Tuberkulosis

DR (MRS) M.B. FETUGA 1

PAEDIATRIC TUBERCULOSIS


HISTORICAL FACTS

• 1882- Robert Kochs described the bacilli

• 1920- BCG was developed• 1948- Use of Streptomycin in the

treatment of TB was commenced• 1952- Isoniazid (H) was introduced in

the treatment of TB


AETIOLOGY OF TB

Mycobacterium tuberculosis-Genus M, sp. tb

-acid & alcohol fast bacilli (waxy outer capsule)

-non motile -non sporulating -aerobic -produces no exotoxin or endotoxin - causes disease by invoking immune

reactions Mycobacterium bovis


EPIDEMIOLOGY OF TB

• About a third of the world population is infected

• 30% of those who develop the disease live in Africa

• TB causes 25% of all preventable deaths in developing countries

• 95% of TB cases & 98% of TB deaths occur in the developing world

• Exact incidence is unknown in Nigeria but 25,000 new cases are reported annually

• Under-5 children & adolescents are more at risk


RESURGENCE OF TB

• Civil wars, strife and conflicts• Increasing poverty, malnutrition and

overcrowding• HIV pandemic• Collapse of the various National TB

Control Programmes• Multi Drug Resistance


TRANSMISSION

• TB is a vaccine-preventable killer disease• Source is usually an adult with smear

pos. TB• Childhood TB is =5-15% of all TB cases• Children usually not infectious:

- often not smear pos.

. TB in children reflects the failure to control TB among adults


TRANSMISSION C’ONTD

• Inhalation of Infected droplets by sneezing, coughing and talking

• Drinking milk infected by M. bovis (cattle TB)• Abrasions on the skin & mucous membranes• Perinatally acquired TB- very rare: -TB bacillaemia can spread to the fetus - Placental TB can spread to the fetus - endocervical TB can spread by aspiration - early neonatal exposure secondary to care

by the infected mother


COURSE OF TB

• TB infection= presence of bacilli (mantoux pos.) but without clinical or radiological features

• TB disease= presence of bacilli (mantoux pos.) + clinical and/or X-Ray features

• Majority of children with TB infection do not develop TB disease

• Chances of progression to disease is greatest shortly after infection & steadily decreases as time goes by


COURSE OF TB C’ONTD

• Risk factors for the progression of TB infection to disease:

-HIV infection -Age->ter extent of glandular involvement -Malnutrition especially, kwashiorkor -Debilitating infections like Measles & Pertussis -Diabetes mellitus -Indiscriminate steroid use -Malignancies & cyto-toxic therapy -Physical & Emotional stress


COURSE OF TB CONTD

• Frequent intense exposure results in more severe infection

• Overcrowding-more freq exposure• Poor vent- > conc of bacilli• Children usually acquire TB from an

infectious parent or close contact• BCG vacc protects against severe forms

of TB


PATHOGENESIS OF TB

• Primary TB is the first phase of infection with M.tuberculosis

• It occurs mainly in the under-5 . The younger the child, the higher the severity of the local reactions

• Lungs are the sites of Primary TB in >98%• Ghon focus is formed when the bacilli settles

in the alveoli with inflammation • Histiocytes carry the multiplying bacilli

through lymphatic channels to regional lymph nodes


PATHOGENESIS C’ONTD

• Ghon focus + Lymphatic channels + Nodes = Primary Complex or Ghon complex

• Silent bacteraemia follows Primary Complex causing metastatic foci in the lung apices, vertebrae, meninges, kidneys

• Development of Delayed Hypersensitivity (by T lymphocytes) follows in the next 2-8 weeks. Cell Mediated Immunity is formed & patient becomes mantoux positive

• Ghon focus is usually subpleural in the mid-& lower lung lobes



• Muco-cutaneous manifestations of Primary TB include:

-Erythema nodosum (painful, red patches in the inner side of leg & foreman)

-Phlyctenular conjuctivitis (small yellowish elevation of the conjuctiva at the edge of the cornea & surrounded by conjuctival vessels

Majority heals + calcificationsSome may be dormant & later re-activates Some may be locally progressive



• Acute dissemination may also follow• Risk of Primary TB progressing to active

TB = 5-15%• Progression occurs when host resistance

is poor, otherwise, the bacilli initially disseminated are killed or they remain dormant

• When healing of the Primary Complex occurs, it is less in the nodes than in the lung parenchyma, hence the nodes are the sites of re-activation later in life.


PATHOGENESIS CONTD

• 20 or adult type with cavitatn with reactivatn of dormant focus or re-attack-erosion into a bronchus- expectoratn of tubercle

• 20 dx spreads by local extensn & not thro LN or bld

• Hypersensitivity accts for much of symptomatology of chidhood TB


WALLGREN TIMETABLE

1.Incubation period: 3-8 weeks

2.Within 3 mo of primary TB:

-Miliary TB & TB Meningitis

3.Within 3-9 mo:

-TB of Lymph Glands

4.Within 1 year:

-TB Pleural Effusion


WALLGREN TABLE C’ONTD

5.Within 3 years:

TB of bones & joints

6.Within 5 years:

Progressive Pulmonary TB

7.After 5 years:

Urogenital TB


PROGRESSION 1.Tuberculous pneumonia2.Consolidation3.TB Pleural Effusion4.Atelectasis / Emphysema - pressure5.Endobronchial TB6.Bronchogenic spread =TB

bronchopneumonia7.Haematogenous spread

=Disseminated TB8.Cavitation from excessive caseation


PROGRESSION

• Healing occurs in most cases (fibrosis & calcification may occur)

• Caseating hilar LNs may burst into pulm vein- miliary dx, TBM

• Host factors determine response to infection; Overt & severe dx likely in malnourished, 20infectns like measles, HIV eg TBM, miliary or progressive I0 dx


DIAGNOSIS OF TB

1.Tuberculin test: -based on delayed hypersensitivity to

tuberculin i.e. asseses cellular imm resp -detects the presence of Mycobacterium

either from vaccination or from natural infection -

-0.1 ml of 5 t.u PPD & read in 48-72 hrs -induration >10mm suggests infection -induration >20mm suggests disease


• Intradermally, very small gauge needle (27G), too deep – false –ve

• look for presence of wheal as fluid is injected

• Read induration in 48-72hrs• BCG effect-most in 3-6/12, wanes by 2-3yrs

• Heaf test- easier, < accurate-multiple puncture


DIAGNOSIS C’ONTD

-Tuberculin reaction to BCG is weaker & last shorter than that to natural infection

- Pos. Tuberculin : >10mm in a child without BCG

- Pos. Tuberculin: >15mm in a child with BCG

- Neg. Tuberculin: <10mm does not exclude TB (HIV, malnutrition, severeTB, viral infections, steroid use, malignancies)


DIAGNOSIS C’ONTD

2. Sputum testing: difficult in children - collection by gastric washing &

bronchoalveolar lavage - Ziehl- Neelsen stain (low yield on other body

fluids) - culture on Lowenstein Jensen medium for 6-8

weeks & sensitivity testing over another 2-4 wks3.CXRay- no pathognomonic feature; widened

superior mediastinum suggestive of TB Cavitations unusual in children unless with HIV

co-infection 4. Gastric washing is done by lavaging the gastic

content every morning for three consecutive days before meal & the aaspirate is sent for Z-N stain


DIAGNOSIS C’ONTD

5.Serology:More rapid, sensitive but expensive and not available for routine use eg. ELISA, PCR, DNA Probes

6. Accelerated BCG reaction: - to be used when 100 t.u PPD fails - induration in 48hrs, pustule on 3rd day,

scab in 6 days & scar in 2 weeks unlike 6-8 weeks in a normal BCG reaction.


DIAGNOSIS C’ONTD

• 7. Biopsies of tissues eg lymph nodes, peritoneum, pleura, bone usually for:

-microscopy (Z-N Stain)

-culture

-histology for tubercules & caseating lesions

. 8. Endoscopic examinations (peritoneoscopy, bronchoscopy etc)


CATEGORIES OF DIAGNOSIS

• 1. Suspected TB- suspicious Chest X-Ray findings

• 2. Probable TB- suspicious CXR in addition to either : weight loss/ history of contact/ strongly positive tuberculin

• 3. Confirmed TB- Positive culture of M. tuberculosis


PULMONARY TBThe commonest form of TB occurring

alone or in combination in > 70% of cases.PTB = Primary Complex + Direct Local

SpreadPresents either as Consolidation,

Pneumothorax, Atelectasis or Pleural Effusion.


Pulmonary Tb c’ontd.

Effusion in TB may be due to:@ immune reaction to the tuberculoprotein @rupture of a sub-pleural focus into the pleural space @ haemogenous spread @ CCF @ TB Constrictive Pericarditis

Management of TB Effusion include @ anti TB drugs @ Steroids. TUBE DRAINAGE IS NOT DONE EXCEPT IN CASES OF SEVERE RESPIRATORY DISTRESS !!

TB Effusion is reportedly uncommon in Africa because the immune system is pre-occupied with many other antigenic stimulation.


Pulmonary TB c’ontd.

Usually vague symptoms: fever, chronic cough, weight loss, anorexia, night sweat, dyspnea, localized wheezing.

Presentation with haemoptysis, which is common among adults is uncommon in children.


Miliary TB

Most severe form of disseminated TB

Common in under-5 usually within the first 3 months of infection.

Follows haematogenous dissemination of a large dose of the bacilli to many body tissues

Presentation is variable depending on the load of bacilli, immunity & the organ involved

May be insidious (with anorexia, weight loss, fever & generalized lymphadenopathy).


Miliary TB

May be fulminant with severe dyspnea & wheezing.

Choroidal Tubercules are pathognomonic

CXR = bilateral miliary mottling + infiltrations : Differential Diagnosis- mycotic pneumonia, chickenpox pneumonia, eosinophilic pneumonia, childhood histiocytosis, idiopathic pulmonary haemosiderosis, sarcoidosis, fibrolysing alveolitis.


TB Meningitis

Gravest form of TB whose prognosis depends on the rapidity with which the diagnosis is made.

Metastatic cerebral foci may manifest immediately after Primary infection or may re-activate many years later.

The Riche’s focus at or near the surface of the brain enlarges, caseates, ruptures & discharges caseous materials into the subarachnoid space provoking hypersensitivity reactions.


TB Meningitis c’ontd.

Pathology: @ Cerebral oedema @ vasculitis & neuritis @ cerebral infarcts.

Presentation in 3 stages: I- Irritability, fever, lethargy II- Features of cerebral involvement &

raised Intracranial Pressure (vomiting, drowsiness, mental changes, seizures, meningeal signs)

III- Multiple CNS signs & coma.


TB Meningitis c’ontd.

Outcome: Stage I- mortality 3%, sequelae 13% Stage II- mortality 14%, sequelae 26% Stage III- mortality 30%,sequelae 42% Investigation: CSF chemistry- low glucose CSF culture- positive in 75% CSF microscopy - low yield (about 20%) Prognosis depends on the stage of

disease at commencement of therapy.


Spinal TB

Commonest & most important bone/joint TB.Usually involves the mid & lower thoracic

spinal segments. Rarely affects the lumbar & cervical areas.

Single or multiple vertebral involvementThe anterior part of the vertebral body is

usually affectedPresentation: Back pain, difficulty in flexing

the spine, abnormal gait (walking on eggs), Kyphosis, scoliosis, paraplegia (spastic or flaccid.)


Spinal TB

Paralysis is spastic when there is cord compression & flaccid when there is cord infiltration and destruction. SPASTIC PARAPLEGIA CARRIES A BETTER PROGNOSIS THAN FLACCID PARALYSIS!

Psoas abscess follows lumbar segment TB while retropharyngeal abscess follows cervical segment TB.

Spinal TB X-Ray= reduced intervertebral spaces, destruction of vertebrae & paraspinal shadows. ***Immobilization in Meniever Spinal Jacket is no longer used.


Abdominal TB

May be part of the Primary disease or may follow PTB

Affects the mesentery & retroperitoneal glands, omentum & the intestine.

Different forms include @ Hyperplastic TB @ TB enteritis @ TB mesenteric adenitis @ TB peritonitis @ Mixed abdominal TB

Presents as abdominal mass, ascites, intestinal obstruction, enteritis & malabsorption.

Doughy abdomen due to the mass formed by the matted omentum & intestine , NOT to ascites.


Lymphatic Gland TB

Primary focus may be in the tonsillar bed or other parts of the oro-pharynx.

Spreads to involve the cervical, submandibular & supraclavicular nodes.

May be unilateral or bilateral. Glands are discrete, mobile, firm & non tender. They become matted if there is periadenitis May rupture through its capsule & leave a

discharging sinus Typically, no constitutional symptoms.


Lymphatic Gland TB c’ontd.

Differrential Diagnosis of Lymphatic TB:

Pyogenic adenitisAtypical Mycobacterium Complex

(AMC) adenopathyHodgkins lymphomaLeukaemiaToxoplasmosis


MANAGEMENT OF PAEDIATRIC TB

• AIMS OF MANAGEMENT:

- To achieve cure

- To reduce transmission

- To prevent relapse.


TB MANAGEMENT New trends in the management of TB aimed at

combating the resurgence in the prevalence of TB include :

CASE DEFINITION- -for registration & notification -for cohort analysis -to prioritise treatment DIRECTLY OBSERVED THERAPY- -to achieve good drug compliance -to reduce chances of resistance -to increase the cure rate in TB.


Components of DOT

Identify the source of infection i.e smear positive cases with good laboratory methods.

Observe the swallowing of the drugs especially during the initial phase.

Monitoring the progress of each case with monthly sputum microscopy.

Provision of the right drug in adequate quantity.

Supports from govt. agencies & NGOs.


WHY DOT(S)

DOT- Directly Observed TherapyDOTS- Directly Observed Treatment Short

Course.Aim is to achieve adherence & prevent

non-compliance.Necessary to protect Rifampicin which is

the only reliable sterilizing anti-TB drug without significant resistance.

IT IS COMPULSORY TO USE DOTS WHEN RIFAMPICIN IS PRESCRIBED.


WHO SHOULD DO DOTS?

Medical & Paramedical PersonnelsCommunity Health WorkersCommunity LeadersRelations of the patientImportant qualities include:

- must be concerned about the course

- must have influence on the patient

- must be accountable to the health system


CASE DEFINITION

Primary TB-involving lung parenchymaExtra-pulmonary TB-involving other parts of

the body apart from lung parenchymaIntra-thoracic -TB adenopathy, TB pleural

effusion are extra-pulmonary TBDisseminated TB = Pulmonary TB + TB of at

least one other organ-system + choroidal tubercules


Case Definition c’ontd.

Severe Extra-pulmonary TB = Miliary TB, TB Meningitis, TB pericarditis, biilateral TB effusion, Tb peritonitis & spinal TB.

Non severe Extra-pulmonary TB = skin TB, Lymphatic TB, bone &joints TB

New Case = smear positive & never treated for more than one month.

Relapse = previously declared cured after full treatment for TB & later sputum positive.


Case Definition c’ontd.

Failure: If still smear positive after 5months of treatment or becomes smear positive again after initial sero-conversion while still on treatment.

Chronic case: Remain or becomes smear positive again after a full course of re-treatment regimen.


Indications for Hospitalization.

To initiate chemotherapyFor life threatening complications

like severe haemoptysisSevere forms of TB eg. TB

meningitis For investigations eg. Excisional

biopsiesFor surgical management eg.

Lobectomy, laminectomy, I & D for abscesses.

Lack of social supports & possibility of poor compliance.

Defaulters.


CHEMOTHERAPY

Mainstay is combination therapy to reduce the risk of drug resistance

HR for 6months is recommended worldwide for all pulmonary & extra-pulmonary TB.

Z must be added in the first 2 months.For extra-pulmonary TB, when R cannot

be used for more than 2 months, then treatment should be for at least 9 months with other drugs.

A fourth drug, E or S is used in places with resistance to that is greater than 10%.


NTBLCP IN NIGERIA

2 phases of treatment: - Initial phase usually 2 months to kill

the largest proportion of the bacilli - Continuation phase between 4 & 10

months to ensure cure & prevent relapse.

Short Course Chemotherapy: -usually 8 months -for new smear positive cases -RHZS daily for 2 months (initial phase) TH daily for 6 months(or RH daily for 4

months)


NTBLCP IN NIGERIA C’ONTD.

Re-treatment regimen (8months): -for relapses, defaults & failures -SERZH daily for 3 months (skip only

S in the third month) -RHE thrice weekly for 5 months.Standard regimen(12months): -for smear negative cases & for

those in whom compliance is likely to be poor.

-SHT daily for 2 months -TH daily for 10 months.


CLASSES OF DRUGS

Bactericidal: - H kills 90% of bacilli within a few

days - H active on metabolically active

bacilli - R kills semi-dormant bacilli which

H cannot kill - Z kills bacilli only in acid

environment eg. in macrophages Sterilizing drug: - kills all population , active or

dormant - R is the most effective drug in this

group.


CLASSES OF DRUGS C’ONTD

Bacteriostatic: TE are examples Second generation anti-TB drugs: -cycloserine -para-amino salicylic acid -quinolones -kanamycin -ethionamide -capreomycin


Drug Resistance

Natural : a wild strain which has never been in contact with the drug

Acquired/Secondary : resistance develops after initial sensitivity to the drug

Primary : bacilli with acquired resistance infecting a new host

Multi-drug resistance – resistance to multiple drugs including H & R


Indications for Adjuvant Steroid Therapy in TB

TB Meningitis TB Pericarditis TB Pleural Effusion TB Laryngitis Endobronchial TB Severe hypersensitivity reactions to

drugs Massive TB lymphadenopathy causing

pressure symptoms Renal Tract TB (to prevent ureteric

scarring) Miliary TB


TB in Special Situations

Therapeutic trial with H, Z, PAS when diagnosis is not obvious & TB is strongly suspected.

Chronic renal failure: -use only HRZ & avoid SET Chronic liver diseases: -use only HSE & avoid RZ Drug-induced hepatitis: -stop all the drugs -after resolution, start all over again

with 2SHE + 10HE


Special Situations in TB c’ontd

Infant of a mother with TB: -Start the baby on H as soon as

positive -When mother is smear negative for

3 consecutive months, do mantoux test for baby

-If mantoux is negative, stop H & give BCG

-If mantoux is positive, do CXR -If CXR is normal, give H for total of 9

months -If CXR is abnormal, treat baby as a

TB case. -Allow breastfeeding & rooming-in.


Prevention of TB

Case finding & effective treatmentContact tracing & H

chemoprophylaxis - all contacts with positive

mantoux but no clinical or CXR feature should have H for 6 months

-under-5 contacts with negative mantoux should have H after 3 months. If repeat mantoux is negative, stop H; if positive, give H for the total of 6 months

BCG vaccination


Prevention of TB c’ontd.

BCG vaccination: - give as soon in the first week of

life as possible -no scientific basis for multiple

vaccination - 0-80% efficacy (50% on the

average) -protects against the severe forms

of TB like TB Meningitis -give to HIV infected children in

Africa but avoid it if they are symptomatic.


HIV/AIDS & TB

HIV increases the burden of TBExact picture in children is

unknownAmong adults: - 70% of TB/HIV dually infected

people live in Sub-Saharan Africa, - HIV is the most potent factor

aiding the progression of tuberculosis infection to disease

- 30-70% of TB patients in Sub Saharan Africa are positive.


HOW HIV AFFECTS CLINICAL PICTURE OF TB

In children, the natural history of TB depends on the stage of HIV disease

Early in HIV, TB is similar to that in children without HIV

Late in HIV, TB tends to be severe & disseminated

Early in HIV, it resembles Post Primary TB, smear positive & CXR shows cavities

Late in HIV, it resembles Primary TB, smear negative & CXR shows infiltrates

Avoid T in TB therapy & replace it with E or S


HIV & CLINICAL TB C’ONTD.

Increased chances of progression to active disease

Accelerated progressionDeath occurs earlier without

treatmentMore cases of extra-pulmonary

involvementFormidable diagnostic difficultiesIncreased rate of MDR & difficulty

with achieving cure.


How HIV affects TB control

Over diagnosis of smear negative TB

Under diagnosis of smear positive TB

Low cure rateHigh Case Fatality RatioHigh default rate from adverse

drug effects eg. Dermatitis from T therapy

Increased emergence of MDR


Differential Diagnosis of PTB in HIV-infected children

Bacterial PneumoniaViral Pneumonia

(Cytomegalovirus)Fungal Pneumonia

(Cryptococcus)Pneumocystis carinii

pneumoniaLymphocytic Interstitial

pneumoniaPulmonary Lymphoma

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