Fibrosis: a distinguishing feature in the pathology of neural leprosy

BACKGROUND Fibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. OBJECTIVES The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. METHODS Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori's trichrome) and fibrosis was evaluated via semi-quantitative estimation. FINDINGS Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. MAIN CONCLUSIONS The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.

Analysis of 6000 skin biopsies of the national leprosy control program in Mexico.

Six thousand skin biopsy specimens taken from April 1978 to January 2002 under conditions as specified by the National Leprosy Control Program (NLCP), were analyzed to obtain information about the work of the program and contribute to the knowledge of this illness in the Mexico. Six-thousand request forms for histologic exam of the NLCP were reviewed. Sixty-two percent of the requests had all the required information and in 38% one or more data items were omitted. The age range was 2 to 98 yrs with a median of 50 yrs; a small number of cases was observed in the age group of 0 to 14 yrs, and the peak was in the age group of 41 to 50 yrs. Of the 6000 biopsies, 3693 were classified. Polar lepromatous (LL) was the most common form of the disease, in 60.3% of cases. Twice as many cases were multibacillary leprosy (MB) as paucibacillary (PB). MB predominated in males, and PB predominated in females. The Cohen's kappa index (kappa) of clinical-histological agreement was 0.202 (95% CI 0.184-0.219) and showed a poor grade of agreement between clinical and histologic diagnosis, with a level of significance of 0.05 (p <0.001). The results may indicate the end of leprosy in Mexico, a country in which the national goal of elimination was reached in 1994, with a prevalence since the year 2000 of 0.17/10 000.

[Perceptions regarding leprosy and resulting handicaps prior to diagnosis in Recife, Brazil]. / Percepción de la lepra y las discapacidades antes del diagnóstico en Recife, Brasil.

This article reports on a case-control study conducted in Recife, Brazil, between November 1993 and July 1994, to determine how leprosy patients' perceptions and notions influence disease management and use of health services. The sample was composed of 183 residents of Recife between the ages of 20 and 70 years who sought diagnostic services in the dermatology clinics of two referral centers situated in the third, fourth, and sixth political and administrative regions. Sixty-four patients having handicaps or their precursor lesions were classified as cases; the remaining 119 were used as controls. All were diagnosed during the study period. For the analysis, adjustments were made for sex, age, schooling, and a previous history of Hansen's disease among patients. The study revealed the simultaneous presence of two types of "invisibility" of the disease in an area where endemicity is increasing: 1) for patients in both groups, the low frequency of spontaneous explanatory models related to the illness, even in the presence of disease, and 2) for health professionals, the limitations of detection methods. Since such deficiencies affect decisions bearing on individual and collective disease management, they are a risk factor in and of themselves and stand in the way of eliminating leprosy as a public health problem.

Percepción de la lepra y las discapacidades antes del diagnóstico en Recife, Brasil / Perceptions regarding leprosy and resulting handicaps prior to diagnosis in Recife, Brazil

Este artículo presenta un estudio de casos y controles realizado en Recife, Brasil, entre noviembre de 1993 y julio de 1994. En él se investigó cómo influyen la percepción y las apreciaciones de los propios pacientes de lepra en el proceso de manejar la enfermedad y en la utilización de los servicios de salud. La muestra estuvo constituida por 183 pacientes de 20 a 70 años de edad, residentes en Recife, que acudieron en busca de un diagnóstico a los servicios de dermatología sanitaria de dos centros de referencia de las regiones politicoadministrativas tercera, cuarta y sexta. Se clasificaron como casos los 64 pacientes que tenían discapacidades o lesiones precursoras de discapacidad; los 119 restantes se consideraron controles. Todos fueron diagnosticados durante el período de la investigación. En el análisis se ajustó según sexo, edad, escolaridad y antecedentes de la enfermedad de Hansen de los pacientes. El estudio reveló la coexistencia de dos tipos de "invisibilidad" de la enfermedad en una zona endémica en expansión: 1) para los pacientes de ambos grupos, la baja frecuencia de modelos explicativos, espontáneos, relacionados con la dolencia, aun en presencia de antecedentes de la enfermedad, y 2) para los profesionales sanitarios, las limitaciones de la detección. Puesto que afectan a las decisiones relacionadas con el manejo individual y colectivo de la enfermedad, esas deficiencias constituyen por sí mismas un factor de riesgo y representan un obstáculo para la eliminación de la lepra como problema de salud pública.

This article reports on a case-control study conducted in Recife, Brazil, between November 1993 and July 1994, to determine how leprosy patients' perceptions and notions influence disease management and use of health services. The sample was composed of 183 residents of Recife between the ages of 20 and 70 years who sought diagnostic services in the dermatology clinics of two referral centers situated in the third, fourth, and sixth political and administrative regions. Sixty-four patients having handicaps or their precursor lesions were classified as cases; the remaining 119 were used as controls. All were diagnosed during the study period. For the analysis, adjustments were made for sex, age, schooling, and a previous history of Hansen's disease among patients. The study revealed the simultaneous presence of two types of "invisibility" of the disease in an area where endemicity is increasing: 1) for patients in both groups, the low frequency of spontaneous explanatory models related to the illness, even in the presence of disease, and 2) for health professionals, the limitations of detection methods. Since such deficiencies affect decisions bearing on individual and collective disease management, they are a risk factor in and of themselves and stand in the way of eliminating leprosy as a public health problem.

Protective effect of BCG against leprosy and its subtypes: a case-control study in southern Vietnam.

A case-control study was conducted to assess the protective effect of intradermal BCG against leprosy and its subtypes in southern Vietnam. A total of 177 cases were selected with a distribution by subtypes as follows: 38 TT, 23 BT, 51 BB, 36 BL, 22 LL, and 7 indeterminate. Two controls were matched with a case for age, sex, ethnic group, socioeconomic status, and district area. The odds ratio assessing the protective effect of BCG varied from 0.44 (0.19-1.03) in the BB subtype to 3.00 (0.24-37.5) in indeterminate leprosy; whereas its overall value was 0.71 (0.45-1.10) for leprosy per se. When all borderline leprosy types were pooled, the protective effect of BCG was found significant with an odds ratio of 0.48 (0.27-0.84). In the polar forms of leprosy, TT and LL, the odds ratio was > 1 with large confidence intervals. It is possible that BCG induces a shift in the immune response to a higher level of cell-mediated immunity. When BCG vaccination is given after primary infection with Mycobacterium leprae, this shift could be the cause of an increase in the risk of the occurrence of milder and transient forms of the disease. In TT forms BCG might reinforce the preexisting subclinical immunopathological reactions, and in stable LL forms BCG might be unable to induce any protective form of immunity. These results confirm the important variability in the protection offered by BCG with respect to the different types of leprosy, and may have important implications for the design and the interpretation of vaccine trials that should take into account the respective proportions of leprosy forms observed in the study region.

An historical and clinical review of the interaction of leprosy and pregnancy: a cycle to be broken.

Since earliest history the person with leprosy has been shut out from society. Laws have prohibited marriage and allowed divorce of those with leprosy. Segregation of the sufferer from the rest of society has been followed by separation of the sexes, and of leprous parents from their children. With the advent of antileprotic drugs, first dapsone then multidrug therapy (MDT), infection can be treated, individuals made non-infectious, and the pool of infection in the community reduced. The clinical signs of leprosy are due not to the degree of infection but to the immunological status of the host. Hormonal changes at puberty and in pregnancy can cause variation of the host's immune status. Pregnancy in women with leprosy is a hazardous undertaking. First appearance of leprosy, reactivation of the disease and relapse in 'cured' patients is likely to occur particularly in the third trimester of pregnancy. Leprosy reactions caused by variation in cell mediated and humoral immunity are triggered off by pregnancy: type 1 reaction (reversal reaction, RR) occurs post partum, while type 2 reaction (erythema nodosum leprosum, ENL) peaks in late pregnancy. Both types of reaction continue long into lactation. Neuritis with loss of both sensory and motor function is associated with relapse and reaction. Relapse, reaction and nerve damage, especially 'silent neuritis', with subsequent deformity and disability, occur not only in women on apparently effective treatment but also in those who have received MDT and have been released from treatment (RFT). To prevent disability, research is urgently needed into the mechanisms of early and late reaction and neuritis. Pregnancy is not only a trigger factor for reaction but an ideal in vivo model for research. Up to 20% of children born to mothers with leprosy may develop leprosy by puberty. While early leprosy in young children is self-healing, when marriage and childbearing take place at an early age the daughters of mothers with leprosy are likely to run the risk of experiencing the adverse effects of pregnancy on leprosy. Increased awareness and health education, as well as long term surveillance of 'cured' leprosy patients, are essential to break a potentially vicious cycle of leprosy and pregnancy. Women with cured leprosy could play an important role in screening for and detection of both early leprosy in children and late, post-MDT RFT, nerve damage in their mothers.

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.

Effect of BCG on the risk of leprosy in an endemic area: a case control study.

The effect of BCG on the risk of leprosy was measured using a case-control design in an area endemic for the disease. In this study, 397 newly diagnosed cases and 669 controls matched for age, sex and locality were selected from a defined population. Information on exposure to BCG, contact with another case of leprosy, and relevant socioeconomic variables were obtained from the subjects. Having infectious (multibacillary) and noninfectious (paucibacillary) contacts in the household increased the risk of disease 11.7 times (p less than 0.001) and 2.7 times (p less than 0.001), respectively. Overall, the protection offered by BCG was not significant (odds ratio = 0.8; p = 0.17). However, BCG appeared to increase the risk for indeterminate leprosy (adjusted odds ratio = 2.7; p = 0.09) while protecting against borderline disease (adjusted odds ratio = 0.39; p = 0.03). It is possible that BCG causes a shift in the overall cell-mediated immune response, thus increasing the risk for milder and transient forms of leprosy while protecting against more serious forms. These findings may have important implications for the design and interpretation of vaccine trials. Namely, trials should be designed to measure the protective efficacy of vaccines against the more serious forms of leprosy, which have the greatest public health significance.

[The evaluation of an anti-leprosy program in Uélés (1975-1989)]. / Evaluation du programme de lutte contre la lèpre dans les Uélés (1975-1989).

Foperda, who took over and continued the work initiated in 1924 by the Congo Red Cross, is responsible for the programme of fight against leprosy in the Ueles region (Zaire). Important results have been obtained since 1975 in the framework of a specialised medical service. These results are exposed and discussed herebelow. The evolution of the endemic leprosy in the region under survey allows to contemplate new trends for the pursuit of the programme in the coming years (controlled integration within polyvalent health services).

Leprosy in low endemic areas of India: an appraisal and suggested measures for control.

Prevalence of leprosy in the low endemic areas of India is described based on the observations of patients attending an Urban Leprosy Centre in the Union Territory of Delhi from the neighbouring states. The rising incidence in these so-called low to moderate endemic places is closely linked to factors related to urbanisation, movement of people in search of employment, etc., which necessitate fresh surveys in these areas. A significant number of leprosy patients attending the Centre were irregular (37.7%) in therapy and many absconded after the initial visit (35.3%), the reasons for which are discussed. These figures are compared to that from similar low endemic areas and known high endemic parts of the country. Suitable modifications to the control programme in these areas are suggested under the purview of the National Leprosy Eradication Programme.

Childhood leprosy in Bombay: a clinico-epidemiological study.

During the years 1976-1985, 2138 cases of leprosy were detected in children aged 0-14 years, in L and M wards of Greater Bombay. Out of these, records of 1084 patients were available for detailed analysis. These were mainly from the deprived sections of society. Most cases were detected through surveys, though in recent years, there is an increasing trend for voluntary reporting. The relevant epidemiological and clinical findings are presented and compared with the data of other workers in this field.

T-cell response to my mycobacterial antigens in lepromatous and tuberculoid leprosy

We showed that a large fraction of lepromatous patients do harbor helper-type circulating T-cells that can be activated in vitro by Mycobacterium leprae. M. leprae and PPD triggered T-cell lines could be then obtained from both tuberculoid and lepromatous patients. The proliferative response of these helper T-cells is predominantly directed against epitopes shared by several species of mycobacteria, in lepromatous patients as well as in tuberculoid patients, but species specific T-cells are also present. When presented in the context of M. leprae, these cross reactive epitopes usually fail to stimulate the T-cell lines of lepromatous patients, because of the contamination of the lines by supressor T-cells actavable by M. leprae. In one lepromatous patient, PPD and M. leprae reactive T-cell lines and clones (of the CD4 phenotype), exhibited a strong cytotoxic activity to autologous target cells coated with antigen: the relevance of this phenomenon to the pathophysiology of lepromatous leprosy remains however unknown.

[Control of the contacts: its interference on the epidemiological status of Hansen's disease]. / Controle dos comunicantes: sua interferéncia na situação epidemiológica da hanseníase.

The control situation of hanseniasis patients' contacts needs a deeper study which would show the reality in the public health centers and their consequence over the whole country. The increasing of the prevalence rate of the disease added to the bad social-economic conditions of the patients and contacts gave us subsidies to important studies to understand the present epidemiological picture. This research had the purpose of diagnosing the control situation of hanseniasis patients' contacts in a public health center which had, at the moment of this research (1983) 160 hanseniasis patients (incidence of 1.2/1000) and 757 contacts registered in a Subprogram of Hansen's Disease Control.