Diagnosis Of Tuberculosis

A major challenge of childhood TB is establishing an accurate diagnosis. Less than 15% of cases are sputum acid-fast bacilli smear positive, Mycobacterial culture yields are 30%40%
Cruz AT, Starke JR. Clinical manifestations of TB in children. Pediatr Respir Rev 2007; 8:107117. Eamranond P, Jaramaillo E. Tuberculosis in children: reassessing the need for improved diagnosis in global control strategies. Int J Tuberc Lung Dis 2001; 5:594603.

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. Childhood pulmonary tubetculosisold wisdom and new challenges. Am J Resp Crit Care Med 2006; 173:10781090. Marais BJ, Pai M. Recent advances in the diagnosis of childhood tuberculosis.Arch Dis Child 2007; 92:446452

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 exposureprimary 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 510 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 childhood intra-thoracic tuberculosis: a critical review of literature from the prechemotherapy era. Int J Tuberc Lung Dis 2004; 8:392402

 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 negative /sputum not available for examination

Sputum smear positive pulmonary TB Child has: 1. already received a complete course of appropriate Antibiotics 2. Sick looking 3. Severe respiratory distress 4. Any other reason for CXR

YES

NO

CXR and TST

7d course of antibiotics which has no anti TB activity

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 normal TST negative

CXR nonspecific shadow , TST +/-

CXR normal TST positive

Review diagnosis

Repeat 7d course of antibiotics if not already received

Review for alternate diagnosis

Persistent shadow GL/IS/BAL If NO, Look for extrapulmonary site Seek expert help, CECT chest+/-

Smear positive t/t as SPPTB

Look for alternative; If no t/t as SNPTB

Sputum smear negative

Smear-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 TB
EPTB is defined as TB of organs other than the lungs Diagnosis 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 officers 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 lymphadenitis
Lymphnode 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 histopathology If 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 MENINGITIS
HISTORY of long duration of fever (>1week) with vague CNS symptoms such as behavior changes, irritability, drowsiness, headache, vomiting and seizures in presence of risk factors like age<5y, Kochs contact, undernutrition, HIV

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 posturing deterioration of vital signs and eventually death

EXAMINATION global encephalopathy with focal neurological deficit is the hallmark.

CSF study: Cytology- mild pleocytosis ( 10-500cells/cumm) with lymphocytosis predominantly CSF 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 4872hrs 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 featuresEvidence 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 a single, 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 fluid: Gross- straw colored Cytology- several hundred to thousands early predominance of PMN later lymphocytosis Proteins- 2 to 4gm/dl Sugar 20-40 mg/dl ADA levels >60 suggestive . Helps to differentiate b/w viral and non viral effusion AFB is rarely positive and cultures are positive in <30%

Pleural effusion

Abdominal TB
Localised diseaseMesentric lymphadenopathy Enteritis Peritonitis

Systemic disseminated diseasehepatosplenomegaly

 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 HIV
Features of PTB Early Clinical feature Often resembles post primary Stage of HIV infection Late Often resembles primary progressive. Disseminated and extrapulmonary forms are common Often negative Often hilar lymphadenopathy with infiltates esp lower lobes

Sputum smear CXR

Often positive Often cavities

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