Leprosy therapy

It is important to note that many non-sulfonamides are known that can compete with j AB (/ -aminobenzoic acid). The most used of these is dapsone 9.17), 4,4 -di(aminophenyl)sulfone, the sheet anchor of all leprosy therapy. Others contain no sulfur atom, but have the requisite steric and electronic resemblance to pAR. For example, the insertion of a chlorine atom into either the 2- or the 3-position of pAR makes an active anti-pAB substance (Wyss, Rubin and Strandskov, 1943). Diaminobenzil 2.15) is several times more active against bacteria than sulfanilamide, and is reversed by / AB (Kuhn, Weygand and Moller, 1943). Again,/ -aminobenzenearsonic acid, atoxyl 6.2) has a typical sulfanilamide-like action (Albert, Falk and Rubbo, 1944). Although, in general, arsonic acids are not antibacterial, atoxyl forms an exception because it resembles pAR sufficiently, sterically and electronically, to compete with it. 

McGeer, P.L., Harada, N., Kimura, H., McGeer, E.G. and Schulzer, M. (1992). Prevalence of dementia amongst elderly Japanese with leprosy apparent effect of chronic drug therapy. Dementia 3, 146-149. 

Mycobacteria are responsible for two diseases tuberculosis, mostly caused by M. tuberculosis, and leprosy due to M. leprae. The therapeutic principle applicable to both is combined treatment with two or more drugs. Combination therapy prevents the emergence of resistant mycobacteria Because the antibacterial effects of the individual substances are additive, correspondingly smaller doses are sufficient Therefore, the risk of individual adverse effects is lowered. Most drugs are active against only one of the two diseases. 

Acedapsone is a derivative of dapsone that has little activity against M. leprae but is converted to an active dapsone metabolite. It is a long-acting intramuscular repository form of dapsone with a half-life of 46 days. It may prove useful in leprosy patients who cannot tolerate long-term oral dapsone therapy. 

Clofazimine is given to treat sulfone-resistant leprosy or to patients who are intolerant to sulfones. It also exerts an antiinflammatory effect and prevents erythema nodosum leprosum, which can interrupt treatment with dapsone. This is a major advantage of clofazimine over other antileprosy drugs. Ulcerative lesions caused by Mycobacterium ulcerans respond well to clofazimine. It also has some activity against M. tuberculosis and can be used as last resort therapy for the treatment of MDR tuberculosis. 

Occasionally dapsone has been added to the usual chloroqutne therapeutic regimen for the prophylaxis of chloroquine-resistant P. falciparum malaria. It is also used in combination therapy for leprosy. 

PABA) incorporation into folic acid (inhibition of folate synthesis). In large proportion of Mycobacterium leprae infections e.g. in lepromatous leprosy, resistance can develop, so combination of dapsone, rifampicin and clofazimine is used in initial therapy. 

Rifampin, usually 600 mg/d (10 mg/kg/d) orally, must be administered with isoniazid or other antituberculous drugs to patients with active tuberculosis to prevent emergence of drug-resistant mycobacteria. In some short-course therapies, 600 mg of rifampin are given twice weekly. Rifampin 600 mg daily or twice weekly for 6 months also is effective in combination with other agents in some atypical mycobacterial infections and in leprosy. Rifampin, 600 mg daily for 4 months as a single drug, is an alternative to isoniazid prophylaxis for patients with latent tuberculosis only, who are unable to take isoniazid or who have had exposure to a case of active tuberculosis caused by an isoniazid-resistant, rifampin-susceptible strain. 

Several drugs closely related to the sulfonamides have been used effectively in the long-term treatment of leprosy. The most widely used is dapsone (diaminodiphenylsulfone). Like the sulfonamides, it inhibits folate synthesis. Resistance can emerge in large populations of M leprae, eg, in lepromatous leprosy, if very low doses are given. Therefore, the combination of dapsone, rifampin, and clofazimine is recommended for initial therapy. Dapsone may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients. 

Rifampin (see earlier discussion) in a dosage of 600 mg daily is highly effective in lepromatous leprosy. Because of the probable risk of emergence of rifampin-resistant M leprae, the drug is given in combination with dapsone or another antileprosy drug. A single monthly dose of 600 mg may be beneficial in combination therapy. 

Clofazimine is effective against Mycobacterium leprae and is used primarily as an adjunct in the treatment of leprosy. During clofazimine therapy, many patients experience problems with red to brownish-black discoloration of the skin. Although this discoloration is reversible, it may take several months to years before skin color returns to normal. Other adverse effects include abdominal pain, nausea, vomiting, and rough, scaly skin. 

For a time, the question of the bacterial origin of these bodies was hotly debated. Hanks,208 from cytological evidence and the fact that such materials were confined to the leprosy bacillus and disappeared during sulfone therapy, persuasively reasoned that they originated in M. leprae. Moreover, since chloroform in aqueous systems declumped and dispersed M. leprae, he concluded that mycobacterial lipids were the major bonding substances in the electron-transparent material. Since the material of the capsule can be stained with Sudan Black B, Fisher and Barksdale209 and Nishiura et al.2 0 had concluded that the electron-transparent zone which surrounds M. leprae in vivo is lipid. 

Oxygen is used for the correction of hypoxia and as a diluent or carrier gas for vapors and gases, primarily anesthetic agents. The use of oxygen at increased pressure is termed hyperbaric oxygen therapy. This therapy is used in diverse conditions such as multiple sclerosis, traumatic spinal cord injury, cerebrovascular accidents, bone graft, fractures, and leprosy. However, there are no available authentic data, as there are no well-controlled clinical trials. 

Effective treatment of leprosy is complex and requires much experience to obtain the best results. Problems of resistant leprosy now require that multiple drug therapy be used and involve ... 

Neuropathy has not been reported in patients with leprosy taking the usually recommended dosage of 100 mg/day. Isolated cases of dapsone-induced peripheral neuropathy, including motor and minor sensory defects, have been published (15,16). The clinical characteristics include a motor neuropathy affecting the extremities with onset within 5 years after the start of dapsone therapy in doses of over 300 mg/day. Complete recovery from the neuropathy almost always occurs after the dose is reduced or the drug is withdrawn. 

Serious cutaneous reactions, such as exfoliative dermatitis, toxic epidermal necrolysis, and erythema multiforme buUo-sum are extremely rare. Erythema nodosum leprosum has been described during dapsone therapy, mostly in the lepro-matous type of leprosy (10). If erythema nodosnm develops before the start of therapy, the drug should be withheld until the reaction has disappeared. Severe erythema nodosum can be controlled by short-term glucocorticoid therapy. Desensitization to dapsone in patients with hypersensitivity reactions has been proposed (29). 

Richardus JH, Smith TC. Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy. Lepr Rev 1989 60(4) 267-73. 

Modderman ES, Huikeshoven H, Zuidema J, Leiker DL, Merkus FW. Intramuscular injection of dapsone in therapy for leprosy a new approach. Int J Chn Pharmacol Ther Toxicol 1982 20(2) 51-6. 

Paradoxical reactions are often observed in patients with pulmonary and extra-pulmonary tuberculosis being treated with HAART. Clinicians need to distinguish these from other adverse reactions related to drug therapy. Reversal reactions in leprosy are increasingly likely as more patients with HIV infection are treated with HAART in developing countries. 

Hepatotoxicity of combined therapy for leprosy has been reported in 39 patients treated with dapsone, pro-tionamide, and rifampicin. There were similar findings in 50 patients treated with dapsone, clofazimine, rifampicin, and protionamide. Deaths probably related to the drngs occurred in both groups after 3-4 months of treatment... 

Ji BH, Chen JK, Wang CM, Xia GA. Hepatotoxicity of combined therapy with rifampicin and daily prothiona-mide for leprosy. Lepr Rev 1984 55(3) 283-9. 

Dapsone in combination with trimethoprim is also used for the treatment of mild to moderate first episodes of TCP, or alone for PCP prophylaxis [115, 198]. The most frequent adverse events are dose related metheglobinemia and hemolytic anemia. Since multi-drug therapy began to be used in leprosy patients, an increasing number of a rare, idiosyncratic reaction with multiorgan involvement... 

It has been e.stimatcd that there arc. about 11 million ca.scs of leprosy in the world, of which about 60% are in Asia (with 3.5 million in India alone). The first reports of dapsonc resi.stancc prompted the use of multidrug therapy with dap-.sonc, rifampin, and clofazimine combinations in some geographic iucas. ... 

In addition to these uses, IL-2 has been found to be effective in the treatment of patients with disseminate cancer of the kidney and melanoma and in adjuvant therapy of acute myeloid leukemia. Attempts have been made to apply it in the treatment of AIDS and leprosy. The most common areas for IL-2 therapy are renal ceU carcinoma, melanoma, and lymphoma. ... 

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