Introduction Of Multidrug Therapy Research Articles

Assessment of Clinical, Histopathological, and Bacteriological Findings in Treated Leprosy Patients with Persistent Skin Lesions: A Retrospective Cohort Study.

Since the introduction of multidrug therapy (MDT), various disabilities/morbidities due to leprosy have been prevented. However, there is a subset of patients in whom the skin lesions do not resolve completely or remain unchanged despite a full course of MDT, which is a great source of anxiety to the patient and their family members. Hence, we tried to ascertain the putative causes and risk factors of persistent skin lesions (PSLs) by analyzing the clinical, histopathological, bacteriological, and drug resistance patterns. This is a retrospective, cohort study wherein 35 patients who had PSLs after completion of MDT were included. The majority of the patients were 18 to 30 years of age, with males predominating. Borderline tuberculoid leprosy was the most common clinical spectrum observed (71.4%). The majority had PSLs distributed predominantly over photo-exposed sites (upper limbs > trunk > face). Eight patients (22.8%) had a history of contact with leprosy patients in their family, and six patients (17.1%) had associated comorbidities. Improvement in histopathological parameters such as a decrease in granuloma fraction was observed in 22 patients (62.8%) with PSLs after release from treatment in comparison with baseline. Four patients (11.4%) were noted to have drug resistance (three to rifampicin and one to dapsone). Thus, our study emphasizes that leprosy patients with PSLs after completion of MDT should undergo histopathological evaluation and drug resistance studies.

A retrospective study on newly diagnosed Hansen’s disease and its spectrum in a tertiary care hospital

Background: Leprosy, a well known ancient disease caused by the pathogen Mycobacterium leprae. Leprosy became curable with the introduction of multi drug therapy (MDT). But the burden of the disease still continues to make an impact in the present society. India is one of the major contributors to the global leprosy case load even after elimination. The main aim of this study was to assess the clinical pattern of newly diagnosed leprosy patients and to emphasize the need of timely intervention. Methods: This was a hospital based retrospective observational study. The medical records of all the newly diagnosed leprosy patients during the period of January 2022 to December 2022 were collected and various clinical and demographic factors were analyzed. Results: Total 139 newly diagnosed leprosy cases were reported. The most common age group affected was 45-60 years. Males were predominantly affected than females. 128 cases were multibacillary leprosy and 11 were paucibacillary. Borderline tuberculoid (48.2%) was the most common spectrum noted. About 19.4% patients presented with lepra reactions and 25.17% patients presented with deformities. Conclusions: Newly diagnosed leprosy cases show that leprosy is active in the society. Active case detection by household contact survey and timely referral &treatment initiation and follow up by the field staff of health facility will prevent disability and stigma.

An evidence and reasoning based differential diagnosis of a case of leprosy reinfection from reaction and relapse

Leprosy is caused by Mycobacterium leprae (M. leprae) and is unique in terms of the chronicity of the disease and its prolonged treatment protocol. Even after the introduction of multidrug therapy (MDT) by World health organization (WHO), large numbers of new cases (nearly 200,000) of leprosy are reported yearly, indicating active transmission, especially in developing countries. Recurrent clinical manifestations after MDT can occur due to leprosy reactions, relapse or reinfection. It is very difficult to differentiate reaction, relapse and reinfection. Here we categorized a recent case of reoccurrence of leprosy as reinfection by differentiating it from reaction and relapse based on evidence and by analysing the clinical data of the patient.

Mycobacterial skin infection.

Purpose of reviewThe aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021.Recent findingsMycobacterial skin infections include a heterogeneous group of cutaneous diseases.Cutaneous tuberculosis is usually the result of hematogenous dissemination or spread from underlying foci and it must be distinguished from tuberculids, resulting from the immunological reaction to Mycobacterium tuberculosis antigens. Leprosy prevalence was drastically reduced after introduction of multidrug therapy in the 1980 s, but cases are still reported due to underdiagnosis, and animal and environmental reservoirs. Recent advances concentrate in the diagnostic field. Specific guidelines for the treatment of nontuberculous mycobacteria skin infections are missing and surgical procedures may be required. Prognosis is better as compared to nontuberculous mycobacteria lung disease. Rapid laboratory-confirmed diagnosis of Buruli ulcer may be achieved by the IS2404 PCR. Among new drugs, telacebec is promising in terms of potency, shorter duration and tolerability in animal studies. A clinical trial in humans is planned.SummaryMycobacterial cutaneous lesions are nonpathognomonic and clinical suspicion must be confirmed by culture or molecular detection. Long-course multidrug treatment is required based on susceptibility tests. Surgical intervention may also be required. Rehabilitation and psychosocial support reduce long-term physical and mental consequences mostly in Buruli ulcer and leprosy.

Epidemiological review of leprosy in WHO's Western Pacific Region: 1991-2019.

BackgroundLeprosy elimination was achieved in the Western Pacific Region of the World Health Organization (WHO) in the late 1980s. However, cases continue to be reported within the Region. This paper analyses leprosy cases in the Region reported to WHO during 1991–2019.MethodsDescriptive analyses were conducted of data from leprosy surveillance reported in the Region. Key indicators included prevalence, the number and rate of new cases detected, proportions of cases with multibacillary leprosy or grade 2 disability, and the numbers and proportions of cases among children and cases by sex.ResultsFrom 1991 to 2019, the number of registered cases detected in the Region decreased by 94% (from 68 313 in 1991 to 4381 in 2019), and the number of new cases detected decreased by 72.1% (from 15 002 in 1991 to 4004 in 2019). The proportion of cases of multibacillary leprosy increased from 67.4% (8045/11 943) in 1995 to 85.6% (3428/4004) in 2019, and between 1997 and 2019 the number of leprosy cases occurring in children decreased from 1240 to 424. The proportion of new cases with grade 2 disability decreased from 15.4% in 1997 to 6.6% in 2019. With few exceptions, nearly two thirds of reported cases occurred in males.ConclusionMost countries and areas in the Region have successfully eliminated leprosy, although some pockets remain in countries with hard-to-reach areas. The introduction of multidrug therapy and WHO’s 1991 elimination goals may have prompted the initial decline in leprosy cases. Continued efforts are required in case-finding, care and prevention in areas with a high burden of disease.

Clinical profile of Relapse in Leprosy and Laboratory Correlation, including Mouse footpad inoculation and Molecular tests, in a Tertiary Leprosy Institution

Introduction According to many studies, the relapse rate in leprosy has come down to negligible levels after the introduction of multi-drug therapy (MDT) by WHO. However, a small number of patients have been known to relapse after release from treatment, even when there has been good compliance. Methods and findings During 2009–2017 (8 years), 23 multibacillary relapse cases were diagnosed clinically at SIHR&LC, and investigated further to confirm relapse; 95.6% of cases were positive by slit skin smear, 78.3% on histopathology and 63.2% through growth in the mouse foot pad (MFP). Conclusion The positive slit skin smear and the presence of active Hansen’s disease with solid stained M. leprae on histopathology are suggestive of relapse. Positive mouse footpad inoculation indicated the presence of viable M. leprae. Relapse was confirmed in 12 patients, but negative mouse footpad results cannot exclude relapse. Where there are no facilities for such investigations, we must develop awareness about possible relapse in all treated patients, especially in field conditions, for early self-reporting, referral, and retreatment (with alternative drugs in cases of drug resistance) as needed.

Leprosy vaccines – A voyage unfinished

Leprosy, a chronic granulomatous disease caused by Mycobacterium leprae, is endemic in many regions of the world. With introduction of multidrug therapy in 1982, there has been a dramatic reduction in the prevalence of leprosy, but new cases continue to appear. There have been more than 200,000 new cases per year for the past 10 years. There is a renewed interest in leprosy vaccines with immunoprophylactic and immunotherapeutic roles. Due to the difficulty in cultivating M. leprae in artificial media, vaccine strategies have centered on the use of cross-sensitizing mycobacteria. Bacillus Calmette–Guerin (BCG) has been the most popular among these, but with a widely varying protective efficacy reported from different parts of the world. In three meta-analyses, BCG has shown strong evidence of efficacy against leprosy. Recently, India has focused interest on another vaccine, Mycobacterium indicus pranii vaccine earlier known as Mycobacterium w. To overcome the limitations of these whole cell vaccines, various recombinant BCGs and subunit vaccines have been developed and studied in experimental models. These often yield inconsistent results. However, a new subunit recombinant vaccine – LepVax holds promise and has completed Phase 1a clinical trials successfully.

Looking into Array of Clinical Presentations of Patients with Leprosy and their Clinico-epidemiological Profile: A Retrospective Study

Introduction: The prevalence of leprosy in India has decreased to <1 per 10,000 population by 2016 after the introduction of Multidrug Therapy (MDT) in 1982; still wide variations in Prevalence Rates (PR) continue to exist across the states and regions in the country. Aim: To determine the current clinical profile of leprosy and study various presenting features of patients with leprosy at a tertiary care hospital in North India. Materials and Methods: A retrospective study, based on seven years data, was conducted on patients diagnosed and registered in the leprosy clinic of a tertiary care hospital in North India, from January 2013 to December 2019. Data regarding their demographic details, presenting complaints, clinical features, associated complications and treatment administered was analysed and was entered into Microsoft Excel and presented as tables. Results: A total of 181 patients of leprosy were registered over a period of seven years. There were 133 males and 48 females with M:F ratio of 2.77:1. Of the total patients registered, 3.86% were children (≤14 years) and 97.8 % patients were immigrants from the adjoining states. The most common clinical type was Multibacillary (MB) leprosy in 88.95% patients whereas most frequent morphological type was Borderline Tuberculoid (BT) leprosy (72.93%). Thirty-three (18.23%) patients presented with leprosy reaction (Type 1 reaction in 16.6% and Type 2 reaction in 1.66%). World Health Organisation (WHO) grade 2 deformities (G2D) were diagnosed in 3 (1.66%) patients, with claw hand being the most common deformity (1.10%). Anaesthetic to hypoaesthetic patches were the most common presenting feature (64.1%). Conclusion: Despite statistical elimination, MB disease and leprosy reactions are commonly seen as presenting manifestations. It highlights the need for high quality leprosy services including good referral system for an active case detection. Varied clinical presentations of leprosy should be contemplated while examining patients that can assist in an early and better case detection that will prevent delay in therapy and associated deformities and also decrease the transmission of disease in the community.

Resurgence of leprosy in post elimination era

<p class="abstract"><strong>Background:</strong> Leprosy is a slowly progressive mildly infectious disease caused by <em>Mycobacterium leprae</em> primarily affecting skin and peripheral nerves. After introduction of multidrug therapy in the country recorded leprosy case load has come down. In December 2005, India announced elimination of leprosy as public health problem at national level under the NLEP but new cases are still being registered.</p><p class="abstract"><strong>Methods:</strong> It was a hospital based cross sectional study conducted on over 109 leprosy patients attending a tertiary care hospital in Narhe, Pune during the period from 1<sup>st</sup> January 2018 to 31<sup>st </sup>December 2018. The statistical package for Social Sciences (SPSS) for Windows version (16.0) was used to analyze the data (SPSS Inc., Chicago, IL). Statistical significance was declared at p<0.05 or mentioned otherwise.<strong></strong></p><p class="abstract"><strong>Results:</strong> Out of 109 patients, 57 were new and 52 were old. Maximum patients belong to age group 40-49 years, 25 patients had type 1 reaction and 18 had type 2 reaction. Out of which 83 were on treatment and 12 are defaulter, 9 were in relapse, 6 patients released from treatment.</p><p class="abstract"><strong>Conclusions:</strong> In post elimination era of leprosy still new cases have been registered and hence the burden and morbidity of the disease is still high in the community. It strongly suggests that by early detection, increasing the duration of treatment and by increasing the community awareness, utilizing information, education and communication at all levels, we can hope to reduce the burden of disease in the community and to achieve the dream of leprosy free India.</p><p class="abstract"> </p>

Current Situation of Leprosy in India and its Future Implications.

The global leprosy situation has changed significantly over the last four decades after the introduction of multidrug therapy (MDT) in 1982 with a reduction in prevalence from over 5 million cases in the mid-1980s to less than 200,000 at the end of 2016. The programme in India also saw a reduction from a prevalence rate of 57.8/10,000 in 1983 to less than 1/10,000 by the end of 2005 when India declared to have reached the World Health Organization (WHO) target of elimination as a public health problem. Post 2005, major changes in the programme were made by the National leprosy eradication programme (NLEP) and the global leprosy programme, which may have affected the new case detection (NCD), disability, and child leprosy trends, which continue to show no appreciable regression. This article reviews the current global and Indian leprosy scenario to bring out its achievements and successes, including the impact of Leprosy Case Detection Campaigns (LCDC) on leprosy numbers. The basis and expected benefits of recent introduction of chemo and immune-prophylaxis in the programme are also discussed. It also discusses the shortcomings, the areas of concern, and the need for an inclusive strategy in the Indian leprosy programme that includes an intersectoral collaboration within the country for reaching the desired goal of leprosy eradication.

Leprosy Reactions: Clinical and Therapeutic Profile of Patients Registered at a Dermatology Reference Center in Brazil

Introduction: During the course of leprosy, 10 to 50% of individuals can be surprised by reaction states, which are immune system reactions of the patient to Mycobacterium leprae. Leprosy reactions constitute the main cause of nerve damage and disability caused by leprosy.
 Objective:To analyze the clinical and therapeutic profile of patients with leprosy reactions registered in a Dermatology Service in the city of Belém-PA.
 Methods:This is a cross-seccional, descriptive study. It was investigated through analysis of medical records, 52 patients who fit the established inclusion criteria. Data were collected in july and august 2016.
 Results: It was found a predominance of men, from the metropolitan region. The clinical form most common of Leprosy was Borderline, and the leprosy reaction type 1. The most of reactions occurred right after the introduction of multidrug therapy,and more than a half of patients with type 1 reaction showed edema of limbs. Regarding the type 2, fever and general symptoms were the most common, present in all cases. The frequency of neural damage was evident, showing reduction of motor force level andloss of protective sensation.
 Conclusion: Early diagnosis and appropriate therapeutic management of reactive events is critical to the prevention of disabilities.

It is time to review concepts on renal involvement in leprosy: pre- and post-treatment evaluation of 189 patients

Background: Functional and morphological renal lesions have been widely described in leprosy for decades. Nevertheless few studies have assessed renal function pre- and during treatment after the advent of multidrug therapy (MDT). Methods: This is a prospective study involving 189 consecutive patients, with all forms of leprosy (Ridley–Jopling scale). Laboratory (serum urea and creatinine, estimated GFR, urinalysis, microalbuminuria, urinary RBP) and clinical features of renal disease were evaluated previously and after onset (3 and 8 months later) of MDT. Results: One hundred and eighty-nine patients (M 1.8: F 1; mean age 44 ± 16 years) were included just after diagnosis of leprosy and before the introduction of MDT. Mean time until manifestation of symptoms and/or signs of leprosy was 29 ± 56 months (25 days–480 months). Microhematuria and microalbuminuria were detected in 7.5% and 9.6% of the cases, respectively. Elevated serum creatinine was detected in 34% pre-MDT; this was statistically more frequent in males, hypertensive and frequent users of non-steroidal anti-inflammatory drugs (NSAID), as well as in patients with erythema nodosum lepromatosum, 45.5% by the time of diagnosis, 18% after 3 months and 9% after 8 months of MDT (p = 0.039). Conclusions: Our results suggest that functional renal lesions in leprosy are currently mild and predominantly of glomerular origin, in opposition to the severe involvement described in the past. This improved outcome of renal disease secondary to leprosy is possibly due to the advent of MDT and effective treatment of episodes of reaction, leading to shorter periods of active infectious disease.

Leprosy in the 21st century.

Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the global incidence remains high, and patients often have long-term complications associated with the disease. In this article, we discuss recent findings related to genetics, susceptibility, and disease reservoirs and the implications of these findings for Hansen's disease control and health outcomes for patients. We describe the continued difficulties associated with treatment of inflammatory episodes known as "leprosy reactions," which cause much of the disability associated with the disease and can affect people for many years after MDT is complete. We also discuss some of the contemporary challenges for physicians and patients, including international and internal migration of people affected by the disease. We suggest some important areas of focus for future Hansen's disease research.

Association of genetic polymorphism of HLA-DRB1 antigens with the susceptibility to lepromatous leprosy

Despite the introduction of multidrug therapy and the overall reduction of leprosy prevalence in Mexico, the disease remains endemic in certain regions of the country. A genetic basis for the immune susceptibility to Mycobacterium leprae has already been established in different populations worldwide. In this study, we investigated the possible association of the HLA-DRB1 alleles with leprosy in a Mexican Mestizo population. The results demonstrated that the HLA-DRB1*01 allele is associated with lepromatous and dimorphic leprosy [P<0.001, odds ratio (OR)=4.6, 95% confidence interval (95% CI): 1.8-11.4; and P=0.03, OR=6.2, 95% CI: 1.1-31.6, respectively] and the frequency of the HLA-DRB1*08 allele was found to be significantly lower among leprosy patients compared to controls (P=0.046, OR=2.4, 95% CI: 1-5.8). In conclusion, although the association of the HLA-DR locus with leprosy has been established in different populations and several studies have demonstrated significant differences in the DR alleles, this study demonstrated an association of the HLA-DRB1*01 allele with susceptibility to lepromatous and dimorphic leprosy, as well as an association of the HLA-DRB1*08 allele with protection against leprosy in a Mexican Mestizo population.

Rifampicin-resistant Mycobacterium leprae in an elderly leprosy patient in the People&amp;#39;s Republic of China

The reported number of registered leprosy patients worldwide declined with the introduction of multidrug therapy. However, the emergence of rifampicin resistance in leprosy patients engenders difficulties for an individual patient, and its dissemination could pose a threat to leprosy control. This study reports an elderly patient who was diagnosed with rifampicin-resistant lepromatous leprosy. This case indicates that inadequate treatment and poor compliance may eventually result in rifampicin resistance in Mycobacterium leprae and clinical relapse.

Current status of leprosy: Epidemiology, basic science and clinical perspectives

Leprosy has affected humans for millennia and remains an important health problem worldwide, as evidenced by nearly 250 000 new cases detected every year. It is a chronic infectious disorder, caused by Mycobacterium leprae, that primarily affects the skin and peripheral nerves. Recent advances in basic science have improved our knowledge of the disease. Variation in the cellular immune response is the basis of a range of clinical manifestations. The introduction of multidrug therapy has significantly contributed to a decrease in the prevalence of the disease. However, leprosy control activities, including monitoring and prevention programs, must be maintained.

Prospects for sustaining leprosy control in Uganda

The Uganda Ministry of Health launched a National Tuberculosis and Leprosy Programme (NTLP) in 1990. The programme functions at three levels: Central, Zonal (intermediate) and District. The first 4 years of NTLP saw the change from Dapsone monotherapy and several Rifampicin and Clofazimine containing treatment regimens to World Health Organization (WHO) recommended Multidrug Therapy (MDT). National coverage with MDT was achieved in 1994. At the time of starting NTLP there were over 2000 leprosy patients on treatment and following introduction of MDT the numbers of registered cases declined dramatically while the number and rate of new cases notified especially the Multibacillary (MB) type showed a more gradual decline (see Figure 1). The country achieved the target of elimination of leprosy in 2004. In 2006 Uganda adopted the WHO Strategy for further reducing the burden of leprosy and sustaining leprosy control services. According to the strategy, quality is one of the essential components of an effective programme. The quality and coverage of a programme are key determinants of its sustainability. This paper presents a review of the performance of the Uganda National Leprosy Control Programme in terms of quality services as defined in the Operational Guidelines of the Enhanced Strategy and suggests steps to take in order to ensure sustainability of quality leprosy control services in the country.

Treatment of leprosy in India

Introduction of multi-drug therapy (MDT) into the National Leprosy Eradication Program (NLEP) of India has brought a decline in both the burden of the disease and the detection of new cases in the country. Despite this success, MDT has had many problems like remarkable relapse rate, non-adherence to the MDT and the emergence of drug resistance associated with it. Moreover, there is no new MDT regimen at present, which could solve all these problems. The current situation suggests that we should look for alternative solutions in the delivery of leprosy-related services. With the introduction of Accredited Social Health Activists under the National Rural Health Mission, there is an opportunity to control some of these problems associated with MDT. Besides, District Nucleus should take initiatives and actively participate in establishment of coordination between departments of Health, Social welfare and justice, education and various non-governmental agencies working in the field of leprosy and disability in order to deliver the best of services to the persons affected by leprosy.

Epidemiological shift in leprosy in a rural district of central India following introduction of multi-drug therapy (April 1986 to March 1992 and April 1992 to March 2002)

This study compares the epidemiological pattern of leprosy in pre- (April 1986 to March 1992) and post- (April 1992 to March 2002) multi-drug therapy (MDT) periods by retrospective analysis of 3274 registered leprosy cases in the rural field area of Regional Leprosy Training & Research Institute (RLTRI), situated in Raipur district of Chattisgarh province of Central India. The area has high endemicity for leprosy. In the post-MDT period, prevalence rate (PR) came down to less than 1 in 10, while New Case Detection Rate (NCDR) remained almost static during the two periods. Of the total new registered cases, 30.1% were registered during the pre-MDT period and the remaining 69.9% during the post-MDT period. Comparison of key leprosy variables among new registered cases showed a 2-fold rise in the proportion of MB cases (14.8 versus 27.6%), 3.0% increase in proportion of child cases (15.3 versus 18.6%) and cases with deformity grade II (3.1 versus 5.9%) and 4.0% increase in female proportion (41.4 versus 45.7%) during the post-MDT period. A decline was noted in mean age of registration for both MB (6.4 years) and PB (5.7 years) groups in the post-MDT period. While comparing treatment and outcome related variables, a marked fall of 25.8 months was recorded in treatment duration in the post-MDT period. The defaulter rate came down by 45.0% and relapse rate by more than 12.0% during the same period. The study shows that MDT is effective operationally, but continued ongoing transmission of infection and delayed diagnosis needs corrective action.

Neuropathic pain in leprosy patients.

The introduction of multidrug therapy by the World Health Organization has dramatically reduced the world prevalence of leprosy but the disease is still a public health problem in many countries, with a world prevalence of almost 600,000 cases in 2001. Damage to peripheral nerves is a key component of leprosy and the sensory and motor loss that follows is the basis for many of the classical features of this disease, such as skin wounds, cracks, plantar ulcers, clawed hands, drop foot, and incomplete closure of the eyelids. One of the most remarkable aspects of leprosy to lay persons and health care workers alike is that patients are reputed to feel no pain. However, neuropathic pain is arising as a major problem among leprosy patients. It can be nociceptive due to tissue inflammation, which mostly occurs during episodes of immune activation or neuropathic due to damage or dysfunction of the nervous system. This study, conducted among 358 leprosy patients, reveals a considerable prevalence of neuropathic pain and presents evidence that this common problem should be a high priority of those in charge of leprosy control programs.