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1.

Background

The ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.

Methodology/Principal Findings

Three hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.

Conclusions/Significance

Leprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.  相似文献   

2.

Background

With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy.

Methods

We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER) between the standard multidrug therapy (MDT) program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case.

Findings

Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214), slightly less cost-effective in next door neighbours (ICER $497) and least cost-effective among household contacts (ICER $856).

Conclusion

Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world.  相似文献   

3.
Objective To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts.Design Single centre, double blind, cluster randomised, placebo controlled trial.SettingLeprosy control programme in two districts of northwest Bangladesh with a population of more than four million.Participants28 092 close contacts of 1037 patients with newly diagnosed leprosy. 21 711 contacts fulfilled the study requirements.Interventions A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient’s treatment, with follow-up for four years.Main outcome measure Development of clinical leprosy.Results 18 869 of the 21 711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT.ConclusionA single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years.Trial registration Current Controlled Trials ISRCTN61223447.  相似文献   

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Leprosy in Colombia is in the post-elimination phase; nevertheless, there are regions of this country where the incidence is still around 3-4/100,000. Early detection of leprosy patients is a priority for achieving control and elimination of leprosy; however, the clinical exam is not very sensitive and thus, the majority of patients are diagnosed only when they demonstrate lesions, and damage to the nerves and skin has already occurred. The goal of the present study was to identify Mycobacterium leprae infection and immune responses in household contacts (HHC) of leprosy patients from three prevalent regions of Colombia. Clinical examination, the Mitsuda test, evaluation of IgM anti-PGL-I in the serum, the bacillar index (BI), and polymerase chain reaction (PCR) from nasal swabs (NS) were performed for 402 HHC of 104 leprosy patients during a cross-sectional survey. Positive titers for IgM anti-PGL1 were found for 54 HHC, and PCR-positive NS for 22. The Mitsuda reaction was negative for 38 HHC, although three were positive for IgM anti-PGL-1 titers. The data document that leprosy transmission among HHC is still occurring in a non-endemic country.  相似文献   

7.
OBJECTIVE: To define diagnostic cytomorphologic features of reactions in leprosy. STUDY DESIGN: Part-retrospective, part-prospective, single-blind, controlled study of the applicability of fine needle aspiration cytology in the diagnosis of reactions in leprosy. Cytomorphologic features were compared in 42 clinically diagnosed patients with reactions in leprosy with those in a control group of patients with nonreactional leprosy. The study groups included type 1 and type 2 reactions in 35 and 9 patients, respectively. May-Grünwald-Giemsa and Ziehl-Neelsen staining methods were employed. RESULTS: Statistically significant (P < .01) cytomorphologic features of type 1 reaction were the presence of fragments of collagen and elastin; giant cells; giant cells exhibiting elastin phagocytosis; loose, epithelioid cell granulomas; and fibroblasts. Type 2 reaction was characterized in aspirates by the presence of an abundance of neutrophils in a background of lepromatous leprosy (P < .01). CONCLUSION: Criteria that are used in histopathology for the diagnosis of leprosy reactions can be applied satisfactorily to cytologic smears. A good correlation between clinical diagnosis and cytomorphology can be achieved. Multiple-site aspirates from the skin, nerve and lymph nodes are helpful in substantiating the diagnosis.  相似文献   

8.

Background

Food shortage was associated with leprosy in two recent studies investigating the relation between socioeconomic factors and leprosy. Inadequate intake of nutrients due to food shortage may affect the immune system and influence the progression of infection to clinical leprosy. We aimed to identify possible differences in dietary intake between recently diagnosed leprosy patients and control subjects.

Methods

In a leprosy endemic area of Bangladesh, newly diagnosed leprosy patients and control subjects were interviewed about their socioeconomic situation, health and diet. Dietary intakes were recorded with a 24-hour recall, from which a Dietary Diversity Score (DDS) was calculated. Body Mass Index (BMI) was calculated and Household Food Insecurity Access Scale (HFIAS) was filled out for every participant. Using logistic regression, a univariate, block wise multivariate, and an integrated analysis were carried out.

Results

52 leprosy cases and 100 control subjects were included. Food shortage was more common, dietary diversity was lower and household food insecurity was higher in the patient group. Patients consumed significantly less items from the DDS food groups ‘Meat and fish’ and ‘Other fruits and vegetables.’ Lower food expenditure per capita, lower BMI, lower DDS and absence of household food stocks are the main factors associated with an increased risk of having leprosy.

Conclusion

Low income families have only little money to spend on food and consequently have a low intake of highly nutritious non-rice foods such as meat, fish, milk, eggs, fruits and vegetables. Development of clinical leprosy could be explained by deficiencies of the nutrients that these foods normally provide.  相似文献   

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Leprosy relapses are mainly due to bacillary persistence and diamino-diphenyl-sulphone (DDS) monotherapy. Case histories were examined for 33 patients with lepromatous leprosy (LL), diagnosed 7-48 years before the relapse and treated only with DDS during 4 to 38 years. Twenty-eight patients received irregular non-supervised polychemotherapy (PCT) since 1983. Five patients received only DDS, and presented relapses 13-20 years after the treatment was stopped. Relapses were diagnosed by clinical methods, including the reappearance of lesions or presence of new anesthetic areas. All cases were confirmed by bacilloscopy, and a subset of 20 cases by skin biopsy. Four patients presented indeterminate leprosy (IL) and one patient borderline tuberculoid leprosy (BT) in the biopsy. The latter 5 demonstrated presence of intraneural bacilli; the remainder were LL. Two patients relapsed even with PCT treatment. The others were cured with supervised PCT. Predisposing factors for relapses were as follows: DDS monotherapy, irregular PCT with inadequate dosage, unsupervised treatment, treatment uncompliance, and inadequate relationship between the patient and the health staff. Inspections for relapse in leprosy is recommended for in all multibacillary patients that were treated with DDS. The clinical appearance of new lesions or new anesthetic zones, the bacilloscopy and skin biopsy, used together, are effective in establishing the presence of relapses.  相似文献   

11.
The increased reliability and efficiency of the quantitative polymerase chain reaction (qPCR) makes it a promising tool for performing large-scale screening for infectious disease among high-risk individuals. To date, no study has evaluated the specificity and sensitivity of different qPCR assays for leprosy diagnosis using a range of clinical samples that could bias molecular results such as difficult-to-diagnose cases. In this study, qPCR assays amplifying different M. leprae gene targets, sodA, 16S rRNA, RLEP and Ag 85B were compared for leprosy differential diagnosis. qPCR assays were performed on frozen skin biopsy samples from a total of 62 patients: 21 untreated multibacillary (MB), 26 untreated paucibacillary (PB) leprosy patients, as well as 10 patients suffering from other dermatological diseases and 5 healthy donors. To develop standardized protocols and to overcome the bias resulted from using chromosome count cutoffs arbitrarily defined for different assays, decision tree classifiers were used to estimate optimum cutoffs and to evaluate the assays. As a result, we found a decreasing sensitivity for Ag 85B (66.1%), 16S rRNA (62.9%), and sodA (59.7%) optimized assay classifiers, but with similar maximum specificity for leprosy diagnosis. Conversely, the RLEP assay showed to be the most sensitive (87.1%). Moreover, RLEP assay was positive for 3 samples of patients originally not diagnosed as having leprosy, but these patients developed leprosy 5-10 years after the collection of the biopsy. In addition, 4 other samples of patients clinically classified as non-leprosy presented detectable chromosome counts in their samples by the RLEP assay suggesting that those patients either had leprosy that was misdiagnosed or a subclinical state of leprosy. Overall, these results are encouraging and suggest that RLEP assay could be useful as a sensitive diagnostic test to detect M. leprae infection before major clinical manifestations.  相似文献   

12.
BackgroundThe Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence.MethodologyThe individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040.Principal findingsIn all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme.ConclusionsThe LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.  相似文献   

13.
The present study aimed to investigate the epidemiological situation of leprosy (Hansen’s Disease), in a hyperendemic metropolis in the Central-West region of Brazil. We studied trends over eleven years, both in the detection of the disease and in disabilities, analyzing disparities and/or differences regarding gender and age. This is an ecological time series study conducted in Cuiabá, capital of the state of Mato Grosso. The population consisted of patients diagnosed with leprosy between the years 2008 and 2018. The time series of leprosy cases was used, stratifying it according to gender (male and female), disability grade (G0D, G1D, G2D, and not evaluated) and age. The calendar adjustment technique was applied. For modeling the trends, the Seasonal-Trend decomposition procedure based on Loess (STL) was used. We identified 9.739 diagnosed cases, in which 58.37% were male and 87.55% aged between 15 and 59 years. Regarding detection according to gender, there was a decrease among women and an increase in men. The study shows an increasing trend in disabilities in both genders, which may be related to the delay in diagnosis. There was also an increasing number of cases that were not assessed for disability at the time of diagnosis, which denotes the quality of the services.  相似文献   

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BackgroundBrazil remains endemic for infection by the human immunodeficiency virus (HIV) and leprosy, having a major impact on public health and the life quality of affected patients. Although the relevance of this co-infection is recognized, several aspects, such as the immune response, are not yet fully understood. The objective of this study was to investigate the expression of FOXP3+ Treg cells in leprosy skin lesions and to correlate their clinical forms, laboratory characteristics (CD4, CD8, and CV), and the immune reconstitution syndrome in HIV-leprosy co-infection.Methodology/Principal findingsAn observational, cross-sectional, and analytical study was carried out comparing four groups of patients: those with concomitant diagnosis of leprosy and HIV infection without a leprosy reaction, those with leprosy and HIV co-infection patients with a reverse reaction (RR), those with leprosy without HIV and without reaction, and those with leprosywithout HIV and with RR. The patients were diagnosed at a dermatology outpatient clinic located in Belém, Pará, Brazil, from 2003 to 2017. In the sample studied, there was a positive correlation between FOXP3+ cell density and viral load, negative correlation with blood CD4+ (not statistically significant), significant positive correlation in CD8 count in patients with leprosy reaction, and positive relationship in patients with IRIS. The density of cells expressing FOXP3 was higher in the BL/LL forms in patients without HIV, although the difference was not statistically significant. However, the cell mean was higher in the TT/BT forms in patients co-infected with leprosy and HIV, showing contradictory results.Conclusions/SignificanceThese findings support that higher activity of the HIV may stimulate or result in a higher expression of FOXP3-Tregs and that they may be involved in active immunosuppression observed at the infection site at the tissue level. This supports the need to expand studies on FOXP3+ Treg cells in co-infected patients.  相似文献   

16.
ObjectiveWe evaluated the profile of patients referred to the Fiocruz Outpatient Clinic, a reference center for the diagnosis and treatment of leprosy in Rio de Janeiro, RJ, and analyzed the origins and outcomes of these referrals.MethodsThis is an observational retrospective study based on information collected from the Leprosy Laboratory database at Fiocruz, Rio de Janeiro, RJ, Brazil. A total of 1,845 suspected leprosy cases examined at the reference center between 2010 and 2014 were included. The originating health service referrals and diagnostic outcomes were analyzed as well as the clinical and epidemiological data of patients diagnosed with leprosy.ResultOur data show that the profile of the patients treated at the Clinic has changed in recent years. There was an increase in both the proportion of patients with other skin diseases and those who had visited only one health service prior to our Clinic. Among the total 1,845 cases analyzed, the outcomes of 1,380 were linked to other diseases and, in 74% of these cases, a biopsy was not necessary to reach a diagnostic conclusion. A decrease in new leprosy case detection among our patients was also observed. Yet, among the leprosy patients, 40% had some degree of disability at diagnosis.ConclusionThe results of the present study demonstrated the importance of referral centers in support of basic health services within the decentralization strategy. But, the success of the program depends on the advent of new developmental tools to augment diagnostic accuracy for leprosy. However, it should be emphasized that for new diagnostic methods to be developed, a greater commitment on the part of the health care system regarding research is urgently needed.  相似文献   

17.
Leprosy remains a public health problem in Brazil with new case incidence exceeding World Health Organization (WHO) goals in endemic clusters throughout the country. Migration can facilitate movement of disease between endemic and non-endemic areas, and has been considered a possible factor in continued leprosy incidence in Brazil. A study was conducted to investigate migration as a risk factor for leprosy. The study had three aims: (1) examine past five year migration as a risk factor for leprosy, (2) describe and compare geographic and temporal patterns of migration among past 5-year migrants with leprosy and a control group, and (3) examine social determinants of health associated with leprosy among past 5-year migrants. The study implemented a matched case-control design and analysis comparing individuals newly diagnosed with leprosy (n = 340) and a clinically unapparent control group (n = 340) without clinical signs of leprosy, matched for age, sex and location in four endemic municipalities in the state of Maranhão, northeastern Brazil. Fishers exact test was used to conduct bivariate analyses. A multivariate logistic regression analysis was employed to control for possible confounding variables. Eighty cases (23.5%) migrated 5-years prior to diagnosis, and 55 controls (16.2%) migrated 5-years prior to the corresponding case diagnosis. Past 5 year migration was found to be associated with leprosy (OR: 1.59; 95% CI 1.07–2.38; p = 0.02), and remained significantly associated with leprosy after controlling for leprosy contact in the family, household, and family/household contact. Poverty, as well as leprosy contact in the family, household and other leprosy contact, was associated with leprosy among past 5-year migrants in the bivariate analysis. Alcohol consumption was also associated with leprosy, a relevant risk factor in susceptibility to infection that should be explored in future research. Our findings provide insight into patterns of migration to localize focused control efforts in endemic areas with high population mobility.  相似文献   

18.

Background

Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis.

Methodology/Principal Findings

Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR) = 4.1; 95% CI: 1.8–8.2) compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2–8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts.

Conclusion

Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis.  相似文献   

19.
BackgroundAlthough incidence of leprosy in Spain has declined steadily over the years, the fivefold increase in immigration since the turn of the century—much of it from countries where leprosy is still prevalent—has been linked to an uptick in registered cases.ObjectiveTo describe the epidemiologic trends of incident leprosy cases detected in Spain among Spanish- and foreign-born population groups.MethodsObservational, retrospective study of suspected leprosy cases in Spain, as reported through the System of Compulsory Notification of Diseases from 2003 to 2013, with results disaggregated by country of birth. We collected statistical data on leprosy burden for other countries from WHO to estimate the expected number of imported cases.ResultsOf the 168 leprosy cases registered during the study period, 40 (24.6%) were in Spanish patients, while 128 (76.2%) were detected in legally resident immigrants. We identified a significantly higher number of imported leprosy cases during the 2008–2010 and 2011–2013 trienniums compared to the reference biennium 2003–2004 (OR 5.38, 95% CI 1.83–14.88 and OR 4.80, 95% CI 1.41–16.33, respectively). Most imported cases were diagnosed in Latin American immigrants (71.9%), especially Brazilians, but also Paraguayans, Bolivians and other nationalities from South and Central America. However, registered incidence was lower than expected for each year. For example, in 2003, the expected new cases in immigrants was 47.12, compared to only four cases that were actually detected (a 91% difference). Likewise, we expected to find 49.6 incident cases among immigrants in 2009, but only 15 new cases were reported (60% fewer than expected).ConclusionImported cases of leprosy are responsible for most leprosy incidence in Spain, and we cannot rule out some under-diagnosis. Clinicians should be made more aware of the potential for leprosy incidence among patients from countries where the disease is endemic.  相似文献   

20.
BackgroundThis study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population.MethodsA cross-sectional study based on a questionnaire posing 14 questions about leprosy symptoms and signs that was distributed to 1,400 prisoners. This was followed by dermatoneurological examination, anti-PGL-I serology and RLEP-PCR. Those without leprosy were placed in the Non-leprosy Group (NLG, n = 1,216) and those diagnosed with clinical symptoms of leprosy were placed in the Leprosy Group (LG, n = 34).FindingsIn total, 896 LSQ were returned (64%), and 187 (20.9%) of the responses were deemed as positive for signs/symptoms, answering 2.7 questions on average. Clinically, 1,250 (89.3%) of the prisoners were evaluated resulting in the diagnosis of 34 new cases (LG), based on well-accepted clinical signs and symptoms, a new case detection rate of 2.7% within this population, while the NLG were comprised of 1,216 individuals. The confinement time medians were 39 months in the LG while it was 36 months in the NLG (p>0.05). The 31 leprosy cases who responded to the questionnaire (LSQ+) had an average of 1.5 responses. The symptoms “anesthetized skin area” and “pain in nerves” were most commonly mentioned in the LG while “tingling, numbness in the hands/feet”, “sensation of pricks and needles”, “pain in nerves” and “spots on the skin” responses were found in more than 30% of questionnaires in the NLG. Clinically, 88.2% had dysesthetic macular skin lesions and 97.1% presented some peripheral nerve impairment, 71.9% with some degree of disability. All cases were multibacillary, confirming a late diagnosis. Anti-PGL-I results in the LG were higher than in the NLG (p<0.0001), while the RLEP-PCR was positive in 11.8% of the patients.InterpretationOur findings within the penitentiary demonstrated a hidden prevalence of leprosy, although the individuals diagnosed were likely infected while living in their former communities and not as a result of exposure in the prison. The LSQ proved to be an important screening tool to help identify leprosy cases in prisons.  相似文献   

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