CLINICAL ASPECTS OF PAEDIATRIC

TUBERCULOSIS

Dr . Arun Kumar.TKarpagam Faculty of Medical Sciences

and Research

Primary infection • Compared to adults, children:

– TB infection occurs for first time– Tend to develop primary active TB more

often after initial infection (0-4yrs)– Are more likely to have extrapulmonary

disease, especially TB meningitis (0-4yrs)

– More lymphnode involvement– Are more likely to have disseminated

TB infection– Are less contagious

• Paucibacillary disease (fewer organisms)• Cannot cough/spread infection as well

Children vs. Adults Cavitatory TB uncommon Majority of deaths by EPTB Are more difficult to diagnose

• May not show typical symptoms

Children vs. Adults In adults, - regional lymphadenitis less

marked - bronchial erosion less frequent - less risk of dissemination - infectious - Cause of death - PTB Thus, adult primary infection

tends to be more local and pulmonary.

Risk factors in children Age < 1yr Steroid therapy Malnutrition Intercurrent infections:

Measles,whooping cough Immunocompromised state Environment : overcrowding,

inadequate ventillation, damp, insanitary and unhygenic conditions

TB infection and disease Infection (LTBI)

Contact w/ infectious pulmonary TB (adult) Child asymptomatic TST +, CXR normal

Disease Contact w/ infectious pulmonary TB TST+/- Child symptomatic or CXR positive for TB

TB overview: infection and disease

– Risk of infection depends on disease burden in the index case, proximity and duration of exposure

– Household exposure from adult with active disease is strongest source

Primary tuberculosis Primary TB infection -acquiring TB directly

after exposure to someone with active disease

Inhaled TB bacilli penetrate into lungs and settle- ”set up shop”

Parenchymal (Ghon) focus develops- At the site of first implantation

- usually single and Subpleural - mostly - heals and disappears, or

fibroses or calcifies Bacilli drain to regional nodes Upper lobes to paratracheal nodes Middle and lower lobes to hilar nodes

Primary tuberculous infection Infection is contained in a small area without

spread or replication (latent TB infection or LTBI) These individuals are not infectious to anyone

Primary Complex: primary focus + lymphangitis +lymphadenitis.

complications arise more commonly from regional adenitis than from the primary focus

Progressive primary complex

Progressive primary infection: Progression of recently acquired pulmonary primary infection

Progression depends on age of the child, number of tubercle bacilli, and host resistance.

Apparently healed focus or nodes may contain viable organisms for many years.

During 1st 4-8 weeks, organisms are disseminated in the blood stream.

Progressive primary complex

Incomplete bronchial obstruction with ball valve thrombus leads to Obstructive emphysema.

Aspiration of caseous material results in bronchopneumonia, consolidation.

Complete obstruction results in collapse of lung distal to the obstruction or collapse consolidation.

Secondary tuberculosis(adult type

of TB) All active tuberculosis which occur after primary infection due to Endogenous reactivation or Exogenous reinfection

Cavity formation seen in lung apices.

Cavitating tuberculosis seen in younger children due to high adult TB incidence in community.

Clinical features Physical manifestations differ by age

of onset Less compared to degree of

radiographic changes Majority develop no signs or

symptoms Young infants & adolescents more

likely to have significant symptoms. Infants --- smaller airways School age children often have

clinically silent disease

Symptoms Primary complex – mild fever,

anorexia, weight loss, decreased activity, cough

Progressive primary complex – high grade fever, cough. Expectoration and hemoptysis – usually associated with cavity and ulceration of bronchus. Abnormal chest signs – decreased air entry, dullness, crepts

Symptoms

Pleural effusion -follows a rupture of a subpleural

focus. -Also by hematogenous spread from

primary focus. Fever, cough, dyspnea, pleuritic chest pain.

Radiology In extra pulmonary tb, presence of lesions

on chest radiograph supports diagnosis. Enlarged lymph nodes in hila, right

paratracheal region Consolidation in progressive primary

disease – heterogenous, poorly marginated with predilection to apical or posterior segments of upper lobe or superior segments of lower lobe.

Pleural effusion Miliary tb – millet sized lesions

Extrapulmonary tuberculosis

Includes TB adenitis(75%) , TB meningitis(13%) , TB effusions (pleural, pericardial & peritoneal), bone & joint TB, miliary TB, abdominal TB, ocular TB, cutaneous TB, genito-urinary TB.

Tuberculous adenitis

Tuberculous adenitis Commonest form of EPTB LNTB is local manifestation of

systemic disease Isolated cervical lymphadenopathy

more common in 2/3 rd with Painless, matted nodes.

Lymphnode abscess can burst & lead to non healing TB sinus and ulcer

FNAC Excision biopsy confirmatory

Tuberculous meningitis TB meningitis seen in 1/300 Primary

infections Rupture of a subcortical caseous focus

(Rich’s) into the subarachnoid space. Inflammatory meningeal exudates,

ependymitis, vasculitis, encephalitis & diturbance of CSF circulation & absorption.

Cerebral endarteritis narrows lumen, reduces blood flow, leads to cerebral thrombosis and infarction.

Hydrocephalus

CN palsy 3, 6, 7

Involvement of cranial nerves III VI VII and optic chiasma

Tuberculous meningitis Risk factors : Age < 5 years, contact with an adult suffering

from tuberculosis, PEM grade III and IV, and HIV infection

Stages of TB meningitis

Stage I Irritability, anorexia, personality change

Occasional vomiting, fever Poor school performanceStage II Focal neurological signs, cranial

nerve palsies, Seizures, hemiplegia, squintStage III Loss of consciousness, Coma,

Papilloedema Decerebrate rigidity

Complications of TB meningitis

Hydrocephalus Subdural effusion Hemiplegia / Paraplegia Late : Intellectual impairment Blindness Deafness Intracranial calcifications leading to hypothalamic and pituitary

dysfunction Growth failure Diabetes insipidus Failure of development of secondary

sexual characteristics

Diagnosis of TB meningitis

Signs of meningeal irritation X-ray chest CT scan – basal exudates, inflammatory

granulomas etc Tuberculin testing Retinoscopy for choroidal tubercles Lumbar puncture Elevated CSF pressure(30 – 40cm

h2o) Cobweb Coagulum/ pellicle on

standing 100 – 500 WBCs / cu.mm

>40 mg% protein Low / Normal sugar AFB smear & culture

Prognosis in TB meningitis

100% mortality in 3-4 weeks without treatment

100% survival with treatment started in Stage I

75% survival with treatment started in Stage II

Stage III – variable survival, all will have sequelae

Tuberculomas Infratentorial tuberculomas Solitary A ring enhancing lesion is not

pathognomonic of tuberculoma A larger lesion >20 mm, disc lesion or

ring lesion with thicker rim and central nodule favors tuberculoma; while multiple, smaller, thin rim with epicentric nodule favor NCC

MR spectroscopy may help in diagnosis of tuberculoma as it shows lipid peak.

D/D Neurocysticercosis, fungus, other tumours.

Tuberculomas

Miliary tuberculosis most common within 1st 3 to 6 months

after infection due to heavy hematogenous spread of

tubercle bacilli Onset: Insidious, with Fever and weight

loss Palpable liver and/or spleen Generalized lymphadenopathy, Papulonecrotic skin lesions,

choroid tubercles Tachypnoea with normal chest

findings

Miliary tuberculosis Hematogenous dissemination leads to

progressive development of small lesions throughout the body, with tubercles in the

lung, spleen, liver, bone marrow, heart, pancreas brain, choroid, skin Radiologic diagnosis: “Snow storm” appearance

(Multiple small lung nodules 1mm size and above in both lung fields).

Miliary TB

Choroidal tubercles

Cutaneous Tuberculosis

Associated with Hematogenous dissemination - Papulonecrotic tuberculids papules with soft centers on trunk, thighs

and face - Tuberculosis verrucosa cutis Large tuberculids on arms and legs

Associated with hypersensitivity to tuberculin - Erythema nodosum painful indurated nodules on shins, elbows,

forearms that subside in 2-3 weeks

TB verrucosa cutis

Large tuberculids on arms and legs

Erythema nodosumpainful indurated nodules on shins, elbows, forearms

Guidelines for presumptive diagnosis of tuberculosis

Pediatr Infect Dis J 1993;12: 499-504)

A combination of at least 3 of the following: Symptoms/signs s/o TB:

(fever., cough>2wks, weight loss)

History of close contact with TB Positive tuberculin skin test

(Mantoux > 10 mm) sputum / gastric juice AFB +ve lymph node / tissue biopsy positivity Radiologic features suggestive of TB

History of contact = any child who lives in a household with an adult taking ATT or has taken therapy in the past 2 years

Early morning Gastric aspirate

Fasting for about 6 hours (at night) Appropriate size intra-gastric tube is passed Initially the aspirate is drawn from the stomach and further washing with 15-30 mL saline is taken. The contents are transferred to the laboratory This specimen can also be collected as an

ambulatory procedure after 4-6 hours fasting with some loss of yield

Sputum collection in children

Induced sputum can be done in children as young as 1 month

6h fasting Pre-treat with inhaled albuterol by MDI 3% hypertonic saline given by jet

nebulizer for 15 minutes followed by chest percussion

Samples are collected from throat or nasopharynx using collector attached to a suction at one end and catheter to the other.

The suction catheter provokes cough and the secretions brought up are collected via suction

Treatment for TB

1st line anti-tuberculous drugs

Isoniazid (INAH) 5 mg/kg/day H Rifampicin 10 mg/kg/day R

Pyrazinamide 25 mg/kg/day Z Ethambutol 20 mg/kg/day E

Streptomycin 20mg/kg/day S

Phases of Treatment Intensive Phase

Eliminate bacterial load Prevent emergence of drug resistant strains Atleast 3 Bactericidal Drugs used

Continuation Phase Continue and complete therapy Atleast 2 Bactericidal drugs used

Steroids Anti inflammatory effect – millary, peritonitis,

pericarditis TB meningitis

RNTCP Treatment

Summary and Pearls• Clinical manifestations in pediatric TB may

be non-specific• TB is much more difficult to diagnose in

children • Undiagnosed or untreated TB in a child is

potentially serious, – More likely to develop severe or

disseminated disease• Diagnosis of TB in a child is a sentinel

event– Contact investigation is critical

CONGENITAL TB

Congenital infection by vertical transmission is rare with only 358 cases reported till 1995 and another 18 cases reported from 2001 to 2005

High neonatal mortality (up to 60%) and morbidity warrant early diagnosis and treatment of newborns suffering from TB

Mother to child transmission of TB

Vertical transmission: Transplacental transmission

through Umbilical veins(occurs in late pregnancy)

Aspiration & swallowing amniotic fluid (occurs in perinatal period)

Transmission through breast milk does not occur

Horizontal transmission in postpartum period is by droplet infection from mother or family members

High risk factors Extra Pulmonary, miliary and

Meningeal TB in Mother

Untreated Mothers.

Diagnosis Cantwell criteria: Presence of proven

tuberculous disease and at least one of the following;

(i) lesions in the newborn baby during first week of life; 

(ii) a primary hepatic complex or caseating hepatic granulomata; 

(iii) tuberculous infection of the placenta or the maternal genital tract; and 

(iv) exclusion of the possibility of postnatal transmission by investigation of contacts, including hospital staff

Clinical Manifestations Of Congenital T.B:

Median Age of Presentation:- 24 days ( 1to 84 days)

FETAL:- IUGR,LBW ,increased risk of mortality Neonate:- Irritability, Poor Feeding, lethargy

(100%) ,Failure to thrive, fever(100%), Cough(88.9%),respiratory distress (66.7) Apnea,Vomiting,cyanosis,seizures,petechiae(<10%case)

Examination

Hepatosplenomegaly (100%) Splenomegaly (77.8%) Abdominal distension(77.8%) Lymphadenopathy(38%)

Babies develop meningitis septicemia, pneumonia, DIVC, ascitis, parotitis, osteomyelitis, otitis media, paravertebral abscess, cold abscess, skin lesions

INVESTIGATIONSConventional Method:- Morphological & histological examination

of placenta. Screening of house hold contact Poor response to conventional treatment

Detection of AFB in gastric aspirates,Sputum(induced), tracheal aspirates,ear discharge,Skin lesions, ascitic fluid,CSF,pleural fluid

Broncho Alveolar Lavage - By PCR (diagnostic)

Chest radiography & computed tomography –

may show scattered infiltrates, bronchopneumonia, consolidation or periportal hypodensity (non specific) Mantoux test-(supportive evidence) Poor utility Used after 3 months of age PPD 2TU

Newer methods Gene expert (real time PCR )

LED Fluoreseance microscopy and liquid based mycobacteria growth indicator tube (MGIT)

RIGAs, QuantiFERON –TB Gold assay and T-Spot –

Inconsistent result in newborn.

Management Of Congenital TB

AIM - To ensure free survival of a newborn infant

Diagnosis of active tubercular lesion

Treatment of the neonate

prevention of infection to the neonate from the mother.

(i)Prevention of Transmission

(A)Maternal disease & therapy: Transmission is less when mother complete ATT Before delivery or Have received ATT for at least 2 weeks before delivery.

ATT drugs safe for fetus expect streptomycin in the first trimester

Safety of second line ATT drugs for resistant TB - Insufficient evidence.

Prevention of transmission

(B) PROPHYLAXIS ( IAP guildelines )

ISONIAZID for newborn at least 6 month (or)

a minimum of three months until mother is Culture negative

DOSE:-10 mg/kg.

Prevention of transmission(C)Nutrition and breast feeding Support for breast feeding.

Expressed breast milk-when mother is sick or smear positive or has MDR TB.

Personal hygiene, hand washing, cough hygiene

First line ATT is safe & excreted in breast milk

Prevention of transmission(D) Isolation

Isolation - sick mother, resistant TB, non adherent therapy, received ATT for less then 2 weeks.

Prevention of transmission (E)Barrier Nursing

Face Mask, Cough hygiene, Hand Washing , Disinfecting nasal secretions & baby wipes.

TREATMENT American Academy of Pediatrics recommends

treatment with INH 10 to 15 mg/kg po, Rifampin 10 to 20 mg/kg po,  Pyrazinamide 30 to 40 mg/kg po, Aminoglycoside (amikacin or kanamycin) for 9-12 months.

Regimen is modified as indicated based on results of testing for resistance.

Pyridoxine is given if the neonate is exclusively breastfed.

(C)FOLLOW UP:-

DOTS recommends

clinical surveillance during treatment & chest x-ray at the end of treatment.

(III)Long Term protection.

IAP Recommendation BCG (Bacillus Calmette Guerin) Vaccination No utility of BCG Vaccine in neonates with

congenital tuberculosis Advised at birth even with INH prophylaxis

(IAP 2012). Need to conduct more studies to evaluate

immunogenicity of BCG Vaccine in infants receiving INH prophylaxis.

 Congenital tuberculosis is diagnosed by Cantwell criteria and treatment includes three or four anti-tubercular drug regimen.

Prophylaxis with isoniazid (3-6 months) is recommended in neonates born to mother with TB who are infectious.

Breastfeeding should be continued in these neonates and isolation is recommended only till mother is infectious, has multidrug resistant tuberculosis or non adherent to treatment.

BCG vaccine is recommended at birth or after completion of prophylaxis (3-6 months) in all neonates.

Peds TB Cases

Meron 4 ½ months old

Well appearing, Normal PE (wt in 10%) developmental screen.

Screened for TB, Hepatitis, syphilis, HIV, parasites, lead

Vision/hearing screening: high frequency hearing loss

Received BCG at birth TST 12 mm enduration, HIV – Hx repeated respiratory infections in

orphanage, treated w/ multiple antibiotics

Meron

CXR 2 views Alert radiologist you are looking for TB

Meron

Laboratory testing Microbiological testing

Sputum, sputum induction (?) BAL (?) Gastric aspirates

CBC, U/A & U/Cx, electrolytes & renal fct, LFT

Treatment? How many drugs?

Meron Gastric aspirate positive Mtb on

second aspirate

Started on 4 drug regime by DOT

Resistant to INH, RIF. Sensitive to PZA, EMB, SM MAC also grew on purity plates

Meron

Use all first line drugs available (unless previously used & associated w/ failing regime)

Use injectable drug (SM, amikacin, capreomycin, kanamycin) by Broviac

Use fluroquinolone Use additional second line drugs to have

4-6 drugs in the regime

Meron

Treatment changed: aminoglycoside (by broviac x 4 mos), PZA, EMB, ethionamide and levofloxacin, Vit B6 by DOT

2 negative gastric aspirates on therapy Gained many pounds CXR normalized Normal growth and development