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[Neurological manifestations of leprosy].

Leprosy, also known as Hansen's disease, is a chronic, infectious disease caused by Mycobacterium leprae. Bacilli localize preferentially in the skin and peripheral nerves and have a propensity to cause nerve damage. The resulting disability has caused great suffering for victims in many countries. Despite recent advances in the immunopathogenesis, epidemiology and prognostic factors of leprosy nerve damage, many aspects of the disease have remained enigmatic. The spectrum of clinical and pathological manifestations of the disease ranges from lepromatous to tuberculoid, depending on the host's T-cell-mediated immune response. Diagnosis is based on three criteria: characteristic skin lesions in association with thickened nerves, demonstration of acid fast bacilli in slit skin smears, and histopathology of skin biopsies. Nerve biopsy is necessary to establish the diagnosis of pure "neural leprosy". In developed countries, the diagnosis is suspected when a patient who has stayed in an endemic area suffers from a peripheral neuropathy of unknown etiology. To facilitate determination of the appropriate antibiotic regimen, patients are classified as either paucibacillary or multibacillary. Some patients may have multibacillary leprosy in nerves and paucibacillary leprosy in skin, which emphasizes the usefulness of nerve biopsy. The course of the disease is often complicated by immune mediated "reactions", which can rapidly lead to further nerve damage, namely reversal reaction and erythema nodosum leprosy. However, nerves are often functionally impaired before developing obvious symptoms such as skin reactions or nevralgia (silent neuropathy). Early recognition and prompt treatment with corticosteroids of leprous reactions and "silent neuropathies" is very important to prevent disability with all its attendant problems. Research progress from clinical trials may improve current methods of prevention and treatment of nerve damage in leprosy.

Anti-Infective Agents↗

Nonhuman sources of leprosy.

Our findings establish that there are known extrahuman reservoirs of M. leprae in three animal species. There is considerable evidence that the armadillo plays a role in the epidemiology of leprosy in humans in Texas and Louisiana. The elimination of leprosy as a public health problem (defined by the World Health Organization as one active patient per 10,000 population) may be attainable by the wide application of current control measures; however, the ultimate eradication of leprosy must take into account extrahuman reservoirs of M. leprae. The impact that attempts to control or to eliminate leprosy in such reservoirs (e.g., the armadillo in Louisiana and Texas) would have on environmental and wild-life considerations would be profound. Whether or not similar situations prevail in other leprosy-endemic geographic areas is not known. Based on the armadillo experience, there seems to be ample justification for undertaking, forthwith, carefully designed surveys for enzootic leprosy in some of the major endemic areas of leprosy. At the current state of our knowledge of the subject, such surveys should be initiated in the natural habitats of the mangabey monkey and chimpanzees--in West Africa.

Animals↗

Elevated free tear lactoferrin levels in leprosy are associated with Type 2 reactions.

PURPOSE: To determine the association of demographics, leprosy and ocular characteristics with altered levels of lactoferrin in the tears of normal subjects and leprosy patients, and to detect the presence of antibodies to lactoferrin in these tear samples. METHOD: We collected light-stimulated tears from 298 leprosy patients and an equal number of normal subjects using the glass capillary method. Free lactoferrin levels were estimated using ELISA and the presence of antibodies to lactoferrin was detected using the immuno-blotting method. Significant associations were looked for between tear lactoferrin levels and demographic characteristics, leprosy characteristics such as type of disease, duration of disease, reactions, deformity and bacterial load, and ocular complications, using chi-square and regression analysis. RESULTS: Tear lactoferrin levels with a mean (SD) of 2.55 (2.83)mg/ml in the control group were significantly different (P<0.000) from leprosy patients with a smean (SD) of 5.66 (7.21)mg/ml. Age showed an inverse correlation with tear lactoferrin levels in controls. Increased bacterial load, grade 2 leg deformity and Type 2 reactions were significantly associated (P<0.05) with increased tear lactoferrin levels. Type 2 reactions remained significantly associated (P=0.01) on multiple regression analysis. Tear lactoferrin levels were not associated with gender, serum lactoferrin levels, Type 1 reactions, face patches, treatment status, orbicularis oculi weakness, lagophthalmos, ectropion, entropion, corneal opacity, cataract and iridocyclitis. CONCLUSION: Age is inversely related to tear lactoferrin levels in normal subjects. Free lactoferrin levels in tears are significantly higher in leprosy patients compared with normal controls. Type 2 reactions in leprosy are significantly associated with elevated tear lactoferrin levels.

Adolescent↗

Trends in detection of new leprosy cases at two centres in Himachal Pradesh, India: a ten-year study.

An impressive decline in leprosy prevalence rate (PR) in all endemic districts of India is seen in the post-MDT era. However, the new case-detection rate, an important statistical indicator in leprosy control programmes, has not shown significant decline in spite of all efforts. In Himachal Pradesh, a decline in PR from 7.8 to 0.56/10000 between 1991 to 2000 is seen, and recently the State has won national acclaim for having achieved the goal of elimination of leprosy in all the districts. The vertical leprosy programme has been integrated into general health services of the state. An analysis of data from 1991 to 2000 of two leprosy control units of Himachal Pradesh, the Urban Leprosy Clinic in Shimla (ULC-S) and the District Leprosy Control Unit in Mandi (DLCU-M), showed no significant decline in the new cases detected. 277 and 271 new cases were detected at these centres respectively; these included 2.2% and 1.5% children of less than 14 years of age. Almost 75% of these cases were males and of MB type. A steadily increasing trend in the annual detection of new cases was seen at both the centres during the decade. The cases registered at DLCU-M were mainly indigenous to the district. At ULC-S, 45 migrant cases from other endemic areas-mainly from Nepal, Bihar, and Uttar Pradesh-had also contributed to the increased number of new cases. Other possible causes discussed for this higher new case detection, e.g. overdiagnosis, detection of backlog "hidden cases" and voluntary reporting of patients, do not differ from those seen in other parts of the country or the world.

Adolescent↗

Neonatal BCG protection against leprosy: a study in Manaus, Brazilian Amazon.

There is clear evidence that BCG protects against leprosy, but cross-immunity with environmental mycobacteria can interfere with vaccination protection. Some have cast doubts whether BCG vaccination can offer a significant impact against leprosy in the Brazilian Amazon, which is an endemic area for leprosy and with a high prevalence of environmental mycobacteria. This study was designed to estimate the vaccine effectiveness of neonatal BCG against leprosy in Amazon region, in Brazil. This is a cohort study nested in a randomized community trial. The study had two main results. First, neonatal BCG vaccination in Brazilian Amazon elicited protection of 74% (95% CI 57-86) against all forms of leprosy cases. Second, the highest protection was observed for multibacillary cases, 93% (95% CI 71-98). It is concluded that the study provides evidence that neonatal BCG may have an important and overlooked impact on the occurrence and transmission of leprosy, maybe even more in the future when the cohort which received a high coverage of BCG reaches the age of high incidence of leprosy.

Adolescent↗

Prevalence of mental distress in the outpatient clinic of a specialized leprosy hospital. Addis Ababa, Ethiopia, 2002.

Leprosy is a chronic disease that leads to physical disability as a result of nerve damage. Stigma and associated psychosocial problems are common and may increase the risk of mental disorders. This study was conducted to estimate the prevalence of mental distress amongst people attending a Specialized Leprosy and Dermatology Hospital, ALERT, Addis Ababa. Alternate patients from the daily register of outpatients were interviewed for symptoms of mental distress using the Self Reporting Questionnaire (SRQ). This questionnaire was administered by two specially trained nurses. The study population consisted of 786 people. Of these, 60% had leprosy and the remainder had other skin diseases. The sex distribution of the study population was approximately equal. The overall prevalence of mental distress was found to be 34.6%. Among people with leprosy the prevalence was 52.4%, compared with 7.9% in those with other skin conditions. This represented a 7-fold increased risk of mental distress in people with leprosy, adjusted OR = 7.14 (95% CI; 4.15, 12.35). Physical disability was also strongly associated with mental distress. This study showed that the 1-month prevalence of mental distress was significantly higher in patients with leprosy compared to patients with other dermatological conditions. Such a study allows identification of non-specific mental distress. Thus, future work should be directed at further characterizing the nature and severity of mental disorder in this group. However, our study has indicated a need for the integration of psychosocial care into our current medical treatment of patients with leprosy.

Adolescent↗

Recent developments in leprosy control.

Leprosy continues to be a major problem in the developing world with over 3.9 million cases registered in 1989. The control of leprosy had been considerably handicapped by the widespread occurrence of resistance of M. leprae to dapsone the most commonly used anti-leprosy drug. Together with problems of treatment compliance and social stigma this lead to leprosy control losing considerable ground. In response to the situation and taking advantage of the availability of more potent drugs, in 1981, WHO recommended standard multidrug therapy (MDT) regimens for treatment of leprosy in control programmes. The experience of implementating MDT all over the world over the last eight years has shown the regimens to be highly effective and acceptable. By 1990, nearly 50% of all the registered leprosy cases in the world were benefitting from MDT. The future prospects for leprosy control appear bright with major reductions in prevalence foreseen in the coming years.

Developing Countries↗

Can social marketing approaches change community attitudes towards leprosy?

This essay explores how the concept of social marketing can be employed to change attitudes towards leprosy. Firstly, the concept of social marketing is discussed, then the attitudes that people have about leprosy, the stigma that people with leprosy and their families may face, and the detrimental effects that this can have on their lives. The effect of knowledge and education on attitudes towards leprosy is discussed, as this can be a key component of social marketing campaigns. Various methods of social marketing used to change attitudes and reduce stigma are examined, such as mass media campaigns, school based education, methods which involve community leaders, and the integration and improvement of leprosy services. Principles of social marketing which can lead to the success of campaigns such as incorporating local beliefs are emphasized. The success of the social marketing campaign in Sri Lanka is described, which aimed to remove the fear of leprosy, and to encourage patients to seek and comply with treatment. Finally, it is argued that social marketing, used correctly, can be highly effective at changing community attitudes towards leprosy, reducing stigma and improving the lives of patients, who become able to seek treatment sooner as they lose their fear of stigmatization.

Attitude to Health↗

Profile of new cases of childhood leprosy in a hospital setting.

A hospital-based prospective study was carried out to assess the frequency of occurrence of leprosy in childhood. Out of 800 patients registered for leprosy, 67 (8.4%) were children aged 4-14 years. The male-to-female ratio was 2.5:1. Family history of leprosy was found in 14.9% of cases. The commonest type of leprosy was BT leprosy (35.8%), followed by BB leprosy (25.4%) and BL leprosy (19.4%). More than half of the patients had more than one lesion. Nerve involvement was noted in 70.1% of cases. Slit-skin smear was positive in 46.3% of cases. Out of 67 children, PB and MB regimens were given to 29 and 38 respectively.

Adolescent↗

Leprosy control activities in India: integration into general health system.

Integration of leprosy control into the general health system is an essential element of a leprosy elimination strategy. In India, the process has been undertaken with the assistance of World Bank in a phased manner. In the first phase (2001-2002), 24 low/moderately endemic provinces for leprosy were targeted. Operational research was undertaken in these low/moderate endemic provinces to assess the progress of integration of leprosy control in general health system using defined categories, viz. structural integration, training status, availability of MDT and recording/reporting of cases. Selection of nine provinces, 18 districts, 86 health facilities and 108 sub-centres was performed using multistage stratified random sampling technique. Data were collected by interviewing GHS/vertical staff, scrutiny of records and spot checking of MDT stock by Health officers of three leprosy institutions of the Government of India. The result showed that district leprosy nuclei had formed in 16 of 18 districts. In 56% of health facilities vertical staff were redeployed for delivering general health care. Forty-five percent of medical officers, 71% of health supervisors and 75% of multipurpose workers were trained in leprosy. MDT treatment was available in >80% of health facilities. In only 2% of health facilities 3 months MDT stock of all types was present. Forty-four percent of sub-centres were delivering subsequent doses (second dose onward) of MDT. Reporting through a simplified information system was universal. This study emphasizes the need for reorientation training of Medical Officers, better MDT stock management and decentralized management of cases up to sub-centre level.

Communicable Disease Control↗

The factors influencing the operational efficiency of leprosy case detection programme.

Under our National Leprosy Eradication Programme, Leprosy cases are being detected by para-medical workers by conducting population surveys. In order to detect the leprosy cases early, for their timely anti-leprosy treatment, it is necessary that the leprosy surveys are implemented and supervised efficiently. However, present experience indicates that the existing survey efficiency needs to be improved, for which it is necessary to analyse the factors which may interfere with the optimal survey efficiency of para-medical workers. An attempt has been made through present piece of work to identify such factors in relation to (i) the para-medical workers and survey facilities, (ii) the implementation and supervision of leprosy survey and (iii) the community involved in survey. These factors are discussed in detail to assist the NLEP Administrators in devising a suitable action plan to improve leprosy case detection efficiency.

Community Health Workers↗

The national leprosy eradication programme in India.

India has the largest leprosy problem in the world, with an estimated 4 million patients. The number of registered cases in the country was 2.4 million by June 1990, and the number of new cases detected during 1989-1990, 0.47 million. The disease prevalence varies widely from state to state and even among districts within states--8 of the 26 states contribute to 90% of all the registered cases. The country has a high priority for leprosy and the National Leprosy Eradication Programme (NLEP) aims to arrest the disease among all known cases in the country by the turn of the century through a strategy which includes multidrug therapy (MDT), early case detection, health education and rehabilitation. The specialized leprosy infrastructure in the country has a total of about 8,500 establishments including 719 leprosy control units, 244 district leprosy units and 49 training centres. By June 1990, 130 districts with 2.15 million patients had come under MDT. It is planned to cover 196 districts by 1992, ensuring coverage for 90% of the patients in the country. The country spends approximately 600 million rupees (US$ 33.3 million) per year on NLEP. In addition, a number of bilateral and international agencies including nongovernmental organizations participate in the programme. WHO supports the NLEP through technical inputs, monitoring and evaluation, and training. Plans to integrate leprosy control within primary health care, particularly after completion of the intensive phase of MDT, are being developed. Operational and technical constraints are constantly reviewed in order to find optimal solutions.

Communicable Disease Control↗

Immunohistologic assessment of cytokine production of infiltrating cells in various forms of leprosy.

The aim of this study was to determine cytokines in human leprosy lesions by means of immunohistologic examination. Cryostat sections of skin biopsies from 57 patients with various forms of leprosy were immunostained according to the APAAP method, using monoclonal antibodies against interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and, in addition, against CD 1 antigen. Granulomas in biopsies of untreated patients with tuberculoid leprosy showed large amounts of cells positive for IL-1 beta, TNF-alpha, IFN-gamma, and CD 1, whereas no positive signals could be detected in untreated patients with lepromatous leprosy. However, in those biopsies obtained from lepromatous leprosy patients undergoing chemotherapy, positive staining for cytokines as well as subepidermal Langerhans cells increased to a detectable amount. Remarkably, in tuberculoid leprosy patients, the number of IL-1 beta--positive cells did not vary under therapy, while the number of TNF-alpha and IFN-gamma reactive cells decreased. These results suggest that immunohistologic determination of cytokines in combination with the assessment of subepidermal Langerhans cells in human leprosy lesions may be used as a parameter for the patient's status of cell-mediated immunity under chemotherapeutic treatment.

Antigens, CD↗

The demystification of leprosy: a multifactorial problem.

Abolishment of misbeliefs and misconceptions, unfounded fear and prejudice are factors as important in leprosy control as prevention, early detection and therapy. Concrete measures of demystification are proposed. Identify and divulge the absolute truth about leprosy. Calling leprosy "Hansen's disease" did not result in demystification. Patients know that the two terms are identical. Treating them as human beings attracts more patients to the healers than the Hansenologian ritual. Contrary to statements, no major advances are being made in the field of bacteriology, immunology, molecular biology, mode of transmission and epidemiology of leprosy. Not a single new drug has been discovered in 26 years. Vaccination is a dubious venture. The question arises as to whether the right priorities are promoted in leprosy research. Cultivation of the leprosy bacillus is the sine qua non of any further progress. This field of research is a lost and totally neglected priority. Consequently we have no pharmacological model for badly needed of ultrapotent antileprosy drugs. Syphilis is now cured with a single dose of penicillin. A drug as potent against leprosy should not be a mission impossible if an appropriate pharmacological model--the in vitro culture--is available. The multifactorial problem of demystification is a difficult but not an impossible task. Less sensationalism, more real progress in research, selecting the right priorities, achieving the "ultimate drug", shelter, food, shoes, soap and broom for every human on this planet constitute the road to demystification.

Anti-Bacterial Agents↗

A passive hemagglutination test for leprosy using a synthetic disaccharide antigen.

There is a need for a simple, sensitive, and specific test for the serodiagnosis of leprosy. A passive hemagglutination (PHA) test for leprosy was developed to meet these requirements. A synthetic disaccharide, conjugated to bovine serum albumin and specific for the phenolic glycolipid of Mycobacterium leprae, was sensitized to aldehyde preserved and tanned sheep erythrocytes (SRBC). The sensitized SRBC were used for testing sera from leprosy and tuberculosis cases and normal controls at 1: 64 and 1:128 serum dilutions. It was found that if the hemagglutination reaction at greater than or equal to 1: 128 is considered positive, the test was positive in 84.2% of 38 cases of multibacillary leprosy, 16.7% of 24 cases of paucibacillary leprosy, 16.7% of 6 contacts of multibacillary leprosy, 11.8% of 51 cases of tuberculosis, and 3.7% of 54 blood donors. If the cutoff value used was 1:64, the test was more sensitive but less specific. The results are similar to that of an ELISA for IgM antibody to the same synthetic antigen. The present PHA test is simple and sensitive, but moderately specific. Its simplicity and sensitivity make it highly suitable for large-scale screening of contacts in leprosy-endemic areas.

Antigens, Bacterial↗

BCG vaccination in leprosy: final results of the trial in Karimui, Papua New Guinea, 1963-79.

The efficacy of BCG vaccine in preventing the clinical manifestations of leprosy in a tuberculosis-free area of Papua New Guinea is reported. Between 1963 and 1966 a total of 5356 subjects, randomized to receive BCG or saline inoculations, were examined for leprosy before the vaccination and surveillance was continued until 1979. BCG afforded 48% protection against clinical leprosy, being most effective against borderline tuberculoid leprosy and in children vaccinated when under 15 years old. Protection was evident within 12 months in those vaccinated between the ages of 10 and 15 years but was delayed in other age groups. There was evidence for accelerated manifestations of tuberculoid leprosy in children vaccinated when under 5 years of age. Tuberculin sensitivity was more likely to be sustained following multiple BCG inoculations; vaccinees with sustained tuberculin sensitivity had the lowest incidence of leprosy, but protection was also evident in tuberculin-negative vaccinees. These results may have implications for ongoing trials of leprosy vaccine incorporating BCG.

Adolescent↗

Leprosy teaching in medical colleges in Bombay--a questionnaire study.

An attempt was made to study the adequacy of leprosy teaching at the undergraduate level of the four medical colleges in Bombay, and to suggest possible routes towards the reorientation of leprosy teaching. Over 55% of the medical faculty contacted expressed dissatisfaction with the existing pattern of leprosy teaching. The survey reveals ample evidence pointing to the necessity of redesigning the curriculum at the undergraduate level, so as to provide increased weightage to both the theoretical and the practical aspects of leprosy. A heartening feature of the study is the inclination shown by a majority of medical teachers to associate themselves with the PSM Department in order to help improve leprosy teaching and thereby help in leprosy control. This offer should definitely be taken advantage of for furthering the cause of leprosy eradication as a part of achievement of "Health for All by 2000 AD".

Curriculum↗

Skin test studies on close contacts of leprosy patients in India.

Skin-test studies with a series of tuberculins have been carried out in close contacts of multibacillary (MB) leprosy patients around three leprosy centers in India, and casual contacts of the disease around two centers. The results show that the rate of acquisition of leprosin A positivity is associated with age and the closeness of contact with MB leprosy. At the age of 15 years, the differences between the two types of contact were highly significant (p less than 0.00001). Many responses to leprosin A are directed toward the group iv species-specific, antigens of the leprosy bacillus, and the significance of positivity is discussed in relation to protective immunity from leprosy. The differences from Iran show that positivity to leprosin A is not solely the effect of the degree of contact with the disease, but must also have a genetic or environmental element, the latter being favored. The results from Miraj show that the high levels of tuberculin, scrofulin, and vaccin positivity seen in Fathimanagar, and to a lesser extent in Karigiri, are not a consequence of contact with leprosy. BCG vaccination made little difference to the leprosin A positivity of close contacts of leprosy patients, although it significantly enhanced positivity among casual contacts around Miraj (p less than 0.002). BCG vaccination significantly increased tuberculin positivity in Miraj and Karigri, and in those under 11 years of age in Fathimanagar. It made no difference to the already high level of positivity found in older persons around Fathimanagar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗