Leprosy - an overview of clinical features, diagnosis, and treatment.

Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely. The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms. Apart from the various characteristic skin lesions, the condition is marked by damage to the peripheral nervous system. Advanced disease is characterized by disfiguring mutilations. Current treatment options are based on WHO recommendations. Early treatment frequently results in complete remission without sequelae. While paucibacillary forms are treated with rifampicin and dapsone for at least six months, multibacillary leprosy is treated for at least twelve months, additionally requiring clofazimine. Leprosy reactions during therapy may considerably aggravate the disease course. Besides individual treatment, WHO-supported preventive measures and strategies play a key role in endemic areas.

Palatal perforation in a patient with borderline lepromatous leprosy: leprosy still not eradicated.

Leprosy was eliminated globally in 2000, but it continues to be endemic in developing countries like India, Brazil and Indonesia, with a prevalence of 0.57/10 000 persons in India (2020). At the end of the year 2020, the prevalence was 129 389, and oral manifestation of the leprosy is luncommon. We hereby report a case of a female patient in her late 30s who presented with palatal perforation. Following a thorough history taking and full body clinical examination, we arrived at a diagnosis of leprosy, and prompt treatment was initiated. Knowledge of cases like this becomes important as the oral lesion is said to form an essential source of leprosy dissemination in the community, and awareness about them becomes crucial, demanding immediate attention.

In vitro and skin lesion cytokine profile in Brazilian patients with borderline tuberculoid and borderline lepromatous leprosy.

OBJECTIVE: We investigated the in vitro and skin lesions production of cytokines in non-treated borderline tuberculoid (BT) and borderline lepromatous (BL) patients. PATIENTS AND METHODS: Seven untreated, non-reactional BT patients and 12 untreated, non-reactional BL patients were studied. Levels of the cytokines IFN-gamma, IL-10, TGF-beta1 and TNF-alpha were measured in supernantant of peripheral blood mononuclear cells (PBMC) cultures, stimulated with specific M. leprae antigen (sonicated and whole). The cytokines iNOS, IL-10 and TGF-beta1 were detected by immunohistochemistry in skin biopsies. RESULTS: BT patients produced higher levels of IFN-gamma than BL patients; iNOS expression in skin lesions was also higher in BT patients. TGF-beta1 was detected in more cells in BL patients; IL-10 expression was similar in both groups. There was a negative correlation between iNOS and TGF-beta1 expression in skin biopsies, positive correlation between TGF-beta1 in skin lesions and bacillary index, as well as positive correlation between iNOS detected in skin biopsies and PBMC IFN-gamma production. CONCLUSIONS: The BT patients had a mainly a Th1-profile of cytokines in their skin lesions and BL patients had a Th2 profile.

Genetic diversity of mycobacterium leprae isolates from Brazilian leprosy patients.

INTRODUCTION: Leprosy is a chronic disease caused by infection with Mycobacterium leprae, an obligate intracellular parasite. A problem in studying the transmission of leprosy is the small amount of variation in bacterial genomic DNA. The discovery of variable number of tandem repeats (VNTRs) allowed the detection of strain variation in areas with a high prevalence of leprosy. Four genotypes of M. leprae based on three single-nucleotide polymorphism (SNPs) were also discovered to be useful for analysis of the global spread of leprosy. METHODS: In this present study, we examined the allelic diversity of M. leprae at 16 select VNTR and three SNP loci using 89 clinical isolates obtained from patients mainly from the neighbouring states of São Paulo and Rio de Janeiro Brazil. RESULTS AND CONCLUSION: By use of a PCR-RFLP-based procedure that allows the recognition of SNP types 3 and 4 without the need for the more expensive DNA sequencing steps, characterisation of the main M. leprae genotypes was easy. When applied on the study population, it was found that the SNP type 3 is most frequent in these two states of Brazil, and that VNTRs provided further discrimination of the isolates. Two Short Tandem Repeats (STRs) were monomorphic, with the remaining 14 STRs represented by two to 18 alleles. Epidemiological associations with township or state were not evident in this random collection and require further investigations. In phylogenetic trees, branches formed by all 16 STRs clearly separated SNP type 3 organisms from the other types while the allelic patterns of two minisatellite loci 27-5 and 12-5 were highly correlated with SNP type 3. This strain typing study provide the basis for comparison of M. leprae strain types within Brazil and with those from other countries, and informed selection of genomic markers and methods for future studies.

Occurrence and management of leprosy reaction in China in 2005.

BACKGROUND: Leprosy reactions are a major cause of disability before, during and after anti-bacterial treatment. Prompt diagnosis and correct management of reaction is a crucial matter for improving the quality of leprosy health services. OBJECTIVES: To describe the pattern of leprosy reaction and its management in China during 2005. METHODS: A retrospective survey using a questionnaire was carried out in all the provinces of China at the beginning of 2006. Patients included were those presenting with leprosy reaction between 1 January and 31 December 2005. RESULTS: 452 questionnaires from 25 provinces were analysed. There were 313 male and 139 female patients who had 159 Type I reactions, 273 Type II reactions and 20 Type I and II mixed reaction. 72.4% of reactions occurred in the first year of MDT and 27.6% of patients during the second year of MDT. The highest frequency of reaction was during the first 6 months of MDT; 57.3% of patients developed new nerve impairment during and after MDT. CONCLUSIONS: New nerve function impairment and disability still occurs among patients during and after MDT. The early detection and management of leprosy reaction remains important.

Clinical course of erythema nodosum leprosum: an 11-year cohort study in Hyderabad, India.

Erythema nodosum leprosum (ENL) or type 2 lepra reactions complicate lepromatous leprosy and borderline lepromatous leprosy. We report an 11-year retrospective case record analysis of 481 outpatients with borderline lepromatous and lepromatous leprosy at the Dhoolpet Leprosy Research Center in Hyderabad, India.. The overall prevalence of ENL was 24%, 49.4% among cases of lepromatous leprosy (LL) and 9% among cases of borderline lepromatous (BL) leprosy. Logistic regression analysis identified LL (odds ratio [OR] = 8.4, 95% confidence interval [CI] = 4.6-15.4, P < 0.001) and BL with a bacterial index > or = 4+ (OR = 5.2, 95% CI = 2.1-12.9, P = 0.001) as major risk factors. The average patient with ENL was male, 34.7 years of age, and had multiple episodes of ENL (mean = 3.1) over an 18.5-month period. Three types of ENL were identified: single acute ENL, multiple acute ENL (repeated discrete episodes), and chronic ENL (continuous episodes). Acute single ENL is rare, accounting for only 8% of cases. Chronic ENL accounted for 62.5% of the cohort. Chronic ENL was of longer duration and more severe. An age > or = 35 years was a risk factor for developing chronic ENL. Patients with chronic ENL were more compliant with multi-drug therapy, especially during the first six doses of multi-drug therapy. Distinguishing these different types of ENL would be useful for patient management and developing improved treatment of these debilitating reactions. Improved strategies for treatment and management of these reactions need to be developed.

A study of the prevalence of smear-positive leprosy cases in a tertiary care center in the post-elimination phase of leprosy.

BACKGROUND: India has declared leprosy to be eliminated in the country, according to the WHO criteria of attaining a prevalence of less than 1 in 10,000. However, smear-positive leprosy cases are frequently being encountered. METHODS: This is an 18-year retrospective study done in the Department of Dermatology and Venereology, Government Medical College, Trivandrum. Data were collected from the records of all cases in the study period, and the prevalence of smear-positive cases was determined in the post-elimination phase and this was compared to the pre-elimination phase. RESULTS: A total of 901 cases were analyzed, which comprised 538 cases in the pre- and 363 cases in the post-elimination phase. The male/female ratio in the pre and post phases was 2.61 : 1 and 2.45 : 1, respectively. Borderline tuberculoid accounted for the commonest type in both the pre and post phases comprising 45.54 and 50.69%, respectively. Type 2 lepra reactions were seen in 40.21% of the reaction cases in the post-elimination phase. The smear-positive cases in the post-elimination phase accounted for 34.99% compared to 14.68% in the pre-elimination phase. Lepromatous leprosy (LL) accounted for 67.71% of the smear-positive cases in the post phase compared to 67.08% in the pre phase. CONCLUSIONS: There was an increase of 20.30% of smear-positive cases in the post-elimination phase, which was statistically significant (P < 0.001), and the majority of them were LL (P < 0.001).

Household costs of leprosy reactions (ENL) in rural India.

BACKGROUND: Erythema nodosum leprosum (ENL) is a common immune-mediated complication of lepromatous (LL) and borderline lepromatous (BL) leprosy. Most patients experience chronic or multiple acute ENL over many years during an economically active period of their lives. Understanding the economic burden of ENL is essential to provide effective patient support, yet this area has not been investigated. METHODS: Ninety-one patients with LL or BL leprosy attending a leprosy hospital in Purulia district of West Bengal, India, were interviewed using a structured questionnaire. Cases (n = 53) were identified as those who had one or more episodes of ENL within the last 3 years. Controls (n = 38) had LL or BL leprosy but no history of ENL. Data were collected on household income, direct and indirect costs, and coping strategies. FINDINGS: The total household cost was Rs 1543 per month or 27.9% (IQR 13.2-52.6) of monthly household income for cases, and Rs 237 per month or 4.9% (IQR 1.7-13.4) of monthly household income for controls. Indirect costs accounted for 65% of total household costs for cases. Direct costs accounted for the remaining 35% of household costs, and resulted almost entirely from treatment-seeking in the private sector. Total household costs exceeded 40% of household income for 37.7% of cases (n = 20) and 2.6% of controls (n = 1) [1 USD = 59 INR]. INTERPRETATION: Households affected by ENL face significant economic burden and are at risk of being pushed further into poverty. Health policy should acknowledge the importance of private sector provision and the significant contribution to total household costs of lost productivity (indirect cost). Further work is needed to explore this area and identify solutions.

Clinical aspects of leprosy.

Leprosy is a chronic, infectious disease caused by Mycobacterium leprae. It mainly affects the peripheral nervous system, skin, and certain other tissues such as the reticulo-endothelial system, bones and joints, mucous membranes, eyes, testes, muscles, and adrenals. Leprosy clinical presentation varies from few to widespread lesions. In most patients, early leprosy presents as macular and hypopigmented lesions. This initial clinical presentation is known as indeterminate leprosy and occurs in individuals who have not developed cell-mediated immunity against M. leprae yet. The number of lesions depends on the genetically determined cellular immunity of the patient. Individuals presenting a vigorous cellular immune response and limited humoral immune responses to M. leprae, usually present few skin lesions. Without treatment, those patients tend to evolve into the polar tuberculoid or borderline tuberculoid form of leprosy. Due to the inability to mount an effective cellular-mediated response to M. leprae and the consequent hematogenous spread of the bacilli, some patients may present with numerous and symmetrically distributed hypochromic lesions. Without treatment these patients evolve to a nonresistant form of leprosy, polar lepromatous.

Ocular complications in newly diagnosed borderline lepromatous and lepromatous leprosy patients: baseline profile of the Indian cohort.

AIM: To describe ocular manifestations in newly diagnosed borderline lepromatous (BL) and lepromatous leprosy (LL) patients in India. METHODS: Ocular complications, at enrolment, occurring in all new borderline lepromatous and lepromatous leprosy patients detected by active case finding within the geographically defined leprosy endemic area of the Gudiyattam Taluk in India from 1991 to 1997 who consented to ocular examinations every 6 months, during and 5 years after treatment with multidrug therapy (MDT), were studied. RESULTS: Orbicularis oculi weakness (4.62%), lagophthalmos (4.20%), ectropion (0.42%), trichiasis (0.84%), blocked nasolacrimal ducts (1.68%), pterygium (11.34%), impaired corneal sensation (53%), corneal opacity (10.5%), corneal nerve beading (1.68%), punctate keratitis (1.26%), keratic precipitates (4.62%), iris atrophy (1.68%), and cataract (12.6%) were ocular complications seen in the 301 lepromatous patients at enrolment. 4.6% had blind eyes. Increasing age was associated with ocular complications. 80% of patients were skin smear acid fast bacilli (AFB) positive. The LL/BL ratio was 1:6.4. 71% had some limb deformity. 44% had only leprosy related ocular complications (LROC), 28% had only general ocular complications (GOC) while 14% had both LROC and GOC. Ocular complications were significantly related to leg deformities. Corneal nerve beading was seen most in LL patients (100%) having high bacterial content. Lagophthalmos and muscle weakness were associated with reversal reactions. CONCLUSIONS: Corneal nerve beading occurs in LL patients with high bacillary count. Patients with reversal reaction are more likely to present with orbicularis oculi weakness and lagophthalmos. Leprosy related ocular complications and general ocular complications are significant problems in newly diagnosed lepromatous patients. Elderly, deformed, skin smear positive, lepromatous patients are associated with increased ocular morbidity and form a group that require acceptable and accessible eye care.

Leprosy in children: correlation of clinical, histopathological, bacteriological and immunological parameters.

The study of leprosy in children has indicated an incidence of 10% amongst leprosy patients attending the clinic. The duration of the disease was usually less than 2 years. The expression of leprosy in this group was either a macule and/or a plaque. Classification was, therefore, different and conforms to indeterminate (I), borderline tuberculoid (BT) and borderline (BB) leprosy. Only occasionally were other clinical variants seen. The bacteriology was largely unproductive by slit-skin smears. The lepromin (Mitsuda) responses were positive in BT and unpredictable in BB patients. Epicutaneous responses to sensitization with dinitrochlorobenzene (DNCB) paralleled responses to lepromin. Microscopic pathology was of very little help. The correlation of these parameters was only 50-60% indicating that the diagnosis of leprosy should primarily be based on clinical features.

Increased incidence of cytoplasmic ANCA (cANCA) and other autoantibodies in leprosy patients from western India.

The prevalence of various autoantibodies was studied in 75 leprosy patients comprising eight patients with lepromatous leprosy (LL), 36 patients with borderline lepromatous leprosy (BL) and 31 patients with borderline tuberculoid leprosy (BT), along with 100 normal controls. Certain autoantibodies such as anti-nuclear antibodies (ANA), anti-single stranded DNA (anti-ssDNA) and anti-neutrophil cytoplasmic antibodies (ANCA) were raised among leprosy patients. When ANCA specificities to anti-myeloperoxidase (anti-MPO), anti-proteinase3 (anti-PR3) and anti-lactoferrin (anti-LF) were studied, it was found that the patterns of immunofluorescence such as perinuclear (p-ANCA), cytoplasmic (c-ANCA) and atypical (X-ANCA) and specificity by ELISA to anti-MPO, anti-PR3 and anti-LF varied in the LL, BL and BT groups. However, a higher amount of c-ANCA was observed in 62.5% of leprosy cases, while the incidences of p-ANCA and X-ANCA were lower. The LL group showed a higher incidence of autoantibodies as compared with the BL and BT groups, along with a male preponderance for autoantibody development. Some unusual antibody profiles such as 'X'-ANCA were also observed. The study suggests that autoantibody formation could be quite prevalent and also variable in the spectrum of leprosy cases, and there seems to be a serological overlap among leprosy and autoimmune disease, which could have pathogenetic importance in the leprosy patients developing complications.

Coronary heart disease risk factors in Hansen's disease sufferers.

In the frame of an epidemiologic study of Hansen's disease (HD) sufferers, several risk factors have been investigated which might explain the high prevalence of coronary heart disease (CHD) among HD patients. The data analyzed in the present study are derived from 293 HD patients (157 men and 136 women). The patients, after having completed a WHO adopted questionnaire, were given a complete physical examination, a resting and an exercise electrocardiogram, and biochemical as well as hematological examinations. Coronary HD patients, when compared to noncoronary HD patients, showed statistically significant differences in the following parameters: (1) mean age, (2) mean concentration of the electrophoretic fraction of alpha-lipoproteins, (3) deviation from mean weight, (4) prevalence of hypertension, and (5) prevalence of the borderline lepromatous form of HD. However, the differences found when comparing other parameters, such as blood pressure, smoking, diabetes mellitus, total cholesterol, triglycerides, pre-beta and beta-lipoproteins, uric acid, erythrocyte sedimentation rate, ABO blood groups, etc., did not reach the level of significance. These findings suggest that HD sufferers are a special population subgroup with reference to CHD risk factors, differing in many ways from the general population.

Association between leprosy and hepatitis B infection. A survey in Goiânia, central Brazil.

This investigation presents the results of hepatitis B virus screening among leprosy patients conducted in central Brazil as a preliminary information for a HBV vaccination programme. The main objectives were to assess the seroprevalence of HBV serum markers among lepromatous patients and to analyse institutionalization as risk factor for HBV infection in this population. Two groups of lepromatous patients were studied, 83 outpatients and 171 institutionalized ones. Screening for HBV serum markers included the detection of HBsAg, anti-HBc by radioimmune assay (RIA). The prevalence of carrier state (HBsAg) was 4.8% and 8.8% among outpatients and institutionalized, respectively, (p > 0.05). Seroprevalence of exposure (all markers) was statistically significant different between outpatients (16.9%) and institutionalized ones (50.3%). Institutionalized patients had an almost four fold risk of HBV infection when compared to the outpatients, and the highest risks were among patients with more than 21 years of residence in the colony, after adjusting for age and sex.

An immunohistochemical and morphological study of amyloidosis complicating leprosy in Malaysian patients.

Congo red screening of tissue blocks from 37 consecutive autopsies on leprosy patients revealed 7 cases of systemic amyloidosis, indicating a prevalence rate of 19%. 5 were males and 2 females. All were ethnic Chinese. Their ages ranged from 52 to 85 years with a mean of 69 years. Six had lepromatous leprosy while the remaining 1 had tuberculoid leprosy. In all 7 cases, the amyloid was AA in type, being permanganate-sensitive and immunoreactive with anti-human AA protein antiserum. Hepatic deposition was limited to blood vessels, a pattern typical of AA (secondary) amyloidosis. With regard to renal involvement, 4 showed a predominantly vascular pattern of infiltration while 3 exhibited the more ominous glomerular pattern. Three died of chronic renal failure and 2 of congestive cardiac failure attributable to renal and cardiac amyloidosis respectively. One patient succumbed to septicaemia and the remaining 1 to acute myocardial infarction. AA amyloidosis remains a serious and significant complication of leprosy among Malaysians.

[An increase in Hansen's disease in northeastern Brazil]. / A expansão da hanseníase no nordeste brasileiro.

The epidemiological aspects of hanseniasis in Recife from 1960 to 1985 were studied. Clinical-epidemiological records of 3,923 leprosy patients reported to the Secretaria de Saúde do Estado de Pernambuco were reviewed. The cruce as well as the age, sex and type-specific detection rates were calculated. The way the cases were detected and the time elapsed between the appearance of the first symptoms and the disease was analysed. The analysis of the time trend during the observation period showed an increase in the detection rate with time, rising from 5.5 per 100,000 inhabitants in 1960 to 36.1 per 100,000 inhabitants in 1985. The higher frequency of the tuberculoid type of leprosy and the high percentage of patients under 15 might refleet the expansion of the disease in Recife. The decline and the stabilization in the time elapsed between the appearance of the disease and its detection, from 1979 onwards, indicates a more prompt detection and, as a consequence of that, that the rate of detection is approaching the incidence rate. From 1970 to 1985 the most common means of detecting cases of Hanseniasis was through dermatological consultation followed by disease notification. Only 14.2% of the cases were discovered through the surveillance of contacts. The analysis of the epidemiological and operational indicators suggest that the increase in the detection rate over the period from 1960 to 1985 was due both to expansion of the disease and improvement in control measures. The prevalence rate of Hanseniasis in Recife in December 1984 was 2.04 per 100,000 inhabitants; according to the WHO criteria Recife may be considered an area of high endemicity.

Leprosy survey in industries in Bombay.

Population surveys for leprosy in industrial cities like Bombay revealed that about 60% of adult subjects especially males could be examined. The fact that the prevalence rate of leprosy particularly multibacillary type is much higher in this segment of population as compared to other groups indicates the importance of examining this population at their workspot like industries. 22287 industrial workers were examined for leprosy by paramedical auxiliaries in their establishments and 270 leprosy cases were detected (P.R. 12/1000). However, only 13 multibacillary cases (P.R. 0.5/1000) could be unearthed. 12 patients were with grade II and above. 184 (83%) were untreated. 161 (60%) patients reported for treatment. With available resources, case holding of patients who are not within the control area of the project becomes a challenging job for paramedical workers though large number of leprosy cases are detected amongst industrial workers. If industrial management arranges treatment for leprosy patients without dislocating them from their service, the pool of infection in the urban community will be reduced and can contribute tremendously towards urban leprosy control programme.

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

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

Leprosy among inmates of a prison.

A leprosy survey carried out in a district prison revealed a gross prevalence of 20 cases per 1000, and active prevalence of 10 cases per 1000 whereas, prevalence of leprosy in the state was 1.12 per 1000. Such prisons thus form hyperendemic pockets. The inmates are a closed community and there is a risk of cases among inmates spreading infection to others inside the prison during their sojourn there and to the community when they are released from the prison. Special efforts are required to identify and eliminate all identifiable sources of infection, especially at this point of time when we are aiming at elimination of leprosy as a public health problem.