this is good presentation about tuberculosis

1. Tuberculosis
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2.  Definition
 Historical Background
 Etiology
 Epidemiology
 Transmission
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Treatment
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3.  It is an infectious disease caused by Mycobacterium
tuberculosis.
 Characteristic features :
 patient-to-patient airborne transmission
a prolonged latency period between the initial infection
and overt disease
a granulomatous response associated with intense tissue
inflammation and damage, and
prominent pulmonary disease, although many other organs
can be involved as well.
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4.  Historically known by a variety of names, including:
 Consumption
 Wasting disease
 White plague
 Pott’s disease
 Phthisis
 Scrofula
 Each of which make reference to the "drying" or "consuming"
affect of the illness, cachexia.
 Earliest evidence of TB in Humans : ≈ 9,000 years ago - Israel
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5. First to visualize a
mycobacterium was
Gerhard Hansen (1873)
Mycobacterium leprae –
couldn’t prove cause
-Used new technology
(microscope) - 1882
-Invented a method to prove
cause (Koch’s postulates).
-lesion is secondary to infection by
a germ.
History ofTuberculosis – 2
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7. 10/11/2023 7

8.  BeforeTB antibiotics,
many patients were
sent to sanatoriums.
 Patients followed a
regimen of bed rest,
open air, and sunshine.
 TB was a death
sentence for many.
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9. 10/11/2023 9

10.  Mycobacteria belong to the family Mycobacteriaceae and
order Actinomycetales.
 Mycobacteria are small, rod-shaped, aerobic, non–spore-
forming bacilli.
 The genus Mycobacterium contains a group of organisms so
closely related that they are referred to as the “tuberculosis
complex”.
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11.  The complex includes:
 M. tuberculosis
 M. bovis (the bovine tubercle)
 M. laprae (related to M. bovis)
 M. africanum (isolated from cases in West, Central, and East
Africa)
 M. microti (the "vole" bacillus, a less virulent and rarely
encountered organism)
 M. pinnipedii (a bacillus infecting seals and sea lions in the
southern hemisphere and recently isolated from humans),
and
 M. canettii (a rare isolate from East African cases).
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12.  However, given the singular epidemiologic, clinical, public
health, and therapeutic considerations associated with M.
tuberculosis, the term tuberculosis should be reserved
exclusively for infection or disease caused by this organism.
 Disease caused by other organisms of this genus should be
referred to as “mycobacteriosis due to M. x”
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13.  Cell walls contain high
concentrations of lipids
or waxes
 Resistant to standard
staining techniques.
 Carbol fuchsin can be
used for staining
 After dye absorption,
they are resistant to the
potent decolorizing
agent acid-alcohol, the
basis of the reference to
acid-fast bacilli (AFB).
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14.  The word tuberculosis refers to disease that occurs when
signs and symptoms or radiographic changes become
apparent.
 The WHO estimates that 30% of the world's population (2
billion people) are infected with M. tuberculosis.
 Tuberculosis is a major cause of morbidity and mortality in
Ethiopia.
 According to the WHO Global TB Report 2011, 22 High
Burden Countries (HBCs) accounted for 81% of all estimated
cases worldwide and Ethiopia is among them.
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15.  Highest infection rate in Africa, Asia, and Latin
America.
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16. The global burden continues to grow due to
several factors:
 HIV epidemics
 migration
 increasing poverty
 social upheaval and overcrowding
 inadequate health coverage
 inefficient tuberculosis control programs.
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17.  Tuberculosis is most common in young adults and
children <5 yr of age.
 The age range of 5-14 yr is often called the “favored
age” - lowest rate of tuberculosis disease.
 Among adults two thirds of cases occur in men, but
in children there is no significant difference in sex
distribution.
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18.  Untreated infants with LTBI(latent TB infection) have
up to a 40% likelihood of developing tuberculosis,
with the risk for progression decreasing gradually
through childhood to adult lifetime rates of 5-10%.
 The greatest risk for progression occurs in the first
2 yr after infection.
 Groups at high risk include children from infancy
through 4 years of age, the infirm elderly, and
immunocompromised subjects.
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19. Child Exposed toTB
Not
TB Infected
LatentTB Infection
(LTBI)
Not
Infectious
PositiveTST
LatentTB Infection
May go on to
developTB
disease
Not
Infectious
NegativeTST
No
TB Infection
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20. 10/11/2023 20

21.  Infection is spread almost exclusively by
aerosolization of contaminated respiratory
secretions.
 Person-to-person transmission of tuberculosis (TB)
occurs via inhalation of droplet nuclei (airborne
particles 1 to 5 microns in diameter).
 Transmission rarely occurs by direct contact with an
infected discharge or a contaminated fomite.
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22.  The chance of transmission increases when the
index case has:
a positive acid-fast smear of sputum
an extensive upper lobe infiltrate or cavity
copious production of thin sputum, and
severe and forceful cough.
 Most adults no longer transmit the organism within
several days to 2 weeks after beginning adequate
chemotherapy, but some patients remain infectious
for many weeks.
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23.  Young children with tuberculosis rarely infect other children
or adults.
 The most infectious patients have cavitary pulmonary disease
or, much less commonly, laryngeal tuberculosis and produce
sputum containing as many as 105–107 AFB/mL.
 Patients with sputum smear–negative/culture-positive
tuberculosis are less infectious, and those with culture-
negative pulmonary disease and extrapulmonary
tuberculosis are essentially noninfectious.
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24.  The inflammation and tissue injury are mediated by products
elaborated by the host during the immune response to
infection otherwise the bacilli do not elaborate classic
toxins.
 The lung is the portal of entry in >98% of cases.
 The source of infection in most children is an infectious adult
in their close environment (usually the household).
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25.  Inhalation of M. tuberculosis and deposition in the
lungs leads to one of four possible outcomes:
1. Immediate clearance of the organism
2. Latent infection
3. Immediate onset of active disease (Primary
disease)
4. Onset of active disease many years following
exposure (Reactivation disease).
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26.  The tubercle bacilli establish infection in the lungs
after they are carried in droplets small enough to
reach the alveolar space.
 If the innate defense system of the host fails to
eliminate the infection, the bacilli proliferate inside
alveolar macrophages and eventually kill the cells,
which eventually form a nodular granulomatous
structure called the tubercle.
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27.  If the replication is not controlled, the tubercle
enlarges and the bacilli enter local draining lymph
nodes.
 This leads to lymphadenopathy, a characteristic
manifestation of primary TB.
 The lesion produced by the expansion of the
tubercle into the lung parenchyma and lymph node
involvement is called the Ghon complex.
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28.  The immune response (delayed hypersensitivity and
cellular immunity) develops about 4–6 weeks after
the primary infection.
 A positive tuberculin skin test (TST) would be the
only evidence of infection.
 Failure by the host to mount an effective cell
mediated immunity(CMI) response and tissue repair
leads to progressive destruction of the lung.
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29.  The tissue reaction intensifies over the next 2-12 wk.
 The parenchymal portion of the primary complex often heals
completely by fibrosis or calcification after undergoing
caseous necrosis and encapsulation.
 Caseous necrosis is frequently associated with TB but can
also be caused by other organisms, including syphilis,
histoplasmosis, cryptococcosis, and coccidioidomycosis.
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30.  Healing is usually less complete in the regional
lymph nodes than in the parenchymal lesion.
 collapse-consolidation or segmental lesion -
combination of pneumonitis and atelectasis.
 Bacterial replication is more likely to occur in organs
with conditions that favor their growth, such as the
lung apices, brain, kidneys, and bones.
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31.  Disseminated tuberculosis occurs if the number of
circulating bacilli is large and the host's cellular
immune response is inadequate.
 The time between initial infection and clinically
apparent disease is variable.
 Extrapulmonary manifestations develop in 25-35%
of children with tuberculosis, compared with about
10% of immunocompetent adults with tuberculosis.
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32.  Disseminated and meningeal tuberculosis are early
manifestations, often occurring within 2-6 mo of
acquisition.
 Significant lymph node or endobronchial
tuberculosis usually appears within 3-9 mo.
 Lesions of the bones and joints take several years to
develop, whereas renal lesions become evident
decades after infection.
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33.  Also called adult-type or secondary tuberculosis or
post primary disease
 Pulmonary tuberculosis that occurs >1 yr after the
primary infection
 is rare in children but is common among adolescents
and young adults.
 The most common pulmonary sites are the original
parenchymal focus, lymph nodes, or the apical
seedings (Simon foci) established during the
hematogenous phase of the early infection.
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34.  The most common form is an infiltrate or cavity in
the apex of the upper lobes, where oxygen tension
and blood flow are great, unlike to primary TB in
which all lobes are equally involved.
 There is little regional lymph node involvement and
less caseation.
 The lesion typically occurs at the lung apices, and
disseminated disease is unusual, unless the host is
severely immunosuppressed.
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35.  Congenital tuberculosis is rare because the most
common result of female genital tract tuberculosis is
infertility.
 Congenital TB is rare and most often is associated
with tuberculous endometritis or disseminated TB in
the mother.
 It can be acquired hematogenously via the placenta
and umbilical vein or by fetal aspiration (or
ingestion) of infected amniotic fluid.
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36.  Primary infection in the mother just before or during
pregnancy is more likely to cause congenital
infection than is reactivation of a previous infection.
 The tubercle bacilli first reach the fetal liver, where a
primary focus with periportal lymph node
involvement can occur.
 Organisms pass through the liver into the main fetal
circulation and infect many organs.
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37.  Neonatal TB develops following exposure of an
infant to his or her mother's aerosolized respiratory
secretions.
 This is more common than congenital TB, and
diagnosis of neonatal TB can lead to identification of
previously unrecognized diagnosis of TB in the
mother.
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38.  In most children, TB presents with symptoms
of a chronic disease after they have been in
contact with an infectious source case.
 In children TB disease presents in various
clinical forms:
Pulmonary Tuberculosis
Extra-pulmonary tuberculosis
Perinatal tuberculosis
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39.  About 15% of tuberculosis cases in adults are
extrapulmonary, and 25-30% of children with
tuberculosis have an extrapulmonary presentation.
 Pulmonary Tuberculosis has different forms:
 Primary Pulmonary Disease
 Progressive Primary Pulmonary Disease
 Reactivation Tuberculosis
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40.  The hallmark of primary tuberculosis in the
lung is the relatively large size of the regional
lymphadenitis compared with the relatively
small size of the initial lung focus.
 All lobar segments of the lung are at equal
risk for initial infection.
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41.  A rare but serious complication of tuberculosis
 occurs when the primary focus enlarges steadily and
develops a large caseous center.
 The enlarging focus can slough necrotic debris into
the adjacent bronchus, leading to further
intrapulmonary dissemination.
 Significant signs or symptoms are common in locally
progressive disease in children.
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42.  The most common clinical presentation is persistent
respiratory symptoms and poor weight gain.
 A child may have nonproductive cough and /or mild
wheezes.
 Pulmonary TB in infants and HIV infected children
may present as acute pneumonia.
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43.  Common symptoms of pulmonary TB in children
include:
Chronic- not improving and has been present for
more than three weeks.
Fever of more than 38ºC for at least two weeks,
other common causes having been excluded.
Weight loss or failure to thrive (review the child's
growth chart).
 However, these symptoms are fairly nonspecific.
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44.  Dissemination of the bacilli into a blood or
lymphatic vessel - a miliary pattern, with
small nodules evenly distributed on the chest
radiograph.
 Physical exam findings may suggest the
presence of a lower respiratory infection, but
there are no specific clinical signs or findings
to confirm pulmonaryTB.
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45. 10/11/2023 45

46.  Discharge of bacilli into the pleural space.
 Focus - pulmonary or caseated lymph node.
 Uncommon in children <6 yr of age and rare in
children <2 yr of age.
 May be small (remain unnoticed and resolve
spontaneously) or may be sufficiently large to cause
symptoms.
 Hx :Pleuritic chest pain, and dyspnea.
 P/E: Flat dullness to percussion, absence of breath
sounds and BBS above the fluid level.
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47.  usually unilateral but can be bilateral.
 A chest radiograph reveals the effusion.
 Chest ultrasound is more sensitive in minimal
effusion
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48.  The most common form of cardiac tuberculosis
 It is rare, occurring in 0.5-4% of tuberculosis cases in
children.
 arises from direct invasion or lymphatic drainage
from subcarinal lymph nodes.
 SX: nonspecific - fever, weight loss, and night sweats
 P/E:fever, tachycardia, increased jugular venous pressure,
hepatomegaly, ascites, peripheral edema
 A pericardial friction rub and distant heart sounds are often
observed.
 Cardiac tamponade may present in 10 percent of patients
with tuberculous pericardial effusion
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49.  Potential complications of tuberculous pericarditis
include:
Constrictive pericarditis
Effusive pericarditis, and
Cardiac tamponade.
 The pericardial fluid is typically serofibrinous or
hemorrhagic.
 Partial or complete pericardiectomy may be required
when constrictive pericarditis develops.
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50.  The most frequent presentations of extrapulmonary
tuberculosis
 Most current cases occur within 6-9 mo of initial
infection
 The tonsillar, anterior cervical, submandibular, and
supraclavicular nodes become involved secondary to
extension of a primary lesion of the upper lung fields
or abdomen.
 Disease is most often unilateral
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51.  The most common presentation is isolated/matted
chronic nontender lymphadenopathy without
systemic symptoms.
 Cervical lymphadenopathy is the most common
manifestation
 The TST is usually reactive, but the chest radiograph
is normal in 70% of cases.
 Confirmation by fine needle aspiration (FNA) or
excisional biopsy.
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52.  The most clinically significant form of disseminated
tuberculosis is miliary disease.
 is most common in infants and young children.
 may be acute, more often it is indolent and
prolonged.
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53.  Characterized by the
formation of
widespread, multiple,
discrete granulomas
macroscopically
resembling millet
seeds. (Latin: milium,
millet seed).
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54.  Occurs when massive numbers of tubercle bacilli are
released into the bloodstream.
 Causing disease in 2 or more organs.
 Usually complicates the primary infection.
 Occurring within 2-6 mo of the initial infection.
 Lesions are often larger and more numerous in the
lungs, spleen, liver, and bone marrow than other
tissues.
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55.  Quantity of organisms released and host
immunity determine the clinical picture.
 The onset is sometimes explosive, and the
patient can become gravely ill in several days.
 More often, the onset is insidious, with early
systemic signs, including anorexia, weight loss,
and low-grade fever.
 At this time, abnormal physical signs are usually
absent.
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56.  Generalized LAP and hepatosplenomegaly develop
within several weeks in about 50% of cases.
 The fever can then become higher and more
sustained.
 Chest radiography is usually normal and respiratory
symptoms are minor or absent.
 Often the patient presents with fever of unknown
origin.
 Within several more weeks, the lungs can become
filled with tubercles, and dyspnea, cough, rales, or
wheezing occur – severe respiratory distress
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57.  Initially the lesions are smaller then coalesce
to form larger lesions and sometimes
extensive infiltrates.
 At this stage frank respiratory distress,
hypoxia, and pneumothorax, or
pneumomediastinum may occur.
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58. DDX
 Histoplasmosis
 Sarcoidosis
 Pneumoconiosis
 Pulmonary siderosis
 Hematogenous metastasis
from primary cancers
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59.  Disease dissemination might also occur to the
meninges, peritoneum, skin and the eye.
 Unfortunately, the TST is nonreactive in up to 40%
of patients with disseminated tuberculosis.
 The resolution of miliary tuberculosis is slow, even
with proper therapy.
 The chest radiographic abnormalities might not
resolve for many months.
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60.  It is one of the most dangerous complications.
 Types:
Tuberculous meningitis
Intracranial tuberculoma, and
spinal tuberculous arachnoiditis
 All three forms are encountered frequently
among children and young adults.
 Usually it follows primary infection
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61.  Subependymal tubercle, with progression and
rupture into the subarachnoid space.
 Complicates about 0.3% of untreated tuberculosis
infections in children.
 Between 30 % and 50 % of children with Miliary TB
have meningitis at the time of diagnosis. ….LP
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62.  It is most common in children between 6 mo and
4 yr of age.
 Usually presents with a subacute febrile illness
which progresses through three phases.
 For the majority of untreated patients, death ensues
within five to eight weeks of the onset of illness.
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63.  The prodromal phase (Stage 1):
Lasting two to three weeks, is characterized by the
insidious onset of malaise, lassitude, headache, low-
grade fever, and personality change.
 The meningitic phase (stage 2):
 Follows with more pronounced neurologic features
Lethargy, nuchal rigidity, seizures, positive Kernig and
Brudzinski signs, hypertonia, vomiting, cranial nerve
palsies, and other focal neurologic signs.
 The paralytic phase (stage 3):
stupor and coma, seizures, and often hemiparesis.
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64.  The prognosis of tuberculous meningitis correlates
with the clinical stage of illness at the time
treatment is initiated.
 1st stage have an excellent outcome
 3rd stage if survived permanent disabilities,
including blindness, deafness, paraplegia, diabetes
insipidus, or mental retardation.
 The prognosis for young infants is generally worse
than for older children.
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65.  About 1/3 of patients on presentation have miliary
tuberculosis.
 Signs of active TB outside the CNS are of diagnostic
importance, but are often absent or nonspecific.
 The TST is nonreactive in up to 50% of cases.
 20-50% of children have a normal chest radiograph.
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66.  Most important laboratory test for diagnosis
 Elevated protein (100 to 500 mg/dL- even
higher)
 Lower glucose (less than 45 mg/dL in 80%
cases)
 CSF cell count: 10 and 500 cells/microL, with a
mononuclear pleocytosis
 PCR testing of the CSF can improve diagnosis.
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67.  Culture and AFB positivity related to the
volume of CSF sample.
 When 5-10 mL of lumbar CSF can be
obtained, the acid-fast stain of the CSF
sediment is positive in up to 30% of cases and
the culture is positive in 50-70% of cases.
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68.  Granulomatous foci within the brain parenchyma.
 Develop from coalescing tubercles acquired during
an earlier period of hematogenous bacillemia.
 Tuberculomas account for up to 30% of brain tumors
in some areas of the world.
 Often infratentorial, located at the base of the brain
near the cerebellum.
 Brainstem is often the site of greatest involvement.
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69.  Lesions are most often singular but may be multiple.
 The most common symptoms are headache, fever,
focal neurologic findings and convulsions – Variable
depending on the site.
 The TST is usually reactive, but the chest radiograph
is usually normal.
 Surgical removal is not necessary because most
tuberculomas resolve with medical management.
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70.  Most commonly seen in endemic areas.
 The pathogenesis is similar to that of meningitis.
 Symptoms develop and progress slowly over weeks
to months and may culminate with a meningitis
syndrome.
 Nerve root and cord compression signs:
 spinal or radicular pain, hyperesthesia or paresthesias;
lower motor neuron paralysis; and bladder or rectal
sphincter dysfunction
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71.  The diagnosis is based on findings of elevated
cerebrospinal fluid protein levels, and MRI findings
of nodular arachnoiditis, combined with tissue
biopsy.
 The treatment is the same as for TB meningitis.
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72.  TB involvement of the bones and/or joints.
 Hematogenous dissemination of bacilli from a
primary focus.
 Rarely, contiguous spread.
 Second commonest form of childhood EPTB.
 Most cases present 6 months to 3 years after the
initial infection.
 Forms of skeletal tuberculosis include spondylitis
(Pott disease), arthritis, and osteomyelitis.
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73.  Any bone or joint may be affected but the most
frequent site is the vertebrae, involved in half of the
cases.
 Large joints of the lower limb (hip, knee and ankle)
and then the large joints of the upper limb shoulder,
elbow and wrist) follow vertebral involvement.
 Vertebrae (50 %), hips (15 %), and knees (15 %).
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74.  Tuberculous spondylitis (Pott disease) most
commonly affects the lower thoracic and upper
lumbar region.
 Infection generally begins with inflammation of the
anterior aspect of the intervertebral joints
 It spreads behind the anterior ligament to involve
the adjacent vertebral body.
 Once two adjacent vertebrae are involved, infection
enters the adjoining intervertebral disc space.
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75.  Gibbus deformity, a
form of structural
kyphosis, distorts
spinal canal anatomy.
 A paravertebral "cold"
abscess may also form.
 The spinal cord is then
at risk of compression,
resulting in paraplegia.
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76.  The most common symptom is local pain, which
increases in severity over weeks to months,
sometimes in association with muscle spasm and
rigidity.
 Constitutional symptoms such as fever and weight
loss are present in less than 40 percent of cases
 A bone biopsy is essential to confirm the diagnosis
while vertebral x-ray together with the clinical
symptoms of TB may also help to make the
diagnosis.
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77.  Commonly begin by the 2nd or 3rd wk of life.
 May present at birth
 Respiratory distress, fever, hepatic or splenic
enlargement, poor feeding, lethargy or
irritability, lymphadenopathy, abdominal
distention, failure to thrive, ear drainage, and
skin lesions.
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78.  Many infants have an abnormal chest radiograph,
most often with a miliary pattern.
 Should be suspected in an infant with signs and
symptoms of bacterial or congenital infection
whose response to antibiotic and supportive
therapy is poor and in whom evaluation for other
infections is non revealing.
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79.  The most important clue - maternal or family
history of tuberculosis.
 The infant'sTST is negative initially but can become
positive in 1-3 mo.
 The CSF should be examined and cultured,
although the yield for isolating M. tuberculosis is
low.
 The mortality rate of congenital tuberculosis
remains very high because of delayed diagnosis.
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80.  HIV andTB form a lethal combination, each
speeding the other’s progress.
 TB HIV Co-infection is 31%
 Tuberculosis in HIV-infected children is often more
severe, progressive, and likely to occur in
extrapulmonary sites.
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81.  Radiographic findings are similar to those in
children with normal immune systems, but
lobar disease and lung cavitation are less
common.
 Nonspecific respiratory symptoms, fever, and
weight loss are the most common
complaints.
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82.  High incidence of adverse drug reactions
 Atypical presentation/EPTB more common
 High pill burden
 Adherence
 Resistance to anti-TB drugs
 Drug interactions
 Immune reconstitution syndrome
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83.  TB treatment is the priority in co-infected patients
 When to begin ART depends on CD4/TLC and level of
immune-suppression.
 The principle of treatment for children with TB/HIV
co-infection is similar to HIV un-infected children.
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84.  Start ART as soon as tolerated in the first 8 weeks of
TB therapy.
 Children on ART and anti-TB medication need to be
closely monitored. (drug-drug interactions between
Rifampicin and some ARV drugs, mainly NNRTIs and
PIs).
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85.  It is easy to over diagnose TB in children and it is also
easy to miss TB in children.
 Tuberculosis (TB) in children is often diagnosed
clinically.
Key features suggestive of TB
 Chronic symptoms suggestive of TB
 Physical signs highly of suggestive of TB
 X-ray suggestive of TB
 A positive tuberculin skin test
10/11/2023 85

86.  Obtaining sputum samples from young
children is challenging - Early morning
gastric aspiration.
 Because pulmonaryTB in children typically presents
with paucibacillary, non-cavitary pulmonary
disease, bacteriologic confirmation is achievable in
only about 30 to 40 % of cases.
10/11/2023 86

87.  In general, cultures of gastric aspirate specimens
are positive for TB in only 30 to 40 % of cases.
 Smears are even less reliable with positive results
in fewer than 10 % of cases.
 Other body fluid/ tissue samples may be necessary
depending on suspicion for extrapulmonaryTB.
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88.  Changed from three samples (spot-morning-
spot schedule) to two samples (spot-spot
schedule).
 One sputum smear positive result confirms
the diagnosis of bacteriologically confirmed
Tuberculosis.
 Xpert MTB/RIF Assay is preferred initial test
for patients who are children and/or people
living with HIV(PLHIV).
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89. Diagnosis of TB
A. Bacteriological Methods
1.Smear Microscopy :Two staining methods
ZN microscopy: has low sensitivity (40-60%) and
requires 5,000-10,000 bacilli per ml of sputum to get
positive results.
Fluorescence auramine staining (LED FM):
requires less time for slide reading and has
additional 10% sensitivity over ZN microscopy to
identify bacillus
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90. Diagnosis of TB
2. Culture :is a bacteriologic confirmatory test for MTB
Solid culture media
Liquid culture media
 DST: is required to make a definitive diagnosis of drug
resistant TB.
3.Molecular Methods
Xpert MTB/RIF Assay
detect MTB and screen for Rifampicin resistance
It produces results in two hours.
Line Probe Assay (LPA):
Line Probe Assay is a rapid DST technique using
molecular technology.
It is a DNA strip test that makes use of PCR +
reverse hybridization
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91. Diagnosis of TB
B. Histo-Pathological Examination
 Fine needle aspiration from accessible mass like
peripheral enlarged lymph nodes
 Aspiration of effusions from serous membranes;
 Tissue biopsy
C. Radiological examination
Chest X-ray is a rapid and convenient method to
evaluate patients who cannot produce sputum or who
have negative Xpert results and are HIV positive, and
where extra pulmonary TB (such as pleural effusions and
pericardial TB) is suspected.
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92. National TB Diagnostic Algorithm
10/11/2023 92

93.  Use Mantoux tuberculin skin test
 0.1 mL of 5-TU of purified protein derivative (PPD)
solution injected intradermally
 Produce a wheal that is 6-10mm in diameter
 Read within 48-72 hours
 Measure induration, not erythema
 Positive reactions can be measured accurately for up
to 7 days
10/11/2023 93

94. PATHOLOGY
• HOST immune response to the organism
• DTH Example :-TST
• 0.1 ml containing 5 tuberculin units of PPD
• induration( measure after 48-72hrs)
10/11/2023 94

95.  Induration ≥5 mm:
 Children in close contact with known or suspected
contagious people with tuberculosis disease.
Children suspected to have tuberculosis disease:
Findings on chest radiograph consistent with active or
previously tuberculosis disease.
Clinical evidence of tuberculosis disease.
Children receiving immunosuppressive therapy or with
immunosuppressive conditions, including HIV infection.
10/11/2023 95

96.  Induration ≥10 mm
Children at increased risk of disseminated tuberculosis
disease:
Children younger than 4 yr of age
Children with other medical conditions, including Hodgkin disease,
lymphoma, diabetes mellitus, chronic renal failure, or malnutrition
Children with increased exposure to tuberculosis
disease:
Children born in high-prevalence regions of the world
Children often exposed to adults who are HIV infected, homeless,
users of illicit drugs, residents of nursing homes, incarcerated or
institutionalized, or migrant farm workers
Children who travel to high-prevalence regions of the world
10/11/2023 96

97.  Induration ≥15 mm
 Children ≥4 yr of age without any risk factors
 A positive TST is not always diagnostic of TB disease
since false positive results can occur.
 A negative TST does NOT rule out TB disease, since
false negative results can occur.
10/11/2023 97

98.  Nontuberculous mycobacteria
 Reactions are usually ≤10mm of induration
 BCG vaccination
 Reactivity in BCG vaccine recipients generally wanes over
time
 Positive TST results is likely due to TB infection if risk factors
are present
 BCG-vaccinated persons with positive TST result should be
evaluated for treatment of LTBI
 QFT(QuantiFERON-TB )is able to distinguish M.tb from
other mycobacteria and BCG vaccine
10/11/2023 98

99.  Weakened immune system
 Overwhelming TB infection
 Recent TB infection (2-10 weeks after exposure)
 Very young age (newborns)
 Recent live-virus vaccination can temporarily
suppress TST reactivity
 Poor TST administration technique (too shallow or
too deep, or wheal is too small)
10/11/2023 99

100.  Required to ascertain the dx.
 straw-colored and at times hemorrhagic
 Exudative with a protein concentration >50% of that
in serum (usually ~4–6 g/dL)
 a normal to low glucose concentration
 a pH of ~7.3 (occasionally <7.2)
 WBC usually 500–6000/L predominant mononuclear
cells
 AFB positivity in 10–25% of cases, but cultures upto
25–75% of cases.
 ADA – low values exclude tuberculosis.
 Tuberculous empyema is a less common complication
of pulmonary tuberculosis.
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101.  Chest radiography:
 Opacification with hilar
or subcarinal
lymphadenopathy –
most common
 Consolidation or a
segmental lesion
A miliary pattern of
opacification
Upper lobe infiltrates,
pleural effusions and
cavitations
10/11/2023 101

102. 10/11/2023 102

103.  In tuberculous
meningitis
 Hydrocephalus and
basilar meningeal
enhancement are
observed in 80 and 90
% of cases.
10/11/2023 103

104. Definition of Terms and Patient Registration
Case Definitions
A Presumptive Tuberculosis case
 Any person who presents with symptoms and/or signs
suggestive of tuberculosis, in particular cough of two
weeks or more duration is a presumed TB case
A bacteriologically confirmed TB case
 Refers to a patient fro at least one biological specimen
is positive for mycobacterium TB by either smear
microscopy, Xpert MTB/RIF, culture or other WHO
approved bacteriologic detection tests
A clinically diagnosed TB case
 Refers to a patient who does not fulfil the criteria for a
bacteriological confirmed case.
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105.  Treatment outcomes in children are generally good,
even in young and immunocompromised.
 There is a low risk of adverse events associated with
use of the recommended treatment regimens.
 Four components:
1. Chemotherapy
2. Nutritional rehabilitation
3. Follow up
4. Family screening
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106. History of previous treatment( Patient registration
Groups
Category Definition
New (N) Refers to Patients have never been treated for TB or have taken anti-TB
drugs for less than 1 month.
Previously
treated
Refers to patients have received one month or more of anti-TB drugs in the
past, may have positive or negative bacteriology and may have disease at
any anatomical site.
They are further classified by the outcome of their most recent course of
treatment.
Treatment
after
failure (F)
Patients who have previously been treated for TB and whose treatment
failed at the end of their most recent course of treatment. .(it is similar with
previous definition, a patient who, while on treatment remained smear or
culture positive at the end of the five ‗months‘ or later, after commencing
treatment)
Treatment
after
LTFU(L)
Patients who have previously been treated for TB and were declared lost to
follow-up at the end of their most recent course of treatment. (Previously
known as ‗treatment after default‘)
Other
previously
treated
Patients are those who have previously been treated for TB but whose
outcome after their most recent course of treatment is unknown or
undocumented.
Transfer In A patient who has been diagnosed and registered for treatment in a facility
10/11/2023 106

107. Drug Resistance
i) Case definitions for DR-TB are used for the following reasons:
 Bacteriologically confirmed DR-TB: refers to those cases
with documented laboratory DST (phenotypic or molecular)
results for DR-TB or Rifampicin Resistant TB.
 Presumptive DR-TB: refers to those cases with no
documented DST results.
ii) Case definitions:
 Mono-resistance: Resistance to only one first line anti-TB
drugs.
 Poly-resistance: Resistance to more than one first line anti-
TB drugs, but not to both isoniazid and rifampicin.
 Multidrug-resistance (MDR): Resistance to at least
isoniazid and rifampicin.
 Extensive drug-resistance (XDR): Resistance to isoniazid
and rifampicin (i.e. MDR) as well as any fluoroquinolone, and
any of the second line injectable Anti TB drugs (capreomycin,
kanamycin, and amikacin).
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108. Treatment of TB
The aims of treatment of Tuberculosis are:
 To cure the patient from TB
 To prevent death from TB disease and its late
effects
 To prevent relapse of TB
 To prevent the development of acquired drug
resistance, and
 To decrease TB transmission
Anti-TB treatment is said to be adequate when it is
administered:
 in appropriate combination of drugs
 in the correct dosage
 regularly taken by the patient, and
 For a sufficient period of time.
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109. Standardized First line TB treatment
regimens for Adolescent and Adults
TB Patient
type
Standard Regimen Patient registration groups
receiving the regimen
Intensive
Phase
Continuation
Phase
Drug
susceptible
TB case (New
and
Previously
treated)
2(RHZE) 4(RH)  New TB patients
 Relapse
 Treatment after LTFU
 Treatment after failure of New
regimen
 Others
2(RHZE) 10 (RH)  New patients with CNS TB(
meningitis, tuberculoma)
 New TB patients involving
vertebra and Osteoarticular
space
RR-/M/XDR-
TB cases
Second line drugs Confirmed cases of RR-
/M/XDR-TB cases
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110. Drug Daily Dose
(mg/kg body
weight)
Maximum
(mg)
Isoniazid 10 (10-15) 300
Rifampicin 15 (10-20) 600
Pyrazinamide 35 (30-40) -
Ethambutol 20 (15–25) -
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111.  All Anti-drugs should be administered daily and
intermittent therapy is not recommended.
 During the intensive drugs should be taken under
observation of the health worker. (DOT)
 Streptomycin should not be used as part of first line
treatment regimen for children with pulmonary
tuberculosis or TB peripheral lymphadenitis.
10/11/2023 111

112.  Pyridoxine is recommended for children who have
severe malnutrition, HIV positive on ART. (INH)
 In general, EPTB can be treated with the same
regimens as pulmonary disease.
 But children with suspected or confirmed
Tuberculous meningitis and osteo-articular TB
should be treated with a four-drug regimen (HRZE)
for 2 months, followed by a two-drug regimen (HR)
for 10 months; the total duration of treatment being
12 months.
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113.  may be used for the management of some
complicated forms of TB:
TB meningitis
Airway obstruction by TB lymph glands, and
Pericardial TB.
 The drug used is prednisone, in a dosage of 2 mg/kg
daily (upto 4mg/kg in seriously ill children), with a
maximum dosage of 60 mg/day for 4 weeks.
 The dose should then be gradually tapered over 1–2
weeks before stopping.
10/11/2023 113

114.  If assessment at 1-2 months of anti TB treatment
shows the following , consider treatment failure::
• No symptom resolution or symptoms
getting worse
• Continued weight loss
• Smear-positive at 2 month follow-up
sputum
 Poor adherence is a common cause of “treatment
failure”.
 It also suggests the possibility of MDR TB and needs
careful assessment.
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115. 10/11/2023 115

116.  According to WHO 2011 report, globally 3.2% of
incident cases of TB (290,000) are estimated to have
MDR-TB.
 There are 27 identified high burden countries that
carry 86% of the world MDRTB burden and Ethiopia
is among those countries.
 Estimated 3.7% of all new TB cases are MDR-TB.
 Estimated 20% of all previously treated TB cases are
MDR-TB.
10/11/2023 116

117. Primary Resistance Caused by person-to-person
transmission of drug-resistant organisms
( most common in children)
Secondary Resistance Develops during TB treatment:
• Patient was not
given appropriate
treatment regimen
OR
• Patient did not
follow treatment regimen as
prescribed
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118. Patient monitoring during TB treatment
At end of intensive phase,
Five month in to treatment,
and at end of treatment to assess for:
Persistence or reappearance of clinical
feature of TB
Bacteriologic monitoring for treatment
response using AFB microscopy
Treatment adherence
Occurrence of Adverse drug reaction,
Development of TB complications.
10/11/2023 118

119. AFB follow-up monitoring for
bacteriologically confirmed New PTB
patients
10/11/2023 119

120. Drug Adverse Reactions
Isoniazid Mild hepatic enzyme elevation, hepatitis,[†]
peripheral neuritis, hypersensitivity
Rifampicin Orange discoloration of secretions or urine,
staining of contact lenses, vomiting, hepatitis,
influenza-like reaction, thrombocytopenia,
pruritus; oral contraceptives may be ineffective
Pyrazinamide Hepatotoxic effects, hyperuricemia, arthralgias,
gastrointestinal tract upset
Ethambutol Optic neuritis (usually reversible), decreased
red-green color discrimination, gastrointestinal
tract disturbances, hypersensitivity
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121.  are less common in children than in adults.
 The most common adverse reaction is the
development of hepatotoxicity, which can be caused
by Isoniazid, Rifampicin or Pyrazinamide.
 Serum liver enzyme increment of <5 times normal
values is not an indication to stop treatment.
 Routine determination of liver enzymes is not
necessary.
 However, the occurrence of liver tenderness,
hepatomegaly, or jaundice should lead to its
investigation.
10/11/2023 121

122.  Clinical assessment alone is sufficient to decide
whether the contact is well or symptomatic.
 Routine assessment of exposed contacts does not
require CXR or TST.
 IPT is recommended for all young children(<5 years)
that are household contacts of a case with sputum
smear-positive TB with no evidence of TB disease.
 Recommended treatment is isoniazid 10 mg/kg daily
for 6 months.
10/11/2023 122

123. Assigning final treatment Outcome for your TB patient
itions
Cured A pulmonary TB patient with bacteriological confirmed TB at the beginning of
treatment who was smear- or culture- negative in the last month of treatment and
on at least one previous occasion.
Treatment
completed
A patient who completed treatment but without evidence of failure BUT with no
record to show that sputum or culture results in the last month of treatment and on
at least one previous occasion were negative, either because tests were not done
or because results are unavailable .
Treatment
failure
A TB patient whose sputum smear or culture is positive at month 5 or later during
treatment.
Died A patient who dies for any reason during the course of TB treatment.
Lost to follow
up(LTFU)
A patient who has been on treatment for at least four weeks and whose treatment
was interrupted for eight or more consecutive weeks.
Not Evaluated A TB patient for whom no treatment outcome is assigned. This includes cases
―transferred out‖ to another treatment unit as well as cases for whom the
treatment outcome is unknown to the reporting unit.
Moved to
MDR-TB
TB Patients who were found to have RR-TB or MDR-TB before fifth month of
treatment and who were referred to MDR TB unit and started on a full MDR-TB
treatment regimen (i.e. patient is moved to the second-line treatment register).
Treatment
success
A sum of cured and completed treatment.
10/11/2023 123

124. 1. Nelson text book of pediatrics – 20th ed.
2. Manson’s , Tropical disease, 22nd ed.
3. Update on National TB-LEPROSY Guideline,2015
10/11/2023 124