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Biomedical subjects

M Becx-Bleumink

Publications and source records attributed to M Becx-Bleumink.

At least 19 recordsLinked to original sources
PubMed1992

Relapses among leprosy patients treated with multidrug therapy: experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia; practical difficulties with diagnosing relapses; operational procedures and criteria for diagnosing relapses.

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All African Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Paucibacillary (PB) patients are treated with 6 months of MDT. Multibacillary (MB) patients are treated with at least 2 years of MDT and until skin-smear negativity. An analysis was made of the relapses which had been diagnosed among self-reporting patients in four rural districts and Addis Ababa. Among 3065 PB patients, 34 relapses (1.1%) were diagnosed during an average period of 6.1 years after stopping MDT (range 2 1/2 to 7 1/2 years). Among 2379 MB patients, 24 relapses (1.0%) were diagnosed during an average period of 4.7 years after stopping MDT (range 2 1/2 to 6 years). The estimated relapse rate per 1000 patient-years after release from MDT was 2.1 for PB patients and 2.4 for MB patients. From the analysis of the clinical, bacteriological, and histopathological findings, it was concluded that there was strong positive evidence for the diagnosis for 16 of the 34 relapses in the PB patients and for 0 of the 24 relapses in the MB patients. The main cause for overdiagnosis of MB relapses was that too much reliance had been put on skin-smear results, without a careful comparison of the results with those from before, during, and at completion of MDT; the diagnosis was based on the finding of positive smears in one set of smears only; insufficient attention was given to finding solid-staining bacilli; and findings in biopsies, if these were examined, did not confirm the diagnosis. The main cause of overdiagnosis of PB relapses was that too much reliance was put on histological findings, while these are often inconclusive for differentiating between a relapse and late reversal reaction. Recommendations are made on how to limit overdiagnosis of relapses. Operational procedures and criteria for making the diagnosis under conditions where facilities for back-up histological and mouse foot pad investigations are not available are proposed.

Clofazimine↗
PubMed1992

Duration of multidrug therapy in paucibacillary leprosy patients; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Of 6042 paucibacillary patients who were put on MDT during a period of 7 years, 5485 patients (90.8%) completed the course of MDT; 437 patients (7.2%) did not fulfill the requirement for clinic attendance and either discontinued MDT themselves or the treatment was discontinued by the service. The remaining 120 patients (2.0%) either died, were transferred, left the control area or continued MDT after 9 months. The urine spot test for the presence of dapsone showed a significantly higher proportion of positive results for patients on MDT than for patients on dapsone. The analysis of the compliance with the prescribed doses of MDT showed that of 963 patients, 81.9% received six doses of MDT and 18.1%, more than six doses; 82.6% of these 963 patients attended with 100% regularity, 12.7%, 3.6%, and 1.1% missed one, two, or three clinic appointments, respectively, while fulfilling the requirement for overall clinic attendance. Of the 429 patients who had not been treated with dapsone before MDT, the skin lesions were clinically active at the time of stopping MDT in 130 patients (30.3%). In all, except one of the 114 patients (0.9%) who attended for follow-up examinations, the skin lesions had become clinically inactive within 2 years after stopping MDT. The recommended duration of MDT is discussed based on findings in the ALERT leprosy control programs and observations by others.

Dapsone↗
PubMed1992

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↗
PubMed1992

Occurrence of reactions, their diagnosis and management in leprosy patients treated with multidrug therapy; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

This paper reports on reactions in leprosy patients who were treated with multidrug therapy (MDT) in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. Only those reactions which occurred in patients who had not been treated with dapsone before MDT and which required treatment with prednisolone were included. Until the end of the second year of MDT a reversal reaction had been diagnosed in 43.6% of 266 borderline lepromatous (BL) patients and in 19.2% of 109 lepromatous leprosy (LL) patients, and an erythema nodosum leprosum (ENL) reaction in 2.7% and 11.1% of the patients, respectively. The reversal reactions were observed in 4.9% of the BL patients and in 0% of the LL patients at the time of diagnosis of leprosy, in 26.3% and 12.8% of the patients during the first year of MDT, and in 12.4% and 6.4% during the second year of MDT. ENL reactions were seen in 0.8% of BL patients at diagnosis, 1.1% in the first year and 0.8% in the second year and 2.8% at diagnosis, 5.5% in the first year, and 2.8% in the second year for LL patients. During a 3 1/2-year period, a total of 405 reactions were diagnosed among multibacillary (MB) patients on MDT; 365 of these reactions (90.1%) were reversal reactions and only 40 (9.9%) were ENL reactions. The point in time of the reversal reactions showed that the risk of reversal reaction is highest during the first year of MDT. Thereafter there is a gradual decline, although reactions were still observed during the fifth year of MDT. A reversal reaction was diagnosed in 21.0% of 438 BT patients; in 3.4% of the patients the reaction was present at the time of diagnosis of leprosy; in 10.3% it occurred during MDT, and in 7.3% during the first year after release from MDT. During a period of 3 1/2 years a total of 183 reversal reactions were diagnosed among BT patients. The point in time showed a declining trend in the risk of reversal reaction after starting MDT. The risk is highest during MDT, followed by the first 6 months after stopping MDT. However, reactions, although few, still occurred during the fourth year after stopping MDT. The analysis of the results of prednisolone treatment in 161 patients who were treated for nerve function loss in the field showed that 142 patients (88.2%) regained complete or partial recovery of the nerve function(s), while no improvement was observed in 19 patients (11.8%).(ABSTRACT TRUNCATED AT 400 WORDS)

Drug Therapy, Combination↗
PubMed1991

In vivo administration of low-dose human interleukin-2 induces lymphokine-activated killer cells for enhanced cytolysis in vitro.

We have examined the effect of the intradermal administration of IL-2 on the generation of natural killer (NK) cell and lymphokine-activated killer (LAK) cell activity. Peripheral blood mononuclear cells (PBMC) obtained from borderline lepromatous (BL) and lepromatous leprosy (LL) patients and normal volunteers prior to and after IL-2 injection were stimulated in vitro with IL-2 and their cytolytic activities compared against 51Cr labeled target K562 cells, Daudi cells, and monocytes. Before IL-2 administration, PBMC obtained from BL/LL patients and normal volunteers possessed similar levels of NK cell activity indicating that the NK cell activity of the BL/LL patients was intact. LAK cell activity was induced with IL-2 in vitro in both BL/LL patients and in normal volunteers. The level of LAK cell activity in BL/LL patients was, however, suboptimal. A single intradermal dose of 25 micrograms IL-2 had no effect on the phenotype of circulating mononuclear cells in either patients or normal volunteers. However, 6-12 days after IL-2 injection and subsequent restimulation of the PBMC with IL-2 in vitro, cytolytic activity of LAK cells obtained from the BL/LL patients was enhanced while cells from normal volunteers expressed the same high levels of activity as observed before IL-2 injection.

Cells, Cultured↗
PubMed1991

Urinary phenolic glycolipid 1 in the diagnosis and management of leprosy.

A simplified assay to measure the phenolic glycolipid 1 (PGL-1) of Mycobacterium leprae in the urine was applied to the diagnosis of leprosy and the monitoring of antileprosy chemotherapy. One hundred seventy-nine previously untreated patients and 25 normal controls were tested. The specificity of the assay was 100%. There were no false-positive results. The sensitivity of the assay varied with the type of leprosy from 92% for lepromatous leprosy to 56% for borderline lepromatous and 18% for borderline tuberculoid patients. After the onset of chemotherapy in lepromatous leprosy patients, there was often a transient increase of urinary PGL-1, followed by a steady decline. Within 3 months of multiple drug therapy, urinary PGL-1 levels were reduced by 90%-99% and were often undetectable. This assay appears to have considerable potential for monitoring chemotherapy and detecting treatment failure and relapse in patients with Hansen's disease.

Antigens, Bacterial↗
PubMed1991

Experience with WHO-recommended multidrug therapy (MDT) for multibacillary (MB) leprosy patients in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center in Ethiopia: appraisal of the recommended duration of MDT for MB patients.

During 1981 a World Health Organization Study Group recommended that multibacillary (MB) leprosy patients should be given multidrug therapy (MDT) for at least 2 years and, wherever possible, until skin-smear negativity. This paper reports on the experience with MDT for MB patients under routine field conditions in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in the Shoa Region of Ethiopia. The period of MDT to reach skin-smear negativity was evaluated for 348 new MB patients. Only 31.6% of these patients could be released after 26 four-weekly doses of MDT, and 19.8% needed over 5 years of MDT. The average period of MDT to reach skin-smear negativity was estimated at about 4 years. Of 3343 patients of cohorts which, almost exclusively, consisted of patients treated with dapsone before MDT, 72.8% were released after 26 four-weekly doses of MDT; whereas of 712 patients of cohorts which mainly included new patients, only 23.5% were released. It was estimated that if MDT would be stopped, regardless of skin-smear results, after 26 four-weekly doses of the drugs collected within a period of 3 years, about 80% of the patients would complete treatment. The operational problems with continuation of MDT until skin-smear negativity are discussed. Although as yet it has not been proven by study results that after 2 years of MDT the relapse rate will be low, the available knowledge indicates that this is likely to be the case. Based on a) probability, b) the finding that 2 years of MDT can be maintained in the majority of the patients, and c) the operational difficulties with the continuation of MDT until skin-smear negativity, it is recommended that MDT should be limited to 2 years. MDT of limited and fixed duration will facilitate the implementation and expansion of the treatment in parts of the world where most patients are not yet benefitting from this treatment.

Cohort Studies↗
PubMed1991

Allocation of patients to paucibacillary or multibacillary drug regimens for the treatment of leprosy--a comparison of methods based mainly on skin smears as opposed to clinical methods--alternative clinical methods for classification of patients.

This paper reports on the experience with classification of patients at the All-Africa Leprosy and Rehabilitation Training Centre (ALERT) in the Shoa Province in Ethiopia. Classification on clinical grounds is compared with classification which is primarily based on the result of skin-smear examinations. In addition, possible alternative clinical methods for the allocation of patients to the multidrug therapy (MDT) regimens are discussed. The analysis includes 1525 new patients. In 730 patients classified clinically as paucibacillary (PB), this classification was not confirmed by skin-smear results in only 1.5%; whereas in 795 patients classified clinically as multibacillary (MB), the classification was not confirmed in 21.1%. Possible reasons, notably for the latter discrepancy, are discussed. Based on an assessment of the correctness of the diagnosis and the most probable classification, it was found that if classification had been based on the skin-smear results, 9.3% of the 795 patients classified as MB would have been classified incorrectly as PB. Classification based on clinical signs resulted in incorrect classification, MB instead of PB, of 8.7% of the 795 patients. Over-classification of MB patients, which was found to be supervisor related, is open to improvement by a strict application of clinical criteria for classification. The experience in the ALERT leprosy control program shows that classification which is based on clinical signs may, in particular, result in some PB patients being classified as MB, while classification based on the results of skin-smear examinations is more likely to result in some MB patients being classified as PB. It was concluded that, provided a number of requirements aimed at limiting the number of misclassified patients are introduced, patients can be classified based on clinical signs and, hence, in the absence of skin-smear services for routine classification purposes.

Drug Therapy, Combination↗
PubMed1990

Intradermal recombinant interleukin 2 enhances peripheral blood T-cell responses to mitogen and antigens in patients with lepromatous leprosy.

Thirty-one patients with lepromatous leprosy received recombinant interleukin 2 (IL-2) intradermally in doses ranging from 10 to 30 micrograms. Before injection and at time intervals of 2-21 days thereafter, samples of peripheral blood mononuclear cells (PBMC) were obtained. Single or multiple injections (1-3) of IL-2 did not modify the total number of circulating lymphocytes or the number of T cells and the CD4/CD8 T-cell ratio. However, IL-2 had a pronounced influence on the [3H]thymidine incorporation in response to various stimuli 4-8 days after intradermal IL-2. Stimulation indices of three- to sevenfold above pre-IL-2 levels were observed with the polyclonal activator phytohaemagglutinin (PHA) and enhanced thymidine incorporation occurred in the presence of antigens to which the patients were already sensitized, such as purified protein derivative and BCG. IL-2 had no effect on the unresponsive state of lepromatous leprosy patient T cells to the antigens of Mycobacterium leprae.

Administration, Cutaneous↗
PubMed1989

The reconstitution of cell-mediated immunity in the cutaneous lesions of lepromatous leprosy by recombinant interleukin 2.

Human rIL-2 (10-30 micrograms) was injected intradermally into the skin of patients with lepromatous leprosy with high bacillary loads. All patients responded to the lymphokine with local areas of induration that peaked at 24 h and persisted for 4-7 d irrespective of whether the site was "normal skin" or a nodular lesion. Within 24 h there was an extensive emigration of T cells and monocytes into the site. The percentage of the dermis infiltrated by mononuclear cells increased by more than sevenfold, peaking at 4 d and persisting for greater than 15 d. Both CD4+ and CD8+ T cells entered the site. T cells of CD4+ phenotype predominated at 2-7 d but by 11 d, CD8+ cells were predominant. Considerable numbers of T6+ Langerhans' cells appeared in the dermis by 72 h and persisted for 3 wk. By 4 d the thickness of the overlying epidermis had increased twofold, and keratinocytes were expressing MHC class II antigen and the IFN-gamma-induced peptide IP-10. Starting at 48 h, there was an extensive destruction of mononuclear phagocytes that contained structurally intact or fragmented M. leprae observed at the electron microscope level. The organisms, either free or contained within endocytic vacuoles, were discharged into the extracellular space and then reingested by blood-borne monocytes. This was followed by marked reductions in the number of acid-fast organisms in the injected site, evident as early as 4-7 d and more marked at 2-3 wk after injection. 13 of 15 patients exhibited a disposal of acid-fast bacilli ranging from 5- to 1,000-fold with a mean value of approximately 100-fold. The administration of IL-2 leads to the generation of an effective cell-mediated immune response, recapitulating an antigen-driven event and leading to striking local reductions in M. leprae. In comparison with the purified protein derivative of tuberculin reaction, bacilli are cleared more promptly, although emigratory cells persist for a shorter time.

Adult↗