PAEDIATRIC TUBERCULOSIS

DR (MRS) M.B. FETUGA

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
DR (MRS) M.B. FETUGA 2

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
DR (MRS) M.B. FETUGA 3

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 DR (MRS) M.B. FETUGA 4

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
DR (MRS) M.B. FETUGA 5

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
DR (MRS) M.B. FETUGA 6

TRANSMISSION CONTD
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
DR (MRS) M.B. FETUGA 7

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 DR (MRS) M.B. FETUGA

COURSE OF TB CONTD
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
DR (MRS) M.B. FETUGA 9

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
DR (MRS) M.B. FETUGA 10

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
DR (MRS) M.B. FETUGA 11

PATHOGENESIS CONTD
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 lobesDR (MRS) M.B. FETUGA 12

PATHOGENESIS CONTD
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 + calcifications Some may be dormant & later re-activates DR (MRS) progressive M.B. FETUGA 13 Some may be locally

PATHOGENESIS CONTD
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. DR (MRS) M.B. FETUGA 14

PATHOGENESIS CONTD
20 or adult type with cavitatn with reactivatn of dormant focus or reattack-erosion into a bronchusexpectoratn of tubercle 20 dx spreads by local extensn & not thro LN or bld Hypersensitivity accts for much of symptomatology of chidhood TB
DR (MRS) M.B. FETUGA 15

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
DR (MRS) M.B. FETUGA 16

WALLGREN TABLE CONTD

5.Within

3 years: TB of bones & joints 6.Within 5 years: Progressive Pulmonary TB 7.After 5 years: Urogenital TB
DR (MRS) M.B. FETUGA 17

PROGRESSION
1.Tuberculous pneumonia 2.Consolidation 3.TB Pleural Effusion 4.Atelectasis / Emphysema - pressure 5.Endobronchial TB 6.Bronchogenic spread =TB bronchopneumonia 7.Haematogenous spread =Disseminated TB 8.Cavitation from excessive caseation 18 DR (MRS) M.B. FETUGA

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
DR (MRS) M.B. FETUGA 19

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 DR (MRS) M.B. FETUGA 20

 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

DR (MRS) M.B. FETUGA 21

DIAGNOSIS CONTD
-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) DR (MRS) M.B. FETUGA 22

DIAGNOSIS CONTD
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 wks 3.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 M.B. FETUGA days before mealDR &(MRS) the aaspirate is sent for Z-N 23 stain

DIAGNOSIS CONTD
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 68 weeks in a normal BCG reaction.

DR (MRS) M.B. FETUGA

24

DIAGNOSIS CONTD
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)
DR (MRS) M.B. FETUGA 25

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
DR (MRS) M.B. FETUGA 26

PULMONARY TB
The commonest form of TB occurring alone or in combination in > 70% of cases. PTB = Primary Complex + Direct Local Spread Presents either as Consolidation, Pneumothorax, Atelectasis or Pleural Effusion.

DR (MRS) M.B. FETUGA

27

Pulmonary Tb contd.
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. DR (MRS) M.B. FETUGA 28

Pulmonary TB contd.
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.
DR (MRS) M.B. FETUGA 29

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). DR (MRS) M.B. FETUGA 30

Miliary TB
May be fulminant with severe dyspnea & wheezing. Choroidal Tubercules are pathognomonic CXR = bilateral miliary mottling + infiltrations : Differential Diagnosismycotic pneumonia, chickenpox pneumonia, eosinophilic pneumonia, childhood histiocytosis, idiopathic pulmonary haemosiderosis, sarcoidosis, fibrolysing alveolitis. DR (MRS) M.B. FETUGA 31

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 Riches focus at or near the surface of the brain enlarges, caseates, ruptures & discharges caseous materials into the subarachnoid space provoking DR (MRS) M.B. FETUGA 32 hypersensitivity reactions.

TB Meningitis contd.
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.

DR (MRS) M.B. FETUGA

33

TB Meningitis contd.
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.
DR (MRS) M.B. FETUGA 34

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 involvement The anterior part of the vertebral body is usually affected Presentation: Back pain, difficulty in flexing the spine, abnormal gait (walking on eggs), Kyphosis, scoliosis, paraplegia (spastic or flaccid.) DR (MRS) M.B. FETUGA 35

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.
DR (MRS) M.B. FETUGA 36

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.
DR (MRS) M.B. FETUGA 37

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.
DR (MRS) M.B. FETUGA 38

Lymphatic Gland TB contd.

Differrential Diagnosis of Lymphatic TB: Pyogenic adenitis Atypical Mycobacterium Complex (AMC) adenopathy Hodgkins lymphoma Leukaemia Toxoplasmosis

DR (MRS) M.B. FETUGA

39

MANAGEMENT OF PAEDIATRIC TB

AIMS OF MANAGEMENT: - To achieve cure - To reduce transmission - To prevent relapse.

DR (MRS) M.B. FETUGA

40

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.
DR (MRS) M.B. FETUGA 41

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.
DR (MRS) M.B. FETUGA 42

WHY DOT(S)
DOT- Directly Observed Therapy DOTS- 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.
DR (MRS) M.B. FETUGA 43

WHO SHOULD DO DOTS?

Medical & Paramedical Personnels Community Health Workers Community Leaders Relations of the patient Important qualities include: - must be concerned about the course - must have influence on the patient - must be accountable to the health system DR (MRS) M.B. FETUGA

44

CASE DEFINITION
Primary TB-involving lung parenchyma Extra-pulmonary TB-involving other parts of the body apart from lung parenchyma Intra-thoracic -TB adenopathy, TB pleural effusion are extra-pulmonary TB Disseminated TB = Pulmonary TB + TB of at least one other organ-system + choroidal tubercules
DR (MRS) M.B. FETUGA 45

Case Definition contd.

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.
DR (MRS) M.B. FETUGA 46

Case Definition contd.

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 retreatment regimen.
DR (MRS) M.B. FETUGA 47

Indications for Hospitalization.

To initiate chemotherapy For life threatening complications like severe haemoptysis Severe forms of TB eg. TB meningitis For investigations eg. Excisional biopsies For surgical management eg. Lobectomy, laminectomy, I & D for abscesses. Lack of social supports & possibility of poor compliance. Defaulters.
DR (MRS) M.B. FETUGA 48

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%.
DR (MRS) M.B. FETUGA 49

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)
DR (MRS) M.B. FETUGA 50

NTBLCP IN NIGERIA CONTD.

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.
DR (MRS) M.B. FETUGA 51

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.
DR (MRS) M.B. FETUGA 52

CLASSES OF DRUGS CONTD

Bacteriostatic: TE are examples Second generation anti-TB drugs: -cycloserine -para-amino salicylic acid -quinolones -kanamycin -ethionamide -capreomycin
DR (MRS) M.B. FETUGA 53

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

DR (MRS) M.B. FETUGA

54

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
DR (MRS) M.B. FETUGA 55

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
DR (MRS) M.B. FETUGA

56

Special Situations in TB contd

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.

DR (MRS) M.B. FETUGA

57

Prevention of TB
Case finding & effective treatment Contact 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
DR (MRS) M.B. FETUGA 58

Prevention of TB contd.
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.
DR (MRS) M.B. FETUGA 59

HIV/AIDS & TB
HIV increases the burden of TB Exact picture in children is unknown Among 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.
DR (MRS) M.B. FETUGA 60

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
DR (MRS) M.B. FETUGA 61

HIV & CLINICAL TB CONTD.

Increased chances of progression to active disease Accelerated progression Death occurs earlier without treatment More cases of extra-pulmonary involvement Formidable diagnostic difficulties Increased rate of MDR & difficulty with achieving cure.
DR (MRS) M.B. FETUGA 62

How HIV affects TB control

Over diagnosis of smear negative TB Under diagnosis of smear positive TB Low cure rate High Case Fatality Ratio High default rate from adverse drug effects eg. Dermatitis from T therapy Increased emergence of MDR
DR (MRS) M.B. FETUGA 63

Differential Diagnosis of PTB in HIV-infected children

Bacterial Pneumonia Viral Pneumonia (Cytomegalovirus) Fungal Pneumonia (Cryptococcus) Pneumocystis carinii pneumonia Lymphocytic Interstitial pneumonia Pulmonary Lymphoma

DR (MRS) M.B. FETUGA

64