In addition to treating pulmonary tuberculosis, you may have to treat ''surgical' tuberculosis in a patient's lymph nodes (29.2), his bones and joints (29.3), his abdomen (29.5), his urinogenital tract (29.6), and in a woman's breasts, where it can present as a lump (21.3), or as an oedematous swelling, due to the involvement of her axillary nodes (31.6). Diagnosing tuberculosis can be difficult. In the developing world, and particularly if BCG has been given, a positive tuberculin test strengthens the diagnosis, only if it is strongly positive (for example Mantoux test [mt]30 mm at 72 hours). A persistently negative one makes the diagnosis of tuberculosis unlikely, unless the patient is severely ill (as with miliary tuberculosis), is HIV-positive (see below), or is very malnourished, or has some other severe illness.
If you can send tissue for histology, especially a lymph node, the diagnosis of tuberculosis is easily confirmed. If this is impossible, or will take too long, you can usually tell if tissue is tuberculous, by cutting it across and looking for caseous areas. Finally, ''If you can't think of a diagnosis, always remember the possibility of tuberculosis''.
The same drugs that are used for pulmonary tuberculosis are highly successful in surgical tuberculosis[md]if a patient takes them regularly, and completes the course. The great danger is that he will stop taking them as soon as he feels a little better. The regime that you choose to use will have to depend on: (1) how much money there is for drugs, (2) how easy it will be for him to attend a clinic for injections of streptomycin, (3) if (based on (1) and (2)) you decide to admit him, and (4) if drug resistance is likely. It is unlikely, except in patients who have been partly treated before. We give several alternative regimes below, and there will probably be a standard one in your area. Most regimes have an initial intensive phase, followed by a continuation phase. Never treat tuberculosis with a single drug, because of the risk of acquired resistance.
Isoniazid is the main drug, and if rifampicin were not so expensive, it would be the best companion drug to go with it. Because it is so expensive, you will probably have to use thiacetazone with isoniazid in a compound tablet. Thiacetazone is widely used in Africa, but some communities elsewhere show an unacceptably high frequency of adverse reactions to it. Fortunately, the prices of rifampicin and ethambutol are falling. In India, streptomycin, INAH, and thiacetazone are provided free at tuberculosis centres; the difficulty is getting patients to go to them. Unfortunately, there are times when even these drugs are not available.
Supervise a patient carefully. If he does not complete his course of treatment, the organisms infecting him may become resistant, his disease may progress, and he may need extensive surgery[md]if he can get it. If he fails to attend for outpatient treatment, see that somebody visits him at home.
Treat surgical tuberculosis with drugs, and try not to drain tuberculous abscesses, unless you have to. If they have to be drained, close the wound without inserting a drain. For a tuberculous spine, or a large joint, use a suction drain. The danger is that they may become secondarily infected. Before the introduction of chemotherapy, draining a tuberculous abscess often led to a persistent sinus, and was sometimes fatal.
HE MUST CONTINUE TO TAKE HIS DRUGS HIV and tuberculosis. Highly pathogenic organisms, such as Myc. tuberculosis may infect HIV-positive patients early, before immune deficiency has fully developed. Less virulent ones, such ]]as Myc. avium-intracellulare, strike later, when immune deficiency is complete. Tuberculosis may thus precede AIDS by several months. The risk of an HIV-positive patient acquiring tuberculosis depends on the prevalence of the disease in the local population. In Zambia, where both diseases are common, about 50% of new tuberculous patients are HIV-positive, commonly with multibacillary forms of the disease.
Fever, fatigue, and weight loss are common in both diseases. In an HIV-positive patient, tuberculosis affects the lungs less often than other parts of the body, and may become widely disseminated to involve: the lymph nodes (these cannot be distinguished from those enlarged by HIV alone), the joints, the spine, the blood (miliary tuberculosis), the genitourinary tract, the liver, the peritoneum, and the central nervous system (tuberculomas, cerebral abscesses, and meningitis). There may be little or no granuloma formation, and few lymphocytes in the lesions (''areactive' tuberculosis).
The X-ray appearances of pulmonary tuberculosis are often atypical in an HIV-positive patient. His hilar and mediastinal lymph nodes are commonly enlarged, as are his middle or lower lobes, while his upper ones are spared; cavitation is rare. There is only a 40% chance that he is tuberculin-positive, and when he is, the reaction is weak and often becomes negative later.
Give him a standard course of treatment. Bacilli will probably disappear from his sputum in one to three months. Treat him for 9 months, and consider giving him daily isoniazid after that to prevent relapse. HIV increases the incidence of adverse drug reactions, particularly, it is said, to thiacetazone, so suspect HIV when these occur. IF YOU CAN'T THINK OF A DIAGNOSIS, THINK OF TUBERCULOSIS
CHEMOTHERAPY [s8]FOR TUBERCULOSIS [em]ISONIAZID (INAH). Daily dose 300 mg, children 10 mg/kg. Intermittent adult dose 15 mg/kg, with pyridoxine 10 mg per dose to prevent neurotoxicity.
THIACETAZONE. Daily dose 150 mg, children 4 mg/kg.
STREPTOMYCIN. Daily dose: if a patient is less than 50 kg give him 750 mg daily, if he is more than 50 kg give him 1 g daily if he is under 40, and 750 mg daily if he is over 40; children 20 mg/kg. The disadvantage of streptomycin is that it has to be injected, but in some communities injections are best.
RIFAMPICIN. Daily dose: less than 50 kg give the patient 450 mg, more than 50 kg give him 600 mg; children 10 to 20 mg/kg. Intermittent adult dose 600 to 900 mg.
PYRAZINAMIDE. Daily dose, less than 50 kg give him 1.5 g, more than 50 kg give him 2.0 g; children 30 mg/kg. Intermittent dose 3 times a week: give him 2.0 g if he is less than 50 kg, and 2.5 g if he is more than 50 kg. Intermittent dose twice a week: give him 3.0 g if he is less than 50 kg, and 3.5 g if he is more than 50 kg.
ETHAMBUTOL. Daily dose 25 mg/kg for 2 months, then 15 mg/kg; children as for adults if aged 12 years or more. Intermittent dose three times a week 30 mg; twice a week 45 mg.
REGIMES (1) Daily throughout. The common regime in India and in East and Central Africa is daily streptomycin for 60 days at 20 mg/kg. Starting at the same time, give thiacetazone and INAH as a compound tablet (''Thiazina' or ''Isozone Forte') for 12 or 18 months. For an adult this contains thiacetazone 150 mg (3 mg/kg) and INAH 300 mg (6 mg/kg). It has a 92% success rate in previously untreated cases[md]if he completes the course. The drugs for the entire course cost $30. You may occasionally have to admit him to give him his streptomycin, which will add to the cost, but the cost of 2 months' admission is low compared with the cost of rifampicin.
(2) Daily throughout. Two months of daily streptomycin, isoniazid, rifampicin, and pyrazinamide, followed by 6 months of daily isoniazid and thiacetazone. Total duration 8 months, success rate 98%.
(3) Partly intermittent. Streptomycin, isoniazid, rifampicin, and pyrazinamide daily for 2 months. Then streptomycin, isoniazid, and pyrazinamide twice a week for 6 months. Total duration 8 months.
(4) Intermittent throughout. Streptomycin, isoniazid, rifampicin, and pyrazinamide 3 times a week for 4 months, then isoniazid, rifampicin, and pyrazinamide 3 times a week for 2 months. Total duration 6 months.
CAUTION ! Always aim to give antituberculous treatment as a complete regime. Shorter courses are likely to be ineffective, and promote drug-resistance.
ADMISSION. If he does not live near a clinic, where he can get injections, admit him to give him his streptomycin.
NO ADMISSION. If you are not going to admit him, and can afford rifampicin, use one of the intermittent regimes. They all contain isoniazid, rifampicin, and pyrazinamide. If giving him an injection is likely to encourage his compliance, then the regime should contain streptomycin. A completely oral intermittent regime of ethambutol, isoniazid, rifampicin, and pyrazinamide is equally effective, but more expensive.
If cost is critical, give him regime (1). But if he lives near a clinic, a fully supervised regime like regime (3) is likely to prove more successful and less toxic.
If cost is less critical, use regime (4).
If, in the local community, there is a high prevalence of strains of bacilli which are resistant to streptomycin and isoniazid, you will have to use a four-drug regime. This is only likely to be the case when there are many people who do not complete their treatment. If so, your follow-up programme needs improvement.
TOXICITY Be aware, and make your staff aware, of the the toxic reactions of antituberculous drugs, especially those outlined below like this.
ISONIAZID (INAH). (1) Peripheral neuritis, [pm]30%. Painful ''hot' soles of the feet, especially in patients whose livers metabolize the drug slowly. You can usually continue treatment, if you notice the condition early. Give him piridoxine 20 or 25 mg/day. If pain forces you to stop INAH, give another drug. (2) Psychoses, [pm]0.5%, reversible, stop INAH immediately. (3) Jaundice [lt]0.5%, reversible if you stop INAH fairly soon.
THIACETAZONE. (1) Dermatosis. 30% of light-skinned persons (Caucasians and mongoloids), [pm]5% of Africans. Typically itchy, black, 2 to 4 cm patches with a centre that may peel. Also, diffuse darkening of the skin with itching (less common). If noticed immediately, partially reversible.
STREPTOMYCIN. (1) Rash, [pm]5%, typically small widespread maculopapules usually accompanied by fever. Stop the drug. (2) Drug fever, [pm]5%. Stop the drug. (3) Dysfunction of the vestibular branch of the 8th nerve (vertigo, giddiness). If mild, continue. If moderate to severe, stop the drug. (4) Dysfunction of the cochlear function of the 8th nerve (deafness). Stop immediately: irreversible unless the drug is immediately discontinued.
RIFAMPICIN. (1) Transient jaundice usually 2 or 3 weeks after starting treatment. Unless jaundice is progressive, continue the drug. Liver function tests nearly always show some abnormality. (2) If his urine becomes orange-red, this is not a sign of toxicity, it always happens. (3) Gastrointestinal symptoms, usually minor. (4) Drug fever (uncommon). (5) An MOI (monoamine oxidase inhibitor)-like action (uncommon), with intolerance to cheese, fish and meat extracts, and sensitivity to alcohol.
PYRAZINAMIDE. Arthralgia, hepatotoxicity, and urticaria are all unusual.
ETHAMBUTOL. (1) Visual impairment, [pm]1%, reversible if recognized quickly and the drug is stopped. Test the visual acuity (24.1) of all patients on this drug every 2 weeks, and make them aware that they must report any slight deterioration in acuity.
Fig. 29-1 NEGLECTED TUBERCULOSIS OF BOTH HIPS for 29 years. This patient could not even crawl. He dragged himself along in a sitting position, with both his hips and knees fully flexed. Kindly contributed by Ronald Huckstep.