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Efficacy of dapsone with pyrimethamine (Maloprim) for malaria prophylaxis in Maputo, Mozambique.

In a randomized controlled study of malaria prophylaxis, dapsone-pyrimethamine at a weekly dosage of dapsone 50-100 mg with pyrimethamine 6.25-12.5 mg or placebo was administered to 166 school children for 17 weeks. Fortnightly parasitological controls revealed 28 infections in the placebo group and none in the dapsone-pyrimethamine group. It is concluded that weekly dapsone-pyrimethamine is effective for the prophylaxis of falciparum malaria in Mozambique.

Child↗

Relapses in leprosy patients after release from dapsone monotherapy; experience in the leprosy control program of the all Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Before implementation of multidrug therapy (MDT), leprosy patients who were clinically inactive, skin-smear negative and had been treated with dapsone monotherapy for at least 5 years (paucibacillary patients) or for at least 10 years (multibacillary patients) were released from treatment. An analysis was made of self-reporting relapses in 1081 paucibacillary (PB) patients and 1123 multibacillary (MB) patients who had been released in Addis Ababa and two rural districts of the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT). During an average period of 6.6 years after stopping dapsone, 44 relapses were diagnosed among the PB patients and 148 relapses among the MB patients. The overall relapse rate was 4.1% or 7.2 per 1000 patient-years after release from treatment for PB patients and 13.2% and 24.8, respectively, for MB patients. The annual relapse rate in PB patients did not differ significantly from year to year. However the relapse rate for MB patients was significantly lower during the fifth to seventh years after stopping treatment compared with the first 4 years. Based on clinical findings there was a strong suspicion of relapse with dapsone-resistant bacilli in 40.4% of MB relapses. It is concluded that the relapse rate for PB patients is acceptable. However, the relapse rate for MB patients is considered too high. It is strongly recommended to administer to all MB patients, including those who have been on long-term treatment with dapsone and have become clinically and bacteriologically inactive, a 2-year course of MDT.

Adolescent↗

Presumed dapsone-induced drug hypersensitivity syndrome causing reversible hypersensitivity myocarditis and thyrotoxicosis.

INTRODUCTION: A 22-year-old Malay soldier developed dapsone hypersensitivity syndrome 12 weeks after taking maloprim (dapsone 100 mg/pyrimethamine 12.5 mg) for anti-malarial prophylaxis. CLINICAL PICTURE: He presented with fever, rash, lymphadenopathy and multiple-organ involvement including serositis, hepatitis and thyroiditis. Subsequently, he developed congestive heart failure with a reduction in ejection fraction on echocardiogram, and serum cardiac enzyme elevation consistent with a hypersensitivity myocarditis. TREATMENT: Maloprim was discontinued and he was treated with steroids, diuretics and an angiotensin-converting-enzyme inhibitor. OUTCOME: He has made a complete recovery with resolution of thyroiditis and a return to normal ejection fraction 10 months after admission. CONCLUSION: In summary, we report a case of dapsone hypersensitivity syndrome with classical symptoms of fever, rash and multi-organ involvement including a rare manifestation of myocarditis. To our knowledge, this is the first case of dapsone-related hypersensitivity myocarditis not diagnosed in a post-mortem setting. As maloprim is widely used for malaria prophylaxis, clinicians need to be aware of this unusual but potentially serious association.

Abdominal Pain↗

Relationship of dietary gluten intake to dapsone dose in dermatitis herpetiformis.

The gluten intake was quantitated utilizing a dietary history method in 43 patients with dermatitis herpetiformis on non-restricted diet. The mean daily gluten intake was 15 g. The individual intake of gluten was related to the maintenance dose of dapsone. It was significantly higher in patients on 100-150 mg dapsone daily than in those taking 0-25 mg daily. There was a significant correlation between amount of gluten in the diet and the dapsone dose (p less than 0.01, rs = 0.43). Villous atrophy was not related to the dapsone dose. It is suggested that the gluten-sensitive enteropathy changes the intestinal permeability and thus contributes to the development of blisters.

Adolescent↗

Sulfasalazine metabolites and dapsone attenuate formyl-methionyl-leucyl-phenylalanine-induced mucosal injury in rat ileum.

The effects of 5-aminosalicylic acid (5-ASA), 4-ASA, N-acetyl-5-ASA, and sulfapyridine on mucosal permeability were determined in an experimental model of acute ileitis. In addition, the antiinflammatory drug dapsone was tested. The distal 10 cm of rat ileum was perfused with formyl-methionyl-leucyl-phenylalanine (FMLP) (10(-5) M), a bacterial peptide that activates and attracts neutrophils. Changes in mucosal permeability were assessed using the blood-to-lumen clearance of 51Cr-ethylene-diamineacetate. Luminal FMLP increased 51Cr-labeled ethylenediamineacetate clearance twofold and fourfold in the first and second hour, respectively. Addition of 5-ASA (10 mM), 4-ASA (10 mM), or dapsone (4 mM) to the luminal perfusate after 60 min of FMLP perfusion greatly attenuated the increased mucosal permeability observed after 120 min of FMLP perfusion. Neither N-acetyl-5-ASA (10 mM) nor sulfapyridine (5 mM) had an effect on the FMLP-induced increase in mucosal permeability. We characterized the inhibitory effect of these drugs on the catalytic activity of myeloperoxidase and tested their ability to scavenge hypochlorous acid in vitro. 5-Aminosalicylic acid, 4-ASA, and dapsone demonstrated a powerful inhibitory effect on the catalytic activity of myeloperoxidase, whereas all drugs were equally effective in scavenging HOCl. In additional in vitro experiments we were unable to demonstrate an inhibitory effect of either of the drugs on the catalytic activity of neutrophilic elastase. Our results indicate that inhibition of neutrophilic myeloperoxidase may be an important mechanism by which 5-ASA, 4-ASA, and dapsone attenuate FMLP-induced mucosal injury.

Aminosalicylic Acid↗

Primary dapsone resistance in China.

Ninety-seven strains of Mycobacterium leprae recovered from patients with previously untreated multibacillary leprosy were tested for dapsone susceptibility. The specimens originated from Shanghai Municipality, Jiang-su Province and Fu-jian Province. Approximately 28% of the strains either did not infect the mice or the results of susceptibility were inconclusive due to the low proportion of viable organisms in the bacterial populations. Among the 70 strains in which dapsone susceptibility could be tested in mice, 31 (44%) strains were found with primary dapsone resistance. Although the majority of the primary dapsone resistant strains were shown to be of a low- or intermediate-degree, one-sixth of them were of high-degree resistance.

Animal Feed↗

[Dapsone inhibition of the bactericidal action of rifampicin on Mycobacterium leprae in mice].

In the experimental infection of mice by Mycobacterium leprae, the bactericidal effect of 4 weekly doses of rifampicin (RMP) is completely suppressed if this administration is preceded by a daily treatment of dapsone (DDS) during one month then continued in conjunction with rifampicin. The application of this methodology: the delayed adding of rifampicin clearly shows the bacillary persistence induced by dapsone (DDS). The rifampicin appears to be less effective on Mycobacterium leprae when its metabolism is inhibited either by the action of a drug such as dapsone (DDS), or spontaneously. The highlighting of this late-appearing antagonism between rifampicin and dapsone in mice, should not at present lead to the questioning of the therapeutic procedures recommended by the WHO, because of the limits of this experimental model, namely the small size of bacillary populations studied over relatively short periods of time.

Animals↗

Neurologic symptoms posing as dapsone-induced polyneuropathy in two patients with dermatitis herpetiformis.

The clinical picture of neuropathy caused by dapsone is usually progressive muscle weakness and wasting, most often involving distal muscles of the extremities. Two patients with neurologic symptoms following the use of dapsone for dermatitis herpetiformis are reported. Both patients had normal motor conduction velocities, and negative results on physical examination of muscle wasting. We conclude that their clinical presentation was not due to dapsone-induced neuropathy. A discussion and a review of cases of this unusual effect of dapsone are included.

Adult↗

Primary and secondary dapsone resistance of M. leprae in Martinique, Guadeloupe, New Caledonia, Tahiti, Senegal, and Paris between 1980 and 1985.

Primary and secondary dapsone resistance were studied among lepromatous patients living in Martinique, Guadeloupe, New Caledonia, Tahiti, Senegal, and Paris. Four hundred fifteen biopsies were taken from clinically active and bacteriologically positive (bacterial index greater than 2) patients in the 6-year period of 1980-1985. Among these, 280 biopsies that contained 5 x 10(4) acid-fast bacilli per ml with a morphological index of at least 0.10 were inoculated into the mouse foot pad, and 229 harbored infective Mycobacterium leprae. Among the 129 infective M. leprae isolated from new cases, 54% had some degree of dapsone resistance, a low degree being prominent in all cases. Among the 100 infective M. leprae isolated from relapsed cases, 79% had a high or an intermediate degree of dapsone resistance. The annual incidence of secondary dapsone resistance was estimated to be about 0.55% in Guadeloupe.

Dapsone↗

[The occurrence of dapsone residues following a one-time oral, intramuscular and intramammary application in healthy dairy cows].

Dapsone is frequently used as a bacteriostatic drug in the treatment of mastitis, endometritis and footrot (necrotic pododermatitis). The farmer usually obtains this drug by 'non-ethical' channels. A regular scheme of checking the milk for residues of sulphonamides will be introduced in 1986. The sensitivity of the test is approximately 25 ppb for Dapsone. This will result in lower milk price in the case of positive tests. In healthy animals, it is shown that intramuscular treatment with 35 grammes (+/- 70 mg/kg-1 body weight) of Dapsone results in residues of Dapsone and its metabolite monoacetyldapsone above this detection level for more than 6 1/2 days. Within 5 days after oral treatment with 48.75 grammes (+/- 100 mg/kg-1 body weight) and 2 1/2 days after single intramammary treatment with 0.8 grammes, the concentrations of residues detected dropped below 25 ppb. The other well-known metabolite diacetyldapsone was only present in detectable quantities in the first milkings after oral treatment.

Administration, Oral↗

Dapsone dependent nodular panniculitis.

A patient recorded to be suffering from tuberculoid leprosy since 1973 and on regular Dapsone monotherapy for about nine years developed asymmetrical, erythematous, subcutaneous, nodular swellings restricted chiefly to the extensor aspects of lower limbs two months after discontinuation of Dapsone therapy. During the course of Dapsone treatment, the patient had developed similar swellings twice previously each time when he stopped the drug for about a month. The swellings disappeared on commencement of Dapsone Treatment. This has been reconfirmed under our supervision. The biopsy of one of the lesions revealed panniculitis with vasculitis. The original diagnosis of leprosy was probably invalid.

Adult↗

Primary dapsone resistance in leprosy.

20 carefully selected untreated patients of bacilliferous leprosy were investigated for primary dapsone resistance by foot pad inoculation. Mice were fed on 0.001 g% and 0.01 g% of dapsone during the period of study. Mice in the control group were given normal rodent feed only. Animals were sacrificed from 6 month onwards at 6 week intervals upto 9 months. In two animals the growth of M. leprae was not inhibited by 0.001 g% concentration of dapsone in diet, but was completely inhibited by 0.01 g% of dapsone.

Adolescent↗

Factors influencing the level of dapsone in blood.

The level of dapsone in the blood 4 and 6 h after the ingestion of the 7th daily dose of 100 mg of the drug was investigated in 36 adult males with leprosy who had normal renal function and were free of diarrhoea and emesis. The bimodal distribution of the dapsone levels at 6 h was shown by multiple regression analysis to be due to a negative correlation between this trait and the haematocrit value. Among the patients with high dapsone blood levels, 81.8% presented haematocrit values under 36%, whereas only 20% of those with low levels showed low haematocrit values. Partial regression coefficients, calculated for the dapsone level on the age, weight of the patient, estimated number of years since the onset of leprosy, number of years under sulfone treatment, and blood levels of haemoglobin, albumin, and globulins, did not show statistical significance.

Adult↗

Fatal thrombocytopenic hemorrhagic diathesis associated with dapsone administration to a dog.

Dapsone was given for six days to a dog with chronic skin disease. The dog then became weak and anorectic, and it vomited and had purpura caused by severe thrombocytopenic hemorrhagic diathesis. Despite treatment, the dog died a week later. There were clinical and pathologic evidence that the dog's platelets and megakaryocytes had been destroyed during the first few days of dapsone therapy. It was concluded that the syndrome was dapsone-induced and that thrombocytopenia should be considered among the adverse reactions to dapsone in the dog.

Animals↗

Dapsone resistance in patients attending Central Leprosy Teaching and Research Institute, Chengalpattu (South India).

The Central Leprosy Teaching and Research Institute (C.L.T. & R.I.) Chengalpattu, took up studies on dapsone resistance in M. leprae from 1974. From 1978, the study was further strengthened by a project under THELEP (TDR) for eliciting information on the efficacy of certain drug regimens. The Thelep studies were to be conducted only on the dapsone sensitive untreated cases and, therefore, directed towards the detection of primary resistance, while the non-THELEP institutional studies were concentrated on secondary dapsone resistance problem. These two studies together detected 99 cases of dapsone resistance in the patients who attended CLTRI Hospital during 1974-81; 23 of them, were of primary origin, 16, 6 and 1 showing mild (RI), moderate (RII), and high (RIII) grades respectively. Of the remaining 76 cases of secondary resistance, 7 and 69 were of RII and RIII grades respectively. The need for vertical and horizontal monitoring of the drug resistance problem has been pointed out.

Adult↗

Primary dapsone-resistant leprosy in San Francisco.

The dapsone sensitivity of strains of Mycobacterium leprae from 54 multibacilliferous untreated leprosy patients presenting to the United States Public Health Service Hospital in San Francisco, California, U.S.A., from 1978 to 1981 was studied by mouse foot pad inoculation. M. leprae from 53 patients were found fully sensitive to dapsone. M. leprae from one patient were resistant to only the lowest dietary level of dapsone, 0.0001%, since growth of the bacilli was inhibited by higher and clinically easily achievable levels. Mouse plasma dapsone levels confirmed the reliability of the drug-containing diets.

Adolescent↗

Primary dapsone-resistant leprosy in Cebu, Philippines.

A survey of the prevalence of primary dapsone-resistant leprosy in Cebu, Philippines, has yielded an estimate of 3.6 per 100. Fifty-three of 55 patients proved to have M. leprae fully susceptible to dapsone. The organisms of two patients multiplied in mice administered the minimal effective dose of dapsone; and those of one of these patients also multiplied in mice administered dapsone in a 10-fold larger dose.

Animals↗

Bioavailability of dapsone on oral administration of Dapsomine--a comparative evaluation.

This study describes a comparative evaluation of dapsone kinetics in humans on administration of Dapsomine, a capsule containing dapsone 100 mg dispersed in oily-base suspension of clofazimine 50 mg. Seven untreated lepromatous leprosy patients were given one capsule of Dapsomine a day for seven days and the pharmacokinetics parameters in this group were compared with those from another group of seven patients who received dapsone 100 mg and clofazimine 50 mg separately. There were no statistically significant differences in parameters such as peak dapsone plasma concentration (Cmax), basal plasma level (C24h), time to peak level (tmax), absorption half-life (t1/2 alpha), elimination half-life t1/2 beta) and areas under plasma concentration-time curves (AUC0-8h) and AUC0-24h) between the two groups.

Biological Availability↗