Lepromatous Type Research Articles

一般病院におけるらい腫型ハンセン病の治療経験

症例は68歳の男性。四肢の腫脹と疼痛を主訴に受診した。ほぼ全身に褐紅色丘疹が多数あり, 生検で末梢神経線維の周囲に泡沫細胞からなる肉芽腫の形成がみられた。Fite染色で泡沫細胞内に多数の陽性桿菌が認められ, らい腫型のハンセン病と診断した。ジメチルスルホン, リファンピシン, クロファジミンの3者による多菌型に対する多剤併用療法により, 臨床的, 菌学的, 血清学的な改善をみた。しかし, 治療開始4ヵ月後に強い1型らい反応が出現した。自験例の治療経験から, らい予防法廃止後におけるハンセン病治療の問題点についても言及した。

A genomic study on the cultivable and nerve invading Mycobacterium HI-75 after the recovery 3 months of the inoculation to nude mice.

The sequence of the polymerase chain reaction (PCR) product of 16S ribosomal RNA (16S rRNA) of the leproma-derived and cultivable Mycobacterium HI-75 (M. HI-75) which was obtained from the infected regions of inoculated mice, was examined and compared with that of the cultured bacteria by the direct sequencing techniques. The sequence was completely consistent with the cultured bacilli in the comparable 837 bases of 16S rRNA. The mycobacterium examined in this study was originally isolated as M. leprae (ML) by Skinsnes, et al. in 1975 from leproma of a lepromatous type Hansen's disease patient and therefore named as Mycobacterium leprae HI-75 by them, and was maintained from 1984 using either Ogawa's or Sauton's media in the beginning and Ogawa's medium enriched with glucronic acid and N-acetyl-D-glucosamine recently. Sasaki and Hamit reported the nerve invasion and the growth of the inoculated bacilli either to the nude mice or the I131 treated immunocompromised Swiss mice. We previously reported that cultured HI-75 was most similar to M. scrofulaceum by the direct sequencing of the gene of 16S rRNA. The 16S rRNA obtained from the mouse tissue in the present study indicated that M. HI-75 would be a variant of M. scrofulaceum possessing an ability to invade into peripheral nerve. The results suggest that the HI-75 strain claims a nature as a pathogen to develop a leproma-like lesion.

Human thyroid gland releases interleukin-6(IL-6) in vitro

Leprous neuropathy, which is due to infection of nerve cells by Mycobacterium leprae, still affects millions of people in many developing countries. The clinical and pathological manifestations are determined by the natural resistance of the host to invasion of M. Leprae. Failure of early detection of leprosy often leads to severe disability in spite of eradication of mycobacterium at a later date. In the lepromatous type, bacilli are easily found in the skin and in nerve cells including Schwann cells, endothelial cells, and macrophages. In the tuberculoid type, a strong cell-mediated immune reaction leads to formation of granulomas and destruction of cells harboring bacilli and neighboring nerve fibers. In many cases, treatment of patients with the multibacillary leprosy is complicated by reversal reaction and further nerve damage. Nerve lesions lead to a symmetrical, pseudo-polyneuritic pattern in most cases of lepromatous leprosy, which is usually associated with typical skin lesions, but pure neuritic forms occur in up to 10% of patients with lepromatous leprosy. In the pure neuropathic cases, only nerve biopsy permits diagnosis. The multifocal pattern is more common in tuberculoid leprosy. Treatment is currently based on multidrug therapy with dapsone, rifampicin, and clofazimine. The use of corticosteroids can reduce or prevent nerve damage in reversal reactions. It is important to remember that sequelae, especially sensory loss, are extremely common, which can lead to secondary trophic changes due to repeated trauma in painless areas.

A case control study on human immunodeficiency virus-1 (HIV-1) infection as a risk factor for tuberculosis and leprosy in Western Kenya

A case control study was undertaken in Western Kenya from April 1989 to August 1990 to evaluate HIV-1 infection as a risk factor for tuberculosis and leprosy. The study involved 144 newly diagnosed sputum smear positive tuberculosis cases with 432 age, sex and neighbourhood-matched controls, and 132 diagnosed leprosy cases with 384 matched controls. Odds ratios obtained by conditional logistic regression (matched) analysis were 4.9 (95% CI 2.6, 6.8), and 1.8 (95% CI 0.9, 3.2), for the association between HIV-1 and tuberculosis and leprosy respectively. Approximately 31% of tuberculosis cases among males, and 11% of cases among females, were attributable to HIV infection.

Leprosy in Saudi Arabia, 1986-89

This study on leprosy includes information obtained from the Ibn Sina Hospital, a specialized centre established 27 years ago for treatment and management of the disease in Saudi Arabia. A total of 792 patients with leprosy were reported during the period of the study (1986-89). A steady decline was observed in the number of patients reported: 432 (54.55%) were non-Saudi and 360 (45.45%) were Saudi. Patients were reported from a total of 22 different countries. The majority of the non-Saudi patients were from the Yemen, 286 (36.11%). The male-to-female ratio was 3.83:1. The age groups comprised: 133 (16.79%), 51 to 80; 575 (72.60%), 21 to 50; and 84 (10.61%), under 20 years of age. The disease was classified into five categories (Ridley and Jopling classification): 295 (37.25%), lepromatous type; 238 (30.05%), tuberculoid type; 146 (18.43%), borderline-tuberculoid type; 29 (3.66%), borderline type; and 84 (10.61%), borderline-lepromatous type. Although the number of registered patients is decreasing, this trend does not suggest an overall decline in the disease in the country. It is recommended, therefore, that the services being provided to patients with leprosy must be integrated with the nationwide network of the Primary Health Care Centres to implement effective control and prevention, including health education for the general population. Furthermore, mutual agreements must be developed with adjacent countries to study the geographic distribution of the disease.

New approach to curb the transmission of leprosy

The effect of local treatment of nose of lepromatous type of patients with different formulations of rifampicin nasal rops/sprays was investigated in a large number of patients. The preparations were either sprayed or instilled into the nostrils after flushing the nostrils with normal saline at 370 C. It was observed that 10 mg/ml of rifampicin was effective in reducing the BI and MI to zero in nose in seven days in majority of the patients. No untoward effect was seen in any of the patients. It is suggested that nasal sprays/drops may be able to prevent the transmission of hanseniasis, as nose is recognised to be an important portal of exit of M. leprae. Further when rifampicin drops/sprays are used as soon as the diagnosis is made, the nasal deformity may be prevented. It is believed that local treatment along with systemic therapy would go a long way in controlling the transmission of hanseniasis.

T cell responses to fractionated Mycobacterium leprae antigens in leprosy. The lepromatous nonresponder defect can be overcome in vitro by stimulation with fractionated M. leprae components.

Protective immunity against Mycobacterium leprae is dependent on M. leprae-reactive T lymphocytes. M. lepare-directed T cell reactivity is high in the localized tuberculoid form of leprosy but specifically absent in the disseminated lepromatous type of the disease. Two important questions that are relevant for the understanding of the immune response in leprosy as well as for the design of rational immunoprophylaxis and -therapy strategies are: (a) what are the antigens that trigger T cell responses in tuberculoid patients and thus protect these individuals from developing lepromatous leprosy and (b) is it possible to restore T cell responsiveness to M. leprae in lepromatous patients by rechallenging the immune system with selected antigens that will trigger help but not suppression? We have addressed these question by directly probing the peripheral T cell repertoire of 10 tuberculoid and 18 lepromatous patients with large numbers of different M. leprae and BCG antigenic components that had been separated on the basis of their relative molecular mass (Mr) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted onto nitrocellulose. This technique allows the identification of T cell-stimulating antigens independent of the expression of B cell epitopes by these antigens. So far T cell epitopes have only been mapped on M. leprae proteins that had previously been defined by antibodies. Our results show that: (a) tuberculoid patients' T cells responded preferentially to M. leprae and BCG antigens in the lower (i.e. less than 70 kDa) Mr range with a peak in the 10-25 kDa range; (b) 6 out of 18 lepromatous patients that did not respond to whole M. leprae responded strongly to isolated M. leprae components; antigens in the lower Mr. range were recognized by five out of these six patients and thus commonly seen by both tuberculoid and lepromatous patients' T cells; however, antigens in the higher Mr range, in particular greater than 150 kDa, were only recognized by lepromatous patients' T lymphocytes; (c) furthermore, the T and B cell repertoires in leprosy patients are skewed towards different antigenic fractions.

Renal Involvement in Leprosy

Renal involvement in Hansen's disease was evaluated in 94 Portuguese patients, average age and duration of disease of 47.6 and 6.8 years respectively. Sixty-seven were studied retrospectively and 27 prospectively; renal biopsy was obtained in 4, fat-tissue needle aspiration for amyloidosis in 20, and tubular function was tested in ten. Mild proteinuria and/or haematuria was found in 33 patients, the severity increasing during erythema nodosum leprosum reactions, but without overt nephritic or nephrotic syndrome. Two patients had renal amyloidosis on biopsy and two more were confirmed by fat biopsy, a 10.5% incidence in those studied prospectively; all but one were of the lepromatous type, with frequent bouts of erythema nodosum leprosum. The two other renal biopsies showed mesangial glomerulonephritis, and one unexplained acute tubular necrosis; none had immune deposits by immunofluorescence. Proximal acidification was always normal, distal acidification tested by bicarbonate infusion was abnormal in one of nine patients, and six of nine patients had concentration defects. Leprosy causes frequent urinary sediment changes and concentration defects, usually without clinical expression; proteinuria and/or glomerular involvement is mainly due to amyloidosis.

The pathology of early leprous neuropathy

A qualitative and quantitative study was made of early changes in nerves from 10 patients with tuberculoid or lepromatous type of leprosy. Five nerve biopsies, taken from sites remote from skin lesions, were considered to be unaffected when examined by paraffin histology but showed abnormalities in semi-thin resin sections and by electron microscopy; 5 showed mild to moderate involvement by paraffin histology. Changes in ‘unaffected’ nerves in both types of leprosy included the presence of subperineurial oedema; occasional evidence of fibre regeneration, sometimes with atypical features; increased numbers of small myelinated fibres, possibly a consequence of axonal atrophy; a few thinly remyelinated fibres, probably due to secondary demyelination, and some loss of unmyelinated axons. In more affected nerves there was variable loss of axons, both myelinated and unmyelinated. Demyelination was not a conspicuous feature; there was evidence of axonal atrophy in some fibres. Similarities in some of the changes observed in tuberculoid and lepromatous types of leprosy suggest a common mechanism of nerve damage, at least in the early stages. The presence of abnormalities in nerves at a distance from skin lesions implies a more diffuse nerve involvement than might have been expected in both types of leprosy.

The Leprous Neuritis of The Lower Limbs

Peripheral nerves of lower limbs from autopsied cases with so-called arrested leprosy (19 lepromatous leprosy and 16 tuberculoid one) were examined histopathologically. The results were as follows ;1. In lepromatous type, pattern and degree of damage of nerve trunks, reduction of myelinated fibers and frequency of M. leprae were almost same in all cases. The sural and peroneal nerves were more damaged than posterior tibial and sciatic nerves. And in same nerve trunk, more distally more heavily damaged.2. Active demyelinations with M. leprae between myelin lamellae, without foreign cells around Schwann cells were frequently observed in proximal sites in lepromatouscases. Teased fibers showed that it proceeded centripetally and was not type of segmental demyelination. Many reserved naked large axons were also found without remyelination.3. Though pattern and distribution of nerve damages of tuberculoid type were basically same as those of lepromatous type, their degrees were different between each cases. M, leprae/foamy cells were not observed.4. The densities of myelinated fibers were remarkably different between nerve fasci-cles and even in same fascicles. They were thought to be due to results of leprous reactions and demyelinations. In addition, finding resembled to Renaut's body was discussed.The possible mechanism of leprous neuritis was briefly discussed. In lepromatous leprosy, M. leprae mainly enter nerve trunks through distally running dermal nerves and primarily demyelinate sensory fibers centripetally during patients' lives. Leprous reactions secondarily involve motor nerves together. During repetitive reactions at different levels, distal nerve trunks are more damaged under anatomical rules of peripheral nerves. The proximal nerve damages in tuberculoid leprosy, without M. leprae are thought to be due to active old day's leprous reactions, of which target M. leprae, had invaded there not via blood stream, but through dermal nerves originating directly from proximal nerves.As far as to nerves in lower legs, most possible portal of entry seems to be areas of course of sural and peroneal nerves. And transmission of the soils to seems to be more reasonable than that of to man . The author recommend that trial of taking shoes in endemic areas, might be worth for preventing leprosy.

On the Control of Hepatitis B in the Sanatoria of Hansen's Disease in Japan

The purpose of this study is to investigate HB virus carriers among in-patients and staffs of our sanatorium and to examine control system of Hepatitis-B in the sanatoria of Hansen's disease in Japan.The prevalence of HBs-Ag and HBs-Ab (HBe-Ag and HBe-Ab in part) in the sera of 646 leprosy patients (527 cases with lepromatous type and 119 cases with tuberculoid type) and 281 staffs of the sanatorium was studied in order to investigate the degree of exposure to HBV.From the statistical analysis it was found that T-type as well as L-type cases had no high prevalence of exposure to HBV in comparison to controls. No significant difference was found between the two polar leprosy. There was no positive HBe-Ag case in this time.It is concluded that Hansen's disease cases are not at a high risk of HBV infection in our sanatorium. Because the in-patients become aged and new ones are very few in Japan, the examination of HBV would be mainly carried out in staffs, especially new staffs for the control of Hepatitis B in the sanatoria of Hansen's disease.

Activation of human monocytes in leprosy.

In leprosy, the common etiologic agent is the same Mycobacterium leprae, but the clinical manifestations are various, including the tuberculoid and lepromatous types. In tuberculoid type leprosy, macrophages in the granuloma differentiate into epithelioid cells; in the lepromatous type, in contrast, they differentiate into lepra cells containing multiple M. leprae. Thus host factors, which regulate macrophage activities, determine the type of leprosy. To understand such regulation of macrophage activities, we assayed superoxide production, hydrogen peroxide production and glucose consumption in monocytes in vitro. Glucose consumption spontaneously increased, with lymphokine enhancing the consumption rate. Superoxide production increased spontaneously and decreased from the 4th day; lymphokine added on the 4th day supressed the decrease of superoxide production. Hydrogen peroxide production increased until the 3rd day of culture. Twenty-four hour incubation with lymphokine, from day 0 to the 1st day, had no effect on hydrogen peroxide production, while from the 2nd to 3rd day it enhanced such production. Supernatants of lymphocytes incubated with M. leprae were prepared from tuberculoid and lepromatous patients. Tuberculoid supernatant enhanced reactive oxygen production and glucose consumption, while that from lepromatous patients had no remarkable effect on glucose consumption or reactive oxygen production. The range of spontaneous increase and decrease of reactive oxygen production was greater than the regulatory effect of lymphokine on these activities. These data show that rapid provision of new monocytes to the granuloma is one of the important factors in the defense mechanism, that lymphocytes separated from lepromatous patients are not activated in response to M. leprae antigen, and that they do not secrete corresponding lymphokines.

Study on Prevention of Leprosy

BCG has been vaccinated for leprosy contact children (under 14 j) from 1963 to 1976 in Okinawa, in order to prevent leprosy.The total number of BCG vaccinated children was 951, who were examined after 3, 6, 8, 10 and 13 years to follow-up onset of leprosy. Ten contact children among 534 have developed leprosy by 6 years-examination and its incidence rate was 18.7 _??_. No leprosy cases have been detected by after 3, 8, 10 and 13 years' examination. Theincidence rate by contact tracing examination for BCG unvaccinated contact children in same period and at same plase was 20.6‰.No special difference was observed in leprosy incidence rate between two groups. The incidence rate of BCG trial in Okinawa was higher than other trials in foreign countries, because lepromatous ratio in Okinawa field was higher than other places and index cases with whom children contacted were mainly lepromatous type. oreoverchildren had contacted with lepromatous index cases before they were vaccinated with BCG and they already might be infected with leprosy bacilli. So it seems that no noticeable effect was observed in BCG trial in Okinawa.

Blindness from cataract formation in leprosy.

Of 744 leprous patients, 61 (8.2%) had cataract-induced blindness; 46 patients (6.2%) were unilaterally blind and 15 (2.0%) were bilaterally blind. The mean age of patients with cataracts was 63.4 years in the tuberculoid-type leprosy and 56.4 years in the lepromatous type. The appearance of cataracts in lepromatous patients at an earlier age than in tuberculoid patients is significant (p less than 0.005). Of 41 cataractous eyes with posterior iris synechiae, 42.1% were observed in patients with tuberculoid-type leprosy and 59.1% in patients with the lepromatous type. Histopathological examination of 24 lenses showed that irregularities of the lens epithelium were present in 79.2%. Posterior iris synechiae were seen in 66.7% and fibrous pseudometaplasia in 41.7%. Posterior migration of the lens epithelium in the posterior subcapsular area was observed in 54.2%. In view of these clinical and histopathological findings, we discuss the probability that most cataracts in leprous patients are complicated in nature.

An Epidemiologic Evaluation of Leprosy in New York City

Leprosy is a transmissible disease that is propagated from human to human. At the US Public Health Service hospital, New York City, the number of new leprosy cases per year during the 1970s was about three times greater than in the previous decade. This review of our 100 most recent leprosy patients shows that 60% were of the lepromatous and borderline lepromatous type. Ninety-nine of the patients were foreign born, originating in more than 26 countries. This emphasizes that, at this time, the leprosy problem in New York City is almost exclusively a reflection of immigration patterns. The majority of the patients were asymptomatic at the time of entering the United States. The average latent period from entering the United States until onset of symptoms was 4.8 years, with a range of 0 to 38 years. These figures emphasize the need for physicians to be aware that leprosy can occur as long as five to 40 years after emigration from endemic areas. For all types of leprosy, the average lag from the onset of symptoms to the time of diagnosis was 29.0 months (range, 0 to 245 months). Our experience indicates that a program of urban leprosy treatment using available drugs and supportive care is feasible.

Study on Prevention of Leprosy

BCG has been vaccinated for leprosy contact children (under 14 j) from 1963 to 1976 in Okinawa, in order to prevent leprosy.The total number of BCG vaccinated children was 951, who were examined after 3, 6, 8, 10 and 13 years to follow-up onset of leprosy. Ten contact children among 534 have developed leprosy by 6 years-examination and its incidence rate was 18.7 _??_. No leprosy cases have been detected by after 3, 8, 10 and 13 years' examination. Theincidence rate by contact tracing examination for BCG unvaccinated contact children in same period and at same plase was 20.6‰.No special difference was observed in leprosy incidence rate between two groups. The incidence rate of BCG trial in Okinawa was higher than other trials in foreign countries, because lepromatous ratio in Okinawa field was higher than other places and index cases with whom children contacted were mainly lepromatous type. oreoverchildren had contacted with lepromatous index cases before they were vaccinated with BCG and they already might be infected with leprosy bacilli. So it seems that no noticeable effect was observed in BCG trial in Okinawa.

Ocular findings in leprosy: results of a survey in the Green Pastures Leprosy Hospital, Nepal (author's transl)

One hundred and seventy leprous patients underwent ophthalmic examination; of those with tuberculoid leprosy, 49.3% had ocular pathology; in patients with lepromatous leprosy the corresponding figure was 61.4%. 4.7 percent of all eyes examined were blind. Early chemotherapy prevents further complications in tuberculoid leprosy, but not in ;the lepromatous type. The results are compared with those of other authors.

A survey of the social situations of leprosy patients in JALMA Leprosy Centre, Agra, India. I. Survey on the medical aspects of inpatients (author's transl)

This is a report of sociological study on 240 inpatients hospitalized in JALMA Leprosy Centre, Agra, India.Results of the survey on the socio-environmental aspects of these Patients are as follows:1. The ratio of Hindu patients to Muslim patients was 4 to 1.2. 32.5 % of total inpatients were vegetarians. 13.3% of non-vegetarian patients stopped taking meats after the onset of the disease. Although there were many religiousvegetarians who were taking milk and eggs, those who became vegetarians after the onset of the disease took some milk but no eggs.3. Most of the male patients had married at the age of 15 according to the local custom. Two women had been divorced when leprosy manisfeted itself after their marriage. They had been thrown out of the family with only small amount of money. In cases of male patients with disease which started after their marriage, they did not divorce their wives, but some wives went home and never came back.4. In north India, most of the houses in the countryside are made of mud and they are very cool in the hot season and are very suitable for the tropical climate. However, the family members are crowded in only one or two rooms available in their houses and this living condition is not so hygenic.5. The ratio of lepromatous type among the patients in this survey was 57.5%. As these L cases are the source of infection in their active stage, it is a big problem how to prevent the infection of contact children in the patients' families.6. As water supply is not much in north India and water-works are not common in the rural areas, villagers are using the common well of the village and carrying water for houses-works is the responsibility of female members of the family. Although south India villages have much more water supply, they have more cases of this disease. So the water-works seem to have no direct relationship to the prevalence of leprosy.7. About half of the patients of this survey did not have any formal education, but most of them could at least read and write Hindi and they could read even Indian classical literatures.8. The cause of leprosy is not correctly understood dy many of Indian patients and their families. They are thinking that their ailment is due to spoilt blood or God's punishment.9. Regarding the patients'occupation, half were laborers. Half of laborers were getting monthly payment and another half were with daily payment. Payment for daylaborers without special technique is usually very cheap and they were getting small money only enough for daily food for their family.10. Regarding the rehabilitation of patients, the important factor of the rehabilitation was the grade of the residual symptomes of the disease.

Testicular and epididymal involvement in leprosy patients, with special reference to gynecomastia.

Sixty-six male patients with leprosy were studied. Only those with the lepromatous type developed testicular and epididymal changes. Nine of the 38 patients showed decreased sexual function, and 7 developed gynecomastia. These changes were believed to be due to the altered gonadal state.

癩におけるガッセル氏神経節の病理組織学的研究

Histopathologic studies of the semilunar (Gasserian) ganglia were conducted in a series of 25 cases of leprosy, 5 with the tuberculoid type and 20 with the lepromatous stype. The tissue specimens examined were bilateral in every case and particularly detailed microscopic examinations made in 14 of the cases, with the results leading to the following conclusions.1. Proliferation of the interstitial connective tissue was evident in the ganglia with focal round cell infiltration, in both the tuberculoid and lepromatous types.2. In patients with lepromatous type the nerve cells were noted to show vacuolar degenera-tion as well as atrophy or enlargement, with deformity, necrosis or loss of nuclei. Such alterations of nerve cells were scarcely demonstrable in the tuberculoid type.3. Leprosy bacilli were consistently demonstrable within the ganglion cells in the majority of the lepromatous cases, whereas in the tuberculoid type, such finding was almost nonexistent.4. Axonal hypertrophy, sewelling or destruction of nerve fibers were noted with a fair degree of frequency in both types of the disease.5. Various organs and tissues other than Gasserian ganglia were also examined microscopi-cally to compare the incidence of leprosy bacilli. These viscera included the liver, spleen, adrenals and testes as well as the skin and peripheral nerves. No bacilli were found in any of the organs examined, in the 5 cases of the tuberculoid type. The organiims were demonstrated in the ganglion cells in practically all 12 cases of lepro-matous type showing no significant absorption of cutaneous lesions of nodular infiltra-tion. Leprosy bacilli were also found in other viscera in many of these cases. Of the remaining 8 cases of this type with complete absorption of leprous infiltration and nodules in the skin, 4 were noted to have no evidence of leprosy bacilli in any of the viscera examined while the organisms were still demonstrable in both the peripheral nerves and ganglion cells of 2 other cases.