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PubMedDate not supplied

Trends in leprosy over fifty years in Gudiyatham Taluk, Vellore, Tamil Nadu.

This paper presents epidemiological trends over a fifty-year period observed in a defined population served by the Schieffelin Leprosy Research and Training Centre (SLR & TC), Karigiri, Vellore District in Tamil Nadu. It covers three distinct periods, namely, the pre-MDT era with dapsone monotherapy, the MDT era under a vertical leprosy control programme and the MDT era after leprosy control services were integrated into the general health services. Prevalence rates have declined steadily from 125 per 10,000 population at the time of introduction of MDT in 1982 to 5 per 10,000 at the time of integration in 1997 to less than 1 per 10,000 in 2005. The new case-detection rate was 5.4 per 10,000 when the field programme started in 1962, and held steady at 15-20 per 10,000 between 1970 and 1980. It then showed a gradual fall from 10.8 per 10,000 in 1985 to 3.9 at the time of integration, and continued to fall in the post-integration period and was 0.8 per 10,000 in 2005. The mean age at detection showed a gradual increase from 23.4 years in the dapsone era to 31.2 years in the post-integration period. The male: female ratio showed a preponderance of males almost throughout the reference period. While polar types of leprosy (TT & LL) were common in the dapsone era, more of borderline leprosy (BT & BL) cases was seen more recently. MB rates that were high initially, declined steadily during monotherapy and stabilized between 10% and 12% during the vertical MDT programme and is showing an increase in the post-integration-period. The proportion of cases with Grade 2 disability at registration showed a gradual decline during the monotherapy period, remained relatively unchanged at 8%-10% during the the MDT period, and showed a sharp rise in the immediate post-integration period before falling. Analysis of trends of leprosy in a well-defined geographical population over a fifty-year period gives useful information on how the disease has evolved over the years. It provides opportunities to explore the reasons for the changes observed, though one has to be cautious while interpreting such data due to changes in definition, the play of operational factors, and changes in policies and strategies.

Adult↗
PubMedDate not supplied

[Epidemiology of leprosy in Guadeloupe from 1970 to 1984].

Analysis of computerized data compiled according to the OMSLEP system in the leprosy control service in Guadeloupe has shown that from 1970 to 1984, 80% of the patients were detected by passive case-finding (symptomatic patients), 10% by active case-finding among the school population and 10% by active case-finding among the house-hold contacts of known patients. During the same period of time, global incidence of new cases of leprosy declined from 24 to 11 per 100,000 inhabitants. The decline was greater for paucibacillary cases (y = -0,94) than for multibacillary cases (y = -0,45), and much greater among persons under 15 years of age (y = -3,22) than among those older ones (y = -0,67). Simultaneously 118 relapses, an annual incidence of 1,3%, were observed among the multibacillary patients previously treated by dapsone monotherapy for five years or more. All cases the biopsies of whom were inoculated for drug sensitivity testing in the mouse foot pad yielded dapsone-resistant M. leprae. The proportions of relapses among the annual sources of infection increased from 16% in 1970 to 47% in 1984. Chemoprophylaxis of relapses among multibacillary patients already treated for more than five years with dapsone monotherapy is one of the priorities for leprosy control in Guadeloupe.

Age Factors↗
PubMed1986

[Erythema annulare centrifugum revealing linear IgA dermatitis of childhood].

Linear IgA dermatitis was diagnosed in a 13-year old girl with erythema annulare centrifugum (EAC) on the basis of the criteria laid down by Jablonska: vesiculo-bullous eruption with specific patterns on subsequent flare-ups, subepidermal vesicles and bullae with papillary eosinophilic abscesses in erythematous areas, positive linear IgA antibody response at direct immunofluorescence in the lamina basal, absence of intolerance to gluten and responsiveness to sulfapyridine and dapsone. This patient was followed up for 10 years. During the first 5 years any attempt at withdrawing dapsone resulted in quick relapse which always remained responsive to that drug. After 5 years discontinuing dapsone was no longer followed by relapse, and the girl was considered clinically cured. Yet direct immunofluorescence in healthy skin remained positive for 2 years after treatment was stopped, as has previously been reported. At the age of 23, after 5 years without treatment the patient remained cured. This case demonstrates that linear IgA dermatitis is one of the causes of EAC. Autoimmune bullous diseases, such as pemphigus with eosinophilic spongiosis, bullous pemphigoid and dermatitis herpetiformis, are known to present as EAC. Direct cutaneous immunofluorescence is necessary to the aetiological diagnosis of EAC.

Adolescent↗
PubMed1982

Rifampicin (RFP) trial in lepromatous leprosy.

Rifampicin trial in 66 lepromatous cases is reported. Some of these cases were previously treated with Dapsone and some were fresh cases, the main criterion for selection being high BI and MI. The cases were divided into 7 groups depending on the dosage and frequency of administration of RFP. Dapsone was given in all the cases. Whenever MI became zero, Rifampicin was stopped but Dapsone continued. In those cases when MI remained high, RFP was stopped either because of non-improvement or reactions or the patient dropped out. Only 2 groups showed good improvement: RFP 900 mg. once a week and RFP 600 mg. 6 times a week. The latter group is preferable and the average period required to render MI zero was about 45 days.

Clinical Trials as Topic↗
PubMed1995

Relapses during long-term follow up with drug-susceptible M. leprae among multibacillary leprosy patients treated with multidrug therapy regimens; case reports.

A controlled clinical trial in highly bacilliferous multibacillary leprosy patients was initiated in 1977. We report here two cases of relapse during long-term follow up of patients 15 years after the start of treatment. The patients reported here were treated with rifampin, isoniazid, clofazimine and dapsone for the first 3 months followed by clofazimine and dapsone until 84 months in one case; the other case received the same treatment but had received dapsone alone for 60-80 months. The relapses occurred 6(1/2) 7(1/2) years after therapy was discontinued.

Drug Therapy, Combination↗
PubMed1993

Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome.

Pneumocystis carinii infection remains extremely common in the immunocompromised patient population, particularly in patients with human immunodeficiency virus (HIV) infection, despite the availability of effective prophylaxis. Although most commonly presenting as an acute pneumonia, the organism can infect a multitude of different organs, and thus may pose difficulty in diagnosis. Because effective treatment regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and parenteral pentamidine are hindered by a high rate of adverse reactions, alternative regimens are continuing to be evaluated. Of greatest promise to date for patients with mild-to-moderate disease are the alternative oral regimens of atovaquone, dapsone with trimethoprim, and clindamycin with primaquine. The addition of corticosteroids to anti-Pneumocystis therapy in patients with severe disease has been shown to improve both the short-term and long-term success of treatment. TMP-SMX and aerosolized pentamidine have been shown to be effective in the primary and secondary prevention of pneumocystosis; prophylactic regimens currently under study include dapsone, dapsone with pyrimethamine, and once-monthly parenteral pentamidine.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The reduction of the leprosy endemicity in northeastern Zaire 1975/1989.

The leprosy endemy in Uele, North Eastern region of Zaire has declined considerably since the 1950's, particularly since 1975. The hypothesis is advanced that the most important causal factor has been the distribution of dapsone for many years, through a vertical programme. The gradual increase of dapsone resistance has been taken care of by the introduction of combined, multidrug therapy in the 1980's. The cost per patient detected and treated rises in inverse proportion to the decline in endemy; therefore, the time has come for the integration of a leprosy control in the primary health care strategy. However, central specialized teams financed by voluntary organisations should be maintained to assure training of personnel, to give advice in diagnosis, prevention and treatment of complications, to provide drugs and to assist in rehabilitation.

Dapsone↗
PubMed1991

Cytogenetic studies in leprosy patients before and after chemotherapy.

The frequencies of chromosome aberrations and sister chromatid exchanges (SCEs), cell proliferation kinetics and mitotic indices were studied in peripheral blood lymphocyte cultures of leprosy patients both before and after chemotherapy. The differences in the frequencies of chromosome aberrations and SCEs between controls, paucibacillary and multibacillary patients were found to be statistically highly significant (P less than 0.001). The extent of cytogenetic damage seemed to depend on the severity of the disease. Lymphocytes of untreated leprosy patients showed a low mitotic index and a slow rate of cell proliferation. Following combined treatment with dapsone and rifampicin there was an increase, but to a lesser degree (P less than 0.01), in the frequency of SCEs and chromosome aberrations while the drug combination of dapsone, rifampicin and clofazamine had a nonmutagenic effect on chromosomes of the patient. Furthermore, after drug treatment, the cell proliferation rate and mitotic indices in paucibacillary patients were comparable to that of controls. These results indicate the clastogenic potency of Mycobacterium leprae and the remedial effects that follow therapeutic drug treatment.

Adult↗
PubMed1977

The immunoglobulin-bearing cells in the lamina propria and the clinical response to a gluten-free diet in dermatitis herpetiformis.

In 17 patients with DH, multiple duodenal and jejunal biopsies were performed. In all patients the small-intestinal biopsy-specimens showed histopathological changes compatible with coeliac disease. Fourteen of the patients maintained a gluten-free diet (GFD) for more than 8 months. The small-intestinal lesions improved in all patients investigated during the GFD. The dosage of Dapsone needed to control the sin lesions could be reduced by more than 50% in 4 patients and the Dapsone could be stopped in 5 other patients on GFD. The immunoglobulin-bearing cells in the lamina propria were counted in 8 patients not on a gluten-free diet, in 6 patients on gluten-free diet, and in 8 healthy controls. The numbers of IgA-, IgM- and IgG-bearing cells were increased in most of the DH patients who were not on a gluten-free diet. The number of IgM-bearing cells in the DH patients who were on a gluten-free diet was the same as that in the control group. This may indicate a mainly IgM response in the lamina propria induced by gluten.

Adult↗
PubMed1995

A pilot study on the efficacy of epiroprim against developmental stages of Toxoplasma gondii and Pneumocystis carinii in animal models.

The new bacteriocidal drug epiroprim (Ro-11-8958) was tested (alone or in combination with dapsone) on its efficacy against Toxoplasma gondii and Pneumocystis carinii in their hosts: laboratory mice and/or nude mice/rats, and was compared to the curative effects of the recent drugs of choice. The experiments clearly pointed out that epiroprim has significant effects on the reduction of both parasites when given alone. In combination with dapsone epiroprim led to a complete cure of toxoplasmosis in mice. This finding is of some importance for AIDS patients mostly suffering from bacteriosis and parasitosis at the same time.

Animals↗
PubMed1994

Chronic methemoglobinemia: improving hemoglobin saturation monitoring during anesthesia.

Methemoglobin interferes with the accuracy of pulse oximetry data. Methemoglobinemia is caused by many factors, both congenital and acquired. However, the increasing usage of dapsone, which converts hemoglobin to methemoglobin, is increasing the number of patients with methemoglobinemia. We present the case of a patient with dapsone-induced methemoglobinemia who was successfully treated with methylene blue, which converts methemoglobin back to hemoglobin.

Aged↗
PubMed1995

[Pyoderma gangrenosum as a precursor of myeloid leukemia].

A 34-year-old woman who was 20 weeks pregnant developed pyoderma gangrenosum while receiving treatment for infarct pneumonia. Because of her septic condition an abortion was performed. The patient received intravenous prednisolone as a pulse treatment for her pyoderma gangrenosum, which was followed by oral methylprednisolone and oral dapsone for 6 weeks. After dose reduction the patient had a severe relapse. The steroid dose was increased and dapsone was replaced by cyclosporin A. The smaller ulcers healed spontaneously, but skin grafting had to be performed for the large ulcer. The steroid therapy was tapered and discontinued. Cyclosporin A was continued for 10 weeks as monotherapy. Subsequently, the patient was free of symptoms for 7 months. Twelve months after the diagnosis of pyoderma gangrenosum the patient developed acute myeloid leukaemia accompanied by a recurrence of the skin disease.

Adult↗
PubMed1989

Delay in emergence of mefloquine resistance in Plasmodium berghei by use of drug combinations.

Blood induced Plasmodium berghei infection in Swiss mice was exposed during successive passages to melfloquine alone or melfoquine in combination with dapsone or primaquine or erythromycin, and the level of resistance to melfoquine in four sub-lines was compared at ED90 level. Treatment with mefloquine alone resulted in a 201.14 fold increase in resistance after 21 passages. Use of drug combination (melfoquine + dapsone) delayed the acquisition of resistance as shown by a marginal increase of ED90 by 5.76 fold after 34 passages. Similarly, there was a 17.84 fold increase of resistance after 32 passages involving exposure to mefloquine-primaquine and a 112.28 fold increase after exposure to melfoquine-erythromycin combination for 31 passages. The study emphasizes that rational drug combinations should be developed to protect the melfoquine against the emergence of resistance in P. falciparum cases.

Animals↗
PubMed1983

Inhibition of the release of prostaglandins, leukotrienes and lysosomal acid hydrolases from macrophages by selective inhibitors of lecithin biosynthesis.

The release of the inflammatory mediators, prostaglandins (PGs), leukotrienes (LT) and lysosomal acid hydrolases (LAH), by macrophages is stimulated by endocytic stimuli such as zymosan. This process can be interfered with by specific inhibitors of phosphatidylcholine (PC) biosynthesis. The diphenylsulfone dapsone and three analogs selectively inhibited [14C]choline incorporation into PC but had varied effects on inhibition of mediator release by macrophages. Dapsone inhibited the release of PGs, LT and LAH, whereas the three closely related structural analogs inhibited LAH release only, with little or no effect on PG production.

Animals↗
PubMed1994

Major aphthous ulcers in patients with HIV disease.

Major aphthous ulcers are associated with a high degree of morbidity in patients infected with human immunodeficiency virus. A large representative cohort infected with human immunodeficiency virus was examined to evaluate the prevalence of major aphthous ulcers, demographic data of patients with major aphthous ulcers, and the usage of major aphthous ulcers as a marker for immune deterioration. The effects of tobacco smoking and the use of specific antibiotics, trimethoprim/sulfamethoxazole or dapsone, on the development of major aphthous ulcers was also investigated. In a population of 767 persons infected with human immunodeficiency virus, major aphthous ulcers were found at a prevalence rate of 3.1% (24 patients). This type of lesion did not show any predilection for human immunodeficiency virus transmission category, ethnic group, or gender. Persons who received trimethoprim/sulfamethoxazole or dapsone or had a history of tobacco smoking showed a decreased prevalence of major aphthous ulcers. All patients (100%) with major aphthous ulcers had CD4+ cell counts below 100 cells/mm3, but only 50% had a previous acquired immunodeficiency syndrome defining illness. Major aphthous ulcers in persons infected with human immunodeficiency virus are suggestive of severe immune suppression and may serve as a marker for human immunodeficiency virus disease progression.

Adult↗
PubMed1988

Chlorproguanil/dapsone for the treatment of non-severe Plasmodium falciparum malaria in Kenya: a pilot study.

Chlorocycloguanil, the active metabolite of chlorproguanil, was synergistic in vitro with dapsone against 2 culture-adapted Plasmodium falciparum isolates from Kenya; maximal synergy occurred at lower concentrations that it did with pyrimethamine and sulfadoxine. 48 children with asymptomatic P. falciparum infections were treated with chlorproguanil (at a target dose of 1.2 mg/kg) and dapsone (target dose of 1.2 or 2.4 mg/kg); all were free of parasitaemia by day 7. The following numbers had recurrences on days 14, 21, and 28, respectively: 1 of 48, 7 of 47, and 7 of 40. All 39 children treated with pyrimethamine (target dose 1.2 mg/kg) and sulfadoxine (target dose 24 mg/kg) were cleared of infection, while the following had recurrences on days 14, 21, and 28: 1 of 39, 2 of 38, and 2 of 36. The rate of decrease in parasitaemia was the same in the 2 groups, and there was no change in haematocrit or haemoglobin during the follow-up. The rate of recurrence in the children receiving chlorporguanil/dapsone was higher, probably because these drugs have a much shorter clearance time than pyrimethamine/sulfadoxine. Chlorproguanil/dapsone is an effective combination for treating P. falciparum malaria and deserves further study.

Animals↗
PubMed1992

Reconstruction of anti-leprosy drug depleted complement haemolytic activity by addition of zymosan-treated sera (a source of C142) and CratEDTA (a source of C3-C9).

This paper describes the mechanism of in vitro interaction of human serum complement system with anti-leprosy drugs (dapsone and clofazimine) and anti-lepra reaction drugs such as chloroquine. These drugs could inhibit the complement-mediated lysis of erythrocytes both via direct and alternative pathways, but only at hypertherapeutic doses. Attempts were made to restore the drug depleted complement-mediated lysis of erythrocytes by adding zymosan-treated guinea-pig sera (a source of C142) and also by adding Crat-EDTA sera (a source of C3-C9). Destroyed complement-mediated haemolytic activity by dapsone could be restored by early complement (C142) components, while complement-mediated haemolytic activity blocked by clofazimine could be regenerated by adding both late (C3-C9) and early (C142) complement component. However, chloroquine-mediated inhibition of the complement-mediated haemolysis activity could not be appreciably restored by adding both early and late complement reagents.

Animals↗
PubMed2006

Validation of incorporating flurbiprofen into the Pittsburgh cocktail.

BACKGROUND: We have previously shown that flurbiprofen metabolism to 4'-hydroxyflurbiprofen provides an in vivo measure of cytochrome P450 (CYP) 2C9 activity. This study evaluated the possibility of incorporating flurbiprofen into the current 5-drug Pittsburgh cocktail. METHODS: In a randomized, 3-way, Latin-square, crossover-design study, 24 healthy subjects (mean age [+/-SD], 47.8 +/- 15.1 years) received flurbiprofen (50 mg) and the Pittsburgh 5-drug cocktail (100 mg caffeine, 100 mg mephenytoin, 10 mg debrisoquin [INN, debrisoquine], 250 mg chlorzoxazone, and 100 mg dapsone) separately and in combination on 3 occasions over a period of 5 weeks. Urine was collected from 0 to 8 hours, and plasma was obtained at 4 and 8 hours after drug administration. Parent drug and metabolite concentrations were measured to determine phenotypic indices for each of the metabolizing enzymes. RESULTS: The geometric mean ratio and 90% confidence interval of the phenotypic indices were included within the 80% to 125% bioequivalence range for each of the probe drugs. There were no statistically significant differences between the phenotypic indices determined after administration of the 5-drug and 6-drug cocktails. However, there was a small but statistically significant increase (7.5%, P = .03) in the 8-hour urinary flurbiprofen recovery ratio after administration of the 6-drug cocktail compared with that after administration of flurbiprofen alone. The 6-drug cocktail was well tolerated. CONCLUSION: The results of this study show that caffeine (CYP1A2), chlorzoxazone (CYP2E1), dapsone (N-acetyltransferase 2), debrisoquin (CYP2D6), flurbiprofen (CYP2C9), and mephenytoin (CYP2C19) can be simultaneously administered in low doses without metabolic interaction.

Administration, Oral↗