|Year : 2005 | Volume
| Issue : 4 | Page : 138-141
Management of tuberculosis in special situations
Rajinder Singh Bedi
Bedi Clinic & Nursing Home, Sher - e - Punjab Market, Patiala - 147001 (Pb.), India
Rajinder Singh Bedi
Bedi Clinic & Nursing Home, Sher - e - Punjab Market, Patiala - 147001 (Pb.)
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bedi RS. Management of tuberculosis in special situations. Lung India 2005;22:138-41
| Introduction|| |
Though the basic principles of management of tuberculosis (TB) remain the same, there are certain special situations like chronic renal failure, liver disease, pregnancy and HIV infection etc., in which either the drugs or the regimes have to be modified or even duration of therapy requires modifications. The management of tuberculosis in these situations is being discussed briefly.
| Chronic Renal Failure|| |
Uraemia and post-renal transplant states are acquired immunodeficiency states, in which these patients are at a higher risk of developing tuberculosis. According to one report, the patients undergoing dialysis have 10 - 12 fold higher risk of developing tuberculosis. 
Rifampicin (R), pyrazinamide (Z) and isoniazid (H) are excreted mainly by the biliary route and are thus safe in normal dosages in chronic renal failure (CRF) patients. Previous recommendations of reducing the daily dose of H to 150 mg is unjustified and there is also convincing evidence that the efficacy of H is reduced significantly when its dose is reduced below 200 mg per day. 
Until a few years ago, the effect of CRF on Z kinetics was not fully studied and various authors had recommended either to avoid Z in CRF or to use it in reduced dosage of 12-20 mg per Kg per day or 40 to 60 mg per kg. thrice or twice a week. Now most of the guidelines, including the WHO recommendations, approve normal dosage of Z in CRF patients. 
Streptomycin (S) and other aminoglycosides are excreted exclusively by kidneys and. therefore, should be avoided in CRF patients. Places where facilities for monitoring renal parameters closely are available, S can be used in reduced dosages.
Ethambutol (E) is excreted predominently by kidneys and should be used in decreased dosages of 5 - 10 mg per kg per day or 25 mg per kg. thrice or twice a week depending upon the creatinine clearance rates. Dosages of Ofloxacin (OF) and other quinolones should also be reduced in CRF patients. Pyridoxine in daily dose of 10-20 mg should always be given in CRF patients to prevent the risk of peripheral neuropathy.
Thiacetazone (T) and Paraaminosalicylic acid (PAS) are relatively weak drugs. Moreover, the margins between their therapeutic and toxic dosages are too narrow. Gastrointestinal upset and vomiting due to PAS can potentiate acidosis in patients of CRF. Both these drug should be avoided in CRF patients.  Ethionamide (Ethio) and Prothionamide (Pr.) are relatively safe drugs in CRF cases.
Though WHO and other guidelines have recommended 6 months therapy in CRF patients, some workers have recommended upto 18 months of treatment. It seems more controlled trials are needed to settle this issue. ,
In view of above mentioned facts, it seems that in CRF patients 2 RZH/4RH is the safest regimen and has also been recommended by WHO. 
| Chronic Liver Disease|| |
Hepatotoxicity is an important and commonly encountered adverse effect of many anti-tuberculosis drugs. R, Z, H, PAS and Ethio are all potentially hepatotoxic drugs where as E, S and other aminoglycosides, Cycloserine (CS) and various quinolones are non-hepatotoxic.  Out of first line drugs, Z is most hepatotoxic and R least,  With H, hepatitis has been reported in 1 percent cases. Though transient hepatic enzyme elevations have been seen in 14 percent cases with R, these return to normal in majority on continuation of therapy with R  . The hepatotoxic effects of R and H are additive  . Z induced hepatic damage is dose and duration related.
A number of conditions predispose to anti-TB drugs-induced hepatotoxicity. These include advanced age, female sex, poor nutritional status, preexisting chronic liver disease, extensive pulmonary disease or serious type of tuberculosis e.g. meningitis and inappropriate high dosages of drugs like Z. 
Majority of studies support the view that chronic hepatitis B virus carriers, chronic alcoholics and patients with past history of acute viral hepatitis do not predispose to increased hepatotoxicity with antiTB drugs and usual treatment can be given in these patients  , though one has to be extra vigilant about occurrence of hepato-toxicity in these cases.
In patients with established chronic liver disease, Z is contraindicated. The half life of Z, which is 9-10 hours in persons with normal hepatic and renal functions, is prolonged in patients having impaired hepatic functions. In these patients
- 2 RHE with or without S/6 HR
- 9 RH
- 2 SHE/10 HE
are appropriate and safe regimes. 
Very rarely, a patient of TB may be suffering from acute hepatitis e.g. viral. In such cases, if patient is not too sick, ATT should be deferred till jaundice clears. If patient is too sick, ATT in form of SE with or without quinolones can be started. After 3 months, if hepatitis resolves, therapy can be continued with R and H for another six months. If jaundice persists even after three months, which occurs only very occasionally, treatment has to be given for 12 months using S and E with or without quinolones.
All hepatotoxic drugs should be stopped, when a patient develops drug-induced jaundice and patient given S and E till hepatitis resolves. Then most of hepatotoxic drugs can be restarted in a phased manner (H- R- Z). Although there is still controversy regarding the safety and wisdom of restarting the same hepatotoxic drugs, which caused hepatitis earlier, the clinical experience has shown that these drugs can be given safely in majority. 
| Pregnancy|| |
Successful management of TB during pregnancy has important implication both for the mother and the new born. Review of literature do not suggest any significant impact of TB on the course of pregnancy or labour. There is no statistically significant increase in congenital malformations in children born to mothers having TB, though prematurity, foetal growth retardation, low birth weight and increased perinatal mortality has been reported. 
Careful history is mandatory for diagnosing T.B. Mantoux test should be carried out, though its role in Indian scenario is doubtful. In high suspicion and mantoux positive cases, chest skiagram should be done under proper abdominal shielding. If possible, X-ray should preferably be deferred till the end of first trimester. Routine screening with radiography during pregnancy is not indicated, because of the low yield and possible hazards.  Sputum examination is as important in pregnant ladies as in general population.
Successful management of TB is important for successful outcome of pregnancy. Treatment should be started without delay. R, Z, H, E are all safe during pregnancy. Although some authors had raised doubts about safety of Z due to lack of data on teratogenecity  in the previous years, now WHO and other organisations have recommended its use in pregnancy. ,
Streptomycin and other aminoglycosides are contraindicated in pregnancy as they are ototoxic and nephrotoxic to the foetus. Ethio is also contraindicated as it has been reported to be teratogenic in animals. Quinolones should be avoided in pregnancy, as they impair growth and can produce injury to the growing cartilage. 
During pregnancy, 2 RZHE/4RH and 2 RZHE/ 6HE have been recommended as safe regimes.  Pyridoxine (50 mg per day) should be given to prevent neurotoxicity in mother (peripheral neurophathy) and newborn (neonatal seizures). Use of Vitamin K has been recommended in infants at birth to cover the risk of postnatal haemorrhage due to R. Total duration of therapy is same for pregnant and non-pregnant ladies.
In addition to the above mentioned reserve drugs, safety of other reserve drugs like PAS, cycloserine etc. have not been proven during pregnancy and therefore elective abortion should be considered while treating a pregnant woman with MDR-TB. 
Breast feeding should not be discouraged. As R is a potent inducer of hepatic enzymes, the protective efficacy of oral contraceptive pills may be decreased. Such ladies suffering from TB and using contraceptive pills should be advised either to use some alternative anti-contraception method or use pills containing higher doses of oestrogens (50 µg). 
If mother is sputum smear positive at birth, the newborn should be evaluated for active TB by Xray, gastric aspirate etc. If active disease is diagnosed, child should receive full therapy with RZH. If active disease is ruled out, give isoniazid prophylaxis to newborn for 3 months and repeat mantoux test. If mantoux test is positive and active disease is ruled out, a total of 6 months prophylaxis with isoniazid should be given. If mantoux test is negative, isoniazid should be stopped and child given BCG vaccination.
| HIV Infection|| |
TB is still a major public health problem in India and with the emergence of HIV infection, the problem of TB has been further complicated. There are more than 12 million dually infected (TB and HIV) persons globally and India accounts for more than one million of them.  Uncontrolled HIV infection leads to progressive immuno-deficiency, due to which, these patients are more prone to various types of infections including TB. The incidence of TB in HIV infected individuals is 60 - 100 fold more than in the general population. HIV infection promotes the progression of recent and old TB infection to active disease. On the other hand there is also convincing evidence that TB too accelerates the course of HIV infection. M. tuberculosis probably increases viral replication by inducing macrophages to produce tumor necrosis factors, IL - 1 and IL - 6. 
The clinical presentation of TB in HIV infected cases depends upon the degree of immunosuppression.  Pulmonary tuberculosis is still the commonest form of TB even in HIV infected cases. In early stages, clinical picture often resembles post primary TB, sputum smear is often positive, chest x-ray shows cavitary lesions often and extra pulmonary tuberculosis (EPTB) is much less common. In late cases, having marked immunosuppression, the clinical picture often resembles primary tuberculosis, sputum smear is often negative, chest skiagram show infiltrative lesions with no cavities (skiagram may be normal too) and EPTB is much more common. Common EP lesion include pleural effusion, lymphadenopathy, pericardial and meningeal involvement and haematogenous dissemination or miliary spread.
Morbidity in HIV infected TB patients is high because they also suffer from other HIV related infections like pneumonia, diarrhoea, fungal infections etc. Similarly fatality is also high in these individuals. The case fatality in HIV/TB cases is 20 percent for new sputum smear positive cases and 50 percent for new sputum smear negative cases. Most deaths are due to other AIDS related opportunistic infections. In any patient with TB, the possibility of associated HIV infection should always be thought if there is presence of generalised lymphadenopathy, chronic diarrhoea, Herpes Zoster, recurrent pneumonia, bactraemia, weight loss more than 10 kg., burning sensation of feet (due to peripheral sensory neuropathy), painful genital ulcerations, Kaposi's sarcoma or oral hairy leukoplakia. As in HIV infected cases, proper sputum specimens may be more difficult to obtain, the need for bronchoscopy may be more in these individuals.
The basic guidelines of anti-TB therapy to be followed in HIV infected patients are same as those for HIV negative cases. As severe reactions, including Stevens - Johnson syndrome with thiacetazone (T) are 20 times more in HIV infected cases,the use of T is contraindicated in these cases. S should be used only if very high standards of sterilization can be ensured. Relapse and failure rates are higher with regimes which do not contain R in the continuation phase.
R interacts with antiretroviral drugs (ARV) and this may result in decreased effectiveness of these drugs. Concomitant use of Protease Inhibitors (PI) and R results in higher serum levels of R and lower levels of PIs. 
Upto 20 percent HIV infected TB cases may require alteration of TB treatment due to various side effects of ATT therapy. Because of non-compliance and higher bacillary load, chances of MDR-TB are high in HIV positive cases and their treatment should be fully supervised. As relapse rates are also high in HIV infected individuals, their follow up should be life long. Some reports have also suggested prolongation of the continuation phase, but more studies are required to settle this issue. ,
Regarding BCG, same principles apply to both HIV infected and negative cases, but BCG is contraindicated in symptomatic HIV cases. In Indian scenario, the role of isoniazid chemoprophylaxis is doubtful because of high resistance to isoniazid and number of other factors. ,
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