PubMed2006
INTRODUCTION: The World Health Organization (WHO) has declared Tuberculosis (TB) a global emergency in 1993. Prevalence of TB and Human Immunodeficiency Virus (HIV) co-infection worldwide is 0.18% and about 8% TB cases have HIV infection. Effective chemotherapy has been available for treatment of TB for over 50 years now. In World Health Organization (WHO)-International Union Against Tuberculosis and Lung Disease (IUATLD) Working Group Global Anti-Tuberculosis Drug Resistance Surveillance (1994-1997), the incidence of MDR TB in Delhi was found to be 14%, of which primary multi-drug resistance was only 1.4%, indicating that most of MDR TB is acquired as a result of poor chemotherapy. DIAGNOSIS OF TB: Since TB is an infectious disease caused by Mycobacterium (M) tuberculosis the diagnosis of TB should (as far as possible) be by demonstration of M. tuberculosis on culture or acid-fast bacilli (AFB) on smear examination. The World Health Organization (WHO) has strongly recommended sputum smear examination as the preferred screening test and suggests examination of 3 deeply coughed out sputum samples - spot sample on day 1, overnight sample and a spot sample in the morning on day 2. Recently it has been shown that sputum smear positivity is greater than 90% where greater than 5 ml of sputum is used for smear diagnosis of pulmonary TB. Culture of M. tuberculosis is the gold standard for diagnosis of TB. Culture of mycobacteria is a much more sensitive test than smear examination and has been estimated to detect 10-100 viable mycobacteria per ml of sample and in case of active disease they are found to be 81% sensitive and 98.5% specific. Culture methods are also required for further drug sensitivity testing in cases of suspected drug resistant cases. Isoniazid and rifampicin resistance can be reliably measured; resistance to pyrazinamide, ethambutol, and streptomycin is more difficult due to limitations of technique. The therapeutic index for a given drug is low for certain second-line drugs such as ethionamide, cycloserine, viomycin and para amino salicylic acid (PAS) and it leads to misinterpretation of results due to failure to distinguish between sensitive and resistant strains. Misdiagnosis of MDR-TB due to laboratory related errors has been reported recently. MANAGEMENT OF TB: Chemotherapy of TB consists of prevention of infection, also called primary chemoprophylaxis, when isoniazid 5 mg/kg is given to prevent infection in newborn infants of infectious mothers till mother is sputum smear positive (2-3months). Treatment of latent tuberculosis, also called secondary chemoprophylaxis, when isoniazid 5 mg/kg is given for 6 months to prevent disease in infected persons (asymptomatic MT positive individuals) and treatment of disease with Short Course Chemotherapy (SCC), as per WHO categories. Essential anti-tuberculosis (ATT) drugs Isoniazid (H), Rifampicin (R), Ethambutol (E), Pyrazinamide (Z) and Streptomycin (S) are the essential first line anti-tuberculosis drugs. Anti TB regimen consists of two phases: an initial intensive phase (IIP) and a continuation phase (CP). Best effective SCC for treatment of TB, for adults and children, for pregnant and lactating females, for cases associated with diabetes mellitus and HIV infection, for cases with pre-existing liver diseases (but normal liver functions) and mild renal failure is 2EHRZ, 4HR given daily or thrice weekly. Higher dose SCC intermittent therapy given in thrice weekly (2E3H3R3Z3, 4H3R3) has now been advocated by WHO and implemented by the Revised National TB Control Programme. DOTS, directly observed therapy short course, where the patient takes the drugs under the direct observation (DO) of a health worker to ensure regularity of consumption of drugs. Fixed dose combinations (FDCs) drugs consisting of two or three antituberculosis medications, provide a realistic and welcome alternative to DO that minimizes the opportunity for a patient to selectively take only a single medication. MANAGEMENT OF TB IN SPECIAL SITUATIONS: Pregnancy: All drugs, that is, rifampicin, isoniazid, ethambutol, and pyrazinamide can be used during pregnancy. Streptomycin is not given due to ototoxicity to the fetus. Prophylactic pyridoxine in the dose of 10mg/day is recommended along with ATT. Diabetes mellitus: The drug regimen is same as in nondiabetic. Strict control of blood glucose is mandatory. Also, doses of oral hypoglycemic agents may have to be increased due to interaction with Rifampicin. Prophylactic pyridoxine is indicated. Renal failure: Dosages may have to be adjusted according to the creatinine clearance especially for streptomycin, ethambutol and isoniazid. In acute renal failure, ethambutol should be given 8 hours before hemodialysis. In post renal transplant patients: Rifampicin-containing regimens are avoided as rifampicin causes increased clearance of cyclosporin. Pre-existing liver disease: In stable disease with normal liver enzymes, all anti-tuberculous drugs may be used but frequent monitoring of liver function tests is required. Treatment in unconscious patient (patients unable to swallow): If patients are fed by Ryle's tube or gastrostomy tube, usual doses and drugs may be powdered and administered avoiding feeds 2-3 hours before and after the dose. In cases where enterostomy has been performed or parenteral nutrition is being used, intramuscular streptomycin and isoniazid and intravenous quinolones may be used and switch to oral therapy once oral feed resume. Treatment of TB with HIV co-infection: In early stages the presentations of TB in TB-HIV co-infection is the same as HIV negative but in late stages extra-pulmonary and dissemination are common. The usual short course chemotherapy is indicated in HIV positive patients. The response is usually good but relapse is frequent. After initiating ATT or anti-retroviral therapy (ART) worsening of preexisting lesions or appearance of new lesions is seen, "paradoxical response" or "immune reconstitution phenomenon". Multidrug resistant TB can occur due to poor compliance to ATT due to behavioural pattern, increased incidence of side effects and malabsorption of drugs due to associated diarrhea. ART for HIV, containing protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) cannot be used along with R, as R induces metabolism of PI and reduces the efficacy. The various options are i) to postpone anti-retroviral therapy ii) to use no PI or NNRTI containing anti-retroviral combinations iii) to use certain PI/ and/or NNRTIs with modification in doses iv) Efavirenz (EFZ) or Saquinavir with Ritonavir, without the need to adjust the doses v) to use non R regimens e.g. 2SHEZ+10HE MANAGEMENT OF MDR TB: As far as possible treatment of MDR TB should be referred to specialized units with facilities for quality controlled DST and experienced in handling such cases. If such referrals are not possible, one must remember that while initiating or revising therapy for MDR-TB, drugs selection must rely on prior treatment history, results of susceptibility testing and an evaluation of the patient's adherence.