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Vasomotor reflex testing in leprosy patients, healthy contacts and controls: a cross-sectional study in western Nepal.

OBJECTIVE: To examine test characteristics of laser Doppler vasomotor reflex testing for leprosy and to determine the prevalence of abnormal responses in leprosy patients, healthy contacts and controls. DESIGN AND PARTICIPANTS: Cross-sectional study including 89 leprosy patients (mean age 35 years, 74% male), 36 healthy contacts (29 years, 64% male) and 47 controls (30 years, 68% male), for a total of 172 participants. SETTING: Leprosy hospital in an endemic region 200 km west of Kathmandu, Nepal. OUTCOME MEASURE: Finger-tip and toe-tip vasomotor reflexes elicited by inspiratory gasp were measured using a laser-doppler flow temperature technique. Results were expressed in per cent as the maximal reduction in bloodflow from baseline. RESULTS: For all 12 measurement sites there were highly significant (p > 0.0001 to < 0.004) differences between the three groups tested. Leprosy patients consistently had the lowest responses and controls the highest, with healthy contacts showing intermediate values. Thresholds defined as mean bloodflow reductions among controls minus 1.64 or minus 1.96 standard deviations provided optimal combinations of sensitivity and specificity. Using these cut-off values around 80% of leprosy patients, 50% of healthy contacts and 20% of controls had two or more abnormal reflexes (p < 0.0001 for differences between groups). CONCLUSIONS: In endemic regions, subclinical autonomic neuropathy may be an early but detectable marker for the risk of subsequent leprosy, making early treatment and prevention of transmission possible. Prospective studies are needed to establish the predictive value of abnormal vasomotor reflexes.

Adult↗

Tuberculosis control is good for established leprosy programmes.

Tuberculosis (TB) control was introduced into part of the Danish Bangladesh Leprosy Mission's large leprosy control programme in 1994. This was in line with the Government's policy of combining leprosy and TB control. We report our experience with integration. Leprosy case-finding has increased during the period, and staff satisfaction and morale has also risen despite the larger workload. We observed that the field work skills of leprosy workers was brought to bear in a very positive way on TB control. TB patients suffer considerable impoverishment as a result of their illness, paralleling the social dehabilitation often seen in leprosy sufferers. TB control is good for established leprosy programmes.

Bangladesh↗

Is knowledge of leprosy adequate among teachers? A comparative study.

A cross-sectional comparative study on the levels of knowledge and attitude on leprosy among teachers and students was carried out in a rural area of Vellore district in Tamil Nadu, India. A total of 30 teachers and 120 students participated in the study. It was found that knowledge about leprosy among teachers was inadequate. Only 23.4% of teachers stated that germs caused leprosy, while 23.4% mentioned immoral conduct, 20.0% marrying a leprosy patient, 6.6% insects and 26.6% did not know the causes of leprosy. While 80.0% of teachers knew that anaesthetic hypopigmented patches were a sign of leprosy, enlarged painful nerves were not mentioned by a single teacher, although this sign was identified by 17.5% of students. Teachers had a more positive attitude towards leprosy than students and this was statistically significant (p < 0.001). This paper discusses the need for continuous education, especially for teachers and through them the students, using different media so as to ensure sustained knowledge for behavioural change in the community.

Adolescent↗

Case detection, gender and disability in leprosy in Bangladesh: a trend analysis.

A trend analysis is presented of all newly detected leprosy cases over an 18-year period (1979-1996) in a highly leprosy endemic area of Bangladesh. A total of 23,678 new cases were registered, with an average of 860 new cases per year in the first 12 years, and increasing to around 3000 in 1996. The male:female (M:F) ratio decreased from 2.3 to 1.4. The proportions of newly detected cases with MB leprosy and of newly detected cases with any disability decreased over time. These reductions were more marked in the higher age groups of both sexes. The reduction in disability was primarily attributable to a decline in grade 2 disability. New case detection rates (NCDR) of all leprosy patients per 10,000 general population increased for males from 3 to 6; and for females from 1 to 4, while the NCDR of MB leprosy decreased in males from 1.4 to 0.6, and in females fluctuated around 0.45. The NCDRs of leprosy patients with disabilities showed an initial decrease in the first period, especially in males, but later showed an increase. The NCDR of males with disability was about twice as high as that of females. Finally, female NCDRs in the ages between 15 and 30 were low by comparison with the male NCDRs at the same time. This may be due to the sociocultural characteristics of the Bangladeshi society, with gender differences in exposure, health seeking behaviour and opportunities for case detection. Operational changes in the control programme have contributed to the changed profile of newly detected cases. This study shows that the application of general population statistics is essential for understanding the dynamics in leprosy control programmes under changing operational conditions. Combining case detection figures with such statistics helps to identify population groups that are possibly not benefiting sufficiently from the services provided, and to clarify the dynamics in control programmes and the future trends and programme requirements.

Adolescent↗

Leprosy elimination through integrated basic health services in Myanmar: the role of midwives.

Myanmar is one of the top 16 countries identified by WHO as being hyperendemic for leprosy. Multi-drug therapy (MDT) was introduced in 1988 as a vertical programme and gradually integrated into the basic health services (BHS), achieving 100% coverage over the registered cases by 1995. To achieve maximum coverage of and benefit for patients, both leprosy vertical staff and BHS staff were trained to implement MDT whilst performing routine BHS activities. This included a total of 8615 trained midwives who were mobilized for the nationwide leprosy elimination programme (LEP). They worked at village level in various parts of the country and were willing and able to carry out basic tasks in leprosy management, such as the implementation of MDT using blister-calender packs carrying a month's supply of drugs. This study was performed to assess the workload of midwives and their attitude towards LEP. The authors conclude that midwives in Myanmar show a high level of commitment and reliability, which are essential contributing factors to achieve the current goal of leprosy elimination by the year 2000. Along with the present trend of decreasing prevalence rate, leprosy could no longer be considered as a public health problem at national level by the year 2000 in Myanmar. However, because of its long incubation period, new leprosy patients may arise even after the elimination target is achieved, whilst many other patients may become disabled. A community-based sustainable approach for the post-elimination phase, after the year 2000, will be essential and the contribution of the midwives may be of considerable importance.

Adult↗

Leprosy elimination campaign, Amazonas-Brazil 1997.

A leprosy elimination campaign (LEC) was carried out in 15 endemic areas of Amazonas State, Brazil, in 1997. The LEC concentrated effort to detect leprosy cases during a multi-vaccination national campaign for serious public health problems other than leprosy, such as polio, diphtheria, hepatitis, measles, etc. The national campaign involved intensive population mobilization, giving a valuable opportunity to examine people for leprosy. The LEC personnel included 2964 individuals (municipal and state health workers and community volunteers), distributed in 688 health units and 53 reference health centres. As a result of the LEC, 74,814 person-to-person communications in the community were given; 10,297 clinical skin examinations were conducted, and 40 new leprosy cases were detected on the day of the campaign in urban areas of the municipalities. This total was low, compared to results in other states of Brazil, possibly due to the development of health education activities and regular community services in the state of Amazonas since 1987 and to the early implementation of WHO multiple drug therapy (MDT) from 1982 onwards. Despite the fact that the LEC was carried out only in the urban areas of the municipalities, the finding of no cases of leprosy in 7 out of 15 of them was surprising and may indicate that the prevalence of hidden cases of leprosy is not all that high, at least in these areas of the Amazonas State.

Brazil↗

Leprosy research--setting priorities and facilitating collaborations: a personal perspective.

In recent years, as the prevalence of leprosy has declined and the tuberculosis epidemic has gained increasing attention, leprosy research has generally taken a 'back seat' to research in tuberculosis and other emerging and re-emerging infections. This has resulted as much from perceived differences of scientific opportunities in these fields as from differences of the disease burden. At the United States National Institutes of Health (NIH), research priority setting is typically based on a number of factors. In the case of leprosy research, the technical difficulties associated with this scientific area have clearly lessened enthusiasm for and progress in this field. Today, however, we are confronted by the reality of not having sufficient scientific understanding to explain a stable or increasing number of leprosy cases detected annually in the face of a dramatically decreasing total number of identified cases. We also lack adequate tools for diagnosis and prevention. At the same time, new molecular and cellular approaches and knowledge of the complete sequence of the genome of Mycobacterium leprae render leprosy research significantly more tractable than ever before. The combination of these factors has led a number of groups, including the National Institute of Allergy and Infectious Diseases of the NIH, to review the current state of knowledge in leprosy research and draft recommendations for future leprosy research priorities. It is clear that many of the necessary and exciting research activities can best be addressed through collaborations among investigators, with control programmes, and among countries of high and low endemicity.

Developing Countries↗

Modified Active Surveillance System (MASS); a novel clinicopathological evaluation of PB leprosy patients after RFT, in Mangalore, India.

The current recommendations for leprosy control programmes include stopping active surveillance in view of the very low relapse rates and a phased integration of leprosy services with the general health services. Passive surveillance may not be adequate, more so because of the introduction of newer, shorter drug regimens. This study is an effort to evolve a modified active surveillance, which is cost-effective, simple and also a novel substitute for the increased workload caused by the dwindling number of PMWS. One thousand one hundred RFT-PB leprosy patients were recalled for a review under the Modified Active Surveillance System (MASS), carried out over two phases. Patients were divided into groups as per the mode of response to the mailed postcards; Responders (patients who reported to the OPD in person), Untraceables (patients whose postcards returned back) and non-responders (patients who did not report of the OPD after receiving the mail). At the end of phase I, we had 120 Responders, 480 Untraceables and 500 Non-responders. In phase II, which began 2 months later, the 500 non-responders were dispatched reminders. In this phase, there were 31 responders, 60 untraceables and 409 non-responders. Thus, at the completion of phases I and II, there were 151 responders, 540 untraceables and 409 non-responders. Of the 151 patients examined, 71 had no complaints (category 1), 41 had fresh leprosy-related complaints (category IIA), 14 had fresh leprosy-unrelated complaints (category IIB) and 25 had persistence of old complaints (category III). Cumulative PYR of the 151 patients was 1155.42. Forty-one patients had fresh leprosy-related complaints. Skin biopsy was done in the 17 patients with fresh skin patches, of whom four showed histopathological evidence of relapse. Relapse rate in our study was 0.35/100 PYR. Mean duration after RFT at relapse was 4.9 years. Our scepticism towards passive surveillance systems is justified by these 41 patients with fresh leprosy-related complaints, who voluntarily reported only after receiving the postcards. We recommend the introduction of a phase III, wherein the services of PMWs may be used to contact the 409 patients who remained unresponsive at the completion of phases I and II. We also recommend the introduction of a universal format for recording addresses of all new patients, which would be of immense help in patient retrieval in all such surveillance systems in the future.

Adolescent↗

Studies on mode of detection of leprosy in China during the years 1981-1998.

Along with the nationwide economic reform initiated in the early 1980s and the rapid decrease of leprosy endemic after the implementation of multi-drug therapy (MDT), the leprosy programme changed from 'vertical' to 'horizontal'. An evolution in the mode of detection of leprosy cases has consequently taken place. Based on the nationwide registration of newly detected cases, the profile of patients at detection has been studied. The proportions of cases corrected significantly with calendar years in detection by dermatological clinics, contact checks, 'clue survey' and mass survey, showing a significant increase in percentage of cases detected through dermatological clinics and contact checks, and decreases through 'clue survey' and mass survey. Detection of cases through dermatological clinics and voluntary reporting have become the main modes of case-finding during 1997-1998, accounting for 37.3% and 28.6%, respectively, where contact check accounts for only 9.1%. In areas with good dermatological services, a significantly higher proportion (75.9%) of cases was detected through dermatological clinics, where voluntary reporting and 'clue survey' were the main modes of detection in endemic areas. As regards confirmation of diagnosis, the great majority of cases were confirmed by leprosy units, even though they were detected in various other situations. Only 6.5% of leprosy cases were detected and subsequently confirmed by doctors in dermatologic clinics. The present modes of detection and their relation to demographical, epidemiological, clinical factors and health services are discussed. This study emphasizes the cardinal importance of the dermatological clinics in the detection of leprosy cases in China at the present time and hence the need to strengthen the training of doctors in these clinics, while continuously encourage their involvement in leprosy control.

Adolescent↗

An epidemiological study on Mycobacterium leprae infection and prevalence of leprosy in endemic villages by molecular biological technique.

One of the most important unsolved questions in epidemiology of leprosy is the highly uneven geographic distribution of the disease. There are many hyperendemic "pockets" in endemic countries. Little is known about the reasons why leprosy is hyperendemic in these areas. We conducted, therefore, a series of epidemiological studies on Mycobacterium leprae infection and prevalence of leprosy in North Maluku district, Maluku Province, Indonesia where leprosy is highly endemic. It was found that considerable number of general inhabitants are seropositive to various mycobacterial antigens and 27% of the villagers were carrying leprosy bacilli on their surface of nasal cavity. These results suggested the importance of M. leprae in the residential environment in infection of the leprosy bacillus and the resulting transmission of the disease. Based on these observations, we conclude that new preventive measures are essential for global elimination of leprosy in addition to early diagnosis and multidrug therapy (MDT).

Antibodies, Bacterial↗

Some aspects of tuberculoid leprosy and chemotherapeutic trials.

The author describes the progress made in our knowledge of tuberculoid leprosy since the original case of Jadassohn in 1898. The numerical importance of T patients in different parts of the world is reviewed and their role in the transmission of the disease discussed. An analysis is made of the subgroups into which T leprosy is divided according to the clinical symptoms, bacteriology, histopathology and immunology in the Madrid classification as well as in the Souza-Lima-Souza Campos and Ridley-Jopling studies. The author concludes that a majority of T patients are immunologically stable and belong to two well defined groups, the first called T annular in the Souza-Lima-Souza Campos study and TT in the Ridley-Jopling classification and the second called T reactional by S.L.-S.C. and BT by R.J. Taking into account the high proportion of T cases in most epidemiological situations, their generally accepted good prognosis under treatment and the present availability of several drugs of proved efficacy, the author suggests to carry out in T leprosy under controlled conditions a trial of a number of therapeutic regimens of not more than 12 months duration. Follow-up periods will make possible medium and long-term evaluation of results after 3 and 5 years respectively of the initiation of the chemotherapeutic regimens. The practical implications of effective and well tolerated short-term therapy in T leprosy is stressed. Its widespread use in field programmes will represent among other advantages a considerable economy in personnel and drugs costs. The use of a single protocol is recommended. The one worked out by THELEP for therapeutic trials in lepromatous leprosy could be adopted with a few changes made necessary because of the morphological and bacteriological differences between L and T leprosy. It is suggested that, if the results of the trial are successful, similar regimens could be tried in indeterminate leprosy.

Clinical Trials as Topic↗

Lucio leprosy with lucio phenomenon.

Leprosy is one of the commonly seen disease in any dermatology outpatient department in our country. India accounts for a major portion of the leprosy patients in the world. All types of the disease, such as tuberculoid, borderline, lepromatous, neuritic and indeterminate leprosy, are seen. However, "lucio leprosy" which is considered a special type of lepromatous leprosy characterised by diffuse involvement has not been reported from India. We are presenting here two cases of "lucio leprosy" with "lucio phenomenon", the lucio phenomenon being a special type of lepra reaction seen in lucio leprosy.

Aged↗

Distinct histopathological patterns in single lesion leprosy patients treated with single dose therapy (ROM) in the Brazilian Multicentric Study.

This paper aims to describe the histomorphologic features of skin biopsies of single lesion leprosy patients recruited at outpatient clinics in four Brazilian states in the Northeast (Amazonas and Rondonia), Southeast (Rio de Janeiro) and Center-West (Goiás) between October 1997 and December 1998. Patients clinically diagnosed as single skin lesion paucibacillary (SSL-PB) leprosy had a standard 4-mm punch biopsy taken from the lesion before rifampin, ofloxacin, minocycline (ROM) therapy. The features of the cellular inflammatory infiltrates, the presence of nerve involvement and acid-fast bacilli (AFB) were used to categorize SSL-PB biopsies into different histopathological groups. Two-hundred-seventy-eight (93.0%) out of 299 patients had a skin biopsy available. Seven single lesion patients were diagnosed as BL or LL leprosy types (MB) by the histopathological exams and 12 cases were excluded due to other skin diseases. Therefore, 259 patients had skin lesions with histomorphological features compatible with PB leprosy categorized as follows: 33.6% (N = 87) of the biopsies represented well-circumscribed epithelioid cell granuloma (Group 1); 21.6% (N = 56) less-circumscribed epithelioid cell granuloma (Group 2); 12.0% (N = 31) were described as mononuclear inflammatory infiltrate permeated with epithelioid cells (Group 3), and 29.7% (N = 77) had perivascular/periadnexal mononuclear inflammatory infiltrate (Group 4). Minimal/no morphological alteration in the skin was detected in only 8 (3.1%) SSL-PB patients categorized as Group 5, who were considered to have leprosy by clinical parameters. SSL-PB leprosy patients recruited in a multicentric study presented histomorphology readings comprising the whole PB leprosy spectrum but also a few MB cases. These results indicate heterogeneity among SSL-PB patients, with a predominance of well-circumscribed and less-circumscribed epithelioid cell granulomas (Groups 1 and 2) in the sites studied and the heterogeneity of local cellular immune response.

Adult↗

Time of presentation for treatment and profile of deformities among leprosy patients in South Eastern Nigeria.

A 10 year review of leprosy patients seen at Leprosy Hospital Ekpene Obom in South Eastern Nigeria (1988-1997) was carried out to evaluate the effect of early identification and treatment of leprosy patients in the limitation of deformities among them. A total of 2,597 patients comprising 1,714 (66%) males and 883 (34.0%) females formed subjects for the study. Of these 288(11.1%) were aged 15 and below while 2,309 (88.9) were above 15 years. Their case records were thoroughly reviewed noting the duration of disease before presentation, type and location of deformity as well as the type of leprosy. Though there was a steady decline in the total number of leprosy patients seen over the study period as well as a decrease in the mean duration of illness before presentation, approximately 19% of patients still had deformities at presentation, a figure much lower than those reported by other workers. Analysis of the pattern of deformities shows that most patients 71.2% presented with affectation of the upper and lower limbs with consequent functional disability. We conclude that early treatment is an effective means of reducing the prevalence of deformity and thus disability from leprosy. More effective implementation of health education and treatment programmes initiated by the W.H.O should further reduce the scourge of leprosy in our community.

Adolescent↗

Distinguishing features of anti-beta2 glycoprotein I antibodies between patients with leprosy and the antiphospholipid syndrome.

Anticardiolipin (ACA), anti-beta2 glycoprotein I (beta2GPI), and antiprothrombin antibodies of IgG and IgM classes were quantitated by enzyme-linked immunosorbent assays in 176 untreated leprosy patients across the histopathological spectrum. Positivity rates ranged from 21% (IgG ACA) to 30% (IgM anti-prothrombin) versus 4% in healthy controls (p <10(-2) to 10(-3)). Levels of IgM anti-beta2GPI and IgG ACA were significantly higher in lepromatous leprosy and multibacillary patient subgroups. IgG3 was the most common subclass reactive to both beta2GPI and prothrombin in selected high-titer leprosy sera, unlike antibodies from patients with the antiphospholipid syndrome (APS) largely restricted to IgG2. In leprosy patients, but not in the APS control group, there was no statistical correlation between ACA and anti-beta2GPI antibody levels. Likewise, a large fraction of anti-beta2GPI positive sera (36/45 and 28/44 for IgG and IgM, respectively) were unreactive in the standard ACA assay. Most assayed anti-beta2GPI antibodies from leprosy patients showed (i) ability to recognize both human and bovine beta2GPI immobilized on non-irradiated polystyrene plates, (ii) concentration-dependent inhibition of binding by cardiolipin, and (iii) relatively high avidity binding to fluid-phase beta2GPI, thereby differing from those found in APS. Finally, the location of the major epitopic region on the beta2GPI molecule targeted by autoantibodies was different in leprosy and APS, as assessed by direct binding to domain I- and V-deleted mutants and competition with the mouse monoclonal antibody 8C3, directed at domain I. Thus, leprosy-related antiphospholipid antibodies comprise persistent IgG and IgM anti-beta2GPI that differ from APS-related ones with respect to IgG subclass, avidity and epitope specificity, possibly reflecting distinct pathophysiological significance.

Adolescent↗

A study on a possibility of predicting early relapse in leprosy using a ND-O-BSA based ELISA.

Serological methods have been used for detecting infection with Mycobacterium leprae. We have applied a serological test to explore the possibility it could detect a bacterial relapse among patients who have been cured with chemotherapy. More specifically we used an indirect enzyme-linked immunosorbant assay (ELISA) using the natural disaccharide (ND) of the phenolic glycolipid antigen of M. leprae linked to bovine serum albumin as antigen. Antibody levels were measured in sera from normal controls, active leprosy cases, cured leprosy patients, and relapsing leprosy patients. We correlated antibody levels with the type of leprosy, the bacterial index, and with relapse among cured leprosy patients. In our hands, the ND-ELISA, when applied to screening for infection with M. leprae, had excellent sensitivity, specificity, positive and negative predictive values, and both a low false positive rate and a low false negative rate. Antibody levels gradually increased among active patients from the tuberculoid to the lepromatous end of the leprosy spectrum. There was a year-by-year fall in antibody levels in patients responding to chemotherapy. Antibody levels and the bacterial index were correlated using the Spearman's rank correlation method. Serial antibody levels were measured in 666 leprosy patients after being cured with dapsone monotherapy. Over a three year follow up, 95 multibacillary patients became antibody positive and 12 of them had bacterial relapses of their disease. In contrast, among 335 cases that remained antibody negative, only one relapse was seen. Among 44 paucibacillary cured patients who became antibody positive, there was one relapse. There were 192 such patients who remained antibody negative and one relapsed. The risk of relapse is 6.7 times higher among cured multibacillary patients compared to cured paucibacillary patients. Overall, the cumulative relapse rate among antibody positive cases was 13.7%, compared to 0.4% among antibody negative patients. We conclude that the ND-ELISA is a useful tool both for screening for early infection with M. leprae and for predicting a relapse in cured patients, particularly in cured multibacillary patients.

Antibodies, Bacterial↗

Microtiter particle agglutination test for diagnosis of leprosy.

The results of studying the microtiter particle agglutination (MPA) test for detecting anti-Mycobacterium leprae antibodies in blood sera are presented. The serodiagnostic test is based on the agglutination of colored polyacrolein latex microparticles (PAMP) conjugated with 3,6-di-O-methyl-D-glucose (DMG). Sera from 45 leprosy patients (LL, BL), 34 leprosy contacts, and 148 control subjects were investigated by the MPA test. A correlation between the anti-M. leprae antibodies and the bacterial load was found. In many long-treated leprosy patients increased titers of anti-DMG antibodies were observed, which might be due to specific polyneuritis in them. Four contacts of leprosy patients were also positive in the MPA test. "Nonleprosy" sera did not react in the test. The method proposed proved to be of high specificity and sensitivity for the serological diagnosis of leprosy. The rapidity, simplicity, and visual assessment of the results allow the method to be used in the field for epidemiological studies of leprosy contacts and the general population in leprosy-endemic areas.

3-O-Methylglucose↗

Role of leprosy villages and leprosaria in Shandong Province, People's Republic of China: past, present and future.

In the late phase of the leprosy control programme in Shandong Province, People's Republic of China, there are a few old and disabled ex-patients living in 54 leprosy villages/leprosaria. The small, and declining number of patients makes the running of these leprosy villages/leprosaria uneconomic. In this paper, we review the history and the role of leprosy villages/leprosaria in the care of leprosy patients and the control programme in Shandong province. We then analyse the present situation of the 643 people still living in these leprosy villages/leprosaria, using information collected from a questionnaire-based survey. Finally, we offer some suggestions and recommendations for policy makers and leprosy control managers, in order to improve the present situation and make better use of existing resources.

Activities of Daily Living↗