1. Tuberculosis
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Kareem Alnakeeb
Tuberculosis
- Mycobacterium tuberculosis, M. bovis and M. africanum of the family Mycobactericeae
 M. TB bacilli are characterized by:
• Non-spore forming, Non-motile
• Obligate aerobe, slow growing on Lowenstein-Jensen medium
• having a lipid-rich cell wall  resistance to antibody and complement
• Acid fasting is a hallmark for Mycobacteria; as it forms stable mycolate complexes
with arylmethane dyes (as carbulfuchsin) that resist decoloration with acid or alcohol.
- About 2 billion people have TB infection worldwide (without disease).
- WHO estimates >8 million new cases of tuberculosis per year and 3 million deaths
- Tuberculosis is most common in young adults and children <5 years.
- Transmission is common from person to person by air-droplet especially from adults with:
o Positive smear.
o Extensive upper lobe infiltrate or cavity.
o Severe forceful coughing.
o Copious thin mucus.
- M. TB ingested by macrophages in alveoli, survive and multiply as they resist killing by
lytic enzymes of non-activated cells.
- Cellular immunity develops 2-12 weeks after infection & usually limits M. TB growth in
“granulomas” which are the hallmark of the disease.
- The balance between the bacterial antigen load, cell mediated immunity (intracellular killing)
and tissue hypersensitivity (extracellular killing) determine the net pathologic events
- e.g. small Ag load and high hypersensitivity  well organized granuloma and self-cure.
Etiology:
Epidemiology:
Immunity to Tuberculosis:

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Kareem Alnakeeb
- The primary complex (or Ghon complex) of tuberculosis includes local infection at the
portal of entry & the regional lymph nodes that drain the area.
- The portal of entry in > 98% of cases is the lung
 So, the primary pulmonary complex (PPC) consists of:
• parenchymal lung lesion
• hilar or paratracheal lymphadenopathy.
1. Regression (95%):
- The parenchymal lesion heals by granuloma organization or clacification after caseation.
- The lymph nodes develop some fibrosis & encapsulation
but viable M. TB can persist for decades.
- Dormant M. TB may regrow after several months of primary infection causing
late progression (reactivation TB).
2. Early Progression (5%):
- Progression of parenchymal lesion results in focal pneumonitis, pleuritis, or cavity.
- The lymph nodes 
may enlarge and compress a bronchus causing localized hyperinflation or atelectasis
or may caseate and erode through a bronchus resulting in endobronchial TB.
3. Lymphohematogenous dissemination:
- It may develop in cases of poor immunity and large number of pathogens.
 Immunosuppression:
- HIV infection or immunodeficiency.
- Corticosteroid /other immunosuppressive therapy
 Substance abuse (esp. drug injection).
 Nutritional status (Severe malnutrition).
 Systemic diseases
- Diabetes mellitus. - End Stage Renal Disease
- Recent infection with M. TB - Measles infection or vaccine
Pathogenesis:
Fate of primary Complex:
Conditions that  risk of progression to TB disease

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Infection 2018
Kareem Alnakeeb
- Inhalation of aerosol droplets containing M. TB with subsequent deposition in the lungs
leads to one of four possible outcomes:
• Immediate clearance of the organism
• Primary disease: immediate onset of active disease
• Latent infection
• Reactivation disease: onset of active disease many years following a period of latent infection
Natural history of infection
Infection
- Initial containment – 95%
- Early Progression - 5%
- Late Progression - 5%
Self-Cure – 90%

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Infection 2018
Kareem Alnakeeb
Pulmonary Tuberculosis Extrapulmonary Tuberculosis
Primary Pulmonary Disease
Progressive Primary Pulmonary Disease
Reactivation Tuberculosis
Pleural Effusion
Lymph Node Disease
Lymphohematogenous (Disseminated) Disease
Abdominal and Gastrointestinal Disease
Central Nervous System Disease
Ocular TB
Genitourinary Disease
Cutaneous Disease
Bone and Joint Disease
i. Pulmonary Tuberculosis
A. Primary Pulmonary Disease
- About 50% of infants and children with primary pulmonary TB may present with:
• Non-productive cough, mild dyspnea
• Less often systemic symptoms as fever, night sweats.
B. Progressive Primary Pulmonary Disease
- Children with progressive primary disease frequently have:
• Productive cough,
• Significant systemic symptoms as fever, night sweats, weight loss
• Physical signs: chest rales, dullness or egophony over cavitary lesions.
C. Reactivation Tuberculosis
- Reactivation pulmonary TB is rare in children but may occur in adolescents
• Usually presents with systemic manifestations, productive cough, hemoptysis
• Minor chest signs.
• The most common radiographic finding is extensive upper lobe infiltrate
Clinical Manifestations:

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Infection 2018
Kareem Alnakeeb
D. Pleural Effusion
- Pleural effusion is infrequent in children < 6 years.
- It is usually unilateral
• presenting with: chest pain, shortness of breath,
• diminished breath sounds that may persist for several weeks post therapy.
ii. Extrapulmonary Tuberculosis:
A. Lymph Node Disease:
- Superficial TB lymphadenopathy (scrofula) is the most common extrapulmonary TB .
- Early, the lymph nodes are firm, discrete, non-tender, often fixed to the surrounding tissue
- Then become matted with disease progression resulting in cold abscess or sinus formation.
B. • Lymphohematogenous (Disseminated) disease:
- This form is more common in infants, young and immunosuppressed children.
 Miliary disease;
- Most clinically significant form with multiple organ involvement, bone & joint affection.
- Meningitis occurs in 20-40% of cases
- Choroid tubercles (13- 80%) are specific for the diagnosis of miliary tuberculosis
- Miliary lesions are usually small (2-3 mm) when first seen in chest X-ray
but may coalesce to form larger lesions.
C. Abdominal and GIT TB:
- Tuberculous Peritonitis:
presents with fever, ascites & doughy abdomen (matted omentum).
- Tuberculous enteritis:
affects the terminal part of small intestine causing shallow ulcers that presents with;
pain, diarrhea, weight loss.

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Kareem Alnakeeb
D. Central nervous system TB :
- Tuberculous meningitis is the most serious complication that occurs mostly
between 6 months and 4 years.
- The course may be rapid (infants) but more commonly is gradual & divided into 3 stages:
i. 1st stage Lasts 1-2 weeks
Characterized by nonspecific symptoms such as fever, headache, irritability,
Focal neurologic signs are absent
ii. 2nd stage Lethargy, seizures
Meningeal signs: nuchal rigidity, positive kernig and brudzinski signs
Cranial nerve palsies,
Other focal neurologic signs.
iii. 3rd stage Coma, deterioration of vital signs, and eventually death.
 Radiographic studies can aid in the diagnosis of TB meningitis.
- CT or MRI of the brain may be normal during early stages
E. TB Choroiditis
Figure: CT brain of TB meningitis
There is a round lesion deep in the right
hemisphere, with ring enhancement.
The ventricles are grossly enlarged, and
the sulci over the hemispheres widened.
Figure: TB Choroiditis
This picture of an optic funds shows fluffy patches
due to localized tuberculous lesions in the choroid.
In the older literature these were stated to be
present in 60% of cases of TBM and miliary TB.

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Infection 2018
Kareem Alnakeeb
F. Genitourinary TB :
 Renal TB :
- Rare in children
- often clinically Silent in its early stages, marked only by sterile pyuria
- Dysuria, flank pain, hematuria develop as the disease progresses.
- Hydronephrosis or ureteric strictures complicate the disease.
 Fallopian tube, endometrium, ovaries, epididymis may be rarely involved in adolescents.
G. Skin Disease
- Raised, tender, bruise-like areas over the shins
(erythema nodosum a phenomenon of hypersensitivity)
H. • Skeletal tuberculosis:
- Constitute 1-3% of all TB cases & 10% of extrapulmonary TB.
- Skeletal TB may be:
• Spinal TB (50%).
• TB arthritis (40%).
• TB osteomyelitis:
 Metaphyseal (9%).
 Diaphyseal (1%).
- Bone and joint infection complicating tuberculosis is most likely to involve the vertebrae.
- The classic manifestation of tuberculous spondylitis is progression to Pott disease,
in which destruction of the vertebral bodies  gibbus deformity and kyphosis
Figure: Gibbus deformity due to
pott’s disease 3500 years a.c.

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Kareem Alnakeeb
- Tuberculous dactylitis:
• Successive periosteal layers,
• Bone destruction,
• Cyst like cavities,
• Ballooning of phalanges
• Medical history
• Physical examination
• Mantoux tuberculin skin test (TST)
 for latent infection, NOT for active TB
• Chest radiograph
• Bacteriologic or histologic exam
 Microscopy
 Culture (ordinary or BACTEC).
 DNA based detection
- 3 sputum specimens for smear examination and culture
- Persons unable to cough up sputum
o bronchoscopy
o gastric aspiration
- Follow infection control precautions during specimen collection
Tuberculin (Mantoux) skin test
- Inject 0.1 ml (5 TU tuberculin units) of PPD tuberculin intradermally
- Produce wheal 6 mm to 10 mm in diameter
- Do NOT recap, bend, or break needles, or remove needles from syringes
- Follow universal precautions for infection control
- Read reaction 48-72 hours after injection
- Measure only induration
- Record reaction in millimeters
Evaluation for TB:
Specimen collection:
Reading:
Figure Ordinary T.B culture
TB colonies that appear after 2-3 weeks.

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Infection 2018
Kareem Alnakeeb
Skin test positive:
>5 mm induration • Contacts of TB cases,
• HIV, immune suppression
• Clinical/CXR suspicion of TB disease
>10 mm induration In high-risk population:
• persons in high prevalence countries,
• medical conditions,
• children < 4 years exposed to adults in high risk categories
>15 mm induration In low-risk population
False positive False negative
• Nontuberculous mycobacteria
• BCG vaccination
• Very young age (< 6 months old)
• Live-virus vaccination
• Recent TB infection
• Overwhelming TB disease
• Anergy
TB exposure TB infection TB disease
- Significant contact with an adult or
adolescent with infectious TB
e.g. household, daycare, schools
- up to 3 months for conversion
(maybe infected & develop TB disease rapidly)
 Negative tuberculin skin test
 Normal Chest x-ray
- occurs after inhalation of
droplet nuclei containing M.
TB, which survive
intracellularly within lung &
lymphoid tissue.
 Positive tuberculin skin test,
 Normal Chest x-ray
occurs when signs
or symptoms or
radiographic
manifestations
caused by M. TB
become apparent.
- In the past, treatment was based on isolation, nutritional support and sun exposure.
- Currently, If TB is suspected, prior to receiving TB culture results, treatment must be initiated
 There are five first-line TB drugs: mnemonic: RESPIratory
Rifampin, Ethambutol, Streptomycin, Pyrazinamide, Isoniazid (INH).
Interpretation:
Factors affecting PPD reaction:
Tuberculosis clinical stages:
Treatment of Tuberculosis:

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Drug Dose
(mg/kg/day)
MAX Dose Method Side effects
Isoniazid (INH) 10-15 300 mg Oral  Induce Hypersensitivity
 peripheral Neuropathy (vit B6)
 Hepatotoxicity
 Seizures, psychosis
Rifampin (Rif) 15-20 600 mg Oral  GIT Irritation
 Red/orange urine
 Hepatotoxicity
 drug interactions
( cytochrome P-450)
 Thrombocytopenia
Streptomycin (SM) 20-25 1 g IM  Ototoxicity
 Nephrotoxicity
Ethambutol (ETB) 15-25 2.5 g Oral  Optic neuropathy
(red-green color blindness)
 GIT Irritation
 Hypersensitivity
Pyrazinamide (PZA) 15-30 2 g Oral  Hyperuricemia
 Hepatotoxicity
Diagnosis Treatment
TB Infection  INH – 9 months
TB Disease  First 2 months – 4 drugs
Rifampin, Isoniazid, Pyrazinamide, Ethambutol or
streptomycin
 Next 4 months – 2 most effective sensitive drugs
(Rifampin, Isoniazid in pansensitive cases)
Multidrug resistant TB Disease
(resistance to at least INH & RIF)
Treat with sensitive drugs (varies) for at least 18 months
Extrapulmonary tuberculosis Same regimens as pulmonary disease.
Disseminated tuberculosis 4th
drug is recommended in the initial phase
The recommended duration is 9–12 months
NB. Corticosteroid treatment is a useful adjunct in treating some forms of extrapulmonary
tuberculosis, specifically meningitis and pericarditis caused by drug-susceptible organisms
Usual pediatric treatment regimens:

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• Case finding and treatment.
• Screening of close contacts
• BCG vaccine:
- Given I.D in the left arm during the first month of life.
- Variable efficacy in different studies ranging from 0-80%.
- Side effects include;
 local ulceration, regional lymphadenitis, rarely osteitis,
 Dissemination in immunocompromised
 Interference with skin test results (False positive)
Prevention: