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Dr Amdekar's Revision Notes

Tuberculosis: An Unconquered Disease

bacteriological culture takes a few weeks but faster methods are now available including the BACTEC system that offers results in a few days, especially in the diagnosis of smear-negative TB. Ideally, every attempt should be made to diagnose TB by bacteriology because it is possible and multi-drug resistant TB (MDR-TB) is a threat in every case today. Molecular diagnosis is now available in the form of GeneXpert test that gives results in a few hours, is fairly sensitive and specific and also defines

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rifampicin sensitivity or resistance. However, it is ideal to order both culture and molecular tests as one of them may be false -ve. Newer tests are now being invented with the idea of improving bacteriological diagnosis.

Supportive evidence is important as bacteriological proof is not possible in every case of childhood TB although an attempt must be made, as mentioned above. The Mantoux tuberculin skin test (TST) suggests whether a person has been infected with TB bacilli but does not equate to diagnosis of TB disease. The test should be performed with 2 or 5 TU of PPD. An induration of 10 or more millimeters is considered positive and suggests infection but not necessarily disease. Hence, Mt test is not recommended for the diagnosis of TB disease. However, the younger the age and positive tuberculin reaction, the more likely it is active disease (see Table 2). Chest X-ray may be supportive although it is not pathognomonic of TB. However, in our epidemiology, fibrocaceous lesion, miliary shadows, mediastinal enlarged lymph nodes and pleural effusion in a healthy older child are most likely indicative of TB. When in doubt, lateral chest X-ray may help localize the lesion. Decubitus film can confirm the presence of pleural fluid. CT scan of the chest is unnecessary, as it does not add any more information than a conventional chest X-ray except for localizing necrotic lymph nodes that may be indicative of TB. CBC and ESR are not useful either. ESR can be used for monitoring; however, there are better parameters available to judge progress. Serological tests such as TB antibodies (TB IgG, TB IgA) are not dependable and are not recommended for use.

• It is estimated that 5 in 1000 people are infected with Mycobacterium tuberculosis, of which half will present as smear positive.

• Children can present with TB at any age, but the most common age is between 1 and 4 years.

• Unexplained fever and/or cough for 2 weeks or more is highly suggestive of TB especially if it is accompanied by loss of appetite, weight loss and a positive contact history.

• Fibrocaseous cavitary lesions on physical examination are quite pathognomonic of TB in India though they can be mimicked by fungal infection as well.

• The acute onset of pleural effusion in a healthy older child is highly suggestive of TB in our epidemiology as are miliary lesions with hepatosplenomegaly.

• Enlarged peripheral lymph nodes are often found in pulmonary TB in children and are a useful clinical finding to substantiate diagnosis.

• It is the size (often >1-1.5 cm), consistency (firm or matted) and progressive enlargement that suggests diseased lymph nodes.

• The gold standard of TB diagnosis is demonstration of acid-fast bacilli in bronchial secretions, sputum or tissue obtained by biopsy such as a lymph node by using liquid culture medium as well as GeneXpert PCR test.

• Mantoux tuberculin skin test (TST) is not recommended in the diagnosis of tuberculosis.

• CT scan of the chest is unnecessary, as it does not add any more information than conventional chest X-ray except for localizing necrotic lymph nodes that may be indicative of TB.

• CBC and ESR are not useful either. ESR can be used for monitoring. Serological tests such as TB antibodies (TB IgG, TB IgA) are not dependable and are not recommended for use.

• The RNTCP in India, had recommended a standard protocol of treatment based on three categories that should be followed universally even in children. However, it is no longer recommended and has been replaced with National TB elimination program with simplified treatment approach.

• MDR-TB should be suspected if there is evidence of contact with a known case of MDR-TB or if there is a past history of anti-tuberculosis treatment and should be referred to experts for further treatment.

NEWER LABORATORY TESTS FOR DIAGNOSIS

Polymerase chain reaction (PCR) is a highly sensitive method to confirm a clinical diagnosis of TB. However, the high number of false-positives that were found suggests that results obtained should be confirmed with BACTEC, which considerably reduces the time required for identification, and makes it possible to carry out an antibiotic assay rapidly. Moreover, it is positive in 95% of culture +ve cases but only 50% of culture –ve cases. In addition, As mentioned above, GeneXpert test is now readily available so it is routinely employed in the diagnosis of TB. Interferon gamma release assays are not recommended as the sensitivity and specificity of QuantiFERON, QuantiFERON-TB Gold, the T-spot TB test and ELISpot TB test have not been determined in children. Instead of trying newer tests, maybe one should

Dr

Amdekar's Revision Notes seek expert advice in difficult cases.

DISEASE CATAGORIES RECOMMENDED NOW

Rifampicin sensitive TB / newly diagnosed TB 2HRZE/4HRE (for neuro and spine TB 2HRZE/8HRE rifampicin resistant TB is suspected in case of relapse, treatment defaulter and one in contact with rifampicin resistant TB such a patient must be referred to an expert as treatment demands use of many more new drugs that are also toxic.

Treatment

The Revised National Tuberculosis Control Program (RNTCP) in India, had recommended a standard protocol of treatment based on three categories (Table 3) that should be followed universally even in children. According to the Directly Observed Therapy-short course strategy (DOTS) strategy it is essential to monitor patient compliance to the treatment, as non-adherence is the major factor responsible for the development of MDR-TB. In addition, patients should receive careful clinical follow-up for two years after completion of a treatment regimen so that any indication of relapse can be diagnosed early and treated promptly. RNTCP has been replaced with NTEP – a national TB elimination program.

Recent National Tuberculosis Elimination Programme recommends only two categories for treatment as mentioned above – RS-TB (Rifampicin sensitive) and RR-TB (Rifampicin resistant TB)

Combination therapy is recommended though ethambutol has to be given separately but the other three drugs are used in fixed drug combination that is available in dispersible tablet form though Ethambutol tablet is not dispersible Drug treatment is available free of charge at the government centers.

MDR-TB should be suspected if there is evidence of contact with a known case of MDR-TB or if there is a past history of anti-tuberculosis treatment (ATT). An adolescent with cavitary fibrocaseous TB is at a high risk of developing MDR-TB.

HIV testing is not routinely performed in childhood TB except if clinical markers of HIV infection are present, there is a history of HIV in parents or there is a history of blood transfusion. In summary, the diagnosis and treatment of TB should be made according to protocol and compliance must be ensured to prevent the development of MDR-TB.

SUGGESTED READING:

• Arora, VK. Issues in pediatric tuberculosis under DOTS strategy. Indian Pediatr 2004;41:891-893.

• Chauhan LS, Arora VK. Management of pediatric tuberculosis under the revised national tuberculosis control program (RNTCP). Indian Pediatr 2004;41:901-905.

• Kabra SK, Lodha R, Sheth V. Category based treatment of tuberculosis in children. Indian Pediatr 2004;41:927-937.

• Shaheb T, Zoha MS, Malik A, Malik A, Afzal K. Prevalence of human immuno-deficiency virus infection in children with tuberculosis. Indian Pediatr 2004;41:595-599.

• Kabra SK, Lodha R. DOTS in pediatric tuberculosis. Indian Pediatr 2006; 43: 276-278.

CME questions on: Tuberculosis: An Unconquered Disease

Fever in childhood tuberculosis may be: a) Intermittent b) High grade c) Absent d) All of the above e) None of the above a) Unilateral pleural effusion b) Fibrocaseous tuberculosis c) Miliary tuberculosis d) Pneumonia e) All of the above a) CT scan of chest b) PCR c) Gastric aspirate d) QuantiFERON TB test e) None of the above

Which of the following does not always indicate tuberculosis?

Which of the following tests should be routinely performed?

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Risk of active disease in an asymptomatic Mantoux +ve child is lowest in: a) Adolescence b) 2-5 years c) 5 years to preadolescence d) 1-2 years

MDR-TB should not be suspected in: a) HIV +ve b) Contact with MDR-TB individual c) Past history of ATT d) Failure of compliant therapy

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