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Behind the story of one paucibacillary patient treated by dapsone monotherapy, the authors discussed on the possibility of relapse. But the therapy course, observed by DDS/Urine examination shows a default of the patient. The problems of follow up and attendance of the patient are discussed.
In two field trials in Nigeria, 74 male and female leprosy outpatients received intra-adipose depot injections of either dapsone (DDS) or monoacetyldapsone (MADDS) at 4-week intervals. Blood samples were taken regularly and sent to Amsterdam to determine the DDS and MADDS concentrations in serum using high-pressure liquid chromatography (HPLC). The DDS injection yielded a good sustained drug release. After repeated administration accumulation occurred, demonstrated by a statistically significant increase in the area under the curve (AUC) in time: until 28 days after the first injection, the mean AUC (+/- S.D.) amounted to 19.3 +/- 5.6 mg d/l in males and 15.1 +/- 5.2 in females; after the fourth injection, 26.4 +/- 7.5 and 24.6 +/- 9.0 mg d/l, respectively (p less than 0.001). One male patient developed an abscess at the injection site; otherwise no side effects were observed. Even better sustained-release results were observed with the MADDS injection. Unfortunately, the injection caused a number of abscesses. Consequently, the DDS injection was very well received by the patients of the DDS study, while half of the patients in the MADDS study would prefer tablets to the MADDS injection. Further investigations are required to find the cause of the abscesses before one of the injections, or possibly a combination of both, could be implemented in the multi-drug treatment regimen proposed by WHO to provide a valuable tool to combat noncompliance among leprosy patients.
A case of junctional epidermolysis bullosa (Herlitz) is reported. The patient has been treated with high doses of Dapson. The result is encouraging.
Pharmacokinetics of aspirin and chloramphenicol was studied in 16 normal and 16 patients suffering from leprosy. A significant increase (p less than 0.05) in the elimination half-life of chloramphenicol was observed before and after dapsone treatment in leprotic patients as compared with the normal volunteers, while no significant difference was observed in any of the pharmacokinetic parameters with aspirin.
A simple urine spot test for monitoring patient compliance to dapsone self-administration in leprosy therapy was recommended by WHO but later abandoned. The present article describes some important improvements to the test, which is characterized by its validity and straightforwardness.
Nine cases of superficial pemphigus that were treated by dapsone as the initial mode of therapy are reported. Five patients, all having low or negative serum anti-intercellular cement substance antibody titers, responded dramatically, while the other four patients, showing high titers of anti-intercellular cement substance antibodies, did not respond to this treatment. Complications of therapy were observed in three cases.
The absolute oral bioavailability of dapsone (DDS) was established in dogs and healthy volunteers by comparing AUC's after oral and intravenous administration. Five female inbred beagles each received 100 mg DDS orally and intravenously as a bolus injection in a randomized cross-over study. DDS serum concentrations were determined using HPLC. After both routes of administration, linear pharmacokinetics were observed, the elimination half-life (t1/2) amounting between 5.8 and 10.2 h. After oral administration, AUC values between 56.1 and 99.2 mg X h X l-1 were found, while after intravenous administration AUC's were between 63.5 and 98.1 mg X h X l-1. The absolute oral bioavailability, corrected for differences in t1/2, averaged 107 +/- 9% (SD). A similar study was carried out in 2 female and 3 male healthy volunteers. The intravenous dose was reduced to 50 mg and given as an infusion. Pharmacokinetics were linear after both routes of administration. The t1/2 values amounted between 15.6 and 30.4 h. AUC's ranged from 24.0 to 75.4 mg X h X l-1 after oral administration and from 13.3 to 37.5 mg X h X l-1 after intravenous infusion of half of the oral dose. The absolute, t1/2-corrected oral bioavailability was calculated to be 86 to 104%. Complete bioavailability of DDS was demonstrated in dogs and healthy volunteers. The method used in this study might help to detect possible DDS malabsorption in leprosy and dermatitis herpetiformis patients.
A 36-yr-old patient suffering from chronic ulcerative colitis complicated by severe pyoderma gangrenosum of the leg is presented. Pyoderma gangrenosum rapidly progressed and failed to respond to a combined treatment of bed rest, prednisone, sulfasalazine, povidone-iodine, compresses, and debridement. Pyoderma gangrenosum responded and disappeared with no recurrence during the following months after the combined treatment of methylprednisolone, dapsone, and zinc sulfate.
A comparative study of the HI test and paper spot test for screening dapsone in urine was carried out in 692 specimens of urine, 149 from the field and 502 from patients attending the C.L.T. and R.I. clinic or admitted in the wards and 41 control urines. A very good correlation was noticed between the 2 tests in relation to positivity or negativity as well as DDS concentration. Fifty one urine specimens showed a specific agglutination, 41 of them were considered HI positive and 10 of them HI negative based on DDS concentration. The results are discussed.
Several prodrugs of dapsone have been prepared and evaluated in vivo for the release of parent drug. The prodrug: 4,4'-dibutyrylaminodiphenyl sulfone gave blood levels above 0.5 micrograms/ml of DDS for about 34 days in rabbits injected intragluteally. The results have been compared with DDS and DADDS.
Combined therapy with prothionamide and dapsone was instituted in fifteen active untreated lepromatous leprosy cases for a period of 18 months. Clinical improvement was good with attainment of zero morphological index in about 66% cases. Bacteriological improvement was rather unsatisfactory as one case only reached zero level. Side effects were observed in few cases necessitating withdrawal of combined therapy and patients' prothionamide compliance was rather unimpressive.
Studies were undertaken in three independent centers to compare the newer, in vitro radiometric macrophage (M phi) assay with the conventional mouse foot pad infection for the diagnosis of dapsone resistance. Results obtained on 12 bacilliferous patients showed good concordance in both assays. One strain diagnosed as sensitive in the M phi assay was found to be resistant in the mouse foot pad. Three Mycobacterium leprae strains considered to be partially resistant in the mouse infection behaved as resistant strains in the M phi cultures. Attention is drawn to a rapid in vitro method for the identification of drug-resistant bacilli in leprosy patients.
An attempt has been made to screen the resistant strains of M. leprae in lepromatous patients from the eight northern States of India. By using the mouse foot pad technique it was found that in a total of 69 clinically suspected patients 33 (47.8%) harboured M. leprae with some degree of dapsone resistance. A detailed epidemiological study in these parts of the country may reveal the prevalence rate.
A 50-year-old man had eosinophilic pustular folliculitis (Ofuji's disease) characterized by follicular pustular papules on the face, confluent vesicles on the fingers, and a papulopustular area on the upper portion of the back. Extensive examinations and cultures of both pustular material and tissue revealed no organisms, except Staphylococcus epidermidis. The disease responded to dapsone therapy.
The in vivo effects of rifampin and dapsone on immunological responses were investigated using mice immunized with sheep erythrocytes. The number of cells producing antibody was not affected by a clinical (1 CD) or a threefold excess dose (3 CD) of the drugs administered for ten days. A similar result was obtained in an experiment using a mouse strain known to be low responders to the antigen. Induction of suppressor cells acting on antibody production was not influenced by 3 CD or 6 CD of the drugs. Neither delayed-type hypersensitivity nor induction of the suppressor cell population acting on delayed hypersensitivity was affected by 3 CD of the drugs. Phagocytosis of sheep erythrocytes by peritoneal cells and the growth of a tumor were not altered by 6 CD of the drugs.
The binding of dapsone to hen egg white lysozyme has been studied using fluorescence spectroscopy. At low concentrations the drug binds lysozyme with a Ka = 3.3 X 10(4) M-1 forming a 1:1 complex. At high concentrations the protein was found to bind the drug in a cooperative manner at two sites with an average association constant of 6.3 X 10(4) M-1. Both Trp-108 and Trp-62 of lysozyme are involved in the association process. Acetylation of the lysine residues increased the affinity of the drug to the protein. However, drug association showed no effect on the enzymatic activity of the protein.
One hundred and two specimens of urine collected from leprosy patients attending the field clinics of Central Leprosy Teaching and Research Institute, Chingleput, Tamil Nadu, India, were screened for dapsone by the paper spot test and Haemagglutination Inhibition (HI) tests. A concordance of about 90% was observed between the two tests. Both tests showed their merits. The lower sensitivity of the spot test finds more cases of irregular compliance (1-2 days), whereas the higher sensitivity of the HI allows the demonstration of the intake of lower doses and the detection of those cases, who have grossly missed their tablets (longer than a week).
Gandhi Memorial Leprosy Foundation conducted a study from 1963-72. Records of 2608 patients pertaining to type of leprosy, year of detection and registration, involvement of nerves, treatment, reactions, deformities, were available for a retrospective study. Patients having problems like neuritis and deformities and of the types lepromatous and borderline were the ones who tended to be regular clinic attenders. Lepromatous and Borderline and Polyneuritic types and N3 group were prone to develop deformities. There seemed to be association between reaction and causation of deformities. Because of the neurotoxic effect and ability to concentrate in the affected nerves, dapsone might enhance the risk of deformities. Low deformity rates in N1 and N2 types of nerve involvement reaffirmed the necessity of early diagnosis of leprosy.