELOPING ACTIVE TB
• HIV (co-infection) due to suppression of cellular immunity.
• Hematologic and other malignancies: lymphoma,
leukemia, malignancies.
• Chronic renal failure
• Diabetes mellitus
• Immune suppressive drugs like long-term corticosteroids
(e.g. prednisolone)
• Old age: decreased immunity
• Malnutrition is a very important factor for the development
of disease.
• Alcohol
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PATHOGENESIS
• Transmission is through droplet infection. Only a small number of bacteria need to be inhaled to
develop infection but not all those who are infected develop active disease.
• M. tuberculosis interacts with host immune system immediately after entry. It initiates the
recruitment of macrophages and lymphocytes.
• Activated alveolar macrophages ingest the bacilli, after which they release neutrophil chemo-
attractants and cytokines to activate other immune system components and try to control the
infection or multiplication of bacilli. This process will recruit cells (cell mediated immune
response).
• Macrophages present the antigen to the T-lymphocytes.
• Macrophages undergo transformation into epithelioid and Langerhans cells which aggregate
with lymphocytes to form the classical tuberculous granuloma.
• A delayed hypersensitivity-type reaction occurs resulting in tissue necrosis and formation of a
granuloma.
• Activated cells aggregate around the lesion and the center becomes necrotic, soft cheese like
material called caseous necrosis.
• Granulomatous lesions consist of a central area of necrotic material (caseation), surrounded by
epithelioid cells and Langhans’ giant cells with multiple nuclei, both cells being derived from
macrophages. Lymphocytes are present and there is a varying degree of fibrosis.

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PATHOGENESIS
• Numerous granulomas aggregate to form a primary lesion or ‘Ghon focus’ characteristically situated in the periphery
of the lung.
• Spread of organisms to the hilar lymph node is followed by a similar pathological reaction and the combination of the
Ghon focus and regional lymph nodes is referred to as the ‘Primary complex of Ranke’.
• The primary complex is encapsulated in a fibrous capsule, limiting the spread of the bacilli, so called latent TB.
• The primary complex of Ranke is seen in ‘healed’ primary pulmonary tuberculosis and is a later manifestation of the
ghon complex (Ghon focus + ipsilateral calcified mediastinal nodes).
• If no further complication arises the lesion may eventually be calcified and is clearly seen on X-ray
• The center however may still contain live bacteria that become dormant. These bacteria will flare up and multiply
when the person’s immunity is depressed.
• But if the bacteria inside the macrophage multiply rapidly, they will kill the macrophage and are released but to be
taken up by other macrophages again. If this process is not arrested, patients may develop disseminated infection.
• On initial contact with infection <5% of patients develop active disease. This percentage increases to 10% within the
first year of exposure.
• In the majority of people who are infected by mycobacterium spp, the immune system contains the infection and the
patient develops cell mediated immune memory to the bacteria. This is termed latent tuberculosis.
• The majority of TB cases are due to reactivation of latent infection. The initial contact usually occurred many years or
decades earlier. In patients with HIV infection newly acquired TB infection is also common. This is called reactivation
tuberculosis.

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CLINICAL MANIFESTATIONS-
PULMONARY TB
• Patients are frequently symptomatic with a
productive cough and occasionally hemoptysis along
with systemic symptoms of weight loss, fever and
sweats (commonly at the end of the day and through
the night).
• This can be classified as
• Primary Pulmonary tuberculosis
• Secondary/ Re-activation Tuberculosis
• Note: extrapulmonary involvement is far less
common in primary disease and is usually only seen
in regions of high endemnicity.

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PRIMARY PULMONARY
DISEASE
• Clinical illness follows after primary tuberculosis (no history of prior TB infection).
• This is common in children <4 years of age, it results from an initial infection.
• Frequently it involves the middle and lower lung zones.
• In the majority it heals spontaneously leaving a healed scar on the lung called
Ghon lesion.
• It may be contained by immunity into dormant stage only to flare up in
immunocompromised state (re-activation).
• In children or in immune compromised individuals the disease is usually rapid
involving lungs, pleura and mediastinal lymph nodes.
• It may disseminate into the blood stream and cause miliary tuberculosis.
• Characterized by 2-3 weeks of fever, night sweats, anorexia, weight loss and a dry
cough.

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SECONDARY/RE-ACTIVATION
PULMONARY TUBERCULOSIS
• If no clinical disease is developed after primary infection, dormant bacilli may persist for years
or decades before being reactivated when this happens, it is called secondary (post primary)
tuberculosis.
• It is more common in adults and typically involves the apical lobes, where oxygen tension favors
survival of the strictly aerobic organism but any portion of the lungs can be involved.
• The disease could extend from small infiltrates to large cavitory lesions. Patients with cavitory
lesion expectorate tuberculosis bacilli with sputum.
• Early in the course patients may have intermittent fever, night sweats, weight loss, anorexia and
weakness. Most patients have cough which may be dry at first but later becomes productive of
whitish sputum, it is frequently blood streaked.
➢ Patients may have exertional dyspnea, and hoarseness of the voice if there is laryngeal
involvement.
• Physical examination:
➢ Chronically sick patient
➢ Pallor
➢ Finger clubbing
• Inspiratory crepitations are seen in some cases

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LABORATORY FINDINGS
➢ ESR: raised
➢ Full blood count: Anemia, Leukocytosis
➢ Sputum examination (microscopy, culture and sensitivity) may
be positive for AFB
➢ GeneXpert
➢ CXR findings are non-specific:
o Infiltrations,
o Consolidation with or without cavitation
o Pleural effusion
o Thickening or widening or the mediastinum caused by hilar
or paratracheal adenopathy

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EXTRAPULMONARY TB
• Accounts for about 20% of cases in those
who are HIV-negative but is more common in
HIV-positive individuals.
• Commonly affected organs are lymph nodes,
pleura, meninges, genitourinary tract, bones,
joints, adrenal glands and peritoneum.

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TUBERCULOSIS MENINGITIS
• It is commonly seen in children and immune-compromised people particularly patients
with HIV.
• More than half have evidence of disease in the lungs.
• Patients with TB meningitis present with headache, behavioral changes and neck rigidity
for about two weeks or more. Patients may have cranial nerve paralysis and seizure.
• Cerebral spinal fluid (Lumbar puncture) analysis
➢ Increased WBC count predominantly lymphocytes and very high protein (usually >2-
3g/L) and low glucose content (<1/2 blood glucose). But any of these could be normal
in the presence of the disease.
➢ AFB can be seen in sediment CSF in only 20% of cases, this percentage increases if
examined CSF volume is increased. Culture may be positive in about 80% but it takes 4
to 6 weeks to grow.

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PERICARDIAL TUBERCULOSIS
(TB PERICARDITIS)
• Arises from ruptured abdominal lymph node or hematogenous dissemination.
• Patients usually present with chronic low-grade fever (particularly in the evening),
associated with feature of acute pericarditis, retro-sternal pain, cough, dyspnea and
generalized edema because of pericardial effusion. Cardiac tamponade may appear later.
• Constrictive pericarditis may develop as a complication of TB pericarditis even after
treatment and patients can present with symptoms and signs of right sided heart failure.
• Diagnosis is usually reached by analyzing the pericardial effusion. It may show
lymphocytosis but yield for AFB is low.
• Chest X ray may show enlarged heart shadow which suggests effusion. Ultrasound should
be done when available and it demonstrates effusion.
• Treatment is as for pulmonary TB but prednisolone 60mg daily for 2-6 weeks is added.

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MILIARY TB
• This is secondary to hematogenous dissemination of the bacilli to multiple sites, including the central
nervous system in 20% cases.
• It is more common in children and immune-compromised patients.
• Manifestations are nonspecific with fever, night sweats, anorexia, weakness and weight loss. Patients may or
may not have respiratory symptoms.
• Physical examination:
➢ Seriously sick patient with hepatomegaly,
➢ splenomegaly and
➢ lymphadenopathy.
• Since symptoms and signs are not specific, high index of suspicion is required for the diagnosis.
• Systemic upset is the rule, with respiratory symptoms in the majority. Other findings are liver and splenic
microabscesses with deranged liver enzymes or cholestasis and GI symptoms.
• Chest X-ray usually shows miliary pattern of infiltration bilaterally (millet seed like lesions)
• Diagnosis:
➢ Blood cultures
➢ Bronchoalveolar lavage fluid (usually smear negative but culture-positive)
➢ Lumbar puncture should be performed in all cases unless contraindicated to assess for CNS
involvement (affects treatment duration)
➢ Sampling of other involved organs often necessary.

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DIFFERENTIAL DIAGNOSIS FOR

MILIARY TB
• Miliary tuberculosis
• Histoplasmosis
• Sarcoidosis
• Pneumoconiosis
• Pulmonary siderosis
• Bronchoalveolar carcinoma
• Hematogenous metastasis from primary thyroid
cancer, kidney, trophoblast and some sarcomas.

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PLEURAL TUBERCULOSIS
• Pleural involvement may be asymptomatic or patients could have fever, pleuritic chest
pain and dyspnea.
• On physical examination, typically there will be decreased tactile fremitus, dullness and
decreased breath sounds on the affected side.
• Fluid should be aspirated from pleural space (thoracentesis) and analyzed.
• Chest X-ray is also helpful in diagnosis; it may show homogenous opacity with meniscus
sign.
• Empyema (pus in the pleural space) may complicate tuberculosis occasionally.

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LYMPH NODE TUBERCULOSIS

(TB LYMPHADENITIS)
• This is the second most common site of infection.
• Seen more in HIV patients.
• Extrathoracic nodes are more commonly involved than intrathoracic or mediastinal.
• The commonest sites are cervical and supraclavicular.
• Other sites include axillary and inguinal.
• The nodes are usually painless (non-tender) and initially mobile but become matted together
overtime, sometimes pus may be discharging (the overlying skin is frequently indurated or there
can be sinus tract formation).
• The node becomes necrotic centrally and can liquefy and be fluctuant if peripheral.
• Characteristically there is no erythema (cold abscess formation)
• Half the cases do not have any constitutional features such as fever or night sweats.
• The diagnosis is made by fine needle aspiration (under radiological guidance) and/or lymph
node biopsy. Histocytopathological examination as well as culture can be done on the sample.
• Mediastinal nodal sampling (endobronchial ultrasound transbronchial needle aspiration
mediastinoscopy/mediastinotomy)
• Nodes typically can be enlarged for several months prior to diagnosis.
• On CT imaging, the central area appears necrotic.

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GASTROINTESTINAL
TUBERCULOSIS
• TB can affect anywhere from the mouth to the anus.
• Bacteria could reach GI by swallowing sputum, hematogenously or by ingesting raw milk. The
commonest sites are terminal ileum and cecum. The colon can also be affected.
• Patients usually present with Abdominal pain (right iliac fossa pain), anemia, diarrhea,
symptoms of intestinal obstruction and hematochezia (frank blood on stool) may be presenting
symptoms.
• One-third of patients present acutely with intestinal obstruction or generalized peritonitis. 50%
have X-ray evidence of pulmonary TB.
• There could be associated fever, night sweats, weight loss and anorexia. There could be a
palpable mass in the abdomen. Patient could have involvement of the peritoneum, liver and
spleen.
• Differential diagnosis includes Crohn’s disease and cecal carcinoma.
• A small bowel follow-through may show transverse ulceration, diffuse narrowing of the bowel
with shortening of the cecal pole.
• Ultrasound or CT shows additional mesenteric thickening and lymph node enlargement.
• Histology and culture of tissue is desirable but not always possible.
• Specimen can be obtained by colonoscopy or laparoscopy but laparotomy is required in some
cases.

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GENITOURINARY
TUBERCULOSIS
• Can involve any part of the system.
• Dysuria, intermittent hematuria and flank pain are common presentations.
• But it may be asymptomatic for a long period of time.
• Urinalysis shows pyuria and hematuria without bacteria in majority of cases (commonly
called sterile pyuria).
• Diagnosis may be reached by culturing urine repeatedly for M. tuberculosis.
• It affects more females and may present as infertility or pelvic pain.

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SKELETAL TUBERCULOSIS
• It is usually reactivation of hematogenous site or extension from a nearby lymph node. The
most common sites are spine, hips and knees.
• Spinal tuberculosis is called Pott’s disease or tuberculous spondylitis. In adults, lower
thoracic and lumbar vertebrae are commonly affected. Patients may present with swelling
(Gibbus) and pain on the back with or without paraparesis or paraplegia due to cord
compression.
• Tuberculosis in other bones or joints usually presents with pain and swelling.
• Joint tuberculosis- any joint can be affected but weight bearing joints, particularly the hip
and knee joints are commonly involved.
• Patients present with progressive joint swelling, usually with pain and limitation of
movement. If left untreated, the joint may be destroyed.

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TB ARTHRITIS
• Occurs as the primary disease in children. In adults, it is usually due to hematogenous spread
from secondary pulmonary or renal lesions.
➢ The onset is insidious and diagnosis often delayed.
➢ The organism invades the synovium or intervertebral disc.
➢ There are caseating granulomas and rapid destruction of cartilage and adjacent bone.
➢ Some patients develop a reactive polyarthritis (Poncet’s disease).
➢ The Hip or knee (30%) is quite commonly affected but around 50% develop spinal disease.
➢ The patient is febrile, has night sweats, is anorexic and loses weight.
➢ The usual risk factors for TB apply- debility, excess alcohol use or immunosuppression
especially with HIV/AIDs.
➢ Investigations should include culture of fluid and culture & biopsy of synovium.
➢ A chest X-ray should be performed. Initially joint or spinal X-rays may be normal but joint
space reduction and bone destruction develop rapidly if treatment is delayed.
➢ MRI shows the abnormality earlier in the spine and CT-guided biopsy from the affected disc
is often necessary to obtain cultures.
➢ Treatment is as for pulmonary tuberculosis with therapy for 9 months. The joint should be
rested and the spine immobilized in the acute phase.

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TB OSTEOMYELITIS
• This is usually due to hematogenous spread from a reactivated primary focus in the lungs
or gastrointestinal tract.
• The disease starts in intra-articular bone.
• The spine is commonly involved (Pott’s disease), with damage to the bodies of two
neighboring vertebrae leading to vertebral collapse and acute angulation of the spine
(gibbus).
• Pus can tract along tissue planes and discharge at a point far from the affected vertebrate.
• Symptoms consist of local pain and later swelling if pus has collected. Systemic symptoms
of malaise, fever and night sweats occur.
• Treatment is as for pulmonary tuberculosis but extended to 9 months together with initial
immobilization.

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SKIN MANIFESTATIONS OF
TB
• Lupus vulgaris: usually arises as a post-primary infection. It usually presents on the head or
neck with red-brown nodules that look like apple jelly when pressed with a glass slide
(‘diascopy’). They heal with scarring and new lesions slowly spread out to form chronic
solitary erythematous plaque. Chronic lesions are at high risk of developing squamous cell
carcinoma.
• Tuberculosis verrucosa cutis: arises in people who are partially immune to TB but who
suffer a further direct inoculation in the skin. It presents as warty lesions on a ‘cold’
erythematous base.
• Scrofuloderma: arises when an infected lymph node spreads to the skin causing ulceration,
scaring and discharge.
• The tuberculides: are a group of rashes caused by an immune manifestation of TB rather
than direct infection. Erythema nodosum is the commonest. Erythema induratum (“Bazin’s
disease) produces similar deep red nodules but these are usually found on the calves
rather than the shins and they often ulcerate.

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DIAGNOSIS OF TB
➢ AFB microscopy
o Specimen: sputum, pleural, peritoneal, CSF and body discharges.
o Stains used Ziehl-Neelsen.
o Definitive diagnosis depends on detection of M. tuberculosis from a culture of specimen. Since culture
routinely takes 4-6 weeks to grow, the culture is often not available to guide initial therapy. It is also necessary
in order to do sensitivity testing.
o Sputum (more than 2 samples are taken to increase diagnostic yield). Induced sputum (inhale hypertonic saline
which induces coughing) gives more diagnostic yield than bronchoscopic samples.
o Bronchoalveolar lavage fluid if cough unproductive and induced sputum not possible.
o Aspiration of pleural fluid and pleural biopsy.
o Gastric aspirates may be useful in pediatric disease.
o Nasoendoscopic or bronchoscopic examination/biopsy of vocal cords with biopsy for smear/culture and
histology in laryngeal disease
➢ Gene expert: PCR
➢ Chest X-ray: varies but typically there will be nodular infiltrates and cavities in the upper lobe, pleural effusion is
also common. Chest X-ray findings do not confirm diagnosis of TB.
➢ Raise ESR: non-specific, there could also be anemia of chronic illness.
➢ Do not use PPD testing to diagnose acute cases of TB. PPD is relatively insensitive and nonspecific with acute
illness.

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DIAGNOSIS OF TB
• Adenosine deaminase test (ADA) can also be done.
➢ ADA is an enzyme present in the body whose main function is to aid in purine metabolism.
➢ It helps in the breakdown of adenosine from food and thereby facilitates the turnover of nucleic acids in
different body tissues.
➢ In humans, the primary function of ADA is to keep the immunity system developed and maintained. It
also has minor function functions such as gestation maintenance, the release of amino acids in the
body, neurotransmission, and epithelial cell differentiation.
➢ ADA test is done to measure the level of ADA in pleural fluid in the diagnosis of TB. In very rare cases it
is done to test other infections.
➢ In rare cases ADA test can also be done on cerebrospinal fluid or peritoneal fluid.
➢ Normal range is less than 40m/L.
➢ If levels are increased in pleural fluid the result is indicative of Mycobacterium tuberculosis infection in
the pleural.
➢ In sarcoidosis, pulmonary embolus, cancer or lupus ADA levels may be mildly or moderately high.
• Urine LAM can also be done
➢ This detects the lipoarabinomannan (LAM) antigens in urine samples
• Other important tests:
➢ Full blood count
➢ Liver function tests
➢ Kidney function tests (Urea, electrolytes and creatinine)

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ANTITUBERCULOSIS
CHEMOTHERAPY
• Patients with fully sensitive TB require 6 months of treatment excluding TB meningitis for which the recommended
duration is at least 12 months.
• In CNS and pericardial disease, corticosteroids are used as adjunct treatment to reduced long-term complications.
(Prednisolone 60mg PO for 2-6 weeks then taper)
• Drugs currently in use include: streptomycin (S), Ethambutol (E), Isoniazid (H), Rifampicin (R) and pyrazinamide (Z)
• The treatment of tuberculosis through drug observed therapy has 2 phases:
➢ The intensive (initial) phase: 4 fixed drug combination (4FDCs) are given for the first 2 months or until
sensitivity testing is known.
o Drugs include: Rifampicin, Isoniazide, Pyrazinamide and Ethambutol (given if sensitivity is not known)
➢ The continuation phase: 2 drugs are used for the remaining 4 months.
o Drugs include Rifampicin and Isoniazide
• The only forms of TB that definitely must be treated for longer than 6 months are TB meningitis (12 months), TB in
pregnancy (9 months) and osteomyelitis.
• HIV positive persons may be treated for 6-9 months, there is no clear evidence that 9 months is necessary even in
HIV positive persons, 6 months therapy is effective.
• Isoniazide should be given with Vitamin B6 (Pyridoxine 10mg OD) to prevent peripheral neuropathy that can be a
side effect of isoniazid.

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SIDE-EFFECTS
• All TB medications can cause liver toxicity except streptomycin and ethambutol.
Isoniazide also causes peripheral neuropathy because of pyridoxine deficiency.
• Rifampicin is associated with causing a benign change in the color of all bodily
fluids to orange/red. This color is dangerous only because it could stain contact
lenses and white underwear.
• Ethambutol is associated with optic neuritis which can cause color blindness and
other visual disturbances.
• Pyrazinamide can cause benign hyperuricemia. Don’t treat the hyperuricemia
unless there are symptoms of gout associated with it, which rarely occurs.

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DRUG SIDE EFFECT PREVENTIVE MEASURE

RIPAMPICIN (inhibits DNA- Major: Hepatitis (inducer of P450), acute renal failure, shock, purpura Stop Rifampicin if transferases
dependent RNA polymerase- (thrombocytopenia) are >3 times elevated.
transcription inhibitor)
Minor: orange, pink or red discoloration of tears, sweat and urine + nausea, Reassurance and advice patient
abdominal pain to take drugs with a small meal

ISONIAZID: inhibits mycolic acid Major: Jaundice and hepatitis (age dependent) Stop isoniazide
synthesis (Cell wall synthesis
inhibitor) Minor: burning sensation in the feet (peripheral neuropathy), sideroblastic Give pyridoxine (Vitamin B6)
anemia. Isonizide inhibits pyridoxine phosphokinase the enzyme that 10mg OD.
converts pyridoxine (vitamin B6) to pyridoxal-5’-phosphate the active form.

PYRAZINAMIDE Major: hepatotoxicity/ jaundice, hyperuricemia Stop pyrazinamide

(unknown mode of action)
Minor: Joint pain (pyrazinamide reduces the renal excretion of urate and Analgesics
may precipitate hyperuricemia gout)
ETHAMBUTOL Major: optic neuritis: visual impairment (dose-related optic retrobulbar Stop ethambutol
(Inhibits the synthesis neuritis that presents with color blindness for green, reduction in visual
arabinogalactan-a cell wall acuity and a central scotoma-commoner at doses of 25mg/kg)
component)
Minor: none
STREPTOMYCIN (aminoglycoside- Major: Ototoxicity: vertigo and hearing impairment, neuromuscular Stop streptomycin
protein synthesis inhibitor) blockade (by decreasing acetylcholine release)
Minor: mild skin rash, perioral paresthesia symptomatic treatment

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NOTE
• Streptomycin should not be given to pregnant women and patients with renal failure and
ear problems. It should be replaced by ethambutol. Streptomycin dose should not be more
than 750mg if the patient’s age is >50 years.
• Children who are 6 years or below should not be given ethambutol because of damage to
the eyes and children may not complain of it.
• Streptomycin is used only if patients are very ill, have multidrug-resistant TB or are not
responding adequately to therapy.
• Patients should be strictly followed after initiation of the drugs.
• Corticosteroids are added to the anti-TB in meningitis, pericarditis and spinal TB to
reduce long term complications. Adrenal TB patients should have replacement therapy.

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DOTS
• Close follow-up is needed and frequently children are put on Direct Observed therapy (DOTS) where
nursing staff observe the therapy being given 3 times a week.
➢ During the intensive phase the health worker or trained person watches as the patient swallows
the drugs in his presence
➢ During the continuation phase the patient is issued medicines for one week in a multi-blister
combo-pack of which the first dose is swallowed by the patient in the presence of the health
worker or trained person.
➢ The consumption of medicines in the continuation phase is also checked by return of the empty
multi-blister combo-pack when the patient comes to collect medicine for the next week.
• DOTS is required especially for:
o Patients thought unlikely to comply
▪ History of serious mental illness
▪ History of non-adherence of TB therapy in past or during current treatment course
o Street or shelter-dwelling homelessness
o Multi-drug resistant TB

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DRUG RESISTANCE
• Drug resistant TB accounts for possibly only 2% of the million cases of TB in the world.
• It arises due to incomplete or incorrect drug treatment and can be spread from person to
person.
• Factors associated with an increased risk of drug-resistant TB:
➢ History of prior drug treatment of TB (particularly if unsupervised, self-administered
treatment)
➢ Co-infection with advanced HIV and previous TB treatment
➢ Infection acquired in region with high rates of drugs resistance
➢ Contact with a known case of resistant TB
➢ Failure to respond to empiric TB therapy despite documented adherence
➢ Exposure to multiple courses of fluoroquinolone antibiotics for presumed community
acquired pneumonia
➢ Healthcare workers exposed to cases of resistant TB.

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TYPES OF DRUG RESISTANCE

• Primary drug resistance: infected with TB
which is already drug resistant
• Secondary (Acquired) drug resistance: drug
resistance develops during treatment

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DRUG RESISTANCE
• Drug resistant TB denotes resistance to one of the first line TB drugs (being Rifampicin or
isoniazid)
• Multidrug resistant (MDR) TB denotes resistance to at least 2 main first line TB drugs i.e.
rifampicin and isoniazide.
• Extreme drug resistant (XDR) TB denotes MDR-TB + resistance to any fluoroquinolone and
at least 1 of the 3 injectable second-line drugs (amikacin, kanamycin or capreomycin)
• The second line drugs include:
➢ Oral: fluoroquinolones
o Ciprofloxacin
o Levofloxacin
o Movifloxacin
o Gatifloxacin
➢ Injectables
o Amikacin
o Kanamycin
o Capreomycin
o Streptomycin
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SOME IMPORTANT TERMS

• TB defaulter: this a patient whose treatment is interrupted for more than 2 consecutive months.
• Treatment failure in TB: This is the presence of continued or recurrently positive cultures during the course of
antituberculosis therapy.
➢ After 3 months of multi-drug therapy for PTB caused by drug susceptible organisms, 90-95% of patients will
have negative cultures and show clinical improvement.
➢ All patients with positive cultures after 3 months of appropriate treatment must be evaluated carefully to
identify the cause of the delayed conversion.
➢ Patients whose sputum culture remains positive after 4 months of treatment should be classified as treatment
failure.
➢ The reasons for this include:
o Non-adherence
o Drug resistance
o Malabsorption of drugs
o Laboratory errors
o A few patients take a long time to respond as part of extreme biological variation.
• TB relapse: this is a patient who has become (and remained) culture negative while receiving therapy but after
completion they become culture positive or have clinical or radiological deterioration that is consistent with active
TB.

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TB PROPHYLAXIS
• Chemoprophylaxis can be offered to reduce the risk of active infection especially
in patients at risk e.g. individuals with TB contact.
• 300mg daily for 6 months, alternatively 300mg daily for 3 months, to be taken
in combination with rifampicin.

• The BCG vaccine is a live attenuated vaccine derived from M. bovis that has lost
its virulence. It has variable efficacy but it is still recommended in certain
situations in developed countries. It has been shown to reduce the risk of
disseminated and CNS TB in babies and children and is therefore used
worldwide. There are safety concerns in babies with HIV. Its efficacy in adults is
very variable.

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COMPLICATIONS OF TB
• Pulmonary complications:
• Pleurisy
• Pleural effusion
• Empyema
• Pneumothorax
• Aspergillosis
• Endobronchitis
• Bronchiectasis
• Laryngitis
• Cor pulmonale
• Ca bronchus
• Miliary TB

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WARM UP: THEORY

A 72-year-old homeless man has been feeling unwell for the past 5 weeks with fever and a productive
cough. His fellow homeless men have brought him to the emergency medical unit and they say he has lost
more than 10% of weight over the past 2 months.

Examination reveals he is confused and tachypneic with a respiratory rate of 36/minute. His BP is
80/50mmHg. You order a CXR and you find that he has infiltrates on upper and middle lobes on the right
side. HIV test is negative.
A. What is your diagnosis? (2 marks) Severe pneumonia (R/O PTB)
B. What are the markers of severity in this patient? Mention 5 (5 marks) Age (72), Confusion, RR>30bpm,
Hypotension, Weight loss>10%
C. Mention 5 complications of this condition? (5 marks) Respiratory failure, sepsis and septic shock,
uncomplicated parapneumonic effusions, empyema, lung abscess
Sputum is sent for Gen-Xpert and report shows: MTB detected (medium): Rif resistance NOT DETECTED
D. You decide to start him on first line TB medication. List the name of the drugs you will prescribe and 2
common side effects of each drug. (8 marks: 2 marks per drug and side effects)-See next slide

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DRUG SIDE EFFECT PREVENTIVE MEASURE

RIPAMPICIN (inhibits DNA- Major: Hepatitis (inducer of P450), acute renal failure, shock, purpura Stop Rifampicin if transferases
dependent RNA polymerase- (thrombocytopenia) are >3 times elevated.
transcription inhibitor)
Minor: orange, pink or red discoloration of tears, sweat and urine + nausea, Reassurance and advice patient
abdominal pain to take drugs with a small meal

ISONIAZID: inhibits mycolic acid Major: Jaundice and hepatitis (age dependent) Stop isoniazide
synthesis (Cell wall synthesis
inhibitor) Minor: burning sensation in the feet (peripheral neuropathy), sideroblastic Give pyridoxine (Vitamin B6)
anemia. Isonizide inhibits pyridoxine phosphokinase the enzyme that 10mg OD.
converts pyridoxine (vitamin B6) to pyridoxal-5’-phosphate the active form.

PYRAZINAMIDE Major: hepatotoxicity/ jaundice, hyperuricemia Stop pyrazinamide

(unknown mode of action)
Minor: Joint pain (pyrazinamide reduces the renal excretion of urate and Analgesics
may precipitate hyperuricemia gout)
ETHAMBUTOL Major: optic neuritis: visual impairment (dose-related optic retrobulbar Stop ethambutol
(Inhibits the synthesis neuritis that presents with color blindness for green, reduction in visual
arabinogalactan-a cell wall acuity and a central scotoma-commoner at doses of 25mg/kg)
component)
Minor: none
STREPTOMYCIN (aminoglycoside- Major: Ototoxicity: vertigo and hearing impairment, neuromuscular Stop streptomycin
protein synthesis inhibitor) blockade (by decreasing acetylcholine release)
Minor: mild skin rash, perioral paresthesia symptomatic treatment

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 THANK YOU
“ONLY GIVE UP WHEN YOU DIE”