Tuberculosis

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…
 More than ⅓ of the world's population is
infected with Mycobacterium tuberculosis.
 53 different species of mycobacterium
 3 species cause TB in humans

2
ETIOLOGY.

 There are 5 closely related mycobacteria in

the M. tuberculosis complex:
1. M. tuberculosis
2. M. bovis
3. M. africanum
4. M. microti
5. M. canetti

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…
 M. tuberculosis is the most important cause
of tuberculosis disease in humans.
 The tubercle bacilli are

non-spore-forming
nonmotile
Pleomorphic
weakly gram-positive curved rods

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…
Obligate aerobes
Grow in synthetic media containing glycerol as the
carbon source and ammonium salts as the nitrogen
source (Loewenstein-Jensen culture media).
Grow best at 37–41°C.

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…
 A hallmark of all mycobacteria is acid fastness.
 Once stained, they resist discoloration with
ethanol and hydrochloric or other acids.
 Microorganisms other than mycobacteria that
display some acid fastness include;
◦ Nocardia
◦ Rhodococcus
◦ Legionella micdadei
◦ Isospora
◦ Cryptosporidium

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…
 Mycobacteria grow slowly, their generation
time being 12–24 hr.
 Isolation from clinical specimens
 Takes 3–6 wk on solid synthetic media and drug
susceptibility testing requires an additional 4 wks
 Takes 1-3 wk on liquid medium and drug
susceptibilities requires an additional 3-5 days

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EPIDEMIOLOGY.

 The global burden of tuberculosis continues

to grow due to several factors, including
 The impact of HIV epidemics
 Population migration patterns
Increasing poverty
Crowded living conditions in developing countries
 Inadequate health coverage
Poor access to health services
 Inefficient tuberculosis control programs

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…
 Tuberculosis remains the second leading
cause of death from an infectious disease
worldwide (after HIV)
 One-third of the world’s population (2.5

billion people) is infected with M.

tuberculosis.
 95% of tuberculosis cases occur in the

developing world.
 The highest numbers of cases are in Asia,

Africa, and the eastern Mediterranean region.

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…
 Tuberculosis is most common in children
younger than 5 yr of age.
 The age range of 5-14 yr has the lowest rate

of tuberculosis disease.
 In children there is no significant difference

by gender.
 Most children are infected with M.

tuberculosis in their home by someone close

to them.

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…
 There are 3 major clinical stages of tuberculosis:
◦ Exposure
◦ Infection
◦ Disease
 Exposure means a child has had significant contact (“shared the air”) with
an adult or adolescent with infectious tuberculosis but lacks proof of
infection.
 In this stage
 The tuberculin skin test (TST) result is negative
 The chest radiograph is normal
 The physical examination is normal
 The child lacks signs or symptoms of disease.
 Infection occurs when the individual inhales droplet nuclei containing M.
tuberculosis, which survive intracellularly within the lung and associated
lymphoid tissue.

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…
 Latent tuberculosis infection (LTBI) occurs
after the inhalation of infective droplet nuclei
containing M. tuberculosis.
 There is reactive tuberculin skin test
 There is absence of clinical and radiographic
manifestations
 The word tuberculosis refers to disease,
which occurs when signs and symptoms or
radiographic changes become apparent.

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…
 Not all infected individuals have the same risk
of developing disease.
 An immunocompetent adult with untreated

tuberculosis infection has approximately a 5-

10% lifetime risk of developing disease.
 In contrast, an infected child younger than 1

yr of age has a 40% chance of developing

disease within 9 mo.

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RISK FACTORS FOR TUBERCULOSIS
 Children exposed to high-risk adults   
 Foreign-born persons from high-prevalence

countries     
 Homeless persons      
 Health care workers caring for high-risk

patients
 Age less than 5 years

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…

 Persons who are immunocompromised,

especially in cases of
Malignancy
Solid organ transplantation
 Immunosuppressive medical treatments including
anti–tumor necrosis factor therapies
Diabetes mellitus
Chronic renal failure, silicosis, and malnutrition

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Transmission.
 Inhalation
 Ingestion of milk
 Transplacental

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…
 Transmission of M. tuberculosis is usually by
airborne mucus droplet nuclei.
 The chance of transmission increases

a) when the patient has an acid-fast smear of

sputum
b) an extensive upper lobe infiltrate or cavity
c) copious production of thin sputum
d) severe and forceful cough
 Environmental factors, especially poor air

circulation, enhance transmission.

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…
 M. bovis penetrate the gastrointestinal
mucosa when large numbers of the organism
are ingested.
 M. bovis is rare in developed countries as a

result of
◦ Pasteurization of milk
◦ Effective tuberculosis control programs for cattle

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Disease development
1. Primary infection
2. Reactivation
3. Reinfection
 Factors affecting disease development
◦ Immunity status
◦ Nutritional status
◦ Intercurrent illness
◦ Length of time of exposure
◦ # of bacteria inhaled
◦ Age at infection

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PATHOGENESIS.

 The lung is the portal of entry in >98% of

cases.
 The tubercle bacilli multiply initially within

alveoli and alveolar ducts.

 Most of the bacilli are killed, but some survive

within nonactivated macrophages

 When the primary infection is in the lung, the

hilar lymph nodes usually are involved.

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…
 The parenchymal portion of the primary
complex heals by fibrosis or calcification after
undergoing caseous necrosis and
encapsulation.
 If caseation is intense, the center of the lesion

liquefies.
 Viable M. tuberculosis can persist for decades

within these foci.

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…
 primary complex (Ghon complex) is the
combination of a parenchymal pulmonary lesion
and a corresponding lymph node site.
 Bacterial replication occurs in organs with
conditions that favor their growth, such as
◦ Lung apices
◦ Brain
◦ Kidneys
◦ Bones
 Disseminated tuberculosis occurs if the number of
circulating bacilli is large and the host cellular
immune response is inadequate.

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…
 Lymph node complications
◦ Extension into bronchus
◦ Hyperinflation
◦ Blood spread of bacilli
◦ Consolidation

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…
 A cavity is formed when
◦ Lesions do not control bacterial growth
◦ Infection damages the lung tissue
◦ Lesion eats into a bronchus
 A cavity is an ideal ground for bacteria due to
◦ Oxygen level is high
◦ Dead tissue is source of food
◦ No longer walled off by a ring of immune cells

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CLINICAL MANIFESTATIONS
 The clinical manifestations of tuberculosis depend on the site of
involvement.
 History:
◦ unexplained weight loss or failure to grow normally
◦ unexplained fever, especially when it continues for more than 2 weeks
◦ chronic cough (i.e. cough for more than 3 weeks)
◦ Night sweating
◦ Loss of appetite
 Examination:
◦ enlarged non-tender lymph nodes or a lymph node abscess, especially in the
neck
◦ Crackles, bronchial breath sound , etc
◦ Signs of fluid in the chest
◦ signs of meningitis, especially when these develop over several days and the
spinal fluid contains mostly lymphocytes and elevated protein;
◦ abdominal swelling, with or without palpable lumps; ascites
◦ progressive swelling or deformity in the bone or a joint, including the spine.

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…
 15% of adult tuberculosis cases are
extrapulmonary
 25–30% of children with tuberculosis have an

extrapulmonary presentation

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Primary Pulmonary Disease.

 Primary infection occurs on the first exposure to

tubercle bacilli.
 The initial focus of pulmonary tuberculosis in children

occurs most frequently in the midlung zones.

 Infection begins with the multiplication of the bacilli in

the lungs.
 This is the ghon focus.

 Lymphatics drain the bacilli to the hilar lymph nodes.

 The ghon focus(parenchymal pulmonary focus ) and

related hilar lymphadenopathy form the primary

complex.

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…
 All lobar segments of the lung are at equal
risk for initial infection.
 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.

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…
 As DTH develops, the hilar lymph nodes
continue to enlarge.
 The usual sequence is

◦ hilar lymphadenopathy
◦ focal hyperinflation
◦ atelectasis
 The resulting radiographic shadows have
been called collapse-consolidation or
segmental tuberculosis.

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…
 Clinical onset of tuberculous pleurisy is often
sudden, characterized by
◦ low to high fever
◦ shortness of breath
◦ chest pain on deep inspiration
◦ diminished breath sounds
 The tuberculin skin test is positive in only 70–
80% of cases.
 The prognosis is excellent, but radiographic

resolution often takes months.

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Disseminated TB.
 Tubercle bacilli are disseminated to distant sites
 Extrapulmonary tuberculosis  — The clinical

presentation of extrapulmonary TB depends on

the site of disease.
 The most common forms of extrapulmonary

disease in children are TB of the superficial

lymph nodes and of the central nervous system
(CNS).
 Neonates have the highest risk of progression to

TB disease with miliary and meningeal

involvement

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Miliary tuberculosis
 The most clinically significant form of
disseminated tuberculosis is miliary disease
 It occurs when massive numbers of tubercle

bacilli are released into the bloodstream, causing

disease in 2 or more organs.
 It occurs within 2–6 mo of the initial infection.
 It is most common in infants and young children.
 Lesions are often larger and more numerous in

the lungs, spleen, liver, and bone marrow than

other tissues.

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…
 More often, the onset is insidious with early
systemic signs, including anorexia, weight loss,
and low-grade fever.
 Generalized lymphadenopathy and
hepatosplenomegaly develop within several
weeks in about 50% of cases.
 The fever may then become higher and more
sustained.
 The lesions of miliary tuberculosis are usually
smaller than 2–3 mm in diameter when first
visible on chest radiograph.
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…
 Diagnosis of disseminated tuberculosis can
be difficult, and a high index of suspicion by
the clinician is required.
 Often the patient presents with fever of

unknown origin.
 The most important clue is usually history of

recent exposure to an adult with infectious

tuberculosis.

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Lymph Node Disease.

 Tuberculosis of the superficial lymph nodes,

in the cervical region, referred to as scrofula,
is the most common form of extrapulmonary
tuberculosis in children.
 It occurs within 6–9 mo of initial infection.
 They are firm but not hard, discrete, and

nontender.
 The nodes often feel fixed to underlying or

overlying tissue.

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…
 Disease is most often unilateral, but bilateral
involvement may occur.
 As infection progresses, multiple nodes are

infected, resulting in a mass of matted nodes.

 Systemic signs and symptoms other than a

low-grade fever are usually absent.

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…
 The tuberculin skin test is usually reactive.
 The chest radiograph is normal in 70% of

cases.
 Lymph node tuberculosis may resolve if left

untreated but more often progresses to

caseation and necrosis.
 The capsule of the node breaks down,

resulting in the spread of infection to

adjacent nodes.

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…
 Tuberculous lymphadenitis can usually be
diagnosed by fine-needle aspiration of the
node and responds well to antituberculosis
therapy.

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…
 If fine-needle aspiration is not successful in
establishing a diagnosis, excisional biopsy is
indicated.
 Culture of lymph node tissue yields the

organism in only about 50% of cases.

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…

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Central Nervous System Disease.
 CNS tuberculosis is the most serious
complication in children and is fatal.
 Tuberculous meningitis develops during the

lymphohematogenous dissemination of the

primary infection.

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…
 The initial lesion increases in size and
discharges small numbers of tubercle bacilli
into the subarachnoid space.
 The brainstem is often the site of greatest

involvement with dysfunction of cranial

nerves III, VI, and VII.
 The exudate also interferes with the normal

flow of CSF, leading to a communicating

hydrocephalus.

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…
Tuberculous meningitis complicates about
0.3% of untreated tuberculosis infections in
children.
 It is most common in children between 6 mo

and 4 yr of age.

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…
 Can be divided into 3 stages.
 The 1st stage

◦ Lasts 1–2 wk
◦ characterized by nonspecific symptoms, such as
 fever
 Headache
 Irritability
 drowsiness
 Malaise
 Focal neurologic signs are absent.

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…
 The 2nd stage
◦ begins more abruptly
◦ The most common features are
 Lethargy
 nuchal rigidity
 Seizures
 positive Kernig or Brudzinski signs
 Hypertonia
 vomiting
 cranial nerve palsies, and other focal neurologic signs

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…
 Some children have no evidence of meningeal
irritation but may have signs of encephalitis,
such as
Disorientation
movement disorders
speech impairment

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…
 The 3rd stage
Coma
hemiplegia or paraplegia
hypertension
decerebrate posturing
deterioration of vital signs, and eventually death.
 The prognosis of tuberculous meningitis
correlates most closely with the clinical stage
of illness at the time treatment is initiated.

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…
 The majority of patients in the 1st stage have
an excellent outcome
 most patients in the 3rd stage, who survive

have permanent disabilities.

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…
 The tuberculin skin test is nonreactive in up
to 50% of cases
 20–50% of children have a normal chest

radiograph.
 The most important laboratory test for the

diagnosis of tuberculous meningitis is

examination and culture of the lumbar CSF.

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…
 The success of the microscopic examination
of acid-fast-stained CSF and mycobacterial
culture is related directly to the volume of the
CSF sample.
 Examinations or culture of small amounts of

CSF are unlikely to demonstrate M.

tuberculosis.

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…
 Another manifestation of CNS tuberculosis is
the tuberculoma, a tumor-like mass resulting
from aggregation of caseous tubercles that
usually presents clinically as a brain tumor.
 In adults tuberculomas are most often

supratentorial
 in children tuberculomas are often

infratentorial, located at the base of the brain

near the cerebellum.

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…
 Lesions are most often singular but may be
multiple.
 The most common symptoms are
◦ headache
◦ fever
◦ convulsions
 most tuberculomas resolve with medical
management.
 On CT or MRI of the brain, tuberculomas
usually appear as discrete lesions with a
significant amount of surrounding edema.

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Bone and Joint Disease.

 Skeletal TB accounts for 10 to 35 percent of cases of

EPTB.
 The most common form of skeletal TB is Pott disease,
a disease of the spine; this entity comprises
approximately half of musculoskeletal TB cases.
 The classic manifestation of tuberculous spondylitis
is progression to Pott disease, in which destruction of
the vertebral bodies leads to gibbus deformity and
kyphosis.
 Skeletal tuberculosis is a late complication of
tuberculosis ,it is more likely to occur in children than
in adults.

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…
 Most common in lower thoracic and lumbar
spine.
 The next most common form of

musculoskeletal TB is tuberculous arthritis,

followed by extraspinal tuberculous
osteomyelitis
 Most occur in the first three years of life.
 The most commonly affected bones and

joints are the spine, hip, knee and feet.

 The joints are swollen but not tender or hot.

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…

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Pericardial Disease.
 The most common form of cardiac tuberculosis
is pericarditis.
 occur in 0.5–4%
 Pericarditis usually arises from direct invasion
or lymphatic drainage from subcarinal lymph
nodes.
 A pericardial friction rub or distant heart
sounds with pulsus paradoxus may be present.
 The pericardial fluid is typically serofibrinous or
hemorrhagic.

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…
 cultures are positive in 30–70% of cases.
 The culture yield from pericardial biopsy may

be higher, and the presence of granulomas

often suggests the diagnosis.
 Partial or complete pericardiectomy may be

required when constrictive pericarditis

develops.

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Abdominal.
 Tuberculous peritonitis is rare in children.
 Generalized peritonitis may arise from subclinical

or miliary hematogenous dissemination.

 Rarely, the lymph nodes, omentum, and

peritoneum become matted and can be palpated

as a “doughy” irregular nontender mass.
 Abdominal pain or tenderness, ascites, anorexia,

and low-grade fever are typical manifestations.

 The diagnosis can be confirmed by paracentesis

with appropriate stains and cultures.

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Gastrointestinal TB
 Tuberculous enteritis is caused by
hematogenous dissemination or by
swallowing tubercle bacilli discharged from
the patient's own lungs.
 The jejunum and ileum near Peyer patches

and the appendix are the most common sites

of involvement.
 The typical findings are shallow ulcers that

cause pain, diarrhea or constipation, and

weight loss with low-grade fever.

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…
 Mesenteric adenitis usually complicates the
infection.
 The enlarged nodes may cause intestinal

obstruction or erode through the omentum to

cause generalized peritonitis.
 Biopsy, acid-fast stain, and culture of the

lesions are usually necessary to confirm the

diagnosis.

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Genitourinary Disease.

 Renal tuberculosis is rare in children because

the incubation period is several years or
longer.
 Tubercle bacilli usually reach the kidney

during lymphohematogenous dissemination.

 Infection then spreads locally to the ureters,

prostate, or epididymis.
 Renal tuberculosis is often clinically silent in

its early stages, marked only by sterile pyuria

and microscopic hematuria.

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…
 Dysuria, flank or abdominal pain, and gross
hematuria develop as the disease progresses.
 Hydronephrosis or ureteral strictures may

complicate the disease.

 Urine cultures for M. tuberculosis are positive

in 80–90% of cases, and acid-fast stains of

large volumes of urine sediment are positive
in 50–70% of cases.

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…
 An intravenous pyelogram or CT scan often
reveals
mass lesions
dilatation of the proximal ureters
multiple small filling defects
hydronephrosis if ureteral stricture is present.
 Disease is most often unilateral.

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…
 Tuberculosis of the genital tract is uncommon
before puberty.
 Adolescent girls may develop genital tract

tuberculosis during the primary infection.

 The fallopian tubes are most often involved (90–

100% of cases) followed by the endometrium

(50%), ovaries (25%), and cervix (5%).
 The most common symptoms are lower

abdominal pain and dysmenorrhea or

amenorrhea.

64
…
 Genital tuberculosis in adolescent males
causes epididymitis or orchitis.
 The condition usually manifests as a

unilateral nodular painless swelling of the

scrotum.

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Diagnosis
 Typical Symptoms
 History of Contact
 Clinical Examination
 Tuberculin Skin Test
 Bacteriological Confirmation
 AFB
 Calture
 Gene x-pert
 Chest X-Ray
 LP
 CT,MRI

66
Bacteriological Confirmation

 Three sputum specimens must be collected

and examined in two consecutive days (spot
early morning-spot).
 The sputum collection procedure is as

follows.
 Day 1:the first "on-the-spot" sample is

collected.
 Day 2:the early morning sample (Sample 2) is

submitted, and then the second "on the-spot"

sample (Sample 3)is collected.

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 Investigations for Common Forms of
Extrapulmonary TB in Children
Site Practical Approach to Diagnosis
Peripheral lymph nodes (especially Lymph node fine needle aspiration or
cervical) biopsy
Miliary TB (e.g. disseminated) Chest X-ray and lumbar puncture (to
test for meningitis)
TB meningitis Lumbar puncture (if not
contraindicated)
Pleural effusion Chest X-ray, pleural tap for
biochemical analysis) (protein and
glucose concentrations), cell count and
culture
Abdominal TB (e.g. peritoneal) Abdominal ultrasound and ascitic fluid
analysis
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What is PPD test`
 The Mantoux tuberculin skin test is the intradermal injection of
0.1 mL containing 5 tuberculin units of purified protein
derivative (PPD).
 The development of delayed-type hypersensitivity in patients
infected with the tubercle bacillus makes the TST a useful
diagnostic tool.
 The immune response (delayed hypersensitivity and cellular
immunity) develops about 4–6 weeks after the primary infection.
 T cells sensitized by prior infection are recruited to the skin
where they release lymphokines that induce induration through
◦ Local vasodilatation
◦ Edema
◦ Fibrin deposition
◦ Recruitment of other inflammatory cells to the area

69
…
 The amount of induration in response to the
test should be measured within 48–72 hr
after administration.
 Immediate hypersensitivity reactions <24 hr

is not considered a positive result.

 In some patients, the onset of induration is

longer than 72 hr after placement; this is also

a positive result.

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…
 The following host-related factors can
depress the skin test reaction.
 very young age
 Malnutrition
 Immunosuppression by disease or drugs
 viral infections (measles, mumps, varicella, influenza)
 vaccination with live-virus vaccines
 overwhelming tuberculosis
 Corticosteroid therapy

71
…
 The appropriate size of induration indicating
a positive PPD test result varies with
epidemiologic and risk factors.

72
Tuberculin Skin Test Recommendations
 Immediate TST :
 Contacts of people with confirmed or suspected
contagious tuberculosis
 Children with radiographic or clinical findings
suggesting tuberculosis disease
 Children immigrating from countries with endemic
infection
 Children with travel histories to countries with
endemic infection
 Annual TST :
◦ Children infected with HIV

73
Definitions of Positive Tuberculin Skin
Test Results
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

74
…
 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
 malnutrition

75
…
 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
 Migrant farm workers
 Children who travel to high-prevalence regions of the
world
INDURATION ≥15 mm
◦ Children ≥4 yr of age without any risk factors

76
…

77
False negative PPD test
 Severe PEM
 Measles
 Overwhelming TB
 Wrong techniques
 HIV
 Steroids
 Cancer

78
False positive PPD test
 Atypical mycobacterial infections
 Hypersensitivity to constituents
 BCG vaccination
 Technical error

79
Definitions of TB Cases Classifications

a. Smear-positive pulmonary TB (PTB+)

 A patient with at least two initial sputum

smear examinations positive for AFB, Or

 A patient with one initial smear examination

positive for AFB and culture positive.

 A patient with one initial smear examination

positive for AFB and radiographic

abnormalities consistent with active TB as
determined by a clinician.

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…
b. Smear-negative pulmonary TB (PTB-)
 A patient having symptoms suggestive of TB with at

least 3 initial smear examinations negative for AFB,

And
 No response to a course of broad-spectrum antibiotics, And
 Again three negative smear examinations, And Radiological
abnormalities consistent with pulmonary tuberculosis, And
 Decision by a clinician to treat with a full course of anti-
tuberculosis Or
 A patient whose diagnosis is based on culture positive for M.
tuberculosis but three initial smear examinations negative by
direct microscopy

81
…
Extra-pulmonary TB (EPTB)
 TB in organs other than the lungs, proven by

one culture-positive specimen from an

extrapulmonary site or
 Histo-pathological evidence from a biopsy,

Or
 TB based on strong clinical evidence

consistent with active EPTB and

 The decision by a clinician to treat with a full

course of anti-TB therapy.

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History of previous treatment: patient
registration group
 New patients have never had treatment for
TB, or have taken anti-TB drugs for less than
1 month.
 Previously treated patients have received 1

month or more of anti-TB drugs in the past.

◦ Further classified by the outcome of their
treatment.

83
Treatment outcome definitions
Relapse A patient who received treatment and was declared cured or
treatment completed at the end of the treatment period and
has now developed TB again.

Cure Patient whose baseline smear (or culture) was positive at the
beginning of the treatment and is smear/ culture negative in
the last month of treatment and on at least one previous
occasion at least 30 days prior.

Treatment Patient whose baseline smear (or culture) was positive at the
beginning and has completed treatment but does not have a negative
completed
smear/ culture in the last month of treatment and on at least one
previous occasion more than 30 days prior. The smear examination
may not have been done or the results may not be available at the end
of treatment.

Treatment Patient whose baseline smear (or culture) was positive

failure and remains or becomes positive again at 5 months or
later during treatment. This definition excludes those
patients who are diagnosed with RR-TB or MDR-TB 84
REGISTRATION OF TB PATIENTS
definition
Pulmonary TB Disease involving the lung
parenchyma.
Extra-pulmonary TB Disease involving organs other
than the lungs: e.g. pleura, lymph
nodes, abdomen, genito-urinary
tract, skin, joints and bones and
meninges

85
…
Before you put patients on anti TB drugs:
 Determine the type of TB:

◦ PTB+(smear +ve pulmonary TB)

◦ PTB- (smear- ve pulmonary TB)
◦ EPTB (extrapulmonary TB)
 Determine previous treatment history:
◦ New patient
◦ Previously treated
 Select based on the three standard treatment regimens:

1. New patient regimen

2. Previously treated patient regimen
3. MDR-TB regimen

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TB treatment regimens
TB patient type Recommended regimen

New Treat as new: 2RHZE/4RH

Previousl Treatment failure Treat as retreatment:

y treated 2RHZES/RHZE/5RHE)

Treatment after default Treat as retreatment:

Or relapse after one 2RHZES/RHZE/5RHE)
course of treatment

Relapse after second or Wait for DST result

subsequent courses of
treatment
Failure of retreatment

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TREATMENT
The aims of TB treatment
 To Cure the TB patient
 To restore quality of life and productivity
 To prevent death from active TB
 To prevent relapse of TB
 To prevent the development and transmission

of drug resistance
 To decrease TB transmission to others.

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…
 TB treatment consists of
◦ Anti -TB
◦ Steroid(if indicated)
◦ Pyridoxine
◦ Nutrition
◦ Followup

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Recommended Treatment Regimens
 Anti-TB treatment is divided into two phases:
1. An intensive phase
2. A continuation phase
 During the intensive phase, four drugs
regimen (HRZE) for two months is
recommended
 In continuation phase two drug regiment(HR)
for four months .

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Recommended doses of first-line
anti-TB drugs for childrena
Drug Recommended Dose (mg/kg/day)
Isoniazid(H) 10-15
Rifampicine(R) 10-20
Pyrazinamide(Z) 30-40
Ethambutol (E) 15-25

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…
 In general, extra-pulmonary tuberculosis in
children can be treated with the same
regimens as pulmonary disease.
 Exceptions are the following for which the recommended
duration is 9 to 12 months.
 disseminated TB disease
 Osteo-arthicular
 meningitis

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Indications of corticosteroids in TB
patients
◦ Tuberculous meningitis
◦ Tuberculoma
◦ Endobronchial tuberculosis
◦ Tuberculous pericarditis
◦ Massive pleural effusion
◦ Miliary tuberculosis
◦ Tb of the adrenal gland

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…
 Pyridoxine is recommended for infants and
children who are being treated with INH and
who are with
◦ nutritional deficiencies
◦ symptomatic HIV infection
◦ breastfeeding.

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Treatment Failure
 Most children with TB will start to show signs
of improvement after 2 to 4 weeks of anti TB
treatment.
 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 two month

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…
 Poor adherence is a common cause of
“treatment failure”.
 If a child stops anti-TB treatment for less

than 2 weeks in the intensive phase and less

than 2 months in the continuation phase and
becomes symptomatic, then restart treatment
for new cases.
 Treatment failure is more common in HIV-

infected children.
 It also suggests the possibility of MDR TB.

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Follow-up of New Smear-Positive PTB
Cases
 The response to anti-TB treatment in smear
positive Pulmonary TB patients is monitored
by follow-up sputum smear examination.
 For new PTB+ patients treated with first-line

drugs, sputum smear microscopy should be

done at the completion of the intensive phase
of treatment.

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…
 As a routine, all new sputum-positive patients on TB
treatment must have one sputum specimen examined
at the end of the 2nd, 5th and 6th ‘month’ of therapy.
 If the sputum smear at the end of 2nd month is

negative for AFB, the continuation phase will be

started.
 If the sputum smear at the end of the 2nd month of

intensive phase is positive for AFB, start continuation

phase treatment and repeat sputum smear at the end
of the 3rd month of therapy.
 Extension of the intensive phase by one month is not

recommended.

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…
 If the sputum smear at the end of 3rd month of therapy is
negative, continue with the continuation phase; and
sputum smear should be done at the end of 5th month of
therapy.
 If the sputum smear at the end of 3rd month of therapy is
positive for AFB, two sputum samples should be taken
and sent for culture and DST.
 The main purpose of obtaining cultures at this stage is to
detect drug resistance without waiting for the fifth month
to shift to appropriate therapy.
 Note that treatment is declared a failure if a patient is
found to harbor MDR-TB at any point in time during
treatment.

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…
 In the continuation phase of treatment, if the sputum
smear result at the end of 5th month of treatment is
negative for AFB, the patient should continue with the
same treatment.
 If the first smear result is positive for AFB at the end of 5th
month, sputum smear examination should be repeated.
 If the second sputum smear result is positive, the patient
is declared as treatment failure.
 But if the second sputum is negative, go for third tie
breaker sputum test and decide accordingly.
 The patient should be registered as treatment failure and
re-started with regimen for previously treated cases.

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…
The sputum is examined again at the end of 6th
month.
 If the result is negative the patient is declared cured.

 If the result is positive in two smears at 5th or

6thmonths, the patient is a treatment failure and

should re-start the treatment regimen for previously
treated cases.
 If for whatever reason, after completion of 6 months

of treatment the final sputum smear examination

result of the patient is not known or not done and the
sputum result at 5th month was negative, the patient
should be declared treatment completed.

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Follow-up of Previously Treated Smear-
Positive PTB Cases
 Sputum smear examination is performed at the end of the
intensive phase of treatment (the 3rd month) as well as at the
end of the 5th and 8th months of treatment.
 In previously treated patients, if the specimen obtained at the
end of the intensive phase (month 3) is smear negative, the
continuation phase of re-treatment regimen is started and
sputum is examined at the end of 5th month of therapy.
 However, if the sputum smear result at the end of 3rd month
of therapy is smear-positive, sputum culture and drug
susceptibility testing (DST) should be performed.
 But patients should continue treatment till the results come.
 Decision on treatment will be made based on the DST result.

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…
 If the smear result at the end of 5th month of re-
treatment regimen is negative for AFB, the
continuation phase is continued and sputum is
examined at the end of 8th month of therapy.
 However, if the patient is found smear-positive at the

end of 5th month of treatment in 2 different

specimens, the patient is declared as treatment failure.
 Sputum specimens must be sent for culture and DST

and the patient should be referred to MDR TB

treatment Center.
 Further decision on treatment must be guided by DST.

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…
 If the sputum smear result at the end of 8th month and in
at least one previous occasion is found to be negative, the
patient is declared cured.
 If the smear result at the end of the 8th month of therapy

is positive in two different specimens, the patient is

declared treatment failure.
 Sputum specimens must be sent for culture and DST and

the patient should be referred to MDR TB treatment Center.

 Further decision on treatment must be guided by DST.
 If for whatever reason after 8 months of treatment, the

final sputum examination cannot be done and the sputum

result at 5th month was negative or not done, the patient
should be declared treatment completed.

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Follow-up of New Smear-Negative PTB
and EPTB Cases
 Follow-up for smear negative PTB and EPTB patients is done by
monitoring weight and clinical conditions.
 For pulmonary TB patient whose sputum microscopy was
negative (or not done) before treatment, there should be a
repeat sputum test at the end of intensive phase in case the
disease has progressed or symptoms persisted.
 If the sputum smear microscopy is found to be negative, the
same treatment should be continued.
 If sputum result turns positive, (it could be due to non-
adherence or drug resistance or an error at the time of initial
diagnosis, i.e. a true smear-positive patient was misdiagnosed
as smear-negative), wait for the third month and repeat
sputum smear microscopy.
 If it remains positive, send for DST.

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…

THANK YOU

By Dr.Tsegaye D

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