Tuberculosis (TB) is one of the most prevalent chronic infections in our country and is responsible for high morbidity and mortality. TB is caused by Mycobacterium tuberculosis, and afflicts the lungs most commonly. In one-third or more, extra-pulmonary involvement is seen. Tubercular lymphadenopathy is the commonest form of extrapulmonary tuberculosis. All cases of TB is a notifiable disease, should be reported to the local/district/state health authorities, as it is a notifiable disease.
Pulmonary TB usually presents with fever, malaise, chronic cough with sputum production, anorexia and weight loss.
Sometimes chest pain and haemoptysis may be the presenting symptoms. Extrapulmonary tuberculosis presents most commonly as prolonged fever and cervical, mediastinal or mesenteric lymphadenopathy.
Abdominal tuberculosis may present as ascites, chronic abdominal pain, diarrhoea, recurrent subacute intestinal obstruction, etc.
CNS tuberculosis presents as irritability, headache, vomiting, chronic meningitis, seizures or focal neurological deficits, altered sensorium.
Skeletal tuberculosis may present as Pott’s spine, tuberculous osteomyelitis, monoarticular arthritis. Tubercular constrictive pericarditis presents with oedema/ascites.
Symptoms of genitourinary TB include tubovarian masses, secondary amenorrhoea in women, chronic epididymo-orchitis in men and painless haematuria in both the sexes. Diagnostic algorithm is given in Figure below. Definitive diagnosis is made only by demonstration of AFB on smear or culture of the sputum or bronchial secretions. Chest radiograph merely localizes the site of pathology and does not define an aetiology. There are no pathognomonic radiological signs of tuberculosis. Chest X-ray is sensitive but less specific with higher inter- and intra-reader variation, should be used judiciously.
Definitive diagnosis of extrapulmonary tuberculosis is made on the basis of FNAC or findings of caseous granuloma with presence of AFB in the tissue, fluid for cytology, biochemical analysis and smear examination; although ultrasonography and radiological examination of the system involved are useful investigations. CT scan is rarely necessary and is not cost and radiation effective. Chest CT scan, however, may offer an opportunity for CT guided biopsy for tissue diagnosis. Tests not recommended in diagnosis of tuberculosis are BCG test, serology (IgM, IgG, IgA antibodies against MTB antigens), PCR tests and Gene expert.
Childhood tuberculosis is suspected, when an ill child has a history of chronic illness that includes cough and fever, weight loss or failure to thrive, an inability to return to normal health after measles or whooping cough, and history of contact with an adult case of pulmonary tuberculosis. The diagnosis of tuberculosis in children is extremely challenging due to relative inability to demonstrate AFB-the gold standard. Diagnostic algorithm for TB in adults
Diagnostic algorithm for TB in children.
1 History of unexplained weight loss or no weight gain in past 3 months; Loss of weight defined as loss of more than 5% body weight as compared to highest weight recorded in last 3 months. 2 Radiological changes highly suggestive of TB are Hilar/paratracheal lymphadenitis with or without parenchymal lesion, Miliary TB, fibrocavitary pneumonia. 3 If the radiological picture is highly suggestive of TB, then proceed to do further investigations irrespective of the TST result as the sensitivity of the test is not 100%. 4 All efforts including gastric lavage (GL)/ induced sputum (IS) or bronchoalveolar lavage (BAL) should be made to look for acid-fast bacilli (AFB) depending upon the facilities. Diagnostic algorithm for diagnosis of tubercular lymphadenitis.
Do not start treatment for TB until a firm diagnosis has been made.
High protein diet. However, routine use of vitamin supplements is not required. Rest, depending upon patient’s symptoms.
Nonspecific. Tab. Paracetamol 500 mg 6-8 hourly till fever resolves.
Symptomatic treatment depending upon site of involvement, e.g. loperamide for chronic diarrhoea, anti-oedema measures for raised intracranial pressure. Specific treatment of TB. DOTS is a recommended strategy for treatment of TB and all paediatric TB patients should be registered under Revised National TB Control Programme (RNTCP). Intermittent therapy is as effective as daily therapy. Intermittent short course chemotherapy given under direct observation as advocated in the RNTCP.
1. The number before the letters refers to the number of months of treatment. The subscript after the letters
refers to the number of doses per week.
The dosage strengths are as follows: Isoniazid (H) 600 mg, rifampicin (R) 450 mg, pyrazinamide (Z) 1500 mg, ethambutol (E) 1200 mg, streptomycin (S) 750 mg.
• Patients who weigh 60 kg or more receive additional rifampicin 150 mg.
• Patients who are more than 50 years old receive streptomycin 500 mg. Patients who weigh less than 30 kg, receive drugs as per paediatric weight band boxes according to body weight.
2. In rare and exceptional cases, patients who are sputum smear-negative or who have extra-pulmonary disease can have recurrence or non-response. This diagnosis in all such cases should always be made by an MO and should be supported by culture or histological evidence of current, active TB. In these cases, the patient should be typed as ‘Others’ and given treatment regimen for previously treated
* New includes former categories I and III
** Previously treated is former category II.
* The number before the letters refers to the number of months of treatment. The subscript after the letters refers to the number of doses per week. Pulmonary TB refers to disease involving lung parenchyma. Extrapulmonary TB refers to disease involving sites other than lung parenchyma. If both pulmonary and extrapulmonary sites are affected, it will be considered as pulmonary for registration purposes. Extrapulmonary TB involving several sites should be defined by most severe site. Smear positive: Any sample (sputum, induced sputum, gastric lavage, bronchoalveolar lavage) positive for acid-fast bacilli. New case: A patient who has had no previous ATT or for less than 4 weeks. Relapse: Patient declared cured/completed therapy in past and has evidence of recurrence. Treatment after default: A patient who has taken treatment for at least 4 weeks and comes after interruption of treatment for 2 months and has active disease. Failure to respond: A case of paediatric TB who fails to have bacteriological conversion to negative status or fails to respond clinically/or deteriorates after 12 weeks of compliant intensive phase shall be deemed to have failed response provided alternative diagnoses/reasons for non-response have been ruled out. Others: Cases who are smear negative or extra-pulmonary but considered to have relapse, failure to respond or treatment after default or any other case which do not fit the above definitions.
In patients with TB meningitis on Category I treatment, the four drugs used during the intensive phase can either be HRZE or HRZS. The present evidence suggests that ethambutol can be used in children.
Children who show poor or no response at 8 weeks of intensive phase may be given benefit of extension of IP for one more month. In patients with TB meningitis, spinal TB, miliary/disseminated TB and osteoarticular TB, the continuation phase shall be extended by 3 months making the total duration of treatment to a total of 9 months. A further extension may be done for 3 more months in continuation phase (making the total duration of treatment to 12 months) on a case to case basis in case of delayed response and as per the discretion of the treating physician.
Steroids should be used initially in hospitalized cases of TBM and TB pericarditis and reduced gradually over 6 to 8 weeks. In all instances before starting a child on previously treated regimen, patient should be examined by a paediatrician or TB expert, whoever available.
Children can tolerate much higher doses than the adults so while calculating the dose, do not round off to a lower amount of drug. As children can have significant increase in body weight on treatment, the doses may be increased in proportion of increase in body weight Treatment in special situations
Treatment of MDR tuberculosis (To be treated under DOTS Plus of RNTCP).
Very important to prevent MDR by avoiding monotherapy/poor compliance to treatment.
Drugs susceptibility testing should be done. If not available, treatment regimen as above. Patients with meningitis, bone and joint tuberculosis and miliary TB should receive minimum of 12 months of treatment.
Pregnant women. Avoid Pyrazinamide, Streptomycin is contraindicated. Give Isoniazid (INH), Rifampicin and Ethambutol for 2 months followed by INH and Rifampicin for 7 months. Lactating women can continue to breastfeed.
Women on oral contraceptives. Switch over to alternate methods of contraception.
Patients with renal disease.
Avoid Ethambutol and monitor for side effects.
Reduce doses of INH and Pyrazinamide in cases of severe renal failure.
Patient with hepatic disease.
Avoid INH, Rifampicin and Pyrazinamide.
Patients with HIV/AIDS.
All patients diagnosed as TB cases should be referred to nearest ICTC for HIV testing. ART to be given to all patients with extrapulmonary TB (stage 4) and all those with pulmonary TB (stage 3) with CD4 count <350 cells/ cu mm.
Patients with pericardial effusion, severe pleural effusion, meningitis.
Steroid (oral/ injectable) to be given along with the antitubercular therapy.
In tubercular meningitis (see section on tubercular meningitis)
Tubercular pericarditis. In addition to ATT, Tab. Prednisolone 40-60 mg for 2 weeks with gradual tapering over next 4 weeks.
Pleural effusion. In addition to ATT, Tab. Prednisolone may be considered, in patients who are toxic or with large effusions.
The dose of INH for chemoprophylaxis was recommended to be 10 mg/kg administered daily for 6 months. TB preventive therapy should be provided to:
All asymptomatic contacts (under 6 years of age) of a smear positive case, after ruling out active disease and irrespective of their BCG or nutritional status. Chemoprophylaxis is also recommended for all HIV-infected children who either had a known exposure to an infectious TB case or are tuberculin skin test (TST) positive (≥5 mm induration) but have no active TB disease.
All tuberculin skin test (TST) positive children who are receiving immunosuppressive therapy (e.g. children with nephrotic syndrome, acute leukaemia, etc.).
A child born to mother who was diagnosed to have TB in pregnancy should receive prophylaxis for 6 months, provided congenital TB has been ruled out.
BCG vaccination can be given at birth even if INH chemoprophylaxis is planned.
Monitoring and evaluation.
Paediatric focused monitoring may preferably be an integral part of programme. Whenever possible, follow-up sputum examination is to be performed with same frequency as in adults. Clinical monitoring of case
Clinical symptomatic improvement is to be assessed at the end of intensive phase of treatment and at the end of treatment. Improvement should be judged by absence of fever or cough, a decrease in size of lymph node(s) and weight gain/no weight loss.
Radiological improvement is to be assessed by chest X-ray examination in all smear-negative pulmonary TB cases at end of treatment.
DOTS is the recommended strategy for treatment in adults and children. All paediatric TB patients should be registered under RNTCP. It is important to ensure completion of treatment in every case put on treatment to prevent emergence of resistance, particularly to Rifampicin. In the rare circumstances where a patient is given daily therapy, observation and completion of therapy remains as important. It is the duty of the prescriber to ensure appropriate and complete treatment in all cases. Management of patients with treatment interruptions
Recording and reporting
In addition to the existing information, especially in relation to paediatric TB patients, the treatment card should include information on:
Basis for starting treatment along with categorization. Documentation of clinical and radiological monitoring as described above. This information could be clubbed with the table for laboratory results in the present treatment card. X-rays should be retained until treatment completion, and a drawing of the X-ray picture with comments, entered in the remarks column. Provision to check correct categorization and drug dosages. A dosage table based on patient’s weight could be printed on the card to ensure correct dosage for the child. Assessment of response to therapy
1. The short course chemotherapy as enlisted above leads to a rapid clinical response in most patients in 2-4 weeks. Inadequate combination or dosage of this can lead to emergence of resistance and should be avoided at all cost.
2. The response to therapy should be monitored by bacteriological conversion in positive cases and by other markers like clinical and/or radiological improvement in AFB negative cases at the end of 2 months of intensive phase. A bacteriological conversion in over 80% of cases after 2 months of therapy is expected. If the patient continues to excrete bacteria after 2 months, the intensive phase needs to be extended by a month, and also ensure patient compliance, as non-adherence is the most common cause for nonresponse.
If a patient continues to be symptomatic or bacteriologically positive after an extended phase of IP, then the patient should be extensively re-evaluated and treatment failure/drug resistance should be suspected. The patient should be referred to a higher centre for further management. Remember persistence or recurrence of symptoms or radiological shadow could be due to secondary or coinfection with other organisms or due to a non-tuberculous lesion. Radiological response may lag behind bacteriologic cure and hence should not be the deciding factor for stopping of treatment. In patients with extrapulmonary tuberculosis, the response to treatment is assessed clinically.
3. All patients should have baseline LFTs; should be monitored regularly in patients at high risk of hepatitis, e.g. old patients, alcoholics, diabetics and malnourished.
4. Monitoring and management of side effects: The suggested therapy is usually well tolerated. However, some patients can develop GI intolerance, vomiting, etc. for which only symptomatic therapy is required. Commonest major side effect with suggested regime is druginduced hepatitis. The easily recognizable symptom of high-coloured urine in jaundiced patient is masked due to discolouration of urine because of rifampicin. Suspect hepatitis, if vomiting is persistent and associated with anorexia. Clinically, icterus may be evident. In all cases of jaundice, stop treatment and refer to a higher centre for evaluation. In most patients, the drugs can be reintroduced after the hepatitis has resolved. Pyrazinamide-induced arthralgia or arthritis usually responds suitably to analgesic therapy. Drug rash and hypersensitivity is a major side effect where patient needs to be referred to a higher centre. Peripheral neuropathy due to INH is treated with oral vitamin B6. Ethambutol can cause optic neuritis particularly when used in high doses and requires omission of the drug once this side effect occurs.
5. In case of hypersensitivity reaction, discontinue all drugs, re-challenge with individual drug to determine the likely offending drug. Do not reintroduce rifampicin in patients who develop thrombocytopenia. Hyperuricaemia can occur due to pyrazinamide. Needs to be discontinued only in case of secondary gout. Patient education
The patients should be impressed upon the necessity of complying with periodic follow-up sputum examination schedule as advised.
In case patients experience any unusual symptoms after initiation/during treatment, they should be instructed to approach the medical officer and report the same. On their own, they should not take a decision either to stop or to continue the drugs.
Smoking of tobacco adversely affects the treatment outcome and, therefore, give simple tips to quit smoking and refer to the smoking cessation clinic and protect from passive smoking. The environment of the patient has to be smoke free at home/ office and at clinic. Check smoking status of the TB patient at every interaction.
Alcohol abuse: Elicit history of addiction to alcohol and if found alcoholic, advise to strictly refrain from alcohol as it would increase the chances of patient developing hepatitis (jaundice), irregularity in drug intake and adverse treatment outcome.
Rifampicin colours the urine as well as other body secretions orange-red. Patient must be warned about this to avoid unnecessary alarm. The patient should also be advised to take Rifampicin on an empty stomach and not to take any meals for about 1 hour afterwards for good absorption of the drug.
The patient or the primary caregiver must be advised regarding the probable side effects and explained when to contact the treating doctor.
A health functionary should preferably supervise the treatment of tuberculosis as far as possible. However, it is of utmost importance that the patient and the family are informed about the need to complete all the treatment for whole of the duration. They must be explained the need for prolonged therapy even after the sickness disappears (symptoms abate). Inadequate or incomplete treatment increases the chance of multidrug resistance which is difficult to treat.
Importance of screening symptomatic contacts and children below 6 years: Encourage patients to bring symptomatic adult contacts and all children aged six years and below for screening at health facility for early detection of cases among them and appropriate treatment. Eligible children will be administered chemoprophylaxis.
Proper sputum disposal and personal hygiene (covering the mouth while coughing) should be explained for infectious patients. The fears of the patient and/or the caregiver regarding the disease should be addressed as this disease has a lot of social stigma.
Ethambutol is a hygroscopic drug which tends to crumble, if not properly stored, particularly during rainy season.