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PubMed1989

Clinical pharmacokinetic considerations in the treatment of patients with leprosy.

On the basis of the efficacy of the available agents, the World Health Organization has recommended only 4 drugs for combined chemotherapy of leprosy: rifampicin, dapsone, clofazimine and ethionamide/prothionamide. Thiacetazone and isoniazid are also used to a lesser extent by some physicians. Pyrazinamide may find a place in treating 'persister' bacilli. Dapsone is absorbed slowly after oral administration. Peak plasma drug concentration is reached at about 4 hours; absorption half-life is 1.1 hours; elimination half-life is about 30 hours. Oral availability is around 90%. Dapsone is approximately 70% protein-bound, while its monoacetylated metabolite is almost entirely bound. Dapsone crosses the placenta and is excreted into breast milk. It is metabolised via acetylation and N-hydroxylation, but acetylation polymorphism has no effect on dapsone handling by leprosy patients. Dapsone penetrates into sciatic nerves of experimental animals but its presence has not been demonstrated in Schwann cells. Oral doses of rifampicin are rapidly and completely absorbed. The bioavailability is greater when the drug is given before meals; peak concentrations occur at 1 to 2 hours. 80 to 90% of rifampicin is bound to plasma proteins, and the drug is found in saliva, cerebrospinal fluid and breast milk. Its main metabolite, desacetyl rifampicin, also exhibits antimycobacterial activity in tuberculosis. Rifampicin induces its own metabolism, as well as that of dapsone and steroids. Absorption of dapsone and rifampicin is reported to be reduced in leprosy patients. Clofazimine has been in use in leprosy treatment since 1960. In higher doses it exerts an anti-inflammatory action which is useful in treating leprosy patients in reaction. Oral absorption of the drug is slow and dose-dependent; faecal excretion also increases with dose. Single- and multiple-dose studies have shown a plasma half-life of around 10 days. Bioavailability of the drug is higher when given with food than when fasting; the peak plasma concentration occurs at 4 to 8 hours when the drug is administered with breakfast. After absorption, the drug is thought to circulate in protein-bound form, accounting for the fact that it is deposited in various tissues. Uneven distribution and prolonged retention in the tissues are special features of clofazimine metabolism. One unconjugated and 2 conjugated metabolites have been detected in urine, and the urinary excretion of both the parent compound and its metabolites is around 1% of the dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1991

In vitro effect of interleukin-2 on proliferative responses of peripheral blood T cells from leprosy patients.

Because of the important role played by interleukin-2(IL-2) in T cell growth and differentiation, we investigated the effect of exogenous IL-2 on the proliferative response of peripheral blood mononuclear cells(PBMCs) from 77 leprosy patients. The proliferative responses of PBMCs from lepromatous leprosy(LL) or borderline lepromatous leprosy(BL) patients to M. leprae were significantly lower(cpm 6,051 +/- 803 for LL type; 4,951 +/- 2,529 for BL type) than those from tuberculoid leprosy(TT) or borderline tuberculoid leprosy(BT) patients (28,853 +/- 28,916 for TT type; 15,884 +/- 334 for BT type). To investigate the effect of exogenous IL-2, purified IL-2 was added at the start of culture at 100 unit/ml. There was an apparent increase in 3H-thymidine incorporation of M. leprae-stimulated PBMCs(18,723 +/- 6,503) in the presence of IL-2 compared to the results without IL-2(6,051 +/- 803) in LL patients. Twenty nine out of 33 LL patients belonged to the responders to IL-2 and four patients were nonresponders. Therefore we conclude that the defective cell mediated immune response in LL patients may result from diminished production of IL-2, but we can not exclude the possibility of diminished expression of the IL-2 receptor. And we suggest that the immunologic heterogeneous response of an individual to M. leprae is important to the pathogenesis of clinical disease in the same LL patients.

Cells, Cultured↗
PubMedDate not supplied

A comparative evaluation of skin and nerve histopathology in single skin lesion leprosy.

BACKGROUND: In spite of leprosy being a disease of nerves, ROM therapy for single skin lesion leprosy was based on clinical trials without much evidence-based studies of nerve pathology. The present study was undertaken to compare the histology of skin and nerve in single skin lesion leprosy, and to assess the scientific rationale and justification of single dose ROM therapy. METHODS: Twenty-seven untreated patients with single skin lesion without significantly thickened peripheral nerves were selected. Skin and nearby pure cutaneous nerve biopsies were studied under both H&E and Fite's stain. RESULTS: All the skin biopsies were negative for AFB and clinico-pathological correlation was positive in 51.85% of skin biopsy specimens. Histopathological diagnosis of leprosy was evident in 55.5% of clinically normal looking nerves, with AFB positivity in 29.6% of nerve biopsy specimens. Correlation between clinical diagnosis and nerve histopathology was poor (26%). CONCLUSIONS: Single skin lesion without thickened peripheral nerves as criteria for single dose ROM therapy is not logical, since the histological diagnosis of leprosy in normal looking nerves with presence of AFB is revealed in this study. Pure cutaneous nerve biopsy is a simple outpatient procedure, without complications. This study emphasizes the need to consider nerve pathology as an important tool for further therapeutic recommendations, than just clinical trials and skin pathology alone. Though single dose ROM therapy has been withdrawn recently, the principle holds good for any future therapeutic recommendations.

Adolescent↗
PubMed1996

[HLA class II alleles and leprosy (Hansen's disease) classified by WHO-MDT criteria].

Human leukocyte antigens (HLA) class II alleles were analyzed in Japanese leprosy patients to ascertain whether immunogenetic differences exist among the forms of leprosy in classification of World Health Organization-recommended multidrug therapy (WHO-MDT). The subjects were 86 unrelated Japanese leprosy patients, including 62 multibacillary leprosy (MBL), 24 paucibacillary leprosy (PBL). Controls were 114 unrelated healthy subjects. Genotyping of HLA class II alleles was performed by using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. The frequencies of HLA-DRB1* 1501, * 1502 and DRB5* 0101,* 0102 and DQA1* 0102 and DQB1* 0602 were significantly increased in the whole patients (44.2%, 34.9%, 44.2%, 34.9%, 53.4% and 41.9%, respectively) as compared with the control subjects (14.0%, 21.1%, 14.0%, 21.1%, 27.2% and 13.2%, respectively). On the other hand, the frequencies of HLA-DRB1* 0405, * 0803, * 0901 and DQA1* 03 and DQB1* 0401 were significantly decreased in the whole patients (10.5%, 5.8%, 16.3%, 41.9% and 9.3%, respectively) as compared with the control subjects (29.8%, 17.5%, 30.7%, 78.1% and 29.8%, respectively). When MBL and PBL patients were compared, the frequencies of HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 were significantly increased in the MBL patients (51.6%, 51.6% and 48.4%, respectively) as compared with the PBL patients (25.0%, respectively). Our results suggest that HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 contribute to the susceptibility to the Japanese MBL.

Aged↗
PubMed1997

[Clinico-pathological findings of gastrointestinal tract in the leprosy patients].

Endoscopic biopsies either or both for the stomach and colon looking for chronic gastritis and carcinomata followed by the histopathologic examinations of the mucosa were applied to long term leprosy inpatients and controls. 1) In chronic gastritis, glandular atrophy with cellular infiltration and submucosal fibrosis likewise intestinal metaplasia were predominated in the leprosy patients, in the comparison of the cases consisted of 30 leprosy patients and 16 controls. No characteristic changes for leprosy cases were encountered accordingly, however, as the sequences of the medications. 2) The observations of Helicobacter pylori (HP) by means of immunohistologic method were also applied to gastritic cases. However, the positive rates in the above groups were not much different one another. 3) The cases of gastric carcinoma were 14 during 14 years period, among which 9 showed protruded lesions indicating metaplastic changes as the precancerous lesion. 4) The carcinoma of the colon tended to be left sided in the leprosy patients.

Aged↗
PubMed2006

Leprosy in Mexico.

The time of the settlement of leprosy in Mexico is uncertain, however recent studies pointed out that leprosy was probably brought by Asian's migration at about 12,000 years ago and not by the Europeans conquerors during XVI and XVII centuries. Registration of leprosy has been done since the colonial era and the disease was considered as a public health problem until the year 2004 in Mexico when the incidence was achieved to be less than 1 per 10,000 as defined by the world health organization (WHO). Although the national epidemiological parameters like prevalence show the leprosy are controlled well, there are still 49 prefectures with higher prevalence in Mexico. In addition, the incidence in last 10 years has not been stably reduced, in other words the infection cycle has not been interrupted. Therefore, it is necessary to keep the careful epidemiological monitoring, and to increase the search and follow-up of new cases and their contacts in order to eliminate leprosy in this country.

Communicable Disease Control↗
PubMedDate not supplied

Ultrastructural observations of small blood vessels in leprosy patients.

In lepromatous leprosy, blood vessels revealed the luminal protrusions of endothelial cells containing M. leprae and thickening of the basement membrane of endothelial and smooth cells. Endothelial projections with increased pinocytotic vesicles were more often encountered in lepromatous leprosy than in the other types of leprosy. On the other hand, in tuberculoid leprosy, the extensive rough endoplasmic reticulum suggesting protein synthesis was observed in the endothelial cells compared with the other types of leprosy and non-specific lesions. It seems that the blood vessels associated with hyperfunction and proliferation in the endothelium could aggravate the degenerative changes in peripheral nerve fibers including the Schwann cells.

Endothelium, Vascular↗
PubMed1994

[Is a false image of the senile plaque in elderly Japanese with leprosy?--pathological findings on the immunohistology].

By the advance of chemotherapy and aging of the inpatients with leprosy (mean age: 75.7 years), geriatric disease are becoming major problems in Japanese National Leprosarium. Dementia is not diagnosed inpatient with leprosy. After autopsy Alzheimer fibrillary tangle and senile plaques in the brain of aged leprosy is not easy demonstrated by routine stains. However, these is easy demonstrable a different senile plaque with accretion to the Alzheimer fibrillary tangle, if it employed the specific immunohistochemical method on these brain. We employed both tau protein and the divided beta protein, and each of protein is able to divide dementia and non-dementia into aged groups in leprosy. Low prevalence in Japanese leprosy patients is demonstrable in dementia of what happened was accurate in alzheimer disease with subtype of senile plaque.

Aged↗
PubMed1994

[The dermal connective tissue of leprosy patients. Part 1. The elastic fibers and the skin appendages].

Leprosy patients who are keeping long quiescent conditions show some characteristic changes clinically on their skins. The elastic fibers and skin appendages are important factors for the peculiar skin characters. We calculated the collagen and elastic fibers in the limbs and redundant facial skins of leprosy patients by automated computerized image analyser. Histopathological studies of these samples were also done. All cases were over sixty years old and many of them were in quiescent conditions. The control cases were taken from the same parts of age matched normal skins. We found the dermal thickness of lower legs of patients was significantly lower than that of controls. The amount of collagen fibers had tendensy of decrease accompanied with decreased dermal thickness, but the elastic fibers of leprosy patients did not show the same tendensy. In the patients' skin, the elastic fibers arranged irregularly, sometimes fragmented and focally coagressed. Skin appendages were greatly decreased and intraepidermal pores of sweat ducts were almost disappeared, but many sweat glands have survived. Of the facial skins, only 1 case showed a compatible feature with solar elastosis. We concluded that the dermal elastic fibers of leprosy patients had characteristic features. The types of leprosy, duration periods of active condition, destructed dermal structures, all these factors were suspected to have some relations with these phenomena.

Aged↗
PubMed1995

Progress and impact of multidrug therapy (MDT) implementation to leprosy control in Thailand.

This paper report the progress and impact of MDT implementation to leprosy control in Thailand since 1984 until 1994. By ten years of MDT implementation, number of registered cases dropped from 44,406 in 1984 to only 4,878 cases in 1994. Which made prevalence rate declined 90% from 8.8 to 0.83 per 10,000 population, the detection rate of new case declined from 6.2 to 1.97 per 100,000 population. Total 39,372 cases have been completely covered by MDT and 22,821 cases are under post MDT surveillance with the low relapse rate only 1.46% other indicators showing natural decline of leprosy were increasing in proportion of multibacillary leprosy and mean age at onset of new case of leprosy together with decreasing in proportion of children among new case. Other impact of MDT showing increasing trend of proportion of new case of patient who voluntarily attend treatment centers. However, there were still no satisfactory impact on decreasing in proportion of deformity and duration since onset to the first detection of new case of leprosy.

Child↗
PubMed1991

Lipid-laden macrophages in bone marrow of leprosy patients.

While conducting a study to observe bone marrow cytomorphological changes in multibacillary leprosy, lipid laden macrophages as seen in sphingolipidoses were noted. The present study was planned to observe the occurrence and morphological characterization of these macrophages in various types of leprosy. Bone marrow records from 48 cases of paucibacillary and 72 cases of multibacillary leprosy were analysed. The macrophages accounting at the most for 3.5% of marrow cells were observed in 5 cases of paucibacillary and 43 cases of multibacillary leprosy with a maximum incidence being observed in patients with ENL (16/17). The lipid present in the cytoplasm of these cells could be derived from the lipid of the cell wall of Mycobacterium leprae. To the best of our knowledge, these cells have not been reported in leprosy so far.

Bone Marrow↗
PubMed1991

The private GP and leprosy: a study.

In urban and rural areas alike, people in India tend to prefer private medical care to the existing government health services. Nevertheless, the large private health care sector has hitherto been virtually alienated from activities of public health importance including priority disease control programmes. This study of 106 private general practitioners (GPs), practising in low socioeconomic areas of Bombay, shows a gross lack of knowledge and awareness among private doctors about leprosy and also about the National Leprosy Control Programme. The possible reasons are discussed. Effective involvement of GPs in the National Leprosy Control Programme should facilitate both integration and better implementation of leprosy control activities. The study also highlights some areas for future interventions at both primary and secondary health care levels and the need for a strategy, based on larger studies, to train and make private doctors participate in controlling diseases of major public health concern like leprosy.

Attitude of Health Personnel↗
PubMed1992

Clinical observations on leprosy patients with HIV1-infection in Zambia.

The clinical observations carried out on 10 leprosy patients with HIV1-infection, admitted between 1.1.1986 and 1.5.1988 to the Salvation Army Hospital at Chikankata, Mazabuka, Zambia are described. A total of 8 of this group were newly-diagnosed borderline leprosy patients. Their clinical data were compared with those of 34 newly-diagnosed borderline leprosy patients, admitted in the same period--50% were men, 50% women. The clinical presentation, with respect to leprosy, on admission, did not differ very much in both groups. The incidence of neuritis in both groups was 50% (respectively 5 and 17). The outcome of specific therapy of neuritis was worse in the HIV1 patients than in the other group: only partial recovery in 4 out of 5 and no response in 1, compared with a complete recovery in 10 cases, and a partial recovery in 7 cases in the other group. A total of 6 patients of the HIV1-group admitted to have had multiple heterosexual contacts, 5 had a history of sexually transmitted disease, 7 had generalized lymphadenopathy and 4 presented with another disease in addition to leprosy. While in hospital the group of 10 HIV1-infected patients suffered 17 episodes of intercurrent disease against none in the other group; 1 patient (male) died with generalized dermatitis and sepsis; 1 woman died with fulminant hepatitis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Appraisal of the knowledge and attitude of Nigerian nurses toward leprosy.

The attitudes of nurses toward leprosy are studied and in this paper. The findings show that their knowledge of leprosy is lacking and that they also fear leprosy. This study recommends that leprosy should be included in the basic nursing curriculum in order to increase awareness and to decrease the stigma of leprosy.

Attitude of Health Personnel↗
PubMed1992

Defining a case of leprosy.

The biological and technical hurdles confronting the development of new diagnostic tools are manifestly great in leprosy. Leprosy diagnosis in the field, for control as well as for research purposes, will have to remain, for the time being, predominantly clinical. It is important that the significance and relevance of diagnosing so-called 'early' lesions must be viewed in the context of the objectives of leprosy control. All evidence suggests that the majority of these 'cases' are not likely to progress in the individual, nor is there any evidence that these 'cases' are of any importance for the transmission of the disease. At its best, such 'cases' may be a sign of temporary infection which will disappear spontaneously within a few months without leaving any residual signs. It is more likely that the majority of these are not cases of leprosy. In making such a diagnosis its ethical implications on the individual, his family and the local society must be considered, given the intense social stigma this diagnosis will generate; besides the cost of treatment and the potential risk of serious side-effects due to treatment. It may be justifiable to have a broad definition if the incidence of leprosy is still high and all reported cases are to be accepted as valid. But once the backlog of cases has been detected and, as a result of control efforts, the number of new cases begins to decrease, there is a need to narrow the case definition for national statistics.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1993

Evolution of early lesions in leprosy.

We observed 29 patients presenting with vague peripheral neurological symptoms for 6 months or more. During this period, 16 developed clinical leprosy, 3 developed borderline tuberculoid leprosy and the other 13 developed neuritic leprosy. Of these 13 cases 11 subsequently developed skin lesions similar to those seen in indeterminate and in borderline tuberculoid leprosy. Based on the above observations, an attempt has been made to explain the evolution of early lesions of leprosy.

Adolescent↗
PubMed1993

Squamous cell carcinoma in plantar ulcers in leprosy. A case control study.

The objective of this case-control study was to identify factors associated with the development of squamous cell carcinoma (SCC) in plantar ulcers of leprosy patients. We examined 2 matched groups consisting of leprosy patients with and without SCC in a plantar ulcer. No correlations were found between the development of SCC and race, profession, place of origin, duration of leprosy, the type and duration of leprosy chemotherapy, presence of bone involvement and type of ulcer care treatment given. The only statistically valid finding was that the duration of the ulcer was significantly lower in the group with malignant change. In this group there was an apparently higher use of pesticides, the difference being not of statistical significance. It is concluded that factors other than ulcer duration need to be looked for, in order to identify factors influencing malignant change in plantar ulcers of leprosy patients.

Carcinoma, Squamous Cell↗
PubMed1996

Correlation of skin and nerve histopathology in leprosy.

Discrepancies have been noted in the histopathological findings between skin and nerve lesions of leprosy patients in some recent works. We studied concurrent skin and nerve biopsies in 27 randomly selected leprosy patients to correlate the histopathological features of skin and nerve lesions, and to assess the importance of neural histology in the classification of leprosy. Skin and nerve biopsies were diagnostic of leprosy in 23 and 26 patients, respectively. A discrepancy was found between the two in 15 cases. Neural histology was helpful in the classification of determinate forms in 24 cases while dermal histology was significant only in 16 patients. A multibacillary nerve and paucibacillary skin picture was observed in 3 patients. It was concluded that nerve biopsy is more informative and specific than skin biopsy in the diagnosis of leprosy and further helps to classify the patients when the skin histology is indeterminate or nonspecific.

Adolescent↗