Diagnosis Of Tuberculosis

A major challenge of childhood TB is establishing an accurate diagnosis.

Less than 15% of cases are sputum acid-fast bacillismear positive, Mycobacterial culture yields are 30%–40%

Cruz AT, Starke JR. Clinical manifestations of TB in children. Pediatr Respir Rev 2007; 8:107–117.

Eamranond P, Jaramaillo E. Tuberculosis in children: reassessing the need for improved diagnosis in global control strategies. Int J Tuberc Lung Dis 2001; 5:594–603.

In non endemic countries, TB is diagnosed based on a triad of

(1) close contact with an infectious index patient,

(2) a positive tuberculin skin test (TST) result

(3) presence of suggestive abnormalities on a chest radiograph.

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These criteria, however, have limited application in countries where TB is endemic, because– Case detection and contact tracing activities are not routine in national TB programs, – Transmission is not restricted to the household, and– Most individuals acquire infection and become TST

positive during childhood and adolescence

Marais BJ, Gie RP, Schaaf HS, Donald PR, Beyers N, Starke J. Childhoodpulmonary tubetculosis—old wisdom and new challenges. Am J RespCrit Care Med 2006; 173:1078–1090. Marais BJ, Pai M. Recent advances in the diagnosis of childhood tuberculosis.Arch Dis Child 2007;

92:446–452

Pulmonary TB suspect • Fever and/or cough >2weeks

– documentation– nature (any type)– evening rise neither specific nor commonly

present• Cough

dry/moist maybe severe recurrent episodes with normal intervening period is less likely to

be TB In suspected EPTB / CLHA cough of any duration

• h/o unexplained weight loss (defined as weightloss of >5%as compared to

highest weight recorded in last 3 months)

• no weight gain in last 3mths

• Recent loss of appetite

• h/o contact with an infectious TB patient(smear positive).

However , in a symptomatic child contact with any form of active TB in last 2yrs may be significant.

Risk of developing disease after infection

• age at exposure- primary infection before 2 years of age frequently progresses to disease

within the first 12 months the risk of disease progression decreases during childhood,is least at 5–10 years of age, and increases again during adolescence

• nutritional and immune status• magnitude of initial infection. • Severe or disseminated disease- young age and HIV infection

are the most important risk factors

Marais BJ, Gie RP, Schaaf HS, et al. The natural history of childhoodintra-thoracic tuberculosis: a critical review of literature from the prechemotherapyera. Int J Tuberc Lung Dis 2004; 8:392–402

• Recent history of whooping cough, measles

• Immunocompromised state : HIV , steroid therapy, chemotherapeutic agents

• Persistant lower respiratory tract infection not responding to antibiotics(non flouroquinolones)

• Significant superficial lymphnode should be specifically looked for , as they may often coexist

Clinically suspected Pulmonary TB case

Sputum examination

Sputum smear positive

Sputum smear positive pulmonary TB

Sputum smear negative /sputum not available for examination

Child has:1. already received a complete course of appropriate Antibiotics2. Sick looking3. Severe respiratory distress4. Any other reason for CXR

YES NO

7d course of antibiotics which has no anti TB activity

CXR and TST

CXR s/o TB and TST positive

GL/BAL/IS to look for AFB, MTb rapid culture or Gene expert wherever facilities

are available

Smear positive: treat as smear positive PTB

Smear negative:Treat as smear negative PTB

Either or both negative

Persistant symptoms

CXR normalTST negative

Review diagnosis

CXR nonspecific shadow , TST +/-

Repeat 7d course of antibiotics if not already received

Persistent shadow

GL/IS/BAL

Smear positive t/t as SPPTB

Look for alternative;If no t/t as SNPTB

CXR normalTST positive

Review for alternate diagnosis

If NO,Look for extrapulmonary siteSeek expert help, CECT chest+/-

Sputum smear negativeSmear-negative tuberculosis is currently defined as • symptomatic illness in a patient • with at least two sputum smear

examinations negative for AFB on different occasions• in whom pulmonary tuberculosis is later

confirmed by culture, biopsy, or other investigations

Extra pulmonary TBEPTB is defined as TB of organs other than the lungsDiagnosis is based on • culture-positive specimen from the extrapulmonary site• histological evidence or• strong clinical evidence consistent with active EPTB disease

followed by a medical officer’s decision to treat with a full course of anti-TB therapy.

Patients suspected of having EPTB should also have their sputum examined for AFB if they have chest symptoms, irrespective of the duration of these symptoms.

A patient diagnosed with both pulmonary and EPTB is classified as a case of pulmonary TB.

Among extrapulmonary manifestations,• Lymphadenopathy is the most common (67%) • Central nervous system(13%) • Pleural (6%), • Miliary and/or disseminated(5%)• Skeletal (4%) TB .

Disseminated (miliary) disease and TB meningitis are usually found in very young children (age <3 years) and/or HIV-infected children [9].

TB lymphadenitisLymphnode enlargement >2cm in one or more sites , with without periadenitis, with without evidence of TB elsewhere or presence of cold abscess with or without discharging sinus

a course of antibiotics for two weeks is prescribed

In case of persistence , suspect TB lymphadenitis

FNAC /pus from discharging sinus , is sent for AFB staining

Diagnosis confirmed if aspirate show ZN stain + for AFB or granulomatous changes on histopathologyIf FNAC results are inconclusive ,exclusive biopsy is advisable

Treat as case

• Mantoux test is positive in a significant proportion.• FNAC is usually adequate for accurate diagnosis

and it co-relates well with biopsy in >90% of cases • Histopathology shows caseous necrosis and

epitheloid granuloma.• AFB in FNAC specimen may be positive in 20-70%

of patients• Reactive lymphadenitis due to recurrent URTI or

tonsillitits may mimic TB ,hence ATT should not be started unless diagnosis is confirmed by FNAC or histopathology.

TUBERCULAR MENINGITISHISTORY of long duration of fever (>1week) with vague CNS symptoms such as behavior changes, irritability, drowsiness, headache, vomiting and seizuresin presence of risk factors like age<5y, Koch’s contact, undernutrition, HIV

EXAMINATION global encephalopathy with focal neurological deficit is the hallmark.

STAGES of TBM:1st stage: lasts typically 1-2 weeks characterized by fever, headache irritabilty, drowsiness and malaise, stagnation or loss of milestones

2nd stage: abrupt onset with lethagy, seizures, positive meningeal signs, hypertonia, vomiting, signs of raised ICT, FND, signs of encephalitis such as disorientation, movement disorders or speech impairment.

3rd stage: coma, hemiplegia/paraplegia, hypertension, decerebrate posturingdeterioration of vital signs and eventually death

CSF study:

Cytology- mild pleocytosis ( 10-500cells/cumm) with lymphocytosis predominantlyCSF protein- markedly high (400-5000mg/dl) CSF glucose-mild reduction (<40mg/dl rarely <20) to be interpreted in conjuction with blood sugar

In inconclusive results, CSF should be repeated 48-72hrs after antibiotic therapy and if it shows no improvement in clinical states and CSF results , it may favor TBM

• CSF show AFB positivity in 30% cases and culture positivity in 50-70% cases, provided 5-10 ml CSF sample is obtained

• Rapid MTb culture has has poor sensitivity (16%) though specificity is high (>90%)

• CSF antibody is not recommended in view of poor sensitivity, specificity and predictive value

• CSF ADA levels cutoff of 7and 11IU/L offer supportive evidence but cannot discriminate between TBM and bacterial meningitis

• CSF PCR(using commercial NAAT) –positive PCR is specific though negative PCR does not rule out TBM

MODIFIED AHUJA CRITERIA:

Mandatory features:•Fever lasting for more than 14 days •Abnormal CSF findings – pleocytosis with more than 20 cells and more than 60% lymphocytes , protein >100mg/dl, CSF sugar <60% of blood sugar

Any of 2 following features-•Evidence of extra neural TB (normal CXR in 20-50%)•Positive TST (1TU) >10mm (nonreactiveTST in upto 50%) •Positive family history of exposure to active TB case•Abnormal CT findings(2 or more) exudates in basal cistern or sylivian fissure hydrocephalus infarcts gyral enhancement

Using response to therapy as the gold standard,modified criteria had the sensitivity of 83%, with a specificity of 63%.

Seth R, S.U., Diagnostic criteria for tuberculous meningitis. Indian J Pediatr, 2002. 69(4): p. 299 303‐

A diagnostic approach to asingle, small, contrast enhancing CT lesion(SSECT)

NCC:

• Size 20 mm• Smooth margin,epicentric

nodule• Min./no surrounding

edema• No midline shift• Greywhite junction of the

cortex

• MRI(T2) : bright

Tuberculoma:

• Size >20mm• Lobulated irregular shape,with central nodule(conglomerate)• Marked oedema causing midline shift • Tuberculomas are usually seen in the base of the brain •MRI(T2): hypointense•MRS : lipid peaks

Pleural effusion• Pleural fluid: Gross- straw coloredCytology- several hundred to thousands early

predominance of PMN later lymphocytosisProteins- 2 to 4gm/dlSugar – 20-40 mg/dlADA levels >60 suggestive . Helps to differentiate b/w

viral and non viral effusionAFB is rarely positive and cultures are positive in

<30%

Abdominal TB

• Localised disease-Mesentric lymphadenopathyEnteritisPeritonitis

• Systemic disseminated disease-hepatosplenomegaly

• Sonography : Corroborative evidence of echogenic

thickened mesentry with lymphnodes >15mm in size, dilated matted bowel loops, thickened omentum and ascites

• Paracentesis: exudative ascites with proteins>3gm/dl with

lymphocytosis• Barium follow through :suggestive of intestinal

disease though not confirmatory

TB in HIVFeatures of PTB Stage of HIV infection

Early Late

Clinical feature Often resembles post primary

Often resembles primary progressive.Disseminated and extra-pulmonary forms are common

Sputum smear Often positive Often negative

CXR Often cavities Often hilar lymphadenopathy with infiltates esp lower lobes

Diagnosis is difficult •TST can be absent•Culture confirmation is difficult•Clinical features mimic other HIV related conditions•Risk of MDR TB